description stringlengths 2.98k 3.35M | abstract stringlengths 94 10.6k | cpc int64 0 8 |
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of U.S. application Ser. No. 10/869,994, filed Jun. 17, 2004 (Atty. Docket No. D0932-00440).
FIELD OF THE INVENTION
[0002] The present invention relates to insulation products, and more specifically to loose fill insulation, batts and board products and methods of making the same.
BACKGROUND OF THE INVENTION
[0003] Thermal insulation for buildings and other structures is available in the form of mats, batts, blankets and loose fill. Mats, batts and blankets are flexible products containing randomly oriented fibers bound together with a binder, and are generally prefabricated before being brought to a construction site and installed. In contrast, loose fill thermal insulation includes a large number of discrete fibers, flakes, powders, granules and/or nodules of various materials. The loose fill can be poured or blown into hollow walls or other empty spaces to provide a thermal barrier.
[0004] Because of cost-effectiveness, speed and ease of application, as well as thoroughness of coverage in both open and confined areas, the practice of using pneumatically delivered or “blown” loose-fill insulation materials, e.g., glass fiber, rock wool, mineral fiber wool, cellulose fibers, expanded mica, and the like, has become an increasingly popular method by which to install insulation in new and existing building constructions.
[0005] Loose-fill insulation blown into attics, basements and outside wall cavities is very effective in reducing heat transfer in existing buildings. Loose-fill insulation can provide a substantial advantage over batt-type insulation in that the loose-fill material readily assumes the actual shape of the interior cavity being filled, whereas the insulative batts are manufactured in a limited number of standard size widths, none of which will as closely match the actual dimensions of wall cavities or accommodate obstructions encountered in the field. Properly installed, loose-fill insulation essentially completely fills a desired area of the building cavity, conforming to the actual shape of the building cavity, including obstructions, such as water, waste and gas lines, electrical conduits, and heating and air conditioning ducts, and provides, in that respect, effective resistance to heat transfer through walls, floors or ceilings.
[0006] Any insulation that is capable of compression has an expanded volume due to included air, within spaced apart, fibers or particles or foam of materials such as glass, polymer or cellulose. An industry standard R-value is a rating number that is printed on the insulation. The R-value refers to the extent to which the insulation reduces the rate of heat transfer through the insulation. The R-value typically increases with increases in thickness and with increases in density of the insulation for a given material. When the insulation is installed, it is capable of compression to fill a building cavity having a width, for example, on 12 inch centers, 16 inch centers, 17.7 inches or 24 inch centers. Further, the insulation is capable of compression to fill the cavity having a length defined by the width of either 9.5 inches for a 2×10 joist, or 11.5 inches for a 2×12 joist, or 13.5 inches for a 2×14 joist, or 15.5 inches for a 2×16 joist. Such a compression is in a direction transverse to the R-value and thickness, which would not substantially reduce the R-value of the insulation.
[0007] While insulation products based upon glass fibers are known, there is still a need to improve the thermal efficiency, “R”, of such products in a cost effective manner.
SUMMARY OF THE INVENTION
[0008] In the first embodiment of the present invention, a fiberglass thermal insulation is provided which contains about 50-95 weight percent of randomly distributed inorganic fibers and about 5-50 weight percent microspheres. The microspheres boost the insulation value of the fiberglass insulation by at least about 0.5 R.
[0009] The present invention can provide fiberglass insulation products such as loose fill insulation, batts or duct boards, for example. When the glass microspheres, preferably hollow microspheres are added to blown loose fill insulation, the thermal performance can be boosted at least about 0.5 R by as little as 5 weight percent of hollow microspheres.
[0010] Hollow glass microspheres, such as those provided by 3M in the form of brand names K1, K20 and K25, have a density of about 0.125 g/cc-0.60 g/cc and a size of about 12-300 microns, preferably about 30-120 microns. Both plastic or inorganic, such as glass or ceramic, microspheres can be used.
[0011] In the further embodiment of the present invention, an insulation batt or board is provided which includes a fiberglass thermal insulation layer containing randomly distributed inorganic fibers, and at least 5 weight percent microspheres, the microspheres boost the insulation value of the fiberglass insulation batt or board by at least about 0.5 R. The insulation layer is joined to a facing layer, such as Kraft paper, or a polymeric layer, such as polyethylene film. In a variation of this embodiment, the microspheres can be adhered to a layer of the insulation layer, such as by applying the microspheres to the bituminous mastic used to join the facing to the insulation layer, for example.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings illustrate preferred embodiments of the invention, as well as other information pertinent to the disclosure, in which:
[0013] FIG. 1 illustrates loose fill insulation blown in an attic between a pair of joists; and
[0014] FIG. 2 illustrates an insulation batt having microspheres in three different locations.
DETAILED DESCRIPTION
[0000] Loose Fill
[0015] With reference to FIG. 1 , a loose fill insulation product 10 having microspheres 11 dispersed therein is provided. The loose fill insulation 10 can be in the form of fibers, flakes, powders, granules and/or nodules of various materials. The loose fill insulation is of the type for insulating an interior of a hollow or open space in a building structure, e.g., a house, office, or other building structure. Preferably, the loose fill can be compressed during storage to save space, and then expanded or “fluffed-up” with air or another gas when poured or blown into a hollow wall or other empty space of a structure. The loose fill insulation 10 can include organic materials, inorganic materials or both. Examples of organic loose fill materials include animal fibers, such as wool; cellulose-containing vegetable fibers, such as cotton, rayon, granulated cork (bark of the cork tree), redwood wool (fiberized bark of the redwood tree), and recycled, shredded or ground newspaper fibers; and thermoplastic polymer fibers, such as polyester; and expanded plastic beads. Examples of inorganic loose fill materials include diatomaceous silica (fossilized skeletons of microscopic organisms), perlite, fibrous potassium titanate, alumina-silica fibers, microquartz fibers, opacified colloidal alumina, zirconia fibers, alumina bubbles, zirconia bubbles, carbon fibers, granulated charcoal, cement fibers, graphite fibers, rock fibers, slag fibers, glass wool and rock wool. The loose fill can include one or more varieties of loose fill material. In an exemplary embodiment, the loose fill insulation includes OPTIMA® fiberglass loose fill insulation available from CertainTeed Corporation, Valley Forge, Pa.
[0016] When manufactured and compressed during storage, the loose fill particles forming the compressed loose fill are dimensioned so as to have an equivalent sphere with a diameter generally smaller than 3 cm, preferably from 0.1 to 1 cm. In one embodiment, after the compressed loose fill is decompressed, expanded and processed through a blowing hose, the loose fill particles forming the expanded loose fill are each dimensioned so as to just fit within a sphere having a diameter of from 0.1 to 4 cm, preferably from 0.5 to 2 cm.
[0017] The thermal insulation product including the microspheres 11 can be formed by dispersing, preferably uniformly, the microspheres 11 in the loose fill 10 before or at the same time as the loose fill is poured or blown into an interior, empty space of a hollow or open object, such as a hollow wall (before application of the drywall) or an attic. Methods of pouring and blowing loose fill 10 are well known in the art and will not be repeated here in detail. Generally, blowing loose fill 10 involves feeding compressed loose fill 10 into a blower where it is mixed with a gas, such as air, expanded, processed through a blowing hose, and then blown into a hollow or open structure to form thermal insulation.
[0018] In certain embodiments, a mixture including one or more microspheres 11 , such as hollow plastic and glass microspheres, and a dry binder (i.e., an adhesive later activated by water at the time of installation of the loose fill) can be sprayed onto or otherwise mixed with the loose fill 10 before the loose fill 10 is compressed and/or when the loose fill 10 is decompressed. Also, a mixture including one or more microspheres 11 and a binder (i.e., an adhesive) can be mixed with the loose fill by spraying on the loose fill at or near the end of the blowing hose before the loose fill is installed in a hollow or open space. The binder serves to join and hold the microspheres 11 and the loose fill insulation together. The binder can be organic or inorganic. The organic binder can include an organic water based binder such as an acrylic latex or a vinyl acetate latex. The organic binder can also include a sprayed hot melt adhesive such as a thermoplastic polymer. The inorganic binder can include an inorganic bonding agent such as sodium silicate or a hydraulic cement. Evaporation of the liquid from the liquid mixture on the loose fill 10 results in a loose fill thermal insulation 10 with the microspheres 11 and/or binder dispersed in the loose fill 10 . In various embodiments, the microspheres 11 and the binder can be added to the loose fill 10 at the same time or at different times. A mineral oil can be used instead of or in addition to the binder for the purpose of dust reduction. In other embodiments, rather than providing the microspheres 11 in a liquid mixture, the microspheres 11 may be provided to the loose fill 10 in its liquid slurry state or as a powder and, optionally, along with a mineral oil and/or binder as described above.
[0019] In one preferred embodiment, loose fill insulation is fed through a loose fill transport duct into mixer to form a mixture of loose fill 10 and microspheres 11 . The microspheres 11 may be provided, for example, in slurry or dry form. In embodiments, a dry binder (to be later activated by water or other material during loose fill application) and/or mineral oil can also be added in the loose fill transport duct or added in and mixed in mixer with the loose fill and phase change material. The phase change material can be added directly to the mixer and/or to the loose fill transport duct. The mixture is then fed to compressor/packager, where the mixture is compressed to remove air and increase density and packaged as compressed loose fill including the microspheres.
[0000] Microspheres
[0020] Microspheres are small solid or hollow spheres with an average diameter in the range of 12-300 microns, preferably about 15-200 microns, and most preferably about 30-120 microns. Microspheres are commonly made of glass, and are desirably made hollow for their thermal and sound insulation qualities. Borosilicate or similar glass is preferred because of its insolubility in water. Alternatively, recycled amber container glass frit is also attractive, since it can be made into hollow glass amber spheres, without the addition of a sulfur-containing compound, since sulfur is a pre- existing constituent. A number of glass microsphere grades are available, in a range of wall thicknesses, strengths, and densities from under 10 pcf to over 20 pcf, preferably about 0.125-0.60 g/cc.
[0021] Fiberglass macrospheres were created to overcome some of the limitations of glass microspheres. As their name suggests, macrospheres are relatively large, with most common diameters in the 0.125″-0.500″ range. A wide selection is available of strengths and densities, in roughly the same range as glass microspheres. Macrospheres increase the overall packing factor to 70% or more, and are often less expensive than glass microspheres.
[0022] As the name implies, microspheres are small, spherical particles. Particle sizes range from 12 to 300 microns in diameter, and wall thickness can vary from several microns to as low as 0.1 micron. They can be composed of acrylonitrile, glass, ceramic, epoxy, polyethylene, polystyrene, acrylic, or phenolic materials. Because they are hollow, the true density of microspheres is lower than that of other non-soluble additives. The true density of hollow microspheres ranges from 0.60 g/cc to as low as 0.025 g/cc.
[0023] There are many potential applications for hollow glass microspheres. Sodium borosilicate hollow microspheres are often used as light-weight fillers of composite plastics for ship-building, aviation and car-making industries, sensitizing additives in manufacture of industrial explosives, varnishes, and paint fillers. In contrast to mineral and organic fillers, hollow microspheres are unique because they have a low density but high strength.
[0024] The production of hollow microspheres is a well-established technology. There are several methods available to produce hollow microspheres, but every approach depends on the decomposition of a substance known as a “blowing agent” to form a gas within in a liquid. The rapid expansion of this gaseous product causes the formation of a bubble. One of the most common methods for producing hollow microspheres is to intentionally mix a trace amounts of a sulfur-containing compound such as sodium sulfate with a sodium borosilicate glass that is similar in composition to traditional Pyrex® glassware. This mixture is then dropped into a hot flame that melts the powdered glass and sodium sulfate. The melting of sodium sulfate results in a decomposition reaction that releases minute amounts of sulfur gas that form bubbles within the molten glass droplets. (Sodium sulfate additions are not necessary when waste or virgin amber glass frit is used, since sulfur-containing compounds are mainly responsible for the amber color of the glass and are already present.) The hollow droplets are then rapidly cooled from the liquid state to form hollow microspheres. As previously mentioned, such an approach relies on the intentional addition of a sulfur-containing compound to the glass.
[0025] Microspheres have found use in many applications over the years. They are widely used in the fiber-reinforced polyester industry to improve the manufacturing process of shower stalls and boats. Lighter, more-durable fiberglass products are a direct result of the creative use of microspheres. Thick-film ink, mining explosives, and rubber and plastic products of all descriptions are just a few other examples of the many products that are made better with these versatile materials. The benefits derived by these diverse end uses vary—some are unique to a specific industry, while others are common goals shared by many manufacturers.
[0026] Likewise, certain types of microspheres may offer a particular set of advantages, and a formulator must carefully select from the many products available in order to obtain the best results. For example, the compressible nature of plastic microspheres is a unique feature that is suited to elastomeric products, while glass microspheres are ideal for areas involving high temperatures and/or chemical resistance.
[0000] Plastic Microspheres
[0027] Developed in the 1970s, thermoplastic microspheres are compressible, resilient, hollow particles. The extremely thin shell wall possible with plastic spheres results in specific gravities as low as 0.025 and allows just a small weight-percent of these materials to displace large volumes when disposed in matrices. Because the resilient plastic can deform under stress, there is virtually no breakage when mixing or pumping these products, even with high shear mixing, as in the case of blowing loose fill insulation. Additionally, the compressible nature of plastic can absorb impacts that might ordinarily deform the finished product, thereby reducing damage caused by stone chips, foot traffic or freeze-thaw cycles.
[0000] Glass Microspheres
[0028] Glass bubbles were developed in the 1960s as an outgrowth from the manufacture of solid glass beads. Since they are made of glass they provide the benefits of high heat and chemical resistance. The walls of glass bubbles are rigid. Products are available in abroad range of densities from as low as 0.125 g/cc to 0.60 g/cc. The collapse strength of the glass bubble is directly related to the density, i.e., the higher the density, the higher the strength. For example, a glass bubble with a density of 0.125 g/cc is rated at 250 psi, whereas one with a density of 0.60 g/cc is rated at 18,000 psi. In order to minimize both the cost and the weight of the final product, the appropriate glass bubble is the one that is just strong enough to survive all of the manufacturing processes and the end use of the product.
[0029] Since microspheres are closed-cell, gas-filled particles, they are extremely good insulators. This characteristic is imparted to materials that contain microspheres, such as batts, boards and loose fill insulation products. As this invention demonstrates, thermal and acoustic insulation properties of batts, loose fill, facings, coatings or substrates can be improved by the addition of microspheres.
[0000] Physical Properties and Composition
[0030] The 3M Type K1 microspheres are manufactured from soda-lime- borosilicate glass and is the most economical 3 M microsphere product at about $0.40 per liter. TABLES 1 and 2, below, contain selected properties of Type K1 microspheres. Trapped within the microspheres are residual gases consisting of a 2:1 ratio of SO 2 and O 2 at an absolute pressure of about ⅓ atmosphere. Amorphous silica is added at 2% to 3% by weight to the microspheres to prevent caking if exposed to water. Caking of the bulk microspheres is caused by bridging of residual salts from the manufacturing process that have condensed on the surface of the microspheres. Amorphous silica, commonly used as a desiccant, has a very high specific surface area. The relatively small percentage of amorphous silica actually makes up the majority of the overall specific surface area and causes the bulk material to have a greater capacity for adsorbed water that must be dried out before or during the evacuation process. The effect on vacuum retention following exposure of microspheres and perlite to atmospheric conditions without a drying process prior to evacuation follows this section.
[0031] Alternative glass bubbles to the Type K1 microspheres are produced by 3M and also by Emerson & Cuming. Options include a floating process that skims off low density (weak) bubbles and removes a portion of the condensed salts. A coating of methacrylaic chromic chloride is then applied that minimizes water pickup. The overall specific surface area is about half that of the Type K1 microspheres, which may allow reduced bake-out requirements due to lower water adsorption capacity. The use of thicker-walled bubbles will benefit applications where microspheres are exposed to intense localized forces.
TABLE 1 Thermal performance of 3M Type K1 microspheres APPARENT COLD THERMAL COMPARATIVE VACUUM CONDUCTIVITY THERMAL PRESSURE (torr) (mW/m-K) PERFORMANCE 1 × 10 −3 0.7 7.0 times worse than MLI 1 × 10 −1 1.4 3.3 times better than perlite 760 22 1.5 times better than polyurethane
[0032] TABLE 2 Selected properties of 3M Type K1 microspheres True density 0.125 g/cc (7.8 lb/ft 3 ) Bulk density (@ 60% packing factor) 0.075 g/cc (4.7 lb/ft 3 ) Particle size (mean/range) 65/15-125 microns Isostatic crush strength 1.7 MPa (250 psi) Maximum operating temperature 600° C. Specific surface area 0.2 m 2 /cc of bulk volume
Fiberglass Thermal Insulation Batts and Boards
[0033] As shown in FIG. 2 , fiberglass thermal insulation batts 20 , or boards, such as duct boards, duct liners, and the like, can be manufactured using the materials provided by this invention. In a further embodiment, a batt 20 is manufactured with a fiberglass insulation layer 23 . The fiberglass insulation layer contains randomly distributed inorganic fibers such as glass fibers and contains about 5 weight percent microspheres 21 which can be randomly distributed among or on the inorganic or glass fibers 22 . Alternatively, the microspheres can be adhered to the top or bottom layer of the insulation layer 23 or mixed with an adhesive 27 , such as a resinous adhesive or bituminous mastic, used to apply the facing 26 to the fiberglass insulation layer 23 . The facing can be applied to one or both major surfaces of the insulation layer 23 , or can be applied to envelope the insulation layer 23 . Still further, the microspheres can be adhered or made integral with the facing 26 , such as by spraying, ink jet, printing or using a roll to apply an adhesive layer followed by applying the microspheres, or applying the microspheres as a slurry in such a process. When applied to the facing, a uniform covering of microspheres is desirable, but the weight percentage may be less than 5%, such as 0.5-3%, based upon the weight of the fibers or the facing 26 . Alternatively, the microspheres may be applied to the top surface of the fiberglass insulation 23 by use of a binder or adhesive, or concentrated in a layer or region near the surface or in the middle of the insulation layer 23 .
[0034] From the foregoing, it can be realized that this invention provides improved loose fill insulation, and batts and boards which include microspheres and/or for increasing the thermal insulation efficiency. The microspheres can be distributed within glass fibers, cellulosic particles, or adhered to facing layers or glass fibers, for example, to provide a great variety of more efficient thermal insulation products. The glass spheres of this invention also can assist in sound deadening and may assist in allowing loose fill insulation to flow through hoses used for blowing such products into attic cavities and wall spaces. Although various embodiments have been illustrated, this is for the purpose of describing, but not limiting the invention. Various modifications which will become apparent to one skilled in the art, are within the scope of this invention described in the attached claims. | The present invention provides thermal insulation products such as loose fill, bats and boards, such as duct boards and duct liner. The insulation products include randomly distributed inorganic fibers which are supplemented with at least about five weight percent microspheres, macrospheres, or both, preferably include hollow microspheres, which boost the insulation value of the fiberglass thermal insulation by at least about 0.5R. | 8 |
CROSS REFERENCE TO RELATED APPLICATION
This claims the benefit of U.S. Provisional Patent Application No. 60/503,609 filed Sep. 17, 2003.
FIELD OF THE INVENTION
This invention relates to shop made jigs and fixtures for positioning, aligning, guiding, and/or holding a workpiece on metalworking or woodworking machines during a cutting or shaping operation.
BACKGROUND OF THE INVENTION
U.S. Pat. Nos. 5,337,641, 5,617,909, and 5,768,966, the disclosures of which are hereby incorporated by reference, disclose improved jigs and fixtures for aligning, guiding, and/or holding a workpiece as it is worked, for example as it is cut, drilled, or routed. While the jigs and fixtures disclosed in U.S. Pat. Nos. 5,337,641, 5,617,909, and 5,768,966 represent a significant advance in the art, room still exists for improvements, particularly in the following respects, among others.
Stops are typically secured in a T-slot of a track There is always a slight variation in the extrusion which compromises the fit. There is no stop base that fits a variety of T-slots that can be located and be removed from the track between two adjacent stops. U.S. Pat. No. 5,337,641 teaches that the stop can be bolted in the down position but this requires threading a bolt through the stop into the base, which is tedious. None of the stops available are designed to allow cutting a miter with either the point in or the point out without any manipulation. Expensive stop systems have large and complicated accessories for supporting the point of a miter.
None of the stops available are designed to accommodate fences of various heights. There is no after market flip stop available with a magnifier lens. There is no after market flip stop that has a mechanism for adjusting the length of the stop so that it can be used with fences of different heights. None of the stops available are designed to accommodate a removable fixture by simply loosening one knob.
SUMMARY OF THE INVENTION
The invention provides an improved woodworking machinery jig and fixture system that has a stop with a half-dovetail surface. One or more T-slots may also be provided in the stop, and the stop may be a flip stop or a fixed stop. The half-dovetail surface can be clamped against a half-dovetail surface on the support, or against a flat surface, to secure the stop to the support.
In another aspect, the base of a stop has multiple through holes, any one of which can be used to mount a flip stop arm so as to vary the height of the arm or use a zero clearance fence.
In another aspect, a track for the system has a flange that helps locate the track along the rear corner of a wood fence. The flange also helps secure the track to the wood fence with fasteners through holes that can be drilled in the flange using a drill guide groove formed in the flange.
In another aspect, tension screws are provided in the stop and in the base for eliminating play between the hinge pin, the flip stop and the base.
In another aspect, the support has a ruler on its top surface that faces up. In this aspect, a lens may be received in a groove of the stop arm. The lens extends from the stop arm in position to view the ruler from above the support.
In another aspect, the projection on the bottom of the base that fits into a T-slot is bordered by an angled surface that cams against the corner of the T-slot to push the other edge of the projection against the other corner of the T-slot when the base is assembled to the track, to provide a snug fit between the base and the track.
A fixed stop with a half-dovetail surface, lens groove and accessory mounting slots can be mounted to a standard 2×4 that has a mating half-dovetail surface or a flat surface.
A miter fixture can be mounted to the accessory slots that has fingers with ends that provide surface support of the mitered end of a workpiece whether the workpiece is supported with its point toward or away from the working plane of the support.
These and other objects and advantages of the invention will be apparent from the detailed description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a perspective view of a curved flip stop and a heavy duty flip stop positioned on an L-shaped track as it is used on a miter saw.
FIG. 1B is an end view of the L-shaped track shown in FIG. 1A .
FIG. 2A is a perspective view of the curved flip stop and heavy duty flip stop positioned on the L-shaped track as it is used on a table saw miter gauge.
FIG. 2B is an end view of an L-shaped track and stops shown in FIG. 2A .
FIG. 3A is an end view of an L-shaped track and a flip stop as it is used on a miter saw.
FIG. 3B is a close up end view of the curved flip stop base positioned on the L-shaped track.
FIG. 4A is an end view of an L-shaped track and a heavy duty flip stop as it is used on a miter saw.
FIG. 4B is a detail end view of the heavy duty flip stop base positioned on the L-shaped track.
FIG. 5A is a perspective view of the curved flip stop and heavy duty flip stop positioned on the top track as it is used on a miter saw.
FIG. 5B is an end view of a top track shown in FIG. 5A showing a drill bit through the back mounting flange.
FIG. 5C is a detail view of FIG. 5B showing the drill guide indentation in the back mounting flange.
FIG. 6A is an end view of a top track and the flip stop as it is used on a miter saw, with screws through the back mounting flange of the top track securing the track to the upper edge of the auxiliary fence.
FIG. 6B is an detail view of FIG. 6A showing a screw through the back mounting flange of the top track securing it to the upper edge of the auxiliary fence.
FIG. 7A is a detail view of the top profile of the track which is common to both the L-shaped track shown in FIG. 1B and the top track shown in FIG. 5B .
FIG. 7B is a detail view of the L-shaped track shown in FIG. 1B .
FIG. 7C is a detail view of the top track as shown in FIG. 5B .
FIG. 8A is a perspective view of the curved flip stop and the top track as it is used on a miter saw fence.
FIG. 8B is an end elevation view of certain components of the system of FIG. 8A .
FIG. 8C is an exploded view of certain components of the system of FIG. 8A .
FIG. 8D is a detail view of the lens and stick-on tape of FIG. 8C .
FIG. 9A is a top view of FIG. 8A showing the flip stop mounted on the track.
FIG. 9B is a detail view of FIG. 9A showing the stick-on tape as it is seen through the lens (not showing magnification, although it would be magnified in actual practice).
FIG. 10A is a top view of the flip stop system showing the flip stop mounted on the top track.
FIG. 10B is an end view of the flip stop system showing the flip stop mounted on the top track.
FIG. 10C is a front view of the flip stop system showing the flip stop mounted on the top track.
FIG. 10D is a detail view of FIG. 10B showing the flip stop base engaging the T-slot of the top track.
FIG. 10E is an end view of the system showing the flip stop mounted on the top track with the stop arm in the standby position as it would be when resting on the workpiece.
FIG. 11A is a perspective view of the heavy duty flip stop and the top track.
FIG. 11B is an end elevation view of certain heavy duty flip stop components of the system of FIG. 11A .
FIG. 11D is an exploded view of certain components of the system of FIG. 11C .
FIG. 12A is a perspective view of FIG. 11A showing the heavy duty flip stop mounted on the track.
FIG. 12B is a detail view of FIG. 12A showing the stick-on tape as it is seen through the lens (not showing magnification).
FIG. 13A is a top view of the system showing the heavy duty flip stop mounted on the top track.
FIG. 13B is an end view of the system showing the heavy duty flip stop mounted on the top track.
FIG. 13C is a front view of the system showing the heavy duty flip stop mounted on the top track.
FIG. 14 is an end view of the heavy duty flip stop base mounted on a board showing that the height of the flip stop arm changes when the hole in the flip stop arm extrusion is aligned with different holes in the heavy duty flip stop base.
FIG. 15 is a side view of the heavy duty flip stop components mounted on the L-shaped track. The arm extrusion is aligned with the front hole of the base allowing space between the arm and the track for attaching a zero clearance board 17 .
FIG. 16 is a side view scale drawing of the flip stop arm shown on a ¼″ grid.
FIG. 17 is a side view scale drawing of the flip stop arm shown inside a 6 inch circle.
FIG. 18A is a perspective view of a fixed stop positioned on a top track as it is used on a miter saw.
FIG. 18B is a detail view of FIG. 1A showing the stick-on tape and the lens.
FIG. 19A is an end view of the fixed stop positioned on the L-shaped track.
FIG. 19B is a detail view of FIG. 19A showing a half-dovetail on the fixed stop positioned against the half-dovetail on the front of the L-shaped track.
FIG. 20A is an exploded perspective view of the fixed stop.
FIG. 20B is a perspective view of the lens.
FIG. 20C is a top view of the fixed stop.
FIG. 20D is a side view of the fixed stop.
FIG. 20E is a front view of the fixed stop.
FIG. 21 is a detail view of the top profile of the track which is common to both the L-shaped track and the top track showing the dovetail required for the fixed stop and the heavy duty flip stop.
FIG. 22A shows a dovetail router bit cutting a half-dovetail shape in a board.
FIG. 22B is an end view of the fixed stop aligned with the half-dovetail shape cut in a ¾″ wide board.
FIG. 22C is an end view showing the heavy duty flip stop base aligned with the half-dovetail shape cut in a 1½″ board such as a 2 by 4.
FIG. 23A is an end view of the L-shaped track shown with a plastic bumper on the bottom which makes the total height 2¾″.
FIG. 23B is an end view of the top track shown screwed to a 2⅜″ by ¾″ board making the total height 2¾″.
FIG. 23C is an end view of the ¾″ board shown in FIG. 22B .
FIG. 23D is an end view of the board shown in FIG. 22C shown with an optional piece of mini-track in the back corner which would allow the use of the flip stop.
FIG. 24A is a perspective view of the flip stop positioned on the top track as it is used on a miter saw, with a miter fixture attached to the flip stop.
FIG. 24B is a detail view of the flip stop and miter fixture shown in FIG. 24A .
FIG. 24C is a top view of the flip stop and miter fixture as shown in FIG. 24A .
FIG. 24D is a top view of the flip stop and miter fixture as shown in FIG. 24A with the point of the mitered board against the fence.
FIG. 25A is an end view of the flip stop and miter fixture as shown in FIG. 24A .
FIG. 25B is a detail view of the flip stop and miter fixture as shown in FIG. 25A .
FIG. 26A is an end view of the fixed stop and miter fixture.
FIG. 26B is a detail view of the fixed stop and miter fixture as shown in FIG. 26A .
FIG. 26C is a top view of the fixed stop and miter fixture as shown in FIG. 26B with the point of the mitered board away from the fence.
FIG. 27A is a perspective view of the miter fixture.
FIG. 27B is a top view of the miter fixture.
FIG. 27C is an end view of the miter fixture.
FIG. 27D is a front view of the miter fixture.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1A illustrates a track of the invention 46 , shown together with a flip stop 54 and a heavy duty flip stop 56 which are pivotable about the axis of a bolt 26 as disclosed in U.S. Pat. Nos. 5,337,641 and 5,768,966, the entire disclosures of which are hereby incorporated by reference for their teachings of how to make and use jigs and fixtures. The drawing is a perspective view of two flip stops 54 with a heavy duty flip stop 56 positioned between them. The stops are positioned on the L-shaped track 46 as it is used on a miter saw 82 . The work piece 78 rests on the miter saw table auxiliary table 76 with one edge against the miter saw fence 29 and miter saw auxiliary fence 35 . A wood shop-made extension table 76 is the same height as the miter saw table 31 so the work piece 80 lays flat on both tables. The extension table 76 is supported by two legs 140 . A wood auxiliary fence 35 is mounted on the back of the wood shop made extension table 76 . The L-shaped track 46 is an L-shaped extrusion with multiple T-slots 210 , 212 , 216 , 218 which is attached to the front side of the wood auxiliary fence 35 . To cut a piece accurately to width the end of the work piece 78 is pressed against the stop arm 10 ( FIG. 2A ) while the other end is cut with the blade 84 . When the flip stop assembly 54 or the heavy duty flip stop assembly 56 is not in use the flip stop arm 10 can rest on top of the work piece 78 in the stand by position 62 ( FIG. 2B ).
FIG. 1B is an end view of the L-shaped track 46 shown in FIG. 1A . The back top T-slot 210 is the mechanism for attaching the flip stop assembly 54 . This track is similar to the L-shaped track of the U.S. Pat. No. 5,768,966 with two new improvement features. One improvement is that the front top T-slot of the U.S. Pat. No. 5,768,966 has been replaced by a half-dovetail 48 which is the mechanism used to attach accessories to the top of the track such as the heavy duty flip stop 56 shown in FIG. 1A and the fixed stop 71 show in FIGS. 18A , 18 B, 19 A, 20 A, 20 B, 20 C, 20 D. The half-dovetail 48 has a 9 degree angle which is a standard router bit angle for making a standard dovetail joint. There is also a 5 degree angle 66 at the back of the track which helps to keep the accessories such as the heavy duty flip stop 56 and the fixed stop 71 from rotating upward. In other words, it biases the stop downwardly when the thumb screw 20 or other fastener that fixes the stop to the track is tightened against it ( FIG. 4B ).
Also replacing the top front T-slot of the U.S. Pat. No. 5,768,966 is a 0.520″ indentation for a stick-on tape 64 on the front of the L-shaped track 46 . The stick-on tape 50 on the top of the L-shaped track 46 is better for use on the miter gauge because the user does not have to lean over the miter gauge to see the measurement. It also avoids the problem of parallax when viewing the tape against the edge of the stop.
FIG. 2A is a perspective view of the flip stop 54 and heavy duty flip stop 56 positioned on the L-shaped track 46 as it is used on a table saw miter gauge 89 . The flip stop assembly 54 and the heavy duty flip stop assembly 56 is used to crosscut boards to length by measuring the distance between the end of the board 78 and the saw blade 84 . The end of the board is pressed against the stop arm 10 while the other end is cut with the blade 84 . When the flip stop assembly 54 or the heavy duty flip stop assembly 56 is not in use the flip stop arm 10 can rest on top of the work piece 78 in the standby position 62 . The flip stop assembly 54 is slideable along the length of a track by loosening knob 20 to loosen the head of the bolt 26 (not shown) which slides in the top T-slots 64 of the track 46 . The exact distance between the saw blade 84 and a stop can be measured with the stick-on-tape 50 attached to the L-shaped track 46 . The flip stop arm 10 of the flip stop assembly 54 rests on the top of the workpiece 78 in the standby position 62 .
FIG. 2B is an end view of the L-shaped track and stops shown in FIG. 2A , illustrating the standby position 62 and also the work position in which the arm 10 is lowered so that the end of the workpiece 78 can engage it.
FIG. 3A is an end view of a L-shaped track and a flip stop as it is used with a miter saw and FIG. 3B is a detail end view of the flip stop base 30 , preferably extruded aluminum, positioned on the L-shaped track 46 , also preferably extruded aluminum. The flip stop assembly 54 is attached to the L-shaped track 46 T-slot 112 with the bolt 26 which is locked in place by the knob 20 which is shown in the exploded view in FIG. 8C . The base 30 has a bottom protrusion 107 which extends laterally along the bottom side of the base 30 and fits into the T-slots 68 of the track to help guide the base and prevent it from rotating relative to the track. The protrusion 107 has a downwardly facing surface that is bordered at its rear edge by an angled surface 90 ( FIGS. 8B and 10D ) and at its front edge by a right angle step 67 . The angled surface cams against the rear edge of the T-slot 68 to push the step 67 against the opposite side of the T-slot 68 when the thumb nut 20 ( FIG. 3B ) is tightened, to eliminate any clearance between the T-slot and the protrusion 107 . The T-slot 68 is designed to take the head of a ¼-20 bolt 26 as is standard.
FIG. 4A illustrates the heavy duty flip stop 56 with the miter saw and FIG. 4B is a detail end view of the heavy duty flip stop base 60 positioned on the L-shaped track 46 . The heavy duty flip stop base 60 is preferably an extruded aluminum block with four 5/16″ holes 13 and two downward protrusions 108 and 109 . The protrusion 108 at the front is flush with the front of the track extrusion. The inside of the front downward protrusion 108 is a 9 degree half-dovetail surface 48 . The 9 degree half-dovetail 48 on the inside of the front downward protrusion 108 corresponds to the same angle at the front of the L-shaped track 46 . The heavy duty flip stop base 60 is secured to the L-shaped track 46 with swivel head stud 52 with a knob 20 secured to the end of it, the stud 52 being threaded into a hole in the protrusion 109 . The rotating end of the swivel head stud 52 presses against the 5 degree angled surface 66 at the back of the top track extrusion 58 , which pulls the base 60 rearwardly and downwardly for a stable connection with the track. As the knob 20 is rotated, the 9 degree half-dovetail 48 on the L-shaped track 46 engages with the half-dovetail surface 48 on the heavy duty flip stop base 60 . This design allows the heavy duty flip stop base 60 to easily be loosened from the track and lifted off the track, and re-assembled to the track from above, for example inside of a stop that is already assembled to the track. This solves the problem of mounting the flip stop 54 to the T-slot 68 which requires that it be slid off the end of the track rather than simply loosening a knob and then lifting it off the track.
FIG. 5A illustrates a top track 58 (preferably extruded aluminum) applied to a miter saw 82 and FIG. 5B is an end view of the top track 58 shown in FIG. 5A showing a drill bit through the back mounting flange 69 . An indentation line or groove 70 is extruded into the back mounting flange 69 that acts as a drill guide to make it easy to drill holes in the extrusion 110 along a straight line so it can be screwed to the edge of the wood auxiliary fence 35 , along the rear corner of the fence 35 . The back mounting flange 69 eliminates the need for aligning the track on top of the fence 35 as the rear corner bearing against the bottom of the track 58 and the flange 69 automatically aligns it. The 9 degree half-dovetail 48 on the front of the track 58 and the 5 degree angled surface 66 at the back of the track allow the use of quick release stops such as the heavy duty flip stop assembly 56 and the fixed stop 71 ( FIG. 18B ).
FIG. 7A is a detail view of the top profile of the track which is common to both the L-shaped track shown in FIG. 1B and the top track shown in 5 B. Both of the tracks share the 9 degree half-dovetail 48 at the front of the track, indentation for a stick-on tape 64 , T-slot 68 and the 5 degree angled back 66 , which may also be considered a half-dovetail surface, although not at the standard 9 degrees that is uniform for woodworking dovetails and a standard size for a woodworking dovetail router bit.
FIG. 8A is a perspective view of the top track 58 screwed to wood fence 35 to make a woodworking support of the invention and FIG. 8B is an end elevation view of certain components of the system of FIG. 8A , including the three custom made extrusions for the track 58 and the stop assembly 54 . The stop arm 10 (preferably extruded aluminum) is generally T-shaped with curved bottom 14 that has a 3 inch radius 81 ( FIG. 17 ) that changes gradually to a curve 83 with a 2.25 inch radius 87 having its center below the center of the radius 81 , so that the end 38 will be high enough to fit into the lowest T-slot 216 in the front of the L-shaped track 46 , so as to penetrate the working plane of the track so as to stop a pointed workpiece with the point adjacent to the working plane. The bottom curves 14 and 83 curve away from the machine table so that the arm 10 can be easily lifted by sliding a workpiece under the surfaces 14 and 83 .
A straight support arm 12 that is angled at approximately 35 degrees intersects near the middle of the curved bottom or shoe at a point so that the end of the surface 14 is high enough to permit sliding a thick board (e.g., 1.5 inch thick or more) while providing a shallow angle between the surface 14 and the top front edge of the board so that the arm 10 will be easily lifted when the board is slid under it. The arm 10 is also preferably made of relatively thin sections to keep the weight down, which also makes lifting easier.
Extending from the curved bottom 83 is a small finger 16 that is parallel to the straight support arm 12 . The ¼″ laterally extending space 21 between the straight support arm 12 and the finger 16 is fixture mounting slot 21 , which extends parallel to the working plane of the woodworking support. A fixture can be mounted simply by sliding a ¼″ bolt that mounts the fixture in the fixture mounting slot 21 (See FIGS. 24A-D ). A transparent plastic magnifying lens 34 slides into the lens opening slot 18 and is secured in place by the lens locking screw 40 that is secured into a threaded hole 74 . This mechanism allows the position of the lens to be fine tuned for accuracy.
The 5/16″ hole 13 in the curved flip arm extrusion 10 is the standard plus or minus 0.015″ accuracy of an aluminum extrusion. Usually holes in extruded aluminum are designed to be oversized so that when the extrusion die wears from use the hole in the extrusion is still within tolerance. Standard bolts vary in size. The lack of a tight fit between the hole and the bolt allows the flip stop arm to rotate laterally or transversely slightly compromising accuracy. To remove any sloppiness between the curved flip arm extrusion 10 and the bolt a threaded hole 74 is made in the extrusion and an arm tension set screw 22 (steel or plastic) is used to tighten against the bolt in the 5/16″ hole 13 in the curved flip arm extrusion 10 , to eliminate any clearance.
To remove any sloppiness between the base extrusion 30 and the bolt a threaded hole 74 is made in the back of the base extrusion 30 . A base tension screw 42 is used to tighten the bolt in the 5/16″ hole 13 in the base extrusion 30 . The preferable material for the base tension screw 42 is nylon which is quite lubricious when the bolt rotates against it, since the bolt 42 turns as it acts like a hinge pin when the flip stop is raised and lowered. This tightening mechanism does not require tools and is easily adjusted with the operator's fingers.
FIG. 8C is an exploded view of certain components of the system of FIG. 8A . FIG. 8D is a detail view of the lens and stick-on tape of FIG. 8C . As shown in FIG. 8A the lens is designed to be positioned closely to the stick-on tape 50 , above it. The lens 34 is clear plastic and magnifies the ruler. Located on the bottom of the lens is a red curser line 86 . The red color allows the viewer to instantly identify the reference line. The red curser line 86 is usually positioned about ¼″ away from the edge of the stop arm which means that the stick-on tape 50 is offset ¼″. The lens locking screw 40 mechanism allows for the fine adjustment of the red curser line 86 .
No known aftermarket flip stop design has a lens. In the original U.S. Pat. No. 5,337,641, the stop was L-shaped and the stick-on tape 50 was adjustable. The measurement was read off the edge of the stop using the cut edge of the extrusion as the reference point. Because the back of the stop is close to the stick-on tape 50 , there was problem fine tuning the set up because only half of the ruler was visible because the other half is covered by the stop arm. The problem is solved by locating the indentation 64 for a stick-on tape 50 in the top of the front corner of the top track 58 and the L-shaped track 46 as seen in FIGS. 9A and 1B respectively and by locating the lens 34 directly above the stick-on tape 50 as shown in FIG. 9B . The measurement is readily visible as the viewer can see both sides of the desired setting on the stick-on tape 50 versus only one side which is the case in the U.S. Pat. No. 5,337,641. The measurement setting is easily seen for either the table saw user, who views it from the back of the track, or the miter and radial saw user who views the tape from the front.
FIG. 11A is a perspective view of the heavy duty flip stop and the top track. The bottom curve 14 of the curved flip stop arm 10 is wide enough to engage the end of a mitered board that is ¾″ by 2¼″ with the point of the miter opposite the fence 35 . Positioning the point of the miter away from the fence is ideal because the force of the blade cutting the miter on the opposite end applies a uniform pressure against the stop guaranteeing that all of the work pieces will be cut at a uniform length. If the piece to be mitered is wider than 2¼″ a fixture can be attached to the curved stop arm 10 by using the fixture mounting slot 21 . FIG. 11B is an end elevation view of certain heavy duty flip stop components of the system of FIG. 11A .
FIG. 11C is an exploded view of certain components of the system of FIG. 11A . The curved flip arm extrusion 10 is the same for both the flip stop assembly 54 and the heavy duty flip stop assembly 56 . A feature that the heavy duty flip stop assembly 56 has is the ability to be configured so that it can be used on machine fences of different height as shown in FIG. 14 . By changing the hole 13 that the arm is bolted through the height of the curved flip arm extrusion 10 in front of the woodworking support changes. FIG. 15 shows that locating the bolt in the front hole 13 allows enough room between the L-shaped track 46 and the point 38 at the back of the flip arm 38 so that a zero clearance fence 17 (a board that can be cut into by the blade to support the workpiece right next to the cut) can be added to the front of the track.
FIG. 17 is an end elevation view of the flip stop arm 10 showing a 6 inch diameter circle 75 that the flip stop arm 10 fits inside of. The front of the flip stop arm 14 has the 3 inch radius 81 of the 6 inch diameter circle 75 . The curve at the bottom of the flip arm 83 is the size of a smaller 4.5 inch diameter circle 77 which has a 2.25 inch radius 87 . A straight arm 12 angles toward the bottom of the stop at approximately a 35 degree angle 79 (relative to horizontal, with the arm supported with its upper leg that extends from arm 12 to attachment hole 13 horizontal) and attaches to the bottom of the stop arm 10 approximately where the 6 inch circle 75 and the 4.5 inch circle 77 intersect with each other.
FIG. 18A is a perspective view of the fixed stop positioned on the top track as it is used on a miter saw. FIG. 18B is a detail view of FIG. 18A showing the stick-on tape 50 and the lens 34 . FIG. 19A is an end view of the fixed stop 71 positioned on the L-shaped track showing how the 9 degree half-dovetail 48 on the fixed stop and L-shaped track 46 mate with each other. The fixed stop 71 is locked to the L-shaped track 46 by the threaded stud knob 90 at the back of the stop. This is similar to the mechanism used by the heavy duty flip stop assembly 56 . The fixed stop 71 is made from a one piece aluminum extrusion 73 that closely follows the profile of the L-shaped track 46 as shown in FIG. 19A . The extension leg 111 , which is parallel to the machine table top extends the front of the fixed stop 71 . This extension leg 111 allows the fixed stop 71 to be used with wide mitered boards. Four fingers 16 on the extension leg 111 create two fixture mounting slots 21 . Jigs and fixtures are easily attached to the fixed stop 71 with a ¼″ bolt located in the fixture mounting slots 21 .
The 9 degree half-dovetail 48 design allows for a number of fence options besides the L-shaped track 46 and the top track 58 . FIG. 22A shows a 9 degree dovetail router bit 91 making a 9 degree half-dovetail cutout 93 in a wood fence 19 . FIG. 22B is an end view of the fixed stop 71 positioned on the wood fence 19 showing how the 9 degree half-dovetail 48 on the fixed stop 71 and a 9 degree half-dovetail cutout 93 in a wood fence 19 mate with each other (screw 90 not shown). Because the fixed stop 71 attaches to a fence by clamping pressure between the 9 degree half-dovetail and the threaded stud knob 90 it can be attached to materials of various widths. FIG. 22C shows the fixed stop 71 positioned on a wood 2 by 4 fence 19 which is an inch and a half thick. Construction material that is an inch and a half thick is common on building sights where contractors often build miter saw table extensions out of it. The fixed stop 71 would be useful for a builder on a job sight where multiple pieces of the same length are often cut.
FIG. 24A is a perspective view of the stop 54 positioned on the L-shaped track 46 as it is used on a miter saw 82 . The mitered work piece 80 rests on the miter saw table auxiliary table 76 with one edge against the miter saw fence 29 and the other end against miter saw auxiliary fence 35 . A wood shop made extension table 76 is the same height as the miter saw table 31 so the mitered work piece 80 lays flat on both tables. Attached to the flip stop 54 is a miter fixture 11 which supports the 45 degree tip 99 of the mitered work piece 80 in surface contact, as opposed to line contact. Positioning the 45 degree point 99 of the mitered work piece 80 away from the fence is ideal because the force of the blade cutting the miter on the opposite end applies a uniform pressure against the stop guaranteeing that all of the mitered work pieces 80 will be cut at a uniform length. FIG. 24B is a detail view of FIG. 24A showing that the miter fixture 11 is comb-shaped with multiple fingers each with a 90 degree pointed tip 95 and having a T-slot 68 running along the side opposite from the fingers, the T-slot housing a bolt (not shown) that attaches it to the flip stop 54 with thumb nut 20 . FIG. 24C is a top detail view of FIG. 24B showing how the 45 degree point 99 of the mitered work piece 80 is supported by two of the fingers each with a 90 degree pointed tip 95 .
The miter fixture 11 is secured to the flip stop by a bolt that is tightened in place with a plastic thumb nut knob 20 . Because the bolt slides in the T-slot, the fingers with a 90 degree pointed tip 95 can be moved to accommodate boards of different widths. The 45 degree point 99 of the mitered work piece 80 is fragile and is easily damaged. By positioning the 45 degree point 99 between the fingers each with a 90 degree pointed tip 95 that supports the tip 99 in surface contact, the point 99 is protected from damage, and the edge of the mitered work piece 80 is secured against the fence 46 .
The 45 degree point 99 of the mitered corner 115 lines up with the 1 inch mark 117 on the miter fixture 11 . The 45 degree point 99 of the mitered corner 115 is located one inch from the edge of the stop so the stick-on tape 50 can be easily used to measure the length of the work piece 80 .
FIG. 24D is a detail view showing the miter fixture 11 with the 45 degree point 99 of the mitered work piece 80 reversed so that it is secured against the working plane of the fence 46 . Surfaces 113 on the inner end of the fixture 11 and on the inner finger, which is shorter than the other fingers, are at 45 degrees, so that together with the finger adjacent to the inner finger the fingers present three surfaces in a 45 degree plane to support the mitered point 99 in surface contact.
FIG. 25B is an end elevation of FIG. 24A . FIG. 26C is a top view of FIG. 26A and FIG. 26B showing the miter fixture 11 secured to the solid stop 71 with two bolts 26 located in the fixture mounting slots 21 . FIG. 26C is a top view of FIG. 26A and FIG. 26B showing the miter fixture 11 secured to the solid stop 71 with two bolts 26 located in the fixture mounting slots 21 . FIG. 27A is an perspective view of the miter fixture 11 . FIG. 27B is a top view of the miter fixture 11 extruded aluminum shape. FIG. 27C is a front view of the miter fixture 11 showing the T-slot 68 machined in the side for the bolt head for securing it to the stop. FIG. 27D is an end view of the miter fixture 11 . | A woodworking machinery jig and fixture system has a stop with a half-dovetail surface and can be provided with one or more T-slots. The half-dovetail surface can be clamped against a half-dovetail surface on the support, or against a flat surface. In one of the stops, the base has multiple through holes, any one of which can be used to mount a flip stop arm so as to vary the height of the arm or use a zero clearance fence. A track for the system has a flange that helps locate the track along the rear corner of a wood fence and also helps secure the track to the wood fence with fasteners through holes that can be drilled in the flange using a drill guide groove formed in the flange. Tension screws are provided in the stop and in the base for eliminating play between the hinge pin, the flip stop and the base. A lens is received in a groove of the stop arm and extends therefrom in position to view a ruler that is mounted on top of the support, facing up. The projection on the bottom of the base that fits into a T-slot is bordered by an angled surface that cams against the corner of the T-slot to push the other edge of the projection against the other corner of the T-slot when the base is assembled to the track, to provide a snug fit between the base and the track. The stops are provided with accessory mounting slots. A fixed stop with a half-dovetail surface, lens groove and accessory mounting slots can be mounted to a standard 2×4 that has a mating half-dovetail surface or a flat surface. A miter fixture can be mounted to the accessory slots that has fingers with ends that provide surface support of the mitered end of a workpiece whether the workpiece is supported with its point toward or away from the working plane of the support. | 8 |
CROSS-REFERENCE TO RELATED APPLICATION
The present application claims priority to U.S. Provisional Application No. 60/905,640, filed Mar. 8, 2007, the entire contents of which are incorporated herein by reference.
TECHNICAL FIELD
The present invention is directed to user interfaces for medical perfusion systems that provide oxygenation, filtering, and recirculation of blood in connection with various medical procedures. In particular, the present invention is directed to user interfaces for use with blood pumps that assist in managing alarms commonly encountered during cardiopulmonary bypass surgeries.
BACKGROUND
Conventional perfusion systems are used to oxygenate, filter, and/or recirculate the blood of a patient during a medical procedure such as during cardiopulmonary surgeries. Such perfusion systems include a fluid conduit that removes blood from the patient during the medical procedure, a separate fluid conduit that returns blood to the patient, one or more blood pumps that pump blood through the conduits, and a plurality of sensing devices, such as flow sensors and/or level sensors associated with blood pumps. The perfusion system may also include air embolus sensors, temperature sensors, flow occluders, etc.
Perfusion systems require a perfusionist operating the perfusion system to closely monitor many different parameters, and manually adjust the speeds of the various pumps in the system on a frequent basis to keep the various parameters in balance and within safe and desired limits. Alarm conditions, when they occur, require immediate, manual action by the perfusionist. Accordingly, mechanisms are needed to help the perfusionist safely, accurately, and quickly manage such alarm conditions control the perfusion system with greater safety, accuracy and speed.
SUMMARY
The present invention provides unique user interface designs that annunciates an alarm condition, describes the nature of the alarm with indicia such as text, and provides the user with options concerning how to best manage the alarm condition. Clear visual indicators are provided to assist in managing the device and handling the alarm condition. For example, visual indicators may use the colors red and yellow to guide the user to quickly manage the machine interface during the management of alarms.
In an aspect of the present invention, a method of managing an alarm condition of a perfusion system during cardiopulmonary bypass surgery is provided. The method comprises the steps of providing a user interface for the perfusion system comprising a touch screen, displaying a color coded alarm condition on the touch screen, and displaying a color coded alarm management icon on the touch screen for managing the displayed color coded alarm condition.
In another aspect of the present invention, a user interface for managing an alarm condition of a perfusion system during cardiopulmonary bypass surgery is provided. The user interface comprises a touch screen, a color coded alarm condition indicator displayed on the touch screen comprising a color coded graphical portion and a color coded textual message portion for providing information related to an alarm condition, one or more color-coded alarm management icons displayed on the display screen for managing the alarm condition based on the color coded alarm condition indicator.
BRIEF DESCRIPTION OF THE DRAWINGS
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate several aspects of the invention and together with description of the embodiments serve to explain the principles of the invention. A brief description of the drawings is as follows:
FIG. 1 is a perspective view of an exemplary pump console according to an aspect of the present invention showing a user interface and a base unit.
FIG. 2 is a schematic block diagram of the pump console of FIG. 1 .
FIG. 3 is a schematic diagram of a safety module that can be used with the base unit according to an aspect of the present invention.
FIG. 4 is an exemplary main screen of a user interface in accordance with the present invention.
FIG. 5 is an exemplary settings screen of a user interface in accordance with the present invention.
FIG. 6 illustrates a user interface in accordance with the present invention in a normal state of operation without an indication of an alert or alarm condition.
FIG. 7 illustrates a user interface in accordance with the present invention showing an alert condition identified by a color coded status bar and a color coded message box and showing color coded information for managing the alert condition.
FIG. 8 illustrates a user interface in accordance with the present invention showing an alarm condition identified by a color-coded status bar and a color coded message box and showing color coded information for managing the alarm condition.
FIGS. 9 and 10 illustrate a user interface in accordance with the present invention showing another alarm condition identified by a color-coded status bar and a color coded message box and showing color coded information for managing the alarm condition.
DETAILED DESCRIPTION
FIG. 1 is an exemplary perspective view and FIG. 2 is a schematic block diagram of a pump console 10 in accordance with the present invention. As shown, the pump console 10 comprises two primary components, including a base unit 12 and a user interface 14 that can communicate via communication link 13 . The pump console 10 may comprise a stand-alone centrifugal pump control system or it may comprise an add-on module to commercially available heart-lung machines or blood pumps. The base unit 12 provides functionality for controlling pump speed, monitoring flow/pressure, battery backup, and providing communications to the user interface 14 , for example. The user interface 14 includes a display 16 and user controls for operating and/or interfacing with the user interface 14 . Display 16 preferably comprises a touch display/screen or other display device that allows input to be provided to an icon displayed on the screen by touching, contacting, or otherwise identifying the icon. Components of the base unit 12 and/or user interface 14 preferably comprise microcontrollers that provide communications through an asynchronous serial interface (RS232) or suitable communications protocol.
As illustrated, the base unit 12 comprises plural functional modules including a system controller module 18 , motion/pressure module 20 , flow module 22 , and safety module 24 . The safety module 24 is schematically shown in further detail in FIG. 3 and preferably comprises a safety module bus interface 41 , system bus interface 26 , watchdog timer 28 , and motor controller servo interface 30 , which motor controller includes speed control input 39 and speed control output 37 . The safety module 24 also preferably includes interfaces to safety systems such as a bubble detector interface 32 , level sensor interface(s) 34 , and an arterial clamp interface 36 , which comprise inputs 31 , 33 , and 35 , respectively. The bubble detector interface 32 provides an alarm to the operator when it detects the presence of bubbles or gross air in the tubing of the flow circuit. The level sensor interface(s) 34 provide an alarm or alert to the operator preferably based upon two separate level detectors placed on the patient blood reservoir. The arterial clamp interface 36 provides automated arterial line occlusion in the event of retrograde flow as determined by operator setup.
FIG. 4 illustrates an exemplary main screen 38 for the user interface 14 in accordance with the present invention. In use, main screen 38 , as well as any other screen or screens of the user interface 14 , are displayed on display 16 and are preferably capable of receiving touch inputs such as with a finger or appropriate stylus. Main screen 38 is preferably configured to display information related to operating parameters such as alert and alarm status, blood flow and pump speed, line pressure, user configurable timers, safety systems (if installed), and power status, for example.
An exemplary settings screen 40 of the user interface 14 is shown in FIG. 5 . Settings screen 40 provides the capability to set parameters such as blood flow range and upper/lower alert/alarm limits, target blood flow rate with cardiac index and height/weight calculator, pressure transducer zeroing and upper/lower alert/alarm limits, three timer presets, and screen backlight intensity, for example.
User interface 14 preferably comprises a system status indicator 42 positioned at the top of a desired user interface screen such as those shown in FIGS. 3 , 8 , 22 , 26 , and 27 . System status indicator 42 preferably comprises an optional color-coded status bar 44 and a color-coded system status message box 46 . The color coded status bar 44 preferably uses three colored light bars 48 , 50 , and 52 that are associated with the operation status of the system and provide a visual cue for assessing system status when lit. Preferably first, second, and third colors such as green, yellow, and red are used for the light bars 48 , 50 , and 52 , respectively, however any desired colors can be used. The status bar 44 and message box 46 , as shown, are preferably positioned at the top of a screen but can be positioned anywhere on a screen as desired. The intensity of the light bars 48 , 50 , and 52 as well as any other color coded icon of the user interface can be varied to provide additional visual information such as the intensity of a condition, alert, or alarm.
The user interface 14 preferably uses distinct alarm/alert sounds or audible signals to inform the user when alarm or alert conditions are present. An alarm sound preferably comprises a repeating sequence of long and short beeps. An alarm condition is more serious than an alert condition and requires a corrective action by the user. An alert sound preferably comprises a steady paced beep.
In FIG. 6 , user interface 14 is illustrated in a state of normal operation. That is, no alert or alarm conditions are active. As shown, illumination of the green light bar 48 of the system status indicator 42 indicates all systems are functioning normally and (as applicable) safety devices are enabled. In this normal state, light bars 50 and 52 are unlit or colorless. Accordingly, no action is indicated or required to keep the system functioning normally in such system state. Additionally, the system status message box 46 displays information about the highest priority alert or alarm. The user interface 14 is preferably pre-programmed so that alerts or alarms are prioritized. Preferably, the highest priority alert or alarm is displayed and when that alert or alarm is corrected the next highest alert or alarm is displayed, if any. In the normal state of operation and as illustrated in FIG. 6 , the system status message box 46 is preferably displayed without a corresponding green color code although the system status message box 46 may be color coded if desired. That is, message box 46 can be white or grey, for example, or match the background color of other screen elements as desired.
In FIG. 7 , user interface 14 is illustrated in a state of malfunction and with an indication of an alert. An alert indicates a condition other than normal operation and that requires attention by an operator. In this case, the state of malfunction is a flow-system malfunction. An alert notification preferably includes a steady paced beep or other audible signal and illumination of the yellow light bar 50 of the system status indicator 42 , as illustrated. Light bars 48 and 52 are preferably unlit or colorless, as illustrated. Additionally, the system status message box 46 displays information about the alert and is preferably displayed with a corresponding yellow color code. The system is preferably configured so an alert or alarm condition is preferably temporarily silenced by pressing the mute button 55 , but will preferably resume after 60 seconds if the condition is not resolved or if a new alert or alarm condition occurs. The mute button 55 preferably only appears when an alert or alarm condition exists and may be color-coded if desired.
The illustrated alert condition of FIG. 7 is a flow system malfunction but any desired condition can be characterized as an alert condition. Exemplary alert conditions include those related to a low reservoir, flow rate, pressure, and clamp air pressure. An alert condition indicates a problem and typically requires a corrective action by the user. The system status message box 46 identifies the alert condition and also provides information regarding how to manage the alert condition using the words “Press Service (Wrench) Button To Acknowledge.” The alert condition can be managed by pressing the service wrench button 54 , which is also preferably color-coded, yellow with the alert condition color. Pressing the service wrench button 54 displays a log of internal system errors. An alert condition may display additional unique yellow icons to aid the user in identifying the source of the alert condition. The user interface 14 thus provides an indication of the alert condition with the yellow light bar 50 and yellow coded system status message box 46 , indication of the particular alert condition and how to manage the alert condition in the system status message box 46 , and an indication of where to manage the alert condition on the touch screen with the color coded icon (e.g., service wrench button 54 ). Any combination of colors, color intensity, sounds, and text can be used in accordance with the present invention to identify an alert condition.
In FIG. 8 , user interface 14 is illustrated in a state of alarm and with an indication of such alarm. An alarm condition is more serious than an alert condition and requires an immediate corrective action by the user. Exemplary alarm conditions relate to communications errors, bubbles in the flow circuit, and motor or pump failure. An alarm notification preferably includes a repeating sequence of long and short beeps and illumination of the red light bar 52 of the system status indicator 42 , as illustrated. Light bars 48 and 50 are preferably unlit or colorless, as illustrated. Additionally, the system status message box 46 displays information about the alarm and is preferably displayed with a corresponding red color code. The illustrated alarm of FIG. 8 is related to detection of a bubble in the flow circuit, but any desired condition of the perfusion system can be characterized as an alarm condition. Accordingly the system status message box 46 identifies the condition and also provides information regarding how to manage the alarm with the words “Press Bubble Detector Button To Acknowledge.” The alarm condition can be managed by pressing the service bubble detector button 56 , which is also preferably color coded red with the alarm color. An alarm may display additional unique red icons to aid the user in identifying the source of the alarm condition. Accordingly, like the alert condition described above relative to FIG. 7 , the user interface 14 provides an indication of the alarm with the red light bar 52 and red coded system status message box 46 , indication of the particular condition and how to manage the condition in the system status message box 46 , and an indication of where to manage the condition on the touch screen with the color coded icon. Any combination of colors, color intensity, sounds, and text can be used in accordance with the present invention to identify an alarm condition.
In FIGS. 9 and 10 another exemplary feature of the user interface 14 is illustrated. FIG. 9 shows user interface 14 in a state of alarm and with an indication of such alarm provided by illumination of the red light bar 52 of the system status indicator 42 . In accordance with the present invention, the system status message box 46 displays information about the alarm and is preferably displayed with a corresponding red color code. In particular, the illustrated alarm of FIG. 26 is related to the state of a clamp system and indicates that the clamp is closed. Accordingly, the system status message box 46 identifies the condition and also provides information regarding how to manage the alarm by pressing the open clamp button 58 which is also preferably color coded red with the alarm color. Also illustrated is a clamp status button 60 color-coded red and which is used to configure the clamp system. In FIG. 10 , a submenu 62 of the open clamp button 58 is shown which is activated and displayed when the open clamp button 58 is pushed and which can be used to provide verification of the action of opening the clamp by selecting a confirm button 64 or a cancel button 66 .
The present invention has now been described with reference to several embodiments thereof. The entire disclosure of any patent or patent application identified herein is hereby incorporated by reference. The foregoing detailed description and examples have been given for clarity of understanding only. No unnecessary limitations are to be understood therefrom. It will be apparent to those skilled in the art that many changes can be made in the embodiments described without departing from the scope of the invention. Thus, the scope of the present invention should not be limited to the structures described herein, but only by the structures described by the language of the claims and the equivalents of those structures. | User interfaces for medical perfusion systems that provide oxygenation, filtering, and recirculation of blood in connection with various medical procedures are provided. In particular, user interfaces for use with blood pumps that assist in managing alarms commonly encountered during cardiopulmonary bypass surgeries are provided. | 0 |
FIELD OF THE INVENTION
The present invention generally relates to wireless communication, and more specifically relates to codeword re-transmission after a multi-codeword transmission in 4-transmit antenna high speed downlink packet access (HSDPA) MIMO, thereby preventing getting stuck in a higher-than-desired rank multi-codeword transmissions for 4-transmit antenna multiple-input-multiple-output (MIMO) HSDPA.
BACKGROUND
Mobile data transmission and data services are constantly making progress. With the increasing penetration of such services, such as mobile broadband usage and possibilities for competitive offerings to customers, a need for increased capacity for conveying the data is emerging. Thus, techniques which allow mobile operators to manage their spectrum resources efficiently are of high importance.
Therefore, in order to support uplink data rates, mobile operators may provide their base stations with additional receiving antennas. Base stations equipped with multiple antennas may improve the downlink performance by introducing support for four antenna branch MIMO transmission. In addition to doubling the peak data rate when compared to two antenna branch MIMO transmission, the possibility of transmitting from four antennas will also increase the coverage for rank- 1 and rank- 2 transmissions. Therefore, 4-branch MIMO transmission schemes are well applicable for increasing the cell and cell-edge user data rates.
Prior art which is related to this technical field can e.g. be found in technical specifications according to 3GPP Release 11, in particular, the Draft Report of 3GPP TSG RAN WG1 #69 v0.2.0.
According to the above mentioned specification, it has been agreed that in case of re-transmissions, relative to the initial transmission of a codeword:
Number of layers (and transport blocks TB) per codeword CW shall be maintained Order of codewords CW shall be maintained Special mappings for re-transmissions are not considered further
This allows for a straight forward extension of the standard to 4Tx MIMO. However, in some particular cases the agreements above can cause suboptimal behavior.
That is, currently, 4-branch MIMO is standardized in 3GPP within Rel 11, wherein in previous 3GPP meetings, the usage of so called codewords CW was decided. A codeword is the combination of up to two transport blocks. The number of transport blocks in one codeword depends on the rank. Only one acknowledgement/negative acknowledgement Ack/Nack is signaled per codeword, i.e. if one transport block in the codeword is not successfully transmitted, the whole codeword has to be retransmitted. That also implies that a CW with two transport blocks can only be retransmitted in the same format (CW with two transport blocks), and codewords with one transport block can only be retransmitted in a 1-transport block per CW format.
The problem is the rank reduction in case of re-transmissions. From the description above, it can be concluded that if a CW with two transport blocks fails, it can be retransmitted with rank 3 or 4 but not with rank 1 or 2 . A codeword with two transport blocks can't be simply mapped to two codewords with one transport block each.
Another problem is that each hybrid automatic repeat request HARQ has an identification ID. Retransmitting for example CW 1 from a rank 4 transmission as CW 2 in rank 3 would require the definition of a special mapping of the HARQ ID.
This is technically feasible but would require undesired exceptions in the standard. The conclusion is that rank reduction for re-transmission is complicated and standard will not introduce explicit mechanisms for supporting it.
The current opinion in 3GPP for those re-transmissions is that re-transmissions should keep the rank. If this rank is too optimistic and the re-transmissions are not successful, the base station NB would simply terminate the HARQ process and start the transmission of the affected transport blocks from scratch.
However, for some cases, this configuration may suffer from problems. That is, as an example, assuming the user equipment UE gets a rank 4 transmission (two CWs, each carrying two transport blocks), one CW succeed and is acknowledged, and the other one CW fails and gets a negative acknowledgement Nack requesting for a re-transmission. As the rank needs to be maintained for re-transmissions, the CW to be retransmitted needs to be accompanied with another CW delivering new data. By the time the re-transmission is to take place the channel may have gotten worse (UE is moving away from NB, or rank 4 was scheduled during an exceptional good transmission time interval TTI) and it is quite likely that the CW with new data also fails (only one of the two contained transport blocks has to fail). The NB could now terminate the 1 HARQ process after the maximal number of re-transmissions is reached for this CW. However, the second CW would still require re-transmissions. And two new transport blocks would be scheduled for the first CW. Since the channel conditions are not adequate for rank 4 , the new CW 1 would also fail. In this manner, the UE can be stuck in rank 4 re-transmissions.
Another problematic case is when the NB transmit buffer is empty, it has CW to be retransmitted with high rank, but no new data to transmit, and hence it is not able to accompany the CW to be retransmitted with another CW carrying new data, preventing the re-transmission to take place at the same rank it was initially transmitted.
SUMMARY OF THE INVENTION
Therefore, it is an object underlying the present invention to provide an enhanced codeword re-transmission which solves the above drawbacks of the prior art. In particular, it is an object of the present invention to provide an apparatus, a method and a computer program product for providing enhanced codeword re-transmission for 4 transmit antenna HSDPA MIMO wireless communication network, thereby preventing getting stuck in a high-rank two-codeword transmissions.
According to a first aspect of the present invention, there is provided an apparatus, which comprises reception means adapted to receive a negative acknowledgement signaling from a terminal upon transmission comprising a first and a second codeword to the terminal, processing means adapted to provide a temporary codeword for the codeword not associated with the negative acknowledgement signaling, and transmission means adapted to cause transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and the temporary codeword.
According to a second aspect of the present invention, there is provided a method, comprising receiving a negative acknowledgement signaling from a terminal upon transmission comprising a first and a second codeword to the terminal, providing a temporary codeword for the codeword not associated with the negative acknowledgement signaling, and causing transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and the temporary codeword.
According to a third aspect of the present invention, there is provided an apparatus, comprising determination means adapted to determine successful reception of codewords comprising a first and a second codeword from a base station, transmission means adapted to cause a transmission of a negative acknowledgement signaling in case of a negative determination to the base station, and reception means adapted to receive transmission of comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and a temporary codeword from the base station.
According to a fourth aspect of the present invention, there is provided a method, comprising determining successful reception of a transmission comprising a first and a second codeword from a base station, causing a transmission of a negative acknowledgement signaling in case of a negative determination to the base station, and receiving transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and a temporary codeword from the base station.
According to a fifth aspect of the present invention, there is provided a computer program product comprising computer-executable components which, when the program is run on a computer, are configured to carry out the method according to at least one of the second and the method according to the fourth aspect.
According to another embodiment of the invention, the temporary codeword is an empty codeword.
In another embodiment, the temporary codeword is a duplicate of the codeword associated with the negative acknowledgement signaling.
According to certain embodiments of the invention, signaling for the usage of the temporary codeword is carried out via transport format resource indicator transmitted over highspeed shared control channel.
Furthermore, the modulation indicator of a code word may be set to a predetermined value and/or the transport format resource indicator of a codeword may be set to a predetermined value in order to indicate a temporary codeword.
Still further, information indicating a transmitted codeword being an initial transmission or re-transmission may be set to a predetermined value in order to indicate that the transmitted codeword is a temporary codeword.
According to certain embodiments of the invention, each apparatus may comprise at least one processor, and at least one memory including computer program code, the at least one memory and the computer program code configured to, with the at least one processor, cause to carry out the method according to at least one of the first aspect and the method according to the third aspect.
Advantageous further developments or modifications of the aforementioned exemplary aspects of the present invention are set out in the dependent claims.
BRIEF DESCRIPTION OF DRAWINGS
For a more complete understanding of example embodiments of the present invention, reference is now made to the following descriptions taken in connection with the accompanying drawings in which:
FIG. 1 schematically illustrates a Transport block TB to Codeword CW to layer mapping;
FIG. 2 shows a principle flowchart of an example for a method according to certain embodiments of the present invention, which may be implemented in a base station;
FIG. 3 shows a principle configuration of an example for an apparatus according to certain embodiments of the present invention.
FIG. 4 shows a principle flowchart of an example for a method according to certain embodiments of the present invention, which may be implemented in a terminal, such as a user equipment UE; and
FIG. 5 shows a principle configuration of an example for an apparatus according to certain embodiments of the present invention.
DESCRIPTION OF EXEMPLARY EMBODIMENTS
Exemplary aspects of the present invention will be described herein below. More specifically, exemplary aspects of the present are described hereinafter with reference to particular non-limiting examples and to what are presently considered to be conceivable embodiments of the present invention. A person skilled in the art will appreciate that the invention is by no means limited to these examples, and may be more broadly applied.
It is to be noted that the following description of the present invention and its embodiments mainly refers to specifications being used as non-limiting examples for certain exemplary network configurations and deployments. Namely, the present invention and its embodiments are mainly described in relation to 3GPP specifications being used as non-limiting examples for certain exemplary network configurations and deployments. In particular, a UMTS/HSDPA communication system is used as a non-limiting example for the applicability of thus described exemplary embodiments. As such, the description of exemplary embodiments given herein specifically refers to terminology which is directly related thereto. Such terminology is only used in the context of the presented non-limiting examples, and does naturally not limit the invention in any way. Rather, any other network configuration or system deployment, etc. may also be utilized as long as compliant with the features described herein.
Hereinafter, various embodiments and implementations of the present invention and its aspects or embodiments are described using several alternatives. It is generally noted that, according to certain needs and constraints, all of the described alternatives may be provided alone or in any conceivable combination (also including combinations of individual features of the various alternatives).
As already indicated above, a codeword is the combination of up to two transport blocks, wherein the number of transport block in one codeword depends on the rank. If one transport block in the codeword is not successfully transmitted, the whole codeword has to be retransmitted, wherein a CW with 2 transport block can only be retransmitted in the same format, i.e. a CW with 2 transport blocks, and codewords with one transport block can only be retransmitted in a 1 transport block per CW format.
FIG. 1 schematically illustrates a Transport block TB to Codeword CW to layer mapping according to certain embodiments of the present invention. In particular, FIG. 1 shows the CW size for each rank. The large boxes contain 2 transport blocks and the small boxes only one, i.e. rank 3 transmission has 1 CW with 1 transport block and one with 2 transport blocks. In rank 4 transmissions, both CWs contain two transport blocks. Furthermore, each hybrid automatic repeat request HARQ has an assigned ID.
If a CW with two transport blocks fails, it can be retransmitted with rank 3 or 4 but not with rank 1 or 2 . A codeword with two transport blocks can't be simply mapped to 2 codewords with one transport block each. Furthermore, re-transmission of for example CW 1 from a rank 4 transmission as CW 2 in rank 3 would require the definition of a special mapping of the HARQ ID.
In order to avoid getting stuck e.g. in rank 4 transmission, a mechanism to avoid interrupt the re-transmission chain is required.
According to certain embodiments of the present invention, an option is provided to transmit an empty codeword without which performing an associated hybrid automatic repeat request HARQ process can be used.
Hence, according to certain embodiments, in case the NB detects the case described above, it would have the possibility to keep the rank, but sent an empty codeword for the correctly received CW and then use all the power on the CW associated with the re-transmission. After a successful re-transmission or when the maximum number of re-transmissions is reached, the rank can be lowered as there are no pending re-transmissions forcing the NB to keep the rank.
The signaling for the usage of such an empty codeword could, as an example, be done via Transport Format Resource Indicator TFRI which is transmitted over the high speed shared control channel HS-SCCH. According to certain embodiments, an a-priori defined (standardized) combination of transport format of CW 1 and CW 2 may indicate the empty codeword.
Optionally, according to certain embodiments of the present invention, the second codeword may also be a duplicate of the first codeword, and hence may provide additional coding gain.
FIG. 2 shows a principle flowchart of an example for a method according to certain embodiments of the present invention.
In Step S 21 , a negative acknowledgement signaling from a terminal is received upon transmission comprising a first and a second codeword to the terminal.
In Step S 22 , a temporary codeword for the codeword not associated with the negative acknowledgement signaling is provided.
In Step S 23 , a transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and the temporary codeword is caused.
FIG. 3 shows a principle configuration of an example for an apparatus according to certain embodiments of the present invention. The apparatus 30 comprises reception means 31 adapted to receive a negative acknowledgement signaling from a terminal upon transmission comprising a first and a second codeword to the terminal, processing means 32 adapted to provide a temporary codeword for the codeword not associated with the negative acknowledgement signaling, and transmission means 33 adapted to cause a transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and the temporary codeword.
FIG. 4 shows a principle flowchart of an example for a method according to certain embodiments of the present invention.
In Step S 41 , successful reception of a transmission comprising a first and a second codeword from a base station is determined.
In Step S 42 , a transmission of a negative acknowledgement signaling in case of a negative determination to the base station is caused.
In Step S 43 , a transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and a temporary codeword from the base station is caused.
FIG. 5 shows a principle configuration of an example for an apparatus according to certain embodiments of the present invention. The apparatus 50 comprises a determination means 51 adapted to determine successful reception of a transmission comprising a first and a second codeword from a base station, transmission means 52 adapted to cause a transmission of a negative acknowledgement signaling in case of a negative determination to the base station, and reception means 53 adapted to receive a transmission comprising a re-transmission of the codeword associated with the negative acknowledgement signaling and a temporary codeword from the base station.
As already indicated above, according to the specification of 3GPP TSG RAN WG1 #69 v0.2.0, in case of re-transmissions the number of layers (and TBs) per CW and the order of code shall be maintained.
However, the following scenarios may occur:
A first case in which the agreements above lead to a not well defined scenario is
if one of two code words (CW) fails, and the buffer for the UE is empty after this transmission.
In this case, the node B is obliged to keep a transmission with two CWs (rank 2 to 4 ) but has actually no data do transmit on the second CW, and thus would not be able to retransmit the CW pending a re-transmission.
A second case occurs when the UE channel condition becomes rapidly worse while in a re-transmission of a CW that was transmitted with a rank higher than rank 1 . In such a scenario it is possible that the second CW which is not in re-transmission fails while the other CW is being retransmitted and starts a re-transmission cycle of its own. After the re-transmission of the first CW is finished (successfully or not), the UE would have to stay in rank 4 and start yet another CW until the second re-transmission is fished. This process would potentially continue and cause severe performance loss for the affected UE.
According to certain embodiments of the present invention, the following 3 options may be considered:
1. Proprietary termination of the pending re-transmission(s), and either transmitting that data as a new transmission, or let RLC re-transmission protocol take care of the lost data 2. Fill the successful codeword with dummy data 3. Keep the successful codeword empty and potentially use double power for the re-transmission
In option 1, the node B would simply fail the affected transport blocks (up to 2 in one CW) and the corresponding HARQ process instead of retransmitting the code word. This would allow for a complete new transmission which can use any rank. This approach would invalidate all soft information stored in the UE and result in a small overall performance loss. However, the added Node B L 1 and L 2 coordination complexity is seen undesirable if it can be avoided.
To enable option 1, the data that is in the HARQ transmission buffer would also need to be kept in the medium access control MAC-ehs buffer until the HARQ terminates successfully in order to be able to terminate the HARQ process before successful TB delivery, reselect the MCS and transmit the same L 2 information as a new HARQ transmission. This leads to an undesired control loop between L 1 and L 2 , and adds complexity to the L 2 data buffer management.
As regards option 2, considering first case scenario described above, the NB would have to make a decision on what to transmit on the codeword not in re-transmission. Since the buffer for this particular UE is empty and a dual codeword transmission is forced by the restriction set for the re-transmission, the node B would have to transmit dummy data in the second codeword. This may be suboptimal since energy is used to transmit useless data which generates on top of this interference. Particularly for the codeword which is retransmitted is sensitive to the unnecessary interference.
A further solution which avoids interference is option 3. Not transmitting anything in the second CW would not only reduce the interference but would allow at the same time to double (or even triple for some rank 3 re-transmissions) the transmit power of the re-transmission. This would increase the probability of a successful re-transmission and allow for quickly leaving the state of rank limitation if needed. To allow for a proper decoding and power estimation of the retransmitted codeword and skipping the empty codeword, the UE needs to be informed that one of the code words is empty.
Hence, according to certain embodiments of the present invention, an empty code word may be transmitted with a retransmitted code word when two CWs are being sent.
In the following, signaling options for empty code words are described.
As example, an indication of the empty code words could be signaled via HS-SCCH. One option is to reserve a special TFRI/modulation combination for this purpose, i.e. if
The HS-SCCH indicates rank >1 One of the two CWs is an initial transmission Another one of the two CWs is a re-transmission a specific TFRI of the initial transmission CW is used,
then only the CW carrying the needed re-transmission is actually transmitted and the other CW contains no data and no energy.
As an alternative an invalid signaling could be used to indicate an empty code word, i.e. if
The HS-SCCH indicates rank >1 Both code words are re-transmissions One of the two CWs was already received correctly, and the unnecessary re-transmission of this CW has a mismatching TB size,
then only the CW carrying the needed re-transmission is actually transmitted and the other CW contains no data and no energy.
Option 2 has the advantage that the full set of TFRIs can be used for new transmissions of successfully transmitted code words.
Therefore, according to certain embodiments of the present invention, a new signaling scheme 2 (alternative) may be introduced to indicate empty codeword to the UE allowing for the Node B to fall back to a single CW re-transmission.
As a background, according to 3GPP Rel-8 TS25.212 subclause 4.6B.1, the 2×2 MIMO HS-SCCH has the following bits:
Part 1:
Code set info (7 bits), notably the # of codes is common for both code words
Modulation and rank (3 bits,)
Precoding information (2 bits)
Part 2 with Two Code Words (Rank 2 ):
TFRI 1 for TB 1 (=CW 1 ) (6 bits)
TFRI 2 for TB 2 (=CW 2 ) (6 bits)
HARQ process information (4 bits)
Redundancy and constellation version for TB 1 (=CW 1 ) (2 bits), a sequence of ‘00’ means first transmission, others mean re-transmission
Redundancy and constellation version for TB 2 (=CW 2 ) (2 bits), a sequence of ‘00’ means first transmission, others mean re-transmission
For 4×4 MIMO case the TFRI 1 and TFRI 2 would both be present for rank 2 , 3 and 4 transmissions, but depending on the rank the corresponding CW could contain 1 or 2 transport blocks TB of the same size. For example for rank 2 the mapping is as with 2×2 MIMO above, and for rank 4 the TFRI 1 tells the sizes (together with modulation and # of codes) of TB 1 and TB 2 , which make the CW 1 , and the TFRI 2 tells the sizes of TB 3 and TB 4 , which make the CW 2 .
Therefore, according to certain embodiments of the present invention,
If The transmission rank is indicated to be >1 (two code words indicated by the modulation and rank field) One of the two code words' ‘redundancy and constellation version’ indicates a new transmission Another one of the two code words' ‘redundancy and constellation version’ indicates a re-transmission The modulation of the new transmission is set to a predetermined value The TFRI of the new transmission is set to a predetermined value Then Only the retransmitted code word is actually sent and the new transmission is considered to contain no data and no energy.
Or alternatively:
If The transmission rank is indicated to be >1 (two code words indicated by the modulation and rank field) Both code words' ‘redundancy and constellation version’ indicate a re-transmission One of the two code words being retransmitted was already received correctly (no need for the re-Tx) The TB size indicated for this code word does not match the TB size of the already successfully received packet The modulation of this code words is set to a predetermined value Then
Only the retransmitted code word of the not yet correctly received transmission is actually sent and the re-transmission of the already correctly received CW is considered to contain no data and no energy.
That is, according to certain embodiments of the present invention, a one zero-power code word for a nominally two-code word transmission is indicated in order to facilitate a one CW re-transmission after a dual CW transmission has one CW successfully received, the other CW was not successfully received and dual CW transmission cannot be continued.
As example, the two cases for the case “dual CW transmission cannot be continued” are:
1. End-of-data, the Node B buffer is empty and there is no new data to put in parallel to the CW that is being retransmitted 2. Need to reduce rank due to poorer channel conditions leading to the Node B not wanting to put new data in parallel to the CW that is being retransmitted due to efficiency.
According to certain embodiments of the present invention, the NodeB may detect the deadlock, i.e., the case that the transmission is stuck due to the high rank e.g. based on the UE channel quality indicator CQI reports, which indicate that the lower rank is preferred (basically lower rank leading to higher throughput due to link conditions). Furthermore, the Node B may decide what the transmission rank should be, but due to the lock-in it is not able to transmit with the lower rank, but is forced to stick with the rank used in the previous transmission attempt of the failed CW.
In the foregoing exemplary description of the apparatus, only the units that are relevant for understanding the principles of the invention have been described using functional blocks. The apparatuses may comprise further units that are necessary for its respective function. However, a description of these units is omitted in this specification. The arrangement of the functional blocks of the apparatuses is not construed to limit the invention, and the functions may be performed by one block or further split into sub-blocks.
According to exemplarily embodiments of the present invention, a system may comprise any conceivable combination of the thus depicted devices/apparatuses and other network elements, which are arranged to cooperate as described above.
Embodiments of the present invention may be implemented in software, hardware, application logic or a combination of software, hardware and application logic. The software, application logic and/or hardware generally, but not exclusively, may reside on the devices' modem module. In an example embodiment, the application logic, software or an instruction set is maintained on any one of various conventional computer-readable media. In the context of this document, a “computer-readable medium” may be any media or means that can contain, store, communicate, propagate or transport the instructions for use by or in connection with an instruction execution system, apparatus, or device, such as a computer or smart phone, or user equipment.
As used in this application, the term “circuitry” refers to all of the following: (a) hardware-only circuit implementations (such as implementations in only analog and/or digital circuitry) and (b) to combinations of circuits and software (and/or firmware), such as (as applicable): (i) to a combination of processor(s) or (ii) to portions of processor(s)/software (including digital signal processor(s)), software, and memory(ies) that work together to cause an apparatus, such as a mobile phone or server, to perform various functions) and (c) to circuits, such as a microprocessor(s) or a portion of a microprocessor(s), that require software or firmware for operation, even if the software or firmware is not physically present. This definition of ‘circuitry’ applies to all uses of this term in this application, including in any claims. As a further example, as used in this application, the term “circuitry” would also cover an implementation of merely a processor (or multiple processors) or portion of a processor and its (or their) accompanying software and/or firmware. The term “circuitry” would also cover, for example and if applicable to the particular claim element, a baseband integrated circuit or applications processor integrated circuit for a mobile phone or a similar integrated circuit in server, a cellular network device, or other network device.
The present invention relates in particular but without limitation to mobile communications, for example to environments under HSDPA, UMTS, LTE, WCDMA, WIMAX and WLAN and can advantageously be implemented in controllers, base stations, user equipments or smart phones, or personal computers connectable to such networks. That is, it can be implemented as/in chipsets to connected devices, and/or modems thereof.
If desired, the different functions discussed herein may be performed in a different order and/or concurrently with each other. Furthermore, if desired, one or more of the above-described functions may be optional or may be combined.
Although various aspects of the invention are set out in the independent claims, other aspects of the invention comprise other combinations of features from the described embodiments and/or the dependent claims with the features of the independent claims, and not solely the combinations explicitly set out in the claims.
It is also noted herein that while the above describes example embodiments of the invention, these descriptions should not be viewed in a limiting sense. Rather, there are several variations and modifications which may be made without departing from the scope of the present invention as defined in the appended claims.
The following meanings for the abbreviations used in this specification apply:
3GPP 3rd Generation Partnership Project Ack/Nack: Acknowledgement/Negative acknowledgement CW: codeword HARQ: Hybrid Automatic Repeat Request (a re-transmission scheme on the physical layer) HS-SCCH: Highspeed Shared Control Channel ID: identifier MIMO: Multiple Input Multiple Output NB: Node B (base station in 3G Wideband-CDMA) TB: transport block TFRI: Transport Format Resource Indicator TTI: transmission time interval | The present invention addresses apparatuses, methods and computer program product for providing enhanced codeword re-transmission for multi-codeword in 4 antenna branch HSDPA MEMO wireless communication network, thereby preventing getting stuck in higher than rank 1transmissions. When a negative acknowledgement signaling is received from a terminal upon transmission including a first and a second codeword to the terminal, the codeword not associated with the negative acknowledgement signaling is replaced with a temporary codeword, and a transmission a re-transmission of the codeword associated with the negative acknowledgement signaling and the temporary codeword to the base station is caused. | 7 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority of European application No. 06000401.7 EP filed Jan. 10, 2006, which is incorporated by reference herein in its entirety.
FIELD OF INVENTION
[0002] The invention relates to a process for preparing turbine blades or vanes for a subsequent treatment, for example the application of a coating and/or a material-removing operation, wherein the turbine blade or vane has an airfoil, which is delimited at at least one end by an endplate with peripheral surfaces, wherein at least one of the peripheral surfaces is at least partially covered prior to the treatment of the turbine blade or vane. The invention also relates to a turbine blade or vane having an airfoil, which is delimited at at least one end by an endplate that has a hot-gas side facing the airfoil and adjoining peripheral surfaces.
BACKGROUND OF INVENTION
[0003] To improve their temperature and/or abrasion resistance, turbine blades or vanes, such as guide vanes and rotor blades which are intended for gas turbines, are coated with suitable metals, metal alloys or ceramics. The coating is done by means of a spray coating apparatus in which the turbine blade or vane is spray-coated. Examples of spray-coating processes include atmospheric plasma spraying (APS) and high-velocity oxyfuel spraying (HVOF) (cf. Ullmanns Encyclopedia of Industrial Chemistry, 2003, Vol 21, pages 573 and 575).
[0004] In the context of turbine blades or vanes, a distinction is drawn between guide vanes and rotor blades. Both have an airfoil which is exposed to the hot gas and at one end merges into a root body which serves to secure the turbine blade or vane either to a rotor (in the case of a rotor blade) or to a holder (in the case of a guide vane). At the other end of the airfoil, a guide vane additionally has a head body which, like the root body, is intended for securing to a holder. At the transition to the airfoil, root and head bodies form endplates in the form of root plates or head plates, which have a hot-gas side facing the airfoil and adjoining peripheral surfaces.
[0005] The coating described above is carried out only on those surfaces which are exposed to the hot gas, i.e. the airfoil and the hot-gas sides of the root plate and if present also head plate. The peripheral surfaces of these endplates and also the remaining parts of the root body and if present head body, according to the specification, must remain free of coating, since they have already been machined to their final dimensions. Therefore, in the spray coating apparatus the root body and if present also the head body are covered as far as possible, apart from the respective hot-gas side. However, it is virtually inevitable that coating material will also reach those parts of the peripheral surfaces of the endplates which are adjacent to the hot-gas side, i.e. that some overspray, as it is known, will occur. This requires the coating to be removed by grinding (overspray grinding) in a subsequent process step. This presents the risk of uncoated parts of the peripheral surfaces also being ground, with the result that their final dimensions change.
SUMMARY OF INVENTION
[0006] An object of the invention is to provide a process which can be used to protect the peripheral surfaces of the endplates of turbine plates or vanes both during the coating operation and during the subsequent overspray grinding. A further object is to design a turbine blade or vane which is suitable for this purpose.
[0007] According to the invention, the first part of the object is achieved by a process in which a covering strip is fitted to at least one peripheral surface to form a plug connection. Therefore, it is a basic concept of the invention for the peripheral surfaces of the endplate(s) to be protected with the aid of covering strips, which are each held on the turbine blade or vane by means of a plug connection. The plug connection allows simple yet secure fixing of the covering strip in the region of the peripheral surfaces. The covering strip protects the peripheral surfaces from being sprayed with coating material during the coating operation. Should overspray, i.e. coating of part of the peripheral surfaces, occur, this overspray can be removed following the coating operation by grinding with the covering strip still attached, in which case the covering strip then protects the uncoated part of the peripheral surfaces. This significantly reduces the risk of the size dropping below the required final dimensions.
[0008] In a refinement of the invention, the covering strip used, or the required number of covering strips used, in the plug-on state covers that region of the respective peripheral surface which extends on the side of the plug connection remote from the airfoil. In this case, overspray can only occur in the part which is left uncovered by the covering strip.
[0009] According to the invention, it is also proposed that peripheral surface(s) and covering strip(s) are matched to one another in such a manner that their plug connection produces a tongue-and-groove connection. This can be done in such a way that a groove is formed into at least one of the peripheral surfaces, and the covering strip used has a plug-in limb which is plugged into the groove. The covering strip can in this case be formed as angle profiled section with a protective limb adjoining the plug-in limb, in which case it is expedient for the plug-in limb and protective limb to be at right angles to one another.
[0010] It has proven expedient to use a covering strip with a length that is greater than the depth of the airfoil, so that the covering strip has a projecting portion.
[0011] According to the invention, a step is also formed into the peripheral surfaces at least in the region of the plug connection. It may project outward on the side of the plug connection remote from the airfoil, but also on the side facing the airfoil.
[0012] According to the invention, the second part of the object is achieved by a turbine blade or vane in which at least one of the peripheral surfaces in each case has at least one plug-connection recess and/or a plug-connection projection. If a plug-connection recess is provided, it may, for example, be formed as a groove.
[0013] As has already been mentioned above, the turbine blade or vane may also be formed in such a way that the peripheral surfaces, in the region of the plug-connection recess or the plug-connection projection, have a step which projects either on the side of the plug-connection recess or plug-connection projection remote from the airfoil or on the side facing the airfoil.
[0014] Furthermore, according to the basic concept of the process according to the invention, it is also provided that a covering strip is fitted onto at least one peripheral surface, so as to form a plug connection to the plug-connection recess or the plug-connection projection, this covering strip advantageously covering that region of the peripheral surface which extends on the side of the plug connection remote from the airfoil. The plug connection should preferably be formed as a tongue-and-groove connection. This can be realized in such a way that the covering strip has a plug-in limb which fits into the at least one plug-connection recess.
[0015] The covering strip is advantageously formed as an angle profiled section having a protective limb which adjoins the plug-in limb at an angle. The limbs may form a right angle with one another. The length of the covering strip should be greater than the depth of the airfoil.
[0016] The covering strip may consist of a suitable material which is able to withstand overspray grinding.
[0017] It should expediently consist of a metal, such as steel or the like.
[0018] If the turbine blade or vane is in the form of a guide vane, the airfoil of which is delimited by endplates at both ends, a covering strip should be fitted onto in each case at least one of the peripheral surfaces of both endplates.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The invention is explained in more detail in the drawing and with reference to exemplary embodiments. In the drawing:
[0020] FIG. 1 shows a perspective view of a guide vane for a gas turbine;
[0021] FIG. 2 shows a partial cross section through the root plate of the guide vane shown in FIG. 1 ;
[0022] FIG. 3 shows a partial cross section through a second variant of a root plate, and
[0023] FIG. 4 shows a partial cross section through a third variant of a root plate.
DETAILED DESCRIPTION OF INVENTION
[0024] The guide vane 1 illustrated in FIG. 1 is intended for a turbomachine onward. This may be a gas turbine for an aircraft or a power plant for power generation, a steam turbine or a compressor.
[0025] The guide vane 1 has, in succession along its extent a securing region 2 , an adjoining root plate 3 , an airfoil 4 and a head part 5 which adjoins the vane tip and has a head plate 6 adjacent to the airfoil 4 . The head part 5 is not present if the turbine blade or vane is configured as a rotor blade.
[0026] In the securing region 2 there is a blade root 7 , which is used to secure the guide vane 1 to a disk (not shown). The vane root 7 is in this case designed as dovetail root. Other configurations, such as a fir-tree or hammerhead root, are also possible. The airfoil 4 has a leading edge 8 and a trailing edge 9 for a medium which passes through the turbomachine, flowing past the airfoil 4 .
[0027] Conventional vanes consist, for example, of solid metallic materials, in particular superalloys. Superalloys of this type are known, for example, from EP 1 204 776 B1, EP 1 306 454, EP 1 319 729 A1, WO 99/67435 or WO 00/44949; these documents form part of the disclosure with regard to the chemical composition of the alloy. The turbine blade may in this case be produced by a casting process, also by means of directional solidification, by a forging process, by a milling process or combinations thereof.
[0028] The turbine blades are provided with a coating protecting against corrosion or oxidation, e.g. MCrAlX (M is at least one element selected from the group consisting of iron (Fe), cobalt (Co), nickel (Ni), X is an active element and represents yttrium (Y) and/or silicon and/or at least one rare earth element, or hafnium (Hf). Alloys of this type are known from EP 0 486 489 B1, EP 0 786, 017 B1, EP 0 412 297 B1 or EP 1 306 454 A1, which are intended to form part of the present disclosure with regard to the chemical composition of the alloy.
[0029] It is also possible for a thermal barrier coating, consisting for example of ZrO 2 , Y 2 O 3 —ZrO 2 , i.e. unstabilized, partially stabilized or fully stabilized by yttrium oxide and/or calcium oxide and/or magnesium oxide, to be present on the MCrAlX coating. Columnar grains are produced in the thermal barrier coating by means of suitable coating processes, such as for example electron beam physical vapor deposition (EB-PVD), or grains which are porous, have microcracks and have macrocracks are produced in the thermal barrier coating by atmospheric plasma spraying (APS).
[0030] Refurbishment means that after they have been used, protected layers may have to be removed from components (e.g. by sand-blasting). Then, the corrosion and/or oxidation layers and products are removed. If appropriate, cracks in the component are also repaired. This is followed by recoating and reuse of the turbine vane.
[0031] The guide vane 1 is hollow in form. On the pressure side, visible in FIG. 1 , of the airfoil 4 it has, in the region of the trailing edge 9 , a row of film-cooling holes—denoted for example by 10 —via which cooling air introduced into the airfoil 4 can flow out, thereby cooling the trailing edge 9 .
[0032] The root plate 3 and the head plate 6 each have a hot-gas side 11 , 12 facing the airfoil 4 . The hot-gas sides 11 , 12 are in each case adjoined by four peripheral surfaces 13 , 14 , 15 , 16 and 17 , 18 , 19 , 20 , respectively, which are each provided with a step 21 , 22 , as can also be seen from FIG. 2 . The steps 21 , 22 project outward with respect to that region of the peripheral surfaces 13 to 20 which is in each case adjacent to the airfoil 4 . The steps 21 , 22 merge into a peripheral groove 23 . Grooves 23 are formed both into the peripheral surfaces 13 to 16 of the root plate 3 and into the peripheral surfaces 17 to 20 of the head plate 6 .
[0033] Covering strips 24 , 25 are plugged into the grooves 23 . The covering strips 24 , 25 extend over the entire width of the peripheral surface 13 or 17 . They are formed as angle profiled sections, each having a plug-in limb 26 and a protective limb 27 , 28 in each case running at right angles to the plug-in limb. The plug-in limbs 26 are seated in the grooves 23 and in this way form a plug connection to the root plate 3 or the head plate 6 . The covering strips 24 , 25 are fitted into the grooves 23 in such a way that their protective limbs 27 , 28 are directed away from the respective hot-gas side 11 or 12 and cover those regions of the peripheral surfaces 13 or 17 which—as seen from the airfoil 4 —lie behind the grooves 23 .
[0034] The guide vane 1 having the covering strips 24 , 25 is provided with the coating described above in a spray coating apparatus, specifically in such a manner that the airfoil 4 and the hot-gas sides 11 , 12 of the root plate 3 and head plate 6 are coated. The coating operation also produces an overspray coating 29 , 30 on those regions of the peripheral surfaces 13 , 17 which are not covered by the covering strips 24 , 25 . The overspray coatings 29 , 30 are manually ground away after the coating operation, with the covering strips 24 , 25 remaining on the root plate 3 and head plate 6 , thereby providing protection against slipping on the part of the grinding unit. In this way, the grinding operation remains restricted to the region which has the overspray coating 29 , 30 . The covering strips 24 , 25 are only removed again after the grinding operation, and can then be reused.
[0035] FIGS. 3 and 4 show forms of peripheral surfaces 31 , 32 of root plates 33 , 34 which differ from the embodiment shown in FIGS. 1 and 2 . In an embodiment shown in FIG. 3 , a step 35 is formed by that region of the peripheral surface 31 which is adjacent to the airfoil 4 projecting outward, an overspray coating 36 having formed on this part. The step 35 merges into a groove 37 , into which the covering strip 24 is plug-fitted by means of a plug-in limb 26 .
[0036] There is no step present in the exemplary embodiment shown in FIG. 4 . A groove 38 has been formed into the peripheral surface 32 , and the covering strip 24 has been plug-fitted into this groove 38 in such a manner that its protective limb 27 extends in the direction away from the airfoil 4 . That region of the peripheral surface 32 which is adjacent to the airfoil 4 has been provided with an overspray coating 39 . | Process for preparing turbine blades or vanes for a subsequent treatment, for example the application of a coating and/or a material-removing operation, wherein the turbine blade or vane has an airfoil, which is delimited at at least one end by an endplate with peripheral surfaces, wherein at least one of the peripheral surfaces is at least partially covered prior to the treatment of the turbine blade or vane. In the process a covering strip is fitted onto at least one peripheral surface to form a plug connection. | 2 |
BACKGROUND OF THE INVENTION
The present invention relates to a band-gripper loom having a band wheel for driving an insertion band and having band guide rollers supported on a housing surrounding the band wheel to prevent the insertion band from lifting off from the band wheel.
In one known embodiment of such a band-gripper loom in which each band guide roller is supported on the outer race of a ball bearing, the ball bearings are damaged after only a relatively short period of operation so that they must be continuously replaced at short intervals.
The closest prior art known to applicant in connection with this application is German Patent No. 826,274.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a band guide roller in which the said disadvantage of the known embodiment is avoided.
This objective is achieved, in accordance with the invention, by the fact that each band guide roller is supported on the inner race of a ball bearing.
With the band guide roller of the invention, the supporting thereof on the inner race of the ball bearing results in a reduction in the speed of rotation of the ball-bearing rollers by about 30 percent, which it is believed is the main reason that the life of the ball bearings is substantially increased and that practically no unexpected damage to the ball bearings occurs any longer when the band guide rollers of the invention are employed. Another advantage of the band guide roller of the invention is that the sealing rings, which are fastened on the outer race of the ball bearings and are intended to prevent the emergence of lubricating oil from the ball bearing, now no longer rotate, as a result of the fact that the outer race is stationary. In the known embodiment, on the other hand, in which the inner race is stationary and the outer race rotates, the sealing rings also rotate and thereby become so greatly worn that they drop out of the bearing within a short time.
Another advantage of the band guide roller of the invention is that the forces required for the accelerating of the band guide roller to a given speed of rotation are considerably less, for the same size of ball bearing and band guide roller, than in the case of the known embodiment.
This has a substantial influence in view of the large filling insertion capacity of modern band-gripper looms.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described below with reference to an illustrative embodiment and the figures of the drawing, in which:
FIG. 1a is a diagrammatic front view of the parts of a band-gripper loom which are necessary for an understanding of the invention;
FIG. 1b is a partial view of a detail of the band guide rollers shown in FIG. 1a;
FIG. 2 is a partial cross-sectional view along the line II--II of FIG. 1b;
FIG. 3 is a partial cross-sectional view along the line III--III of FIG. 1b;
FIG. 4 is a partial cross-sectional view along the line IV--IV of FIG. 1b;
FIG. 5 is a view looking in the direction of the arrow V in FIG. 4; and
FIG. 6 is a further detailed view looking in the direction of Arrow V of FIG. 4.
DESCRIPTION OF PREFERRED EMBODIMENTS
FIG. 1a illustrates diagrammatically a portion of a band-gripper loom of known construction having a base plate 2 supported on the machine frame 1 in order to hold a band wheel 4 which is protected by a removable cover 3. The cover 3 is partially cut away in this figure. The filling threads are arranged in the form of a large supply on the side of the loom (not shown) and are offered to a first insertion head 5. The first insertion head 5 is fastened to one end of a flexible insertion band 6 which rests on the wheel rim of the band wheel 2 and is connected to the wheel rim at its other end.
The band wheel 4 is driven in an oscillating manner so that the first insertion head 5 is continuously transported towards the center of the shed (not shown) when the shed is formed and then again pulled out of the shed. At the center of the shed the filling thread is turned over to a second insertion head (not shown), by which the filling thread is introduced from the center of the shed into the second half of the shed, thus completing a thread insertion. After the insertion has been effected, the filling thread is beaten-up by a reed 8 fastened to a batten 7.
As a result of the firm attachment between the band wheel 4 and the insertion band 6, the latter is pushed upon the unwinding and pulled upon the winding. As a result of the pushing upon the unwinding, the insertion band 6 is pressed outwards from the circumference of the band wheel 4 and slides along band guide elements 9 which are arranged fixed in position along a part of the circumference of the band wheel 4. Another band guide 10 is arranged between the band wheel 4 and the shed.
The guide elements 9 are shown in greater detail in FIGS. 1b and 2 through 5, the cover 3 being omitted in FIGS. 1b, 3, 4, 5, and 6 for greater ease in reading the drawings. FIG. 1b shows a part of the band wheel 4 in the region of the wheel rim, as well as the associated guide elements 9; FIGS. 2, 3, 4, and 5 each shows a section through a guide element 9; and FIGS. 5 and 6 show portions of FIG. 1b on a larger scale.
The guide elements 9 consist essentially of two support rails 11 which are arranged parallel to and spaced from each other, three disks guide rolls 12 per guide element being arranged in said rails. The support rails 11 are spaced from and connected with each other by two spacer plates 13, the said spacer plates being screwed by screws 14 to the base plate 2. The band guide rolls 12 have the shape of a disk with two protruding stub shafts 15, each of which is supported in the inner race of a ball bearing 16 whose outer race is seated in one of the two support rails 11. The ball bearings 16 are each covered on the outside by a plastic disk 17, the disks lying on the side thereof facing the ball bearing 16 against said ball bearing 16 and being provided with a guide projection 18 on the side which faces away from the ball bearing 16. In the region of each band guide roller 12, a spring yoke 19 is placed from above over the guide elements 9, said yoke being provided with a cutout 20 which corresponds to the guide projection 18. The guide projection 18 engages in said cutout 20, as a result of which the disks 17 are held fast.
The band guide rollers 12 consist of a material, the bearing surface of which has a coefficient of friction which is small in the case of slight difference in speed from the speed of the insertion band 6 and relatively large in the case of a large difference in said speed, This has the result that the band guide rollers 12 operate practically free of slippage and there is no heating as a result of slippage. A material having a base of polytetrafluoroethylene which is sold by the du Pont Company under the name "RULON" has these properties.
By the supporting of the band guide rollers 12 on the inner race of the ball bearings 16, a reduction in the speed of rotation of the ball bearing rollers of about 30% is obtained as compared with support on the outer race. Furthermore, for the same size band guide roller 12, the forces of acceleration required are substantially less. These factors contribute essentially to the long life of the ball bearing 16, the supporting of each band guide roller 12 on two ball bearings 16 also having a favorable effect, and resulting in an increase in the life of the ball bearings 16 by about four times as compared with a band guide roller having only one ball bearing.
The guide elements 9 are mounted on the base plate 2 in such a manner that there is a distance of a few tenths of a millimeter, preferably about 0.3 mm, between the insertion band 6 and the bearing surface of the band guide rollers 12. In the case of the first guide element 9, referring to the direction of travel of the insertion band 6, upon the withdrawal of the first insertion head 5 out of the shed (FIG. 1), and therefore the top guide element 9 in FIG. 1b, the distance between the bearing surface of the band guide rollers 12 and the insertion band 6 is selected somewhat larger, and preferably amounts to about 0.4 to 0.7 mm.
A yoke 21 is shown in FIGS. 1b and 2. A plurality of such yokes 21, for example three, are provided over the periphery of the band wheel 4, the yokes being screwed by screws 22 to the base plate 2, and thus serve to hold the cover 3, as can be noted from FIG. 2.
FIG. 6 shows essentially the same view as FIG. 5 but for greater ease in reading the drawing, the plastic disk 17 with guide projection 18 and spring yoke 19 are omitted.
Every guide element 9 consists essentially of two parallel support rails 11 which are spaced by the spacer plates 13, the spacer plates and the support rails being welded together in the region of the dotted edges of spacer plate 13 shown in FIG. 6. In the region where a band guide roll 12 is to be mounted, each support rail 11 is provided with a bore 23 for seating the outer race of ball bearing 16. The bores 23 are not closed over their circumference but have an opening 24 extending through the adjacent wall of support rail 11. The width of the opening 24 is larger than the diameter of stub shafts 15.
When producing a guide element 9, in a first step two support rails 11 are welded together with two spacer plates 13. Then the bores 23 are made. In a next step a band guide roll 12 with its stub shafts 15 is moved through openings 24 in the interior space of bores 23. Then in the direction of arrow V in FIG. 4 and in the counter-direction, a ball bearing 16 is pressed between each stub shaft 15 and its corresponding bore 23. After having mounted disks 17 and spring yokes 19, the production of guide element 9 is finished and the guide element can be screwed by screws 14 to the base plate 2.
Although the invention is described in detail for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims. | A band-gripper loom having band guide rollers supported on a housing surrounding the band wheel to prevent the insertion band from lifting off the band wheel, with each band guide roller supported on the inner race of ball bearings. | 3 |
BACKGROUND OF THE INVENTION
Glaucoma is an ocular disorder associated with elavated intraocular pressures which are too high for normal function and may result in irreversible loss of visual function. If untreated, glaucoma may eventually lead to blindness. Ocular hypertension, i.e., the condition of elevated intraocular pressure without optic nerve head damage or characteristic glaucomatous visual field defects, is now believed by many ophthalmologists to represent the earliest phase of glaucoma.
Many of the drugs formerly used to treat glaucoma proved not entirely satisfactory. Only recently have clinicians noted that many β-adrenergic blocking agents are effective in reducing intraocular pressure. While many of these agents are effective in reducing intraocular pressure, they also have other characteristics, e.g. membrane stabilizing activity, that are not acceptable for chronic ocular use. Other agents which are used for treatment of glaucoma include carbonic anhydrase inhibitors and prostaglandins. Carbonic anydrase inhibitors work by blockade of inflow into the eye. Prostaglandins exert a reduction of scleral outflow. To date, only muscarinic agents work by directly increasing outflow. Since glaucoma is considered to be a result of decreased outflow from the eye, this approach provides greater therapeutic benefit by the nature of more direct action.
There have been recent advances made in the understanding of the cholinergic nervous system and the receptors thereto. Cholinergic receptors are proteins embedded in the wall of a cell that respond to the chemical acetyIcholine. Particularly, it is now known that the cholinergic receptors are subdivided into nicotinic and muscarinic receptors and that the muscarinic receptors are not all of the same type. Recent literature indicates that there are at least five types of cholinergic muscarinic receptors (types m1 through m5). Receptors of type m1 are those present in abundance and thought to be enriched in the brain neural tissue and neural ganglia. The other receptors are concentrated in other tissues such as the heart, smooth muscle tissue or glands. While many pharmacological agents interacting with muscarinic receptors influence several types of receptors, some agents are known to have a major effect on a single type of receptor with relative selectivity. Still other agents may have a significant effect on more than one or even all types of receptors. For example, there is strong evidence that the receptors in the back of the eye responsible for outflow are comprised of the m2 and m3 subclass.
Topical administration of muscarinic agonist, pilocarpine, lowers intraocular pressure by increasing outflow. However, pilocarpine is a non-selective agonist, interacting with muscarinic receptors of several types. Additionally, the side effects associated with pilocarpine are miosis (decrease of pupil size) and systemic CNS effects which limit usefulness.
It is therefore an object of this invention to develop compounds which exhibit few side effects by selectively interacting with a muscarinic receptor.
SUMMARY OF THE INVENTION
This invention is concerned with novel 1- cycloalkylpioeridin-4-yl!-2H benzimidazolones, their compositions and method of use. The novel compounds are selective muscarinic agonists of the m2 subtype with low activity at the m3 subtype. The compounds have good ocular penetration (bioavailability) when dosed at 0.1% to 15% by weight of medicament, especially about 0.5 to 2% by weight of medicament and are effective for the treatment and/or prevention of glaucoma with fewer side effects than the pilocarpine therapy, due to lower activity at the m3 subclass of muscarinic receptors.
DETAILED DESCRIPTION OF THE INVENTION
The novel compounds of this invention are represented by the structural formula I: ##STR1## or pharmaceutically acceptable salts thereof, or diastereomers, enantiomers or mixtures thereof;
wherein:
R 1 -R 4 are independently H, alkyl, halo, alkoxy, OH, HOCH2--, aryl, 3-pyridyl, 5-pyrimidinyl, amino, dialkylamino, alkene, thioalkyl, or alkylamino;
X is C or N;
A is alkyl, alkoxy, carboxyalkyl, alkoxyamino, alkylamino, dialkylamino, dialkoxyamino, carboxylic acid, ═O, hydroxy, C═O, N, or does not exist;
E is H, alkyl, alkylamino, dialkylamino, aryl, heteroaryl, heterocycle, alkoxy, alkoxyaryl, carbonyl heterocycle, alkoxyheteroaryl, alkoxyheterocycle, or does not exist; and
Y is H, alkyl, halo, alkylamino, alkoxyamino, alkoxy, dialkylamino, or amino.
The term heterocycle or heterocyclic, as used herein except where noted, represents a stable 5- to 7- membered monocyclic heterocyclic ting, which is either saturated or unsaturated, and which consists of carbon atoms and from one to three heteroatoms selected from the group consisting of N, O and S, and including any bicyclic group in which any of the above defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic rings include pyridine, pyrazine, pyrimidine, pyridazine, triazine, imidazole, pyrazole, triazole, quinoline, isoquinoline, quinazoline, quinoxaline, phthalazine, oxazole, isoxazole, thiazole, isothiazole, thiadiazole, oxadiazole, pyrrole, furan, thiophene, hydrogenated derivatives of these heterocyles such as piperidine, pyrrolidine, azetidine, tetrahydrofuran, and N-oxide derivatives of heterocyles containing basic nitrogen. Any fused combinations of any of these above-defined heterocyclic rings is also a part of this definition. Attached to the heterocyclic ring can be substituents such as alkyls, amines, or halogens (F, Cl, Br, I).
The term alkyl is intended to include branched, cyclic and straight chain saturated aliphatic hydrocarbon groups having 1 to 15 carbon atoms, unless otherwise defined. Preferred straight or branched alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, t-butyl and the like. Preferred cycloalkyl groups include cyclopentyl and cyclohexyl.
The term alkoxy represents an alkyl group of indicated carbon atoms attached through an oxygen linkage.
The term alkylamino represents an alkyl group of indicated carbon atoms attached through a nitrogen atom linkage.
The term dialkylamino represents two alkyl groups of indicated carbon atoms attached through a nitrogen atom linkage.
The term small alkyl is intended to indicate those alkyls with C1 to C6 carbon atoms, either branched or linear in connection.
The term halo as used herein, represents fluoro, chloro, bromo or iodo.
The term aryl refers to aromatic rings e.g., phenyl, substituted phenyl and the like groups as well as rings which are fused e.g., naphthyl and the like. Aryl thus contains at least one ring having at least 6 atoms, with up to two such rings being present, containing up to 10 atoms therein, with alternating (resonating) double bonds between adjacent carbon atoms. The preferred aryl groups are phenyl and naphthyl. Aryl groups may likewise be substituted with 1-3 groups such as alkyl, halo, carboxyalkyl, alkylamino, dialkylamino, alkoxy, alkoxyamino and the like.
The term heteroaryl refers to a monocyclic aromatic hydrocarbon group having 5 or 6 ring atoms, or a bicyclic aromatic group having 8 to 10 atoms, containing at least one heteroatom, O, S, or N, in which a carbon or nitrogen atom is the point of attachment, and in which one additional carbon atom is optionally replaced by a heteroatom selected from O or S, an in which from 1 to 3 additional carbon atoms are optionally replaced by nitrogen heteroatoms. The heteroaryl group is optionally substituted with up to three groups. Heteroaryl thus includes aromatic and partially aromatic groups which contain one or more heteroatoms. Examples of this type are pyrrol, pyridine, oxazole, thiazole and oxazine. Additional nitrogen atoms may be present together with the first nitrogen and oxygen or sulfur, e.g., thiadizaole.
A preferred embodiment of the novel compounds of this invention is realized when,
R 1 -R 4 are independently H, alkyl, or halo;
A is alkyl, alkoxyamino, N, C═O, ═O, or carboxyalkyl;
E is H, alkyl, aryl, heteroaryl, heterocycle, alkylamino, or dialkylamino; and
Y is H, alkyl, or halo.
The pharmaceutically acceptable salts of the compounds of formula I include the conventional non-toxic salts or the quaternary ammonium salts of the compounds of formula I formed e.g. from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.
The pharmaceutically acceptable salts of the present invention can be synthesized from the compounds of formula I which contain a basic or acidic moiety by conventional chemical methods. Generally, the salts are prepared by reacting the free base or acid with stoichiometric amounts or with an excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or various combinations of solvents.
The compounds of the present invention may have asymmetric centers and occur as racemates, racemic mixtures, and as individual diastereomers, with all possible isomers, including optical isomers, being included in the present invention.
Non-limiting examples of the novel compounds of this invention are as follows:
1,3-dihydro-1-{1- 4-oxo-cyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one;
5-methyl-1,3-dihydro-1-{1- 4-oxo-cyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one;
5-chloro-1,3-dihydro-1-{1- 4-oxo-cyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one;
5-fluoro-1,3-dihydro-1-{1- 4-oxo-cyclohex-1-yl!piperidin-4-yl}-2-H-benzimidazol-2-one;
1,3-dihydro-1-{1- 2-fluoro-4-oxo-cyclohex-1-yl!piperidin-4-yl}-2-H-benzimidazol-2-one;
1,3-dihydro-1-{1- 2-oxo-1,3-dioxolan-5-yl!piperidin-4-yl}-2H-benzimidazol-2-one;
1,3-dihydro-1-{1- 2(1H)-oxo-tetrahydropyrimidin-5-yl!piperidin-4-yl}-2H-benzimidazol-2-one; and
1,3-dihydro-1-{1- 1,3-dimethyl-2(1H)-oxo-tetrahydropyrimidin-5-yl!piperidin-4-yl}-2H-benzimidazol-2-one.
The novel compounds of this invention are prepared by the following non-limiting procedures: ##STR2##
The reaction is carded out at room temperature (20°-30° C.) at a pH in the range of 2-7 (acidic) by the addition of glacial acetic acid or hydrochloric acid. For the preferred examples where X is C and A is ═O, a suitably mono protected 1,4-cyclohexandione such as 1,4-cyclohexanedione mono-ethyleneketal can be used as an intermediate. Similarly, for examples where X is N a suitably protected 4-piperidone such as A-E is CO 2 Et, CO 2 CH 2 Ph, or CO 2 C(CH 3 ) 3 can be used as an intermediate. Deprotection by known methods (hydrogenation or acidic hydrolysis followed by basification) provides the free amine compound which can be acylated or alkylated by standard procedures. By this route the most preferred compounds can be obtained after isolation and purification.
The starting materials Compounds II and III are either commercially available or can be obtained by conventional procedures such as those described in the Examples section.
The selectivity of the compounds can be measured by radioligand displacement from m1-m5 receptors expressed in chinese hamster ovary cells (CHO) as described in the Examples section. The functional activity of the compounds can be assessed by measuring the agonist induced contractile response on muscle tissue from rabbit vas deferens (M1), the guinea pig left atria (M2), or the guinea pig ileum (M3) as described in the Examples section. The functional activity at the human muscarinic receptors can be assessed by measuring agonist induced phosphoinositide hydrolysis in CHO cells expressing the human m1 and m3 receptors or agonist inhibition of foskolin-stimulated adenylate cyclase activity in CHO cells expressing the human m2 receptor as described in the Examples section.
The instant compounds of this invention are useful in treating and/or preventing the development of glaucoma. Therapy to increase outflow can be administered by the use of the agent in eye drops. Indeed, in the vast majority of cases, treatment agents are administered to human eyes by the application of eye drops. Eye drops typically contain about 0.1% to 15% by weight of medicament, especially about 0.5 to 2% by weight of medicament, the remainder being comprised of carriers and other excipients well known in the art. A pH of about 4.5 to about 7.5 is expected to be acceptable as an ophthalmic drop and practical in terms of known solubility and stability of piperidine. Phosphate buffering is also common for eye drops and is compatible with the instant muscarinic agonist. A common regimen for application of eye drops is one to four times a day spaced evenly throughout waking hours. More effective agents may require fewer applications or enable the use of more dilute solutions.
The novel pharmaceutical formulations of this invention are also adapted for oral administration such as tablets, capsules and the like; for nasal administration, especially in the form of a spray; for injection, in the form of a sterile injectable liquid; or for topical ocular administration in the form of solutions, ointments, solid water soluble polymeric inserts, or gels.
The following example is provided in order that this invention might be more fully understood; it is not to be construed as limitative of the invention. The compounds are characterized analytically using techniques such as nuclear magnetic resonance, mass spectrometry, chromatography and the like.
EXAMPLE 1
1,3-Dihydro-1-{1- 4-oxocyclohex-1-yl!piperidin-4-yl}-2-H-benzimidazol-2-one
Step 1: A mixture of 5 g of 1,4-cyclohexanedione mono-ethyleneketal, 4.3 g of 1,3-dihydro-1-(4-piperidinyl)-benzimidazol-2H-one, 75 mL of 1,2-dichloroethane, 1.2 mL of acetic acid and 5.45 g of sodium triacetoxyborohydride was stirred at room temperature for 48 h. The reaction mixture was poured into 500 mL chloroform and 500 mL saturated aqueous Na 2 CO 3 and the layers separated. The aqueous layer was extracted with 2×250 mL of chloroform and the combined organic layers dried over MgSO 4 and concentrated under reduced pressure. Trituration of the crude product with 200 mL of ethyl ether gave 7.0 g of the ethylene ketal of 1,3-dihydro-1-{1- 4-oxocyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one as a white solid: mp=208°-210° C.; 1 H NMR (400 MHz, CDCl 3 ) 9.14 (br s, 1H), 7.3 (m, 1H), 7.1 (m, 1H), 7.05 (m, 2H), 4.35 (br s, 1H), 3.96 (s, 4H), 3.05 (br d, J=6.6, 2H), 2.45 (m, 4H), 1.84 (br d, J=2.8, 5H), 1.72-1.55 (m, 6H).
Step 2: A mixture of 7.0 g of the ethylene ketal of 1,3-dihydro-1-{1- 4-oxocyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one, 80 mL of glacial acetic acid, 80 mL of water and 20 mL of conc. HCl was heated under reflux for 2 h, then allowed to cool overnight. The mixture was concentrated under reduced pressure, diluted with 100 mL of saturated Na 2 CO 3 and extracted into 3×200 mL of CHCl 3 . The combined organic extracts were dried over MgSO 4 and concentrated under reduced pressure. Trituration with ether-ethyl acetate and drying under vacuum gave 5 g of 1,3-dihydro-1-{1- 4-oxocyclohex-1-yl!piperidin-4-yl}-2H-benzimidazol-2-one as a white solid: mp=221°-223° C.; 1 H NMR (400 MHz, CDCl 3 ) 8.68 (br s, 1H), 7.28 (m, 2H), 7.07 (m, 2H), 4.35 (br s, 1H), 3.12 (br d, J=8.7, 2H), 2.82 (br t, J=9.74, 2H), 2.50 (br t, J=13.76, 2H), 2.44-2.32 (m, 6H), 2.06 (br s, 2H), 1.87 (br d, J=10.9, 4H). Analysis calculated for C 18 H 23 N 3 O 2 .0.4 H 2 O: C: 67.44, H: 7.48, N: 13.11. found C: 67.44, H: 7.41, N: 12.86. The citrate salt was crystallized from ethyl acetate/methanol: C 18 H 23 N 3 O 2 .1.0 H 2 O.1.0 C 6 H 8 O 7 : C: 55.06, H: 6.35, N: 8.03. found C: 55.35, H: 6.25, N: 7.89.
EXAMPLE 2
Radioligand Binding Studies
The affinity of muscarinic agonists for m1-m5 receptors expressed in chinese hamster ovary cells (CHO) were determined using the technique described by Dorje et al., J. Pharmacol. Exp. Ther. 256: 727-733 (1991).
When 80-100% confluent, CHO cells were harvested, and transferred to centrifuge robes containing CHO buffer (20 mM HEPES at pH 7.4 containing 5 mM MgCl 2 ). The cells were homogenized using a Brinkman Polytron homogenizer for 30 seconds at a setting of 5, on ice. The homogenate was centrifuged at 40,000×g for 15 minutes at 4° C. in a Beckman J2-21M centrifuge. The supernatant was discarded and the homogenization/centrifugation step repeated once. Pelleted membranes were resuspended in CHO buffer to a concentration of one flask harvested (75 cm 2 ) per mL of buffer, mixed well and aliquoted in cryovials (1 mL/vial). The vials were stored at -70° C. until used in the assay. The binding incubation was done in polypropylene macrowell tube strips in a final volume of 0.5 mL of HEPES buffer (20 mM; pH 7.4 containing 5 mM MgCl 2 ) containing 0.1 mL of cell membrane suspension, 3H-N-methylscopolamine (NEN Corporation, NET-636, 70-87 C i /mmole) at a final concentration of approximately 0.2 nM and the competing drug in a varying range of concentrations or vehicle. After the addition of the cell homogenate the tubes were agitated on a vortex mixer and then placed in a water bath at 32° C. After 90 minutes of incubation, the membranes were harvested on a Skatron filtermat (#11734) or a Wallac filtermat (#205-404) using three washes of HEPES buffer (4° C.). The radioactivity on the filters was counted in a Packard 2200CA scintillation counter or in a Wallac 1205 Betaplate scintillation counter. Specific binding was defined as the difference in binding observed in the presence and absence of 10 micromolar atropine and accounted for at least 80% of total binding. K i values were calculated using the program LIGAND. Compounds displayed K i values at m1, m2 and m4 in the range of 1 nM to 5,000 nM. All compounds described herein displayed typically greater than 300-fold less potency at the m3 receptor subtype, in the range of 300 nM to 114,000 nM.
EXAMPLE 3
m2 receptor agonist activity on the guinea pig left atria
The technique described by Feifel et al., Brit. J. Pharmacol. 99: 455-460 (1990) was used as follows: Duncan-Hartley guinea pigs (Hazelton) weighing 300-600 g, are asphyxiated with CO 2 . The abdomen is opened and the left atria is rapidly removed. The tissues are placed in a Petri dish containing oxygenated Krebs solution NaCl, 118 mM; KCl, 4.7 mM; CaCl 2 , 2.5 mM; KH 2 PO 4 , 1.2 mM; MgSO 4 , 1.2 mM; NaHCO 3 , 25 mM; dextrose, 11 mM! warmed to 37° C. Each atria is attached to platinum electrodes with 4-0 surgical silk and placed in a 10 mL jacketed tissue bath containing Krebs buffer at 37° C., bubbled with 5% CO 2 /95% O 2 . The tissues are connected to a Statham-Gould force transducer; 0.75 gram of tension is applied and the tissues are electrically stimulated. EFS parameters are 3 Hz; 4 ms duration; voltage is set to 5 V.! The contractions are recorded on a Gould strip chart recorder. The tissues are washed every 20 minutes and allowed to equilibrate. A concentration response curve to the agonist is determined. Tissues are washed every 20 minutes for 60 minutes. The vehicle or compound is added to the bath and the tissues are incubated for 30 minutes. Agonist EC 50 values are determined for both vehicle and compound treated tissues before and after treatment. The compounds displayed EC 50 values at M2 in the range of 5 to 100 nM. | This invention is concerned with novel 1- cycloalkylpioeridin-4-yl!-2H benzimidazolones, their compositions and method of use. The novel compounds are selective muscarinic agonists of the m2 subtype with low activity at the m3 subtype. The compounds are effective for the treatment of glaucoma with fewer side effects than the pilocarpine therapy. | 2 |
[0001] The application claims priority from previously filed U.S. provisional patent application No. 60/767,063, titled “DICING AND CUTTING DEVICE” on Mar. 1, 2006 by Mike Livie.
FIELD OF THE INVENTION
[0002] The present invention relates to devices used for dicing and cutting primarily fruits, vegetables, herbs and spices and particularly relates to a kitchen utensil which is a dicing and cutting device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0003] The present invention will be described by way of example only with reference to the following drawings:
[0004] FIG. 1 is a top plan view of the bottom housing.
[0005] FIG. 2 is a side elevational view of the bottom housing.
[0006] FIG. 3 is a bottom plan view of the bottom housing.
[0007] FIG. 4 is a side elevational view of the bottom housing.
[0008] FIG. 5 is a cross sectional view taken along lines 5 - 5 in FIG. 1 of the bottom housing.
[0009] FIG. 6 is a bottom perspective view of the bottom housing.
[0010] FIG. 7 is a top perspective view of the bottom housing.
[0011] FIG. 8 is a top perspective view of the bottom blade holder.
[0012] FIG. 9 is an assembly drawing showing the bottom blade holder being position into the bottom housing.
[0013] FIG. 10 is a top plan view of the top housing.
[0014] FIG. 11 is a side elevational view of the top housing.
[0015] FIG. 12 is a bottom plan view of the top housing.
[0016] FIG. 13 is a side elevational view of the top housing.
[0017] FIG. 14 is a bottom perspective view of the top housing.
[0018] FIG. 15 is a top perspective view of the bottom housing.
[0019] FIG. 16 is a top plan view of the dicing and cutting device.
[0020] FIG. 17 is a side elevational view of the dicing and cutting device in a partial open position.
[0021] FIG. 18 is a side elevational view of the dicing and cutting device in the closed position.
[0022] FIG. 19 is a cross sectional view of the dicing and cutting device taken along lines 19 - 19 and FIG. 16 .
[0023] FIG. 20 is a top perspective view of the dicing and cutting device in the open position.
[0024] FIG. 21 is a front side plan view of a single blade.
[0025] FIG. 22 is a top plan view of a single blade showing the radius of the blade.
[0026] FIG. 23 is a backside plan view of a single blade.
[0027] FIG. 24 is an end plan view of a single blade.
[0028] FIG. 25 is a top plan view of a three plan oriented and spaced apart as they would be in the blade holder.
[0029] FIG. 26 is a front side top perspective view of a single blade.
[0030] FIG. 27 is a back side top perspective view of a single blade.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0031] The present invention a dicing and cutting device shown generally as 100 includes the following major components, namely male top housing 102 , which cooperatively engage with female bottom housing 104 . Cutting device 100 further includes top blade 106 and bottom blades 108 , the top locating tube 110 slideably engaging with a bottom pin 111 . Bottom housing 104 includes a bottom rim 114 and top housing 102 , includes a top rim 112 . Bottom rim 114 and top rim 112 are used to engage with the hand for rotating the top housing 102 relative to the bottom housing 104 . Top blades 106 are held in position by top blade holder 118 and bottom blades 108 are held in position with bottom blade holder 120 . Bottom housing 104 defines cavity 130 within tubular walls 16 and bottom rim 114 . Food stuffs such as fruits, vegetables, herbs and spices are placed within cavity 130 and top housing 102 is slideably engaged into bottom housing 104 and is positively located with a bottom pin 111 , slideably engaging with a top locating tube 110 such that it rotatably pivots about pivot axis 191 . Other pivoting arrangements having the same function may also be used in place of the arrangement depicted. In the closed or engaged position as shown in FIGS. 18 and 19 , the top housing 102 is rotated relative to bottom housing 104 by applying twisting action with left and right hand. Top blades 106 and bottom blades 108 interpenetrate, but do not make contact with each other.
[0032] With food stuffs such as vegetables, fruits, herbs and/or spices and/or any other items positioned within cavity 130 are sliced and diced as top housing 102 is rotated relative to bottom housing 104 . Top blades 106 and bottom blades 108 , sheer, cut, slice and dice any material within cavity 130 which makes contact with the blades.
[0033] Top blades 106 and bottom blades 108 are preferably dimensionally the same and depicted as blades 200 . Details of blade 200 are shown in FIGS. 21 through 27 inclusively. Blade 200 includes the following major features namely, blade 200 has a width shown as W 202 and a height shown as H 204 , the blade has a curvature to it or a radius as shown as R 206 in FIG. 22 . The blade also has a thickness shown as T 208 and a cutting angle A 210 related to each cutting edge 218 . The opening shown as O is the space between the front side and the back side of two adjacent blades 200 and is shown as opening O 212 in FIG. 25 . The distance between the blades D as shown in FIG. 25 is the distance from the cutting edge 218 of one blade to the adjacent blade cutting edge 218 and is shown as distance D 214 .
[0034] Each blade 200 has a chamfered portion 216 related to each cutting edge 218 .
[0035] Referring now to FIG. 19 in particular, the space between the inner diameter 230 of tubular wall 1116 and the outer most top blade 106 is shown as space S 220 in FIG. 19 .
[0036] The inner diameter of bottom housing 104 is shown as ID 230 in FIG. 5 .
[0037] The dimensions of blade 200 and other important dimensions of dicing and cutting device 100 are summarized below as follows:
Dimension of Blade 200
230 ID=Inner Diameter=3″
202 W=Width=0.375″+/−0.125″
204 H=Height=0.75+/−0.25″
206 R=Radius=1.5″+/−0.5″=ID/2+/−0.5″
208 T=Thickness=0.035″+/−0.025″
210 A=Cutting Angle=31° (Range=21° to 55°)
212 O=Opening=0.165″
214 D=Distance=0.20+/−0.07
220 S=Space=0.18″ (Range=0.10″+0.22″)
[0038] The inventor has determined through trial and error testing that radius R 206 of blades 200 is preferably equal to ½ inner diameter ID 230 of tubular walls 116 of bottom housing 104 . Therefore, as inner diameter ID 230 of tubular walls 116 of bottom housing 104 becomes smaller and/or larger, Radius R 206 is adjusted accordingly to maintain radius R 206 of approximately ID÷2+/−0.5″.
[0039] Therefore for the example given above, for a 3″ inner diameter ID 230 , the preferable radius R 206 is 1.5″.
[0040] Preferably for a inner diameter ID 230 =3″, the cutting angle A 210 is preferably 31° and the space S 220 between tubular wall 116 and outer most top blade 106 is preferably 0.18″ and the distance 214 between blades is preferably 0.20″ when the width W 202 of blade 200 is 0.375″.
[0041] A person skilled in the art will note that there is a relationship between the distance D 214 and the width W 202 and the radius R 206 of the dicing and cutting device 100 . Certain minimum distances are adhered to prevent the blades 200 from contacting each other.
[0042] The inventor has also observed that deviating substantially from the preferred dimensions renders the unit inoperable and/or very difficult to use.
[0043] Referring to FIG. 19 with top housing 102 co-operatively engaged with bottom housing 104 in an engaged position 141 , the reader will note that the top and bottom blades interpenetrate, such that the opening O 212 defined by the bottom blades 108 receives a top blade 106 there between the space approximately equally distant between the two bottom blades 108 .
[0044] In this manner the top housing 102 can be rotated relative to the bottom housing 104 by manually spinning and/or turning top housing 102 relative to bottom housing 104 in the engaged position 141 . In this manner any food stuff such as garlic 151 as depicted in FIG. 19 will be engaged between the top blades 106 and the bottom blades 108 as the top housing 102 is turned relative to the bottom housing 104 , thereby cutting and dicing garlic 151 due to rotationally passing top blades 106 between bottom blades 108 .
[0045] A person skilled in the art will note that blade 200 is a planar curved section having a thickness T 208 and a radius R 206 . The curvature or the radius R 206 of blade 200 is required in order to produce a smooth operation of the dicing and cutting device 100 .
[0046] It should be apparent to persons skilled in the arts that various modifications and adaptation of this structure described above are possible without departure from the spirit of the invention the scope of which defined in the appended claim. | A dicing and cutting device comprising a male top housing slideably co-operatively engaging with a female bottom housing, wherein the top housing including downwardly projecting top blades, and the bottom housing including upwardly projecting bottom blades, such that food stuffs located with a cavity defined within the housings are sliced and diced upon rotation of the top housing relative the bottom housing. | 1 |
The present invention relates to a double chainstitch sewing machine for forming stitches for applying a cover thread at the lower side or upper and lower sides of a workpiece.
BACKGROUND OF THE INVENTION
FIG. 11 shows a double chainstitch sewing machine for forming stitches related to stitch type number 407 and others designated in the United States Federal Standards No. 751a.
In this sewing machine, the needle thread is first passed from a thread tension device 117 into a thread eye of a first thread take-up 116 through a fixed thread guide 114 . In succession, the needle thread is passed into a thread eye of a movable thread guide 115 through a U-shaped second thread take-up 118 , and is passed into an eyelet of a needle holder 120 at the lower end of a needle bar 112 and an eyelet of a needle 119 .
When forming stitches for applying a cover thread at the upper and lower sides of a workpiece by this double chainstitch sewing machine, an upper cover thread mechanism disclosed in Japanese Utility Model 63-26144 is disposed beneath a sewing machine head 111 a. The upper cover thread is supplied into the upper cover thread mechanism by way of a thread take-up for upper cover thread (not shown) provided in the first thread take-up 116 from the thread tension device 117 .
The movable thread guide 115 is affixed to the upper end of the needle bar 112 , and moves up and down together with the needle bar. The first thread take-up 116 is affixed to an oscillating shaft 113 , and oscillates about the shaft. All these members move up and down or oscillate outside of the sewing machine arm 111 and are hence dangerous. Accordingly, to protect the operator from danger, a guard is required, but such guard makes it difficult to pass the thread. If the guard is designed to be opened and closed for the ease of passing of thread, it leads to a cost increase.
Further, in this sewing machine, there is a probability of oil leak from the support parts of the needle bar projecting from the top of the sewing machine arm, and the oscillating shaft projecting to the front side of the sewing machine arm.
In such double chainstitch sewing machine, the needle thread from the thread tension device to the workpiece runs for a long thread pathway extending from the thread tension device to the workpiece by way of the fixed thread guide, first thread take-up, second thread take-up and movable thread guide. Accordingly, it is likely to have effects of stretchable characteristic of thread, and it is hard to obtain an optimum thread take-up amount.
Especially in largely stretchable thread such as woolly thread, the movable thread guide, first thread take-up and second thread take-up act more to stretch thread than to take up thread, so that the take-up action is unstable. It is hard to adjust by the first and second thread take-up amounts and is hence difficult to obtain a double chainstitch of a desired touch. Still more, since the upper cover thread is taken up at the same timing as the needle thread, it is hard to obtain a desired covering chainstitch.
It is hence an object of the present invention to eliminate the difficulty in threading without substantially increasing the cost, by eliminating movable thread take-up members on the upper side and front side of the sewing machine arm, and installing substituent movable thread guide and first and second thread take-ups centrally at the lower end of the needle bar or jaw of the sewing machine arm so as to decrease the dangerous positions for the operator. It is other object of the present invention to avoid the probability of oil leak from the support parts of the needle bar projecting from the top of the sewing machine arm, and the oscillating shaft projecting to the front side of the sewing machine arm.
It is a further object of the present invention to present a double chainstitch sewing machine capable of obtaining a desired stitch tension easily by shortening the thread pathway length from the workpiece to the thread tension device and decreasing effects of thread stretchable characteristic on take-up of needle thread, and a double chainstitch sewing machine related to a flat seam for taking up upper cover thread at optimum timing by installing a thread take-up for upper cover thread independently of a thread take-up for the needle thread.
SUMMARY OF THE INVENTION
In a first aspect of the double chainstitch sewing machine according to the present invention, a movable thread guide for guiding the needle thread is fixed to the lower end of the needle bar. A fixed thread guide is fixed to the jaw of the sewing machine arm. A thread take-up cam is also fixed to the jaw of the sewing machine arm, and the cam section of the thread take-up cam extends in the vertical direction by intersecting with the needle thread pathway between the fixed thread guide and the movable thread guide. The needle thread from the fixed thread guide to the movable thread guide is oscillated up and down from the fixed thread guide by the movable thread guide moving up and down together with the needle bar, and is supplied into the cam section of the thread take-up cam. Thus, by interaction of the movable thread guide and the cam section of the thread take-up cam, the needle thread is taken up from the thread tension device to the needle.
In a second aspect of the double chainstitch sewing machine according to the present invention, a movable thread guide for guiding the needle thread is fixed to the lower end of the needle bar, and a fixed thread guide having mutually opposite right and left thread eyes is fixed to the jaw of the sewing machine arm. A thread take-up cam is also fixed to the lower end of the needle bar, and the cam section of the thread take-up cam is disposed between the thread eyes of the fixed thread guide. The needle thread from the fixed thread guide to the movable thread guide is oscillated up and down from the fixed thread guide by the movable thread guide moving up and down together with the needle bar, and the needle thread between the thread eyes of the fixed thread guide is bent by the vertical motion of the cam section of said thread take-up. Thus, by interaction of the movable thread guide and the thread take-up cam, the needle thread is taken up from the thread tension device to the needle.
According to these aspects of the present invention, since the thread take-up oscillating vertically at the front side of the sewing machine arm and the movable thread guide moving vertically as being affixed to the upper end of the needle bar are eliminated, the operator is liberated from the danger during operation of the sewing machine at the front side and upper side of the sewing machine arm. At the same time, the support parts of the needle bar projecting from the top of the sewing machine arm, and the oscillating shaft projecting to the front side of the sewing machine arm in the conventional sewing machine can be eliminated, and probability of oil leak is avoidable. Further, the movable thread guide of the thread take-up mechanism is attached to the lower end of the needle bar, the fixed thread guide is fixed and installed at the jaw of the sewing machine arm, and the thread take-up cam is attached to the lower end of the needle bar or fixed and installed at the jaw of the sewing machine arm, so that the thread take-up action of the needle thread takes place near the needle, and the thread pathway length from the workpiece to the thread tension device can be shortened, and the thread take-up action of the needle thread is done without substantially having effects of the stretchable characteristic of the thread.
In a third aspect, relating to a double chainstitch sewing machine having a plurality of needles, two or more thread eyes are provided in the movable thread guide, and are disposed obliquely to the motion direction of needle bar.
In a fourth aspect, relating to a double chainstitch sewing machine having a plurality of needles, two or more thread eyes are provided in the movable thread guide, the fixed thread guide is composed of a plurality of thread guide members, and each thread guide member can adjust the guiding position of the needle thread individually.
In the double chainstitch sewing machine having a plurality of needles, the eye of each needle is different in height in order to match the timing with the eyelet of the looper, and the needles are arranged obliquely. In the present invention, since the thread eyes of the movable thread guide are arranged obliquely, or the thread guide members of the fixed thread guide can be adjusted individually, the thread take-up amount necessary for each needle thread can be assured.
In a fifth aspect of the double chainstitch sewing machine according to the present invention, the thread tension device for adjusting the tension of the upper cover thread is provided at the front side of the sewing machine arm, and an upper cover thread mechanism having a spreader for swinging the upper cover thread laterally to be engaged with the needle thread is provided at the jaw of the sewing machine arm, said upper cover thread mechanism is comprised a fixed thread guide for guiding the upper cover thread and a thread swing guide. The thread swing guide has a thread eye for leading the upper cover thread from the fixed thread guide to a thread lead tool, and a slot for leading the upper cover thread from the thread lead tool to the spreader. The spreader includes a thread take-up tool for taking up the upper cover thread by engaging with the upper cover thread from the fixed thread guide to the thread swing guide.
According to the present-invention, since the thread take-up tool for the upper cover thread is attached to the spreader, the motion of the thread take-up tool is synchronized with the motion of the spreader, and the upper cover thread is taken up independently of the thread take-up tool of the needle thread.
In a sixth aspect, since the upper end of the needle bar is positioned within the sewing machine frame and the length of the needle bar is shortened, it is able to reduce the weight of the needle bar and to increase the sewing machine speed.
In a seventh aspect, the needle bar drive mechanism comprises an oscillating shaft crossing orthogonally with the upper shaft and oscillating in cooperation with the rotation of the upper shaft, and a lever fixed to the oscillating shaft for driving the needle bar as being coupled to the upper end of the needle bar.
Other features and effects of the present invention will be more clearly understood in the following detailed description of the embodiments by those skilled in the art. It must be, however, noted that the technical scope of the present invention is not limited to the embodiments and the accompanying drawings alone.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view showing an essential mechanism of a double chainstitch sewing machine of the present invention.
FIG. 2 is a magnified front view of the jaw of the sewing machine in FIG. 1 .
FIG. 3 is a side view thereof.
FIG. 4 is a perspective view showing an essential mechanism of other double chainstitch sewing machine of the present invention.
FIG. 5 is a magnified front view of the jaw of the sewing machine in FIG. 4 .
FIG. 6 is a magnified front view of the jaw of the sewing machine in FIG. 2 further provided with an upper cover thread take-up mechanism.
FIG. 7 is a perspective view showing essential parts of a needle bar mechanism.
FIG. 8 is a perspective exploded view of the needle bar mechanism.
FIG. 9 is a perspective view of a looper mechanism.
FIG. 10 is a perspective view of an upper cover thread mechanism.
FIG. 11 is a perspective view of a conventional double chainstitch sewing machine.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A double chainstitch sewing machine in a first embodiment of the present invention comprises a needle bar mechanism, a looper mechanism, a sewing thread take-up mechanism, and is designed to form stitches of stitch type number 406 designated in the United States Federal Standard No. 751a.
Each mechanism is sequentially described below.
Needle Bar Mechanism
At the lower end of a needle bar 1 shown in FIG. 7 and FIG. 8, a needle 5 is provided through a needle holder 3 as shown in FIG. 2 and FIG. 5. A pi-shaped guide 7 formed at the upper end of the needle bar is coupled to a lever 11 through a pin 12 , and the lever 11 is fixed to one end of an oscillating shaft 9 which oscillates in cooperation with the upper shaft not shown. The oscillating shaft 9 is orthogonal to the upper shaft, and is supported by a bearing 13 fixed to the sewing machine frame. A crank 15 fixed to other end of the oscillating shaft 9 is coupled to a rod 17 fitted to an eccentric cam (not shown) of the upper shaft, and when the upper shaft rotates, the lever 11 fixed to the oscillating shaft 9 oscillates vertically, thereby making the needle bar 1 supported by a bush 19 to move up and down. By vertical motion of the needle bar, the needle moves up and down by penetrating through a throat plate (not shown).
Looper Mechanism
As shown in FIG. 9, a looper 21 is mounted on a platform 24 fixed to a looper shaft 23 . The looper shaft 23 is coupled to a leading end of a lever 27 fixed to an oscillating shaft 25 . A crank 29 affixed to the oscillating shaft 25 is coupled to an eccentric cam 35 of a lower shaft 33 through a rod 31 , and when the lower shaft 33 rotates, the oscillating shaft 25 oscillates, and the lever 27 swings right and left to move the looper shaft 23 reciprocally to right and left. By this reciprocal motion of the looper shaft 23 , the looper 21 moves back and forth almost horizontally toward the needle 5 .
Needle Thread Take-up Mechanism
The needle thread take-up mechanism controls take-up of needle threads 51 a, 51 b from a thread tension device 45 to the needle 5 , and comprises a movable thread guide 37 , a thread take-up cam 39 , fixed thread guide 41 , and others as shown in FIG. 1 and FIG. 2 . The movable thread guide 37 is fixed to the needle bar 1 on the needle holder 3 as shown in FIG. 3, and has thread eyes 48 for passing the needle threads 51 a, 51 b in oblique upward arrangement. The movable thread guide 37 moves up and down together with the needle bar 1 , and takes up the needle threads 51 a, 51 b leaving the fixed thread guide 41 by swinging up and down.
The fixed thread guide 41 attached to the leading end of an L-shaped bracket 47 fitted to the outside of a jaw 43 a of a sewing machine arm 43 by a screw 44 so that the lateral position may be adjustable, and is composed of three needle thread guide members 41 a, 41 b, 41 c having thread eyes for guiding the needle threads 51 a, 51 b, 51 c individually. These needle thread guide members 41 a, 41 b, 41 c are fixed to the bracket 47 by screws (not shown) so that the vertical position may be adjustable individually, and the needle thread guide member closer to the needle bar 1 is set higher as shown in FIG. 2 . The bracket 47 has a needle thread lead plate 42 for passing the needle threads 51 a, 51 b from the thread tension device 45 to the fixed thread guide 41 .
The thread take-up cam 39 is attached to the portion folded forward at one end of a bracket 49 by a screw 51 so as to be adjustable in vertical position, and the bracket 49 is fixed to the outside of the jaw 43 a of the sewing machine arm 43 by a screw 52 so as to be adjustable in lateral position.
This thread take-up cam 39 has a cam section intersecting with the thread pathway between the fixed thread guide 41 and movable thread guide 37 , and extending in the vertical direction, and the cam section is engaged with the needle threads 51 a, 51 b between the fixed thread guide 41 and movable thread guide 37 , and takes up the needle threads 51 a, 51 b from the workpiece to the thread tension device 45 by way of the thread guide members 37 , 41 , 42 together with the movable thread guide 37 .
In the illustrated embodiment, the thread tension device 45 of the needle thread is provided at the front side of a base part 43 b of the sewing machine arm 43 , but it is not limited to this structure. For example, to shorten the thread pathway length ranging from the workpiece to the thread tension device 45 further, the thread tension device 45 may be disposed in a wider part 43 c of the sewing machine arm 43 , or may be set closer to the sewing portion of the workpiece.
A double chainstitch sewing machine in a second embodiment of the present invention comprises a needle bar mechanism, a looper mechanism, a needle thread take-up mechanism, and the needle bar mechanism and looper mechanism are same as in the double chainstitch sewing machine in the first embodiment.
Needle Thread Take-up Mechanism
The needle thread take-up mechanism differs from the needle thread take-up mechanism in the first embodiment in the following points.
As shown in FIG. 4 and FIG. 5, a thread take-up cam 55 is supported by a needle bar 1 . That is, a mounting part 55 a of the thread take-up cam 55 is affixed to a bracket 57 fixed to a needle holder 3 by a screw 58 so as to be adjustable in lateral position, and the thread take-up cam 55 is supported by the needle bar 1 , and it moves up and down together with the needle bar 1 unlike the first embodiment. A fixed thread guide 52 is composed of a pair of right and left plates, and a pin 61 for fitting a holder 63 is provided at its upper end. The fixed thread guide 52 is disposed at the right and left side of the thread take-up cam 55 . The holder 63 is affixed to the outside of a jaw 43 a of a sewing machine arm 43 by a screw 62 so as to be adjustable in vertical position. A pin 61 projecting to a side is supported by the holder 63 so as to be slidable laterally and rotatable, and is fixed to the holder 63 by a screw 64 . The fixed thread guide 52 has mutually confronting right and left thread eyes.
The thread take-up cam 55 is engaged with needle threads 51 a, 51 b, 51 c passed in the fixed thread guides 52 at both sides, and moves up and down together with the needle bar 1 , thereby taking up the needle threads 51 a, 51 b, 51 c. A movable thread guide 65 has a mounting part 65 a affixed to the needle holder 3 by a screw 66 so as to be adjustable in vertical direction, and also has plural thread eyes 65 b for passing the sewing threads 51 a, 51 b, 51 c.
The movable thread guide 65 moves up and down together with the needle bar 1 same as in the first embodiment, and takes up the needle threads 51 a, 51 b, 51 c, ranging from the work piece to the thread tension device 45 through the fixed thread guide 52 .
A double chainstitch sewing machine in a third embodiment of the present invention is similar to the double chainstitch sewing machine in the first embodiment, except that the upper cover thread mechanism and upper cover thread take-up tool are further added.
The upper cover thread mechanism and upper cover thread take-up tool are described sequentially below.
Upper Cover Thread Mechanism
As shown in FIG. 10, an oscillating shaft 69 rotatably supported by a bushing 68 in a sewing machine arm 43 is provided parallel to an upper shaft 67 . An oscillating lever 71 attached to the oscillating shaft 69 is coupled to the upper shaft 67 through a rod 73 fitted to an eccentric cam of the upper shaft 67 , and by rotation of the upper shaft 67 , the oscillating shaft 69 oscillates. A crank arm 75 is affixed to the leading end of the oscillating shaft 69 . A longitudinal shaft 77 supported rotatably by the sewing machine arm 43 has a lever 79 at its upper end, and a spreader 81 is fixed to the lower end extended to the outside of the sewing machine arm 43 . This spreader 81 is composed of a spreader holder 81 a fixed to the lower end of the longitudinal shaft 77 and a spreader piece 81 b fitted to the spreader holder 81 a.
The leading end of the lever 79 of the longitudinal shaft 77 is provided a pin 83 . The pin 83 is coupled to a cylindrical part 76 at the lower end of the crank arm 75 through a columnar peg 85 . Accordingly, when the upper shaft 67 rotates, the oscillating shaft 69 oscllates and the crank arm 75 oscillates back and forth, so that the longitudinal shaft 77 oscillates rotatably through the columnar peg 85 and the pin 83 . By rotatable oscillation of the longitudinal shaft 77 , the spreader piece 81 b of the spreader 81 oscillates as with swinging right and left.
Upper Cover Thread Take-up Mechanism
As shown in FIG. 6, a fixed thread guide 91 is provided in the jaw 43 a of the sewing machine arm 43 . The fixed thread guide 91 has a long thread eye 92 and a round thread eye 93 for passing the upper cover thread 89 passing from a thread tension device (not shown) through a thread lead piece 105 . The needle holder 3 has a thread lead tool 95 having a thread eye 94 for passing the upper cover thread 89 .
A thread swing guide 97 affixed to the outside of the jaw 43 a of the sewing machine arm 43 by a screw 96 so as to be adjustable in vertical direction has a first thread eye 101 and a second thread eye 102 for passing the upper cover thread 89 from a cover thread take-up tool 99 to the thread lead tool 95 . A small tension device 103 is provided in the thread pathway between the two thread eyes 101 , 102 . The upper cover thread 89 positioned between the both thread eyes is pressed to the front side of the thread swing guide 97 by means of the small tension device 103 .
An arc-shaped slot 98 is provided at the leading end of the thread swing guide 97 . The upper cover thread 89 from the thread lead tool 95 to the spreader 81 is passed into the arc-shaped slot 98 . The cover thread take-up tool 99 is provided in the spreader holder 81 a attached to the lower end of the longitudinal shaft 77 shown in FIG. 10 . This cover thread take-up tool 99 has a thread eye 100 for passing the upper cover thread 89 from the fixed thread guide 91 to the first thread eye 101 of the thread swing guide 97 .
As shown in FIG. 6, the upper cover thread 89 is passed into the long thread eye 92 or round thread eye 93 of the fixed thread guide 91 from the thread tension device (not shown) to the thread lead piece 105 , and runs through the small tension device 103 by way of the thread eye 100 of the cover thread take-up tool 99 and the first thread eye 101 of the thread swing guide 97 . The upper cover thread 89 running through the small tension device 103 is engaged with the hook let 81 c of the spreader piece 81 b by way of the second thread eye 102 , thread eye 94 of the thread lead tool 95 , and slot 98 of the thread swing guide 97 .
While the sewing machine is running, the upper cover thread 89 is mainly taken up by the cover thread take-up tool 99 , and the thread take-up amount varies depending on the difference of passing into the long thread eye 92 and round thread eye 93 formed in the fixed thread guide 91 . This difference corresponds to the type of thread, for example, the cotton thread corresponds to the long thread eye 92 , and the woolly thread to the round thread eye 93 .
The cover thread take-up tool 99 is preferred to be designed so that the distance to the longitudinal shaft 77 of the upper cover thread mechanism may be variable. The thread tension device for the upper cover thread is not described in detail, but its position is preferred to be closer to the sewing part, such as the wide part 43 c of the sewing machine arm 43 , in order to shorten the thread pathway length of the upper cover thread. | In a double chainstitch sewing machine, a movable thread guide 37 is fixed to the lower end of a needle bar 1. A fixed thread guide 41 and a thread take-up cam 39 are fixed to a jaw 43 a of a sewing machine arm 43. The thread take-up cam 39 has a cam section to be engaged with needle threads 51 a, 51 b from the fixed thread guide 41 to the movable thread guide 37, and takes up the needle threads oscillating up and down by vertical motion of the movable thread guide 37. Thread take-up members such as movable thread guide 37, fixed thread guide 41, and thread take-up cam 39 are disposed centrally at the lower end of the needle bar near the needle and in the jaw 43 a of the sewing machine arm 43. As a result, there is no member for thread take-up moving at the upper side and front side of the sewing machine arm, and dangerous positions for the operator can be decreased. Further, the thread pathway length from the workpiece to the thread tension device is shortened, and the effects of thread stretch properties can be decreased. | 3 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 13/122,388, filed Apr. 1, 2011, which is a U.S. National Phase application under 35 U.S.C. §371 of International Patent Application No. PCT/US2009/059004, filed Sep. 30, 2009, and published in English on Apr. 8, 2010, which claims priority to U.S. Provisional Application 61/101,932, filed Oct. 1, 2008. The entirety of each of the foregoing applications is hereby incorporate by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to medical devices, systems and methods for bone fixation. Specifically, the invention is directed to stabilize adjoining vertebrae in the cervical, thoracic, and lumbosacral spine. More specifically, the invention is directed to fusion or stabilization of vertebrae in the lumbar spine to alleviate axial back pain. Most specifically, the invention is directed to improving minimally invasive surgical (MIS) approaches to pedicle screw fusion by reducing the number and size of incisions and the size of the medical instruments inserted therein.
[0004] 2. Description of the Related Art
[0005] While some lower back conditions can be ameliorated with non-surgical approaches, spinal fusion is recommended for certain conditions when non-surgical approaches fail. Non-surgical approaches include medications, physical therapy, chiropractic treatment, traction, epidural steroid injections, facet blocks or rhizotomy, weight loss, smoking cession, and acupuncture. Conditions that commonly serve as indications for spinal fusion or stabilization surgery can be divided generally into three categories: (i) trauma induced, (ii) curvature, and (iii) degenerative.
[0006] Trauma induced conditions include fractures and ligamentous injuries. Fractures typically result from an unfortunate incident involving an extraneous force or fall but may also arise from pathologic conditions, such as cancer or osteoporosis. Fractures are often compressive in nature and typically lead to a pathological curving of the spine resulting in a loss of the natural lordotic curvature in the lumbar and cervical spine, known as kyphosis. Fractures of the spine also occur with translational or rotational forces perpendicular to the axis of the spine. These forces result in fractures of the facet or pars interarticularis (pars). If the external forces are large enough, vertebrae can collapse resulting in a burst fracture that can injure all 3 columns of the vertebrae (anterior, middle, and posterior columns). Many traumatic injuries can heal without surgery, but unstable injuries that pose a risk for neurologic injury and/or pain require stabilization through a procedure such as fusion.
[0007] A condition called spondylolisthesis characterized by slippage of the spine bones or vertebrae relative to one another can result from fractures of the pars interarticularis (pars fracture) known as spondylolysis. Spondylolisthesis can also develop from malformation of the facet joints by degenerative arthritis as well as congenital malformation and pathologic conditions such as tumors. If the pars on both sides are fractured, then the spinous process and lamina are essentially completely disconnected from the pedicle and vertebral body. This large fragment is called the Gill body. Pars fractures are actually common in people of all ages (often acquired in the teenage years). While, many of these patients are mildly symptomatic and do not require surgery, those with progressive symptoms may require surgical decompression with or without fusion. Spondylolisthesis results in misalignment of the spine and increases the risk of a nerve becoming entrapped. Nerves travel within the spinal canal bounded by the vertebrae and their roots protrude from the curved openings in the sides of the vertebrae called foramina (singular is foramen). These spinal nerves are suspected to be the source of back and radicular pain when they become entrapped or when the nerve endings become irritated by irregular or abrasive motion around a disc, bone, or joint. Spondylolisthesis can also aggravate or be accompanied by degeneration of disc or facet joint which can lead to axial back pain.
[0008] The normal curvature of the lumbar and cervical spine is lordosis, where the posterior aspect of these spinal levels forms a concave curve. The thoracic spine normally has a kyphotic or convex curve. Curvature conditions include straightening of the natural curvature as well as abnormal lordosis, abnormal kyphosis or lateral/rotational bending called scoliosis. Curvature conditions can occur idiopathically during adolescence, i.e. adolescent idiopathic scoliosis, or develop as a secondary problem in situations where spinal muscle activation is abnormal such as cerebral palsy, spina bifida, or tethered cord syndrome. Abnormal spinal curvature is common in spinal degeneration when the discs and joints degenerate asymmetrically leading to a progressive curvature (scoliosis, kyphosis, or lordosis) as the biomechanics of the spine are disrupted. Curvature conditions also occur after trauma with compression or burst fractures or with ligamentous injury. Additionally, curvature conditions can occur iatrogenically after previous spinal surgery where the anatomy and biomechanics of the spine have been altered. Such situations include the removal of the posterior tension band after laminectomy as well as the alteration of physiologic movement after spinal fusion leading to adjacent level compensation and degeneration. Curvature conditions lead to abnormal biomechanical stress on the discs and facet joints accompanied by compensatory measures such as facet or ligamentous hypertrophy. Patients can develop both axial back pain and radicular pain. In patients who have failed conservative therapy and bracing, surgery can be effective. Surgery in these conditions includes decompression of nerve or spinal cord compression as well as fusion or stabilization. Curvature can be corrected through surgery, and fusion prevents further curvature from developing.
[0009] Degenerative conditions include spinal arthritis and recurrent disc herniation. Spinal arthritis is the most common indication for fusion and may exist in the form of severe disc degeneration (also called Degenerative Disc Disease, DDD) or facet disease. Degenerative arthritis can also be a cause of spondylolisthesis in addition to traumatic fractures discussed above. Degenerative conditions are generally accompanied by nerve compression causing radicular pain in the distribution of the nerve's receptive field, which usually correlates with and is manifested in arm or leg pain. Pure nerve compression syndromes such as herniated nucleus propulsus (herniated discs) or foraminal stenosis (narrowing of the side foramina canals through which the nerves pass) can often be treated with decompression without fusion. Pure disc degeneration syndromes can be treated with fusion without decompression of the nerves. However, most commonly disc degeneration occurs in combination with nerve compression causing both axial back pain and radicular limb pain. In these circumstances fusion surgery is combined with nerve decompression surgery.
[0010] Fusion functions to eliminate motion in the disc space and facet joints between adjacent vertebrae. The vertebrae provide the rigid structural framework of the spine and the fibrocartilagenous disc space acts as a cushion or shock-absorber. Degradation of the disc space can distort alignment and alter the biomechanical cushion that the disc affords the adjacent vertebrae. This degradation alters the forces impacted upon the vertebrae and results in axial back pain. Fusion is designed to eliminate movement between adjacent vertebrae by either forming a solid bridge of bone across the disk space and/or creating new bone formation in the posterolateral space to provide stabilization, rigidity, and strength. Sometimes fusion involves a bone graft taken from another location in the body (i.e. autograft from the iliac crest in the pelvis) or from an external source, i.e. allograft. Physicians commonly refer to the level of a fusion. A single level fusion involves stabilizing the two vertebral bones adjacent to a diseased disc. A two-level fusion involves stabilizing three adjacent vertebral bones spanning two problematic disc spaces. Each vertebra makes contacts (joints) with adjacent vertebrae at three points, the paired facet joints located posteriorly and the intervertebral disc located anteriorly. Thus, lumbar fusion can be directed either at the posterior facet joints or at the anterior interbody/disc space or both. When an anterior interbody fusion is performed in combination with posterior fusion, the procedure is termed 360° fusion. One commonly used technique of posterolateral fusion is pedicle screw fusion where screws are directed into the pedicle portions and the bodies of adjacent vertebrae and then rods are connected to the screws across the disc spaces. The screws and rods hold the adjacent vertebrae motionless relative to one another and allow the bone graft that is placed either in the interbody (disc) space or in the posterolateral space to grow into solid bone. Conventional pedicle screws and rods are metal, typically titanium (Ti) alloy but have been made from stainless steel as well. Recently rods have been made from a minimally flexible polymer called polyetheretherketone (PEEK).
[0011] Interbody fusion involves placing one or more spacers (typically pre-loaded with bone graft material) within the interbody (disc) space between bony vertebral bodies after the degenerated disc has been cleaned out and removed. Spacers are made from bone grafts, titanium, carbon fiber, or polymers such as PEEK. Interbody fusion can be performed through several approaches including: an anterior approach (anterior lumbar interbody fusion, ALIF), a posterior approach (posterior lumber interbody fusion, PLIF, or transforaminal lumbar interbody fusion, TLIF), or a lateral approach (direct lateral interbody fusion, DLIF™—Medtronic, or extreme lateral interbody fusion, XLIF™—Nuvasive). The aim of these approaches is to remove the degenerated disc and replace the disc with material that induces bony fusion. Alternatively the disc can be replaced with an artificial joint/disc (discussed below). Each of these interbody approaches has advantages and disadvantages. Anterior procedures require a retroperitoneal dissection and risk injury to the large blood vessels anterior to the lumbar vertebrae. Also injury to the nerve plexus anterior to the vertebrae can result in sexual dysfunction. The lateral approach is promising but is limited to the upper and mid lumbar levels (rostral to L5,S1) because of obstruction by the iliac crest. The posterior interbody approach is more time consuming and typically requires more muscle dissection and retraction. However, the posterior approach allows the placement of the interbody graft, posterior pedicle screw fusion, and decompression of nerves all to occur through the posterior incision(s).
[0012] Although anterior and lateral approaches can be performed stand-alone (without posterior instrumentation), many surgeons will back-up or supplement anterior or lateral interbody fusions by placing pedicle screws posteriorly after the interbody cage or graft has been placed. This 360° fusion limits movement more than just an isolated anterior or posterior fusion, and fusion rates are increased. However in ALIF and lateral interbody (DLIF, XLIF) cases, two sets of incisions are required for a 360° fusion.
[0013] The posterior approaches (TLIF and PLIF) allow an interbody fusion, pedicle screw fusion, and neural decompression to be done all through the same posterior incision(s). In the TLIF, a single large interbody spacer is inserted on the side ipsilateral to the patient's symptomatic side after neural decompression is completed. If both sides are symptomatic then decompression is required on both sides. A PLIF is performed by placing two interbody spacers, one on each side. Posterior procedures may be done according to: (i) an invasive open procedure in which a large incision and/or several incisions are made, (ii) a percutaneous approach in which small incisions and/or few incisions are made, and potentially (iii) an endoscopic approach in which small incisions are made and all tools and devices are inserted through portals with visualization provided on an external monitor.
[0014] As an alternative to fusion, recent advances in interbody stabilization have resulted in the development of artificial disc technology. Artificial discs replace the degenerated discs and allow continued motion at the joint. Both cervical and lumbar artificial discs have been developed. Additionally, dynamic stabilization techniques have been developed for the posterior spine. These posterior techniques utilize pedicle screws and a dynamic rod. Typically the dynamic rod has a mechanism to bend under certain loads or forces, thereby absorbing some stress and strain that is applied to the spine. The advantage of dynamic stabilization is that motion is preserved in the spine. However, the durability of these systems may be an issue. In fusions, the bone graft (interbody or posterolateral) eventually fuses the vertebrae eliminating the need for the spinal instrumentation (screws and rods). However in dynamic stabilization, fusion does not occur so the screws and dynamic rods will always be subjected to the strain and forces of the spine. Over time the possibility of loosening of the pedicle screws or mechanical failure may increase. Sometimes the use of a slightly flexible rod such as a rod made of PEEK may actually increase fusion by reducing stress shielding. Stress shielding occurs with rigid fusion constructs that shields the vertebral bone in contact with the bone graft from the stresses required to form and remodel bone.
[0015] Posterior lumber stabilization (fusion and dynamic stabilization) techniques have evolved into minimally invasive approaches because such minimized exposures reduce patient morbidity and facilitate patients' recovery to function. Blood loss and hospital stays are shorter. The process of performing a minimally invasive pedicle screw fusion is the same as that for dynamic stabilization and involves two basic parts. First, screws are placed percutaneously through the pedicle into the vertebral body. For minimally invasive systems, cannulated screws are placed percutaneously over a fluoroscopically (an X-ray that can be seen on a video screen) guided wire. Generally, two screws are used on each vertebral body being fused, one on a right side and the other on a left side. The second part of the process involves connecting the screws with a rod and locking the rod and screws together. In dynamic stabilization, the rod or rod-like device (flexible connector) is bendable, but the process of inserting this bendable rod is the same as that for fusion. For example, a rod-like device (flexible connector), like a rod, fits within the screw heads, but may also include an element (a shock absorber, a spring, etc.) that allows some motion. The variations between different minimally invasive systems mostly arise in the method of placing the rod and locking the rod with the screws through a minimal incision.
[0016] After the screws are inserted and before the intervertebral body spacer is inserted, the damaged or degenerated disc within the disc space must be removed. In the TLIF approach, the disc space is accessed through a facetectomy in which the foramen around the nerve roots is opened with a bone-cutting tool such as an osteotome or a high speed drill. In the PLIF approach, laminectomies or laminotomies are performed to access the disc space. Both TLIF and PLIF allow for decompression of the spinal thecal sac and the nerve roots; however, the facetectomy in a TLIF allows the maximum decompression of the exiting nerve root on that side. With gentle retraction of the thecal sac, the disc space is easily accessed. Then the instruments used for clearing out the degenerated disc may be inserted into the disc space to complete the discectomy.
[0017] Following removal of the disc, the surgeon should prepare the bony surfaces, known as the end plates, of the vertebral bodies on each side of the disc that was removed. Peeling off the end plate with a tool such as a curette induces bleeding which stimulates healing and assimilation of the bone graft to be inserted into the interbody space. The spacer or cage that is to be inserted is typically constructed of bone, titanium, carbon fiber, or polymers such as PEEK. The spacer is usually hollow or at least porous to accommodate bone graft material therein. Bone inducing protein such as bone morphogenetic protein (BMP) is also commonly placed within the spacer. After placing the spacer and bone graft, the rods may be inserted into the pedicle screws and the screws can be tightened to lock the rods in place.
[0018] Typically the placement of the percutaneous screws is fairly straight forward. The insertion of the rod through the screw heads and locking of the rod with the screws are the steps that are currently most difficult through a minimal incision. In most of the minimally invasive surgery (MIS) systems used today, a guide wire is placed percutaneously under fluoroscopic guidance through the pedicle. Then, dilating tubes and finally a tower is inserted over the wire to both dilate the tissue and also allow the screw to be placed through the tower. Therefore, the tower has to be larger than the maximum diameter of the screw head. Once the towers are in place and screws have been placed in each tower, the rod is then inserted through one of a variety of methods. The leading MIS system is Sextant™ by Medtronic. In this system, the rod is placed by forming a pendulum like mechanism. The two or three towers (for one or two-level fusion, respectively) are coupled together to align the towers, and the rod is swung around through a separate incision superior or inferior to the towers in a pendulum fashion. Once the rod is swung in place, locking caps are placed through the towers and tightened. Alternatively, most of the other systems insert the rod through one of the towers and then turn the rod approximately 90° to capture the other screws in the other towers. Inserting the rod through the screw heads in a minimally invasive system is done blindly, i.e. without direct visualization of the screw head. Thus this process is sometimes tedious and frustrating.
[0019] The Sextant™ system and other systems that use towers are limited by both the number of incisions required and the size of each incision. The use of a separate tower for each screw requires a separate incision for each screw. The Sextant™ system also requires an additional incision for the rod, equaling six incisions (three on each side) for a single level fusion and eight incisions for a two level fusion. The other tower systems that use the direct rod insert and turn mechanism still require one incision for each screw and each incision has to be larger than the size of a tower through which the screws are inserted. Typically, each incision is at least 15 mm in length.
[0020] U.S. Pat. No. (hereinafter USP) 7,306,603 entitled “Device and method for percutaneous placement of lumbar pedicle screws and connecting rods” by Frank H. Boehm, Jr., et al. and assigned to Innovative Spinal Technologies (Mansfield, Mass.) discloses a system of connecting a rod to the pedicle screws using a pin and recesses within the screw heads. According to this system the rod can pivot about a longitudinal axis of the pin between a first position in which the rod is parallel to the longitudinal axis of the screw (i.e. vertically oriented) and a second position in which the rod is transverse to that axis in order to bridge screws on adjacent vertebrae. U.S. Pat. No. '603 teaches various guide systems (see FIGS. 5 and 6), rod holder systems (see FIGS. 8, 9, 10, and 11), and a rod guide system (see FIG. 12 ) but does not include a sleek, detachable wire-guided system among them. Rather, the systems illustrated are tower-like with rather bulky dilators (80 and 86 in FIGS. 6 and 8), sheaths (81 in FIG. 6), and/or outer housing (120 in FIGS. 11 and 12).
[0021] U.S. Patent Application Publication No. (hereinafter US Pub. No.) 20080140075 entitled “Press-On Pedicle Screw Assembly” by Michael D. Ensign and assigned to Alpinespine, LLC (American Fork, Utah) discloses attaching the rod to screw heads indirectly via a tulip assembly. The tulip assembly has a housing with an inner diameter smaller than an inner diameter of the screw head such that it is easily pressed into position upon the screw head. The rod is then placed by attaching directly to the tulip assembly after connecting the assembly to the screw head. The publication mentions using a Kirschner wire (or K-wire) for inserting both the pedicle screws and the tulip member (see [0030], [0032], and [0045]) but does not disclose how the rods are guided into position.
[0022] US Pub. No. 20080097457 entitled “Pedicle screw systems and methods of assembling/installing the same” by David R. Warnick and unassigned, like US Pub. No. '075, also discloses using a tulip assembly as an intervening means to join a rod to the screws. In this system, rather than a press-on locking mechanism, the structure is tightened by rotating an inner member and outer housing of the tulip assembly relative to one another. Also like US Pub. No. '075, US Pub. No. '457 mentions wires only with respect to using a K-wire to direct insertion of the pedicle screws and does not teach using wires to guide the rods.
[0023] U.S. Pat. No. 7,179,261 entitled “Percutaneous access devices and bone anchor assemblies” by Christopher W. Sievol, et al. and assigned to Depuy Spine, Inc. describes one of the several tower systems for placement of pedicle screws percutaneously. The patent describes a situation where the angle of the screws intersect and the towers may interfere with each other. This situation is rather typical in the lordotic lumbar spine, especially the lumbo-sacral junction. In order to solve this problem, they describe cut-outs in the tubes so that two tubes can intersect. Given that the angles of the vertebrae are variable from patient to patient and the depth of the vertebrae from the skin is also highly variable, the variations on the cutouts would have to be numerous. The present invention would provide the maximum form of “cut-out” where only wires are left. Thus interference of a number of wires from adjacent vertebrae is not a problem. Also, in the cut-out tubes taught by U.S. Pat. No. '261 the screws or any other element inserted using the tubes would still have to be inserted through the tube at some point. The cut-out tubes require that the screw (or other inserted element) is oriented longitudinally parallel to the long axis of the tube as it is directed into the body until it reaches the cut-out section, at which point it may optionally be turned perpendicularly to the long axis and directed out of the lateral cut-out. In the present invention by using the wires, the element that is inserted along them (i.e. a screw, a rod, etc.) does not have to be inserted through any lumen outside of the body. In the present invention when a screw is inserted using the wires, the wires can simply be attached to the screw head. When a rod is inserted using the same wires, the wires can simply be fed through the outer edges of the rod body, through a retaining element or clasp attached to the rod body, or between the outer edges of the rod body and a retaining element (retention thread). Thus, in the present invention it is possible for the inserted screws and rods to be oriented perpendicular to the long axis or oriented in any other manner during the entire entry pathway. This provides greater flexibility for avoiding interference between adjacent stabilization system pieces and eliminates the need for a surgeon to identify the cut-out sections before turning the screw/rod laterally and/or reorienting it. U.S. Pat. No. '261 also does not teach using the cut-out tubes for the placement of spinal fixation elements such as rods. It discloses using the cut-out tubes for screws. (See 6:9-61, 14:9-31 and FIG. 2 with slots 60, 62). If rods were inserted through the tubes and towers disclosed in U.S. Pat. No. '261, the rods would still have to be aligned parallel to the long axis of the tube (percutaneous access device) and inserted through the central lumen of the tube at the beginning, the same as for rods inserted through non-cutout tubes. The cut-out tubes are still tubes with a completely whole (not cut-out) circumference at their proximal and distal ends such that a rod could not pass entirely transversely through the tube. A rod could not pass through the tube unless parallel to the long axis within the lumen at some point such as during initial entry into the tube. In the conventional case of pedicle screw towers, the rod has to be precisely inserted through the small opening within each rigid tower. In the present invention, the wires can be manipulated (spread outward or bent) to open the encatchment area for the rod (see FIG. 13A-13C and 14 A- 14 C herein). For addressing spinal fixation element placement in greater detail, two related commonly owned co-pending applications are cited and incorporated by reference in U.S. Pat. No. '261. These rod placement methods are very different from that of the present invention. In published application no. 20050131422 (U.S. patent application Ser. No. 10/737,537) entitled “Methods and devices for spinal fixation element placement” everything is through a single incision (see FIG. 10-11) and a rod must be inserted through lumen of a tube/tower at some point although this point may be external to body. Inside the body, the second end of the rod must be matched up with a side slot before it can be rotated perpendicularly to the long axis of the insertion pathway. In published application no. 20050131421, U.S. patent application Ser. No. 10/738,130, especially FIG. 10-16.) In the present invention, the same wires used to guide the screws can be used to place the rods, thereby avoiding a step of inserting an additional percutaneous access device. The present invention can be used to guide rods oriented perpendicular to the long axis of the guiding element (i.e. wires) at any point along the long axis.
SUMMARY OF THE INVENTION
[0024] The present invention is directed towards improved minimally invasive (optionally adaptable for use with the percutaneous or endoscopic approach) TLIF and PLIF approaches and backing up the ALIF, DLIF, and XLIF approaches. TLIF provides several advantages including: (i) stabilization of both the anterior and posterior portions of the spine through a single posterior incision; (ii) the ability to fill with bone graft material a greater volume and diversity of spaces (front disc space with the spacer, amongst the screws and rods on the sides, and in the back of vertebrae) increasing the chances of a successful stabilization through the development and solidification of bone; (iii) the spacer placed within the front disc space maintains the natural interbody disc height to reduce pressure on nerve roots (from bone spurs, thickened, ligaments, etc.); and (iv) enhanced safety because the spinal canal is accessed from one side only and this reduces the risk of pinching, stretching, or otherwise agitating the spinal nerves.
[0025] The invention provides a Microfusion™ product for performing a minimally invasive posterior and/or transforaminal lumbar pedicle screw fusion or stabilization procedure. Hereinafter references to “fusion” implicitly include stabilization which offers somewhat greater motion short of completely fusing the bone. Likewise, hereinafter references to “stabilization” implicitly include fusion. The main situations in which a surgeon can use the Microfusion™ system are similar to the situations in which the Sextant™ system from Medtronic is used. These situations include a minimally invasive TLIF procedure with either: (i) a micro-lumbar interbody fusion, MLIF™, or (ii) mini-open TLIF on the symptomatic side to decompress the neural compression, and a pedicle screw fusion through a minimally invasive incision on the contralateral side. Similarly the Microfusion™ system herein would be used bilaterally in a PLIF approach with the decompression and interbody spacer placement performed bilaterally. Alternatively, the Microfusion™ system is ideal for “backing up” (with a minimal posterior incision) anterior interbody fusions (ALIF) and lateral interbody fusions (XLIF™ and DLIF™) MLIF™ collectively encompasses (i) transforaminal lumbar interbody fusions and stabilizations, (ii) posterior lumbar interbody fusions and stabilizations, (iii) anterior lumbar interbody fusions and stabilizations, and (iv) lateral lumbar interbody fusions and stabilizations through a minimally invasive “micro” approach using the guidance system described herein. Since the lateral fusions are truly minimally invasive, a minimal posterior incision for pedicle screw fusion would be very complementary. Lateral interbody fusions are becoming more popular and more spine companies are coming out with their own lateral interbody fusion systems.
[0026] The lumbar spine has a lordotic curvature such that the lowest levels, L4, L5 and S1, are posteriorly oriented, while the mid levels, L2-L3, are straight or anteriorly oriented. This curvature sets up a unique situation in which the trajectories through the pedicles (the trajectories to insert the pedicle screws) from L2 to S1 are not parallel. Rather, the trajectories commonly intersect at a point just posterior to the skin. This configuration is similar to the spokes of a wheel in which the spokes (trajectories) meet at a common center point (a hub). Given that many patients have such a lordotic configuration of the lumbar spine, it is possible to insert pedicle screws through a single incision centered in the middle of the lumbar curvature. However, if each screw required a separate tower (or tube) (as in conventional tower/tube systems) in order for multiple screws to exist simultaneously, then the sum cross sectional area of the towers/tubes does not permit a single small incision. The towers/tubes interfere with each other and get in the way of one another due to their size.
[0027] An alternative method is necessary to in order to minimize the number and size of incisions. Reducing the number and size of incisions minimizes the tissue trauma needed to place pedicle screws for lumbar stabilization or fusion. An ideal system and procedure would take full advantage of the natural curvature of the lumbar spine in order to provide this reduction.
[0028] One objective of the present invention is to provide a simple method to place two or more pedicle screws through one small hole. This provides a better cosmetic and functional result with just a single skin incision of small size (approximately 1 to 2 cm in length) regardless of the number of screws used.
[0029] Another objective of the present invention is to be able to insert, position, and manipulate a rod and a locking assembly through the same small incision in order to lock the rod within the screws. The invention provides novel ways to insert a rod into pedicle screws and ways to lock the rod within the screws through a single small incision. The method involves the attachment of one or more flexible yet firm wires (or threads, strings, cords, cables, etc.) to each pedicle screw head to be used to guide the rod down to the screw. By using flexible wires instead, the towers/tubes currently used with each screw are not needed. The screws, rods, and locking assemblies can all be placed through a single small incision and yet still be appropriately interconnected within because of the natural lordotic curvature of the lumbar spine. By attaching at least one wire on each side of the screw head, the two or more symmetrically balanced wires assist to align the screw head. The wires also trap or restrict displacement of the rod, forcing it to fit between the wires and directly into the screw head.
[0030] The wires can also be used to guide the locking assemblies down to the screw heads for embodiments in which the locking assembly is not part of the screw head itself (and already down there). In such embodiments, wire guidance is not needed for the locking assembly because it is built into or part of the screw head. Examples of this latter situation are a hinged door over the rod that swings and snaps into position to hold the rod in place in the screw head. In this situation the built-in locking assembly (on the screw head) is inserted into the pedicle contemporaneously with the screw.
[0031] In a preferred embodiment, the locking assembly is also guided down to the screw by small loops placed on the sides of the insertion tools. The wires pass through these loops (the loops pass over the wires) to guide the insertion tools down to the screws to deposit (i.e. drop off or detach) the rods and locking means. Due to the flexibility of the wires coupled with their ability to possess a high strength while maintaining a small diameter, several of them can coexist simultaneously even in a small incision.
[0032] An alternative embodiment is a hybrid system where each screw is placed through short towers that do not come to the skin surface. Wires are attached to the top of the towers so that the screw, rod, locking assembly, and tools used for insertion, adjustment, locking, compression, distraction, and removal are guided by the wires close to the skin but through individual towers close to the bone and pedicle screw. This hybrid system offers both the advantages of the wires in which many wires can overlap in a single incision at the skin level and the advantages of a tower system are preserved at the bone level. Some surgeons who are comfortable with the tower system but who want the advantages of the wire system may want to use this hybrid system.
[0033] A further objective of the present invention is to reduce patient discomfort and the potential for iatrogenic injury. Providing a system and method designed for use through a single incision assists this purpose. Only one quality incision need be made. With every incision that is made there is at least a small risk of inadvertent injury, including nerve damage, even by a skilled surgeon. However, incising is not the only risky stage of the procedure, nor the only stage capable of causing patient trauma yet having the potential for improvement to reduce these risks and liabilities. Another step of the procedure commonly causing post-surgical patient discomfort and diminished motor/sensory function is placement of the rods within the screws. The wires not only guide the rods to the screws but also function to hold nerves and muscles out of the screw head for easier insertion of the rods and locking assemblies. With nerves and muscles restrained from entering the trajectories along which the rods are delivered, there is a reduced risk of pinching, tearing, or severing a nerve or muscle.
[0034] Other objectives and advantages of the invention will be set forth in the description which follows. Implicit modifications of the present invention based on the explicit descriptions will be, at least in part, obvious from the description, or may be learned by practice of the invention. Such subtle, predictable modifications and adaptations are taken to be within the scope of the present invention. Additional advantages of the invention may be realized and obtained by means of the instrumentalities and combinations particularly pointed out hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention, and together with the general description given above and the detailed description of the embodiments given below, serve to explain the principles of the invention.
[0036] FIG. 1A-1C shows a pedicle screw with a tapered shaft directed downwards, concave U-shaped screw head, and detachable elongated guide wires directed upwards (one on each side of the head). The elongated guide wires may attach directly to the screw head ( FIG. 1A ) or they may attach to 2 or more short wires on each side of the screw head. This configuration creates a wire cage that forces the screw head and the rod to align with each other as the rod is lowered into the seat of the screw head.
[0037] FIG. 2 shows the pedicle screw being inserted into the pedicle portion of a vertebra on the anatomical right side of the central lamina.
[0038] FIG. 3 shows two pedicle screws in position on two adjacent vertebrae on one side of a vertebral column, with the screw shafts buried within the vertebral bones and the U-shaped screw heads protruding from the pedicles' surfaces. Also shown is a rod being guided down (at an angle) to the screw heads, between each of two sets of two wires, one for each screw.
[0039] FIG. 4 shows the rod in a proper final position fully inserted within the screw heads of the pedicle screws in adjacent vertebrae along one side of a vertebral column for a partial (half-finished, the other side having yet to be stabilized) one-level stabilization. The locking assemblies are not shown here but may also be guided by the wires down to the screw heads.
[0040] FIG. 5 shows the wires (for guiding the rods, locking assemblies, etc.) having been detached from the screw heads of the pedicle screws along the anatomical right side of the vertebral column, but with the same screw head-wire system still in place on the anatomical left side of the vertebral column ready to accept and guide a rod down to the pedicle screws. The locking assemblies are not shown.
[0041] FIG. 6 shows the second rod in place within the screw heads on the anatomical left side pedicles of the vertebral column, with the detachable screw head wires remaining on only the anatomical left side.
[0042] FIG. 7 shows a preferred embodiment in which the rod also has wires or threads (called rod retention threads) on each side extending between its longitudinal ends to form a loop with the body of the rod for securing the rod along the screw head wires during placement.
[0043] FIG. 8 shows the rod with retention threads being directed down to two screw heads (one for each longitudinal end of the rod), along screw head guide wires (corresponding to each side of each pedicle screw head) inserted through the rod retention loop on each side of the rod. The rod retention threads “trap” the guide wires so that the ends of the rod cannot be pushed out of the screw head.
[0044] FIG. 9A-9F shows a preferred embodiment in which two guide wires are attached to the top of the screw head, one on each side. Three orientations (left to right) show the process of lowering the rod into the screw head guided by the guide wires ( FIG. 9A-9C ) along with the final position in which the rod is completely within the screw head ( FIG. 9D-9F ).
[0045] FIG. 10A-10C shows a locking assembly being lowered to attach to the screw head to secure the rod within. An instrument used to lock a locking assembly onto the screw head can also be guided by the wire but is not shown in this diagram.
[0046] FIG. 11A-11F shows another preferred embodiment in which the guide wires are connected to flexible strands. The strands are then connected to the top of the screw shaft or the base of the screw head. As the rod is lowered into the screw head, guided by the guide wires, the flexible strands wrap around the rod. Each strand is just long enough (approximately half of the circumference of the rod) to wrap around the rod so that the ends of the guide wires meet together above the rod.
[0047] FIG. 12A-C shows how the threads, as in FIG. 11A-11F , can be wrapped around the rod and brought together to guide a cannulated locking assembly (i.e. cap) as well as other cannulated tools (not shown) down to the screw head.
[0048] FIG. 13A-13C shows the insertion of a longer rod through 4 sets of guide wires attached to 4 pedicle screws in a three level stabilization. FIG. 13A shows the guide wires in a neutral, straight position. FIGS. 13B and 13C show the guide wires of the two superior vertebrae (L3 and L4) splayed open so that the rod can be easily tunneled in between the wires.
[0049] FIG. 14A-14C shows a preferred embodiment using a tool to separate the guide wires deep below the skin surface. In this manner, the skin incision remains small. A “T”-shaped tool with a hinged “T” portion is attached to the guide wires and slid partially down towards the screw head. As the hinged “T” is opened, the middle section of the guide wires is separated. This opened window allows the rod to be tunneled in between the guide wires, especially in instances where the rod and pedicle screw heads are inserted through separate incisions, as shown in FIG. 13A-13C and FIG. 15A-15C .
[0050] FIG. 15A-15C shows two preferred embodiments of inserting a rod through guide wires that do not share an incision with the rod. Here the lowest two levels (L5 and S1) do share a single incision but the upper two levels (L3 and L4) have separate incisions. Rod retention threads only span the inferior half of the rod and only capture the guide wires of the lower two vertebrae (L5 and S1). The superior end of the rod is then pushed through the guide wires of the upper two vertebrae (middle figure). Alternatively, a thread that is attached to the superior end of the rod can be used to pull the rod through the guide wires of the upper two vertebrae. This thread can be introduced in between each set of guide wires by a large suture needle that is inserted in one incision and is pulled out of the next incision in between the guide wires.
[0051] FIG. 16A-16D shows a preferred embodiment of flanged attachments that help the rod to find the proper orientation to best fit into the screw head. As shown, each attachment is preferably convex in a direction towards the rod so that as the rod approaches the screw head, the entrance to the screw head can accept a large range of angles in which the rod is oriented and still receive the rod, gradually improving the rod's orientation as it gets closer to the seat of the screw head.
[0052] FIG. 17A-17B shows the sequence of lowering a rod into a malaligned screw head (or, alternatively, of lowering a malaligned rod into a properly aligned screw head) using the flanged attachments as in FIG. 16A-16D . The bi-convex nature of the flanged attachments permits the rod to twist and adjust as it is lowered. Otherwise, without the flanged attachments, in a malaligned situation the rod would hit the edges of the screw head and would not be able to be lowered further. The flanged attachments are shown here as detachable elements on the screw head; however, another preferred embodiment is a flanged and convex shaped rod guide built into the tops of opposing sides of the “U” shaped screw head (i.e. may be integrally part of the screw head interior itself).
[0053] FIG. 18A-18C shows another preferred embodiment in which a wire is connected to a screw with break off extended tabs. Extended tabs are used to help reduce the rod into the screw head in cases of malalignment of the screw heads. Extended tabs are removed by snapping them off after the rod is locked in place. A wire attached to the extended tab helps to guide the rod and locking assembly into the screw head. The wire is removed when the extended tab is removed. Extended tabs that are tapered or triangular in shape also act similarly to the flanged attachments in FIG. 16A-16D and 17 A- 17 B to guide a rod into the seat of a malaligned screw head.
[0054] FIG. 19A-19C shows another preferred embodiment in which a wire is connected to a clamp or device that holds the screw head. A preferred embodiment of the clamp or device is composed of at least two parts that can be broken apart after the rod is locked in place so that the pieces of the device can be removed with the wire. The clamp or device is attached to the screw before insertion into the bone. The clamp or device is shaped so not to impede the placement of the rod into the seat of the screw head. The parts of the clamp are held together by a thin strand that is cut or snapped apart after the rod is locked in place. The clamp or device is made from metal, polymer, or plastic materials such that no residual is left after the clamp is removed.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0055] The invention involves at least a screw, a rod, and a locking assembly being wire-guided down to pedicles of the vertebrae and the rod secured to stabilize the vertebrae. The locking assembly may be built into the screw head or be a separate element. The locking assembly may be guided down to the screw before or after insertion of the rod depending upon the details of the locking mechanism used to secure the rod. In some cases, the locking assembly is already present on the screw head before the rod is received and in other cases the rod is inserted into the screw head first and the locking assembly follows.
[0056] A preferred embodiment of the present inventive system and method is to use one wire 103 on each side of a screw head 102 such that there are two wires 103 per screw shaft 101 to securely trap a rod 104 over the screw shaft 101 within the screw head 102 . This embodiment is believed to provide the most rod 104 stability for the least volume of stabilizing elements (thereby enabling a very small incision without stressing it). The wire 103 can be attached to the screw head 102 through (i) the wire itself, (ii) an extension of the wire that is formed of a material that is the same as a material from which the wire itself is derived, (iii) a thread material thinner than the wire, (iv) a short tower, or (v) an intermediate element including an extensor/extended tab 112 , flexible sheet, flange 110 , or mechanical device/clamp 113 as discussed further herein, among other possibilities. A single wire 103 may be attached to a screw head 102 at a single location or in two or more locations 111 as illustrated in FIG. 1A-1C .
[0057] FIG. 1A-1C shows a first configuration, in which a single guide wire 103 is attached to the screw head 102 ( FIG. 1A ), and a second configuration, in which one more shorter wires 111 are attached to the screw head 102 and also attached to a single elongated guide wire 103 at their other end ( FIG. 1B-1C ). Multiple short wires 111 attached directly to the screw head 102 may provide greater stability for an easier alignment. To accommodate this multiple wire configuration 111 , insertion instruments having side loops (not shown) through which the guide wire passes also have side loops to accommodate the larger area created by the fanning out configuration of the multiple short wires 111 close to the screw head 102 . Thus, the side loop attached near the tip of the insertion tool will be as wide as the screw head to accommodate all the short wires at the screw head. Above the transition zone (from multiple wires 111 to a single wire 103 ) the insertion tool will have smaller side loops that only allow a single wire to pass.
[0058] In an alternative embodiment there may be a single wire 103 on only one side of each screw 101 / 102 or screw head 102 . This embodiment further reduces the volume of stabilizing elements (screw head wires) that must fit through the minimal incision but also reduces rod stability. When only one screw head wire 103 is used per pedicle screw 101 / 102 it is recommended that at least one rod retention thread 105 also be used (see FIGS. 7 and 8 for illustration of the rod retention threads 105 ). The screw head wire 103 should be inserted through the loop formed by the rod retention thread 105 along the lateral side of the rod body 104 .
[0059] In another alternative embodiment, instead of one or more wires 103 , there may be one or more upwardly directed shafts that are not round (not shown) and are attached to a side of the screw head 102 . The unique shape of the shaft would prevent insertion tools from turning or rotating around the shaft (i.e. during their descent to approach the screw head 102 ). Thus any shaft that is not cylindrical would be capable of guiding tools that have a complementary non-cylindrical shaft holder attached to the tool. For example, a shaft that has a cross section of an oval, square, rectangle, triangle, cross, trapezoid, star, or any other shape besides a circle would be able to prevent an insertion tool from rotating around the shaft as long as the insertion tool is equipped with a complementary shaped holder through which the shaft fits precisely. A single shaft guidance mechanism that is thicker than a wire would also likely be more rigid than a wire. However, as long as the screw head 102 is multi-axial, there would be some flexibility in moving the shaft around in the incision.
[0060] The screws 101 and screw heads 102 themselves may also have any one of several different vertical and horizontal cross-sections including both circular and non-circular, rectangular, square, hexagonal, etc. The screws 101 and screw heads 102 are preferably made of a titanium alloy or stainless steel.
[0061] The rods 104 are preferably cylindrical but may alternatively have a non-circular cross-section (triangular, square, hexagonal, etc.) so long as the seat of the screw head 102 is shaped correspondingly to accommodate. The rods 104 are preferably formed of polyetheretherketone (PEEK) but may also be made of any other biocompatible minimally flexible polymer or metal.
[0062] In another alternative embodiment there may be more than two wires 103 per pedicle screw 101 / 102 . Preferably, if more than two wires per screw are used, there is at least one wire on each side of the screw with more than one wire on at least one side. An equal number of wires on each side improves stability and prevents lopsidedness. However, every patient's anatomy is slightly different and when curvature (i.e. scoliosis) and/or other aggravating conditions are present stability during rod 104 insertion may be best achieved by an asymmetric distribution of screw head wires 103 around the perimeter of a screw head 102 . In any case, the spinal surgeon is in the best position to make this decision about the appropriate screw head wire 103 and rod retention thread 105 set-up to use based on the individual needs of a particular patient.
[0063] The wires 103 on any one screw 101 / 102 can be placed at various positions around the periphery of a screw (rather than just on the sides) for enhanced stability and control. Screw 101 / 102 is used to refer to the entire screw including the screw shaft 101 and the screw head 102 collectively. The wires may be uniformly distributed and symmetrical around the periphery or they may be asymmetrical and staggered. For example, having four wires on a screw head (i.e. one wire on each edge: north/top, east/right, south/bottom, west/left) ensures that the screw head 102 is oriented along the axis of the rod 104 during transport of the rod through the incision and into a first screw head. Limiting the open regions around the perimeter of a screw head 102 by effectively creating a wire cage can also force the rod 104 to turn in the right direction (or force the screw head to turn to accommodate the rod) when it moves from a vertical longitudinal to a transverse lateral orientation after placement of a first end in a first screw head while the other end is being directed for placement in a second screw head. The number of wires, their sizes (i.e. diameters and lengths), shapes, flexibility, and strength may be adjusted to suit a particular procedure in a particular patient based on the incision size to optimize screw stability and facilitate rod alignment while avoiding entanglement of too many wires. Contemplated embodiments include those with from 1 to 10 wires per screw/screw head, especially those with 2 to 4 wires.
[0064] Instead of multiple long wires connected to the screw head 102 on each side, a single long wire 103 (or thread) is connected to several short wires 111 which in turn are connected to each side of the screw head. Thus, multiple wires 111 are still connected to each screw head 102 but these multiple wires are also connected to one another in an area above the screw head to form single wire 103 extending through the incision. These multiple short wires 111 may still function to bound or limit the movement of a rod 104 at least at the base of the screw head 102 . The short wires 111 give the advantage of creating a wire cage by which the rod 104 is forced to sit down into the seat of the screw head 102 . The long single wire (or thread) 103 reduces clutter and confusion at the skin incision that occurs when too many wires are present. The multitude of short wires 111 distributed away from the longitudinal entry axis into approximately the same axis along which the rod 104 will ultimately lay also allows the long wire 103 and accompanying instruments to adjust the orientation and angle of the screw head 102 in this axis (the rod axis, approximately perpendicular to the longitudinal entry axis used during rod insertion). The screw head 102 is configured to form a concave channel in which the rod 104 will eventually come to sit/rest. The concave channel may be U-shaped when a vertical cross-section is taken but any substantially concave shape suited to retain a rod 104 and with dimensions corresponding to those of the rod 104 will work. The upper edges of the screw head 102 itself or those of another intermediate element 110 / 112 / 113 to which it is attached, are configured to receive an incoming rod at a wide range of angles and smoothly direct it into the proper angular configuration to fit into the screw seat.
[0065] As an alternative to the screws 101 or the screw heads 102 being attached directly to upwardly directed guide wires 103 or guide shafts, there may be an intermediary flange, flanged leaflet, sheet 110 , extensor/extended tab 112 , a mechanical clamp/device 113 , or other element in between the two. The screw 101 / 102 or screw head 102 at its outer edges may transform into (integral therewith) or attach to a separate element that is directly attached to the guidance wire/shaft 103 such that the screw 101 / 102 or screw head 102 and the guidance element 103 are indirectly connected. The intermediate element is preferably specially adapted to readily detach from the screw 101 / 102 or screw head 102 when desirable, such as after securing the rod 104 in proper position and locking it in place. Detachment may be through a snap-off/pop-off mechanical mechanism that might be activated through a push-button at the proximal end of a surgeon's tool; through tearing along a perforation; through cutting, twisting, wagging, burning, heating, radiating, ultrasonically vibrating, electrifying/electrocuting, dissolving, unscrewing, or any other means. In this case with the guidance wires or upward shafts 103 attached directly to the intermediate and readily detachable element 110 / 112 / 113 the guidance wires 103 themselves may be more securely fastened to the intermediate element 110 / 112 / 113 . For example, the wires 103 might be soldered or welded to an extensor tab 112 that snaps into/onto and snaps out of/off of a groove or protrusion on the screw head 102 . At least a portion of the extensor tab 112 may be threaded to mate with a screw 101 / 102 or screw shaft 101 having corresponding threads or to align a rod 104 having some corresponding threads.
[0066] The intermediate element may be in the form of a sheet 110 of a very thin material that is both flexible and can be tensed by pulling or tightening. When pulled tight the sheet 110 functions to guide the rod 104 into the seat of the screw head 102 . Such material may be rubber.
[0067] An intermediate element may be an inwardly tapered flange 110 attached to an inner top edge of the screw head 102 and placed symmetrically about the screw seat in which the rod 104 sits. Such a flange 110 is configured to allow a malaligned rod 104 or screw head 102 to rotate and adjust relative to one another as the rod is inserted into the seat of the screw head until the two are acceptably aligned. The inwardly tapered sides of the flange 110 may take the form of convexly curved wings 110 that form a channel for the rod 104 between them.
[0068] Alternatively, the intermediate element may be an extensor tab 112 with straight rather than convex sides. Preferably, the tab is triangular which may be formed by removing the corners of an otherwise rectangular tab. The wider base of the triangle may attach to the screw head 102 as shown in FIG. 18A-18C .
[0069] The function of the screw head 102 or intermediate element 110 / 112 / 113 is to create a channel into which a rod 104 can be easily guided by the upwardly directed guide wire 103 /guide shaft. The screw head or intermediate element is adapted to accept a large degree of malalignment of the rod and the screw seat relative to one another and then guide the rod into the screw seat until substantially perfect alignment is achieved. The advantage of this is that the system does not require starting over, pulling out, and reinserting the rod when it turns out the initial positioning is not ideal.
[0070] The wires, threads, and intermediate elements described herein may be attached to the screw or screw head on the outside, on the inside, or through a cannulated portion of the downwardly directed screw shaft 101 . Many attachment locations are possible so long as it does not interfere with the ability of the screw shaft 101 to be drilled into the pedicle and the ability of the rod 104 and locking assembly 106 to be received into the seat of the screw head 102 .
[0071] The wire, thread, or upwardly directed shaft 103 may be attached to the downwardly directed screw shaft 101 , the screw head 102 , or an intermediate element (i.e. flange, sheet 110 , extensor/extended tab 112 ) with glue, soldering, thread, sutures, string, a mechanical clamp 113 , etc.
[0072] In embodiments in which a mechanical clamp 113 is used to connect the upwardly directed guidance element 103 to the screw head 102 , the clamp 113 preferably has 2 leaves that are connected under the head 102 or at least below where the rod 104 comes down so as not to impede the path of the rod. After closing the locking assemblies 106 to secure the rod 104 in place within the screw head 102 , the clamps 113 can be removed. Removing the clamps 113 from the screw head 102 also removes the wires 103 attached to the clamps 113 . The clamps 113 may be removed by any means feasible in the limited space including (but not limited to): (i) by breaking the connection (like detaching the extended tabs 112 ), (ii) by cutting a material that holds the 2 leaves together, (iii) unclamping or unbuckling, and (iv) unvelcro-ing.
[0073] Alternatively, in some embodiments the locking assembly may be part of the clamp 113 such that the clamp is not removed but remains to hold the rod 104 (see FIG. 19A-19C ). In such situations, the guidance wires 103 only are simply detached from the clamp-locking assembly combination unit.
[0074] Instead of a mechanical clamp with moving parts, the intermediate element (between screw head 102 and wires 103 ) may also simply be a metal or plastic device that has no moving parts but traps the head 102 securely into it. The intermediate metal or plastic device can be removed by means including (i) snapping a thin center part connecting 2 halves of the device, or (ii) cutting a string that connects 2 parts of the device. If the locking assembly 106 for the rod 104 is distinct from the intermediate metal or plastic device, then the device can be removed along with the wires after the rod is placed. If the locking assembly is integrated with or dependent upon the intermediate metal/plastic device, then the device should stay in place after the wires 103 / 111 only are detached from it.
[0075] In another embodiment illustrated in FIG. 11A-11F , the wire 103 or an extension thread 107 thereon, can be attached to the area within the screw head 102 where the rod 104 would eventually sit, such as at the base of the screw head and/or to the upper end of the downwardly directed screw shaft 101 . For example, the wire 103 or its extension 107 may be attached within the cannulated portion of a cannulated screw. By using flexible wire or extension thread 107 , the wire/thread can wrap around the rod 104 as the rod is seated into the screw head 102 . The wire/thread can then be threaded through cannulated tools and a cannulated locking assembly 106 above the rod.
[0076] Optionally, color-coded wires 103 and/or screws 101 may be provided to assist doctors, technicians, and medical personnel in identifying elements, performing the procedure, and monitoring progress during follow-up visits. Alternatively, some other form of visual coding, such as with particular materials and/or only visible under certain conditions may be used to distinguish wires, screws, and other elements (i.e. fluorescent markers, radioactive isotopes, radioopaque markers visible on X-rays, magnetic nanoparticles, etc.). Another alternative or complementary coding means can be sensed by touch (different surface textures) or sound (tactile or auditory) rather than or in addition to visually. The coding could be correlated with right and left sides of the body, medial vs. lateral elements, wire/screw sizes, wire/screw shapes, wire flexibility, and/or wire strengths, among other possibilities. This list of variables with which a coding or tagging system may correspond is intended to be illustrative rather than exhaustive. One preferred coding system provides markers or color coding for wires that are intended for the medial side of the rod versus those intended for the lateral side of the rod. This coding would allow for easy separation of the wires 103 when the rod 104 is inserted. This coding would also help the insertion of tools and the locking assembly 106 along the medial side and lateral side wires 103 . Some elements (wires 103 , screws 101 , screw heads 102 , rods 104 , retention threads 105 , locking assemblies 106 , etc.) with similar characteristics may be coded in groups such as all medial side wires being red while all lateral side wires are green.
[0077] Any locking assembly 106 can be used with the present invention. The precise design of the locking assembly 106 is not important so long as it is configured to retain the rod 104 within the screw head 102 for a secure and lasting stabilization. Examples of locking assemblies 106 that might be employed include screw-on nuts, press-on caps, fast-drying glue, a tiny swinging gate or door with a latch, a series of elements that can be deployed to tighten around the periphery of the rod, etc.
[0078] Since a rod connects two or more separate vertebrae, the rod can first be secured into position (locked or tightened) though the locking assembly on a first vertebra and then subsequently on a second vertebra. In some cases after the rod is firmly secured to the screw on the first vertebra, the relative positioning of the vertebrae can be adjusted by the surgeon by moving the vertebrae closer together or farther apart before the rod is secured to the screw on the second vertebra. With only one side of the rod locked into place the other side of the rod can easily be adjusted in position. For example, the rod can vertically slide forward or backward through the locking assembly until the desired distance spanned by the rod between locking assemblies is obtained.
[0079] The wires 103 can be attached to the screw heads 102 by a number of mechanisms. The retention threads 105 can be attached to the ends of the rods 104 by the same assortment of mechanisms. The simplest attachment mechanism is to solder or glue the wire/thread to the screw head/rod. The solder or glue can then be cut or broken off later. Neither the lateral retention threads 105 on the rod 104 nor the upwardly directed guidance wires 103 on the screw 101 / 102 , or on the screw head 102 , are needed after the rod 104 has been securely placed within the screw head 102 .
[0080] The retention threads 105 on the rod 104 that hold it close to the guide wires 103 as it is guided into position are preferably made of a flexible material including metal wire, nitinol, rubber, suture, plastic, polymer, and biodegradable material. The retention thread 105 should be easily removable after the rod 104 has been secured in an aligned position in the seat of the screw head 102 and locked in.
[0081] Alternatively, the wire/thread could be threaded into a threaded connector in the side of the screw head/rod so that the wire/thread is unscrewed at the end of the case.
[0082] Other embodiments include attaching the wire 103 /retention thread 105 by dissolvable sutures tied to the screw head 102 /rod 104 and to the end of the wire/retention thread with a small loop or grooves in the screw head/rod. Suitable dissolvable suture materials include biocompatible synthetic absorbable materials such as those made primarily of polyglycolic acid (PGA) or other proven compositions. Specific brands of materials include Vicryl™ (from Ethicon), Biovek™ (from Dynek), Visorb™ (from CP Medical), Polysorb™ (from Covidien's Syneture), and Dexon™ (also from Covidien's Syneture). The materials can be tailored to degrade or absorb in an amount of time that corresponds with sufficient internal healing to successfully hold the fusion. For example, standard Vicryl™ typically maintains tensile strength for three to four weeks. The materials may also be impregnated with drugs or biomolecules (i.e. triclosan) to accelerate the healing process and prevent infection. When the biodegradation (i.e. bioabsorption, bioerosion, etc.) time for the suture material is too long and the sutures are unnecessary immediately following the procedure the sutures can instead be promptly cut or burned at the end to disconnect the wire/retention thread from the screw head/rod.
[0083] Yet another option for the “wire to screw head” or “retention thread to rod” attachment mechanism is to secure using a material that burns, breaks, or dissolves upon the application of current (i.e. radiofrequency current). This option permits the connection to be easily broken by simply passing current through the wire or thread. Preferably, the wire/retention thread breaks down in response to current applied outside the skin. Alternatively, an insulated guide wire can be used to apply current internally in a targeted and minimally invasive manner. An insulated guide wire would allow the current to pass directly from an external tip (outside the body) to the current-sensitive material at an interior tip near the pedicle screw.
[0084] In still another preferred embodiment for attachment, the selected material (i.e. elastic string or rubber) is both flexible and can be tensed by pulling or tightening. The key is to use very thin material that can be both flexible and become tense. These dual properties allow the material to reliably guide the rod and tools down through the small incision without breaking while adapting to share the limited space. Unless it is also biodegradable the flexible, tensile material of string/rubber will need to be cut/broken/burned off or untied from the screw head and wire (or rod and retention thread) at the end of the procedure.
[0085] Instead of using an intermediary material to connect the wire to the screw head and/or to connect the retention thread to the rod, another possibility is for the wire and/or retention thread to be formed of the same materials as the intermediary connectors described above. In this situation, it is the wire or retention thread that is itself burned or cut at the end of the procedure.
[0086] The final result in all cases is a clean, successful pedicle screw fusion just like that which results from screws and rods used in an open procedure but with a smaller incision and fewer components.
[0087] The material through which the rod-guiding wire is attached to the screw head may be the same material of which the wire itself is derived or a separate material. The wires themselves are preferably formed of a biocompatible metal having both strength and durability. In a preferred embodiment, the wires are formed of nitinol (nickel titanium alloy).
[0088] The material through which the retention threads 105 of the rod 104 are attached to the ends of the rod may be the same material of which the retention threads themselves are derived or a separate material. The retention threads are preferably formed of a biocompatible metal having both strength and durability. In a preferred embodiment, the retention threads are formed of nitinol (nickel titanium alloy). Alternatively, another preferred embodiment is for the retention threads of the rod to be made from a biodegradable thread so that it does not have to be removed after placement. Another advantage of thread is that it would not interfere with the rod and cap locking mechanism 106 if it were caught in between the cap 106 and screw head 102 threads.
[0089] To complement the wire guides 103 , the present invention also provides a special rod 104 , with its own retention threads 105 , that can fit between the wires. By attaching a small loop or ring at the ends of the rod, two threads can be tied though the loops with good tension along the sides of the rod. This way the wires 103 will pass in between the rod 104 and the thread 105 to prevent the rod from slipping out and around the most superior or inferior wires. (See FIGS. 7 and 8 .) The retention thread 105 may also be attached to the rod by means other than loops or rings at its ends. The rod 104 may have holes or piercings therein for securing the thread to it. The rod may have grooves at its ends with which the thread engages. The thread 105 may be glued on near the ends of the rod. Rod retention threads 105 restrain the rod 104 to riding the wires 103 and eliminate the risk of internal rod displacement away from the target screw site 102 . The retention threads 105 also expedite rod 104 placement into the screws 102 / 101 to decrease total procedure time.
[0090] The retention thread 105 may take the form a strip or long sheet of material rather than an ordinary thread. The retention thread material should be flexible, strong, and biocompatible.
[0091] The steps for the placement of the pedicle screws and rods for a “Micro open” approach are as follows. First, using fluoroscopy or stereotactic guidance, a single small skin incision 1-4 cm lateral to a midline that will accommodate all pedicle screws is localized. Next, using either a percutaneous Jamshedi/Kirschner-wire (K-wire) approach, a Wiltse muscle splitting approach, or tube system, the pedicle screws are placed (see FIG. 2 ). The pedicle screw inserter has loop attachments that hold the side wires of the pedicle screw during placement. After each pedicle screw is placed, the side wires are pushed to the side of the incision to make room so that the other screws can be placed without entanglement. After all screws are placed, a screw head turner is inserted and guided down to the screw heads along each pair of guide wires to align the heads of the screws in preparation for receiving the rods (see aligned screw heads in FIG. 3 ).
[0092] With the screw heads aligned, the side wires are split between the medial and lateral sides. Then a rod is slid in between the medial and lateral wires into the screw heads. Preferably, the rod should be bent before insertion. Markers on the guide wires at predefined distances from the tip of the guide wires can help guide the surgeon in bending the rod to the correct curvature. Guide wires coming out of a single incision are similar to light rays that have been focused by a convex lens. These light rays converge at a point and then create a mirror virtual image on the other side of the focal point. This same concept can be used to create a mirror image of the curvature of the rod to guide the bending of the rod to accurately fit into the screw heads. (See FIGS. 4 and 15 A- 15 C). After each end of the rod is properly positioned within a screw head, locking nuts or caps are screwed on the screw heads to secure it in place. Alternatively, a compressor that is guided by the wires is used to compress pedicle screws on adjacent levels and then final tightening can be done during compression. The screw head guide wires are then removed by any means including cutting, twisting, wagging, burning, radiating, dissolving, unscrewing, etc. (see FIG. 5 and FIG. 6 , left side). Once the screws and rods in all vertebrae to-be-fused along one side of the vertebral column are stabilized, their mirror-image counterparts should be placed along the opposite side of the same vertebrae using similar fluoroscopic localization or other imaging means (see FIG. 5 with one rod, preparing for the second, and FIG. 6 with two rods placed).
[0093] The present invention can be used to dynamically stabilize or fuse vertebrae while at the same time removing a defective intervertebral disc and inserting a spacer in its place. The spacer may include bone graft material or bone inducing material incorporated therein to encourage healing. Exemplary bone inducing materials include bone morphogenetic protein, tricalcium phosphate, hydroxyapatite, and collagen.
[0094] The various elements (wires, screws, screw heads, rods, retention threads, locking assemblies, etc.) of the present invention may be provided in a range of sizes, shapes, strengths, flexibilities, and other physical characteristics to best accommodate individual patients and particular applications.
[0095] FIG. 13A-13C shows how for a three level stabilization the rod can be guided down by the wires on a first screw head while the wires on a second and third screw head are splayed outward or bent to open the encatchment area for the rod to easily enter. In the conventional case of pedicle screw towers, the rod had to be precisely inserted through the small opening within each rigid tower. The present invention overcomes this difficulty.
[0096] As shown in FIG. 14A-14C a refined T-shape tool 108 / 109 may be used to separate the wires 103 . This gesture prevents them from becoming tangled (or disentangles them) and opens the space in between them such that a rod can be passed through it to enter the screw head. The horizontal arms 109 of the “T” extend outward perpendicular to the longitudinal insertion axis 108 . These arms 109 may be aligned parallel against the main longitudinal body during insertion and removal. They may also be inside the main body and deployed from within via telescopic extension or a spring-like mechanism. The end of each horizontal arm 109 may be U-shaped, V-shaped, or circular such that a wire 103 can be retained within it. If the ends are U-shaped or V-shaped the T-shaped tool 108 / 109 can be disconnected from the wire 103 easily after spacing by collapsing the arms to realign against the longitudinal insertion axis 108 or to collapse into the main body. If the ends are a closed loop shape such that the wires 103 are fed through them and trapped within them, the loops should be configured to open to release them (like a jewelry clasp) after the tool 108 / 109 has performed its function.
[0097] The present invention is not limited to the embodiments described above. Various changes and modifications can, of course, be made, without departing from the scope and spirit of the present invention.
[0098] Additional advantages and modifications will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details and representative embodiments shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents. | An improved system and method for positioning screws and rods to immobilize bones is provided. Specifically, the system and method is optimal for performing transforaminal lumbar interbody fusion (TLIF) and other interbody fusions in the spine. The system involves pedicle screws detachably connected to wires that guide rods down to the screws. The wires are strong, narrow, flexible, adjustable in tension, and easily disconnected from the screws after rod placement via a process such as cutting, radiating, burning, dissolving, etc. The use of wires to place the rods avoids the conventional bulky tower apparatuses of the prior art while at the same time enhancing the accuracy of placement. One of the preferred methods involves relying upon the natural lordotic curvature of the spine and the narrow diameter of the wires to insert many elements through a single minimally invasive incision. | 0 |
FIELD OF THE INVENTION
[0001] The present invention relates to gas distribution plates (GDPs) which distribute gases into a processing chamber such as an etch chamber used in the etching of material layers on a semiconductor wafer substrate during the fabrication of integrated circuits on the substrate. More particularly, the present invention relates to an anodized aluminum gas distribution plate having an alumina anodized coating or layer to impart durability to the plate and reduce particle generation during etching or other processes.
BACKGROUND OF THE INVENTION
[0002] Integrated circuits are formed on a semiconductor substrate, which is typically composed of silicon. Such formation of integrated circuits involves sequentially forming or depositing multiple electrically conductive and insulative layers in or on the substrate. Etching processes may then be used to form geometric patterns in the layers or vias for electrical contact between the layers. Etching processes include “wet” etching, in which one or more chemical reagents are brought into direct contact with the substrate, and “dry” etching, such as plasma etching.
[0003] Various types of plasma etching processes are known in the art, including plasma etching, reactive ion (RI) etching and reactive ion beam etching. In each of these plasma processes, a gas is first introduced into a reaction chamber and then plasma is generated from the gas. This is accomplished by dissociation of the gas into ions, free radicals and electrons by using an RF (radio frequency) generator, which includes one or more electrodes. The electrodes are accelerated in an electric field generated by the electrodes, and the energized electrons strike gas molecules to form additional ions, free radicals and electrons, which strike additional gas molecules, and the plasma eventually becomes self-sustaining. The ions, free radicals and electrons in the plasma react chemically with the layer material on the semiconductor wafer to form residual products which leave the wafer surface and thus, etch the material from the wafer.
[0004] Referring to the schematic of FIG. 1, a conventional plasma etching system, such as an Mxp+ Super-E etcher available from Applied Materials, Inc., is generally indicated by reference numeral 10 . The etching system 10 includes a reaction chamber 12 having a typically grounded chamber wall 14 . An electrode, such as a planar coil electrode 16 , is positioned adjacent to a dielectric plate 18 which separates the electrode 16 from the interior of the reaction chamber 12 . Plasma-generating source gases are provided by a gas supply (not shown) and flow into the reaction chamber 12 through openings 18 a in the gas distribution plate 18 . Volatile reaction products and unreacted plasma species are removed from the reaction chamber 12 by a gas removal mechanism, such as a vacuum pump 24 through a throttle valve 26 .
[0005] Electrode power such as a high voltage signal is applied to the electrode 16 to ignite and sustain a plasma in the reaction chamber 12 . Ignition of a plasma in the reaction chamber 12 is accomplished primarily by electrostatic coupling of the electrode 16 with the source gases, due to the large-magnitude voltage applied to the electrode 16 and the resulting electric fields produced in the reaction chamber 12 . Once ignited, the plasma is sustained by electromagnetic induction effects associated with time-varying magnetic fields produced by the alternating currents applied to the electrode 16 . The plasma may become self-sustaining in the reaction chamber 12 due to the generation of energized electrons from the source gases and striking of the electrons with gas molecules to generate additional ions, free radicals and electrons. A semiconductor wafer 34 is positioned in the reaction chamber 12 and is supported by a wafer platform or ESC (electrostatic chuck) 36 . The ESC 36 is typically electrically-biased to provide ion energies that are independent of the RF voltage applied to the electrode 16 and that impact the wafer 34 .
[0006] Typically, the voltage varies as a function of position along the coil electrode 16 , with relatively higher-amplitude voltages occurring at certain positions along the electrode 16 and relatively lower-amplitude voltages occurring at other positions along the electrode 16 . A relatively large electric field strength is required to ignite plasmas in the reaction chamber 12 . Accordingly, to create such an electric field it is desirable to provide the relatively higher-amplitude voltages at locations along the electrode 16 which are close to the grounded chamber wall 14 .
[0007] As discussed above, plasma includes high-energy ions, free radicals and electrons which react chemically with the surface material of the semiconductor wafer to form reaction produces that leave the wafer surface, thereby etching a geometrical pattern or a via in a wafer layer. Plasma intensity depends on the type of etchant gas or gases used, as well as the etchant gas pressure and temperature and the radio frequency generated at the electrode 16 . If any of these factors changes during the process, the plasma intensity may increase or decrease with respect to the plasma intensity level required for optimum etching in a particular application. Decreased plasma intensity results in decreased, and thus incomplete, etching. Increased plasma intensity, on the other hand, can cause overetching and plasma-induced damage of the wafers. Plasma-induced damage includes trapped interface charges, material defects migration into bulk materials, and contamination caused by the deposition of etch products on material surfaces. Etch damage induced by reactive plasma can alter the qualities of sensitive IC components such as Schottky diodes, the rectifying capability of which can be reduced considerably. Heavy-polymer deposition during oxide contact hole etching may cause high-contact resistance.
[0008] The gas distribution plate 18 illustrated in FIG. 1 may serve multiple purposes and have multiple structural features, as is well known in the art. For example, the gas distribution plate 18 may include features in addition to the openings 18 a for introducing the source gases into the reaction chamber 12 , as well as those structures associated with physically separating the electrode 16 from the interior of the chamber 12 . The openings 18 a typically have a diameter of about 0.5 mm, and the gas distribution plate 18 is constructed of quartz.
[0009] One of the limitations inherent in the quartz gas distribution plate 18 is that plasma may damage or corrode the gas distribution plate 18 during plasma processes carried out in the chamber 12 . Furthermore, over prolonged periods of use the quartz gas distribution plate 18 deteriorates and generates particles which have the potential to contaminate a wafer 34 processed in the reaction chamber 12 . Accordingly, a new and improved gas distribution plate which is characterized by enhanced durability and resistance to damage and deterioration is needed for a reaction chamber.
[0010] According to the present invention, an anodized aluminum gas distribution plate is provided which is durable and resistant to plasma-induced damage and deterioration. Anodizing is a type of electrolysis by which a protective oxide coating is formed on a metal. Anodizing may serve several purposes, including forming a tough coating on a metal as well as imparting electrical insulation and corrosion resistance to the metal. Anodized aluminum and magnesium are commonly used in airplanes, trains, ships and buildings.
[0011] Anodizing processes are carried out in an electrolyte solution, in which the metal to be anodized acts as an anode or positive pole of the cell. Negatively charged oxide ions pass through the electrolyte solution and oxidize the surface of the metal. Aluminum is typically anodized in a sulfuric acid electrolyte solution, whereas magnesium is often anodized in a dichromate electrolyte solution. The thickness of the anodized coating is a function of the magnitude of the electric current which is passed through the solution. The anodized metal surface may be subjected to special treatments to give the metal a porous layer that can absorb dyes which are incapable of being rubbed or scratched off the surface.
[0012] An object of the present invention is to provide a new and improved gas distribution plate for a process chamber.
[0013] Another object of the present invention is to provide a new and improved gas distribution plate which is characterized by longevity and durability.
[0014] Still another object of the present invention is to provide a new and improved gas distribution plate which is suitable for use in etch chambers used in the fabrication of integrated circuits on semiconductor wafers.
[0015] Yet another object of the present invention is to provide a new and improved, anodized aluminum gas distribution plate.
[0016] A still further object of the present invention is to provide a method of fabricating an anodized aluminum gas distribution plate.
SUMMARY OF THE INVENTION
[0017] In accordance with these and other objects and advantages, the present invention is generally directed to a new and improved, anodized aluminum gas distribution plate for process chambers, particularly an etch chamber. The gas distribution plate includes an aluminum body having multiple gas flow openings extending therethrough and an alumina anodized coating or layer on the plate. The gas distribution plate is characterized by enhanced longevity and durability and resists particle-forming deterioration and damage throughout prolonged
[0018] According to a preferred method of fabricating the gas distribution plate, the plate body is constructed of aluminum and is immersed in a hard anodizing electrolyte solution such that all surfaces of the plate body are exposed to the electrolyte solution. The anodizing electrolyte solution has a concentration of typically about 15%, a current density of about 2-2.5 A/dm 2 and a voltage of about 20-60V, and the solution is maintained at a temperature of about 0-3 degrees C. during the anodizing process. The hard anodizing electrolyte may be sulfuric acid, although chromic acid or other anodizing electrolytes known by those skilled in the art may be used.
[0019] The alumina anodized coating or layer on the anodized aluminum plate body may be about 0.04 mm thick. Typically, the gas distribution plate includes about 88 gas flow openings. Each of the gas flow openings may have a diameter of about 0.78 mm to about 0.82 mm, and preferably, about 0.8 mm.
[0020] The present invention further includes a gas distribution plate fabricated by providing a plate body of aluminum and providing an alumina anodized layer on the plate body by immersing the plate body in an anodizing electrolyte solution and passing a current through the anodizing electrolyte solution while maintaining the solution at a selected temperature. The anodizing electrolyte is typically a hard anodizing electrolyte such as sulfuric acid, although alternative electrolytes such as chromic acid may be used. The sulfuric acid may have a concentration of about 15%, and the sulfuric acid bath is typically maintained at a temperature of about 0-3 degrees C. The current passed through the bath may be on the order of about 20-60V, and the electrolyte bath may have a current density of about 2-2.5 A/dm 2 .
[0021] Preferably, the gas distribution plate fabricated according to the foregoing method has about 88 gas flow openings extending therethrough. Each of the gas flow openings may have a diameter of about 0.78 mm to about 0.82 mm, and preferably, about 0.8 mm. The alumina anodized layer may have a thickness of about 0.04 mm.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The invention will now be described, by way of example, with reference to the accompanying drawings, in which:
[0023] [0023]FIG. 1 is a cross-sectional, partially schematic view of a typical conventional etch chamber for processing semiconductor wafers;
[0024] [0024]FIG. 2 is a top view of an illustrative embodiment of the anodized aluminum gas distribution plate of the present invention;
[0025] [0025]FIG. 3 is a cross-sectional view of the anodized aluminum gas distribution plate, taken along section lines 3 - 3 in FIG. 2;
[0026] [0026]FIG. 4 is an enlarged cross-sectional view of the anodized aluminum gas distribution plate, taken along section line 4 in FIG. 3;
[0027] [0027]FIG. 5 is a cross-sectional, partially schematic view of a conventional process chamber in implementation of the present invention;
[0028] [0028]FIG. 6 is a schematic view of an anodizing electrolyte bath in typical fabrication of the anodized aluminum gas distribution plate of the present invention; and
[0029] [0029]FIG. 7 is a flow diagram which summarizes typical steps in fabrication of the anodized aluminum gas distribution plate of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0030] The present invention is directed to an anodized aluminum gas distribution plate which is particularly applicable to etch chambers, particularly the MxP etch chamber available from Applied Materials, Inc. of Santa Clara, Calif. However, the anodized aluminum gas distribution plate of the present invention may be applicable to other types of process chambers used for the fabrication of integrated circuits on semiconductor wafer substrates.
[0031] Referring initially to FIGS. 2-4, an illustrative embodiment of the anodized aluminum gas distribution plate (GDP) of the present invention is generally indicated by reference numeral 40 . The GDP 40 includes a circular, aluminum plate body 42 having a top surface 44 , a bottom surface 46 and a circular edge 48 . Multiple gas flow openings 50 extend through the thickness of the plate body 42 and open onto the top surface 44 and the bottom surface 46 , respectively. In a preferred embodiment, the plate body 42 includes eighty-eight (88) of the gas flow openings 50 . However, it is understood that any desired number of the gas flow openings 50 may be provided in the plate body 42 in any desired pattern. An alumina anodized layer 52 is coated on the top surface 44 and the bottom surface 46 , as well as the edge 48 and opening surfaces 51 inside the gas flow openings 50 . In a preferred embodiment, the alumina anodized layer 52 has a thickness of about 0.04 mm, leaving each of the gas flow openings 50 with a diameter of typically from about 0.78 mm to about 0.82 mm.
[0032] Referring next to FIGS. 6 and 7, the anodized aluminum GDP 40 may be fabricated in the following manner. First, the aluminum plate body 42 is fabricated with the multiple gas flow openings 50 extending therethrough in a selected pattern, according to the knowledge of those skilled in the art. Next, an anodizing electrolyte bath 58 is prepared by placing an anodizing electrolyte solution 56 in an electrolyte tank 54 . In a preferred embodiment, the anodizing electrolyte solution 56 is sulfuric acid (H 2 SO 4 ). However, it is understood that other suitable anodizing electrolyte solutions known by those skilled in the art may be used instead. The plate body 42 is completely immersed in the anodizing electrolyte solution 56 , with the top surface 44 , the bottom surface 46 , the edge 48 and the opening surfaces 51 (FIG. 4) directly exposed to the anodizing electrolyte solution 56 . As the anodizing electrolyte solution 56 is maintained at a temperature of typically about 0-3 degrees C., an electric current of typically about 20-60 volts is transmitted through the electrolyte solution 56 , with a current density of typically about 2-2.5 A/dm 2 . The anodizing process is carried out for about 60-200 minutes in order to form the alumina anodized layer 52 having a thickness of about 0.04 mm. The fabrication steps for the anodized aluminum gas distribution plate 40 are summarized in FIG. 7.
[0033] Referring next to FIG. 5, the anodized aluminum GDP 40 may be installed in a reaction chamber 62 of a conventional plasma etching system 60 such as an Mxp+Super-E etcher available from Applied Materials, Inc. The reaction chamber 12 includes a typically grounded chamber wall 64 . An electrode, such as a planar coil electrode 66 , is positioned adjacent to the gas distribution plate 40 which separates the electrode 66 from the interior of the reaction chamber 62 . A semiconductor wafer 68 is positioned in the reaction chamber 70 and is supported by a wafer platform or ESC (electrostatic chuck) 70 . The ESC 70 is typically electrically-biased to provide ion energies that are independent of the RF voltage applied to the electrode 66 and that impact the wafer 68 . Plasma-generating source gases are provided by a gas supply (not shown) and flow into the reaction chamber 62 through the gas flow openings 50 in the gas distribution plate 40 . Volatile reaction products and unreacted plasma species are removed from the reaction chamber 62 by a gas removal mechanism, such as a vacuum pump (not shown) through a throttle valve (not shown), in conventional fashion.
[0034] Ignition of a plasma in the reaction chamber 62 is accomplished primarily by electrostatic coupling of the electrode 66 with the source gases, due to the large-magnitude voltage applied to the electrode 66 and the resulting electric fields produced in the reaction chamber 62 . Once ignited, the plasma is sustained by electromagnetic induction effects associated with time-varying magnetic fields produced by the alternating currents applied to the electrode 66 . The plasma may become self-sustaining in the reaction chamber 12 due to the generation of energized electrons from the source gases and striking of the electrons with gas molecules to generate additional ions, free radicals and electrons. The plasma contacts the wafer 68 and etches material layers from the wafer 68 to define an electrically conductive circuit pattern on the wafer 68 , as is known by those skilled in the art. It will be appreciated by those skilled in the art that the alumina anodized layer 52 on the plate body 42 prevents plasma-induced corrosion, deterioration and/or damage to the anodized aluminum GDP 40 , thereby preventing generation of particles which would otherwise potentially contaminate the circuits being fabricated on the wafer 68 and prolonging the time intervals needed for periodic maintenance of the aluminum GDP 40 . Furthermore, the anodized aluminum GDP 40 is capable of withstanding RF powers of up to 1200 watts, whereas conventional quartz GDPs can withstand RF powers of up to about 650 watts. In the event that it wears thin or becomes depleted due to prolonged use of the anodized aluminum GDP 40 , the alumina anodized layer 52 can be replaced on the plate body 42 by re-subjecting the plate body 42 to the aluminum anodizing process heretofore described with respect to FIGS. 6 and 7.
[0035] While the preferred embodiments of the invention have been described above, it will be recognized and understood that various modifications can be made in the invention and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the invention. | A new and improved, anodized aluminum gas distribution plate for process chambers, particularly an etch chamber. The gas distribution plate includes an aluminum body having multiple gas low openings extending therethrough and an alumina anodized coating or layer on the plate. The gas distribution plate is charcterized by enhanced longevity and durability and resists particle-forming deterioration and damage throughout prolonged use. | 8 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of and claims priority to U.S. Ser. No. 13/895,034 filed May 15, 2013, which is a continuation of U.S. Ser. No. 12/640,376 filed Dec. 17, 2009, which claims the benefit of U.S. Provisional Application No. 61/140,344, filed Dec. 23, 2008, the entire disclosures of which are herein incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular of a blood sample liquid. The present invention also relates to a corresponding measuring system and method.
[0003] It is essential for survival that a wound stops bleeding, i.e. that the body possesses an adequate mechanism for haemostasis. The process of blood clotting can be activated in the case of injuries or inflammations by either extrinsic or intrinsic factors, e.g. tissue factor (TF) or Hagemann factor (F XII), respectively. Both activation channels are continued in a common branch of the cascade resulting in thrombin formation. The thrombin itself finally initiates the formation of fibrin fibres which represent the protein backbone of blood clots.
[0004] The other main constituent of the find blood clot are the thrombocytes which are interconnected by the fibrin fibres and undergo a number of physiological changes during the process of coagulation. Within limits a lack of thrombocytes can be substituted by an increased amount of fibrin or vice versa. This is reflected in the observation that the thrombocyte counts as well as the fibrinogen concentration varies even within a healthy population.
[0005] Various methods have been introduced to assess the potential of blood to form an adequate clot and to determine the blood clots stability. Common laboratory tests such as thrombocyte counts or the determination of fibrin concentration provide information on whether the tested component is available in sufficient amount but lack in answering the question whether the tested component works properly under physiological conditions (e.g. the polymerisation activity of fibrinogen under physiological conditions can not be assessed by common optical methods). Besides that, most laboratory tests work on blood-plasma and therefore require an additional step for preparation and additional time which is unfavourable especially under POC (point of care) conditions.
[0006] Another group of tests which overcomes these problems is summarized by the term “viscoelastic methods”. The common feature of these methods is that the blood clot firmness (or other parameters dependent thereon) is continuously determined, from the formation of the first fibrin fibres until the dissolution of the blood clot by fibrinolysis. Blood clot firmness is a functional parameter, which is important for haemostasis in vivo, as a clot must resist blood pressure and shear stress at the site of vascular injury. Clot firmness results from multiple interlinked processes: coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activation and fibrin-platelet interaction and can be compromised by fibrinolysis. Thus, by the use of viscoelastic monitoring all these mechanisms of the coagulation system can be assessed.
[0007] A common feature of all these methods used for coagulation diagnosis is that the blood clot is placed in the space between a cylindrical pin and an axially symmetric cup and the ability of the blood dot to couple those two bodies is determined.
[0008] The first viscoelastometric method was called “thrombelastography” (Harlert H: Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschrift 26:577-583, 1948). As illustrated in FIG. 1 , in the thromboelastography, the sample as a sample liquid 1 is placed in a cup 2 that is periodically rotated to the left and to the right by about 5°, respectively. A probe pin 3 is freely suspended by a torsion wire 4 . When a clot is formed it starts to transfer the movement of the cup 2 to the probe pin 3 against the reverse momentum of the torsion wire 4 . The movement of the probe pin 3 as a measure for the clot firmness is continuously recorded and plotted against time. For historical reasons the firmness is measured in millimetres.
[0009] The result of a typical measurement of this kind is illustrated in FIG. 2 . One of the most important parameters is the time between the activator induced start of the coagulation cascade and the time until the first long fibrin fibres have been build up which is indicated by the firmness signal exceeding a defined value. This parameter will be called clotting time or just CT in the following. Another important parameter is the clot formation time (CFT) which gives a measure for the velocity of the development of a clot. The CFT is defined as the time it takes for the clot firmness to increase from 2 to 20 mm. The maximum firmness a clot reaches during a measurement, further on referred to as maximum clot firmness or just MCF, is also of great diagnostic importance.
[0010] Modifications of the original thromboelastography technique (Hartert et al. (U.S. Pat. No. 3,714,815) have been described by Cavallari et al. (U.S. Pat. No. 4,193,293), by Do et al. (U.S. Pat. No. 4,148,216), by Cohen (U.S. Pat. No. 6,537,819). A further modification by Calatzis at al. (U.S. Pat. No. 5,777,215) illustrated in FIG. 3 is known under the term thromboelastometry.
[0011] Contrary to the modifications mentioned above, thromboelastometry is based on a cup 2 fixed in a cup holder 12 while the probe bin 3 is actively rotated. For this purpose the probe pin 3 is attached to a shaft 6 which is suspended by a ball bearing 7 in a base plate 11 and has a spring 9 connected to it. An oscillating motion perpendicular to the drawing plane induced at the opposite end of the spring is transformed into a periodically rotation of the shaft 6 and the connected cup 2 around a rotation axis 5 by about 5° in each direction. As the sample liquid 1 begins to coagulate the motion amplitude of the shaft 6 which is detected by the deflection of a light beam from detecting means 10 and a mirror 9 starts to decrease.
[0012] During coagulation the fibrin backbone creates a mechanical elastic linkage between the surfaces of the blood-containing cup 2 and a probe pin 3 plunged therein. A proceeding coagulation process induced by adding one or more activating factor(s) can thus be observed. In this way, various deficiencies of a patient's haemostatic status can be revealed and can be interpreted for proper medical intervention.
[0013] A general advantage of viscoelastometric, e.g. thromboelastometric, techniques compared to other laboratory methods in this field therefore is that the coagulation process and the change of mechanical properties of the sample are monitored as a whole. This means that—in contrary to other laboratory methods mentioned above—thromboelastometry does not only indicate if all components of the coagulation pathways are available sufficient amounts but also if each component works properly.
[0014] To obtain detailed information on the correct amount and function of the thrombocytes as well as the fibrinogen and certain factors nowadays there is an increasing amount of compounds available which activate or inhibit certain components of the coagulation system. This allows determining at which point of the coagulation system a problem is located.
[0015] For practical reasons theses compounds are usually injected into the disposable plastic cup which later on is used for the measurement by using a pipette (either a manual or an automatic one). In the last preparation step, after the blood or plasma sample has been added, the whole amount of sample (blood/plasma and the additional chemicals) is mixed by drawing it into the pipette tip and dispensing it into the cup again.
[0016] The possibility to activate or to inhibit certain components of the coagulation system is especially useful in conjunction with state-of-the-art thromboelastometers such as the ROTEM (Pentapharm GmbH, Munich, Germany) which allows conducting four measurements in parallel. This allows detailed information on the current status of the coagulation-situation of a patient to be achieved and therefore allows an appropriate therapy within several minutes.
[0017] This is of particular importance in case of patients struck by massive blood loss as it often occurs in context with multiple traumata or major surgery. The blood of such patients often is diluted due to infusions which are administered to replace the loss in volume. This leads to a decrease of the concentration of thrombocytes as well as coagulation factors including fibrinogen.
[0018] Main advantages of thromboelastometry and thromboelastography are the possibility to perform several differential tests in parallel in order to precisely determine which kinds of blood products are the appropriate medication, the possibility to perform the measurement at or close to the point of care (POC) and—compared to other methods—the relatively small amount of time until valid results are available.
[0019] On the other hand the operator has to perform a significant number of steps in order to start the measurement (preparation of the reagents, attachment of the probe pin and the cup to the instrument, pipetting and mixing the blood sample and the reagents, adjustment of computer settings, etc.) on which the time spent is considerable, especially in the case of surgery being performed.
[0020] Furthermore this rather complex preparation also increases the risk of operating errors. There have been several approaches to simplify the usage of thromboelastometers. The Rotem-System (Pentapharm GmbH, Munich, Germany) e.g. is supplied with an automatic pipette which simplifies the handling to a large degree and thereby decreases the risk of operating errors.
[0021] WO 2008093216 describes the approach to provide the adequate amount of each of the reagents needed for one specific test in a ready-to-use mixture. In order to prevent the reaction of the reagents prior to the measurement, they are supplied in a lyophilisate state. This is additionally advantageous as the reagents can be stored at room temperature. Using this approach the preparation is reduced to the steps of adding the blood sample into the reagent container, mixing of blood with the reagent and transferring the mixture to the instrument.
[0022] US 2007/0059840 A1 describes a hemostasis analysis device and method. The device includes a container for holding a sample to be tested and a bobber configured to be buoyantly suspended on the sample. A magnet is secured to the bobber. The container can be driven in an oscillating motion. An external magnetic field is generated adjacent to the bobber. A magnetic field strength detector detects changes in the magnetic field as a result of movement of the bobber and magnet responsive to the oscillating motion of the container and clotting of the sample.
[0023] Such a new measuring system entails acceptability problems and uncertainties for a user. Moreover, that analysis device does not fit in existing measuring systems. Therefore new systems have to be completely designed.
[0024] All these modifications lead to a significant improvement of handling of modern thromboelastometers and thromboelastographs, however, no successful approach to develop a widely automated technique has been made since Hartert's invention 60 years ago. One of the two main reasons of that is the fact that the measurement requires two disposable parts (cup and pin) being moved in relation to each other and thus have to be reversibly attached to different parts of the measurement device. E.g. in FIG. 3 , the probe pin 3 is attached to the shaft 6 and the cup 2 to the cup holder 12 , respectively. The other main reason is that different tests are required to get comprehensive information of a current bleeding status of a patient. These different tests require different reagents which have to be mixed with the blood sample.
SUMMARY OF THE INVENTION
[0025] It is a problem underlying the presented invention to provide a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample.
[0026] Directly connected to this invention is the problem to provide a corresponding measuring system for measuring viscoelastic characteristics of a sample liquid, in particular the coagulation characteristics of a blood sample liquid.
[0027] It is a further problem underlying the invention to provide a method for measuring viscoelastic characteristics of a sample liquid using said measuring system.
[0028] These problems are solved by the subject-matter of the independent claims. Preferred embodiments are set forth in the dependent claims.
[0029] In a first aspect, the present invention provides a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample, comprising
[0030] a cartridge body having at least one measurement cavity formed therein and having at least one probe element arranged in said at least one measurement cavity for performing a test on said sample liquid; and
[0031] a cover being attachable on said cartridge body;
[0032] wherein said cover covers at least partially said at least one measurement cavity and forms a retaining element for retaining said probe element in a predetermined position within said at least one measurement cavity.
[0033] In a second aspect, the present invention provides a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample, comprising: at least one interface element; at least one shaft rotatably supported by the interface element to be rotated by drive means; at least one cartridge device fixed to the interface element for holding the sample liquid, the at least one cartridge device comprising a cartridge body with a cover and at least one probe element arranged in a measurement cavity formed in said cartridge body for cooperating with the at least one shaft; at least one detecting means cooperating with the shaft for measuring viscoelastic characteristics of the sample liquid; and
[0034] control means to control the measuring system.
[0035] In a third aspect, the present invention provides a method for measuring viscoelastic characteristics of a sample liquid by means of said measuring system, comprising the following steps:
[0036] a) providing the cartridge device having at least one measurement cavity with at least one probe element arranged therein;
[0037] b) attaching the cartridge device to said interface element, said shaft being inserted into said probe element;
[0038] c) filling said measurement cavity of said cartridge device with sample liquid;
[0039] d) rotating said shaft in an oscillating motion around said rotation axis; and
[0040] e) measuring viscoelastic characteristics of said sample liquid by detecting the rotation of said shaft by said detecting means.
[0041] In a preferred embodiment the probe element comprises a probe pin to cooperate with the sample liquid and a connector section for a connection to the measuring system. The connector section is formed e.g. as a bore extending within the probe element and comprises frictional connection means which can be e.g. clip means or a thread. An insertion guide facilitates an insertion of a part, in particular a shaft, of a measuring system. Thereby the shaft can be connected securely to the probe element.
[0042] The at least one measurement cavity can comprise bearing or supporting means for the probe element to align or hold the probe element prior to insertion of the shaft.
[0043] After the shaft has been inserted into the connector section, the shaft can be lifted to position the probe element at a working position.
[0044] In an alternative preferred embodiment the probe element is formed as a detachably fixed component part of the cover. An operator only has to attach the cartridge device to the measuring system the shaft being inserted into the probe element will detach the probe element from the cover and hold it securely in a position ready to carry out a measurement. Therefore the probe element comprises a fixing section for detachably fixing the probe element at fixing means of the cover.
[0045] After a measurement the cartridge device can be detached from the measuring system wherein the shaft is removed from the probe element. Then the probe element will seal the measurement cavity against the cover by means of e.g. a flange adapted to form a sealing. The cover retains the probe element within the measurement cavity.
[0046] It is preferred that the fixing means of the cover comprises clip means cooperating with corresponding clip means of the fixing section of the probe element.
[0047] In an alternative embodiment the fixing section of the probe element is integrally formed with the cover, the fixing means of the cover comprising a perforation.
[0048] The cover can be fixed on the cartridge body either by bonding or welding. In an alternative embodiment the cover is integrally formed with the cartridge body, e.g. made of a plastic material. It is also possible that the cover is made of a material which is different from the cartridge body. That can be done for example by two- or more-component-moulding.
[0049] In a further preferred embodiment the cartridge device further comprises at least one receiving cavity formed therein for receiving the sample liquid; at least one reagent cavity for holding at least one reagent; a ductwork connecting said cavities and the at least one measurement cavity; and at least one pump means connected to the ductwork for transporting the sample liquid from the at least one receiving cavity to the at least one measurement cavity by means of the ductwork, wherein the cover covers and at least partially forms said cavities and said ductwork and forms at least partially the pump means.
[0050] In a further embodiment the at least one reagent cavity is integrally formed with the pump means or/and with the at least one measurement cavity or/and with one or more of the ductworks. The reagent cavity can be formed as a deep cavity or just a small place where reagent can be deposited. Thus the sample liquid being pumped through the ductwork end the pump means into the measurement cavity can be mixed with the reagent.
[0051] The pump means comprise at least one valve for a directed flow of the sample liquid in order to direct the pumped liquid into the measurement cavity.
[0052] In another embodiment the reagent or an additional reagent can be stored in at least one reagent receptacle which can be opened by external means.
[0053] In a further embodiment the at least one reagent receptacle storing a reagent is integrated in the cover.
[0054] In another embodiment the at least one reagent receptacle comprises a bottom part which can be opened by external means to discharge the reagent into the ductwork and/or into one of the cavities. The receptacle can be adapted as a blister receptacle, for example.
[0055] The at least one reagent can be stored within the cartridge device in pulverized, solid or liquid form.
[0056] The cartridge device can be further provided with at least one reagent stored therein.
[0057] Filling in sample liquid can be done directly into the measurement cavity if no receiving cavity is provided. To this end the sample liquid can be injected through the cover via an opening or passage hole in the interface element or through a ductwork by an operator or by a control apparatus.
[0058] In case of a receiving cavity the sample liquid can be filled into the receiving cavity and be pumped by the pump means to the measuring cavity.
[0059] To fill in sample liquid, operate the pump means, add reagents and/or open the reagent receptacle the measuring system is equipped with a control apparatus. The control apparatus has means to access the pump means through a pump access formed as a passage of the interface element. Further the control apparatus can inject sample liquid through an inlet opening in the interface element into the receiving cavity. The control apparatus comprises also operating means to inject or to add reagents into the cartridge device as well as to open reagent receptacles.
[0060] Further features and advantages of the present invention will be evident from a description of embodiments with reference to the figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0061] The figures are showing the following:
[0062] FIG. 1 is a schematic drawing of the principle of thromboelastography according to Hartert.
[0063] FIG. 2 is an exemplary diagram showing a typical thromboelastometric measurement.
[0064] FIG. 3 is a schematic drawing of the thromboelastometry.
[0065] FIG. 4 is a schematic drawing of a first embodiment of a cartridge device according to the invention.
[0066] FIG. 5 is a schematic drawing of a variation of the first embodiment of the cartridge device according to the invention.
[0067] FIG. 6 is a schematic drawing of another variation of the first embodiment of the cartridge device according to the invention.
[0068] FIG. 7 a is a schematic drawing of a first embodiment of a probe element.
[0069] FIG. 7 b is a schematic drawing of the first embodiment of the probe element of FIG. 7 a within a measuring cavity of the first or a second embodiment of the cartridge device according to the invention before use.
[0070] FIG. 7 c is a schematic drawing of the first embodiment of the probe element of FIG. 7 a within a measuring cavity of the first or the second embodiment of the cartridge device according to the invention in use.
[0071] FIGS. 8 a - c are technical drawings of the preferred probe element of FIG. 7 a.
[0072] FIG. 9 a is a side view of a third embodiment of a cartridge device according to the invention.
[0073] FIG. 9 b is a sectional view B-B of the cartridge device of FIG. 9 a.
[0074] FIG. 9 c is a sectional view C-C of the cartridge device of FIG. 9 a.
[0075] FIG. 9 d is a sectional view D-D of the cartridge device of FIG. 9 a.
[0076] FIG. 10 a is a top view of the cartridge device of FIG. 9 a.
[0077] FIG. 10 b is a sectional view E-E of the cartridge device of FIG. 10 a.
[0078] FIG. 11 a is a sectional view of a pump means of the cartridge device of FIG. 9 a.
[0079] FIG. 11 b is a sectional view of the pump means of FIG. 11 a in operated position.
[0080] FIG. 12 is a schematic top view of the pump means of FIG. 11 a.
[0081] FIG. 13 a is a side view of an embodiment of a measuring system according to the invention.
[0082] FIG. 13 b is a top view of the measuring system of FIG. 13 a.
[0083] FIG. 13 c is a sectional view H-H of the measuring system of FIG. 13 b.
[0084] FIG. 14 is a sectional view of a reagent receptacle of a third embodiment of the cartridge device according to the invention.
[0085] FIG. 15 is a schematic drawing of a second embodiment of the probe element.
DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0086] Parts and components having same functions are depicted with same references.
[0087] Prior to a detailed description of the preferred embodiments the basic features and a basic practical implementation are summoned as follows. All embodiments refer to a cartridge device 50 (see FIG. 13 c ) which can be formed in a first embodiment (see FIGS. 4, 5 and 6 ), in a second embodiment (see FIGS. 7 b, 7 c and 15 ) or in a third embodiment (see FIGS. 9 to 10 ). The cartridge device 50 contains all parts coming into contact with a sample liquid 1 to be tested. These can be also reagents the sample liquid has to be mixed with for a measurement. The cartridge device 50 is part of a measuring system 40 (see FIG. 13 c ) to which the cartridge device 50 is attached before measurement. The measuring system 40 also comprises a control apparatus (not shown) which has been adapted to interact with the cartridge device 50 by electrical and/or mechanical means to control flow of sample liquid 1 (see FIG. 7 c ) and measurements as well as collect data. Furthermore this apparatus contains mechanical and electronic parts required for measurement, data analysis and user interaction. The present invention is not only suitable for thromboelastometry, thromboelastography and platelet aggregometry but also for other blood tests usually performed regarding surgery.
[0088] A first embodiment of a cartridge device 50 of the invention will be described with reference to FIGS. 4 and 5 . The cartridge device 50 for the measuring system 40 for measuring medical relevant, e.g. viscoelastic, characteristics like coagulation or platelet function of a sample liquid 1 , particularly a blood sample, comprises a receiving cavity 16 for receiving the sample liquid 1 , pump means 18 for pumping the sample liquid, a reagent cavity 19 for storing a reagent 21 , a measurement cavity 20 for measuring the sample liquid 1 and a ductwork connecting said cavities. The ductwork comprises an inlet duct 13 from the receiving cavity 16 to the pump means 18 , an intermediate duct from the pump means 18 to the reagent cavity 19 and an outlet duct 15 from the reagent cavity 19 to the measurement cavity 20 . In a variation said cavities and ducts can be arranged in different ways one of which is shown in FIG. 5 , wherein pump means 18 and reagent cavity 19 are changed.
[0089] In this embodiment the receiving cavity 16 consists of a cavity within the cartridge device 50 . The sample liquid 1 can be applied by means of a syringe, pipette etc, e.g. through a self sealing cap shown as a receiving cavity cover 33 a in FIG. 10 b. By operating the pump means 18 , e.g. by means of the control apparatus mentioned above, the sample liquid is transported to the reagent cavity 19 , where the reagent 21 required for measurement is mixed with the sample liquid 1 . Further pumping the sample liquid 1 will transfer it into the measurement cavity 20 in which the measurement (described below) is carried out.
[0090] In an alternative embodiment the reagent cavity 19 is integral formed with the pump means 18 and/or with the measurement cavity 20 and/or with the ductwork. The transport of the sample liquid 1 can be controlled by said control apparatus.
[0091] FIG. 6 shows another variation of the first embodiment. Two arrangements of FIG. 4 with only one receiving cavity 16 are arranged in parallel, wherein a first inlet duct 13 communicates with a second inlet duct 13 ′ connected to second pump means 18 ′. A second intermediate duct 14 ′ leads to a second reagent cavity 19 ′ storing a second reagent 21 ′. A second outlet duct 15 ′ connects the second reagent cavity 19 ′ to the second measurement cavity 20 ′. FIG. 6 shows only one possible variation of a plurality of different arrangements easily imagined. The sample liquid 1 is shared among the arrangements in parallel. Controlled by the external control apparatus the shared portions of the sample liquid 1 are mixed with different reagents 21 , 21 ′ during transport. It is apparent to a person skilled in the art that in order to achieve a maximum benefit for a user different types of tests can be combined in one cartridge device 50 .
[0092] In a preferred embodiment the cartridge device 50 comprises four arrangements of FIG. 4 or 5 having 4 measurement cavities 20 , 20 ′. Thus measurements can be done with different reagents on the same liquid sample or with same reagents as well to check plausibility.
[0093] Regarding e.g. blood coagulation there are different reagents available which activate or suppress different parts of the coagulation cascade. Pentapharm GmbH (Munich, Germany) for example amongst others provide tests for intrinsic and extrinsic activation of a blood sample (INTEM or EXTEM respectively), and also a test for extrinsic activation in which the thrombocyte function is suppressed by administration of cytochalasin D (FIBTEM). It is state of the art that it is possible by wise combination of such tests to be able to determine very precisely at which point within the coagulation cascade a problem occurs. This is of great importance in order to determine a proper medication. By comparison of the results on an EXTEM test of a pathologic sample to those of a FIBTEM test of the same sample it is possible to e.g. precisely determine if a coagulation disorder results from lack of fibrinogen or a malfunction of platelets. Generally, there are different typical medical scenarios in which coagulation disorders are very likely to occur. For example coagulation disorders occurring during liver transplantation are merely caused by lack of certain coagulation factors etc., while coagulation disorders during open heart surgery are most likely due to the influence of heparin. This means basically that different medical settings require different coagulation tests. Referring to FIG. 6 it is possible and worthwhile to provide different cartridge devices 50 for different typical operations. It is also possible to combine e.g. an INTEM, an EXTEM and a FIBTEM coagulation test with a platelet aggregometry test within one cartridge. Using such a cartridge the preparation of a measurement which provides almost overall information about the coagulation status of a patient merely requires the two steps of attaching the cartridge device 50 to the measuring system 40 with the external control apparatus and injecting the blood sample as one sample liquid 1 . Considering the significance of more complex and time consuming preparation of several thromboelastography or thromboelastometry tests, it is evident that the invention is of great advantage for easier, safer and more accurate POC-tests.
[0094] It is important to note that the cartridge devices 50 of the described embodiments are suitable for different diagnostic tests like thromboelastometry, thromboelastography, platelet aggregometry and others. Depending on which type of test or tests the cartridge device 50 is designed for, there are different additional parts required which interact with the sample during measurement and/or an external control apparatus. Possible adaptations for thromboelastometry and platelet aggregometry are described below.
[0095] FIG. 7 a is a schematic drawing of a first embodiment of a probe element 22 arranged in the measurement cavity 20 (see also FIGS. 10 b and 13 c ). FIGS. 7 b and 7 c show a second embodiment of the cartridge device 50 in form of a cartridge body 30 which comprises only the measurement cavity 20 . In the shown example this cavity 20 is accessible via a ductwork 15 , 15 ′ through a cavity wall. Alternatively the cavity 20 can be filled through a cover 31 , e.g. by injection needles or the like.
[0096] The probe element 22 comprises the probe pin 3 (see FIG. 1 ) which is connected to a flange 24 and a fixing section 25 via an intermediate section 23 . The probe element 22 is formed as a rotational part and further comprises a connector section 26 formed as a bore extending within the probe element 22 along its longitudinal axis, which is the rotational axis 5 as well (see FIG. 3 ).
[0097] The probe element 22 is arranged in the measurement cavity 20 of the cartridge body 30 of the cartridge device 50 as shown in FIG. 7 b. The measurement cavity 20 is covered by the cover 31 (see also FIGS. 10 b and 13 c ). The cover 31 comprises an opening with fixing means 32 above the measurement cavity 20 . The probe element 22 is arranged such that its fixing section 25 corresponding to the fixing means 32 engage with them. In this manner the probe element 22 is detachably fixed to the cover 31 . The fixing means 32 in this example are equipped with a circular nose corresponding to a circular notch of the fixing section 25 of the probe element 22 . Other fixing means e.g. clip means or the like are possible. The flange 24 is in contact to the inner side of the cover 31 .
[0098] During attaching the cartridge device 50 to the measuring system 40 (see also FIG. 13 c ) the shaft 6 of the measuring system 40 (see FIG. 3 and FIGS. 13 a . . . c ) is inserted with its bottom portion, an insert section 6 a, into the connector section 26 . By insertion into the connector section 26 of the probe element 22 the probe element 22 will be detached from the cover 31 not before the insert section 6 a is completely inserted in the connector section 26 . Then the probe element 22 will be put into in a measuring position as shown in FIG. 7 c and kept there. The insert section 6 a of the shaft 6 is engaged with the connector section 26 of the probe element 22 e.g. by friction, clip means, thread or the like. In case of a thread the probe element 22 will be hold by the engagement with or perforation of the cover 31 . The shaft 6 having a corresponding thread on its insert section 6 a will be inserted into the connector section of the probe element 22 by rotation until the insert section 6 a will be completely inserted into the connector section 26 . Then the shaft 6 can be pushed down and/or rotated together with the fully engaged probe element 22 until the probe element 22 will be detached from the cover 31 . FIG. 7 c shows the sample liquid 1 , which has been pumped into the measurement cavity 20 . The probe pin 3 of the probe element 22 is immersed in the sample liquid 1 . A measurement as described above can be carried out. After the measurement the cartridge device 50 is detached from the measuring system 40 , wherein the shaft 6 is drawn up together with the probe element 22 against the cover 31 . The insert section 6 a of the shaft 6 will be drawn out of the connector section 25 of the probe element 22 the flange 24 thereof contacting and sealing the opening of the cover 31 . Instead of a flange 24 the upper end of the probe element 22 can have a larger diameter than the opening in the cover 31 . It is preferred that the insert section 6 a of the shaft 6 and the measurement cavity 20 , 20 ′ are formed symmetrically.
[0099] It is also possible to insert the insert section 6 a of the shaft 6 into the connector section 26 of the probe element 22 and push the probe element 22 down until its bottom contacts the bottom of the measurement cavity 20 , 20 ′ ensuring that the insert section 6 a is completely inserted into the connector section 26 . Then the shaft 6 will be moved up into the measuring resp. working position of the probe element 22 as shown in FIG. 7 c.
[0100] FIGS. 8 a . . . c are technical drawings of a preferred embodiment of the probe element 22 of FIG. 7 a FIG. 8 a shows a side view and FIG. 8 b shows a top view of the probe element 22 parts of which have been described above regarding FIG. 7 a. Finally, FIG. 8 c illustrates a sectional view along rotational axis 5 . The connector section 26 extends over more than about 75% of the length of the probe element 22 .
[0101] Now a third embodiment of the cartridge device 50 will be described with reference to FIGS. 9 a, . . . , d and FIGS. 10 a, . . . b.
[0102] FIG. 9 a is a side view of a second embodiment of a third embodiment of the cartridge device 50 according to the invention. FIG. 9 b is a sectional view B-B of the cartridge device 50 of FIG. 9 a. FIG. 9 c is a sectional view C-C of the cartridge device of FIG. 9 a. FIG. 9 b is a sectional view D-D of the cartridge device of FIG. 9 a. FIG. 10 a is a top view of the cartridge device of FIG. 9 a. FIG. 10 b is a sectional view E-E of the cartridge device of FIG. 10 a.
[0103] The cartridge device 50 of this example is equipped with the ductwork 13 and 15 . The ducts are formed with an diameter of approximately 1 mm in this embodiment. The ductwork requires that the cartridge device 50 comprises two parts: the cartridge body 30 and the cover 31 , which are glued or welded together to obtain a leak-proof device. The cartridge body 30 is relative rigid and the cover 31 is formed as an elastic part. So it is possible to integrate the pump means 18 into the cover 31 . Moreover, the cover 31 covers the receiving cavity 16 with the receiving cavity cover 33 a and forms a type of liner wall 33 and a separation wall 34 forming an inlet for the inlet duct 13 within the receiving cavity 16 . The receiving cavity cover 33 a might act as a self seal for injection of a sample liquid 1 by a syringe for example. The cover 31 forms top parts of the ductwork 13 an 15 and a cover of the measurement cavity 20 (see also FIGS. 7 b . . . c ). In this example the pump means 18 comprises a pump membrane 35 formed by the cover 31 . The pump membrane 35 cooperates with a pump cavity 36 termed with a pump cavity bottom 36 a in the cartridge body 30 below the pump membrane 35 .
[0104] In this embodiment a reagent cavity 19 , 19 ′ is formed, e.g. by sections of the ductwork or/and the pump means 18 , 18 ′ in which the reagents can be stored resp. deposited, especially on the pump cavity bottom 36 a, for example.
[0105] The pump means 18 will now be described with reference to FIGS. 11 a . . . b and FIG. 12 .
[0106] FIG. 11 a is a sectional view of the pump means 18 , 18 ′ of the cartridge device 50 , FIG. 11 b is a sectional view of the pump means 16 of FIG. 11 a In operated position, and FIG. 12 is a schematic top view of the pump means 18 of FIG. 11 a.
[0107] In this example the pump cavity 36 is connected to the inlet duct 13 via an inlet valve 37 and to the outlet valve via an outlet valve 38 . Actuation of the pump membrane 35 (shown in FIG. 11 b in a working cycle) by an appropriate actuating means (not shown) of the control apparatus the pump means 18 will create a directed flow of the sample liquid 1 in a flow direction 39 depicted by the arrows. The pump membrane 35 being an integrated part of the cover 31 can be made of the cover material or a part made of another material integrally manufactured with the cover 31 , e.g. two components manufacturing. The valves 37 , 36 can be a type of non-return valve. FIG. 12 shows a top view of the pump means in a schematic way.
[0108] An external force exerted on the pump membrane 35 increase the pressure within the pump cavity 36 and opens outlet valve 38 and doses inlet valve 37 . Releasing the external force the elastic pump membrane 35 returns into the position shown in FIG. 11 a whereby outlet valve 38 will be closed and inlet valve 37 opened to let sample liquid 1 into the pump cavity 36 . This mechanism is state of the art according to DE10135569. In context with the present invention the actuation means of the control apparatus activating the pump membrane 35 from outside has the advantage of strict separation between those parts coming into contact with the sample liquid 1 and the control apparatus. At the same time the total number of parts required for the cartridge device 50 being a disposable part as well is kept on a minimum.
[0109] Now the measuring system 40 according to the invention is described in an embodiment with reference to FIGS. 13 a . . . c.
[0110] FIG. 13 e , is a side view of an embodiment of the measuring system 40 , FIG. 13 b is a top view of the measuring system 40 of FIG. 13 a, and FIG. 13 c is a sectional view H-H of the measuring system 40 of FIG. 13 b.
[0111] The measuring system 40 comprises an interface element 41 to which the cartridge device 50 is attached and fixed. The interface element 41 is shown in FIGS. 13 a to 13 c in way of example as a base plate. The function of the interface element 41 is to support the shaft 6 and to maintain its position and thus the position of the probe element 22 fixed to the insert section 6 a in a measurement position. The interface element 41 can be connected to the whole cover 31 as shown in FIGS. 13 a to 13 c or only to parts of the cover 31 , e.g. surrounding the rotation axis 5 . The shaft 6 is rotatable supported in a bearing 7 within a shaft passage 44 ( FIG. 13 c ) and can be rotated around the rotation axis 5 (see also FIG. 3 ) by driving the spring 9 via driving means (not shown). The detecting means 10 cooperate with the mirror 8 fixed on the shaft 3 , also shown in FIG. 3 . The control apparatus mentioned above is not shown as well, but easy to imagine. Its actuation and/or operating means can access the pump means 18 through an opening pump access 42 in the interface element 41 . The receiving cavity 16 is accessible through another inlet opening 43 . These and other different passages or passage ways of the interface element 41 to have access to the cartridge device 50 and/or its cover 31 are illustrated by FIG. 13 b as a top view of the measuring system 40 of FIG. 13 a . Passage holes 44 a are arranged next to the rotational axis 5 to form an access to the cover 31 above the measurement cavity 20 , 20 ′, e.g. for injection of liquid sample or reagents. Additional access passage holes can be arranged in the interface element 41 , e.g. above the ductwork to access said ductwork.
[0112] FIG. 13 c illustrates a sectional view H-H of FIG. 13 b showing the mounted cartridge device 50 and the measuring system 40 . The shaft 6 with its insert section 6 a is inserted into the probe element 22 and keeps it in a measurement position as mentioned above. This embodiment comprises only one measurement cavity 20 , but it is apparent to a person skilled in the art that modifications and combinations of the invention can be carried out in different ways.
[0113] Thus it is possible to e.g. arrange a reagent receptacle 19 b in a blister receptacle e.g. as shown in FIG. 14 which is a sectional view of the reagent receptacle 19 b of a third embodiment of the cartridge device 50 according to the invention. The receptacle 19 b contains reagent 21 hold within a chamber defined by a buster cover 49 , a bottom part 48 and a frame 47 hold in a retaining ring 46 within an reagent cover opening 45 in the cover 31 above the reagent cavity 19 , 19 ′ with a reagent cavity bottom 19 a, 19 a ′. Upon exertion of a force by the control apparatus onto the blister cover 49 the bottom part 48 will open and discharge the reagent 21 into the reagent cavity 19 , 19 ′. The receptacle 19 b can be fixed to the cover by e.g. clip means as depicted. The frame 47 can be a reinforced ring. The blister cover 49 is reinforced so that it will not break when a force is exerted on it. Thus the leak-tightness of the cartridge device 50 will be ensured. In this way a unitized construction system can be made, wherein the respective reagents can be easily integrated into the cartridge device 50 . It is also advantageous that the reagents can be designed as a small component being cooled reap, transported and supplied easily.
[0114] It is also possible to insert reagent receptacles into provided cavities being connected to the ductwork. The reagents can be designed as globules with an appropriate diameter so that they cannot flow through openings into the ductwork before being dissolved by the sample liquid.
[0115] FIG. 15 is a schematic drawing of a second embodiment of a probe element 22 ′. The probe element 22 ′ is arranged in the measurement cavity 20 . The probe pin 3 is provided with a dimple 29 at its bottom side. The dimple 29 forms with a nose 29 a a toe bearing to support the probe element 22 ′. The probe element 22 ′ is similar to the probe element 22 of FIG. 7 a, but has no fixing section 25 , only the flange 24 . The connector section 26 comprises a top end formed with an insertion guide 27 for the insertion section 6 a of the shaft. The probe element 22 ′ is hold in the measurement cavity 20 in a specific manner so that the insertion section 6 a of the shaft 6 can be inserted easily through an opening 32 a of the cover 31 which has no fixing means. The insertion section 6 a can engage with a groove 28 inside the connector section 26 of the probe element 22 ′. After that engagement which is supported by the toe bearing the shaft 6 will be drawn up together with the probe element 22 ′ in the measuring position. It is a matter of fact that other engagement means can be used.
LIST OF REFERENCE NUMERALS
[0116] 1 Sample liquid
[0117] 2 Cup
[0118] 3 Probe pin
[0119] 4 Torsion wire
[0120] 5 Rotation axis
[0121] 6 Shaft
[0122] 6 a Insert section
[0123] 7 Bearing
[0124] 8 Mirror
[0125] 9 Spring
[0126] 10 Detecting means
[0127] 11 Base plate
[0128] 12 Cup holder
[0129] 13 , 13 ′ Inlet duct
[0130] 14 , 14 Intermediate duct
[0131] 15 , 15 ′ Outlet duct
[0132] 16 , 16 ′ Receiving cavity
[0133] 17 Branch duct
[0134] 18 , 18 ′ Pump means
[0135] 19 , 19 ′ Reagent cavity
[0136] 19 a, 19 ′ a Regents cavity bottom
[0137] 19 b Reagent receptacle
[0138] 20 , 20 ′ Measurement cavity
[0139] 21 , 21 ′ Reagent
[0140] 22 , 22 ′ Probe element
[0141] 23 Intermediate section
[0142] 24 Flange
[0143] 25 Fixing section
[0144] 26 Connector section
[0145] 27 Insertion guide
[0146] 28 Groove
[0147] 29 Dimple
[0148] 29 a Nose
[0149] 30 Cartridge body
[0150] 31 Cover
[0151] 32 Fixing means
[0152] 32 a Opening
[0153] 33 Wall
[0154] 33 a Receiving cavity cover
[0155] 34 Separation wall
[0156] 35 Pump membrane
[0157] 36 Pump cavity
[0158] 36 a Pump cavity bottom
[0159] 37 Inlet valve
[0160] 38 Outlet valve
[0161] 39 Flow direction
[0162] 40 Measuring system
[0163] 41 Interface element
[0164] 42 Pump access
[0165] 43 inlet opening
[0166] 44 Shaft passage
[0167] 44 a Passage hole
[0168] 45 Reagent cover opening
[0169] 46 Retaining ring
[0170] 47 Frame
[0171] 48 Bottom foil
[0172] 49 Blister cover
[0173] 50 Cartridge device | The present invention is directed to a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid. In particular a blood sample, comprising a cartridge body having at least one measurement cavity formed therein and having at least one probe element arranged in said at least one measurement cavity for performing a test on said sample liquid; and a cover being attachable on said cartridge body; wherein said cover covers at least partially said at least one measurement cavity and forms a retaining element for retaining said probe element in a predetermined position within said at least one measurement cavity. The invention is directed to a measurement system and a method for measuring viscoelastic characteristics of a sample liquid. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for the production of lactide in which highly pure lactide usable as a raw material for the synthesis of a polyacetic lactic acid can be industrially produced at low cost.
Although highly pure lactide has heretofore been produced by using lactic acid as the starting material, a salt of a 2-halopropionic acid is used in place of lactic acid in the process of the present invention.
2. Description of the Prior Art
Usually, lactide is produced by heating lactic acid at about 200° C. at a pressure of 20 mmHg or less to condense it with the elimination of water. Since readily obtainable lactic acid is used as the starting material, this process is often employed to synthesize a labo-use amount of lactide. However, this process must be carried out in a relatively high vacuum and, moreover, the reaction rate is low. Accordingly, high equipment costs will be required in order to carry out this process on an industrial scale. Furthermore, highly pure lactic acid will be required in order to produce highly pure lactide according to this process. A high degree of purification of lactic acid, in turn, will require considerable purification costs. For these reasons, it has been difficult to produce lactide of polymer grade industrially at low cost.
SUMMARY OF THE INVENTION
We have made a detailed study of the production of lactide with a view to developing a process by which lactide having a sufficiently high purity to be usable as a raw material for the synthesis of a polylactic acid is produced. As a result, we have found that an alkali metal or alkaline earth metal salt of a halopropionic acid can be converted into lactide by heating the salt in a non-aqueous solvent. The present invention has been completed on the basis of this finding.
According to the present invention, there is provided a process for the production of lactide which comprises the steps of heating an alkali metal or alkaline earth metal salt of a 2-halopropionic acid in a non-aqueous solvent to convert the salt into lactide, and separating the lactide so formed.
More specifically, the present invention relates to a novel process for producing lactide according to the following equation (1) or (2): ##STR1## wherein A is an alkali metal, B is an alkaline earth metal, and X is a halogen atom. The lactide thus obtained is a compound useful as a raw material for the synthesis of a polylactic acid.
DETAILED DESCRIPTION OF THE INVENTION
The term "2-halopropionic acid" as used herein comprehends 2-chloropropionic acid, 2-bromopropionic acid and 2-iodopropionic acid. Among them, 2-chloropropionic acid is preferably used in the process of the present invention because it is most readily obtainable in industry and suitable for the intended purpose of the present invention.
Alkali metal or alkaline earth metal salts of such 2-halopropionic acids can readily be prepared by reacting a 2-halopropionic acid with an alkali metal such as lithium, sodium, potassium, rubidium or cesium; an alkaline earth metal such as magnesium, calcium, strontium or barium; or an oxide, hydroxide or weak acid salt of an alkali metal or alkaline earth metal, such as calcium oxide, strontium oxide, magnesium oxide, sodium oxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, calcium hydroxide, barium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, strontium carbonate, barium carbonate, sodium hydrogencarbonate or potassium hydrogencarbonate.
Specific examples of the alkali metal or alkaline earth metal salts of 2-halopropionic acids prepared from the above-described materials include alkali metal or alkaline earth metal salts of 2-chloropropionic acid, such as lithium 2-chloropropionate, sodium 2-chloropropionate, potassium 2-chloropropionate, rubidium 2-chloropropionate, cesium 2-chloropropionate, magnesium 2-chloropropionate, calcium 2-chloropropionate, strontium 2-chloropropionate and barium 2-chloropropionate; alkali metal or alkaline earth metal salts of 2-bromopropionic acid, such as lithium 2-bromopropionate, sodium 2-bromopropionate, potassium 2-bromopropionate, rubidium 2-bromopropionate, cesium 2-bromopropionate, magnesium 2-bromopropionate, calcium 2-bromopropionate, strontium 2-bromopropionate and barium 2-bromopropionate; alkali metal or alkaline earth metal salts of 2-iodopropionic acid, such as lithium 2-iodopropionate, sodium 2-iodopropionate, potassium 2-iodopropionate, rubidium 2-iodopropionate, cesium 2-iodopropionate, magnesium 2-iodopropionate, calcium 2-iodopropionate, strontium 2-iodopropionate and barium 2-iodopropionate.
Since these 2-halopropionic acid salts can readily be purified by such techniques as recrystallization, the purity of the resulting lactide can be enhanced by purifying the 2-halopropionic acid salt used as the starting material.
When these salts are synthesized or purified by recrystallization, water may be used as the solvent. However, in order to obtain the salts in the form of crystals, low-boiling alcohols, ketones, esters, ethers and the like are preferably used. Among them, low-boiling alcohols such as methanol, ethanol and isopropyl alcohol are especially preferred.
The non-aqueous solvent used in the process of the present invention must be one which can dissolve at least a part of the alkali metal or alkaline earth metal salt of 2-halopropionic acid under reaction conditions and does not react with lactide to reduce the yield thereof. In particular, non-aqueous solvents having a low-boiling point, a high solubility for lactide and a low solubility for alkali metal or alkaline earth metal halides are preferred for the purpose of obtaining a highly pure form of lactide.
Such solvents include, for example, ketones, esters and ethers. Specific examples of preferred solvents are acetone, methyl ethyl ketone, methyl isobutyl ketone, isopropyl acetate, diethyl ether, dioxane and tetrahydrofuran.
Among these solvents, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone are especially preferred.
In carrying out the process of the present invention, an alkali metal or alkaline earth metal salt of 2-halopropionic acid is dissolved in the above-defined non-aqueous solvent which has been heated to a temperature in the range of 100° to 250° C.
The solvents preferably used in the process of the present invention have a relatively high vapor pressure in the above-described temperature range. Accordingly, the process of the present invention is preferably carried out under pressure, especially in the vicinity of the pressure produced by the solvent itself at the reaction temperature.
Under these temperature and pressure conditions, the reaction time usually ranges from 0.1 to 6 hours and preferably from 0.5 to 2 hours, though it may vary according to the reaction temperature.
Another advantage of the present invention is that the lactide obtained in the above-described manner can readily be purified by recrystallization to yield a purer form of lactide. This is due to the fact that the greater part of the impurities which may present in the lactide produced according to the process of the present invention comprises unreacted o-halopropionate and this impurity can readily be removed by recrystallization. Preferred examples of solvents usable for the recrystallization of lactide include ketones, esters, ethers and alcohols. Among them, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl acetate, isopropyl acetate, diethyl ether and the like are especially preferred because they are easy to handle and can yield lactide having a relatively high purity.
The present invention is further illustrated by the following examples.
REFERENCE EXAMPLE 1
Preparation of sodium 2-chloropropionate
108.5 g (1 mole) of 2-chloropropionic acid was dissolved in 1,000 ml of methanol, and the resulting solution was neutralized by adding a (ca. lN) methanol solution of sodium hydroxide dropwise thereto. Thus, there was obtained a methanol solution of sodium 2chloropropionate
Then, the above solution was evaporated at about 50° C under reduced pressure until all of the methanol was removed. Thus, there was obtained about 130 g of sodium 2-chloropropionate in the form of crystals.
EXAMPLE 1
10 g of the sodium 2-chloropropionate prepared according to the procedure of Reference Example 1 was dispersed in 100 ml of acetone, and the resulting suspension was heated in an autoclave at 200° C for 2 hours. During this process, the pressure within the autoclave was maintained at about 25 atmospheres. After the autoclave was cooled to room temperature, the lid was opened and the reaction mixture was taken out. Since the reaction mixture consisted of a liquid phase (acetone layer) and a solid (sodium chloride), the solid was removed by filtration and the acetone layer was concentrated by vacuum distillation (at 40° C.) to obtain about 6 g of crude lactide in the form of crystals. When a sample of the lactide was hydrolyzed and then analyzed by acid-base titration, its yield was found to be 76% based on the amount of sodium 2-chloropropionate used as the starting material. Then, this crude lactide was recrystallized from an ethyl acetate solution to obtain about 1.7 g of purified lactide having a purity of 99.7% or higher.
EXAMPLE 2
Potassium 2-chloropropionate was prepared in the same manner as described in Reference Example 1, except that potassium hydroxide was used in place of the sodium hydroxide.
In the same manner as described in Example 1, the above potassium 2-chloropropionate was heated in acetone at 190° C. for 1.5 hours to obtain about 4 g of crude lactide in the form of crystals. In this case, the yield of lactide was found to be 78% based on the amount of potassium 2-chloropropionate used as the starting material. When this crude lactide was recrystallized in the same manner as described in Example 1, there was obtained 1.3 g of purified lactide having a purity of 99.7% or higher.
REFERENCE EXAMPLE 2
Preparation of calcium 2-chloropropionate
108.5 g (1 mole) of 2-chloropropionic acid was dissolved in 1,000 ml of ethanol. To the resulting solution was slowly added about 28 g (0.5 mole) of calcium oxide which had been finely ground in dry air. This mixture was stirred in a warm water bath at about 50° C. until the calcium oxide dissolved completely.
Then, using a rotary evaporator, the above solution was evaporated at 50° C. under slightly reduced pressure until all of the ethanol was removed. Thus, there was obtained about 128 g of calcium 2-chloropropionate in the form of crystals.
EXAMPLE 3
10 g of the calcium 2-chloropropionate prepared according to the procedure of Reference Example 2 was dispersed in about 100 ml of dioxane, and the resulting dispersion was heated in an autoclave at 180° C. for 1 hour to effect reaction.
After completion of the reaction, the presence of lactide in the reaction product mixture was confirmed by comparing its infrared absorption spectrum with that of a standard sample.
EXAMPLE 4
Barium 2-chloropropionate was prepared in the same manner as described in Reference Example 2, except that 99 g of barium carbonate was used in place of the calcium oxide.
Then, the barium 2-chloropropionate thus-obtained was reacted in the same manner as described in Example 3. The formation of lactide was confirmed in the same manner as described above.
REFERENCE EXAMPLE 3
Preparation of sodium 2-bromopropionate
Sodium 2-bromopropionate was prepared in the same manner as described in Reference Example 1, except that the same molar amount of 2-bromopropionic acid was used in place of the 2-chloropropionic acid.
EXAMPLE 5
10 g of the sodium 2-bromopropionate prepared in Reference Example 3 was dispersed in 100 ml of methyl ethyl ketone, and the resulting dispersion was heated in an autoclave at 160° C. for 0.5 hour to effect reaction.
After completion of the reaction, the presence of lactide in the reaction product mixture was confirmed by examining its infrared absorption spectrum.
REFERENCE EXAMPLE 4
Preparation of sodium 2-iodopropionate
Sodium 2-iodopropionate was prepared in the same manner as described in Reference Example 1, except that the same molar amount of 2-iodopropionic acid was used in place of the 2-chloropropionic acid.
EXAMPLE 6
10 g of the sodium 2-iodopropionate prepared in Reference Example 4 was dispersed in 100 ml of methyl isobutyl ketone, and the resulting dispersion was heated in an autoclave at 140° C. for 1 hour to effect reaction.
After completion of the reaction, the presence of lactide in the reaction product mixture was confirmed by examining its infrared absorption spectrum as described previously. | Disclosed is a process for the production of highly pure lactide, especially having a sufficiently high purity to be usable as a raw material for the synthesis of polymers, by heating a 2-halopropionate in a non-aqueous solvent. | 2 |
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a distributed computer system and management thereof.
[0002] Computers have now become an integral part of our society both in business and personal lives. Almost every business of sufficient size in the United States and other developed countries have one or more computers to assist them in running their businesses. Similarly, most families in the United States now have one or more computers at home that are used to run various applications as well as playing games.
[0003] Some attribute the popularity of the computers to the Internet. The Internet provides people with a ready access to vast amounts of data. Many people now get their news, sports, stock, entertainment, and other information primarily from the Internet.
[0004] The businesses have also embraced the Internet. The Internet provides the opportunity for computers to communicate instantly with other computers or individuals. Business processes that were once restricted to intranets and their users are now moving to the Internet. Accordingly, companies are moving more and more of their data to electronic forms. In addition, companies have amassed huge amounts of data in an effort to understand their business, improve performance, and build stronger employee, customer, and partner relationships.
[0005] Today distributed computer systems are widely used by various organizations to accommodate the ever increasing demand for the computer resources from consumers and businesses alike. Servers are grouped or clustered to perform certain functions. That is, Web servers are grouped into a first group, and unification servers are grouped into a second group, and so on. Accordingly, each distributed system generally has a plurality of groups of servers. One example of such a distributed system is the enterprise portal system of SAP AG, a German software company. Such a portal system includes servers that primary perform functions relating to presentation of data (or first server cluster) and servers that primary execute business applications (or second server cluster). As the importance of server clusters increases, the businesses are becoming more aware of the need to more efficiently managing these server clusters.
BRIEF SUMMARY OF THE INVENTION
[0006] In one embodiment, a method for managing a plurality of servers includes launching a cluster manger in response to a request from a user. The cluster manager is operable to manage system preference settings of a plurality of servers in a cluster group. A first server is selected from the plurality of servers provided in the cluster group according to an input from the user. The selected first server is designated to be a master server. A new system preference setting for the first server is receiving from the user. A second server from the plurality of server provided in the cluster group is selected according to an input from the user. A system preference setting of the second server is synchronized to the new system preference setting of the first server according to an input from the user.
[0007] In one embodiment, a method for managing a plurality of servers in a portal environment includes selecting a first server from the plurality of servers provided in a cluster group, the selected first server being designated to be a master server; changing a system preference setting of the first server, the changed system preference setting being a new system preference setting for the first server; selecting a second server from the plurality of server provided in the cluster group; synchronizing a system preference setting of the second server to the new system preference setting of the first server; and applying the synchronized system preference setting to the second server.
[0008] In another embodiment, a computer system having a plurality of servers includes means for launching a cluster manger in response to a request from a user, the cluster manager being operable to manage system preference settings of a plurality of servers in a cluster group; means for selecting a first server from the plurality of servers provided in the cluster group according to an input from the user, the selected first server being designated to be a master server; means for receiving a new system preference setting for the first server from the user; means for selecting a second server from the plurality of server provided in the cluster group according to an input from the user; and means for synchronizing a system preference setting of the second server to the new system preference setting of the first server according to an input from the user.
[0009] In yet another embodiment, a computer readable medium includes a computer program operable to manage system preference settings of a plurality of server provided in a cluster group. The computer program includes code for selecting a first server from the plurality of servers provided in the cluster group according to an input from a user, the selected first server being designated to be a master server; code for receiving a new system preference setting for the first server from the user; code for selecting a second server from the plurality of server provided in the cluster group according to an input from the user; and code for synchronizing a system preference setting of the second server to the new system preference setting of the first server according to an input from the user.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1A illustrates a client-server system including a presentation layer, an application layer, and a database layer according to one embodiment of the present invention
[0011] FIG. 1B illustrates a schematic interactions between the three functional layers of FIG. 1A .
[0012] FIG. 2 illustrates an enterprise portal that couples a client to a plurality of information sources according to one embodiment of the present invention.
[0013] FIG. 3 illustrates a process for updating the system preferences for servers in a given cluster group according to one embodiment of the present invention.
[0014] FIG. 4 illustrates a main user interface page of a portal cluster manger according to one embodiment of the present invention.
[0015] FIG. 5 illustrates a log file of a server in a portal cluster group according to one embodiment of the present invention.
[0016] FIGS. 6A-6C illustrate exemplary screen shots relating to synchronization of a sever to the master settings according to one embodiment of the present invention.
[0017] FIGS. 7A and 7B illustrate exemplary screen shots relating to restarting a server in a portal cluster group using a restart button provided on the main user interface page of the FIG. 4 .
[0018] FIG. 8 illustrates an exemplary screen shot for adding a server to a cluster group according to one embodiment of the present invention.
[0019] FIG. 9 illustrates an exemplary screen shot for editing a server in a cluster group according to one embodiment of the present invention.
[0020] FIG. 10 illustrates an exemplary screen shot for removing a server from a cluster group according to one embodiment of the present invention.
[0021] FIG. 11A illustrates a system preference page according to one embodiment of the present invention.
[0022] FIG. 11B illustrates an XML file used to launch the system preference page of FIG. 11A according to one embodiment of the present invention.
[0023] FIG. 12 illustrates an exemplary screen shot providing a portal host server list.
[0024] FIG. 13 illustrates a system preference page that has been provided with new settings according to one embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Embodiments of the present invention relate a distributed computer system and management thereof. The present invention is described in terms of portal servers for illustrative purposely only. Accordingly, the present invention is not limited to the portal system and may be implemented with any computer system having a plurality of computers that are linked together in one or more networks.
[0026] A portal serves as a gateway to information sources to one or more users. By definition, the portal is provided in a client-server environment or system that distributes the workload of a computer application across a plurality of cooperating computer programs. This type of computing separates user-oriented tasks, application tasks, and data management tasks. That is, these three types of tasks or functions are distributed to different layers: the presentation, application, and database layers. Generally, each layer has one or more software programs dedicated to provide services to their respective layers.
[0027] FIG. 1A illustrates a client-server system 100 including a presentation layer 102 , an application layer 104 , and a database layer 106 according to one embodiment of the present invention. Each layer has one or more servers that are primarily dedicated to provide functions relating to that layer. The system 100 illustrates a three-tier client-server system; however, a two-tier client-server system or multi-layer cooperative client-server system may also be used to implement the embodiments of the present invention.
[0028] The above three layers represent functional groups in the system 100 . Each group is configured to support the demands of its functions. The database layer includes database servers that are primarily utilized to read or write data to and from storage locations. These storage locations may be provided in one or more storage subsystems that are linked to the database servers via a communication network, e.g., network attached storage (NAS) or storage area network (SAN). The application layer includes servers that contain the processing logic of the system, including services such as spooling, dispatching user requests, and formatting data. The presentation layer has servers that are primarily configured to perform tasks relating to presentation of the data. Each of these layers generally handle data differently so interfaces are needed to facilitate communication among them. Application layer serves as an intermediary between the presentation and database layers. The application layer and database layer, in turn, communicates with each via a middleware.
[0029] FIG. 1B illustrates a schematic interactions between the three functional layers. In the present embodiment, the application layer is implemented using SAP R/3. The application layer 104 receives the data or requests inputted by users using client systems, which are part of the presentation layer 102 . The data received is converted to a format that is compatible with the application logic residing in the application layer. The data is then sent to a dispatcher 112 .
[0030] The dispatcher is a control program that manages the resources of the applications residing in the application layer. The dispatcher initially keeps the requests in queues and processes them one by one. The dispatcher sends the requests to those work processes 114 that have sufficient resources to handle the requests. The work processes are services offered by the application servers (or services requested by a client).
[0031] Each work process executes the received request. This may involve accessing a database 107 in the database layer 106 to retrieve needed data. As understood by those skilled in the art, he database layer 106 generally includes a plurality of databases 107 and a plurality of database servers 109 . Once the request has been executed, the work process sends resulting data to the dispatcher that, in turn, forwards it to the presentation server. The work process generally transforms the data received from the database 107 using application logic. Upon received the transformed or processed data, the presentation layer displays the data in a user-friendly format.
[0032] FIG. 2 illustrates an enterprise portal 202 that couples a client 204 to a plurality of information sources 206 according to one embodiment of the present invention. The client 204 may be a personal computer (PC) that is linked to the portal 202 via the Internet, intranet, wide area network, local area network, or the like. The portal is configured to provide users with a common entryway to various applications and information.
[0033] In the present embodiment, the portal 202 integrates a plurality of different technologies, enabling users to access applications and information that are both internal and external to the enterprise. The information sources 206 include an external application 214 , internal application 216 , external document source 218 , internal document source 220 , and Web 222 .
[0034] The portal includes a unification server 208 , a portal server 210 , and a knowledge management 212 . The unification server is configured to provide a business unification layer that enables dynamic integration of both applications and information from various sources. The business unification layer enables the creation of a unified object model, so that a portal user may dynamically integrate applications and information. Logical business objects, provided in component systems, are used to create a unification object model that is stored in a repository. The objects are mapped to each other by links, so that users are able to dynamically pass content from one information source to another.
[0035] The logical business objects are used to represent a thing, concept, process or event in operation, management, planning or accounting of an organization. Each busines object specify attributes, relationships, and actions/events. For example, the business objects may be used to represent purchase orders, vendors, and users of a system.
[0036] The portal server includes a web server 232 that communicates with the client and a portal content directory (PCD) 234 that includes a plurality of presentation components, e.g., iViews. The PCD is a file-based directory that also includes roles and the systems with which the portal is to interact. In one implementation, the PCD runs on a Java 2 Enterprise Edition™-compliant application server.
[0037] The knowledge management (KM) 210 is a set of services for managing knowledge and collaboration. The KM 210 provides a platform to harmonize various business tools under one business management platform regardless of the physical location of data. In one implementation, the KM includes a repository framework that manages the content of documents and corresponding document attributes, classification engine that organizes contents in folder or tree structures, and other components for managing information.
[0038] FIG. 3 illustrates a process 300 for changing preference settings using a portal cluster manager according to one embodiment of the present invention. At a step 302 , the portal cluster manager is launched by a network administrator who wishes to change preference settings for servers in a cluster. These servers may be associated with the presentation layer, application layer, or database layer. In one embodiment, the portal cluster manager is launched by pressing a Cluster Manager button on a portal system preference page. The system preference page or screen is available from any portal client.
[0039] FIG. 11A illustrates a system preference page 1102 according to one embodiment of the present invention. The system preference page 1102 displays the current system settings and values. The page 1102 results from executing an XML file 1104 ( FIG. 11B ) and retrieving “*.ini files,” “*.properties files,” and “*.dat files” from the windows registry and also retrieving metabase files from the Internet Information Server registry files.
[0040] A master server is selected from a portal server host dropdown list 1202 , as shown in FIG. 12 (step 304 ). The portal server host list displays all servers within a given cluster group. Any server in the cluster group may be selected as the master server. The selected server is the master server for that particular session and its setting field 412 indicates this with the following: “Master Settings.” Different servers may be selected as the master servers for subsequent sessions. In one embodiment, the selected server is made the default master server for the subsequent sessions, where the default master server may be unselected if the administrator so wishes.
[0041] This capability of allowing the administrator to select different master servers for different sessions enables the administrator to choose a server that is likely to least impact the entire system if the selected server crashes due to the input of new settings or is taken off-line during the preference update. For example, the administrator may not want to choose a given server as the master server for a given session performed at the end of the month if he know that server is heavily used by the accounting department for the monthly payroll functions.
[0042] A main user interface 402 ( FIG. 4 ) is displayed with a selected server 401 as being the “Master Server.” The UI 402 lists all the servers for that cluster group. If the cluster group has too many servers to fit within a single screen, a scrolling feature button may be provided with the main UI.
[0043] The main UI 402 is generated by retrieving a cluster group table from a lock server. The cluster group table includes address and port information of each of the servers in a given cluster group to which the table is assigned. The lock server may be a dedicated lock server or one of the servers in the cluster that process client requests as well as serve as the lock server.
[0044] The main UI 402 includes an address field 404 , a port field 406 , a status field 408 , an update field 410 , and a setting field 412 . The address field lists the address of a given server. The port field lists a port to which a given server is coupled. Generally, each port services a plurality of servers. A server can be uniquely identified by using the address and port information.
[0045] The status field 408 indicates the status of a given server, e.g., “started,” “stopped,” and “unavailable.” The update field 410 indicates the time and date that a given server was last updated with a new preference setting. The setting field 412 indicates whether a given server has been selected as a master server or has been synchronized with the master server. The setting field also provides information as to whether or not the new settings have been applied after the synchronization.
[0046] The main UI 402 also includes a restart button 414 , an edit button 416 , and a delete button. 418 , a new button 420 , and a close button 422 . Pressing the restart button 414 of a given server causes that server to restart and apply the new setting to the server. The edit button is used to edit the information about the server. The delete button is used to remove the server from that cluster group. The new button is used to add a new server to the cluster group. The close button 422 is used to end the cluster manager session.
[0047] Referring back to the process 300 , the administrator edits the preference setting of the selected server (step 306 ). The edits may relate to maximum number of concurrent requests that may be handled by the server, minimum CPU load, maximum CPU load, display help links, and the like. The edits to the settings are saved in a temporary file. FIG. 13 illustrates a system preference page 1302 that has been provided with new settings.
[0048] Once the new setting values have been inputted, they are applied to the master server (step 308 ). This is done by pressing a save button 1304 ( FIG. 13 ). When the button is pressed, a delta compare is performed between the temporary file and the existing setting values in a preference setting file. The preference setting file is updated with the new values or the delta from the comparison.
[0049] At this time, a log file 502 of the master server is updated to indicate the changes made (see FIG. 5 ). Each server has a log file to provide information about the updates to its settings. The log file 502 includes a date field 504 to indicate the date and time of the update, a description field 506 to describe the updated setting, an old value field 508 to indicate the value prior to the update, a new value field 510 to indicate the value after the update.
[0050] A server, e.g., server 403 , to be synchronized with the master server is selected using the setting field/button 412 of the UI 402 (steps 310 and 312 ). Pressing of the “Sync with master” button 412 causes the delta value from the temporary file of the master server to be copied onto the system preference file of the serve 403 . FIGS. 6A, 6B , and 6 C illustrate exemplary screen shots relating to steps 310 and 312 .
[0051] In the present embodiment, steps 310 and 312 may be considered as a single step. A check mark in the field 412 indicates that the new setting has been applied. An exclamation mark indicates that the server has not been synchronized with the new settings of the master server.
[0052] The new system preference is applied to the server 403 by pressing the “Restart” button 414 corresponding to the server 403 (step 314 ). Pressing the button causes a restart command to be generated. The address and port information of the server 403 is attached to the restart command. In the present embodiment, the synchronization and rebooting of the selected server 403 may be done using the buttons provided on the same page.
[0053] The server 403 reboots itself upon receiving the restart command (step 314 ). FIGS. 7A and 7B illustrate exemplary screen shots during step 314 . Once rebooted, the new system preference is applied to the server 403 . The log file of the server 403 is updated (see FIG. 5 ).
[0054] The process 300 returns to step 310 if the administrator selects another server to be synchronized. Otherwise, the process ends. In the present embodiment, the synchronization and restart steps 312 and 314 are performed one server at a time, so that only one server is taken offline at a time. In another embodiment, the administrator may select to have these steps performed with two or more servers at a time.
[0055] FIG. 8 illustrates a dialog box 802 that is used to add a server to the portal server host list according to one embodiment of the present invention. The dialog box 802 is displayed if the new button 420 of the cluster manager is pressed. The address of the server is entered in an address field 804 . The port number of the server is entered in a port field 806 . Thereafter, a save button 808 is pressed to save the entered information to the lock server and add the server to the portal server host list.
[0056] FIG. 9 illustrates a dialog box 902 that is used to modify the parameters of a server provided in the portal host server according to one embodiment of the present invention. The dialog box 902 is displayed if the edit button 416 of the portal cluster manager is pressed. Each server in the cluster manager is provided with its own edit button. Accordingly, the parameters of a given server is edited by pressing the edit button of that selected server. The address and port information of the selected server may be edited on address and port fields 904 and 906 . A save button 908 is pressed to save the changes to the cluster group table in the lock server.
[0057] FIG. 10 illustrates a screen 1002 that is used to remove a server from the portal server host list according to one embodiment of the present invention. The screen 1002 is displayed if the delete button 418 is pressed. Each server in the cluster manager is provided with its own delete button. Accordingly, any server may be removed from the list by pressing the delete button for that server. The server is removed from the list once an OK button 1004 is pressed to confirm the selection to remove the server. The server is removed from the cluster group table, so that the removed server would no longer appear in the portal server host list thereafter.
[0058] The present invention has been illustrated using specific embodiments above. The above embodiments may be amended, modified, or altered without departing from the scope of the invention. Accordingly, the scope of the invention is defined by the appended claims. | A method for managing a plurality of servers includes launching a cluster manger in response to a request from a user. The cluster manager is operable to manage system preference settings of a plurality of servers in a cluster group. A first server is selected from the plurality of servers provided in the cluster group according to an input from the user. The selected first server is designated to be a master server. A new system preference setting for the first server is receiving from the user. A second server from the plurality of server provided in the cluster group is selected according to an input from the user. A system preference setting of the second server is synchronized to the new system preference setting of the first server according to an input from the user. | 7 |
FIELD OF THE INVENTION
The present invention relates primarily to compression type refrigeration systems which utilize an evaporator to cool a fluid stream.
The invention further relates to refrigeration systems having condensing means for delivering refrigerant liquid at a relatively high saturated temperature and slight subcooling, to an expansion device feeding such an evaporator.
The invention further relates to refrigeration evaporators which have two heat exchange elements; a first element for cooling the fluid stream through heat exchange with evaporating refrigerant, and a second element positioned in the fluid stream entering the first element for cooling and further subcooling the refrigerant liquid which is then directed through an expansion device and the second element seriatim.
BACKGROUND OF THE INVENTION
Compression type refrigeration systems employ an evaporator which is supplied with low pressure refrigerant liquid. The low pressure refrigerant boils away or evaporates when supplied with heat from a medium to be cooled. The most common media which are cooled by such systems are streams of air, and streams of water or aqueous brines. The refrigerant vapor emitted from the evaporator is delivered by a pipe called a suction line to a mechanism which simultaneously acts as a vacuum pump to draw vapor from the evaporator and as a condensing device to restore the refrigerant vapor to a liquid condition so it can be reused in the evaporating part of the refrigerating cycle. The evacuating and condensing mechanism is called a condensing unit. The condensing unit has two major components. The evacuating device is most frequently a mechanical compressor driven by an electric motor. The compressor draws refrigerant vapor from the evaporator and compresses it and delivers it via a pipe to a condenser. The condenser condenses the hot refrigerant vapor to a refrigerant liquid by bringing it into heat exchange with a coolant. The most commonly employed coolants are air, employed in air-cooled condensers, water, employed in water cooled condensers and a mixture of air and water employed in so-called evaporative condensers.
The refrigerant liquid is then generally transmitted from the condenser to a holding tank called a receiver, where it is stored until needed by the evaporator. The refrigerant liquid when stored in the receiver generally has a temperature which is a few degrees cooler than the temperature at which it condensed called the saturated condensing temperature. The number of degrees which the refrigerant liquid is cooler than the saturated condensing temperature is called the subcooling or the degrees of subcooling. When the refrigerant liquid leaves the receiver it is in the form of liquid without any bubbles. However, if the subcooling is reduced to zero either by warming the refrigerant liquid those few degrees of subcooling or by lowering the pressure on the refrigerant liquid, bubbles, often called flash-gas, will form in the refrigerant liquid.
When the refrigerant liquid flows toward the evaporator from the receiver in a pipe called the liquid line, it is at high pressure. In order for the refrigerant liquid to evaporate and cool the fluid needing refrigeration, its pressure must be reduced. This pressure reduction is secured by passing the high pressure refrigerant liquid through a flow restrictor, also called an expansion device. Flow restrictors come in many forms. One is in the form of a length of tubing having a very small bore called a capillary tube. It is the form of restrictor most often used in domestic refrigerators, freezers and room air-conditioners. Another is in the form of a fixed orifice, frequently used in automotive air-conditioners. The form of restrictor most frequently employed in larger commercial or industrial refrigeration systems of the type toward which the present invention is primarily directed is a valve which senses both the pressure in the evaporator and the temperature at the refrigerant vapor outlet of the evaporator. This dual sensing valve is called a thermal expansion valve or TEV or TXV for short.
TEV's work best when the refrigerant liquid fed to them is free of bubbles. Such bubble-free liquid is also called clear liquid or "solid" liquid. Used in this sense, "solid" liquid is not frozen liquid but is simply refrigerant liquid which is free of bubbles.
Since the refrigerant liquid which is stored in the liquid receiver has only a few degrees of subcooling, it is not uncommon for the refrigerant liquid to reach the TEV inlet in a bubbling state. Expansion valves receiving bubbling refrigerant liquid tend to act erratically. Erratic TEV performance has a detrimental effect on evaporator capacity and therefore on overall system capacity.
To overcome the tendency of refrigeration systems to deliver bubbling refrigerant liquid to their TEV so-called suction-liquid heat exchangers are frequently employed. These heat exchangers are installed in the system suction line. The piping is arranged to pass the vapor emitted from the suction outlet of the evaporator in heat exchange relation to the high pressure refrigerant liquid flowing from the receiver to the TEV. This heat exchange cools the refrigerant liquid and either condenses bubbles if any have formed in the liquid, or increases the degree of subcooling of the refrigerant liquid, thereby reducing the propensity of the refrigerant liquid to form bubbles.
Unfortunately, suction-liquid heat exchangers have a series of disadvantages.
First, they introduce pressure drop in the suction line. Suction line pressure drop has the effect of reducing compressor capacity and therefore system capacity.
Second, they warm the suction vapor returning to the compressor from the evaporator with exactly the same number of heat units (Btus, calories etc) that are extracted from the refrigerant liquid flowing through the exchanger. The warmed suction vapor has dual negative effects: that of reducing the compressor capacity by presenting to the compressor warmed and therefor less dense refrigerant vapor to compress; and that of causing the high pressure vapor discharged by the compressor to be hotter than necessary. The higher the compressor discharge temperature, the thinner the compressor lubricant and the more likely the lubricant will suffer some thermolytic degradation resulting in shortened compressor life.
Third, suction-liquid heat exchangers fail to work when most needed. For example, when the TEV is in the mode of receiving a mixture of liquid and vapor, its flow capacity is so reduced that the evaporator cannot be fully flooded. Therefore the refrigerant vapor leaving the evaporator is warm and relatively ineffective to substantially cool the liquid/vapor mixture flowing toward the TEV.
Fourth, the suction-liquid heat exchanger cannot reduce the temperature of the refrigerant liquid flowing to the TEV to near the temperature of the fluid entering the evaporator, though the greatest improvement in evaporator capacity and stability of TEV performance is achieved with coldest liquid entering the TEV.
Finally, the suction-liquid heat exchanger is costly both to manufacture and to install.
It is against this background that I have conceived the present invention which avoids all the problems described above.
My improved evaporator with integral liquid subcooling does not contribute to any suction line pressure drop.
My improved evaporator does not contribute to any warming of the suction vapor enroute from the evaporator to the compressor.
My improved evaporator works to subcool refrigerant liquid flowing to the TEV even when the evaporator is not fully flooded with refrigerant liquid.
My improved evaporator cools the refrigerant liquid flowing to the TEV to a temperature close to the temperature of the fluid entering the evaporator.
My improved evaporator, when fabricated as described, is essentially free of extra material and installation cost.
In addition, compared to a conventional evaporator, my improved evaporator has the following further advantages:
It guarantees 100% refrigerant liquid at the TEV inlet.
It increases both the evaporator and the system capacity.
In low and medium temperature refrigeration applications it reduces the amount of surface participating in frost accumulation, thereby reducing both the time and energy required for a complete defrost.
In medium temperature refrigeration systems, i.e. those operating with box temperatures in the range of 32° F. to 42° F. (0° C.-5.5° C.), it provides increased sensible heat ratio of the evaporator, thereby maintaining higher relative humidity in the storage area for less dehydration of fresh food stored within.
In airconditioning applications with high sensible heat loads, i.e. computer room applications, it provides increased sensible heat ratio of the evaporator.
In heat pump applications, it causes the evaporator to operate with higher air temperatures entering the evaporator, thus enhancing system coefficient of performance (COP).
It is adaptable to both finned coil evaporators for cooling air and to shell type evaporators for cooling liquid.
SUMMARY OF THE INVENTION
Briefly stated the present invention comprises an improved evaporator for cooling a fluid stream. The evaporator is adapted for use in a refrigeration system having evacuating means for withdrawing vapor from the evaporator and condensing means for converting the vapor to a high pressure liquid flowing to the evaporator.
The evaporator comprises first heat transfer means for receiving the high pressure refrigerant liquid from the condensing means and for exchanging heat between the high pressure refrigerant liquid and the fluid stream thereby cooling the high pressure refrigerant liquid and discharging it and warming the fluid stream and discharging it.
The evaporator includes pressure reducing means for receiving the cooled high pressure refrigerant liquid discharged by the first heat transfer means and for discharging the refrigerant at reduced pressure.
The evaporator further includes second heat transfer means for receiving the warmed fluid stream discharged by the first heat transfer means and for receiving the reduced pressure refrigerant liquid discharged by the pressure reducing means and exchanging heat between the warm fluid stream and the reduced pressure refrigerant liquid thereby cooling the fluid stream and evaporating the reduced pressure refrigerant liquid.
BRIEF DESCRIPTION OF THE DRAWINGS
The forgoing summary, as well as the following description of preferred embodiments of the present invention, will be better understood when read in connection with the appended drawings. For the purpose of illustrating the invention, there is shown in the drawings embodiments which are presently preferred. It must be understood, however, that the invention is not limited to the specific instrumentalities or the precise arrangements of the disclosed elements. In the drawings:
FIG. 1 is a schematic piping diagram of a conventional prior art refrigeration system.
FIG. 2 is a schematic representation of a version of the present invention.
FIG. 3 is an end elevation of a multi-pass prior art refrigeration evaporator for cooling air.
FIG. 4 is a sectional view of the evaporator of FIG. 3 taken at A--A identifying the tubing rows in the direction of airflow.
FIG. 5 shows a side elevation of the evaporator core of FIG. 3 recircuited to embody the elements of a preferred embodiment of the present invention.
FIG. 6 displays a schematic piping diagram of a first embodiment of the present invention including a liquid chilling evaporator.
FIG. 7 shows a schematic piping diagram of a second embodiment of the present invention including a liquid chilling evaporator.
FIG. 8 is a schematic representation of a third embodiment of a liquid chilling evaporator embodying the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the drawings, wherein like references are employed to indicate like elements, there is shown in FIG. 1 a schematic piping diagram and major element representation of a conventional compression refrigeration system of the type which is common to most residential central airconditioning systems, and substantially all commercial and industrial refrigeration systems. Evaporator 24 is the cooling element. In systems employed to cool refrigerated storage rooms, one or more fans, not shown, are associated with evaporator 24 for the purpose of drawing warm air from the storage, circulating the air through evaporator 24, thereby cooling the air, and discharging the cooled air back into the storage room. Evaporator 24 is fed refrigerant liquid from the expansion device 22. The refrigerant liquid fed to the evaporator 24 is generally mixed with a quantity of flash gas which forms in the TEV during the pressure reduction process, even when the refrigerant liquid fed to the TEV is bubble-free.
The vapor leaving evaporator 24 flows back to evacuating device/compressor 10 through suction line 26. This vapor is the sum of the vapor arising from the liquid evaporated in the evaporator 24 and the flash gas arising in the TEV. Evacuating device/compressor 10 is simultaneously a compressor and an evacuating device, depending on whether the observer is looking at its function of drawing refrigerant vapor from the evaporator or compressing the refrigerant vapor. For the remainder of this detailed description, item 10 will be referred to as compressor 10.
The vapor having been withdrawn from evaporator 24 is compressed by compressor 10 and delivered through discharge line 12 to condenser 14, where a coolant such as ambient air or water removes the latent heat of condensation from the refrigerant vapor, thereby causing it to condense to a liquid. The refrigerant liquid flows from condenser 14 through pipe 16 to receiver 18 where it is stored until needed as refrigerant liquid pool 20. The refrigerant liquid is then delivered as needed from pool 20 to TEV 22 via liquid line 28, thereby repeating the cycle. The inlet end of liquid line 28 is immersed in the liquid pool 20.
The refrigerant liquid stored as pool 20 within receiver 18 normally has about 6° F. (3° C.) subcooling. If the refrigerant liquid flowing to TEV 22 is warmed that number of degrees or if its pressure is reduced, flashing of the refrigerant liquid occurs. Pressure reduction in the refrigerant liquid can be caused either by an increase in elevation of liquid line 28, as would be required if TEV 22 were located many feet over receiver 18, or by pressure drop in liquid line 28 or pressure drop in a flow element contained in liquid line 28 or both. Among pressure drop producing flow elements normally found in liquid lines, but not shown in the figures are driers, solenoid valves, hand valves, check valves and pressure regulating valves.
In order to control these flash gas producing factors many costly design stratagems are employed. Among these are increasing the diameter of the liquid line 28, raising the condenser and receiver to a level near that of the TEV, oversizing all the pressure-drop producing flow elements or providing a suction-liquid heat exchanger. In some cases, it is so difficult to maintain a bubble-free supply of refrigerant liquid to the TEV 22 that the TEV is deliberately oversized to allow a semblance of reasonable, though significantly degraded, performance with bubbles entering the TEV.
FIG. 2 shows a schematic piping diagram of a system containing an embodiment of the present invention. In the system of FIG. 2, TEV 22, evaporator 24, suction line 26, compressor 10, discharge line 12, condenser 14 and receiver 18 remain unchanged from the system of FIG. 1. In accord with the present invention, subcooling heat exchanger 30 has been positioned in the air stream 34 entering evaporator 24. Refrigerant liquid from the pool 20 residing in receiver 18 is conveyed by liquid line 28 to subcooling heat-exchanger 30. In one mode of operation the refrigerant liquid reaches the subcooling heat exchanger 30 in bubble-free condition but having only about 6° F. (3.3° C.) subcooling. The subcooling heat exchanger 30, through its heat exchange interaction with cold entering air stream 34, further cools the refrigerant liquid, thereby sharply increasing its subcooling and placing the refrigerant liquid in a perfect condition to be controlled by TEV 22. In a second mode of operation the refrigerant liquid reaches subcooling heat exchanger in bubbling condition, that is, having refrigerant vapor or flash gas mixed with the refrigerant liquid. In that mode of operation, subcooling heat exchanger 30 first acts to completely condense all the vapor or flash gas. When condensation of the flash gas is complete, the subcooling heat exchanger 30 proceeds to subcool the now bubble-free stream of refrigerant liquid, again providing a perfect liquid condition for control by TEV 22.
Referring now to FIG. 3 there is shown an end elevational view of a fin/tube core having seven layers of six tubes 52 each. The core is circuited as a prior art refrigeration evaporator 24, having 7 layered refrigerant circuits, each circuit having six tubes 52. Each circuit is fed a substantially equal amount of refrigerant liquid from distributor 44 via small distributing tubes 54. The refrigerant liquid fed into the circuits abstracts heat from the airstream 34, thereby cooling it and simultaneously evaporating all the refrigerant liquid to vapor. The vapor from each of the 7 layered circuits is collected in manifold 48 which connects with suction line 26 of FIG. 1 by way of suction outlet connection 50. Row 1 is identified as the first vertical row of tubes affected by entering air stream 34.
FIG. 4 shows a cross section of evaporator 24 of FIG. 3 taken at section A--A. Although only a few transverse fins 5; are shown, fins 51 are spaced uniformly over the full length of the tubes 52 of the evaporator. The rows are numbered in the direction of airflow 34. Note that each circuit is arranged with the evaporating refrigerant in counterflow with the airflow.
FIG. 5 is an end elevational view of the same fin/tube core of FIG. 3 except circuited in accord with the present invention. The core is mounted within a casing 80 adapted for the flow of air stream 34. The suction manifold 48 is connected to the end of tubes 52 comprising row 3 so that coil rows number 3, 4, 5 and 6 are connected to the distributor 44 and suction manifold 48 for the evaporating function. The position of the suction manifold is marked by `x` in the sectional view of a single circuit of FIG. 4.
In the embodiment shown in FIG. 5, the tubes 52 in rows 1 and 2 are joined into a single series subcooling circuit 30. Subcooling circuit 30 is connected at one end to liquid line 28 and at the other end to one end of conduit 32. The other end of conduit 32 is connected to the inlet of TEV 22. In other embodiments of the present invention, the tubes 52 in rows 1 and 2 which are the subcooling heat exchanger 30 are circuited in two circuits each circuit having seven tubes or in other combinations of circuits and number of tubes.
Calculations have shown that, despite the reduced surface available to the evaporating function generated by use of rows 1 and 2 for the construction of the subcooling heat exchanger 30, the capacity of the remaining portion of the evaporator 24 and the total capacity of the system employing the integrated subcooling-evaporator of FIG. 5, is greater than the capacity of the same system employing the prior art evaporator 24 of FIG. 3, having six rows of coil used for evaporation. The reasons for this completely unobvious and unexpected performance of the subcooling evaporator of the present invention, as shown in FIG. 5 and described above, are: first, that the TEV performs in a completely stable manner having a stream of totally bubble free, subcooled liquid fed to its inlet; second, that the evaporating heat exchanger 24 has a substantially higher capacity when its TEV 22 is fed a stream of highly subcooled refrigerant liquid. Cold and highly subcooled refrigerant liquid flowing through the TEV generates much less flash gas in the TEV than warm or hot refrigerant liquid flowing through the TEV. With much less flash gas formed initially in the TEV, there is a higher percentage of refrigerant liquid in the evaporator tubes, thereby providing better wetting of the inside of the tubes 52 by the refrigerant liquid, and therefore higher heat transfer coefficients, resulting in improved evaporator performance. Third, the subcooling heat exchanger 30, positioned in the entering airstream to the evaporator coil 24, warms the air entering evaporator 24. This warmer air serves to raise the temperature differential between the refrigerant liquid evaporating inside tubes 52 of the evaporator heat exchanger 24 and the air stream traversing it. With the evaporator 24 of the subcooling evaporator of FIG. 5 operating at a higher temperature differential than the prior art evaporator 24 of FIG. 3 its capacity is greater and therefore the system suction pressure is greater resulting in improved compressor and therefore system capacity.
In one mode of usage of the present invention as represented by FIGS. 2 and 5, the evaporator 24 and its associated subcooling heat exchanger 30 are located within a room designed for frozen food storage having a storage temperature of 0° F. (-18° C.). Entering airstream 34 is at 0° F. If no measures to avoid flashing of refrigerant 20 are taken, and the refrigerant liquid is subject to flashing conditions, the bubbling refrigerant liquid at one condition enters subcooling heat exchanger 30 at 115° F. (46° C.). Within the heat exchanger 30 all the flash gas is condensed and the refrigerant liquid is cooled to about 5° F. (-15°C.). The now bubble-free refrigerant liquid has a subcooling of about 110° F. (61° C.), more than enough to ensure flow to TEV 22 as a pure bubble-free liquid for effective control by the TEV 22 and to achieve the effects described above.
The above advantages are achieved as well when liquid cooling evaporators are employed. In FIG. 6 liquid cooling evaporator 58 has liquid inlet connection 64 and liquid outlet connection 66. The liquid-to-be-cooled 59, flowing through the heat exchanger 58 through its inlet and outlet connections 64 and 66, respectively, is typically water, though a wide variety of other liquids such as brines of various types and many organic chemicals are commonly cooled in such heat exchangers. Refrigerant liquid is fed into liquid cooling evaporator 58 under the control of TEV 22. Refrigerant vapor resulting from the evaporation of the refrigerant liquid in liquid cooling evaporator 58 is conveyed to suction line 26 of the system in FIG. 2 through evaporator outlet connection 50. Positioned in the pipe conveying the liquid to be cooled to the inlet connection 64 of the liquid cooling evaporator 58 is a subcooling heat exchange element 62. Refrigerant liquid, having slight subcooling, or no subcooling and containing a quantity of bubbles or flash gas, flows from the receiver 18 of FIG. 2 through liquid line 28 and is conveyed to subcooling heat exchanger element 62. There it is cooled and the flash gas and bubbles if any condensed to liquid. The then bubble free liquid stream is FIG. 2, and delivered to TEV 22 by way of subcooled liquid conduit 32.
FIG. 7 is another embodiment of the present invention. In FIG. 7 the subcooling heat exchanger 74 is in a flow loop which includes pump 72 positioned to withdraw a fraction of the liquid from the full flow stream 59 entering the liquid chilling heat exchanger 58 via conduit 70 and circulate the liquid fraction through subcooling heat exchanger 74. The warmed liquid fraction is then returned, by way of conduit 76, to the main liquid flow stream entering heat exchanger 58. Slightly subcooled refrigerant liquid, or refrigerant liquid mixed with vapor which enters subcooling heat exchanger 74 via liquid line 28 is cooled and the vapor, consisting of flash gas or bubbles, is condensed. The then bubble free refrigerant liquid is subcooled, exactly as described in connection with the system of FIG. 2, and delivered to TEV 22 by way of subcooled refrigerant liquid conduit 32.
FIG. 8 is an embodiment of the present invention directed toward liquid cooling evaporator 58 having shell 57. Warm bubble laden liquid refrigerant is conveyed via conduit 28 toward TEV 22. Enroute the warm liquid within conduit 28 enters subcooling heat exchanger 96, positioned within shell 57 of liquid cooling heat exchanger 58, through its inlet fitting 92. The warm liquid refrigerant having been cooled by its passage through subcooling heat exchange element 96 exits the subcooling heat exchanger 96 and enters subcooled liquid refrigerant conduit 32 by way of exit fitting 94, flowing therethrough to TEV 22.
From the foregoing description, it can be seen that the present invention comprises an improved subcooling evaporator for use in air cooling refrigeration, in liquid cooling and in airconditioning systems. It will be appreciated by those skilled in the art that changes could be made to the above described embodiments without departing from the broad inventive concepts thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but is intended to cover all modifications which are within the scope and spirit of the invention as defined by the appended claims. | An improved refrigeration evaporator having a first heat exchange element including a fluid inlet and a fluid outlet, for cooling a fluid stream traversing the evaporator by evaporating a volatile refrigerant liquid in heat exchange relation to the fluid stream. The volatile refrigerant liquid is supplied to the evaporator at relatively high saturated condensing temperature and slightly subcooled. The improvement in the refrigeration evaporator comprises a second heat exchange element, positioned in the fluid stream entering the first heat exchange element. The second heat exchange element cools and thereby further subcools the volatile refrigerant liquid prior to the refrigerant liquid entering the first heat exchange element via a pressure reducing device. The fluid stream being cooled may be either gas or liquid and the evaporator may be of the type best adapted for the type of fluid being cooled. | 5 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to an air conditioning system for an automotive vehicle. More particularly, the present invention relates to a method and system for controlling an automotive heating, ventilating and air conditioning system to prevent fogging.
2. Disclosure Information
A fundamental goal of automotive heating, ventilating and air conditioning (HVAC) systems is to provide comfort to vehicle occupants as well as to avoid window fogging conditions. During normal air conditioning operation, moisture retention on the evaporator and within the evaporator case of the HVAC system has been the cause for fogging within the vehicle cabin. Additionally, moisture brought into the vehicle as a result of natural human functions such as breathing, perspiration, wet umbrellas, snow on clothing, etc., all contribute to the overall moisture content within the passenger cabin of the vehicle. In general, interior window fog elimination is simply a process of dehumidifying the cabin by operating the air conditioning system and further by warming this "dry air" and distributing it to the effected glass areas.
The process of keeping the vehicle glass fog free for general operating conditions is understood and currently controlled by the operator of a vehicle in an open loop fashion. For example, it is commonly known to turn the air conditioning on or activate the defrost mode (which also activates the air conditioning in many vehicles) when fogging is visible. Improvements to existing systems have been suggested, such as in U.S. Pat. No. 5,516,041, assigned to the assignee of the present invention and herein incorporated by reference. The system of the '041 patent closes the known open loop with a humidity sensor which provides input to an algorithm which calculates fog probability and automatically takes fog preventive correction actions. These processes work well as intended, however, they are limited to "normal" air conditioning operating conditions.
Presently, the typical air conditioning system as described above controls window defogging only for temperatures down to approximately 42° F. Normally, at temperatures below 42° F., the air conditioning operation is deactivated to prevent a wet evaporator core from freezing. A frozen evaporator core will block air flow through the ducting system of the air conditioning system.
However, the greatest probability of fogging occurs in the spring and fall of the year between temperatures of 25°-45° F. During this time of year, a low pressure switch in the A/C system keeps the A/C system off, offering no dehumidification and when the vehicle heater is in the medium to full operation, the fogging probability is high. As the passenger cabin warms up, it has a greater capacity to hold moisture and the interior relative humidity increases. If the dew point is reached, moisture will form on the cooler surfaces within the passenger cabin, normally the inside of the glass which is exposed to a cooler exterior ambient temperature. Interior relative humidity can increase significantly during these conditions and are further increased when the operator brings moisture into the cabin in the form of a wet raincoat or clothing covered with snow. This combination of warming the cabin, melting snow and a cold ambient temperature is a perfect condition for fogging to occur. In current air conditioning systems, the air conditioning does not operate at the ambient temperatures at which these conditions typically occur.
Therefore, it would be advantageous to modify an air conditioning system to provide for air conditioning operation during the times of high fogging probability and yet prevent freezing of the evaporator within the system. Furthermore, it would be advantage to provide such a system at relatively low cost with no equipment changes to the present air conditioning system. It is an object of the present invention to provide such a system and a method for preventing fogging during these conditions.
SUMMARY OF THE INVENTION
The present invention overcomes the disadvantages of the prior art by providing a method and system for controlling a heating, ventilating and air conditioning system of a vehicle which discharges a flow of air to a passenger cabin of the vehicle. The system includes a variable speed blower, ducting, a compressor, an evaporator, a heater core for heating air in the duct, a control element having control positions for varying refrigerating and heating capacity of the compressor and evaporator, a pressure cycling switch for controlling operation of the compressor, a plurality of blend doors having various control positions for controlling the direction of air flow and the ratio of fresh air to recirculated air through the duct work, a humidity sensor for sensing relative humidity within the cabin and providing a corresponding relative humidity signal and temperature sensors for sensing temperature within the cabin and of the evaporator and providing corresponding temperature signals for ambient and evaporator temperatures. The method of the present invention comprises the steps of measuring the ambient and evaporator temperatures and generating an ambient temperature and evaporator temperature signal. The method then bypasses the pressure cycling switch and cycles a control element on and off within the system according to a predetermined duty cycle when the ambient and evaporator temperature signals are within a predetermined range. The method further contemplates moving the blend doors to predetermined positions based upon the ambient and evaporator temperature signals to pass a predetermined amount of recirculated air through the evaporator. The method of the present invention will operate the air conditioning system of the vehicle at ambient temperatures between 20° and 40° F. to prevent fogging of the passenger cabin windows.
It is an advantage of the present invention that interior window fogging can be prevented by operating the air conditioning system of the vehicle at temperatures lower than 40° F. It is an advantage that the air conditioning system can be operated during conditions of highest probability of fogging within the passenger cabin of the vehicle.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic diagram illustrating an air handling system which can be controlled by the method and control system of the present invention.
FIG. 2 is a schematic block diagram of the control system of the present invention.
FIGS. 3A and 3B are schematic representations of the operation of A/C systems.
FIG. 4 is a flow diagram illustrating the general sequence of steps associated with the operation of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
In general, control of temperature and defogging of the windshield within an automobile is accomplished using various actuators to adjust the temperature and flow of air supplied to the cabin of the vehicle. FIG. 1 shows schematically an air handling system of an HVAC (heating, ventilating and air conditioning) system, generally indicated at 20. The system 20 includes the arrangement of air flow doors, including panel-defrost, floor-panel, and outside recirculated air actuators or doors 22, 24, and 28, respectively. The doors are part of a second air distribution system for directing the flow of conditioned air to various locations within the passenger cabin, such as to the windshield, floor or instrument panel as is commonly known. The doors 22, 24 and 28 are typically driven by vacuum motors (not shown) between their various vacuum, partial vacuum and no vacuum positions in a conventional fashion as indicated in FIG. 1, or may be driven by an electric servo motor. A temperature control blend door 26 is also provided, and preferably driven by an electric servo motor (not shown) also in a conventional fashion.
The system 20 also includes a variable speed blower motor or fan 30 including a blower wheel 32. The system further includes heating and cooling elements such as a heater core 34 and an evaporator core 36 and a typical vehicle air conditioning plant including a compressor 37. Each of the above components is in communication with the HVAC case in a first airflow distribution system and associated ducting 38 in order to control temperature, the direction of air flow and the ratio of fresh air to recirculated air. The system further includes a low pressure cycle switch 39 which communicates with the compressor 37. As will be explained in greater detail below, the low pressure switch 39 deactivates the compressor and evaporator when ambient temperature drops below a predetermined value to prevent freezing of the evaporator.
For automatic control of the temperature and flow of air in the cabin, conditions within and outside the cabin are monitored by sensors and an electronic controller generates signals to control the actuators according to the conditions as indicated by the sensors. As illustrated in FIG. 2, a typical complement of sensors of the HVAC system, schematically shown as passenger cabin temperature sensor 29, ambient temperature sensor 31, engine coolant temperature sensor 33, evaporator temperature sensor 35 and humidity sensor 41 provide signals which are representative of interior cabin temperature, ambient (outside) air temperature, evaporator temperature, engine coolant temperature (ECT), relative humidity of the passenger cabin, discharge air temperature and sunload. In addition, there is a set signal or set temperature value indicating the desired temperature that is set manually by the driver.
The signals are provided to a hardware controller 44 as inputs. Hardware controller 44, in turn, controls the doors 22 through 28 to regulate the temperature and flow of air and ultimately to maintain the comfort of driver and passengers in the vehicle. The controller 44 also receives signals from the ignition switch 29 and the HVAC system 20 to indicate the operating of the switch 29 and system 20. The controller 44 preferably continually monitors the state of the ignition switch 29 and the state of the HVAC system 20.
Turning now to FIG. 3A, there is shown a schematic diagram illustrating the general operation of the cooling system of a typical air conditioning system. In the Area designated as "1", at ambient temperatures greater than 42° F. and evaporator temperatures greater than 38° F., the air conditioning system functions normally, with the compressor cycling on and off as a function of load. This is typically a 50% duty cycle with a 40 second period at an ambient temperature of 60° F. The Area marked "2" represents the window of the highest fogging probability at ambient temperatures of between 20° F. and 42° F. In the Area marked "3", the evaporator temperature is decreasing because the ambient temperature is below freezing. In the typical air conditioning system, the compressor is deactivated and kept off in the Areas marked "2" and "3". The low side pressure switch will keep the A/C off when the ambient temperature is below 42° F. to prevent freezing of the evaporator. Airflow cannot pass through the evaporator when it is frozen.
FIG. 3B is a schematic illustration of an A/C system operated in accordance with the method of the present invention. In Area "1", the A/C system functions as normal. In Area "2", the highest fogging probability window, the A/C is cycled according to a predetermined duty cycle with the blend doors being positioned to allow a predetermined ratio of fresh/recirculated air to pass through the evaporator. This positioning is determined by the controller to keep the evaporator temperature between 35° F. and 41° F. Allowing the compressor and A/C system to operate and partial recirculating air to flow through the second distribution system of air flow doors to the windows assists in defogging the windshield and windows by dehumidifying the passenger cabin area during these conditions which present the highest probability of window fogging. There is no change from a normal A/C system in Area "3". The specific duty cycles employed by the method the present invention depend on the inputs to the controller as will be explained with reference to FIG. 4.
FIG. 4 shows the general sequence of steps associated with the method of the present invention. Although the steps shown in FIG. 4 are depicted sequentially, they can be implemented utilizing interrupt-driven programming strategies, object-oriented programming, or the like.
The method begins with the step of receiving the ambient temperature signal at block 100. If the ambient temperature is greater than 42° F., the A/C system functions normally as shown at block 102. If the ambient temperature is less than 42° F., the method determines whether the ambient temperature is greater than 20° F. at block 104. If the ambient temperature is less than 20° F., the A/C system functions as normal and the low side pressure switch deactivates the compressor to prevent freezing of the evaporator. When the ambient temperature is between 20° F. and 42° F., the method of the present invention will bypass the low side pressure switch and operate the A/C according to one of two ways. In order to bypass the pressure switch without incurring system damages as a result of low refrigerant, the evaporator temperature sensor should record a cooler temperature upon turning the air conditioning system on (for all ambient conditions). If a cooler evaporator temperature is not observed within three minutes of operation, this low ambient override feature will not operate. The graph shown at 106 represents an open loop method of operating the A/C system according to the present invention. The compressor will be operated at a specific duty cycle as shown by the solid line on the graph depending on the ambient temperature. For example, at 30° F. ambient temp, the A/C compressor will be run at a 30% duty cycle, meaning that the compressor will be cycled on for 18 seconds and off for 42 seconds at intervals of approximately sixty seconds. Simultaneously, the blend door controlling the ratio of fresh air to recirculating air will be positioned as shown by the dotted line on the graph to allow recirculating air to pass through the evaporator. This will prevent the evaporator from freezing since the recirculating air is warmer than 32° F.
Graph 110 shows an alternative method of the present invention, it representing a closed loop system. Graph 110 is a measure of "% Function" versus evaporator temperature. The solid line represents the % duty cycle for the A/C system while the two dotted lines, lines A and B, represent the position of the recirculated blend door (26) expressed as percent opened. In an A/C system using this method, a relative humidity sensor measures the relative humidity of the interior passenger cabin. Line A represents the algorithm for operating the compressor when relative humidity is less than 50%, while line B represents the compressor operating algorithm when relative humidity is greater than or equal to 50%. As can be seen, the A/C duty cycle will increase linearly as the evaporator temperature increases. As the relative humidity and evaporator temperature increases, the recirculating door position is moving closer to closing since evaporator freezing is less likely to occur as ambient temperature increases. Stated another way, the percent opening of the recirculating air door decreases (door closes) as evaporator temperature and relative humidity increases. The percent open position of the recirculating air door changes as a linear function of the evaporator temperature.
In bypassing the normal operation of low side pressure switch and operating the A/C system between ambient temperatures of 20° F.-42° F., the probability of fogging is greatly decreased and evaporator freezing does not occur because warmer recirculating air is passed through the evaporator. It will be evident that the method of the present invention can be changed depending on ambient temperature, evaporator temperature and relative humidity, as well as other variables. Therefore, it is the following claims, including all equivalents, which define the scope of the invention. | There is disclosed a system and method for preventing fogging of the windows of an automotive vehicle. The system and method operate the air conditioning system of the vehicle at temperatures where a high degree of probability of fogging exists. The method includes the steps of measuring the ambient temperature, the evaporator core temperature and operating the air conditioning compressor at specific duty cycles depending upon these temperatures. The duty cycle will be determined based upon these temperature variables as well as the relative humidity within the passenger cabin of the vehicle. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the invention
This invention relates in general to wellhead equipment for oil and gas wells, and in particular to an emergency casing hanger seal.
2. Description of the Prior Art
In a well of the type concerned herein, a wellhead housing has a landing profile or shoulder within its bore. When running casing conventionally, a casing hanger is installed on the upper end of the string of casing. The casing hanger lands on the landing shoulder in the bore of the wellhead housing.
After cementing, a seal is positioned between the casing and the wellhead housing. The seal locates between machined surfaces on the wellhead housing and the casing hanger. A tubing hanger may be installed over the uppermost casing hanger. The tubing hanger is normally held by lockdown screws if the wellhead housing is located at the surface. The tubing hanger secures to the tubing which extends into the well. A tubing hanger seal locates between the tubing hanger and the wellhead housing.
Occasionally, the casing will not proceed smoothly to the bottom of the well. When this occurs, the casing hanger will not be properly positioned to land in the wellhead housing. Generally, when this happens, the casing cannot be retrieved to the surface and becomes stuck. In that case, the casing must be cut above the landing shoulder after cementing. In the prior art, the casing is supported by slips in the wellhead housing.
A problem exists in sealing against the casing stub, because the casing does not have a smooth machined surface for receiving a seal. The casing outer diameter has a high dimensional variation. The outer diameter may be slightly oval shaped. The surface of the casing may have many defects, such as rust, pock marks and tong marks. Various seals have proposed for sealing against the casing stub. However, improvements in locking the seal in the wellhead housing are desired.
Another desirable feature would be a means that would prevent the casing from moving upward due to temperature increase in the well during production. Movement of the casing could have damaging effects on the seal. Also, it would be desired to have a tubing hanger lockdown that did not employ lockdown screws, and would allow the seal to be removed without removing the lockdown.
SUMMARY OF THE INVENTION
The wellhead system of this invention utilizes a seal which carried a split load ring. The seal has a cam member at its lower end that holds the split load ring in a retracted position as the seal is being lowered into the bore of the wellhead housing. Once the seal lands on previously installed structure in the bore of the wellhead housing, the ring is released to spring out into a groove formed in the bore of the wellhead housing. The load ring then supports the downward force placed on the seal when it is being energized.
Preferably the seal is of a type having inner and outer walls separated by an annular cavity. An energizing ring moves downward in the cavity to cause the inner and outer walls to seal to the wellhead housing and to the tubular member or casing in the well. Also, preferably, the load ring is an inward biased ring that is retained initially in place by a shear pin.
A lockdown mechanism then will lock to the upper end of the seal to prevent the energizing ring from moving upward. The lockdown mechanism employs inner and outer sleeves which are secured by mating threads. Rotating one of the sleeves relative to the other advances a locking member into an upper groove. The locking member bears against the energizing ring to prevent it from moving upward.
Further, a casing lock ring secures by threads to the locking mechanism. The casing lock ring has an inward extending flange that locates over the upper end of the casing to prevent its upward growth.
The tubing hanger lands on a shoulder. A lock ring is carried by the tubing hanger in a collapsed position. An actuating ring, when moved downward by a running tool, urges the lock ring outward to engage a groove for holding the tubing hanger in place. The actuating ring and lock ring have a mating locking taper to maintain the lock ring in the outer position. A tubing hanger seal then lands on top of the actuating ring and is energized to seal between the tubing hanger and the wellhead housing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a quarter vertical sectional view illustrating a lower portion of a wellhead system constructed in accordance with this invention.
FIG. 2 is an enlarged quarter sectional view illustrating an upper portion of a wellhead system constructed in accordance with this invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1, wellhead housing 11 is a tubular member located at the upper end of a well. Wellhead housing 11 has an axial bore with a bore wall 13. A lower groove 15 extends circumferentially around bore wall 13. Lower groove 15 has a conical load shoulder 17 that faces upward and inward. The inner diameter of load shoulder 17 is the same as the inner diameter of bore wall 13 directly below and above groove 15. The inner diameter of load shoulder 17 is no less than the inner diameter of bore wall 13 at any point above groove 15.
A set of wickers 19 are formed in bore wall 13 above lower groove 15. Wickers 19 are small triangular parallel grooves. An upper groove 21 locates in bore wall 13 above wickers 19. Upper groove 21 has the same general configuration as lower groove 15. It has a conical lock shoulder 23 that faces downward and inward.
A section of casing 25 extends through wellhead housing 11. In this instance, casing 25 has become stuck and cannot be moved further downward into the well or pulled upward. As a result, casing 25 has an upper end 27 that has been cut.
After cutting, a slip bowl 29 is placed over casing 25. Slip bowl 29 has slips 31 that grip casing 25 to support it coaxially in the bore wall 13 and prevent downward movement. Casing 25 will be cemented into place. Slip bowl 29 will land on previously installed structure located in wellhead housing 11. For example, the previously installed structure might be an upper portion of a casing hanger seal 33 which has been installed previously for sealing between a casing hanger for a larger diameter string of casing (not shown) and wellhead housing 11.
After slips 31 are installed and casing 25 cemented in place, a seal 35 will be lowered into the annular space between bore wall 13 and casing 25. Seal 35 is of a metal-to-metal type having an outer wall 37 and an inner wall 39 spaced inward. In the embodiment shown, outer wall 37 embeds into wickers 19. Inner wall 39 has a plurality of deformable cylindrical bands 41 separated by an inlay of soft metal for sealing against the rough exterior of casing 25. Outer wall 37 and inner wall 39 are joined at the bottom by a base 43. An annular central cavity 45 separates outer wall 37 from inner wall 39.
An energizing ring 47 is used to deform outer wall 37 and inner wall 39 outward into contact with the bore wall 13 and casing 25. Energizing ring 47 moves downward in cavity 45 from an upper position to the lower position shown. Energizing ring 47 has an upper section 49. Upper section 49 has an inner diameter containing grooves 51. Upper section 49 is engaged by a running tool (not shown) and serves as part of a means for lowering seal 35 into wellhead housing 11.
A cam member 53 is secured by threads 55 to base 43 of seal 35. Cam member 53 is a ring having a conical shoulder or cam surface 57 that faces downward and outward. A lower section 59 depends downward from cam surface 57 and is cylindrical.
A load ring 61 is carried by cam member 53. Load ring 61 has a mating conical surface that mates with cam surface 57. Load ring 61 is a split ring, preferably inwardly biased, and initially held in place by a shear pin 63. In the initial retracted position, load ring 61 will be located in a contracted position further downward on cam surface 57. Load ring 61 contacts the upper end of slip bowl 29 as the running tool lowers seal 35 in place. This causes shear pin 63 to shear. Cam surface 57 then pushes load ring 61 outward to engage groove 15. An outer conical surface on load ring 61 mates with load shoulder 17. Downward load imposed on seal 35 transmits through base 43, cam member 53, and load ring 61 to load shoulder 17.
After seal 35 is installed, a locking assembly 65 is secured to the upper end of seal 35 to prevent seal 35 from moving upward due to pressure in the well. Locking assembly 65 includes an inner sleeve 67 and an outer sleeve 69. Inner sleeve 67 has a lower end that abuts an upper portion of energizing ring 47. Inner sleeve 67 has external threads 71 that engage internal threads of outer sleeve 69. A running tool (not shown) will engage slots 68 in the upper end of inner sleeve 67 to cause it to rotate downward relative to outer sleeve 69. Outer sleeve 69 has slots 70 on its upper end that prevent its rotation while inner sleeve 67 is rotated.
Outer sleeve 69 locates above energizing ring upper portion 49. Outer sleeve 69 has a plurality of windows 73, each window 73 having a conical lower end. A dog 75 slides within each window 73. A cam surface 77 on inner sleeve 67 pushes each dog 75 out each window 73 when inner sleeve 67 is rotated downward with threads 71. Dogs 75 enter upper groove 21. Each dog 75 has a conical upper edge that abuts lock shoulder 23 to prevent upward movement of locking assembly 65.
A casing lock ring 79 secures by threads 81 to the inner diameter of inner sleeve 67. Casing lock ring 79 has an inward extending flange 83 that will contact the upper end 27 of casing 25. Slots 84 on the upper end of casing lock ring 79 enable it to be rotated downward against the upper end 27 of casing 25. Any upward force on casing 25 due to thermal expansion will be transmitted through casing lock ring 79 to inner sleeve 67, and from there to outer sleeve 69, to dogs 75, and to lock shoulder 23.
A tubing hanger 85 may then be installed over locking assembly 65. In the embodiment shown, tubing hanger 85 lands on a load ring 87 which forms a shoulder in wellhead housing 11. Tubing hanger 85 is secured to production tubing 89 through which fluid from the well will be produced.
Referring to FIG. 2, wellhead housing 11 has a tubing hanger groove 91 which has a downward facing locking shoulder 93. A set of wickers 95 locate above groove 91. A similar set of wickers 99 are located on tubing hanger 85 across from wickers 95 and above an upward facing shoulder 97.
Upward facing shoulder 97 locates at the lower end of groove 91. When tubing hanger 85 is lowered into place, a lock ring 101 will be installed in a contracted position on upward facing shoulder 97. Lock ring 101 is a split ring, inwardly biased.
An actuating ring 103 will also be carried by upward facing shoulder 97 as tubing hanger 85 is lowered into place. Actuating ring 103 locates above lock ring 101. Actuating ring 103 has a wedge surface 105 that engages a mating wedge surface on the inner side of lock ring 101. The inclination of wedge surface 105 is a locking taper, such that once actuating ring 103 is moved downward, it will lock in place. Upward force on lock ring 101 will not dislodge actuating ring 103. If retraction of lock ring 101 is desired, a running tool must be employed to pull actuating ring 103 upward in order to allow lock ring 101 to contract.
A seal 107, preferably a metal-to-metal type, may then be employed for sealing between the tubing hanger 85 and bore wall 13. Seal 107 is shown to be of a type having inner and outer walls separated by a cavity which receives an energizing ring 109. Seal 107 embeds into wickers 95 and 99.
In operation, if casing 25 becomes stuck, it will be cut off at upper end 27. Slips 31 will be installed and casing 25 will be cemented in place. Then, seal 35 will be lowered into wellhead housing 11. Load ring 61 will be in a contracted position held by shear pin 63. Load ring 61 will contact the upper end of slip bowl 29. Downward force of the running tool causes shear pin 63 to shear. Load ring 61 is moved outward into groove 15 as a result.
Continued downward force of the running tool (not shown) causes energizing ring 47 to move downward in cavity 45. This causes the outer wall 37 to embed into wickers 19. The inner wall 39 seals against casing 25. Fluid in cavity 45 is displaced out displacement passages formed in energizing ring 47.
Then, locking assembly 65 is lowered into place by a running tool. Initially, dogs 75 will be retracted, and inner sleeve 67 will be located in an upper position relative to outer sleeve 69. The running tool rotates inner sleeve 67 relative to outer sleeve 69. Inner sleeve 67 will move downward and abut energizing ring 47. The downward movement causes dogs 75 to move out in the windows 73, engaging groove 21. Then, the running tool rotates casing lock ring 79 downward and secures it in place with its flange 83 engaging upper end 27 of casing 25.
Then, tubing hanger 85 may be run in place with tubing 89. After landing on load ring 87 (FIG. 1), a running tool will push actuating ring 103 (FIG. 2) downward. Actuating ring 103 pushes lock ring 101 outward into groove 91, locking tubing hanger 85 in place. Then, a running tool will lower seal 107 into place and move energizing ring 109 downward to cause seal 107 to embed into the wickers 95, 99.
If it is desired at a later date to replace seal 107, it may be replaced by pulling upward on energizing ring 109 and retrieving seal 107. Actuating 103 will remain in its lower position as it will be held in place by the locking taper of wedge surface 105.
The invention has significant advantages. By carrying the load ring on the seal, the seal can be landed in and supported directly by the wellhead housing. The downward energizing force imposed on the seal is not transmitted to some other structure located in the well, such as slips. The locking assembly will lock the seal in its energized position directly to the wellhead housing. The locking assembly further will lock the upper end of the casing to prevent upward thermal growth. By locking the tubing hanger with a tapered wedge actuating ring, the tubing hanger will remain in place even though the tubing hanger seal is removed for replacement.
While the invention has been shown in only one of its forms, it should be apparent to those skilled in the art that it is not so limited, but is susceptible to various changes without departing from the scope of the invention. | A well completion system utilizes a seal which carries its own load ring. The seal is lowered into the bore of a wellhead housing around a tubular member. The seal carries a split load ring, which once positioned will move outward into engagement with a groove formed in the wellhead housing. A locking assembly will lock the seal to the wellhead housing. The locking assembly has a casing lock ring which will secure to the upper end of a section of casing, if the casing has been cut due to an emergency stuck condition. A tubing hanger lands over the locking assembly. The tubing hanger is retained by an actuating ring and lock ring that are independent of the tubing hanger seal. | 4 |
BACKGROUND OF THE INVENTION
This invention relates to a method and an apparatus for use in processing a substrate to remove or form a film on a processing region of the substrate. It should be noted throughout the instant specification that the method and the apparatus are used in manufacturing a photomask, a photomask blank, a reticle, a reticle blank, a reticle testing substrate, a semiconductor substrate, a magnetic disk, a color filter, and the like, although description will be mainly made about the photomask blank and the reticle testing substrate.
Recent requirements have been directed to a photomask blank which can delineate a fine pattern at a high precision and a high resolution by the use of a photolithography technique. To this end, a phase shift method has been proposed in Japanese Unexamined Patent Publication Sho 58-173744, namely, 173744/1983, and so on. With this method, it is possible to manufacture a phase shift photomask blank which comprises a transparent substrate, a plurality of opaque patterns on the substrate, and a transparent film covered on the substrate and the patterns. The transparent film is selectively etched into transparent patterns by 9 photolithography technique to manufacture the phase shift photomask.
Herein, the transparent film is formed by a spin coating technique in consideration of flatness of the transparent film. A flat transparent film is produced by the use of the spin coating technique at a center portion of the transparent film and may be, for example, a resist film. However, the flatness of the transparent film is not kept at a peripheral portion of the film because the transparent film tends to become thick at the peripheral portion due to the spin coating technique is used, as well known in the art. In other words, the peripheral portion of the transparent film has an irregular thickness when the spin coating technique is used to form the transparent film.
Moreover, the periphery of the phase shift photomask is intended to be attached or supported by other equipment, such as a support member when optically coupled to an optical system for the photolithography. This means that the periphery of the phase shift photomask is preferably flat as, otherwise, optical adjustment of the phase shift photomask becomes difficult because of the irregular thickness of the peripheral portion of the transparent film.
In order to avoid the irregular thickness of the peripheral portion, disclosure is made in Japanese Patent Publication No. Sho 58-19350, for removing the transparent film at the peripheral portion thereof from the substrate. More specifically, a solvent for the transparent film is discharged from a nozzle onto the peripheral portion of the transparent film. However, the solvent is not confined only to the peripheral portion of the transparent film. In this case, the peripheral portion of the transparent film is refered to as a processing region while the remaining portion is an unprocessing region. With this method, the solvent undesirably spreads from the processing region to the unprocessing region. As a result, the unprocessing region of the transparent film is often dissolved by the solvent in addition to the processing region.
Alternatively, a reticle testing substrate is used for optically testing a reticle which has a pattern on a reticle surface. In other words, the reticle testing substrate serves to determine whether or not a failure is included in the pattern on the reticle. To this end, such a reticle testing substrate comprises a quartz substrate having a substrate surface, an opaque film of chromium deposited on a peripheral region of the substrate surface, and a resist film uniformly coated on the substrate surface and the opaque film. In this situation, the pattern on the reticle surface is optically transcribed onto the resist film coated on the substrate surface of the reticle testing substrate by the use of a step and repeat technique. Such optical transcription of a pattern is carried out by adjusting a focus of an optical system to the opaque film. Thus, a resist pattern is formed on the substrate surface and is identical with the pattern on the reticle to be tested.
Under the circumstances, light is emitted onto the resist pattern through the reticle testing substrate so as to form a pattern image of the resist pattern by the light and to check whether or not a failure is included in the pattern image. When a failure is found on the pattern image, the reticle which corresponds to the reticle testing substrate is rejected as a faulty reticle and, otherwise, the reticle is accepted as a non-faulty reticle.
Herein, it is to be noted that the opaque film of chromium is left only along the periphery of the quartz substrate and may not be always precise in size. In order to leave the opaque film only along the periphery of the quartz substrate, a chromium film is deposited on the quartz substrate and the photoresist layer is left only on a peripheral portion of the chromium film. Thereafter, the chromium film is etched by an etchant to leave the opaque film along the periphery of the quartz substrate. In this way, it is very simple to leave the photoresist film only along the peripheral portion, namely, the processing region of the chromium film in a simple manner.
SUMMARY OF THE INVENTION
It is an object of this invention to provide a method of processing a substrate, which is capable of readily and accurately processing only a processing region on the substrate by the use of a processing solution.
It is another object of this invention to provide a method of the type described, which is capable of removing superflous film in the processing region by a solvent used as the processing solution.
It is still another object of this invention to provide a method of the type described, which is capable of forming a desirable film only in the processing region.
It is yet another object of this invention to provide an apparatus which is capable of effectively processing only a processing region by the use of a processing solution.
It is another object of this invention to provide an apparatus of the type described, which is capable of desirably removing superfluous film only in the processing region by the solvent.
It is another object of this invention to provide an apparatus of the type described, which is capable of forming a desirable film only in the processing region.
It is a further object of this invention to provide a product, such as a photomask blank, a reticle blank, which can be manufactured by the above-mentioned method and apparatus.
A method according to an aspect of this invention is for use in processing, by the use of a processing solution, a substrate which has a principal surface divisible into an unprocessing region and a processing region surrounding the unprocessing region. The method comprises the steps of preparing a guide member having a bottom portion and an extended portion which is contiguous to the bottom portion and which defines an end portion corresponding to the processing region, locating the guide member and the substrate with a gap between the end portion of the guide member and the processing region of the substrate and with an internal space between the unprocessing region and the bottom portion and which is wider than the gap, and supplying the processing solution to the gap to process the processing region by the processing solution with the processing solution confined in the gap alone.
An apparatus according to another aspect of this invention to carry out the method comprises a guide member having a bottom portion and an extended portion which is contiguous to the bottom portion and which defines an end portion corresponding to the processing region, a spacer member located between the guide member and the substrate with a gap left between the end portion of the guide member and the processing region of the substrate and with an internal space between the unprocessing region and the bottom portion and which is wider than the gap, and a solution supplying member for supplying the processing solution to the gap to process the processing region by the processing solution with the processing solution confined in the gap alone.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a schematic sectional view of a conventional apparatus for use in removing an unnecessary film from a substrate;
FIG. 2 is a sectional view of an apparatus according to a first embodiment of this invention;
FIG. 3 is a schematic sectional view for use in describing operation of the apparatus illustrated in FIG. 2;
FIG. 4 is a partial sectional view for use in describing a state of a substrate processed by the apparatus illustrated in FIG. 2;
FIG. 5 is a partial sectional view for use in describing a process carried out by the apparatus illustrated in FIG. 2;
FIG. 6 is a partial sectional view of an apparatus according to a modification of the first embodiment of this invention;
FIG. 7 is a similar view of an apparatus according to another modification of the first embodiment of this invention;
FIG. 8 is a sectional view of an apparatus according to a second embodiment of this invention;
FIG. 9 is a plan view of a guide member for use in the apparatus illustrated in FIG. 8;
FIG. 10 is a partial sectional view for use in describing a process carried out by the apparatus illustrated in FIG. 8;
FIG. 11 is a similar view for use in describing another process carried out by the apparatus illustrated in FIG. 8;
FIG. 12 is a plan view for use in describing a phase shift mask blank manufactured by the apparatus illustrated in FIG. 8;
FIG. 13 is a plan view of another guide member used in the apparatus illustrated in FIG. 8;
FIG. 14 is a plan view of a product manufactured by the use of the guide member shown in FIG. 13; and
FIG. 15 is a partial sectional view of an apparatus according to a modification of the second embodiment illustrated in FIG. 8.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1, description will be directed to a conventional method which is substantially equivalent to that mentioned in Japanese Patent Publication Sho 58-19350, described previously in the instant specification. The conventional method is for use in manufacturing a phase shift photomask blank formed from a substrate block as shown in FIG. 1. In the illustrated example, the substrate block comprises a transparent substrate 21 having a principal or front surface directed upwards in FIG. 1, a plurality of opaque or shading films 22 on the principal surface, and a coated film 23 covering the principal surface and the opaque films 22. The principal surface is divided into an unprocessing or a center region located at a center portion of the principal surface and a processing or a peripheral region surrounding the center portion. Thus, the processing region is placed at a peripheral portion of the principal surface.
The illustrated substrate block is supported by a turntable 24 and is rotated on the turntable 24 as indicated by an arrow. A nozzle 25 is directed towards a peripheral region of a back surface opposite the principal surface of the substrate 21. Thus, the nozzle 25 is placed under the substrate 21 in the example being illustrated.
It is assumed that the coated film 23 is coated by a spin coating method and is therefore flat on the center portion of the principal surface and is irregularly thick or heaped at the peripheral region of the principal surface. A solvent 26 is discharged through the nozzle 25 so as to dissolve the coated film 23 in the processing region thereof and to remove the coated film 23 from the processing region, namely, the peripheral portion while the substrate block is rotated on the turntable 24.
In this event, the solvent 26 travels along a side surface of the substrate 21 by surface tension and moves on the coated film 23 of the peripheral region of the principal surface. As a result, the coated film 23 is resolved on the peripheral region of the principal surface and the side surface, as illustrated in FIG. 1. Thereafter, the solvent is blown off the substrate block by centrifugal force resulting from the rotation of the block, as shown in FIG. 1. Thus, the processing region of the coated film 23 is removed from the substrate 21.
With this method, it is difficult to determine conditions for removing only the coated film 23 at the processing region. Consequently, the coated film 23 in the unprocessing region is often removed, as pointed out previously in the instant specification.
Referring to FIG. 2, an apparatus according to a first embodiment of this invention is for use in manufacturing a phase shift photomask blank by removing a superfluous or an undesired coated film from a substrate block. As in FIG. 1, the substrate block comprises a transparent substrate 21 of quartz glass which has a size of 6 (inches)×6 (inches)×0.25 (inch) and a principal or front surface 21a directed downwards of FIG. 2 and a back surface 21b opposite the principal surface 21a. A plurality of opaque films or shading films 22 are deposited on a center region of the principal surface 21a of the substrate 21 to form a shading pattern and are covered with a coated film 23 which may be, a poly-siloxane SOG (Spin-On-Glass) film as known in the art and which is assumed to be coated by spin coating in the illustrated example. The spin coating may be carried out by the use of a coating solution which includes silicon oxide and which may be, for example, ACCUGLASS211S manufactured and sold by Allied Signal Company Ltd.
Referring to FIGS. 3 and 4 together with FIG. 2, the coated film 23 extends over the entire principal surface 21a and may be extended to a side surface 21c of the substrate 21 and the back surface 21b of the substrate 21. In FIGS. 3 and 4, the coated film 23 is on the principal surfaces 21a and both the side and the back surfaces 21c and 21b. The coated film 23 has a thickness of about 4,000 angstroms at the center region and is formed by spin coating the above-mentioned coating solution at a rotation speed of 1,000 rpm for ten seconds.
As illustrated in FIGS. 3 and 4, the coated film 23 has a flat or uniform portion 23a at the center region of the substrate 21, a heaped up portion 23b at the peripheral region 21d of the substrate 21, a side portion 23c on the side surface 21c of the substrate 21, and in pack portion 23d onthe back surface 21b of the substrate 21. Thus, the coated film 23 is flat in the center region of the principal surface 21a and is uneven on the peripheral region 21d surrounding the central surface of the substrate 21. In other words, the spin coating tends to undesirably form the heaped up portion 23b at the peripheral region 21d of the substrate 21, as pointed out in conjunction with FIG. 1. The back portion 23d is also heaped up on the back surface 21b as on the peripheral portion 21d of the substrate 21.
In the illustrated example, the coated film 23 on the peripheral region 21d is removed or processed together with the coated film 23 of both the side surface 21c and the back surface 21b in a manner similar to the spin coating. In this connection, the peripheral portion 21d and the center region of the principal surface will be referred to as a processing region and an unprocessing region, respectively.
The apparatus shown in FIG. 2 serves to remove the heaped up portion 23b, the side portion 23c and the back portion 23d by the use of a solvent which can resolve the coated film 23 and which may be, for example, acetone.
The illustrated apparatus comprises a guide member 31 of cup shape which is rotatable with a rotation axle 32. The rotation axle 32 is mechanically coupled to a motor or the like (not shown) and can be rotated at a rotation speed determined by the motor. The guide member 31 has a bottom section 31a fixed to the rotation axle 32, an extended portion 31b contiguous to the bottom section 31a and offset from the bottom portion 31a, and a wall portion 31c extending upright from the extended portion 31b. The wall portion 31c is contiguous to an external portion 31d disposed horizontally outside of the wall portion 31c. In the example being illustrated, the extended portion 31b defines an end portion which is offset upwards in FIG. 2 and which faces the peripheral region 21d of the principal surface 21a in a manner to be described later in detail.
As shown in FIGS. 3 through 5, a block setting zone is formed within the guide member 31 to locate the substrate block and is defined by the bottom portion 31a, the extended portion 31b, and the wall portion 31c. The block setting zone serves to keep the substrate block substantially horizontal and therefore has a size which can accommodate the substrate block in the block setting zone.
In addition, a plurality of nylon threads 36a each of which is 0.1 millimeter thick are arranged on the extended portion 31b, with a top of each nylon thread 36a projecting upwards, as shown in FIG. 2. Each of the nylon threads 36a forms a loop or a ring, as illustrated in FIG. 2, and is called a nylon ring. The nylon rings 36a may be positioned with a spacing between two adjacent nylon rings 36a and the nylon rings serve as spacers between the extended portion 31b and the substrate block, as will later be described. In the illustrated example, the nylon rings 36a are equal in number to eight.
Moreover, a plurality of additional nylon threads 36b are also arranged at the external portion 31d and the wall portion 31c. Each of the nylon threads 36b is formed as a loop and is called a nylon loop. The additional nylon loops 36b are arranged so that each additional nylon loop 36b surrounds the wall portion 31c as shown in FIG. 2. Each additional nylon loop 36b serves as an additional spacer between the side surface 21c of the substrate 21 and the wall portion 31c and is sixteen nylon loops 36b are employed in the illustrated example. Every other one of the additional nylon threads 36b has a thickness or a diameter of about 0.44 millimeter while each of the remaining additional nylon threads 36b has a thickness or a diameter of about 0.21 millimeter. The thinner nylon threads also serve to cause the solvent to flow smoothly along the thin nylon threads and, as a result, to guide the solvent as will become clear later.
A nozzle 40 is opposite the guide member 31 and is perpendicular to the bottom portion 31a of the guide member 31. The solvent is sprayed through the nozzle 40 downwards in FIGS. 2 through 5, as depicted at 41 in FIG. 2.
In operation the substrate block is set in the block setting zone of the guide member 31 illustrated in FIGS. 2 through 5, with the principal surface 21a of the substrate 21 directed downwards in FIGS. 2 through 5. In this situation, the nylon rings 36a are brought into contact with the heaped up portion 23b of the coated film 23 formed on the peripheral region 21d of the substrate 21. Thereby the substrate block is kept substantially horizontal with a gap left between the extended portion 31b of the guide member 31 and the coated film 23 on the substrate 21. The gap is determined by the thickness or a diameter of each of the nylon threads 36a. The gap may have a size of about 0.17 millimeter. Likewise, the substrate block is spaced from the wall portion 31c within the block setting zone by a side gap determined by the additional nylon loops 36b, as shown in FIG. 2. The side gap may have a width of 0.44 millimeter.
Thus, the peripheral region 21d of the substrate 21 faces the extended portion 31b of the guide member 31 with the gap left therebetween. On the other hand, the center region 21a of the substrate 21 faces the bottom portion 31a of the guide member 31 at an internal spacing which is wider than the gap, as readily understood from FIGS. 2 through 5. In other words, the processing region and the unprocessing region of the substrate 21 are opposed the extended portion 31b and the bottom portion 31a respectively of the guide member 31 through the gap and the internal spacing, respectively.
At first, the guide member 31 is rotated at a first rotation speed of 50 rpm. During the rotation of the guide member 31, the solvent, for example, acetone, is sprayed in an amount of 25 milliliters from the nozzle 40 towards the back surface 21b of the substrate 21, as shown in FIG. 2. During this process, the solvent is caused to flow from the back surface 21b of the substrate 21 along the side portion 23c of the coated film 23 to the peripheral portion 23b of the coated film 23. On the peripheral portion 23b of the coated film 23, the solvent travels by capillarity towards the center region 21a of the substrate 21 through the gap defined by the nylon rings 36a.
When the solvent has reached an offset portion, namely, a boundary between the extended portion 31b and the bottom portion 31a of the guide member 31, the solvent stops due to the surface tension of the solvent. Therefore, the solvent does not travel to the center region 21a, namely, the unprocessing region of the substrate 21. Consequently, the coated film 23 is not removed by the solvent at the center region 21a of the substrate 21. On the other hand, the back portion 23d and the side portion 23c of the coated film 23 are contacted by the solvent together with the peripheral portion 23b, which causes dissolution reaction to occur between the solvent and the coated film 23. The dissolution reaction brings about dissolving of the coated film 21 by the solvent and removal of the coated film 21 at the peripheral, side, and back portions 23b, 23c, and 23d. Thus, the coated film 23 is dissolved only at the processing region of the substrate 21 and not at the unprocessing region of the substrate 21.
After the dissolving action is finished between the solvent and the coated film 23, the guide member 31 is rotated at a high or a second rotation speed of 1500 rpm for one second. During this high speed rotation, the coated film is scattered outside the substrate block. Thus, unnecessary films coating at the peripheral region, the side surface 21c, and the back surface 21b are removed from the substrate 21. Herein, it is to be noted that the above-mentioned solvent scattering process should be completed before the volatile solvent has thickened.
In order to thoroughly remove the unnecessary coated film, dissolving is carried out at a third rotation speed of 70 rpm for ten seconds after the solvent scattering process. Subsequently, dissolving is carried out at a fourth rotation speed of 100 rpm for ten seconds and this is followed by a drying and scattering process carried out at a fifth rotation speed of 1500 rpm for ten seconds. The substrate block is converted into the phase shift mask blank by removal of the unnecessary coated film.
Finally, rotation of the guide member 31 is stopped and the phase shift mask blank is taken out of the guide member 31. The phase shift mask blank manufactured in the above-mentioned manner comprises a phase shift film which is composed of the coated film and which is left in a square shape on the center region of the substrate 21.
The solvent may be replaced by methanol, isopropyl alcohol, or the like.
In FIG. 5, the side gap between the wall portion 31c of the guide member 31 and the side surface 21c of the substrate 21 is assumed to be equal in width to 0.44 millimeter in the above-mentioned example. However, the side gap may have a gap width such that the solvent 41 can flow through the side gap along the side surface 21c of the substrate 21 towards the peripheral region 21a.
In addition, although the gap between the extended portion 31b of the guide member 31 and the peripheral region 21d of the substrate 21 is assumed to be equal to 0.17 millimeter, the size or width of the gap may be determined in consideration of the viscosity of the solvent so that the solvent can flow into the gap and can be held within the gap by the surface tension of the solvent. Furthermore, the gap need not have a uniform width but may be gradually tapered from the outer periphery of the substrate 21 towards the center region of the substrate 21. In the latter case, the gap gradually narrows as the gap approaches the center region of the substrate 21. With this construction the solvent can be readily introduced into the gap.
In the above-mentioned method, the guide member 31 is rotated so as to dissolve the coated film 23 and to scatter the solvent which dissolved the coated film 23. Although such rotation processes are alternately repeated three times for each of the dissolving and the scattering steps in the above-mentioned example, the rotation processes may be carried out at least one time for each of the dissolved and the scattering operation. The rotation speed and the rotation time may be optionally selected in consideration of the solvent used, the thickness of the coated film 23, and the like.
In practice, the method illustrated with reference to FIGS. 2 through 5 has been applied to removal of the heaped up portion 23b of the coated film which provides a maximum thickness of about 1.6 micronmeters at a position about 10 millimeters from the outer periphery of the substrate 21 and a thickness of about 0.3 micronmeter at a position 21 millimeters from the outer periphery of the substrate 21. In this case, the coated film 23 has been removed over a width of about 20.0 millimeters from the outer periphery of the substrate 21. Stated otherwise, the heaped up portion 23b of about 20.0 millimeters has been removed in a rectangular shape from the peripheral region 21d of the substrate 21. As a result, the remaining coated film 23 has a thickness of about 0.3 micronmeter at a position about 21 millimeters from the outer periphery of the substrate 21. It has been found that the coated film 23 which is about 0.3 micronmeter thick has no cracks therein and is very convenient for the phase shift mask blank.
Thus, the phase shift mask blank retains the coated film 23 except for the peripheral region 21d, the side surface 21c, and the back surface 21b. With this mask blank, it is possible to prevent adherence of any dust to the back and the side surfaces 21c and 21b of the substrate 21 and to therefore keep the phase shift mask blank clean. Moreover, the phase shift mask blank can be accurately attached to an exposure device or other optical device by mounting the peripheral region 21d onto such an exposure device.
Referring to FIG. 6, an apparatus according to a modification of the first embodiment illustrated in FIGS. 2 through 5 further comprises a through hole 44 formed in the extended portion 31b of the guide member 31 and an additional nozzle 45 which is placed under the guide member 45 and which faces the through hole 44. The guide member 31 has an internal side surface defining the through hole 44.
In the illustrated example, the solvent 41 is discharged from the nozzle 40 placed over the substrate 21 and is simultaneously discharged from the additional nozzle 45. With this structure, the superfluous coated film is very quickly removed from the substrate 21, which is helpful to manufacture the phase shift mask blank at a high speed in comparison with the method illustrated in conjunction with FIGS. 2 through 5.
Referring to FIG. 7, an apparatus according to another modification of the first embodiment illustrated in FIGS. 2 through 5 comprises no additional nozzle 45, although the through hole 44 is formed through the guide member 31. In this case, the through hole 44 serves to discharge unnecessary solvent therethrough. The discharge of the unnecessary solvent can be smoothly carried out when a thread or a needle is inserted in the through hole 44.
The nylon threads 36a and 36b which act as spacers may be replaced by projections formed by screws or tapes which are composed of a material insoluble is the solvent.
Referring to FIG. 8, an apparatus according to a second embodiment of this invention is shown for manufacturing a phase shift mask blank by removing superfluous coated film from a substrate block, as in the first embodiment. It is to be noted that the substrate block is directed upwards in FIG. 8, which differs from the apparatus illustrated in FIGS. 2 through 7. In this connection, the substrate block comprises similar parts designated by like reference numerals. Specifically, the substrate block comprises the substrate 21 of glass having the principal or front surface 21a directed upwards in FIG. 8, the back surface 21b directed downwards of FIG. 8, and the side surface 21c contiguous to the principal and the back surfaces 21a and 21b. The principal surface 21a is divided into the center region and the peripheral region 21d.
A plurality of opaque or shading films 22 are selectively formed on the principal surface 21a and are covered with coated film 23 which extends over the entire principal surface 21a and which may be, for example, a poly-siloxane spin-on-glass (SOG) film as in the first embodiment.
In practice, the illustrated substrate comprises the substrate of quartz glass having a size of 6 (inches) ×6 (inches)×0.25 (inch), the shading films 22 of chromium, and the coated film 23 of the poly-siloxane SOG. The shading films 22 are deposited at the center region of the principal surface 21a and are not deposited at the peripheral region 21d. On the other hand, the coated film 23 is coated by spin coating and extends from the center region of the principal surface 21a to the peripheral region 21d. At the peripheral region 21d, the coated film 23 is heaped up as mentioned in conjunction with FIG. 4. Specifically, the spin coating has been carried out at a rotation speed of 1000 rpm for ten seconds. The resultant coated film 23 has a thickness of 4,000 angstroms in the center region, a thickness of 1.6 micronmeters at the heaped up portion, and a thickness of 0.3 microameter at a distance of 2.1 millimeters from the outer periphery of the substrate block.
The apparatus shown in FIG. 8 comprises a support member 51 which is similar in structure to the guide member 31 shown in FIGS. 2 through 7 and which serves to support the back surface 21b of the substrate 21. The support member 51 is fixed to a rotation axle 52 mechanically coupled to a motor or the like and is rotated at a rotation speed determined by the motor. More particularly, the support member 51 has a bottom part 51a of a dish shape in section, an extended part 51b offset from the bottom part 51a with an offset part between the bottom part 51a and the extended part 51b, a wall part 51c extending upright from the extended part 51b, and an external part 51d horizontally extending outward from the wall part 51c.
A plurality of nylon rings 53a are arranged on the extended part 51b so that the top of each nylon ring 53a projects from the extended part 51b. In the illustrated example, the nylon rings 53a are equal in number to eight and are spaced from one another at the periphery of the extended part 51b and have individually a thickness or diameter of 0.15 millimeter. Thus, the nylon rings 53a rest on the extended part 51b in a manner similar to the nylon rings 36a illustrated in FIG. 2. As readily understood from FIG. 8, the bottom part 51a defines an inner space smaller in size than the size of the substrate block while the wall part 51c defines an internal space somewhat greater in size than the substrate block. Accordingly, the substrate block can be accommodated within the support member 51 in the illustrated manner.
The apparatus further comprises a guide member 55 which is operable in a manner similar to the guide member 31 mentioned in conjunction with FIGS. 2 through 7 and which is supported on the support member 51 so that the substrate block is covered by the guide member 55. More specifically, the guide member 55 has a cup shape in section as in FIGS. 2 through 7 but is upset relative to that illustrated in FIGS. 2 through 7. Thus, the illustrated guide member 55 covers the substrate block and is referred to as a cover member.
The guide member 55 has an outer configuration substantially corresponding to that of the support member 51 and is of square shape in the illustrated example. The guide member 55 further has a base portion 61 directed upwards in FIG. 8 and a wall portion 62 which extends downwards in FIG. 8 from the base portion 61 and which defines an inside space therein. In any event, the guide member 55 has a cup shape in section while the inside space has a square shape.
The base portion 61 operates similarly to the bottom portion 31a of the guide member 31 shown in FIGS. 2 through 7 and is called a bottom portion. The base portion 61 of FIG. 8 has a base surface 61a directed upwards in FIG. 8 and an inside surface 61b directed downwards. The wall portion 62 has a wall end surface 62a which is directed downwards in FIG. 8 and which faces the principal surface of the substrate 21. The inside space is defined by the inside surface 61b and the wall portion 62.
As readily understood from FIG. 8, the wall end surface 62a of the guide member 55 covers the peripheral region of the principal surface of the substrate 21 while the inside surface 61b is opposite a center region of the principal surface of the substrate. Thus, the wall end surface 62a faces with a processing region of the substrate 21 while the inside surface 61b faces the region of the substrate 21 not to be processed, as in the guide member 31 shown in FIGS. 2 to 7. In the illustrated example, the difference in height between the inside surface 61b and the wall end surface 62a is equal to 1.5 millimeters while the peripheral region of the substrate 21 is spaced by a distance of about 20 millimeters from the wall portion 62.
Referring to FIG. 9 in addition to FIG. 8, the guide member 55 has an inside surface of square shape surrounded by the wall end surface 62a. At the wall end surface 62a, a number of holes 63 are formed along an inside edge of the wall end surface 62a and the holes 63 are spaced from one another at a predetermined distance. In addition, the guide member 55 has four projected portions and four openings 64 formed in the projected portions. In FIG. 9, the projected portions are placed in a center region of each outer side edge of the wall end surface 62a. The openings 64 serve to insert positioning pins 65 (FIG. 8) and to fasten the guide member 55 to the support member 51, as shown in FIG. 8. Consequently, the guide member 55 can be rotated around the rotation axle 52 together with the support member 51 and the substrate block.
Moreover, four nylon loops or rings 66 are disposed at positions radially inwards of the openings 64. Each of the nylon rings 66 is partially protrudes at the wall end surface 62a and the base surface 61a, as depicted at FIG. 8. The nylon rings 66 protruding at the wall end surface 62a serve as spacers which keep a gap between the guide member 55 and the substrate 21, as for the nylon rings 36a shown in FIG. 2. In the illustrated example, the nylon thread used for each of the nylon rings 66 has a thickness or a diameter of about 0.15 millimeter. As a result, the gap between the wall end surface 62a and the substrate block is kept at 0.15 millimeter while the space between the substrate block and the inside surface 61b of the guide member 55 becomes equal to 1.65 millimeters.
Turning back to FIG. 8, the nozzle 40 is placed over the guide member 55 to discharge the solvent 41 at a preselected speed onto the the base surface 61a of the guide member 55. Thus, the nozzle 40 illustrated in FIG. 8 faces the base surface 61a of the guide member 55 and is connected to a solvent feeder (not shown) for feeding the solvent 41 to the nozzle 40. The solvent 41 may be, for example, acetone or the like when the coated film 23 is formed by poly-siloxane SOG.
Referring to FIG. 8 again and to FIGS. 10 and 11, the coated film 23 of the poly-siloxane SOG covers the shading films 22 and the principal surface 21a of the substrate 21 by the use of spin coating to form the substrate block illustrated in FIG. 10. The substrate block is set on the apparatus as shown in FIG. 8 with the principal surface 21a of the substrate 21 directed upwards in FIG. 8. Hence the substrate 21 is not inverted, which is different from FIGS. 2 through 7. Therefore, the apparatus of FIG. 8 is more effective in handling the substrate in comparison with that shown in FIGS. 2 through 7.
Next, the guide member 55 is covered over the substrate block and is fixed to the support member 51 by the positioning pins 65. In this event, the guide member 55 covers the peripheral region 21d of the principal surface 21a with the gap of 0.15 millimeter between the coated film 23 and the wall end surface 62a, as best shown in FIG. 10 and with the inside space of 1.65 millimeters between the inside surface 61a and the substrate block. As mentioned before, the nylon rings 66 serve to preserve the gap between the coated film 23 and the wall end surface 62a. It is assumed that the guide member 55 covers the peripheral region 21d of a width of 20 millimeters. In addition, a side gap is also left between the outer periphery of the substrate 21 and the wall part 51c of the support member 51.
In this condition, the solvent 41 is discharged from of the nozzle 40 to remove the coated film 23 on the peripheral region 21d of the substrate and to consequently manufacture the phase shift mask blank which has an uncovered area on the peripheral region 21d of the substrate 21. Specifically, acetone in an amount of about 25 millimeters is supplied as the solvent 41 through the nozzle 40 while the support member 51 is rotated together with the substrate block and the guide member 55 at a rotation speed of 200 rpm for about 15 seconds. During this process, the solvent 41 is caused to flow through the holes 63 downwards in FIG. 8 from the base surface 61a of the guide member 55 and into the gap between the substrate block and the wall end surface 62a. Thereafter, the solvent 41 quickly passes outwards of the substrate block due to the capillarity and the centrifugal force resulting from the rotation of the support member 51, as illustrated in FIG. 10. The solvent 41 also passes through the side gap between the support member 51 and the substrate block to be brought into contact with the side surface 21c and the back surface 21b of the substrate 21.
As a result, the coated film 23 is removed from the peripheral region 21d, the side surface 21c, and the back surface 21b of the substrate 21 by the solvent 41 in the manner described with reference to FIGS. 2 through 7.
On the other hand, the solvent 41 does not passes towards the center region of the principal surface 21a of the substrate 21 due to the surface tension of the solvent 41, as shown in FIG. 9. This is because the inside space between the substrate block and the inside surface 61b of the guide member 55 is very much greater than the gap between the substrate block and the wall end surface 62a.
Thus, the coated film 23 is dissolved by the solvent 41 at the peripheral region 21d of the substrate 21, namely, the processing region and is not dissolved at the center or the unprocessing region of the substrate 21, as best shown in FIG. 11.
After the above-mentioned reaction is finished for dissolving the coated film 21 by the solvent 41, the support member 51 is rotated again at the rotation speed of 200 rpm for about 20 seconds together with the substrate block and the guide member 55 with supply of the solvent stopped. During this rotation of the support member 51, the solvent 21 is scattered outwards, as symbolized by arrows in FIG. 8, and the unnecessary coated film is removed from the substrate 21. Herein, such a scattering process of the solvent 41 should be made before the viscosity of the solvent 41 becomes undesirably high due to volatilization of the solvent 41.
Subsequently, the support member 51 is further rotated at the rotation speed of 400 rpm for 10 seconds together with the substrate 21 and the guide member 55 so as to thoroughly carry out the removal of the unnecessary coated film and to dry the substrate 21. Thereafter, the rotation of the support member 51 is stopped. Then, the substrate block from which the coated film 23 is removed at the peripheral region 21d of the substrate 21 is separated from the apparatus illustrated in FIG. 8 and is subsequently baked to convert the coated film 23 to a phase shift film. Thus, the substrate block becomes the phase shift mask blank.
Referring to FIG. 12, the phase shift mask blank manufactured in the above-mentioned apparatus and manner has the phase shift film 23 left in the center region of the substrate 21 and at the peripheral region 21d it is uncovered. The uncovered peripheral region 21d has a width of about 20 millimeters and forms a processed region. Thus, when the heaped up portion 23b has the maximum thickness of about 1.6 micronmeters and a thickness of 0.3 micronmeter at a position 20.5 millimeters from the outer pheriphery of the substrate blank before the above-mentioned process is carried out by the use of the above-mentioned apparatus, the maximum thickness portion is completely removed from the phase shift film 23 which has a thickness of about 0.3 micronmeter at the edge portion thereof. The peripheral region 21d is completely flat because the coated film 23 is thoroughly removed from the peripheral region 21d. With this structure, no cracking takes place in the phase shift film 23 because the phase shift film 23 is only 0.3 micronmeter thick.
Furthermore, the solvent 41 smoothly and reliably travels through the gap between the wall end surface 62a and the substrate block due to capillarity. However, the solvent 41 does not pass to the unprocessing or center region of the principal surface 21a because no influence takes place due to wind force resulting from the rotation. Therefore, the processing region, namely, the peripheral region 21d alone is accurately processed or removed by the solvent 41.
Referring to FIGS. 13 and 14, an apparatus according to a modification of the second embodiment of this invention comprises a guide member 55a illustrated in FIG. 13. As shown in FIG. 13, the guide member 55a has a wall end surface 62a which covers not only the peripheral region 21d of the substrate 21 but also the center region of the substrate 21 in a crisscross manner. In other words, the inside surface 61b of the guide member 55a is divided into four square surfaces 61b' each of which is surrounded by the wall end surface 62a, as illustrated in FIG. 14. In the wall end surface 62a, a number of holes 63 are arranged so that each of the square surface 61b' is surrounded by a line of the holes 63. In addition, the openings 64 are provided in the projected portions of the guide member 55a as in the guide member 55 shown in FIG. 9 to fix the guide member 55a to the support member 51 by the positioning pins 65 (FIG. 8). The nylon rings 66 are placed in the vicinity of the openings 64 like in FIG. 8.
The guide member 55a shown in FIG. 13 is set into the apparatus of FIG. 8 in a manner similar to the guide member 55 to process the substrate block with the gap left between the wall end surface 62a and the substrate block. The solvent 41 is discharged from the nozzle 40 onto the guide member 55a to be supplied through the holes 63 onto the substrate block. The solvent 41 passes through the gap over the wall end surface 62a of the guide member 55a and is maintained within the gap. On supply of the solvent 41, the support member 51 may be rotated in a manner similar to that illustrated in conjunction with FIGS. 8 through 11 or it may not be rotated.
At any rate, the phase shift mask blank shown in FIG. 14 is manufactured by the above-mentioned process. In FIG. 14, the phase shift mask blank has four partial phase shift films 23a to 23d left on the substrate 21 with the remaining parts uncovered or exposed.
Referring to FIG. 15, another apparatus according to a modification of the second embodiment of this invention comprises a support member 51' somewhat modified from that illustrated in FIG. 8. Specifically, the support member 51' has a bottom part 51a, an extended part 51b, a wall part 51c, and an external part 51d as in FIG. 8. The extended part 51b is offset from the bottom part 51a and has an opening 71 formed through the extended part 51b. The opening 71 serves to discharge superfluous solvent 41 which is supplied to the back surface 21b of the substrate 21. In this case, a guide thread or needle (not shown) may be suspended from the opening 71 so as to smoothly guide the superfluous solvent 41 and discharge the same.
Although the above description has been made only with reference to the phase shift mask blank, this invention may be also applied either to removal of an unnecessary resist film on manufacturing a photomask, a photomask blank, a semiconductor substrate, and the like or to the removal of an insulating film deposited on an electrode portion formed on a display substrate.
To the contrary, this invention may be used for forming a coated film on a substrate. More particularly, assume the apparatus illustrated in FIG. 2 or 8 is used for manufacturing a reticle testing substrate which comprises a quartz substrate, an opaque film of chromium deposited on a peripheral region of the quartz substrate, and a resist film coated on a center region of the quartz substrate and the opaque film. In this event, the opaque film is deposited on the entire surface of the substrate to be etched from the center region of the quartz substrate and is left only on the peripheral region of the quartz substrate. Before etching the opaque film from the center region, a photo resist film is formed or left only on the peripheral region of the quartz substrate. Such a photo resist film must be deposited on the entire opaque film and thereafter selectively exposed to leave the photo resist film only on the peripheral region.
However, such a photo resist film can be selectively formed on the peripheral region of the quartz substrate directly by the use of the apparatus according to this invention. To this end, the guide member 31 or 51 covers the center region of the quartz substrate after the opaque film is deposited all over the entire principal surface. In this situation, the guide member is opposed to the opaque film formed on the peripheral region of the quartz substrate with the gap left between the guide member and the opaque film. The gap is extended on the peripheral region of the quartz substrate. A resist solution is discharged from the nozzle to flow to the gap and be kept within the gap. Consequently, a resist film is formed on the opaque film only on the peripheral region of the quartz substrate. Thus, the resist film can be formed only on a desirable region by the use of the apparatus according to this invention. In this connection, the resist solution and the solvent may be collectively called a processing solution.
Likewise, this invention may be used either for forming a protection film on manufacturing a magnetic disk or for forming a protection film on manufacturing a color filter.
Stated otherwise, this invention is effective to process a substrate by the use of a solution which may either remove a film or form a film. In addition, such a film processed by this invention may be formed by sputtering, chemical vapor deposition (CVD), ion plating, evaporation, or the like.
While this invention has thus far been described in conjunction with a few embodiments thereof, it will be readily understood for those skilled in the art to put this invention into practice in various other ways. For example, removal of the poly-siloxane SOG film may be made by the use of methanol, isopropyl alcohol while removal of the resist film may be made by the a ketone, ester, aromatic hydrocarbon, hydrocarbon halide, ether, or the like.
In the second embodiment illustrated in FIGS. 8 through 14, the holes 63 may be moved on the wall end surface 62a outwards in FIG. 8. However, it is preferable that the holes 63 be adjacent to an inner edge of the wall end surface 62a because the solvent 41 is caused to flow in an outward direction. Two lines of the holes 63 may be arranged on the wall end surface 62a instead of a single line of holes 63. With this structure, it is possible to protect the solvent 41 from being dried and left on an outer peripheral region of the substrate 21.
The gap between the wall end surface and the substrate block need not be restricted to 0.15 millimeter but may be selected in consideration of the viscosity of the solvent. In addition, the gap need not be uniform but may be changed within a range in which capillarity takes place. Various kinds of spacers may be used in lieu of the nylon rings.
Moreover, the guide member 55 illustrated in FIG. 8 may have a pyramidal shape in section, as shown in Japanese Patent Publication No. Sho 58-19350 or it may have a dome shape in section. Finally, the substrate to be processed may be circular, triangular, rectangular, polygonal, or the like. | A method for applying or removing coatings at a confined peripheral region of a substrate to produce on a front surface of the substrate an interior unprocessed region surrounded by an outer processed region. According to the method, a guide member is positioned in adjacent facing relation to the front surface of the substrate and the guide member is formed with a central portion and a raised peripheral portion offset from the central portion. The central portion of the guide member faces and corresponds to a region of the substrate not to be processed, while the peripheral portion of the guide member faces and corresponds to an outer region of the substrate which is to be processed. The peripheral portion of the guide member is closer to the substrate and forms a gap with the opposed region of the substrate, which is less than a space formed between the central portion of the guide member and the opposed region of the substrate. A processing solution is introduced into the gap by spinning the guide member and the substrate together about a substantially vertical axis which keeps the processing solution confined to the gap by surface tension of the processing solution to achieve processing only of the outer region of the substrate while the central region of the substrate remains unprocessed. | 7 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of International Application PCT/DE 00/02389, which has an international filing date of Jul. 17, 2000 and was published as WO 01/05628 (incorporated by reference herein in its entirety).
BACKGROUND
[0002] The invention relates to a device including a circuit for actuating electric functional elements having at least two physically separate actuating modules.
[0003] Such a device can be used to trigger electric functions selectively from one or the other actuating module and hence from different locations. Each actuating module has actuating elements for triggering the electric functions, with those actuating elements of different actuating modules which are provided for triggering the same electric function being connected in parallel with one another.
[0004] Such devices are used in motor vehicles, for example, so that particular electric devices in a motor vehicle, such as a car radio or a window lifter, can be operated both by the driver and by the passenger. Two physically separate actuating modules are provided for triggering the electric functions. One actuating module is positioned within reach of the driver and the other is positioned within reach of the passenger.
[0005] Problems arise with such circuits if the electric actuating modules are each provided for triggering a plurality of electric functions and accordingly have a plurality of actuating elements, each of which is associated with a particular electric function. Precautions are required to deal with the situation when different electric functions which are not meant to be performed simultaneously are triggered simultaneously as a result of incorrect operation of the actuating elements. Such a situation arises, for example, if the driver of a motor vehicle activates a particular electric system while the passenger simultaneously triggers an actuating element used to deactivate the system.
[0006] This problem is frequently solved in known electric circuits by giving priority to one of the actuating elements in the event of different actuating elements being operated simultaneously. The electric circuit is designed so that, when a plurality of actuating elements are operated simultaneously, only that electric function which is associated with the actuating element having the highest priority is triggered. However, such circuits have the drawback that, to prevent contradictory control commands which may result from incorrect actuation, some of the information contained in the electric signals triggered by the incorrect actuation is suppressed. This is because only the signals which have been triggered by actuation of the actuating element having the highest priority are processed. All other signals are masked out or suppressed.
[0007] In other circuit arrangements, the “prioritization” described previously is avoided by allocating each actuating element a dedicated signal line. In such a case, an appropriate control unit can evaluate the signals coming from the individual signal lines individually and can trigger the appropriate electric functions on the basis of this evaluation. However, these known devices have the drawback that they require a very high level of circuit complexity, particularly in cases in which each actuating module has a relatively large number of actuating elements associated with it.
[0008] Problems of the type described above may additionally arise if the actuating modules are incorporated in a circuit along with other manually triggerable electric units.
[0009] U.S. Pat. No. 4,801,812 (incorporated by reference herein) discloses an electric arrangement for actuating a window lifter on the passenger side of a motor vehicle, in which raising and lowering of the window can be selectively triggered both from an actuating device on the driver's side and from an actuating device on the passenger side; in which each of these two actuating devices has two switch positions for raising and lowering the window; and in which each of the two switch positions has an associated defined electric code which can be used to identify the respective electric function performed (raising or lowering of the window on the passenger side).
[0010] Accordingly, it is an object of the present invention to provide a device for actuating electric functions which uses simple means to permit extensive evaluation of the control commands produced by operation of the actuating elements in the different actuating modules.
SUMMARY OF THE INVENTION
[0011] According to the present invention a device for actuating electric functional elements having at least two physically separate actuating modules is provided. The device includes defined electric functions that may be selectively triggered from one or the other actuating module (A 1 -A M ). Each of the actuating modules (A 1 -A M ) has at least two electric actuating elements ( 1 -N) for triggering different electric functions, and those actuating elements ( 1 -N) of different actuating modules (A 1 -A M ) which are provided for triggering the same electric function are connected in parallel with one another, wherein the actuating elements ( 1 to N) provided for triggering the same electric function have a respective electric assembly (B 1 -B N ) arranged in parallel with them which may be used to produce an electric code which is characteristic of the electric function to be triggered, wherein the electric actuating elements ( 1 -N) within an actuating module (A 1 -A M ) are respectively connected in series with one another..
[0012] Accordingly, the electric actuating elements within an actuating module are respectively connected in series, the actuating elements associated with a particular electric function on different actuating modules having a respective electric assembly connected in parallel with them which has an electric code which is characteristic of the electric function.
[0013] The inventive solution has the advantage that, with the actuating elements in each module in a simple series circuit, evaluating the electric code makes it possible, at any time, to clearly establish which actuating elements have been actuated to trigger a particular electric function. This is because any actuation of an actuating element influences the electric code of the electric assembly arranged in parallel with the appropriate actuating element in a defined manner. Evaluating the code signals in a suitable evaluation unit thus allows the appropriate electric function to be performed either immediately or with a delay or else not at all, depending on the state of the system to be driven. Prioritization of the individual switching functions, which is always associated with information losses, is not necessary.
[0014] If a plurality of electric functions are triggered simultaneously in the inventive device (e.g. by different operators on different actuating modules), the evaluation unit records corresponding changes to the associated electric codes. The programming of the evaluation unit is then used to decide whether the individual electric functions are being performed simultaneously, in succession or only in part.
[0015] In this context, the different electric functions which may be controlled by the individual actuating elements of the actuating modules may be both associated with various electric functional elements and may affect different functions of one and the same functional element, such as in the case of two actuating elements for changing the volume of a car radio to a higher or lower volume.
[0016] In this context, a suitable electric code may easily be produced by virtue of the electric assembly being one or more passive electric components having an electric value which is characteristic of the respective electric function. Thus, the electric assembly may be formed by a nonreactive resistor whose resistance value is characteristic of the electric function to be triggered. By way of example, a resistor having a resistance value of 10 ohms is used for a first electric function, a resistor having a resistance value of 100 ohms is used for a second electric function, a resistor having a resistance value of 1000 ohms is used for a third electric function etc.
[0017] Instead of a simple nonreactive resistor, a complex resistor or a frequency-dependent resistor (e.g., an inductor or a capacitor), and also a voltage-dependent or current-dependent resistor, a diode circuit, in particular a zener diode circuit, or else a voltage reference circuit are suitable as alternatives. In addition, the electric components may also be combined with one another to form an appropriate electric assembly.
[0018] Alternatively, the electric assembly for producing a characteristic electric code may be an active electric circuit, for example a circuit for producing a characteristic pulse train and/or a characteristic frequency. Naturally, a frequency mix or characteristic amplitude modulation are also suitable in this regard.
[0019] In one preferred embodiment of the invention, all the actuating modules with their electric actuating elements and the associated electric assemblies are incorporated into an integrated electric circuit supplied with current via two external electric connections. This produces a particularly simple circuit design for the device.
[0020] The electric assemblies used for assigning the individual actuating elements to particular electric functions are preferably arranged in the actuating modules themselves. In this context, the connection of the electric assemblies in parallel with the appropriate electric actuating elements means that only one corresponding electric assembly is required per electric function to be controlled. The electric assembly is accordingly arranged in one of the actuating modules from which the appropriate electric function may be triggered using an actuating element.
[0021] In this case, the electric assemblies are preferably distributed over the actuating modules such that an electric current may flow through the device meanderingly when the electric actuating elements are fully off, the current passing through all of the electric assemblies, and, in this context, each leg of the meandrous current path running through all the (parallel-connected) actuating modules. Such a circuit arrangement may be produced, for example, by alternately assigning each of the electric assemblies used for producing a characteristic electric code to one of the actuating modules whose actuating elements form an outer edge of the parallel circuit.
[0022] This embodiment of the invention allows simple monitoring of the lines of the circuit arrangement and, in particular, reliable detection of line breakage or plug contact interruption when the electric actuating elements are fully off. This is because, when the actuating elements are fully off, the current may flow through the electric assemblies connected in parallel therewith and may thus meander through the entire circuit arrangement.
[0023] In this context, the two external electric connections form the two end points of the meandrous current path, for which purpose the two connections are connected to a respective actuating element which is at a maximum distance (in relation to the flow of current) from the connections of the associated, parallel-connected electric assembly.
[0024] The electric actuating elements may be formed both by electric switches and by pushbutton switches or other suitable switching elements.
[0025] The inventive device may be used, in particular, in motor vehicles, one of the actuating modules being able to be arranged in the steering wheel of the vehicle in order to allow the driver to reach it easily.
[0026] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only, and are not restrictive of the invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] These and other features, aspects and advantages of the present invention will become apparent from the following description, appended claims, and the accompanying exemplary embodiments shown in the drawings, which are briefly described below.
[0028] [0028]FIG. 1 is a circuit diagram of a circuit according to the present invention, the circuit having two actuating modules which each have two actuating elements for triggering two different electric functions;
[0029] [0029]FIG. 2 is a circuit diagram of a circuit according to the present invention, the circuit having two actuating modules which each have N actuating elements for triggering N different electric functions;
[0030] [0030]FIG. 3 is a circuit diagram of a circuit according to the present invention, the circuit having M actuating modules which each have N actuating elements for triggering N different electric functions.
DETAILED DESCRIPTION
[0031] [0031]FIG. 1 shows a circuit arrangement for actuating electric functions which have two actuating modules A 1 and A 2 arranged at a physical distance from one another. In this case, the actuating modules A 1 , A 2 are in the form of touch sensor modules which are connected in parallel by means of terminals K 2 -K 4 and K 6 -K 8 and in which in each case two actuating or switching elements in the form of pushbutton switches 1 , 2 are connected one after the other (in series). Each of the two pushbutton switches in one of the actuating modules A 1 , A 2 is used to trigger a particular electric function, for example to control a radio, a window lifter or other electric functional elements in a motor vehicle.
[0032] Connected in parallel with each pushbutton switch 1 , 2 of the actuating modules, A 2 is a respective corresponding pushbutton switch 1 , 2 of the other actuating module A 2 or A 1 . The two parallel-connected pushbutton switches are each used to trigger the same electric function. The circuit arrangement shown in FIG. 1 thus makes it possible to trigger two electric functions firstly by actuating the two pushbutton switches 1 , 2 of the first actuating module Al and, alternatively, by actuating the pushbutton switches 1 , 2 of the second actuating module A 2 . Since the two actuating modules A 1 , A 2 are arranged at a physical distance from one another, this circuit arrangement allows the two electric functions mentioned to be actuated from two different locations. In a motor vehicle, for example, the first actuating module A 1 may be arranged within the grasp of the driver and the second actuating module A 2 may be arranged within the grasp of the passenger, so that either of the two may trigger the appropriate electric functions.
[0033] In accordance with the invention, each of the two electric functions which may be controlled using the circuit arrangement shown in FIG. 1 now has an associated electric assembly B 1 and B 2 , respectively, which is provided for producing an electric code which is characteristic of the respective electric function. The two electric assemblies B 1 and B 2 are arranged in parallel with the associated pushbutton switches 1 and 2 which may be used to trigger the appropriate electric function. In this case, one of the electric assemblies B 1 , B 2 is associated with the first actuating module A 1 and the other is associated with the second actuating module A 2 , specifically such that the connections of the appropriate electric assembly B 1 or B 2 are respectively situated on both sides of the associated pushbutton switch 1 or 2 in the respective actuating module A 2 or A 1 .
[0034] Actuating one of the pushbutton switches 1 or 2 in one of the actuating modules B 1 or B 2 results in the associated electric assembly B 1 or B 2 being shorted. This measurably influences the electric code produced by the appropriate electric assembly B 1 or B 2 .
[0035] Suitable electric assemblies may be selected from a multiplicity of electric circuits which may be used to produce a characteristic electric code. In the present case, for the sake of simplicity, it may be assumed that the electric assemblies B 1 and B 2 are two nonreactive resistors having different resistance values.
[0036] It is obvious that the nonreactive resistance of the entire circuit arrangement is characteristically changed when one of the pushbutton switches 1 , 2 is actuated to trigger a particular electric function. Another characteristic change in the nonreactive resistance of the circuit arrangement when two pushbutton switches 1 , 2 used for triggering different electric functions are actuated simultaneously.
[0037] The entire circuit arrangement may connected to a suitable voltage source by means of two external electric connections L 1 , L 2 . In this case, the first external connection L 1 is connected to the first actuating module A 1 and the second external connection L 2 is connected to the second actuating module A 2 , specifically such that the two connections L 1 , L 2 are respectively associated with a pushbutton switch 1 or 2 which is at a maximum distance from the associated electric assembly B 1 or B 2 . The external connections L 1 are connected to those pushbutton switches 1 , 2 of the actuating modules A 1 , A 2 which do not have an electric assembly B 1 , B 2 directly associated with them.
[0038] On the basis of the described arrangement of the electric assemblies B 1 , B 2 and of the external connections L 1 , L 2 in the circuit arrangement shown in FIG. 1, a current may flow through the entire circuit arrangement when the pushbutton switches 1 , 2 are fully off. For an assumed flow of current from the first connection L 1 to the second connection L 2 , the current would flow via the external connection point K 1 of the first actuating module A 1 , via the connection terminals K 2 and K 8 , the first electric assembly B 1 , the connection terminals K 7 and K 3 , the second electric assembly B 2 , the connection terminals K 4 and K 6 and also the external connection point K 5 of the second actuating module A 2 to the second external connection L 2 .
[0039] The electric current flows meanderingly from the first external connection L 1 to the second external connection L 2 , the three connecting lines which run via the terminals K 2 , K 8 ; K 3 , K 7 and K 4 , K 6 between the parallel-connected actuating modules A 1 , A 2 forming the legs of the meandrous current path, and each of these legs of the meandrous current path running through the two actuating modules A 1 and A 2 . This flow of current when the pushbutton switches 1 , 2 are fully off is made possible because the current may flow through the electric assemblies B 1 and B 2 arranged in parallel with these pushbutton switches.
[0040] When the pushbutton switches 1 , 2 are fully off, the circuit arrangement shown in FIG. 1 readily allows diagnosis of the line functions of the entire arrangement for possible line interruptions or detached plug connections at one of the terminals K 1 to K 8 . The signals produced by actuating the pushbutton switches 1 , 2 to trigger defined electric functions may be evaluated, and the circuit may be checked for correct line functions, by a normal electronic evaluation unit which is connected to the circuit arrangement shown in FIG. 1.
[0041] [0041]FIG. 2 shows a generalization of the exemplary embodiment from FIG. 1 to two actuating modules A 1 , A 2 which each have any desired number of series-connected pushbutton switches 1 , 2 , . . . , N−1, N, with the pushbutton switches provided for triggering the same electric function being respectively connected in parallel with one another in the two actuating modules A 1 , A 2 , and an electric assembly B 1 , B 2 , . . . , B N−1 , B N additionally being respectively arranged in parallel with these pushbutton switches, which electric assembly may be used to produce an electric code which is characteristic of the respective electric function to be triggered.
[0042] [0042]FIG. 2 reveals that the electric assemblies B 1 to B N are each alternately associated with the two actuating modules A 1 and A 2 , which means that, in this case as in the exemplary embodiment from FIG. 1, the current may meander from the first external connection L 2 through the entire circuit arrangement to the second external connection L 2 when the pushbutton switches 1 to N are fully off. The meandrous current profile is schematically shown in FIG. 2 by the line S in this case.
[0043] As in the case of the exemplary embodiment shown in FIG. 1, the first external connection L 1 is connected to the first touch sensor module A 1 , and the second external connection L 2 is connected to the second touch sensor module A 2 in this case too. This kind of arrangement of the external connections L 1 , L 2 is produced by virtue of the external connections L 1 , L 2 being respectively assigned to a pushbutton switch 1 or N which is at a maximum distance from the associated electric assembly B 1 or B N . This means that, when there is an even number of series-connected pushbutton switches 1 to N, the two external connections L 1 and L 2 are respectively associated with different actuating modules A 1 and A 2 . (Accordingly it is thus assumed in FIG. 2 that N is an even number.) By contrast, with an uneven number of pushbutton switches (and accordingly an uneven number of controllable electric functions), the two external connections L 1 and L 2 are respectively associated with the same actuating module.
[0044] [0044]FIG. 3 shows another generalization of the exemplary embodiment from FIG. 2, in which an arbitrary number of parallel-connected actuating modules A 1 , A 2 , . . . , A M-1 , A M having a respective arbitrary number of pushbutton switches 1 , 2 , . . . , N−1, N is provided. In this case, the pushbutton switches of all actuating modules used for triggering the same electric function are respectively connected in parallel. The appropriate function is identified using an electric assembly which is again arranged in parallel with these pushbutton switches and is provided for producing a characteristic electric code.
[0045] [0045]FIG. 3 reveals that the electric assemblies B 1 to B N are alternately respectively associated with the two actuating modules A 1 and A M forming the outer edge of the circuit arrangement comprising a plurality of parallel-connected actuating modules. This arrangement of the electric assemblies B 1 to B N and a suitable arrangement of the external connection terminals L 1 , L 2 means that, in this case, too, a current may flow meanderingly from the first external connection L 1 through the entire circuit arrangement to the second external connection L 2 when the pushbutton switches 1 to N are fully off. In this case, the two external connections L 1 , L 2 form the ends of the meandrous current path.
[0046] Given the disclosure of the present invention, one versed in the art would appreciate that there may be other embodiments and modifications within the scope and spirit of the invention. For example, all the circuits described above may also be produced using switches instead of pushbutton switches as actuating elements. Accordingly, all modifications attainable by one versed in the art from the present disclosure within the scope and spirit of the present invention are to be included as further embodiments of the present invention. The scope of the present invention is to be defined as set forth in the following claims. | A system for actuating electric functional elements comprising at least two physically separated actuating modules is provided. A defined electric function may be selectively triggered by any of the actuating modules. Each actuating module may have an electric actuating element for triggering the electric function and both actuating elements for triggering the electric function are connected parallel to each other. One electric subassembly may be connected in parallel to both actuating elements, whereby the subassembly is used to produce a characteristic electric code for the electric function which is to be triggered. A line controlled sensor circuit can thus be produced without any sensor prioritization. | 4 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates an apparatus and method using expandable tubulars to complete a well. More particularly, the invention relates to the installation of an expandable sand screen. More particularly still, the invention relates to a single trip installation process to set a liner hanger in a wellbore and then expand a sand screen.
[0003] 2. Description of the Related Art
[0004] Hydrocarbon wells are typically formed with a central wellbore that is supported by steel casing. The casing lines a borehole formed in the earth during the drilling process. An annular area formed between the casing and the borehole is filled with cement to further support and form the wellbore.
[0005] Some wells are produced by perforating the casing of the wellbore at selected depths where hydrocarbons are found. Hydrocarbons migrate from the formation through the perforations and into the wellbore where they are usually collected in a separate string of production tubing for transportation to the surface of the well. In other instances, a lower portion of a wellbore is left open and not lined with casing. This “open hole” completion permits hydrocarbons in an adjacent formation to migrate directly into the wellbore where they are subsequently raised to the surface, possibly through an artificial lift system.
[0006] Open hole completions can provide higher production than cased hole completions and they are frequently utilized in connection with horizontally drilled boreholes. However, open hole completions leave aggregate material, including sand, free to invade the wellbore. Sand entering an open hole wellbore causes instability within the open hole which enhances the risk of complete collapse. Sand production can also result in premature failure of artificial lift and other downhole and surface equipment due to the abrasive nature of sand. In some instances, high velocity sand particles can contact and erode lining and tubing.
[0007] Sand can also be a problem where casing is perforated to collect hydrocarbons. Typically, casing is perforated with a perforating assembly or “guns” that are run into a wellbore and fired to form the perforations. Thereafter, the assembly is removed and a separate assembly is installed to collect the migrating hydrocarbons. The perforations also create a passageway for aggregate material, including sand to enter the wellbore. As with an open wellbore, sand entering the cased wellbore can interfere with the operation of downhole tools, clog screens and damage components, especially if the material enters the wellbore at a high velocity.
[0008] To control particle flow into a wellbore, well screens are often employed downhole. Conventional wellscreens are placed adjacent perforations or unlined portions of the wellbore to filter out particulates as production fluid enters a tubing string. One form of well screen recently developed is the expandable sand screen (ESS). In general, the ESS is constructed of different composite layers, including a filter media.
[0009] A more particular description of an ESS is found in U.S. Pat. No. 5,901,789, which is incorporated by reference herein in its entirety. That patent describes an ESS which consists of a perforated base pipe, a woven filtering material, and a protective, perforated outer shroud. Both the base pipe and the outer shroud are expandable, and the woven filter is typically arranged over the base pipe in sheets that partially cover one another and slide across one another as the sand screen is expanded. The ESS is expanded by a cone-shaped object urged along its inner bore or by an expander tool having radially outward extending rollers that are fluid powered from a tubular string. Using expansion means like these, the ESS is subjected to outwardly radial forces that urge the expanding walls against the open formation or parent casing. The components of the ESS are expanded past their elastic limit, thereby increasing the inner and outer diameter of the tubular.
[0010] A major advantage to the ESS in an open wellbore is that once expanded, the walls of the wellbore are supported by the ESS. Additionally, the annular area between the screen and the wellbore is mostly eliminated, and with it the need for a gravel pack. A gravel pack is used with conventional well screens to fill an annular area between the screen and wellbore and to support the walls of the open hole. With an ESS, the screen is expanded to a point where its outer wall places a stress on the walls of the wellbore, thereby providing support to the walls of the wellbore to prevent dislocation of particles. Solid expandable tubulars are oftentimes used in conjunction with an ESS to provide a zonal isolation capability. In addition to open wellbores, the ESS is effectually used with a perforated casing to control the introduction of particulate matter into the cased wellbore via the perforations.
[0011] While an ESS can reduce or eliminate the inflow of particles into a wellbore, the screen must be installed and expanded in order to operate effectively. Any delay in the installation permits additional time for sand to enter the wellbore and the time period is especially critical between the formation of perforations in a casing wall and the expansion of screen against the perforations. The delays are especially critical if the newly formed wellbore is placed in an over balanced condition prior to expanding the ESS. An overbalanced condition permits fluids to enter the formations and hamper later production of hydrocarbons.
[0012] In current installation procedures of ESS the operator makes two trips downhole. In the first trip, the operator sets a liner hanger to secure the ESS in the wellbore. After returning from the first trip downhole, the operator must make a second trip with an expansion tool in order to expand the ESS.
[0013] There are several disadvantages to a multiple trip installation procedure. The biggest disadvantage relates to expensive downtime necessary to make both trips. Also, a delay between the first and second trips can cause well control problems due to fluid loss. For example, pressurized fluid in the wellbore used to actuate various mechanical components during the installation process can enter the formations causing formations to clog-up or collapse, restricting the flow of hydrocarbons. In addition, loss of drilling fluid increases the completion cost of the well. In other instances, a delay between perforating a casing and expanding a sand screen against the perforations increases the likelihood that solids from the formations will enter the wellbore. In addition to the foregoing, packers used to fix an ESS in a wellbore often have a relatively small inside diameter. These packer-like components remain in the wellbore and can cause access problems for remedial work required below the suspension device.
[0014] There is a need therefore, for an apparatus to reduce the time needed to install an expandable sand screen in a wellbore. There is a further need to set a sand screen in a wellbore and then expand the sand screen in a single trip. There is a further need for a method and apparatus to facilitate the setting of a liner hanger in a wellbore prior to the expansion of an ESS. Still further, there is a need for an apparatus to minimize the exposure to formation solids before expanding the ESS There is a further need for a single trip ESS apparatus that uses a liner hanger that does not restrict access within the wellbore after the ESS is expanded.
SUMMARY OF THE INVENTION
[0015] The present invention includes a method and apparatus for installing and expanding an ESS in a wellbore in a single trip. In one aspect of the invention, a liner hanger and expandable screen are provided and are run into the wellbore with an expansion tool and work string. After the hanger is set, the expansion tool is used to expand the screen. In another aspect, an annular area within the apparatus is utilized in order to set the hanger with pressurized fluid. Thereafter, cup packers used in sealing the annulus are lifted from the liner prior to expanding the screen. The expansion tool and work string are then removed leaving the expanded ESS and hanger in the wellbore.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] So that the manner in which the above recited features, advantages and objects of the present invention are attained and can be understood in detail, a more particular description of the invention, briefly summarized above, may be had by reference to the embodiments thereof which are illustrated in the appended drawings.
[0017] It is to be noted, however, that the appended drawings illustrate only typical embodiments of this invention and are therefore not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
[0018] [0018]FIG. 1 is a partial cross section view of an expansion tool assembly.
[0019] [0019]FIG. 2 is a partial cross section view of a liner and sand screen assembly.
[0020] [0020]FIG. 3A illustrates an upper portion of the expansion tool assembly and liner assembly.
[0021] [0021]FIG. 3B illustrates a middle portion of the expansion tool assembly and liner assembly.
[0022] [0022]FIG. 3C illustrates a lower portion of the expansion tool assembly and liner assembly.
[0023] [0023]FIG. 4 illustrates an annular area formed between the expansion tool assembly and liner assembly.
[0024] [0024]FIG. 5 illustrates the expansion tool assembly and liner assembly after a first ball has been dropped into a lower ball seat and sleeve.
[0025] [0025]FIG. 6 illustrates the expansion tool assembly and liner assembly after slips have been set to fix the liner in the wellbore.
[0026] [0026]FIG. 7 illustrates the lower ball seat and sleeve shifted to a second position relative to the liner assembly to reestablish a fluid pathway through the bore of the tool assembly.
[0027] [0027]FIG. 8 illustrates an upper ball seat and sleeve in a second position relative to the liner assembly.
[0028] [0028]FIG. 9 illustrates an upward movement of the tool assembly in relation to the liner assembly.
[0029] [0029]FIG. 10 illustrates the tool assembly lifted out of the liner assembly permitting dogs to clear the top of the liner assembly.
[0030] [0030]FIG. 11 is an enlarged view of FIG. 10, showing the expansion tool assembly suspended by dogs at the upper end of the liner assembly.
[0031] [0031]FIG. 12 illustrates downward movement of the expansion tool assembly in relation to the liner assembly and dogs in order to expand the ESS.
[0032] [0032]FIG. 13 illustrates the rotary expander tool expanding the sand screen.
[0033] [0033]FIG. 14 illustrates the expansion tool assembly as it is removed from the liner assembly after the screen has been expanded.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0034] The present invention provides a method and apparatus to install an ESS in a wellbore and to expand the screen in a single trip. The invention includes a hanger which is used to set the screen in a wellbore before the screen is expanded by an expansion tool in the same trip into the wellbore.
[0035] [0035]FIG. 1 illustrates a partial cross section view of an expansion tool assembly 100 and FIG. 2 illustrates a partial cross section view of a liner and sand screen assembly 200 . While a portion of liner or non slotted tubular is shown in FIG. 1, it will be understood that the invention can be used with a section of liner above an expandable sand screen or with only a section of expandable sand screen. Further, while the Figures illustrate the invention in use with an open, noncased wellbore, it will be further understood that the methods and apparatus disclosed are equally usable in a cased wellbore with perforations formed therein. FIGS. 1 and 2 show the tool assembly 100 and the liner assembly 200 separated to illustrate the major components of each assembly. In use, the expansion tool assembly 100 is housed within assembly 200 . FIGS. 3 to 14 will fully describe the interface between the tool assembly 100 and the liner assembly 200 . In FIG. 1, the expansion tool assembly 100 includes a dust cover 110 at the upper end to seal the end of assembly 200 and to prevent wellbore contaminates from entering the liner. The assembly 100 further includes a carry nut 115 with male threads 130 that mates with female threads 205 near the top of the liner assembly 200 to secure the tool assembly 100 in the liner assembly 200 .
[0036] A carrying tool 125 is located at the lower portion of the assembly 100 to facilitate removal of the tool assembly 100 from the liner assembly 200 after expanding a screen 215 . A mud motor 120 is located adjacent to a rotary expander tool 105 at the lower end of the tool assembly 100 . In operation, fluid is pumped from the surface of the well down a bore of the tool assembly 100 and into the mud motor 120 . The mud motor 120 uses the fluid to rotate the rotary expander tool 105 , thereby expanding the screen 215 disposed at the lower end of the liner assembly 200 . A hydraulic liner hanger assembly 210 is located at the upper portion of the liner assembly 200 to secure the assembly 200 in a wellbore.
[0037] [0037]FIG. 3A illustrates the upper section of the expansion tool assembly 100 and the liner assembly 200 . The dust cover 110 sits on top of the liner assembly 200 . The carry nut 115 is shown threaded into the liner assembly 200 . An upper ball seat and sleeve 305 is located below the carry nut 115 and is secured to the tool assembly 100 by a first shear pin 310 . A first circumferential groove 330 is used in a later step to reestablish a fluid passageway in the bore of the assembly 100 . The liner hanger assembly 210 includes a plurality of cones 325 and slips 328 disposed about the circumference of the liner assembly 200 . The slips 328 include a tapered surface that mates with a corresponding tapered surface on the cone 325 . During the setting of the liner assembly 200 in the wellbore, the cones 325 are used to displace the slips 328 radially outward as an axial force is applied to the slip 328 in direction of the cones 325 .
[0038] [0038]FIG. 3B illustrates a middle section of the expansion tool assembly 100 and the liner assembly 200 . A lower ball seat and sleeve 385 is located below the slips 328 (not shown) and is secured in the tool assembly 100 by a second pin 380 . Below the lower ball seat and sleeve 385 is a second circumferential groove 340 which is used in a later step to reestablish a fluid passageway down the bore of the assembly 100 . A plurality of swab cups 390 used to seal an annular area between the tool assembly 100 and the liner assembly 200 are located below the second shear pin 380 . Expandable dogs 350 , shown in the retracted position, are located below the swab cups 390 . The dogs 350 are used to hold a portion of the tool assembly 100 above the top surface of the liner assembly 200 as will be described herein. A third shear pin 375 is located between the swab cups 390 and the dogs 350 to temporarily hold the dogs 350 and cups 390 around the work string. FIG. 3C illustrates a lower portion of the tool assembly 100 and the liner assembly 200 . As shown, the expander tool 105 on the tool assembly 100 is housed at an upper end of the expandable sand screen 215 . The screen 215 includes a funnel shaped opening to facilitate entry into the screen 215 by the expander tool 105 .
[0039] [0039]FIG. 4 illustrates an annular area formed between the expansion tool assembly 100 and liner assembly 200 . The annulus is created upon insertion of the tool assembly 100 into the liner assembly 200 . The annulus is separated into an upper annulus 355 , a middle annulus 360 and a lower annulus 365 . The carry nut 115 separates the upper annulus 355 from the middle annulus 360 . The swab cups 390 separate the middle annulus 360 from the lower annulus 365 . The middle annulus 360 serves as a fluid pathway between a first port 315 and a second port 320 which is later used to set the slips 328 that fix the liner 200 in the wellbore.
[0040] [0040]FIG. 5 illustrates the expansion tool assembly 100 and liner assembly 200 after a first ball 345 has been dropped into a lower ball seat and sleeve 385 . The view further illustrates, the liner assembly 200 prior to setting the slips 328 . As shown, there is no contact between the teeth 335 on the slips 328 and a casing 475 . At a later point the tapered portion of the slips 328 will be urged up cones 325 by a plurality of longitudinal members 415 that are connected to an annular piston 395 . The piston 395 has a top O-ring 405 and a bottom O-ring 410 for creating a fluid tight seal.
[0041] [0041]FIG. 6 illustrates the expansion tool assembly 100 and liner assembly 200 after the slips 328 have been set to fix the liner 200 in the wellbore. Ball 345 blocks fluid flow through the bore of the tool assembly 100 , thereby redirecting the fluid flow to a first aperture 420 formed in the sleeve 305 . The first aperture 420 is aligned with the first port 315 formed in a wall of the tool assembly 100 to form a fluid passageway to the annulus 360 . A first arrow 425 illustrates the fluid flow into the annulus 360 and a second arrow 430 illustrates fluid flow from the annulus 360 through a second port 320 . The fluid exiting the second port 320 acts on the piston 395 , thereby urging the piston 395 upward in the direction of the cones 325 . The longitudinal members 415 connecting the slips 328 to the piston 395 urges the slips 328 up the tapered portion of the cones 325 , thereby expanding the slips 328 radially outward in contact with the casing 475 . The teeth 335 formed on the outer surface of the slips 328 “bite” into the casing surface to hold the liner assembly 200 in position in the wellbore. FIG. 6 illustrates that the inner diameter of the assembly 200 is largely unobstructed by the set hanger and the bore is open to the passage of tools downhole.
[0042] [0042]FIG. 7 illustrates the lower ball seat and sleeve 385 shifted to a second position relative to the liner assembly 200 to reestablish a fluid pathway through the bore of the tool assembly 100 . After the liner assembly 200 is set in the casing 475 , the fluid becomes pressurized acting against the first ball 345 which is housed in the lower ball seat and sleeve 385 . At a predetermined pressure, pin 380 is sheared allowing the ball seat and sleeve 385 to shift downward to a second position. In the second position, a first by pass port 435 formed in the sleeve 385 aligns with the second circumferential groove 340 to reestablish a fluid pathway through the bore of the tool assembly 100 as illustrated by an arrow 432 .
[0043] [0043]FIG. 8 illustrates the upper ball seat and sleeve 305 in a second position relative to the liner assembly 200 to establish a fluid pathway through the bore of the tool assembly 100 . The flow path is established in order to provide a source of pressurized fluid to the expander tool 105 in order to expand the sand screen 215 at a lower end of the liner assembly 200 . The second ball 440 is dropped into the tool assembly 100 and lands on an upper seat and sleeve 305 which is held in place by pin 310 . Fluid thereafter becomes pressurized acting against the second ball 440 . At a predetermined pressure the pin 310 is sheared allowing upper ball seat and sleeve 305 to shift downward to the second position. In the second position, the ball seat and sleeve 305 aligns a second bypass port 450 with the first circumferential groove 330 to provide a fluid passage way. The fluid flow down the bore of the assembly 100 bypasses the ball 440 as illustrated by arrow 445 . In addition to reestablishing flow down the bore of the tool assembly 100 , the seat and sleeve 305 also misaligns the first aperture 420 and the first port 315 , thereby blocking fluid communication into middle annulus 360 .
[0044] [0044]FIG. 9 illustrates an upper movement of the tool assembly 100 in relation to the liner assembly 200 . After the liner assembly 200 has been set in the wellbore, the expansion tool 100 with the carry nut 115 is rotated clockwise, thereby removing the male threads 130 on the carry nut 115 from the female threads 205 on the liner assembly 200 . The tool assembly 100 is then lifted axially upward in relation to the liner assembly 200 as illustrated by a directional arrow 460 . A shoulder 455 on the tool assembly 100 urges the carry nut 115 upward with the tool assembly 100 as the tool assembly 100 is partially lifted from the liner assembly 200 .
[0045] [0045]FIG. 10 illustrates the tool assembly 100 lifted out of the liner assembly 200 permitting dogs 350 to clear the top of the liner assembly 200 . To prepare the tool assembly 100 to expand the screen 215 , the expansion tool assembly 100 is partially pulled from the liner assembly 200 exposing the dust cover 110 , carry nut 115 , swab cups 390 and dogs 350 . Upon removal from the liner assembly 200 , the dogs 350 expand outward. Pin 375 holds the various components together.
[0046] [0046]FIG. 11 is an enlarged view of FIG. 10, showing the expansion tool assembly 100 suspended by dogs 350 at the upper end of the liner assembly 200 . After the tool assembly 100 is lifted from the liner assembly 200 and the dogs 350 expanded, it is then lowered until the expanded dogs 350 rest on top of the liner assembly 200 . As shown, the dogs 350 are outwardly biased members that are constructed and arranged to ride along a tubular surface and then to extend outward when pulled out of contact with the tubular. With the components in position shown in FIG. 11, the expander tool 105 is ready to be lowered into the ESS 215 .
[0047] [0047]FIG. 12 illustrates downward movement of the expansion tool assembly 100 in relation to the liner assembly 200 and dogs 350 in order to expand the expandable sand screen 215 . A downward force is placed the tool assembly 100 , thereby exerting pressure on the pin 375 . At a predetermined pressure, the pin 375 is sheared, thereby allowing the mud motor 120 and expander tool 105 along with the carrying tool 125 to drop down into the liner assembly 200 while the dust cover 110 , the carry nut 115 , the swab cups 390 and the dogs 350 remain above the top of the liner assembly 200 . The tool assembly 100 is lowered until the expander tool 105 comes in contact with the ESS 215 .
[0048] [0048]FIG. 13 illustrates the rotary expander tool 105 expanding the sand screen 215 . Fluid is pumped from the surface of the well down the bore of tool assembly 100 into the mud motor 120 . The mud motor 120 provides rotational force to the expander tool 105 while causing radially extending rollers to extend outwards, thereby expanding the sand screen 215 into the borehole. FIG. 13 illustrates expanding a sand screen 215 in a vertical open hole. However, this invention is not limited to the one shown but rather can be used in many different completion scenarios such as casing that has been perforated.
[0049] [0049]FIG. 14 illustrates the expansion tool assembly 100 as it is removed from the liner assembly 200 after the ESS 215 has been expanded. As the tool assembly 100 is pulled upward, a top surface 470 of the carrying tool 125 contacts a bottom surface 465 of the dogs 350 , thereby urging the dogs 350 off the top of the liner assembly 200 . The entire tool assembly 100 is moved up out of the liner assembly 200 and then out of the wellbore. The ESS 215 allows hydrocarbons to enter the wellbore as it filters out sand and other particles. The expanded sand screen 215 is connected to production tubing at an upper end, thereby allowing the hydrocarbons travel to the surface of the well. In addition to filtering, the sand screen 215 preserves the integrity of the formation during production.
[0050] While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. | The present invention includes a method and apparatus for setting a liner in a wellbore and then expanding a screen in the wellbore in a single trip. In one aspect of the invention, a liner and expandable screen is provided with a slip assembly to fix the liner in the wellbore. An expansion tool and work sting is run into the wellbore in the liner. After the liner is set, the expansion tool is used to expand the screen. In another embodiment, an annular area between the expansion tool and work string is utilized in order to set the slips. Thereafter, cup packers used in forming the annulus are lifted from the liner prior to expanding the screen. | 4 |
DESCRIPTION OF TERMS
SPROCKET PITCH: The distance between the center of one chain pin to the center of the adjacent chain pin.
SPROCKET TOOTH ROOT DIAMETER: Twice the distance from the bottom of one sprocket tooth to the center of the sprocket.
SPROCKET PITCH DIAMETER: The sprocket tooth root, diameter plus the diameter of one chain pin or bushing. (if the chain has bushings).
SPROCKET OUTSIDE DIAMETER: Twice the distance from the outer point of sprocket tooth to center of sprocket.
SPROCKET TOOTH SHANK: The part of tooth extending towards center of sprocket to secure tooth to adaptor disc.
It is apparent from the foregoing that the present invention provides an adjustable pitch sprocket effecting equal pitch adjustment of all sprocket teeth simultaneously, with gradual adjustment over a wide range being obtainable. Moreover, the tapered shank adjustment bolts assure positive and gradual adjustment without danger of being broken. The adjustable pitch sprocket may be used in applications where existing sprockets fit splined shafts or have expensive hubs, simply by adapting the existing hub to the adaptor disc, and may be substituted for existing sprockets without the necessity of replacing the existing chain carried by the sprocket.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 shows a front view of an adjustable pitch sprocket assembly;
FIG. 2 shows a cross sectional view of FIG. 1;
FIG. 3 shows a rear view of an adjustable pitch sprocket assembly;
FIG. 4 shows a front view of an adaptor disc;
FIG. 5 shows a side or end view of an adaptor disc with a sectional view of a hub;
FIG. 6 shows a front view of a pitch adjustment disc;
FIG. 7 shows a front view of an adjustable tooth;
FIG. 8 shows a cross sectional view of FIG. 7; and
FIG. 9 shows a tapered shank adjustment bolt.
DETAILED DESCRIPTION
The sprocket assembly would consist of five different parts: an adaptor disc (or plate), shown in FIG. 4, a pitch adjustment disc (or ring), shown in FIG. 6, individual adjustable teeth, shown in FIG. 7, tapered shank adjustment bolts shown in FIG. 9, and standard bolts, which may be used to secure teeth to the adaptor disc.
The teeth would be secured to the adaptor disc with bolts. The teeth would be mounted individually, with bolts through the slotted bolt holes 6 in the adaptor disc allowing the teeth to be adjusted from the center of the disc outward, thereby increasing the pitch diameter. The adjustment would be accomplished with an adjustment disc of the type shown in FIG. 6. The adjustment disc would have a number of protruding areas 7 (one or two each) equal to the number of teeth. The tooth shorter shank 9 would have an inner surface 8 on one side of the adaptor disc bearing against the pitch adjustment disc protruding areas 7 (i.e., against the adjustment disc cam surface). When rotated, the adjustment disc forces all teeth outward simultaneously. This action increases the pitch diameter of all teeth and in turn increases the distance (known as the sprocket pitch) between all teeth equally. The adjustment disc and the adaptor disc will have a series of bolt holes 10, 11 on the same diameter bolt circle. Each of these holes for one half of the bolt circle would be offset (as to distance apart by 25 percent of the hole size). That is, the bolt holes 10, 11 along each 180 degree arc, are arcuately offset from one another due to the unequal arcuate spacing between the bolt holes through one of the discs. When the adjustment bolts shown in FIG. 9 are inserted in the mismatched holes 10, 11 and the nuts tightened on the bolts, the adjustment disc will be forced to rotate (by 25 percent of the hole diameter distance) by the action of the axially extending wedge surface provided by the conical cam surface around the shank of the tapered adjustment bolt, thereby adjusting all teeth. The holes on the one half of the adjustment disc will be exactly 180 degrees from the opposite holes. To adjust the sprocket pitch it is necessary to loosen all bolts in all teeth, insert. Insert two adjustment bolts in through both pairs of opposite holes 10, 11 that are 25 percent mismatched, tighten the nuts on the two adjustment bolts until the sprocket is in pitch with the chain, and then tighten all tooth shank bolts. If one hole adjustment is not sufficient to adjust the pitch, remove the two adjustment bolts and insert them in the next adjoining holes 10, 11 which have been brought within 25 percent of alignment during the previous hole alignment. This procedure may be continued until the sprocket is adjusted to the correct pitch to match the chain's pitch, or the total adjustment allowed is accomplished.
The teeth, shown in FIG. 7, would be secured to the adaptor disc, shown in FIG. 4, with standard bolts. The teeth would be mounted individually, with bolts through the slotted bolt holes, 6 in the adaptor disc, shown in FIG. 4, allowing the teeth to be adjusted from the center of the disc outward (or radially), thereby increasing the pitch diameter. The adjustment would be accomplished with an adjustment disc, shown in FIG. 6. The adjustment disc would have a number of protruding areas 7 (one or two each) for each of the teeth. The shorter shank would have an inner surface 8 on one side of the adaptor disc, bearing against the pitch adjustment disc protruding area 7. When rotated, the adjustment disc forces all teeth outward simultaneously. This action increases the pitch diameter of all teeth and in turn increases the distance (known as the sprocket tooth pitch) between all teeth equally. The adjustment disc and the adaptor disc will have a series of bolt holes, 10 & 11 on the same diameter bolt circle. Each of these holes for one half of the bolt circle would be offset, (as to distance apart by 25 percent of the hole size). When the adjustment bolts, shown in FIG. 9, are inserted in the mismatched holes, 10 & 11 and the nuts tightened on the bolts, the adjustment disc will be forced to rotate (by 25 percent of the hole diameter distance), thereby adjusting all teeth. The holes, 10 on the one half of the adjustment disc will be exactly 180 degrees from the opposite holes. To adjust the sprocket pitch it is necessary to loosen all bolts in all teeth insert two adjustment bolts in opposite holes, 10 & 11 that are 25 percent mismatched, tighten the nuts on the two adjustment bolts until the sprocket is in pitch with the chain, and then tighten all tooth shank bolts. The outer bolts are secured through holes 6 and 12. The inner bolts are secured through holes 6, 13, and 14. If one hole is not sufficient to adjust pitch, remove the two adjustment bolts and insert them in the next adjoining holes, 10 & 11 which have been brought within 25 percent of alignment from the previous hole alignment. This procedure may be continued until the sprocket is adjusted to the correct pitch to match the chain pitch, or the total adjustment allowed is used up.
It is apparent from the foregoing that the present invention provides an adjustable pitch sprocket effecting equal pitch adjustment of all sprocket teeth simultaneously, with gradual adjustment over a wide range being obtainable. Moreover, the tapered shank adjustment bolts assure positive and gradual adjustment without danger of being broken. The adjustable pitch sprocket may be used in applications where existing sprockets fit splined shafts or have expensive hubs, simply by adapting the existing hub to the adaptor disc, and may be substituted for existing sprockets without the necessity of replacing the existing chain carried by the sprocket. | As the sprocket teeth wear, the pitch of the sprocket teeth decreases. As the chain wears, the pitch of the chain increases, this causes the rate of wear to increase. A sprocket after being in use for 1000 hours may have four times the wear as it had after 500 hours use. This invention, a sprocket with simultaneous adjustable pitch of the teeth, will keep the wear rate to the minimum. | 5 |
BACKGROUND OF THE INVENTION
[0001] The invention relates to a method for insulating stator windings for rotating electrical machines, in particular, direct current machines and alternating current machines.
[0002] In general, such electrical machines are provided with a stator and a rotor in order to convert mechanical energy into electrical energy (i.e., a generator) or, vice versa, to convert electrical energy into mechanical energy (i.e., an electric motor). Depending on the operating status of the electrical machine, voltages are generated in the conductors of the stator windings. This means that the conductors of the stator windings must be appropriately insulated in order to avoid a short circuit.
[0003] Stator windings in electrical machines can be constructed in different ways. It is possible to bundle several individual conductors that are insulated against one another and to provide the conductor bundle created in this manner, often called a conductor bar, with a so-called main insulation. To produce the stator windings, several conductor bars are connected with each other at their frontal faces. This connection can be made, for example, with a metal plate to which both the respective insulated individual conductors of the first conductor bar as well as the respective insulated individual conductors of the second conductor bar are connected in a conductive manner. The individual conductors of the conductor bar are therefore not insulated from each other in the area of the metal plate.
[0004] Alternatively to bundling the individual conductors into conductor bars, a long, insulated individual conductor is wound to a flat, oval coil that is called an original coil form, or “fish.” In a subsequent process, the so-called spreading, the original coil forms are transformed into their final shape and built into the stator.
[0005] With both of the above-described manufacturing techniques, both round and rectangular individual conductors can be used. The conductor bars or original coil forms produced from several individual conductors for the stator windings again may have round or rectangular cross-sections. The invention at hand preferably looks at conductor bars or original coil forms with a rectangular crosssection that were made from rectangular individual conductors. The conductor bars may be manufactured either as Roebel transpositions, i.e., with individual conductors twisted around each other, or not as Roebel transpositions, i.e., with untwisted individual conductors that extend parallel to each other.
[0006] According to the state of the art, mica paper that has been reinforced with a glass fabric carrier for mechanical reasons, is usually wrapped tape-like around the conductor in order to insulate the stator windings (e.g., conductor bars, original coil forms, coils). The wound conductor, which may also be shaped after being taped, is then impregnated with a hardening resin, resulting in a duroplastic, non-meltable insulation. Also known are mica-containing insulations with a thermoplastic matrix that are also applied to the conductor in the form of a tape, such as, for example, asphalt, shellac (Brown Boveri Review Vol. 57, p. 15: R. Schuler: “Insulation Systems for High-Voltage Rotating Machines”), polysulfone and polyether ether ketone (DE 43 44044 A1). These insulations can be plastically reshaped when the melting temperature of the matrix is exceeded.
[0007] The insulations of stator windings that have been applied by wrapping have the disadvantage that their manufacture is time-and cost-intensive. In this context, special mention should be made of the wrapping process and impregnation process since they cannot be significantly accelerated any further because of the physical properties of the mica paper and impregnation resin. This manufacturing process is particularly prone to defects especially in the case of thick insulations, if the mica paper adapts insufficiently to the stator winding. In particular, an insufficient adjustment of the wrapping machine after wrapping the stator winding may result in wrinkles and tears in the mica paper, for example, because of a too steep or flat angle between the mica paper and the conductor, or because of an unsuitable static or dynamic tensile force acting on the mica paper during the wrapping. An excessive tape application may also result in overlaps that prevent uniform impregnation of the insulation in the impregnation tool. This may create a locally or generally defective insulation with reduced short-term or long-term stability. This significantly reduces the life span of such insulations for stator windings.
[0008] In addition, manufacturing processes for encasing conductor bundles are known from cable technology, whereby conductor bundles with a round cross-section are always encased with a thermoplast or with elastomers in an extrusion process. Document US-A-5,650,031, which is related to the same subject matter as WO 97/11831, describes such a process for insulating stator windings in which the stator winding is passed through a central bore of an extruder. The stator winding, which has a complex shape, is hereby encased simultaneously with an extruded thermoplastic material at each side of the complex form, especially by coextrusion.
[0009] Also known from cable technology are polymeric insulations applied to the cables using a hot shrink-on technique. This relates to prefabricated sleeves with a round cross-section of curing thermoplasts, elastomers, polyvinylidene fluoride, PVC, silicone elastomer, or Teflon. After fabrication, these materials are stretched in their warm state and cooled. Once cooled, the material retains its stretched shape. This is accomplished, for example, because crystalline centers that fix the stretched macromolecules are formed. After repeated heating beyond the crystalline melting point, the crystalline zones are dissolved, whereby the macromolecules return to their unstretched state, and the insulation is in this way shrunk on. Also known are cold shrink-on sleeves that are mechanically stretched in their cold state. In the stretched state, these sleeves are pulled over a support structure that holds the sleeves permanently in the stretched state. Once the sleeves have been pushed and fixed over the components to be insulated, the support structure is removed in a suitable manner, for example, by pulling a spiral, perforated support structure out. But such shrink-on techniques cannot be used for stator windings with a rectangular cross-section since the sleeves with their round cross-section easily tear along the edges of the rectangular conductors, either immediately after shrinking or after strained briefly while the electrical machine is operated, because of the thermal and mechanical stresses.
[0010] Even while the stator windings are being manufactured, especially during the bending and handling of the conductors, particularly during installation into the stator, the insulation must be able to bear a significant high mechanical stress which could damage the insulation of the stator windings. The insulation of the stator winding conductors is also exposed to a combined stress during operation of the electrical machine. On the one hand, the insulation is dielectrically stressed between the conductor, to which is a high voltage is applied, and the stator, by a resulting electrical field. On the other hand, the heat generated in the conductor exposes the insulation to a thermal alternating stress, whereby a high temperature gradient is present in the insulation while the machine passes through the respective operating states. Because the materials involved expand differently, mechanical alternating stresses also occur. This results both in a shearing stress of the bond between conductor and insulation and a risk of abrasion at the interface between insulation and slot wall of the stator. Because of these high stresses, the insulation of the stator windings may tear, resulting in a short circuit. Consequently, the entire electrical machine will fail, and the repair will be time-and cost-intensive.
SUMMARY OF THE INVENTION
[0011] The invention involves a process for insulating stator windings for rotating electrical machines, whereby insulated stator windings are produced that ensure the insulation of the stator winding over the intended life span of the electrical machine.
[0012] The invention utilizes the fact that the elastomer is highly elastic, yet is able to withstand high thermal and electrical stresses. In the case of higher thermal stresses, silicone elastomer can be used advantageously.
[0013] Elastomers as a material for the main insulation promote the application of an injection molding process. The individual parts of the injection mold are preferably constructed in a modular manner for covering the conductor bar geometries that occur more frequently.
[0014] It is preferred that the conductor bars are centered with spacer elements or adjustable mandrels in the casting mold. The centering must be accomplished in such a way that the void between conductor bar and casting form has the same height at any point. The scope of this invention also includes providing main insulations with different thicknesses around the conductor bar. A uniform thickness of the main insulation is, however, a preferred embodiment.
[0015] In another method according to the invention, an internal corona shielding is applied between the insulating layer and the conductor surface. This is accomplished, for example, with a suitable injection molding process, in which several individual layers can be placed on top of each other.
[0016] In a particularly preferred method, the conductor bars are only brought into their final shape after being encased with the elastomer. The bending of the involutes greatly stretches the applied insulation. The use of elastomer according to the invention is hereby found to be particularly advantageous, since it reduces or even completely avoids the mechanical, electrical or thermal injury to the insulation that is being stressed by bending.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] The invention is described in more detail below with reference to the drawings, using exemplary embodiments.
[0018] [0018]FIG. 1 a shows a cross-section through an injection mold in which two conductor bars are centered by spacer elements in the casting mold;
[0019] [0019]FIG. 1 b shows a longitudinal section through an injection mold in which one conductor bar is centered by spacer elements in the casting mold;
[0020] [0020]FIG. 1 c shows a longitudinal section through an injection mold in which one conductor bar is centered by spacer elements with different shapes in the casting mold;
[0021] [0021]FIG. 2 a shows a cross-section through an injection mold in which two conductor bars are centered by adjustable mandrels in the casting mold;
[0022] [0022]FIG. 2 b shows a longitudinal section through an injection mold in which one conductor bar is centered by adjustable mandrels in the casting mold;
[0023] [0023]FIG. 3 shows a detail of the adjustable mandrel in FIG. 2 b ; and
[0024] [0024]FIG. 4 shows a device for bending the insulated conductor bars.
[0025] The figures only show the elements and components essential for understanding the invention. The shown methods and devices according to the invention therefore can be supplemented in many ways or can be modified in a manner obvious to one skilled in the art, without abandoning or changing the concept of the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0026] [0026]FIG. 1 a shows the cross-section through an injection mold 30 in which two conductor bars 2 are centered by spacer elements 40 in the mold chambers. The injection mold 30 consists of a cover 32 and a bottom plate 34 . Between two mold chambers, a center part 36 is provided, which forms a side wall of each of one of the adjoining mold chambers. The other two side walls of the two mold chambers are formed by edge parts 38 .
[0027] The conductor bars themselves are usually constructed from a bundle of individual, insulated conductors. In the case of Roebel-transposed conductor bars, the individual conductors are in part twisted around each other, while in nonRoebel-transposed conductor bars the individual bars extend parallel to each other without twisting. In the invention, conductor bars with individual conductors having a round cross-section can be used. It is especially advantageous, however, if the method according to the invention is used for conductor bars with individual conductors having a rectangular cross-section. When using rectangular crosssections, the advantages of the invention are also realized when the cross-sections of the individual conductors and/or of the conductor bar slightly deviate from the rectangular shape. If the conductor bar is constructed of individual conductors, it is advantageous that the latter are connected with each other temporarily in order to enable a uniform and cavity-free encasing of the conductor bar with the main insulation, for example, by temporarily bonding the individual conductors with an elastic material or an adhesive with low mechanical strength against shearing forces, so that later bending is not impeded. Alternatively, an adhesive that loses its bending power during moderate heating (e.g., before bending) and thus promotes the bending process.
[0028] The injection mold of FIG. 1 a shows two mold chambers. The number of mold chambers per injection mold can be varied at any time, however. A reduction to one casting mold is achieved, for example, by removing the center part 36 and moving at least one of the two edge parts 38 in the direction of the other edge part. On the other hand, the number of mold chambers can be increased by using, for example, several center parts 36 with reduced width. In this way, the center part 36 shown in FIG. 1 a can be replaced with two narrower center parts, between which another casting mold is formed.
[0029] The geometrical dimensions of the individual parts of the injection mold 30 , i.e., in particular cover 32 , bottom plate 34 , center part(s) 36 , and edge parts 38 , can be varied in such a manner that they form elements of a modular system and in this way cover a variety of possible bar geometries (cross-section, length). The use of center parts 36 and edge parts 38 with different heights while retaining the same geometrical extensions of the injection mold, makes it possible to coat conductor bars with different cross-sections, for example, conductor bars 2 having the same width but different heights. Alternatively, a conductor bar of corresponding height which is twisted by 90° around its longitudinal axis can be placed into the casting mold in order to coat conductor bars 2 of identical height but different widths. Smaller variations in the conductor cross-section can also be compensated by greater layer thicknesses of the main insulation to be cast. A variety of different cross-sections of conductor bars can be coated by combining center parts 36 and edge parts 38 of different heights with center parts 36 and edge parts 38 of different widths. The flexibility of the modular system for the injection molds can also be increased by using spacer plates. These plates can be provided advantageously at the side, bottom, or ceiling plates of the mold chambers in order to reduce the width or height of the mold chamber.
[0030] In a preferred embodiment, the insulation thicknesses are identical on the narrow and wide sides of the conductor bar. In a particularly advantageous embodiment, the insulation thickness is greater on the narrow sides of the conductors than on the wide sides, so that the electrical field elevation is reduced at the conductor edges without hindering the dissipation of heat over the wide side.
[0031] [0031]FIG. 1 b shows a longitudinal section through one of the mold chambers shown in FIG. 1 a . The cylindrical spacer elements 40 hereby center the conductor bar 2 in such a way in the mold chamber that the layer thickness of the main insulation has the same height on all sides. By using spacer elements with different heights, a main insulation with a varying layer thickness can be applied around the conductor bar, if needed. It is hereby not necessary that cylindrical spacer elements 40 are used. Spacer elements with a square or rectangular crosssection fulfill the same purpose, but facilitate the spacing of the conductor bars from the side walls since they can be placed with one of their narrow sides onto the bottom of the casting mold without rolling off. Fig. lc shows spacer elements 40 with a rectangular cross-section. Alternatively to this, spacer elements that completely enclose the conductor bar can be used. It is preferred that completely enclosing spacer elements 40 are cut open on one of their sides so that they can be placed more easily around the conductor bar.
[0032] An elastomer is used as a material for the main insulation. The elastomer is characterized by high elasticity. It also has a high electrical and thermal stability. In particular for thermally highly stressed machines it is preferred that silicone elastomers are used. Especially the advantageous use of elastomer (in contrast to other materials), permits the use of injection molding processes and fulfills the high requirements for material resistance and mechanical flexibility. The elastomers may be cold-or hot-curing types. The curing for coldcuring types is initiated, for example, by mixing two components, whereby one of the components contains a curing agent. In the case of hot-curing types, the elastomer can be heated already in the injection mold and/or after the encasing of the conductor bar. The latter is done preferably with hot air (oven) or by a resistive or inductive heating of the conductor bar.
[0033] The material properties of the main insulation can be adjusted in such a way by adding chemically active (e.g., silicic acid) and passive (e.g., quartz sand) fillers, so that they fulfill the respective mechanical requirements of the electrical machines into which the stator windings provided with the main insulation are installed.
[0034] The centering of the conductor bars in the mold chamber (given a main insulation with identical layer thickness) or the spacing of the conductor bar from the individual walls of the mold chamber is accomplished, as already mentioned, by using spacer bars 40 with different shapes and heights that are placed at a suitable distance from each other onto the bar or into the mold chamber. It is preferred that the spacer elements are made from the same material as the main insulation. The spacer elements are provided with a certain dimensional stability by partially curing the material. On the other hand, they still have sufficient reactive bonds, however, to be able to form a tight chemical bond with the cast material of the main insulation. Depending on the material used, simple trials can be conducted to establish the degree of curing that must be present in the material of the spacer elements so that the same or equivalent mechanical and electrical strengths can be obtained at the interfaces as in the homogenous material of the main insulation that does not have any interfaces.
[0035] In FIG. 2 a and b , adjustable mandrels 42 are used to center the conductor bars 2 within the mold chamber of the injection mold or space them from the walls of the mold chamber. A control element 44 permits a precise adjustment of the individual mandrels 42 , which also can be moved in a defined manner when the injection mold is closed. During the injection process of the elastomer and the initial curing, the conductor bar is held by the mandrels in the desired position. As curing progresses, the elastomer injected as material for the main insulation reaches a firmness that holds the conductor bar in its desired position even without the mandrels. After the main insulation has reached this firmness, the mandrels 42 are withdrawn, and the resulting voids are filled with liquid elastomer. The liquid material is injected into the voids through the injection channels 46 (see FIG. 3) inside the mandrels 42 . The material injected in the area of the mandrels can be in liquid or gel form, but must still have sufficient reactive bonds so that the mechanical and electrical properties of the main insulation at the interface correspond to those of the homogenous material of the main insulation. The adjoining material around the mandrel may already be firm yet must still be reactive. To promote the curing at the interface, a heating region 50 may be provided, for example, between two spacer mandrels. In this way, the heat and thus the curing front spreads starting from the heating region in the direction of the mandrels so that the start of curing is delayed, and the material near the mandrels therefore is still able to sufficiently react with the elastomer freshly supplied through the injection channel 46 . As an alternative or additionally to this, the mandrels 42 can be cooled. This cooling makes it possible to delay the curing of the material in and around the mandrel.
[0036] The injection molds shown in FIGS. 1 and 2 preferably are designed open at their longitudinal ends. They are closed off with sealing caps that enclose the conductor in a pressure-proof manner during the injection molding. This permits the processing of bars with different lengths. In order to insulate the conductor bar along its entire length, the main insulation may be applied in one or more steps, or several injection molds of the modular system are put together to form a partial or complete injection mold. The seams created in this way can be constructed according to the above described curing process. This also ensures that the required material properties are present at the seams.
[0037] In some applications, it is preferred that the conductor bars are provided with slot corona shielding and termination (yoke corona shielding) as well, if applicable, with an internal corona shielding. The internal corona shielding of a stator winding is usually a conductive material layer located between main insulation and conductor bar. It provides for a defmed potential coating around the conductor bar and prevents electrical discharges that can be caused by voids between the conductor bar and the main insulation. The slot or external corona shielding of a stator winding is usually a conductive material layer located between the main insulation and the stator slot. The external corona shielding, which again creates a defined potential coating, is supposed to prevent electrical discharges that can be caused, for example, by varying distances of the high potential insulated conductor bar from the grounded stator nut. The termination (yoke corona shielding) usually prevents electrical discharges at the slot exit of a conductor bar. Options for applying such protective layers within the scope of this invention include, for example, conductive or semi-conductive elastomer-based finishes, suitable tapes (possibly self-fusing), which can be cured by irradiation or heat. Alternatively, cold- or heat-shrink-on sleeves (for example, for bars) or cuffs (for example, for coils) can be used. When using shrink-on sleeves or cuffs for the internal corona shielding, these may be provided advantageously on their inside with a flowable, plastic material to fill the voids on the surface of the conductor bar. This is basically also possible for an external corona shielding.
[0038] In another preferred embodiment of the method, internal corona shielding, main insulation, and/or external corona shielding are applied with the help of several consecutive injection molding processes. This may be accomplished in different injection molds with different cross-sections or in the same mold, whereby the mold chamber is then provided during the corresponding injection molding steps with filler profiles (spacer plates) in order to leave room for the next layer. It is also possible to provide the mold chamber with movable sections. Movable sections are part of a casting mold that can be arranged so that an additional layer is injected, for example, only in the area of the termination (slot corona shielding end to termination end).
[0039] [0039]FIG. 4 shows a bending device that has been modified from the state of the art. The insulated conductor bars are placed into the gripping jaws 18 of the bending device and are brought there into their final shape by moving the gripping jaws 18 in relation to the radial tools 20 . Between the radial tools 20 and the insulating layer 4 of the conductor bar 2 , is a protective layer 22 that distributes the pressure generated at the radial tools over the surface and in this way prevents an excessive pinching of the insulation layer. The uniformly distributed mechanical stress on the elastomer insulation layer prevents damage to the insulation layer. The bending of the involute causes very high tensile forces in the insulation layer that, in the case of standard materials, such as high-temperature thermoplasts, lead to breaks in the insulation layer. Polyethylene would have the necessary flexibility, but does not have the temperature stability required for the typical electrical machines, but could in principle be used in a similar manner for machines with low thermal utilization (T<90° C). The same holds true for other flexible thermoplasts.
[0040] If the conductor bar is constructed of a bundle of individual conductors, the bending of conductor bars already provided with the main insulation causes both a relative movement of the individual conductors against each other as well as a relative movement of the individual conductors at the surface of the conductor bar against the main insulation. It is advantageous that the interface between conductor bar and main insulation has properties that enable a shifting of the individual conductors against the main insulation with reduced friction. This may be achieved, for example, by treating the conductor bar with separating agents. The occurrence of gaps due to this relative movement at the interface to the conductor is meaningless if an internal corona shielding connected tightly with the main insulation is used in this area. Without internal corona shielding, the shifting is, in most cases, uncritical because the field is reduced in the bend area (following the termination).
[0041] When using an internal corona shielding, it is advantageous that it has good adhesion to the main insulation, but has a lesser adhesion to the surface of the conductor bar . This is preferably achieved in that insulation and corona shielding are based on the same chemical materials (chemical bond), while the internal corona shielding and wire lacquering each have a different material base with, preferably, little affinity. Separating agents may be able to increase this effect. The conductor bars themselves are preferably not even Roebel-transposed in the area where the later bending takes place.
[0042] In another embodiment (not shown), injection molds are provided that can be used to apply main insulation to already bent sections of the conductor bar. For this purpose, the injection mold has three-dimensionally shaped sections that preferably can be adapted to certain tolerances of the conductor bar. Part of the advantages gained by using simple and cheap injection molds are lost with the injection molds designed for bent conductor bars. Nevertheless, this can be compensated for large volumes, especially if the molds adapted to already bent conductor bars can be used for several types as a result of standardization.
[0043] The complicated molds are also justified when internal corona shielding, insulation, and external corona shielding can be applied in one step. This can be accomplished, for example, with movable sections used to apply the layers by injecting, curing, moving the section, injecting, curing, etc. Alternatively, a multishot injection molding process can be used. | The invention relates to a method for applying the main insulation of conductor bars, in particular conductor bars for stator windings, whereby the conductor bars have a rectangular cross-section. The method comprises the following steps: insertion of a conductor bar with ends in an injection mold; centering of the conductor bar in the injection mold so that a void for holding an insulation material remains between the conductor bar and the injection mold; filling of the void with an elastomer in order to form the main insulation. | 8 |
TECHNICAL FIELD
This invention relates to measuring contact potential differences.
BACKGROUND
A contact potential difference (CPD) is a difference between an electrostatic potential at a surface of a sample and a contact potential of a metal electrode of a CPD probe, which is determined by the probe electrode's work function. CPD measurements are non-contact measurements that are particularly useful for characterizing numerous structures extensively used in semiconductor electronics, such as dielectric layers disposed on semiconductor substrates. Examples of these applications are described by J. Lagowski and P. Edelman in “Contact Potential Difference Methods for Full Wafer Characterization of Oxidized Silicon,” Inst. Phys. Conf., Ser. No. 160, p. 133-144 (1997), and by D. K. Schroder in “Contactless Surface Charge Semiconductor Characterization,” Material Science and Engineering, B91-92, p. 196-210 (2002). In cases where the sample is a dielectric film on a semiconductor substrate the contact potential difference of the sample, V CPDS , can be expressed as:
V CPDS =V S −φ el ,
where φ el is the contact potential of the CPD probe electrode and V S is the sample surface potential:
V S =V diel +V SB +φ s .
Here, V diel is the potential drop across the dielectric layer, V SB is the semiconductor surface barrier, and φ s is the contact potential corresponding to the semiconductor work function at the flatband condition (i.e., when V SB =0).
Electrical charge residing in a dielectric layer, on the surface of the dielectric layer, or at the interface between the dielectric layer and the semiconductor substrate can be monitored by measuring a change in a V CPDS in response to an electric charge, ΔQ, intentionally placed on the dielectric layer's surface, for example, by a corona discharge in air. This change in V CPDS , can be expressed as:
Δ V CPDS =ΔV diel +ΔV SB ,
where ΔV diel =ΔQ/C diel , C diel being the dielectric layer capacitance. ΔV SB =ΔQ/(C SC +C it ),
where C SC and C it are the capacitance of the semiconductor space charge and interface traps, respectively.
Electrical current in the dielectric layer can also be monitored by measuring a rate of change of V CPDS , after corona charging of dielectric, dV CPDS /dt. In this type of measurement, V CPDS is recorded as a function of time. A current, J, is obtained from the rate of change of the voltage across the dielectric layer, V diel : J = C diel V diel t ≈ C diel V CPDS t .
Key properties of dielectrics (e.g., electrical conductance, charge trapping) important for semiconductor device functioning are temperature dependent. Therefore, characterization of dielectrics would clearly benefit if CPD could be measured over wide temperature range including elevated temperature as high as 400° C. or even 500° C.
SUMMARY
Typical CPD probes incorporate elements such as a measuring electrode, an operational FET preamplifier, an electromagnetic or piezoelectric vibrator, soldered electric wires, elements connected with glue or epoxy. These elements can be affected, or even destroyed, by elevated temperature. For example, currently manufactured probes would generally fail at temperatures in excess of 400° C.
Measurement systems can be designed to avoid overheating of the probe during measurement of samples at elevated temperature, without any modification of the probe assembly and without a need for probe cooling devices that would stabilize the probe temperature during a measurement of hot samples. To avoid overheating, the probe is cycled between two positions: a room temperature position in the proximity of a reference plate; and a “hot” position in the proximity of sample at elevated temperature. The cycle can be asymmetric in time. For example, for the majority of a typical cycle lasting about 15 seconds, the probe is in a room temperature position. The time the probe spends in this position (e.g., about 10 seconds) is referred to as resting time Δt rest . For a short portion of the cycle (e.g., about 2 seconds), referred to as measuring time, Δt measure , the probe is in the proximity of the sample at elevated temperature. This cycle limits the heating of the probe while it measures the sample and helps to cool the probe back to a room temperature while the probe is in the proximity of a reference plate.
When the sample is at high temperature, such as 400° C. or 500° C., a noticeable heating of the probe can take place even during a short 2-second sample measuring time. This can alter the contact potential, φ el , of the probe electrode, and change the probe reading of the sample V CPDS =V S −φ el . The present method makes the sample measurements substantially independent of changes in φ el . In other words, the described method provides compensation for any changes in φ el that may occur due to probe heating. This is done using two measurements: the contact potential of the sample V CPDS =V S −φ el , which is measured with the probe positions in the proximity of the sample; and, the measurement of a reference plate that is done immediately after returning of the probe to position in the proximity of a reference plate. The second measurement provides V CPDR =φ ref −φ el , where φ ref is the contact potential of the reference plate. From these two measurements a difference is obtained ΔV CPD =V CPDS −V CPDR =V S −φ ref , φ ref is constant because the reference plate is kept at a constant reference temperature (e.g., typically room temperature). Thus, ΔV CPD provides an accurate measure of the sample contact potential, V S , that is not substantially affected by any changes in φ el .
While the described methods and systems focus on elevated temperature measurement done with CPD probes, it shall be pointed out that the methods can be applied to measurement with any non-contact probe that may be affected by exposure to elevated temperature. Such probes may include, for example, photovoltaic probes for the surface photovoltage measurement, or optical probes for probing light reflected from the sample or emitted by the sample.
In general, in a first aspect, the invention features a method for elevated sample temperature measurement. The method includes heating a sample to a sample temperature, T, and moving a probe from a first position to a second position, wherein the first position is proximate to a reference plate held at constant temperature, T 0 , and the second position is proximate to the sample, and T is greater than T 0 . The method further includes measuring a contact potential difference of the sample, V CPDS , with the probe being held in the second position for a measuring time, Δt measure , sufficiently short to prevent substantial heating of the probe. The method also includes returning the probe to the first position, measuring a contact potential difference of the reference plate, V CPDR , and determining a difference ΔV CPD =V CPDS −V CPDR as a measure of a sample contact potential at T.
Implementations of the method can include one or more of the following features.
The probe need not be actively cooled while in the second position. Δt measure can be 2 seconds or less.
The method can further include holding the probe in the first position for a probe resting period, Δt rest , of 5 seconds or more after returning the probe to the first position.
T 0 can be less than 100° C. (e.g., less than 80° C., less than 50° C., less than 30° C., less than 25° C., such as 23° C.). During the measurement of V CPDS and V CPDR , the temperature of the probe can be kept within 5° C. of T 0 (e.g., within 3° C. of T 0 , within 2° C. of T 0 , within 1° C. of T 0 ). The sample temperature T can be between T 0 and 500° C.
The sample can include a dielectric layer. The reference plate can include gold or platinum.
The method can also include cycling the probe between the first position and the second position, and during each cycle, measuring V CPDS in the second position and V CPDR in the first position, and determining a sample contact potential difference from a difference between V CPDS and V CPDR from each cycle. In some embodiments, the method can also include changing the sample temperature between measuring V CPDS of successive cycles and measuring the sample temperature, T, each time the probe measures V CPDS . Alternatively, or additionally, the method can further include determining a dependence of A V CPD on the sample temperature. A corona charge can be deposited on sample surface prior to changing the sample temperature.
Once the system acquires data from cycling the probe between the first and second positions, the method can include characterizing the sample in one or more ways. For example, the method can include identifying contaminant ions present in the sample from the dependence of ΔV CPD on the sample temperature. Alternatively, or additionally, the method can include determining the concentration of each contaminant ion in the sample from the dependence of ΔV CPD on the sample temperature. As another example, the method can include monitoring desorption of contaminants from the sample from a rate of change of the dependence of ΔV CPD on the sample temperature.
In a second aspect, the invention features a system, including a sample stage for supporting a sample, a heating element for heating the sample to a sample temperature, a reference, a probe for making contact potential difference measurements mounted on a probe arm, and an electronic controller, which during operation causes the probe arm to position the probe relative the sample to measure a contact potential difference between the probe and the sample, and then causes the probe arm to position the probe relative to the reference and to measure a second contact potential difference between the probe and the reference.
The system can be adapted to implement the methods of other aspects of the invention. The system can also include one or more of the following features.
The system can include a cooling element positioned relative the reference sample, and during operation, the cooling element can stabilize the reference plate temperature. The probe can be a Kelvin probe, a Monroe probe, or a Trek probe.
In a third aspect, the invention features a method, including moving a probe at a first temperature from a first position to a second position, wherein the first position is proximate to a reference at the first temperature and the second position is proximate to a sample, the sample being heated to a sample temperature greater than the first temperate, measuring a first contact potential difference of the sample with the probe in the second position, returning the probe to the first position, and measuring a second contact potential difference of the reference, wherein the probe is held in the second position for a period wherein the probe's temperature is substantially unchanged from the first temperature during the measuring.
Implementations of the method can include any of the features of the other aspects of the invention.
In a fourth aspect, the invention features a method, including moving a probe at a first temperature from a first position to a second position, wherein the first position is proximate to a reference at the first temperature and the second position is proximate to a sample, the sample being heated to a sample temperature greater than the first temperate, measuring a first contact potential difference of the sample with the probe in the second position, and removing the probe from the second position. The probe is held in the second position for a sufficiently short time so that the probe's temperature is substantially unchanged from the first temperature during the measuring.
Implementations of the method can include any of the features described in regard to other aspects of the invention. Implementations of the method can also include one or more of the following features.
The method can include measuring a second contact potential difference of the reference with the probe in the first position. Additionally, the method can include determining the sample contact potential difference from the first and second contact potential differences.
After positioning the probe in the first position, the first contact potential difference can be measured before the sample can substantially heat the probe.
The method can also include returning the probe to the first position after removing the probe from the second position.
Note that substantial heating of the probe includes any heating that would damage the probe and/or cause errors in the measurement that could not easily be corrected for to provide measurements within the desired accuracy of the particular application (e.g., errors that are not corrected for by the methods disclosed herein). Substantial heating can include, for example, heating that would change the probe temperature more than 10° C. from T 0 .
Embodiments of the invention can include one or more of the following advantages.
Commercial CPD probes designed for operation at or near room temperature (e.g., between 20° C. and 25° C.) can be used without any modification while measuring samples at elevated temperatures (e.g., more than 100° C., such as more than 200° C., 300° C., 400° C., or even 500° C.). Effects of probe heating on the CPD measurements can be corrected for using a reference measurement, providing precise CPD measurements of samples at elevated temperatures.
The measurement techniques enable CPD characterization of samples as a function of sample temperature. For example, these techniques can be used to monitor electrical current in a dielectric as a function of temperature. Transport of ionic contaminants in a dielectric can also be monitored. The temperature dependence of contaminant transport can be used to determine the type and concentration of the contaminant.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and apparatus similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and apparatus are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the apparatus, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.
DESCRIPTION OF DRAWINGS
FIG. 1 is a plan view schematic of an apparatus for elevated temperature measurement of contact potential difference;
FIG. 2 is a side view schematic of the apparatus shown in FIG. 1;
FIG. 3 is a schematic of contact potential difference probe of FIG. 1 positioned above a sample;
FIG. 4 is plot showing a temperature scan of the CPD of a SiO 2 film on a silicon substrate;
FIG. 5 is a metal ion drift spectrum corresponding to the temperature scan shown in FIG. 4; and
FIG. 6 is an example of derivative spectrum of a SiO 2 film on a silicon substrate showing.
Like reference symbols in the various drawings indicate like elements.
DETAILED DESCRIPTION
At least in part, the invention is related to measuring a contact potential difference of a sample at elevated temperatures (e.g., temperatures about 500° C.).
Referring to FIG. 1 and FIG. 2, a system 100 includes a contact potential difference (CPD) probe 1 mounted on a rotating arm 2 . A CPD probe controller and meter 15 and a motion controller 4 that moves rotating arm 2 with CPD probe 1 . On command from motion controller 4 , a motorized rotating stage 3 (or equivalent pneumatic rotating stage) moves rotating arm 2 to position CPD probe 1 back and forth between a first position A and a second position B.
In first position A, CPD probe 1 is positioned above a reference plate 5 and measures a contact potential difference between probe 1 and reference plate 5 . Reference plate 5 is a plate of material that provides a stable value of contact potential, φ ref that is not substantially affected by ambient changes (e.g., changes in humidity). For example, noble metals, such as high purity platinum or gold, are suitable materials for reference plate 5 . Reference plate 5 is electrically grounded and maintained at a reference temperature, T 0 (e.g., at room temperature), by a fan 14 .
In second position B, CPD probe is positioned above a sample 6 and measures a CPD between a reference electrode of probe 1 and sample 6 . CPD probe controller and meter 15 records the measured CPD in each position. The substrate of sample 6 is electrically grounded and supported by a variable temperature hot chuck 7 , which heats sample 6 to an elevated temperature, T (e.g., to 500° C.). Hot chuck 7 is mounted on a translation stage 17 , which is controlled by motion controller 4 . Translation stage 17 moves sample 6 relative to probe 1 in position B, enabling system 100 to measure a sample CPD at multiple positions on sample 6 . A temperature sensor 9 monitors the temperature of hot chuck 7 , which is approximately the same as the temperature of sample 6 . Temperature sensor 9 communicates with a temperature controller 10 via signal line 11 . Based on signal line 11 , temperature controller 10 adjusts the temperature and rate of change of the temperature of hot chuck 7 by adjusting a power level sent via a cable 12 to a heating element 8 . Cooling fans 13 a and 13 b assist the cooling of heat chuck 7 , for example, when a measurement procedure needs temperature T reduced.
A computer (not shown) controls motion controller 4 , CPD probe controller and meter 15 , and temperature controller 10 , and coordinates measurement sequences. The computer records data from CPD probe controller and meter 15 and temperature controller 10 , and performs additional analysis on the recorded data, which will be discussed in detail below.
During a typical measurement sequence, rotating arm 2 cycles probe 1 back and forth between position A and position B. During each cycle, probe 1 measures a reference CPD, V CPDR , and a sample CPD, V CPDS , in position A and position B, respectively. While the temperature of reference plate 5 is maintained at reference temperature T 0 , hot chuck 7 and/or fans 13 a and 13 b vary the temperature of sample 6 between successive measurements. As the sample temperature is typically elevated with respect to T 0 , sample 6 heats probe 1 via radiation and convection when in position A. To reduce this heating well below the probe damage threshold, the time probe 1 spends in position B (i.e., the measuring time, Δt measure ) during each measurement cycle is as short as possible, (e.g., 5 second or less, 2 seconds or less). On the other hand, the time that probe 1 spends in position A (i.e., the resting time, Δt rest ) is longer to promote cooling of the probe. For example, the resting time can be more than 8 seconds, such as 10 seconds or more. In some embodiments, a typical measurement sequence lasts about 15 seconds: 1.5 seconds to move probe 1 from position A to position B; 1 second to measure V CPDS ; 1.5 seconds to move from position B to position A; 1 second to measure V CPDR and the rest of the 9 seconds to cool probe 1 in position A.
Referring to FIG. 3, when in position B a distance, d, separates probe 1 from a top surface of sample 6 . Distance d is sufficiently large to prevent heat damage to probe 1 by sample 6 during a measurement cycle (e.g., at least 0.2 mm, such as 0.5 mm or more). Accordingly, distance d depends on the type of probe, the temperature of the sample, and the length of time the probe is held in position B to make a measurement. A distance of 1 mm, for example, is sufficient to prevent thermal damage to a commercial Monroe CPD probe (e.g., a 1017 Isoprobe from Monroe Electronics, Lydonville, N.Y.) by a sample heated to 450° C. during a CPD measurement with Δt measure =2 seconds and Δt rest =10 seconds.
While no damage occurs to probe 1 during the measurement cycle, exposure of probe 1 to hot air above the sample, while in position B, can affect the accuracy of CPD measurements. For example, hot air can cause desorption of polar water molecules from an electrode of probe 1 , which can change the contact potential of the probe electrode φ el . However, effects of this heating on the probe reading are compensated using the reference plate CPD, V CPDR . For this purpose, a V CPDR is measured immediately after probe 1 returns to position A after making a V CPDS measurement of the heated sample. During data analysis, a difference V CPDS −V CPDR is used, rather than V CPDS =V S −φ el . Note that ΔV CPD =V CPDS−V CPDR =V S −φ ref and thus V CPD it is not affected by changes in φ el .
In a measurement that uses multiple sample temperatures ranging from T 1 to T 2 (for example when the sample temperature is ramped from T 1 =25° C. to T 2 =400° C.), ΔV CPD corresponding to any particular temperature Tin that range is determined from corresponding values of V CPDS and V CPDR . Further data analysis is performed using the data V CPD (T). The sample temperature T is measured when the probe is in the position B.
Probe 1 can be a commercially available CPD probe, such as a Kelvin probe, a Monroe probe, or a Trek probe. These probes include a measuring electrode, typically formed from a gold plate, or a gold-plated metal plate. During a CPD measurement, a capacitance between the electrode and a sample is varied by periodic vibrations in the probe. In a Kelvin probe, for example, these vibrations cause the distance between the probe electrode and the sample surface to vary. In a Monroe probe, the probe includes a tuning fork between the probe electrode and the sample. During operation, the tuning fork vibrates, thereby varying the probe capacitance. These vibrations cause a current signal in the probe, which is proportional to the rate of change of the capacitance and is given by: J = C t ( V CPD + V bias ) ,
where V bias is the bias voltage applied between the probe electrode and the sample by CPD probe controller and meter 15 via electric cable 16 . V CPD is determined from current J by calibrating the current with a known bias voltage or by measuring the bias voltage that produces J=0. In this latter method, known as the compensation method, V CPD =−V bias at J=0. Commercial meters perform automatic compensation, providing a V CPD measurement in times as short as 0.1 second.
In some embodiments, system 100 can be used as an ion drift spectrometer. In these applications, V CPDS data measured as a function of temperature are used to identify mobile ion contaminants (e.g., Na + , Li + , Cu + , and/or K + ) in a dielectric film in a sample (e.g., in a SiO 2 film on a silicon substrate). The concentration of these contaminants can also be determined from the V CPDS vs. temperature data.
A typical ion-drift spectrometry characterization of an SiO 2 film on a silicon substrate is as follows. In preparation, a positive charge is placed on a surface of the SiO 2 film at room temperature using corona discharge in air. Large positive corona ions (H 2 O)nH + deposited on the SiO 2 surface create an electric field within the SiO 2 film. These ions do not typically move into SiO 2 even at elevated temperature. The user then places the charged sample on variable temperature hot chuck 7 and begins the measurement sequence. During the measurement sequence, the chuck temperature is ramped up at a constant rate, and the probe is cycled between position A and position B where it measures V CPDS and V CPDR , respectively. Accordingly, the CPD meter acquires a series of V CPDS and V CPDR measurements as a function of chuck temperature. The temperature increment between each measurement depends on the timing of probe cycling and the temperature ramp rate. For example, measurements are made at 2.5° C. increments for a 15 second probe cycling period and a ramp rate of 10° C. per minute. The computer determines ΔV CPD =V CPDS −V CPDR as a function of temperature from the acquired V CPDS and V CPDR data.
Referring to FIG. 4, a plot of ΔV CPD versus temperature shows three steps in which ΔV CPD decreases as the sample temperature increases. In this example, these steps occur at about 100° C., 180° C., and 240° C., respectively. These steps are due to increasing of the mobility of contaminant ions in the SiO 2 film as a function of temperature. At lower temperatures (e.g., less than about 70° C.), typically all ion contaminants are immobile, and remain trapped in the SiO 2 film despite the electric field within the film. At elevated temperatures, however, the ions become increasingly mobile and begin to drift towards the silicon substrate pushed away by the positive charge on the film surface. The specific temperature range when an ion species becomes mobile is different for different ion species. The most mobile sodium ions (Na + ) move at about 100° C., copper ions (Cu + ) move at about 180° C. and the potassium (K + ) ions begin to move at a temperature of about 240° C. A drift of N ions from within the SiO 2 film to the SiO 2 /silicon interface causes a drop in ΔV CPD corresponding to qN/C ox , where q is the charge of each ion.
Since different ions produce voltage steps at different temperatures, they can be readily identified from a derivative spectrum, i.e., a plot of d(ΔV CPD )/dT versus temperature, T.
Referring to FIG. 5, the derivative spectrum corresponding to the ΔV CPD spectrum shown in FIG. 4 reveals three peaks corresponding to Na + , Cu + , and K + . The peak temperature is used to identify the ion in each case. In this example, the peak at about 100° C. corresponds to Na + ions, the peak at 180° C. corresponds to Cu + ions, and the peak at 240° C. corresponds to K + ions. Additionally, the integrated area under each peak provides a measure of the concentration of each ion in the sample.
In some embodiments, system 100 can be used to monitor the thermal desorption of polar molecules on a dielectric surface. Polar molecules (i.e., molecules having a permanent dipole moment) affect CPD measurements when adsorbed on or desorbed from a dielectric surface. Hence, CPD measurements made as a function of temperature can be used to monitor corresponding thermal desorption of polar molecules taking place in the measurement temperature range. For example, water physisorbed on SiO 2 desorbs at temperatures below 140° C., while organic molecules desorbs at higher temperatures (e.g., greater than 150° C.). Referring to FIG. 6, an example of a derivative desorption spectrum (i.e., d(ΔV CPD ) versus temperature) includes a lower temperature peak at about 95° C. and a broad band of opposite sign to the peak extending from about 150° C. to above 300° C. In this example, the sample was a 20 Å thick SiO 2 film on a silicon substrate. The lower temperature peak corresponds to water desorption, while the higher temperature band corresponds to desorption of molecular airborne contamination. Molecular airborne contamination includes organic molecules adsorbed onto the sample surface during storage in plastic containers and/or in a clean room environment.
While application of system 100 for ion-drift spectrometry and to monitor thermal desorption of polar molecules on sample surfaces has been described, system 100 can also be used in other applications. For example, system 100 can be used in conjunction with a corona source to monitor thermal affects on stress induced leakage current. Measurement of stress induced leakage current is described in U.S. patent application Ser. No. 09/451,652, filed Nov. 30, 1999, entitled “METHOD FOR MEASURING STRESS INDUCED LEAKAGE CURRENT AND GATE DIELECTRIC INTEGRITY USING CORONA DISCHARGE,” by Jacek Lagowski et al. Another example application is monitoring of charge traps in a dielectric layer that hold charge at room temperature and release charge at elevated temperatures. One could also use the described apparatus for distinguishing between various conductive processes in insulators. For example, Frenkel-Poole transport via traps is exponentially dependent on temperature, while tunneling and field emission are independent of temperature. By monitoring current vs. temperature, one can determine which transport mechanism is active and determine parameters characterizing the conduction process. This application may facilitate development of new dielectrics for microelectronics.
Furthermore, system 100 can include additional probes and/or devices to increase its functionality and capabilities. For example, a corona source can be included in system 100 to facilitate automated deposition of corona charge on the sample surface. In another example, system 100 can include a surface photovoltage (SPV) probe for monitoring a sample SPV as a function of temperature. Examples of SPV measurements are described in U.S. Pat. No. 5,663,657, entitled “DETERMINING LONG MINORITY CARRIER DIFFUSION LENGTHS,” by Jacek Lagowski et al.
A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims. | Techniques for measuring a contact potential difference of a sample at an elevated temperature using a probe designed for room temperature measurement are disclosed. In such measurements, probe damage by excessive heating can be prevented without any probe modifications to include probe cooling. This can be achieved by minimizing the time the probe spends in close proximity to the heated sample. Furthermore, the effect of probe heating by the sample on the probe reading can be corrected by including an additional contact potential difference measurement of a reference plate kept at room temperature in the measurement cycle. | 6 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a device for controlling the thread lever of a braiding machine comprised of the combination of a circular ring-shaped, closed curved path and correlated sliding block, wherein the thread lever has a pivot axle which is connected above the lower feed bobbins to the gear housing, which is rotatingly driven in a first rotational direction about the central pipe of the braiding machine, wherein the thread lever describes as a result of the rotational movement of the gear housing a rotational plane and, by means of the sliding block, is imparted with an oscillating pivot movement about its pivot axle in this rotational plane, and wherein the rotational movement of the gear housing is transformed into a second rotational direction opposite to the first rotational direction via a reversing gear with intermediate wheel and is then imparted onto the bobbin carriers of the warp thread bobbins. The present invention further relates to a braiding machine with a central pipe and a housing rotatingly driven about the central pipe in a first rotational direction, on which bobbin carriers for the lower feed bobbins are seated as well as with upper bobbin carriers for the upper feed bobbins which are also rotatably supported to rotate about the central pipe, wherein between the lower feed bobbins and the upper feed bobbins a positive-locking reversing gear with intermediate wheel is provided which at the input side is loaded by the rotational direction of the housing and at the output side generates the second rotational direction opposite to the first rotational direction with which the upper bobbin carriers of the upper feed bobbins are loaded.
2. Description of the Related Art
Such braiding machines are known; see, for example, the catalog of Spirka “Spirka-Schnellflechter”. These rapid braiders, according to the catalog, allow rotational speeds up to approximately 150 per minute, depending on the number of bobbin groups rotating in opposite directions, respectively.
The plurality of required gear couplings and kinematic parameters make it difficult to increase this rotational speed at will.
One of the decisive parameters of a braiding machine is the rotational speed limit. It depends on several factors, i.e., the type of control of the thread lever and/or the type of gear coupling between the drive members, the reversing gear, and the bobbin carriers.
The thread lever, on the one hand, must be pivotably supported above the weft thread bobbins, and, on the other hand, below the warp thread bobbins.
In this connection, the upper end of the thread lever must project past the warp thread bobbins to such an extent that the corresponding weft thread can be received by a thread guide which defines the movement plane of the weft thread above the warp thread.
Conventionally, the control of the thread lever results from a combination of a circular ring-shaped, closed curved path with corresponding sliding block. The curved path is arranged outside of the rotation plane on which the thread lever circulates during rotation of the weft thread bobbins.
The curved path thus encompasses the entire braiding machine.
However, since the thread lever has a relatively great length, relatively high moments of inertia are to be expected which must be exerted as forces by the sliding path pair—comprised of the sliding block and the curved path—in order to impart onto the thread lever its fast pivot movement. The relatively large spacing of the curved path from the center of rotation moreover effects relatively high relative speeds between the sliding block and the curved path so that relatively high surface pressures are to be expected in this connection.
On the other hand, the reversing gear of braiding machines with central pipes is an important component in order to impart onto the upper bobbin carriers a rotational movement about the central pipe opposite to that of the lower bobbin carriers.
Since these mechanical gears contribute significantly to the power requirements of a braiding machine, there is always the tendency to use gears with minimal consumption of power.
However, this causes the problem that, in addition to a reversal of the rotational direction between lower thread bobbins and upper thread bobbins, also a predetermined ratio of transmission must be maintained which is prescribed by the braiding process.
It is therefore the object of the present invention to improve the braiding machine such that higher rotational speeds are enabled.
SUMMARY OF THE INVENTION
On the one hand, this object is solved by the invention in regard to the device for controlling the thread lever in that the sliding block and the curved path are located within the rotational plane, and, on the other hand, in regard to the braiding machine in that the reversing gear comprises an internal ring gear stationarily arranged on the central pipe with a large reference diameter, a pinion revolving therein, and an external ring gear with small reference diameter rotatably supported on the central pipe, and wherein the revolving pinion is rotatably supported on a revolving axle fixedly connected with the housing as well as provides the positive-locking connection between the internal ring gear and the external ring gear.
There are therefore two different measures with which the rotational speed limit of such braiding machines can be increased.
These measures can be realized independently from one another and also in combination with one another on a single braiding machine.
In the following, the inventive measures of the device for controlling the thread lever will be discussed first.
This part of the invention results in the advantage that for a more compact configuration of the braiding machine the weft thread bobbins and the warp thread bobbins become more easily accessible.
This advantage is achieved in that the previously known enclosure of the braiding machine by the stationary curved path is eliminated and replaced with an inwardly displaced curved path; this facilitates access to the weft thread bobbins and the warp thread bobbins.
An important factor of this part of the invention is that the sliding block and the curved path are positioned within the rotational plane which is described by the thread lever upon its rotation about the central pipe of the braiding machine.
On this rotational plane the thread lever additionally carries out the pivot movement which results in the braiding of the warp threads and the weft threads.
With this part of the invention, on the one hand, the relative speed between the sliding block and the curved path is reduced, because the engagement circle between the sliding block and the curved path is on a smaller radius in comparison to a curved path arranged outside of the rotational circle.
Since the law of movement of the thread lever, moreover, is defined by the curvature of the so-called thread guide, the exact geometric shape of the curved path results automatically so that the weft thread traverses up and down with constant contact on the thread guide.
The more the engagement circle between the curved path and the sliding block is moved toward the central axis of the braiding machine, the smaller the relative speeds, without the predetermined law of movement of the thread lever being negatively affected. In this respect, it is desirable to position the engagement circle between the sliding block and the curved path within the circle which is described by the inner end of the pivot axle. This provides the additional possibility of positioning the pivot axle of the thread lever in a bore of the gear housing where the sliding block and the curved path can be positioned in an oil bath.
With the permanent oil lubrication enabled in this way, relative speeds between the sliding block and the curved path which have been unattainable previously should be permissible.
For simplifying the configuration, the curved path can be arranged on an annular console which is connected as a separate component stationarily to the central pipe.
Moreover, the pivot axle can be positioned at a slant such that it is inclined with its end facing the central pipe toward the braiding point. This practically means the exit end of the material to receive the braid from the central pipe. This enables an effective pivot movement above the warp thread bobbins and below the warp thread bobbins with minimal forces. The decisive limit angle—measured relative to the normal plane of the central axis—is 45 degrees. This results in a permissible angle range of 45°>alpha>0°.
When the curved path is then inclined additionally about an angle L like the pivot axle, an excellent surface contact between the sliding block and the curved path results.
In order to compensate moreover tension fluctuations which result upon pivoting of the thread lever, a thread buffer roll is additionally provided which serves for a temporary thread deposition of the weft thread upon pivoting in the sense that the weft thread tension is practically maintained constant.
From the additional dependent claims advantageous embodiments of the invention result. The second part of the invention has the advantage that the housing for receiving the gear of the braiding machine can be configured significantly smaller and more compact so that in this way also an excellent accessibility to the weft thread bobbins and the warp thread bobbins is ensured.
With the compact configuration of the housing, the resonance behavior of the braiding machine is favorably affected, and the rotational speed limit can thus be increased. In principle, this part of the invention is based on the reversing effect which is caused by the pinion revolving within the internal ring gear. The internal ring gear is stationary; the pinion circulating in its interior is supported at its engagement location with the external ring gear with smaller reference diameter on the output side of the gear, and the reversal of the rotational direction is caused in this way.
At the same time, this planet wheel arrangement enables the adjustment of the required rotational speed ratios which are required for the braiding process.
However, the special advantage of this part of the invention resides also particularly in its independence from the measures in regard to the device for controlling the thread lever.
Even though, this part of the invention can be used in combination with the features of the device for controlling the thread lever.
BRIEF DESCRIPTION OF THE DRAWINGS
In the following, the invention will be explained with the aid of embodiments in more detail. It is shown in:
FIG. 1 a first embodiment of the invention;
FIG. 2 an embodiment of the invention with slanted pivot axle;
FIG. 3 a schematic illustration of the inner curved path with engaged sliding block;
FIG. 4 an embodiment of the invention with a special configuration of the reversing gear;
FIG. 5 the reversing gear according to FIG. 4 on a braiding machine with a curved path positioned outside of the rotational plane.
DESCRIPTION OF PREFERRED EMBODIMENTS
If not indicated differently, the following description applies to all Figures.
The Figures show a braiding machine 1 in a schematic view.
A central pipe 3 is mounted rigidly on a machine frame 2 .
The central pipe 3 serves in its lower area for receiving a gear housing 5 which is arranged by means of a gear housing bearing 6 rotatably on the central pipe 3 .
By means of the drive 4 a rotational movement is imparted on the gear housing 5 , and the rotation is carried out also by the sliding path carrier 7 connected to the gear housing 5 .
In the lower area of the gear housing 5 , lower bobbin carriers 8 are arranged which support a weft thread bobbin 9 , respectively.
The weft thread is guided through a penetration, not illustrated in detail, in the thread lever 10 and extends from there to a deflection device 13 which is positioned on the upper end of the thread lever 10 .
The thread lever 10 can be pivoted about a pivot axle 11 which is movable in a pivot axle bearing 12 .
From the deflection device 13 , the weft thread runs toward the braiding point 14 which can be found on the outer circumference of the elongate article 15 to receive the braid.
While the elongate article 15 is transported only in the vertically upward direction, the weft thread bobbins carry out a rotational movement in a predetermined rotational direction about the central pipe 3 . This rotational movement is predetermined by the drive 4 .
It can now be envisioned that the thread lever 10 when rotating about the central axis 50 describes a rotational plane which is concentric to the central axis 50 . At the same time, the thread lever 10 carries out a pivot movement about its pivot axle 11 . The pivot axle 11 is positioned above the lower feed bobbins—the weft thread bobbins 9 —and is connected to the gear housing 5 such that the rotational movements of thread lever 10 and the gear housing 5 are synchronized.
Accordingly, the thread lever 10 and the gear housing 5 rotate in a first rotational direction about the central pipe 3 of the braiding machine.
At the same time, the thread lever 10 is automatically controlled by the positive-locking engagement between a sliding block 31 and a correlated curved path 30 such that it carries out an oscillating pivot movement 35 about its pivot axle 11 on the rotational plane 32 on which it rotates about the central axis 50 . This pivot movement is caused by the course of the curved path 30 with which it is provided on its closed path about the central axis 50 .
The positive-locking engagement between the sliding block 31 and the curved path 30 imparts therefore by means of a corresponding moment a movement onto the pivot axle which, depending on the configuration, is transmitted directly or indirectly onto the thread lever 10 . In order to generate with this arrangement a braid, it is required to rotate the warp thread bobbins 9 in a second rotational direction 29 b opposite to the first rotational direction 29 a.
For this purpose, a reversing gear 20 is provided which is comprised of a transmission stage 23 and an intermediate wheel 21 .
The reversing gear has the purpose to transform the rotational movement of the gear housing 5 into a rotational direction which is opposite to the first rotational direction and to then impart this rotation onto the warp thread carriers 18 which each support a warp thread bobbin 19 . The warp thread carriers 18 move thus in a rotational direction opposite to the first rotational direction 29 a about the central axis 50 and are guided when doing so on the sliding path carriers 7 which are provided only in segments like the warp thread carriers 18 .
In this way, an alternating immersion and retraction movement results in the area of the sliding path carrier 7 and the warp thread carriers 18 in that the sliding path carrier 7 and the warp thread carriers 18 rotate in opposite directions to one another about the central axis 50 .
For this purpose, the reversing gear 20 is provided which comprises the intermediate wheel 21 as an important component.
The intermediate wheel 21 is connected by means of the intermediate gear shaft 22 rigidly with the sliding path carrier 7 . It is a bevel wheel which engages, on the one hand, the warp thread carrier 18 and, on the other hand, the internal ring gear 16 positive-lockingly. The internal ring gear 16 is independent of the gear housing and also rotatably supported on the central pipe 3 . The bearing for this internal ring gear thus enables rotation of the internal ring gear 16 about the central pipe 3 independent of the gear housing 5 .
Moreover, since the gear housing 5 and the internal ring gear 16 must have different rotational speeds, according to FIGS. 1 through 3 a transmission stage 23 is provided which is supported on an annular console 24 .
The annular console 24 is fixedly connected on the central pipe 3 .
The transmission stage 23 will be explained again in connection with a deviating embodiment with the aid of FIGS. 4 and 5.
In this embodiment, the transmission stage 23 is comprised of an internal ring gear 25 which is fixedly connected to the stationary annular console 24 .
The internal ring gear has the greatest reference diameter within the transmission stage 23 .
A pinion 26 revolves within the internal ring gear 25 and is rotatably supported on a revolving axle 28 .
The revolving axle 28 is fixedly connected with the gear housing 5 .
While the revolving pinion 26 , on the one hand, is in engagement with the internal ring gear 25 , the internal ring gear 16 has an external ring gear 27 with a small reference diameter with which the revolving pinion 26 also meshes.
The pinion 26 is thus constantly in engagement with the internal ring gear 25 having a large reference diameter as well as with the external ring gear 27 having a small reference diameter and rotates thus together with the gear housing 5 about the central axis 50 and on its revolving axle 28 because it is forced to do so by engagement of its toothing on the rigid internal ring gear 25 .
Therefore, the rotational movements of the internal ring gear 16 and of the gear housing 5 are oriented in the same direction. However, the rotational movement is reversed by the intermediate wheel 21 so that the warp thread carrier 18 is rotated in a rotational direction opposite to that of the sliding path carrier 7 .
This is indicated by the symbols for the first rotational direction 29 a and the second rotational direction 29 b , independent of the respective rotational speeds (absolute).
Since the sliding block 31 during this movement in the first rotational direction 29 a moves in the stationary curved path 30 , it is possible to impart onto the thread lever a pivot movement with a corresponding arrangement, for example, as illustrated in FIG. 3 and in FIG. 5 .
The pivot movement 35 is carried out between lower pivot positions 33 a and upper pivot positions 33 b while the thread lever 10 is rotated about the central axis 50 .
As illustrated additionally in FIG. 3, the sliding block 31 is seated on a guide lever 44 which has a spacing from the geometric pivot axis 45 of the pivot axle 11 .
Since the pivot axle 11 , in turn, is rotatably supported, by means of a correspondingly configured curved path 30 the thread lever 10 can be caused to perform a reciprocating pivot movement while it rotates about the central axis 50 .
In the embodiments according to FIGS. 1 through 4, the pivot axle 11 is supported in the gear housing 5 .
In principle, this also applies to the support of the pivot axle in the embodiment according to FIG. 5 .
However, in this embodiment the pivot axis is not oriented in the direction toward the central pipe 3 but away from it.
Accordingly, the curved path 30 is positioned in an area outside of the rotational plane 32 of the braiding machine and has on the mantle surface facing in the direction toward the central pipe 3 an engagement zone for the sliding block 31 moving in this area.
The curved path 30 is a component of a ring which surrounds the braiding machine and can have a relatively small diameter as a result of the configuration of the reversing gear as compact as possible in the embodiment according to FIG. 5 .
Moreover, the compact reversing gear in the embodiment according to FIG. 5 also favors increasing the rotational speed limit of such braiding machines because the sliding pair between the sliding block 31 and the curved path 30 operates with relatively minimal circumferential speeds.
The geometry of the gear housing 5 according to FIG. 5 is not to scale. The actual size of the gear housing 5 is significantly smaller and allows shrinking of the inner diameter of the ring with the curved path 30 correspondingly.
The respective path-time law of the thread lever movement is predetermined by the principal contour of the thread guide 34 .
In the embodiments according to FIGS. 1 through 4, it is decisive that the sliding block 31 as well as the curved path 30 are positioned within the rotational plane 32 which is described by the thread lever when carrying out its rotational movement about the central axis 50 .
The forces which are introduced onto the thread lever for its control will thus originate from an engagement circle whose radius is smaller than the rotational plane 32 described by the thread lever 10 .
In addition, it can be provided that the sliding block 31 and the curved path 30 are positioned within the inner end 36 of the pivot axle 11 . In this case, the engagement circle between the sliding block 31 and the curved path 30 is within the circle which is described by the inner end 36 of the pivot axle 11 .
Moreover, FIGS. 1 and 4 show that the pivot axle 11 is rotatably supported in a bore 37 of the gear housing 5 .
When it is moreover provided that the bearing of the gear housing on the central pipe as well as on the outer circumference of the internal ring gear 16 as well as the pivot support of the pivot axle 11 on the gear housing are sealed by radial seals 39 a-c , the oil level 38 within the gear housing 5 can be realized such that the sliding block 31 and curved path 30 are positioned within the oil bath. The oil-tight gear housing 5 can be optionally provided with a suitable drainage plug.
Since the curved path 30 , in turn, is mounted on the annular console 24 , it is thus possible to generate a wear-free and environmentally clean permanent lubrication between the sliding block 31 and the curved path 30 , in connection with the advantage of significantly higher relative speeds and thus higher rotational speeds for the braiding machine.
In any case, it is however fulfilled that the curved path support, in the illustrated embodiments the outer circumference of the annular console 24 , is practically positioned on an extension of the central axis 50 of the annular rotational plane 40 which is defined by the pivot axle 11 .
This results in a direct and effective transmission of the course of the curved path 30 onto the thread lever 10 because the force-transmitting members between the sliding block 31 and the pivot axis 11 are short and compact.
Additionally, the pivot axle 11 can be inclined with its end 41 oriented to the central pipe 3 in the direction to the braiding point 14 . This measure provides an effective braiding geometry and is known in the art.
In order to provide an effective engagement between the sliding block 31 and the curved path 30 , the curved path should be inclined with the same slant angle such that the sliding block engages with a contact surface as large as possible the walls of the curved path 30 .
In addition, it is also provided that a thread buffer roll 43 is correlated with the pivot axle 11 of the thread lever 10 and has a weft thread groove 46 concentrically arranged to the pivot axle 11 .
This measure provides for compensation of tension changes in the weft thread which can be caused by the pivot movement of the thread lever 10 between lower pivot position 33 a and upper pivot position 33 b.
The geometrically optimal course of the curved path 30 , and thus the alternating movement of the sliding block 31 during its revolution, is in principle determined by the curved thread triangle which is defined between the braiding point 14 and the deflection device 13 on the thread lever 10 and is positioned above the envelope which is described by the warp threads between their warp thread bobbins 19 and the individual braiding points 14 .
Since these laws of movement are however sufficiently known, see, for example, catalog “Spirka-Schnellflechter”, no further explanation is provided in this connection.
In the embodiments according to FIGS. 4 and 5, it is also shown that the internal ring gear 25 , the revolving pinion 26 , and the external ring gear 27 are positioned in one and the same radial plane 48 relative to the central pipe 3 and mesh with one another in this radial plane.
This measure serves for preventing possible bending moments on the bearing of the pinion axle which rotates together with the gear housing and is therefore referred to as revolving axle 28 .
Moreover, with one and the same outer toothing on the revolving pinion 26 the entire gear coupling, including the transmission between the drive motor and the internal ring gear 16 , is effected.
This is achieved in that the pinion 26 meshes directly with the internal ring gear 25 as well as directly with the external ring gear 27 , wherein the intermediate wheel 21 is loaded by the output side of the external ring gear 27 and at the same time engages a gear which is mounted on the upper bobbin carriers 18 .
For this purpose, the intermediate wheel is positioned on an intermediate wheel shaft 22 which is connected fixedly with the gear housing 5 and positioned above the radial plane 48 in which the internal ring gear 25 , revolving pinion 26 , and external ring gear 27 mesh with one another.
List of Reference Numerals
1 braiding machine
2 machine frame
3 central pipe
4 drive
5 gear housing
6 gear housing bearing
7 sliding path carrier
8 lower bobbin carrier
9 weft thread bobbin
10 thread lever
11 pivot axle
12 pivot axle bearing
13 deflection device
14 braiding point
15 elongate article to receive braid
16 internal ring gear
17 internal ring gear bearing
18 warp thread carrier
19 warp thread bobbin
20 reversing gear
21 intermediate wheel
22 intermediate wheel shaft
23 transmission stage
24 annular console
25 internal ring gear
26 revolving pinion
27 external ring gear
28 revolving axle
29 a first rotational direction
29 b second rotational direction
30 curved path
31 sliding block
32 rotational plane
33 a lower pivot position
33 be upper pivot position
34 thread guide
35 pivot movement
36 inner end of pivot axle
37 bore of the gear housing
38 oil level
39 a, b, c radial seal
40 rotational plane of the pivot axle
41 end of the pivot axle pointing to the central pipe
42 slant angle
43 thread buffer roll
44 guide lever
45 geometric pivot axis
46 weft thread groove
48 radial plane
50 central axis | The present invention relates to a braider ( 1 ) comprising a device for controlling the thread lever ( 10 ). Said braider is formed by a curved path ( 30 ) that is closed in a circular ring-shaped manner, a sliding block ( 31 ) appurtenant thereto and a reverse gear ( 20 ) by means of which the direction of rotation of the drive motor is reversed in such a way that the group of the upper delivery bobbins and the group of the lower delivery bobbins rotate in opposing directions. The aim of the invention is to enable such a braider ( 1 ) to have a higher ceiling speed. The sliding block ( 31 ) and the curved path ( 30 ) are situated within the surface ( 32 ) of rotation, whereby said surface is circumscribed by the course of the thread lever ( 10 ) around a central axis ( 50 ) in relation to the braider ( 1 ), and/or the reverse gear ( 20 ) is provided with an internal ring gear which is fixed to the central pipe ( 3 ) and has a great reference diameter, a pinion circulating therein and an outer ring gear that is rotatably mounted on the central pipe ( 3 ) and has a small reference diameter. The pinion is rotatably mounted on a circulating axle which is rigidly connected to the housing. Said pinion causes the positive fit between the internal ring gear and the outer ring gear. | 3 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of Ser. No. 256,219 filed Apr. 21, 1981 now abandoned.
BACKGROUND OF THE INVENTION
The present invention relates to an encapsulated epoxy adhesive system and, more particularly, to a water based adhesive system employing a hydrophobic curing agent.
Most common epoxy adhesives are prepared from a two-part system comprising an epoxy resin and a curing agent. Prior to application, the two parts are mixed and the resin and curing agent mixture are applied to the bonding site where the resin is cured into a hard adherent mass. The common two-part adhesive system is inconvenient to work with because the two parts must be mixed and the adhesive cannot be applied directly to the bond site. One of the techniques that has been used to make the two part system more convenient has been to microencapsulate the epoxy resin and the curing agent. Encapsulated resin and curing agent do not react. Therefore, a mixture of the capsules can be formed and applied directly to a bonding site. There, when the capsules are broken the resin and curing agent react and the epoxy resin bonds. Encapsulated adhesive systems such as this have been employed with threaded fasteners. The encapsulated resin and curing agent are applied to the fastener. As the fastener is tightened, the capsules break and the adhesive bond is formed.
Some of the problems which have been associated with prior epoxy adhesive systems have been that the curing agents used are relatively hygroscopic and have a short shelf life, and the systems have employed a polymeric vehicle. Capsules of curing agent produced by prior encapsulation techniques have been to some extent moisture permeable and the shelf life of the system has not been appreciably enhanced. In accordance with the present invention these drawbacks have been overcome by an encapsulated adhesive system employing a hydrophobic and therefore less hygroscopic curing agent. In accordance with a preferred embodiment of the invention, the polymeric vehicle is replaced by water without sacrificing the adhesive qualities of a polymer based system.
The system of the present invention has the following advantages:
1. Much higher breakaway torques.
2. Much greater consistency and reproducibility.
3. Much less moisture sensitivity which means coated bolts may not have to be protected from the environment.
4. Much longer pot-life. This enables a 1-part ready-to-apply aqueous based epoxy adhesive.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention an encapsulated epoxy adhesive system is provided comprising epoxy resin capsules and an encapsulated hydrophobic curing agent. The curing agent is preferably Ancamine TL by Pacific Anchor Chemical Corp. Ancamine TL is a 45% solution of methylene dianiline in a non-volatile plastizer.
The epoxy system of the present invention is prepared by forming epoxy resin capsules. These capsules can be formed using techniques which are well known in the art. One convenient method is to form a polyvinyl alcohol capsule wall via coacervation and graft onto it a urea-resorcinol-formaldehyde resin. Epon 828 by Shell Oil Co. is a suitable epoxy resin but those skilled in the art will recognize that other epoxy resins can be used. These capsules may range in size from about 10 to about 1000μ and preferably 50 to 150μ. Normally the epoxy content of the capsules is on the order of 86%. The capsules may be used as a free flowing powder although it is not necessary to isolate them.
The epoxy capsules are, in one embodiment of the invention, mixed with a coacervate emulsion of the curing agent. Using Ancamine TL as an example, this is accomplished by (1) dispersing a 75% solution of Ancamine TL in xylene into a Glevitol 20-90 PVA solution as 50-100μ droplets, (2) at about 45° C. coacervating the PVA and promoting encapsulation of the Ancamine TL by the sequential addition of solutions of gum arabic, resorcinol and sodium sulfate, (3) allowing the swollen walled capsules to settle overnight, and (4) decanting off the supernatant phase and gently agitating the coacervate phase with a spatula to produce a 1°20μ "coacervate emulsion" of the Ancamine TL.
Thereafter the epoxy capsules are added to the emulsion together with sufficient binder solution to prepare a slurry with a viscosity suitable for hand application. One such formulation is shown in the table below:
______________________________________Coating Formulation______________________________________Epoxy Capsules 4.0 partsCocervate emulsion 4.0 partsBinder Solution As required______________________________________
A suitable binder for the above formulation is a solution of 2.5% Elvanol PVA 71-30 and 0.5% Kelzans xanthum gum.
Another method of preparing the Ancamine TL coacervate emulsion is by preparing the PVA-resorcinol coacervate without the curing agent and decanting off the supernatant after settling overnight. Then the Ancamine TL curing agent is emulsified into the coacervate using the Waring Blender and with or without the addition of some of the supernatant to adjust viscosity. The emulsion prepared by this method will be referred to as a "precoacervate emulsion".
In accordance with a preferred embodiment of the present invention, water is substituted for the xanthum gum/PVA binder solution in the coating formulation discussed above. It has been found that in some applications no viscosity builder or added binder is necessary. The PVA coacervate serves as the binder. In addition, by eliminating the xanthum gum which promotes bacterial growth, the problem caused by the limited shelf life of this component is eliminated. Initial testing indicates that the test results obtained through use of water as the diluent in the coating formulation are comparable to those obtained through use of the xanthum gum/PVA binder. Preparing this formulation, it is been found desirable to use less water in preparing the Ancamine TL coacervate emulsion. The result is a coacervate emulsion from which a supernatant phase need not be decanted, and which requires no additional water as a binder for the preparation of the coating formulation. The entire process can be carried out in much less time than that required by the original procedure, for example, a total manufacturing time of 2.5 hours. Initial test results are very encouraging. Settling of the coacervateAncamine TL complex does occur during storage, but is not expected to present any formulation or coating difficulties.
In comparison to a system containing a binder, it has been found that a simple water dilution provides good breakaway torques, but addition of a binder may provide better prevailing-off torques in some cases. This may be due to the binder system filling the bolt threads to a greater extent. The water-no binder system is more cost effective and production-oriented.
In another embodiment of the invention, it has been found that the presence of filler in the encapsulated epoxy coating formulation improves prevailing off torque. When the encapsulated adhesive is applied to a fastener which is tightened, the filler is believed to pack around the threads of the fastener increasing abrasive interference and thereby increasing the force necessary to back the fastener off. A typical filler useful in the present invention is fumed silica such as Syloid 244 (W. R. Grace & Co.). The filler may be used in amounts ranging from about 0.2 to 15% by weight based on the weight of the coating formulation. Amounts on the order of 3% by weight are preferred.
The present invention is illustrated in more detail by the following non-limiting example.
EXAMPLE
Epoxy Capsule Preparation
150 ml of a 5% by weight aqueous solution of Gelvatol 20-90 (a partially hydrolized polyvinyl alcohol manufactured by Monsanto Chemical Co. having a hydrolization degree of about 85.5 to 88.7%, a molecular weight of about 125,000 and a viscosity of 35 to 45 centipose in a 4% by weight aqueous solution at 20° C.) and 100 ml of distilled water are placed in a beaker equipped with a turbine blade agitator and stirred while heating to 75° C. In a separate beaker 15 g of gum arabic in 135 ml distilled water is heated to 65° C. In a third container 150 ml of Epon 828 (a liquid epoxy resin manufactured by Shell Chemical Co.) is heated to 65° C. The liquid epoxy resin is poured into the polyvinyl alcohol solution while stirring. Agitation of the mixture is increased to produce a droplet size of about 50 to 200 microns. Thereafter, the gum arabic solution is slowly added. Agitation is reduced to prevent further emulsification but maintained at a level sufficient to retard coalesence of the internal phase droplets. The beaker contents are cooled to 45° C. and 4 g urea and 8 g resorcinol and 40 ml distilled water are added drop wise to the beaker from a dropping funnel. Five minutes after the completion of the addition, 10 ml of 10% (v/v) aqueous sulfuric acid solution is added to the beaker. Five minutes after the acid addition, 20 ml of 37% methanol-inhibited formalin is slowly poured into the beaker.
One hour after the formalin addition, 3 g urea, 5 g resorcinol, 40 ml distilled water, and 20 ml of 37% formaldehyde solution are added while the temperature of the beaker is held at 45° C. Agitation is continued for 16 hours at 45° C. The pH of the beaker is adjusted to 4.5 using a 10% aqueous solution of sodium hydroxide and the contents of the beaker are agitated an additional 15 minutes and removed from the heat source and set aside.
After the contents of the beaker settle, the supernatant liquid is removed and the microcapsules which result are washed five times by decantation using distilled water and filtered on coarse filter paper and dried to a free flowing powder.
Coacervate Emulsion Preparation
150 ml of a 5% by weight aqueous solution of Gelvatol 20-90 and 100 ml of distilled water are added to a beaker equipped with a turbine blade agitator. With stirring, the contents of the beaker are heated to 60° C. In a separate container 15 g of gum arabic in 135 ml distilled water is heated to 60° C.
75 ml of liquid Ancamine TL curing agent and 25 ml p-xylene are mixed in a third container and heated to 60° C. The Ancamine TL is poured into the polyvinyl alcohol solution with stirring and the contents of the beaker are agitated to form an emulsion having a droplet size of approximately 100 microns. Thereafter, the gum arabic solution is slowly added and agitation is reduced to prevent further emulsification but maintained at a level sufficient to retard coalescence. Agitation is continued until droplets of polymer-rich coacervate are microscopically visable. Thereafter the beaker is cooled to 45° C.
1 g urea, 10 g rescorcinol and 40 ml distilled water are added dropwise to the polymer rich coacervate. Upon completion of this addition, transparent complex coacervate walls surround the Ancamine TL internal phase. These walls are hardened and densified by adding dropwise 25 ml of a solution of 7.5 g anhydrous sodium sulfate in 92.5 ml distilled water. Upon stirring for 15 minutes, soft microcapsules settle to the bottom of the beaker. The supernatant liquid is decanted and a viscous yellow slurry of Ancamine TL droplets is obtained which is further agitated to reduce the droplet size to the 1-20 micron range.
Coating Formulation Preparation
4 g coacervate emulsion and 4 g microencapsulated epoxy resin are combined with 0.3 g fumed silica (Syloid 244). Distilled water is added to the composition to adjust the viscosity to a consistency suitable to form a coatable slurry suitable for application to the threaded fasteners. The slurry is gently stirred until all components are thoroughly dispersed.
The coating composition prepared as above is applied by hand to threaded bolts and dried for 15 minutes in an oven at 100° C. Mating nuts can be applied to these threaded bolts at any time up to at least 6 months with no loss in locking performance. The adhesive system of the present invention is cured by breaking the microcapsules such that the resin and curing agent contact and react.
Prior to curing and after application, the coating should be allowed to dry. If it does not, the breakaway torque is diminished and the results are not as reproducible. A typical drying condition is 15 minutes at 100° C. Excessive heating may volatize components necessary for an optimum cure that yield good breakaway torques, but a certain amount of drying is essential to eliminate excess moisture from the coating. A coating which is more thoroughly dried in a relatively rapid manner may provide more abrasive interference and, therefore, higher prevailing off torques. The effect of the drying conditions on the adhesive system illustrated in the Example is shown below.
______________________________________Drying Prevailing BreakawayConditions Off Torque Torque (inch-pounds)______________________________________ 5 min. at 100° C. 67 18210 min. at 100° C. 76 15115 min. at 100° C. 97 158 5 min. at 75° C. 12 10310 min. at 75° C. 26 14215 min. at 75° C. 32 17320 min. at 75° C. 79 180 5 hours at ambient 19 178______________________________________
The effect of the epoxy capsule size on the torque is shown in the following table for thread adhesive system of the example.
______________________________________Capsule Size Breakaway(microns) (Majority Prevailing Torqueof Capsules) Off Torque (inch-pounds)______________________________________50-150 74 15850-150 61 149100 61 130125 47 206 53 86 16850-150 59 170150 51 154______________________________________
The table below shows the effect of cure time on the torques for the example system.
______________________________________Cure Prevailing BreakawayTime Off Torque Torque (inch-pounds)______________________________________ 8 hours 18 5516 hours 55 18024 hours 68 21448 hours 65 19272 hours 106 190______________________________________
Having described my invention in detail and by reference to preferred embodiments thereby it will be apparent to those skilled in the art that numerous variations and modifications thereof are possible without departing from the invention as claimed. | A microencapsulated epoxy adhesive system is disclosed comprising in admixture epoxy resin capsules and encapsulated Ancamine TL (Pacific Anchor Chemical Co.) as the curing agent. When applied, for example to a zinc plated bolt and the bolt is tightened, the capsules break and the resin cures and provides good breakaway torques. | 8 |
FIELD OF THE INVENTION
This invention relates to apparatus, methods and articles of manufacture for electrical connectors. More particularly, this invention relates to apparatus, methods and articles of manufacture for right angle electrical connectors for printed circuit boards and the like.
BACKGROUND OF THE INVENTION
A printed circuit board (PCB) connector is often used to provide an electrical interface between a PCB and a cable. A right angle PCB connector is often used to minimize the space required by PCB connectors and to ease the installation of cables to the connector.
Care must be taken when attaching to the connector. For example, the connections must be securely fastened so they do not come apart after installation. Additionally, they must be properly aligned so that an electrical connection is made upon installation.
In order to attempt to resolve these and other difficulties, various mechanisms have been used. Snap-in mechanisms are one such mechanism. Snap-in connectors provide convenient operation, allowing for quick and accurate installation. Moreover, a right angle snap-in connector permits a high board mount density, thus allowing for a number of connectors to be installed in a small area.
However, snap-in mechanisms may be confusing for the installer because of their similar appearance. If the confusion among possible connections leads the installer to make the wrong connection, the result could be disastrous.
In order to attempt to minimize confusion between snap fit type connectors, various standards have been established. One of those standards is referred to as FAKRA. This standard provides a system, based on keying and color coding, for proper connector attachment. Like connector keys can only be connected to like cable keys in FAKRA connectors. Thus secure locking and positioning of connector housings is provided.
Use of a standardized FAKRA and other similar connectors may lead to difficulties when designing a connector, however. A FAKRA connection may increase the space required for the connector. Additionally, and perhaps most importantly, a FAKRA connector, which is made of plastic, may interfere with the desired electrical connection, so, for example, grounding may be inhibited or non existent. Yet modification of a FAKRA type connector is extremely difficult because of their standardized construction.
Accordingly, it would be beneficial to have a small, effectively integrated mechanism for use in grounding FAKRA and other similar types of electrical connectors. Therefore, it is an object of the present invention to provide an small, integrated electrical connector.
It is yet a further object of the present invention to provide a small, lightweight electrical connector with an integrated grounding mechanism. It is a further object of the present invention to provide an FAKRA or similar type of electrical connector with grounding mechanisms that minimally, if at all, increases the size of the connector.
SUMMARY OF THE INVENTION
The present invention comprises right angle connector apparatus, methods and articles of manufacture. The preferred embodiments are used to connect printed circuit boards with cables and the like. The components of the preferred embodiments comprise a body, which in the especially preferred embodiment is a diecast printed circuit board jack, as well as ground and keying elements.
Upon assembly of the elements, and insertion in a device, the embodiment provides grounding to the device. In the embodiments used in a vehicle, grounding will usually be to the vehicle chassis.
The preferred embodiments provide grounding within a FAKRA or other similar type of standardized connector without altering the necessary standardized components and dimensions. Moreover, any desired audible and tactile feedback—assuring the connection has been established—is maintained.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a plan view of a preferred embodiment.
FIG. 2 shows a plan view of a preferred embodiment.
FIG. 3 shows a plan view of a preferred embodiment.
FIG. 4 shows a plan view of a preferred embodiment.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a preferred embodiment of the present invention as it might be passed through surface a. Surface a is the desired grounding surface. In the especially preferred embodiment, surface a is a vehicle chassis.
Also visible in FIG. 1 is keying mechanism 10 . Keying mechanism 10 provides appropriate snap fit or other connection as is known in the art for a cable or other connector. In the especially preferred embodiments, keying mechanism 10 is a color insert defined as appropriate according to the FAKRA standard.
Gasket 20 provides a grounding connection to surface a. In the especially preferred embodiments this is an EMI/RFI gasket, as the especially preferred embodiment is used in a RF environment, e.g. for digital satellite radio connections, global positioning systems, etc. Body 30 provides the plug in connection to the printed circuit board.
Turning now to FIG. 2 a view of a preferred embodiment is seen. Keying mechanism 10 is shown, as well as gasket 20 and body 30 . Depending from body 30 are legs 31 , 32 , 33 and 34 providing plug in mounting to the printed circuit board as is known in the art. Also seen is electrical lead 35 which provides the electrical connection from the printed circuit board also as known in the art. Electrical lead 35 passes through body 30 , gasket 20 , and keying mechanism 10 , terminating in end 36 .
FIG. 3 shows body 30 with grounding extension 38 protruding therefrom. Grounding extension 38 provides a mounting for grounding element 20 . Grounding extension 38 also provides cutouts 11 and 12 for mounting keying mechanism 10 in mating contiguous relationship thereupon. It should be noted that grounding extension 38 may provide any desired configuration for mating with keying mechanism 10 , such as, in the especially preferred embodiments, when keying mechanism 10 comprises a standardized connector means, e.g. a FAKRA mount. In other embodiments, other mounting mechanisms may be used for keying mechanism 10 as desired.
FIG. 4 shows a view of separated elements of a preferred embodiment. Keying mechanism 10 with engagement means shown generally at 15 mates with grounding extension 38 , such as, for example, at cutouts 13 and 14 , thus providing positive engagement with grounding extension 38 . Annular grounding element 20 is displaced over grounding extension 38 once assembled as had been shown in FIG. 2 . It should be noted that keying mechanism 10 shown in the embodiments of the Figure is a FAKRA connector. In other embodiments other mechanisms may be used as desired.
It should be noted that grounding element 20 and grounding extension 38 are used herein to denote a first and second grounding element respectively. The first and second elements are to be understood as connector components so that, when properly connected, a desired ground is made between the elements.
Other connector elements apart from FAKRA or similar types may be used in various embodiments as desired. In the especially preferred embodiment a FAKRA SMB connector is used. However other connectors known in the art may also be used.
The various elements are made of materials such as are known in the art. For example a FAKRA compliant keying mechanism may be made of various plastics, such as Teflon, polypropylene, and polymethylpentene. A Body element is also constructed from suitable material as is known in the art, such a diecast zinc or similar materials. Grounding elements may be constructed of suitable grounding material as known in the art. Preferably the embodiment is weighted as well thus preventing tipping during installation.
The above description and the views and material depicted by the figures are for purposes of illustration only and are not intended to be, and should not be construed as, limitations on the invention.
Moreover, certain modifications or alternatives may suggest themselves to those skilled in the art upon reading of this specification, all of which are intended to be within the spirit and scope of the present invention as defined in the attached claims. | Right angle apparatus, methods and articles of manufacture for connecting electrical components are disclosed. The preferred embodiments comprise a printed circuit board body element, grounding and keying elements, used to connect printed circuit boards with cables and the like. The preferred embodiments provide a grounded connection to a vehicle chassis or other ground. | 7 |
BACKGROUND OF THE INVENTION
This invention relates generally to electronic toys. More particularly, this invention relates to educational toys wherein the user's interaction with the toy is facilitated by electronic processing and communication.
In toys to which the invention relates, the user, through manual manipulation, voice command or other techniques, provides an input. The toy is programmed to provide an output in response to the input of the user. The usage of microcomputers and speech synthesizers has found widespread application in conjunction with numerous toys, games and educational devices of various forms.
SUMMARY OF THE INVENTION
Briefly stated, the invention in a preferred form is an interactive toy which tells a story in a creative and interesting fashion. A platform supports a story board which may take the form of an illustrated sheet, a page of a book or other similar media. A CPU is mounted in fixed relationship to the platform. An output device, which “tells” the story, communicates with the CPU. A plurality of readers, each of which communicate with the CPU, comprises an RF transmitter which defines a communication field and is mounted at a fixed position to the platform. Story figures, each comprising a transponder and having a unique electronic code, are placeable at selected locations of the story board. Upon placement of at least one story figure within a field, an output is produced by the output device. The output is a function of the code and corresponding reader of each placed figure.
The output device may take a number of forms including a speaker, which broadcasts synthesized speech narrating the story, noise, sounds or other audibly perceptible outputs, one or more lights and an action module. The story figures comprise one or more representational figures selected from the group consisting of a person, an animal, a tree and an object. The electronic story board may be configured in a case which houses the story figures and is hinged. Outer panels of the case form the platform to which an illustrated sheet or a story book may be placed. The action module may be mounted to the platform and project generally above the story board.
The CPU sequentially polls each of the readers and identifies any story figure which is placed at a corresponding station on the story board. Each of the readers is polled, and a responsive output is then generated to partially narrate or illustrate the story by sound, sight or movement.
An object of the invention is to provide a new and improved electronic story board wherein interaction between the user and the board is accomplished in a creative and entertaining manner.
Another object of the invention is to provide a new and improved electronic story board which provides an educational interaction with the user to facilitate appreciation and enjoyment of a story.
A further object of the invention is to provide a new and improved electronic toy which is capable of providing a multiplicity of sensory outputs in response to a creative method of personal inquiry by the user.
Other objects and advantages of the invention will become apparent from the specification and the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representational view, partly in phantom, illustrating a representative electronic story board and its usage in accordance with the present invention;
FIG. 2 is a top plan view of a representative electronic story board in accordance with the present invention;
FIG. 3 is a bottom view, partly broken away and partly in schematic, of the electronic story board of FIG. 2;
FIG. 4 is an enlarged elevational view, partly broken away, partly in section and partly in schematic, of a toy figure mounted to the electronic story board, partially illustrated, of FIG. 1;
FIG. 5 is an enlarged elevational view, partly broken away, partly in section and partly in schematic, illustrating a second form of a toy figure for the electronic story board of FIG. 1;
FIG. 6 is a flow chart illustrating the processing performed by the electronic story board of FIG. 1;
FIG. 7 is a schematic block diagram illustrating the electronic circuitry for the electronic story board of FIG. 1;
FIG. 8 is a schematic diagram illustrating the circuitry for a reader for the electronic story board of FIG. 1;
FIG. 9 is a schematic diagram illustrating the circuitry for a toy figure of FIG. 1; and
FIG. 10 is a schematic circuit diagram illustrating the circuitry for a passive toy figure for the electronic story board of FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
With reference to the drawings, wherein like numerals represent like parts throughout the figures, an electronic story board in accordance with the present invention is generally designated by the numeral 10 . The electronic story board 10 functions to communicate a story through sound, light, motion and sensory outputs in response to the selection and placement of one or more toy figures 20 - 24 (FIGS. 1, 4 and 5 ). An output module 26 is optionally employed to aid in the “telling” of the story. The figures and the module are intended to be representational of numerous possibilities of figures and modules that may be employed according to the specific story.
The electronic story board is preferably packaged in a compact case 30 (FIG. 3) which ho uses the electronic circuitry and components, as will be further described, as well as functions as a carrying case for the toy figures 20 - 24 and output module 26 . The case comprises a pair of sections 32 , 34 which are pivotal about a hinge 36 . In an open inverted position, the sections cooperate to form a platform 38 to which is affixed an illustrated story board 40 , such as a printed sheet or panel, representative of a story or which forms the support for a story book 42 . A carrying handle 39 facilitates portability.
With reference to FIG. 3, the case section 32 encloses a self-contained battery pack 33 which via an on/off switch 35 provides power for the device. An on/off LED indicator 37 indicates the on/off condition. The case section 32 houses most of the circuitry and electronic components for the electronic story book. The case section 34 functions also as the storage receptacle for the figures 20 - 24 and the module 26 .
The story board 40 and/or pages of book 42 designate a multiplicity of story stations or contact points 44 a , 44 b , 44 c . . . which have a defined relationship with the case. The stations or points may be distinctive circles, squares, shapes, indicia, etc. on the board or page. The board and book also preferably include visual representations, including drawings and text, to aid in “telling” the story and are hereafter individually and/or collectively referred to as story board 50 .
The story is electronically communicated in segments by a creative serial questioning by the user. The story segments may be communicated in a non-chronological sequence which is a function of the interactive questioning by the user. The user selects one or more of the figures 20 - 24 and places each selected figure at a station or contact point 44 on the board 50 . The specific figure and corresponding contact point is electronically identified, and an output in the form of a synthesized voice output and/or sound and/or a light output and/or a movement or motion of a portion of the module occurs in response to the selection and placement on the board. The serial placement of the various figures at various selected locations on the board will then, in time, result in the communication of the entire story with the user essentially communicating with the “storyteller” by inquiring through the selection and placement of the various figures. The number of and configuration of figures may vary, and the number and placement of contact points may vary depending on the story. The toy figures are shaped to represent individuals, animals, objects, etc. from the story. The action module 26 may also be constructed to represent a key “prop” or “scene” of the story. The module 26 is mounted to the top of the platform and electrically connected through connectors 46 and 48 to facilitate the multi-mode “telling” of the story.
With reference to FIGS. 3, 4 , 7 and 8 , an IC card reader 60 is mounted at the underside of the story board 50 directly below each of the contact points 44 a , 44 b , 44 c . . . and are designated by corresponding identifiers 60 a , 60 b , 60 c . . . . Each of the toy figures 20 - 24 has a transponder 52 and must also have an IC card 54 which has a unique identification ID code. With references to FIGS. 7 and 8, each reader 60 includes a driver 62 which drives a signal generator 64 to provide an RF signal to a push-pull driver 66 . The driver 66 connects with a coil or an inductor 65 which generates an RF field 61 and receives the ID coding signal from the toy figure. The coding signal is amplified by an amplifier 68 whose output is gated by driver 62 and becomes the data signal to the CPU 70 . The reader thus functions to provide an RF power source which is supplied to the transponder for powering the toy figure through a non-contact connection. The toy figure then sends an ID coding signal which identifies the specific toy figure to the CPU 70 for processing as described below.
With additional reference to FIG. 9, the transponder 52 includes a coil or an inductor 51 and a capacitor 53 connected in parallel for powering a voltage converter 56 which provides a power source to the encoder 58 . An address and data select chip 54 provides an address and data (ID code) to the encoder. The encoder 58 generates the output signal via a driver 57 which communicates the ID of the figure through to the RF field to the reader.
For certain embodiments, such as that illustrated in FIGS. 5 and 10, the RF power source from the reader may also be applied to an indicator or an LED 28 on the toy figure so that, upon application of the RF power source from the reader, the LED 28 is illuminated. Toy figure 23 may optionally be a passive device in which no ID is communicated back to the reader and no story telling output is initiated.
Each of the readers connects with a circuit board 72 which conditions the signals and communicates with the CPU 70 . The CPU 70 includes an 80C51 microprocessor and an HCS512 I.D. decoder. Input devices 73 , 75 and 77 , each of which may be a ROM corresponding to a given toy figure, provide unique data to the CPU 70 . The power supply connects with the CPU 70 and a sound circuit 76 . The sound circuit 76 includes a W52906 voice synthesizer. The circuit 76 connects with an 0.25 watt speaker 78 which communicates through a panel or shelf 80 attached to the case section 32 .
The electronic story board 10 operates by means of an RF object identity system which includes one or more of the readers 60 and one or more figures 20 - 24 . When the power of the system is switched on at switch 35 , each of the readers 60 radiates RF radiation to form a field 61 which extends above the story board 50 and intersects the corresponding contact points 44 . A selected figure is placed near or on a contact point 44 near the reader so that the transponder 52 will be powered up by the RF power radiated from the reader. The transponder 52 will transmit its own ID code to the reader through the RF field 61 .
With reference to FIGS. 7 and 8, the readers are each controlled by the CPU 70 . The CPU 70 generates control signals and polls each reader sequentially as described by flow chart 90 . When one of the readers has found a transponder 52 of a toy figure, the CPU 70 continues its polling until all of the readers 60 have been polled. At the termination of the polling sequence, if only one reader found a transponder of a toy figure, the CPU 70 performs an action corresponding to the ID of the transponder found as well as the specific contact point 44 , i.e., the specific reader. If more than one reader has a different toy figure, the CPU will perform a different action according to the ID of the first transponder found and the location of its contact point and the ID of the second transponder found and its corresponding contact point and so on until the relative position of all the readers and transponders has been communicated to the CPU. The chart below illustrates representative examples for purposes of explanation.
Chart 1
Example
Reader
Figure
Action
I
60a
20
A
II
60a
21
B
III
60b
20
C
IV
60a and 60b
20, 21
D
The CPU is programmed via, for example, input devices 73 , 75 , 77 . . . to perform the various actions which may correspond to a chapter or part of the story. Action A would be a voice action which is generated through the speaker 78 to tell a narrative concerning toy figure 20 (girl) as suggested by the illustrated environment of contact point 44 a within the communication field of reader 60 a . Action B would be a different voice narrative and sound effects relating to toy figure 21 (dog) and conveyed through speaker 78 . If toy figure 20 were instead placed at contact point or station 44 b , Action C would energize lights 27 on the action module 26 . If figure 20 were placed at station 44 a and figure 21 were placed at station 44 b , Action D would result in the door 29 of the action module 26 opening through the power transmitted and a signal transmitted from the CPU and a corresponding voice action through speaker 78 .
It will be appreciated that the story would unfold by, for example, first putting only toy figure 20 on the location of the page or story board; then sequentially selecting a figure 21 and placing that on the book page or story board; and subsequently placing both figures 20 and 21 simultaneously on different contact locations of the story board. Each selection and placement essentially constitutes an inquiry and triggers a corresponding sensory response in terms of one or more sound, voice, light, sight or motion outputs. The story would then be communicated through the various identification and electronic processing among the different figures as well as the different locations on the board wherein the book story would essentially be “told” interactively and in a sequence determined by the user. For example, if Examples I-IV occur in a different order, the story would be told in a different chronological sequence.
While preferred embodiments of the foregoing invention have been set forth for purposes of illustration, the foregoing description should not be deemed a limitation of the invention herein. Accordingly, various modifications, adaptations and alternatives may occur to one skilled in the art without departing from the spirit and the scope of the present invention. | An interactive toy employs a plurality of figures which are employed by the user to tell a story. The figures are selected and placed at selected locations on a story board or a book. The selection and placement results in the device telling the story by synthesized speech and other visual communications. The device is also configured in a compact case for carrying and storage. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to cargo storage facilities and more particularly pertains to a new automated mechanical storage facility for allowing the convenient storage and retrieval of a parked vehicle.
2. Description of the Prior Art
The use of cargo storage facilities is known in the prior art. More specifically, cargo storage facilities heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art cargo storage facilities include U.S. Pat. No. 5,314,285; U.S. Pat. No. 5,069,592; U.S. Pat. No. 5,066,187; U.S. Pat. No. 5,039,269; U.S. Pat. No. 5,032,053; and U.S. Pat. No. 5,024,571.
In these respects, the automated mechanical storage facility according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of allowing the convenient storage and retrieval of a parked vehicle.
SUMMARY OF THE INVENTION
In view of the foregoing disadvantages inherent in the known types of cargo storage facilities now present in the prior art, the present invention provides a new automated mechanical storage facility construction wherein the same can be utilized for allowing the convenient storage and retrieval of a parked vehicle.
The general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new automated mechanical storage facility apparatus and method which has many of the advantages of the cargo storage facilities mentioned heretofore and many novel features that result in a new automated mechanical storage facility which is not anticipated, rendered obvious, suggested, or even implied by any of the prior art cargo storage facilities, either alone or in any combination thereof.
To attain this, the present invention generally comprises a plurality of oval-shaped track assemblies each spacedly situated in vertical alignment. Each track assembly comprises a pair of parallel track rails each having an outer face, a top face, and a bottom face. As shown in FIG. 6, the rails of the track define an open inner face and an interior space. Also included is a plurality of storage units each having a bottom face with a planar rectangular configuration. A peripheral lip is integrally coupled to a periphery of the bottom face and extends upwardly therefrom. Two pairs of arms are each fixedly coupled to opposite sides of the bottom face of the storage unit and extend upwardly to define a triangular configuration. As shown in FIGS. 5 & 6, a roller assembly is provided including a vertically oriented plate with a pair of rollers rotatably coupled to opposite ends thereof. These rollers are adapted for being situated within the interior space of an associated one of the rails of the corresponding track assembly. The apex of each pair of arms is pivotally coupled to a central extent of the corresponding plate. The storage unit thus is adapted to move along the associated track assembly. An elevator assembly includes a bottom face with a planar rectangular configuration. Similar to the storage unit, a peripheral lip integrally is coupled to a periphery of the bottom face of the elevator assembly and extends upwardly therefrom. Two pairs of arms are each fixedly coupled to opposite sides of the bottom face of the storage unit and extend upwardly to define a triangular configuration. During use, an elevator cable is coupled to an apex of the pairs of arms for allowing the raising and lowering of the elevator assembly level with a selected one of the track assemblies. As shown in FIGS. 3 & 4, each of the storage units and elevation assemblies further include a pair of halves each including a plurality of elongated rollers rotatably coupled between opposite sides. These rollers reside level with an upper peripheral edge of the peripheral lip. As such, the rollers remain in a common horizontal plane. A pair of drive cylinders are mounted on opposite sides of the rollers in parallel therewith. Wrapped about the rollers and drive cylinders is a belt. The drive cylinders are adapted to move the belt such that cargo may be moved on to and removed from the storage units and elevation assemblies.
There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are additional features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto.
In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.
As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.
Further, the purpose of the foregoing abstract is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature an essence of the technical disclosure of the application. The abstract is neither intended to define the invention of the application, which is measured by the claims, nor is it intended to be limiting as to the scope of the invention in any way.
It is therefore an object of the present invention to provide a new automated mechanical storage facility apparatus and method which has many of the advantages of the cargo storage facilities mentioned heretofore and many novel features that result in a new automated mechanical storage facility which is not anticipated, rendered obvious, suggested, or even implied by any of the prior art cargo storage facilities, either alone or in any combination thereof.
It is another object of the present invention to provide a new automated mechanical storage facility which may be easily and efficiently manufactured and marketed.
It is a further object of the present invention to provide a new automated mechanical storage facility which is of a durable and reliable construction.
An even further object of the present invention is to provide a new automated mechanical storage facility which is susceptible of a low cost of manufacture with regard to both materials and labor, and which accordingly is then susceptible of low prices of sale to the consuming public, thereby making such automated mechanical storage facility economically available to the buying public.
Still yet another object of the present invention is to provide a new automated mechanical storage facility which provides in the apparatuses and methods of the prior art some of the advantages thereof, while simultaneously overcoming some of the disadvantages normally associated therewith.
Still another object of the present invention is to provide a new automated mechanical storage facility for allowing the convenient storage and retrieval of a parked vehicle.
Even still another object of the present invention is to provide a new automated mechanical storage facility that includes at least one closed loop track assembly. Also included is a plurality of storage units for being slidably moved along the track assembly and further adapted to contain cargo. Further included is a belt for discharging the cargo from the storage units and further receiving cargo thereon.
These together with other objects of the invention, along with the various features of novelty which characterize the invention, are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be had to the accompanying drawings and descriptive matter in which there is illustrated preferred embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood and objects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings wherein:
FIG. 1 is a perspective view of a new automated mechanical storage facility according to the present invention.
FIG. 2 is a top view of one of the storage units and elevator assemblies of the present invention in abutment.
FIG. 3 is a cross-sectional view of the belt and rollers of either one of the storage units or elevator assemblies of the present invention.
FIG. 4 is another cross-sectional view of the components of FIGS. 5.
FIG. 5 is a side view of one of the rails of the track assemblies of the present invention.
FIG. 6 is a side view taken along line 6--6 shown in FIG. 3.
FIG. 7 is a side view of the storage unit and elevator assembly of FIG. 2.
FIG. 8 is an illustration of an alternate embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference now to the drawings, and in particular to FIGS. 1 through 8 thereof, a new automated mechanical storage facility embodying the principles and concepts of the present invention and generally designated by the reference numeral 10 will be described.
The present invention, designated as numeral 10, includes a plurality of oval-shaped track assemblies 12 each spacedly situated in vertical alignment. Each track assembly comprises a pair of parallel track rails 14 each having an outer face, a top face, and a bottom face. As shown in FIG. 6, the rails of the track define an open inner face and an interior space. An inner surface of the top face and bottom face has a protrusion integrally formed thereon with a rectangular configuration along an entire length thereof for reasons that will become apparent hereinafter.
Also included is a plurality of storage units 16 each having a bottom face with a planar rectangular configuration. A peripheral lip is integrally coupled to a periphery of the bottom face and extends upwardly therefrom. Two pairs of arms IS are each fixedly coupled to opposite sides of the bottom face of the storage unit and extend upwardly to define a triangular configuration.
As shown in FIGS. 5 & 6, a roller assembly 20 is provided including a vertically oriented plate 22 with a pair of rollers 24 rotatably coupled to opposite ends thereof. These rollers are adapted for being situated within the interior space of an associated one of the rails of the corresponding track assembly. It should be noted that the rollers each have annular flanges for encompassing the protrusion, as shown in FIG. 6. The apex of each pair of arms is pivotally coupled to a central extent of the corresponding plate. The storage unit thus is adapted to move along the associated track assembly. Preferably, a motor is associated with at least one of the rollers of each storage unit which has teeth for engaging teeth formed in the track for allowing the selective control of the movement of the storage units by a user.
Various alternate embodiments of the present invention includes track assemblies with different configurations. Further, the elevator may be replaced with staggered linearly moving transporters 27. Note FIG. 8. This embodiment would be used when the track assemblies reside at a similar elevation.
An elevator assembly 28 includes a bottom face with a planar rectangular configuration. Similar to the storage unit, a peripheral lip integrally is coupled to a periphery of the bottom face of the elevator assembly and extends upwardly therefrom. Two pairs of arms are each fixedly coupled to opposite sides of the bottom face of the storage unit and extend upwardly to define a triangular configuration. During use, an elevator cable is coupled to an apex of the pairs of arms for allowing the raising and lowering of the elevator assembly level with a selected one of the track assemblies.
As shown in FIGS. 3 & 4, each of the storage units and elevation assemblies further include a pair of halves each having a plurality of elongated rollers 30 rotatably coupled between opposite sides of the unit or assembly. These rollers reside level with an upper peripheral edge of the peripheral lip and are preferably only slightly spaced. During use, the rollers remain in a common horizontal plane. A pair of drive cylinders 32 are mounted on opposite sides of the rollers in parallel therewith. Wrapped about the rollers and drive cylinders is a belt 34.
In use, the drive cylinders are adapted to move the belt such that cargo may be moved on to and removed from the storage units and elevation assemblies. To accomplish this, at least one of the drive cylinders of each half arc each connected to a common motor is selectively controlled by a user. In the preferred embodiment, auxiliary rollers 35 are mounted between the peripheral lip and the drive rollers for facilitating the removal of the cargo. As best shown in FIG. 2, a pair of belt and roller assemblies are included for specifically accommodating automobiles or the like.
As to a further discussion of the manner of usage and operation of the present invention, the same should be apparent from the above description. Accordingly, no further discussion relating to the manner of usage and operation will be provided.
With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention. | An automated mechanical storage facility is provided including at least one closed loop track assembly. Also included is a plurality of storage units for being slidably moved along the track assembly and further adapted to contain cargo. Further included is a belt for discharging the cargo from the storage units and further receiving cargo thereon. | 4 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a spray coating system. More specifically, the present invention relates to a spray coating system for fiber web.
[0003] 2. Description of the Related Art
[0004] Treating agents are typically applied to fiber webs to augment the functionality of the fiber web beyond that of a non-treated fiber web. The composition of the treating agent depends on the functionality desired from the fiber web.
[0005] The fiber web surface may, depending on the material from which the web is manufactured, be uneven. In paper and paperboard manufacturing, non-coated paper and paperboard surfaces generally assume the shape and local contour of the pulp and wood fiber at the surface of the paper or paperboard. This material profile may be undesired for downstream processing or use.
[0006] In the manufacture of fiber webs such as paper and paperboard, treating agents such as coatings are applied to augment the functionality of the fiber web. For example, applying a coating to paperboard makes it possible to use the material for diverse packaging purposes, ranging from preserving dry goods (such as tobacco) to perishables (such as frozen food). The requirements of the coating depends on the appearance and performance expected of the surface of the packaging.
[0007] Dictated by the desired eventual purpose of the treated fiber web, multiple treating agent applications may be made. An initial treating agent application can be made to improve the evenness of the fiber web such that subsequent treating agent applications can be made to provide the desired surface appearance and performance characteristics, such as smoothness, gloss, whiteness, opacity, and printability. A plurality of applications may be made to effect a result consistent with a desired performance level.
[0008] Many different techniques are used for spreading treating agents onto fiber webs. For example, doctor blading (also known as blade or knife coating) describe a series of techniques where a treating agent is brought in direct contact with the fiber web. The treating agent may be applied by submerging the fiber web in the treating agent (held in a pan), spraying the treating agent onto the fiber web, gravity feeding the treating agent onto the fiber web (also known as curtain coating), or using a treating agent applicator. The thickness of the resulting treating agent deposition is governed by a “doctor blade”, also referred to as doctoring. The purpose of the doctor blade is to mechanically remove excess treating agent, thus smoothing the profile of the treating agent on the fiber web. Other than doctoring with a physical scraping device, it is also possible to use a gas (e.g., air) to remove excess coating. The excess coating, which is contaminated by the presence of fiber, is then reclaimed through filtration and recirculation. Unfortunately, a large percentage of the excess coating is wasted due to the inability to completely remove the unwanted fiber therefrom. The application of a treating agent may be followed by the use of nip rolls to improve the bond between treating agent and fiber web.
[0009] Transfer coating refers to the process of applying a treating agent to a roller over which a fiber web is moving. Treating agent can be applied in various states, such as a liquid or a gas. Treating agent may be applied to either side of the fiber web. The process may additionally be followed by one or more nip rolls. Nip rolls use close proximity to combine the treating agent and fiber web through modification of parameters such as pressure and temperature.
[0010] The techniques mentioned here may also be used without a post-processing step such as doctoring. In such cases, intermediate steps may be taken to ensure that a treating agent profile is consistent with the desired result. An example of an intermediate step may include the guiding of the treating agent over an intermediate planar surface.
[0011] There is, therefore, a need in the art for improved systems and methods of spray coating for fiber web.
SUMMARY OF THE INVENTION
[0012] Embodiments of the present invention are concerned with the directing of a treating agent onto a fiber web. The treating agent deposition is improved such that the portion of treating agent directly deposited onto a fiber web is increased. Furthermore, increased deposition of treating agent reduces waste of treating agent, which diminishes the need for potential treating agent screening and recycling.
[0013] Additional embodiments may further provide for the application of an insulating or strengthening treating agent, known as a coating, to a fibrous web such as paper or paperboard. The application of a treating agent to paperboard has particular advantages, including, but not limited to, improved strength (e.g., tensile strength, stiffness), improved printability or ink absorption, applicability to food grade applications (e.g., food heating and preparation in domestic grade microwave ovens, odor absorption), surface finish (e.g., smoothness, color, gloss), foldability, and water absorbency.
[0014] Embodiments of the present invention may further include methods for directing a treating agent onto a moving fiber web. Such methods may provide that the application of the treating agent result in a beneficial reduction in the volume of treating agent required in order to coat a moving fiber web, minimize the necessity to reclaim and recirculate the excess treating agent that is applied on the surface, and provide improved control on the amount of treatment agent applied on the fiber web to provide the desired surface characteristics. The improved control of the coating process may also allow for an increase in the processing speed as the process is no longer governed by the gravity fed or dipped applications.
[0015] In possible embodiments, a treating agent may be collected in a feeding chamber. The feeding chamber may serve to equalize pressure of the treating agent and subsequently direct the treating agent to a linear continuous nozzle system. In another possible embodiment, the feeding chamber may direct the treating agent to a plurality of linear continuous nozzle systems. The linear continuous nozzle system, in contrast to prior art dependent on arrays of spray nozzles, may utilize a uniform slit arrangement which projects and directs the treating agent towards the moving fiber web.
[0016] In further embodiments, the treating agent may be modified by the continuous nozzle system such that the adherence to the fiber web is improved. Modification of the treating agent may be realized by atomization induced by a vibrating component internal to the linear, continuous nozzle system. Atomizing treating agents with high viscosity may improve the ability to direct said treating agent where a non-atomized treating agent would be difficult to adequately direct to maintain production requirements.
[0017] In a further embodiment, an electrostatic charge may be created in the treating agent to improve the distribution pattern of individual treating agent particles onto the moving fiber web. Atomized treating agent particles may lack sufficient kinetic energy to adhere to the moving fiber web. In exemplary configurations, the fiber web may have a directional momentum perpendicular to the application angle at which treating agent particles are emitted from the spray nozzle. To aid in the directional transfer of treating agent particles, an optional charge, opposite to that of the treating agent, may be induced in the moving fiber web to attract treating agent particles.
[0018] In a simple form, the treating agent application method disclosed in the present invention may apply a treating agent to a fiber web once. However, consistent with industry practice and manufacturing requirements, it is possible to apply the method of the present invention multiple times in order to achieve a desired result. Not only does the system create consistency in the finish, but also allows for custom coating effects such as anti-reflectivity coatings. Each embodiment of the present invention may be governed by distinct manufacturing requirements in that the modification of process parameters may guide the process step outcomes. Depending on manufacturing requirements and desired outcomes, treating agent applications may be made to one or both sides of the moving fiber web.
BRIEF DESCRIPTION OF DRAWINGS
[0019] FIG. 1 is a magnification of a cross-section of an exemplary fiber web with a build-up of treating agents to result in a desired finish.
[0020] FIG. 2 is a schematic diagram of the top right and top left perspective views of an exemplary arrangement of the treating agent coating system and associated accessories, as well as the moving system of fiber web and respective associated accessories.
[0021] FIG. 3 is an orthographic (top, side, and front) view of an exemplary spray coating system.
[0022] FIG. 4 is a cross-sectional view of an exemplary sprayer body and how its componentry fits together.
[0023] FIG. 5 is an exploded view of internal parts of an exemplary linear, continuous sprayer.
[0024] FIG. 6 is a cut-away view of an exemplary linear continuous nozzle tip arrangement.
DETAILED DESCRIPTION
[0025] Embodiments of the present invention provide for a fiber web treatment apparatus that coats an oriented fiber web by focusing a pressurized treatment material through a continuous, linear nozzle 25 that utilizes ultrasonic and electrostatic principles to smoothly and efficiently apply a thin coat of material. The fiber web can be passed through a succession of the continuous linear nozzle systems in order to get the proper level of finish desired on the web surface. FIG. 1 illustrates a cross-section of the fiber web 1 where the succession of coats for desired finish can be seen in 21 and 22 for side A and 23 and 24 for side B. A prime coat of treating agent 21 or 23 may first be applied to create an even surface on the uneven fiber web followed by subsequent coats and then a final coat 22 or 24 to provide the desired surface appearance and performance characteristics. Those familiar with the trade will appreciate that multiple treating agent applications could be made on one or both sides of the fiber web in order to be consistent with the predetermined finish characteristics desired.
[0026] The spray system in FIG. 2 may preferably utilize a continuous, linear spray tip 25 to coat the entire length of a fiber web 1 (4 to 40 ft) at a height range from 0.01 to 3 inches from the surface of the web depending on the variability of pressure and waste due to the viscosity differences in various treatment materials. The various treatment materials can be water-based, solventless, or hot melt materials such as latex, soy, or wax.
[0027] The embodiments described herein may all be used independently or in tandem to satisfy the needs of coating thickness and desired finish depending on which coat is being applied ( 21 or 22 , for side A, 23 or 24 for side B) at necessary quantities to keep the production of the fiber web moving at the necessary speed to enable the production goals of the fiber web manufacturing facility. In addition to the treating agent applications 21 , 22 , 23 and 24 , further treating agent applications may be made on top of, for example, coatings 22 or 24 , depending on the desired characteristics associated with the fiber web to be treated.
[0028] In FIG. 3 , the treatment material may first be pumped into the treatment material tank 2 from an outside source such as a tanker truck or from a larger, external tank that can be filled intermittently without disrupting the fiber coating process. From the treatment material tank 2 , the treatment material may be pumped, via an internal tank pump, through hard lined pipes 19 connected to both ends of the continuous, linear spray body 11 ( FIG. 4 and FIG. 5 ) in order to supply sufficient material as required to accommodate the coating of a fast-moving fiber web. Once the material enters through the material inlet 5 into the internal chamber 6 ( FIG. 4 ), the material may then pass through a slotted baffle 12 in order to equalize the pressure of the material along the full length of the continuous, linear tip assembly. Just after the treatment material passes through the baffle, the treatment material may surround the pintle 8 of the sprayer assembly.
[0029] The pintle 8 may have multiple functions within the system. The pintle may be electrostatically charged by the electrostatic generator 14 and as a result, induces the same charge in treating agent molecules excited by the pintle 8 . The pintle 8 may be connected to the ultrasonic generator 13 by a connecting frame 10 , so that as the pintle is pulled back to allow material flow, an ultrasonic frequency is produced on the pintle that further breaks apart the similarly charged, somewhat viscous material particles into a mist that spreads evenly across the surface of the fiber web.
[0030] The electrostatic charge imparted may be varied to control the treating agent deposition rate. The deposition rate may determine how closely the treating agent mimics the contours of the surface it is deposited on. For example, the base or prime treating agent layer ( 21 or 23 ) may have a lower degree of charge, which may lead to treating agent build-up inconsistent with the profile of the fiber web 1 . As a result, the treating agent layers ( 21 or 23 ) may have a profile more smooth than that of the fiber web 1 . An increased electrostatic charge of treating agent intended for subsequent layers (such as 22 or 24 ), may lead the treating agent particles to mimic more closely the profile of the surface it is deposited on. Such deposition may lead to consistent and even coating of previous deposition layer using less treating agent.
[0031] The fiber web 1 passed under the sprayer assembly ( FIG. 5 ) may hold a charge opposite to the charge of the treatment material, promoting even and controllable levels of treating agent across the surface of the fiber web, depending on the degree of charge associated with the treating agent. The fiber web, which may not be electrically conductive, may be grounded by the two conveyors 15 ( FIG. 3 ) below it. The material recycling tray 16 between the two conveyor assemblies may have a charge opposite to the charge of the treatment agent and therefore acts as a collector of any sprayed material when the fiber is not passing through or during the priming or cleaning of the sprayer body. The material recycling tray may be connected to a vacuum line 20 that pulls excess material back into the reservoir for recycling or to a waste container.
[0032] To aid in the application of the mist created by the ultrasonically atomized, electrostatic charged, continuous linear nozzle 25 ( FIG. 6 ), a stream of pressurized gas emitted from the gas ports 26 may help focus the spray of the treatment material in a manner that facilitates the focus the flow of charged treating agent particles, as well as non-mechanically smooth the finish of the treatment material on the web which helps to reduce the waste of treatment material that is considered standard practice. This approach reduces the need for post-processing steps such as nip rolls or doctor blades, commonly used in the industry.
[0033] Such a gas system that helps to direct and sharpen the mist created by the ultrasonic and electrostatic spray tip 9 may originate from a gas compressor 17 that charges the gas in gas tank 3 . The gas may be regulated at the air inlet 4 of the outer chamber 7 , as needed by valves 18 that open or close to create the desired effect on the treatment material by travelling through hard lined tubes 19 that enter into the gas outer chamber 7 of the sprayer body 11 . The electrostatic tip of the sprayer may be a metallic housing that may be also connected to the electrostatic generator 14 , which may induce a corona discharge to charge the gas and to further charge any treatment material particles that were not previously charged by the pintle 8 . Excess gas may, like the treating material, be pulled into the material recycling tray 16 to exhaust to the waste filtration vacuum line 20 .
[0034] After each application of the treatment material on to the fiber web, the treatment material may then be rapidly cured by a system such as an infrared heater or a heated roller in order to cure the material before the web moves on to successive coating processes on either side of the fiber web.
[0035] These embodiments (ultrasonic, electrostatic, linear continuous nozzle and non-reacting gas assist) can be used independently or in any combination and in any order to achieve the desired finish on the fiber web.
[0036] While various embodiments have been described above, it should be understood that they have been presented by way of example only, and not limitation. The descriptions are not intended to limit the scope of the invention to the particular forms set forth herein. Thus, the breadth and scope of a preferred embodiment should not be limited by any of the above-described exemplary embodiments. It should be understood that the above description is illustrative and not restrictive. To the contrary, the present descriptions are intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims and otherwise appreciated by one of ordinary skill in the art. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents. | The invention relates to a method for ensuring even and consistent application of a treating agent onto a fiber web. The method of the invention improves coating agent deposition process such that the fiber web is evenly coated using less raw material by improving the deposition method and atomization quality, better control of the deposition rate and improving the adhesion properties. The method collects a treating agent in a chamber directing the agent through a linear continuous nozzle onto a fiber web. The treating agent is electrostatically charged and ultrasonically nebulized before being directed towards the fiber web. | 3 |
BACKGROUND
The present invention is concerned with various surface antigens of human cancer identified by mouse monoclonal antibodies and more particularly, with mouse monoclonal antibodies recognizing various antigens expressed by human malignant astrocytoma.
Astrocytoma tumors are normally found only in the brain and are difficult to diagnose in a manner wherein a useful prognosis can be generated and the most effective treatment predicted. The present invention provides monoclonal antibodies which may be used in identifying or phenotying astrocytoma tumors whereby the course of the disease can be predicted and suitable therapy, e.g. chemotherapy versus radiotherapy--can be accomplished.
Furthermore, the present invention provides monoclonal antibodies which may be coupled with various side or toxic agents which then may be used for actual treatment or containment of astrocytoma tumors. Imaging of the tumor may also be possible using various radio labels; however, other means which are believed to be more practical, are available for this purpose.
The present invention also provides a process by which the inventive materials can be raised by sensitization of mice to raise the antibodies and the application of hybridoma fusion techniques to immortalize the cell line.
Work has been done in general with cell surface antigens of human cancers and cell surface antigens of human malignant melanoma and human renal cancer identified by mouse monoclonal antibodies have been described in the literature (1,2).
BRIEF DESCRIPTION
Abbreviations used in this disclosure: GFA, glial fibrillary acidic protein; AB, monoclonal antibody; EBV, Epstein-Barr virus; NP-40, Nonidet P40; conA, concanavalin A; PMSF, Phenylmethylsulfonylfluoride; PAGE, polyacrylamide gell electrophoresis; 2-D, two-dimensional electrophoresis; IEF, isoelectric focusing.
The surface antigens of cultured human malignant astrocytomas were analyzed using mouse monoclonal antibodies. BALB/c mice were immunized repeatedly with either SK-MG-1 [a glial fibrillary acidic protein (GFA)-negative astrocytoma line] or SK-A02 [a GFA-positive astrocytoma line]. Following fusion with NS/1 mouse myeloma cells, 12 antibody-producing clones were selected for detailed study. Serological analysis permitted the identification of 9 distinct antigen systems. Four antibodies (Ab AJ225, Ab A010, Ab AJ8, Ab A0122) identified cell surface antigens preferentially expressed on tumors of neuroectodermal origin, and these antibodies subdivided the astrocytoma panel into distinguishable subsets. The determinants detected by Ab A010 and Ab AJ8 showed mutually exclusive expression on the astrocytoma lines. The A010 and AJ8 phenotypes appeared to reflect the differentiation state of the cultured cells; 4/7 A010-positive astrocytomas expressed GFA, an intracellular astrocyte differentiation antigen, whereas all AJ8-positive astrocytomas (9/9) were GFA-negative. Five antibodies (Ab AJ10, Ab AJ9, Ab AJ17, Ab AJ425, Ab AJ2) recognized determinants widely distributed on normal and malignant cells. AJ2 was highly immunogenic in mice, and antibody to AJ2 was commonly found in the serum of mice immunized with human cells. Four antibodies defined in this study precipitated proteins from reduced preparations of radioisotope-labelled SK-MG-1 and SK-A02 cells: Ab AJ225 (M r 145,000), Ab A0122 (M r 265,000), Ab AJ10 (M r s 195,000, 165,000) and Ab AJ2 (M r s 170,000, 140,000, 140,000, 28,000).
IN THE DRAWINGS
FIG. 1 Autoradiograms of immunoprecipitates obtained with Ab AJ225, Ab AJ2, Ab AJ10 and Ab A0122 from 125 I-labelled membrane extracts of SK-MG-1 and SK-A02 analyzed by NaDodSO 4 /PAGE. Labelled SK-MG-1 cells were used for the analysis of Ab AJ225, Ab AJ2 and Ab AJ10 and labelled SK-A02 cells for the analysis of Ab A0122. Lanes (a) and (c) are control immunoprecipitates obtained with nu/nu mouse serum. (b) and (d) are immunoprecipitates obtained with the designated monoclonal antibody. Lanes (a) and (b) are reduced samples; (c) and (d) are non-reduced samples. Ab AJ225 and Ab AJ2 immunoprecipitates were analyzed with 9% acrylamide gels; Ab AJ10 and Ab A0122 immunoprecipitates with 7.5% acrylamide gels. Control immunoprecipitates for the analysis of Ab AJ2 were the same as those shown for Ab AJ225. Optimal immunoprecipitation was obtained with 1.0 μl Ab AJ225, 0.5 μl Ab A0122 and Ab AJ10, and 0.1 μl Ab AJ2. The molecular weight standards were myosin (212,000), β-galactosidase (116,000), phosphorylase (97,500), bovine albumin (66,000), ovalbumin (43,000), concanavalin A (26,000) and myoglobin (17,000).
FIG. 2. Autoradiograms of immunoprecipitates obtained with Ab AJ2 from 125 I-labelled SK-MG-1 membrane extracts analyzed by two-dimensional electrophoresis. Isoelectric focusing (IEF)(the first dimensional separation) was carried out in the horizontal direction, and NaDodSO 4 /PAGE (the second dimensional separation) was carried out in the vertical direction on a 9% acrylamide gel. A: immunoprecipitates reduced before separation by IEF; B: immunoprecipitates reduced after separation by IEF; and C: unreduced immunoprecipitates. Control immunoprecipitates obtained with nu/nu mouse serum gave no significant spots.
FIG. 3. Autoradiograms of immunoprecipitates obtained with (BALB/c×C57BL/6)F 1 mouse (CBF 1 ) antisera or Ab AJ2 from [ 35 S]methionine-labelled cultured human cell lines analyzed by NaDodSO 4 /PAGE (9% gels). Lanes (a)-(e) are immunoprecipitates from labelled MeWo melanoma cell line; (f) is an immunoprecipitate from labelled 2774 ovarian cancer cell line. The precipitating antibodies were: (a) control: 3 μl normal CBF 1 mouse serum; (b) 3 μl CBF 1 anti-human ovarian cancer (2774) serum; (c) same as (b) but precleared with Ab AJ2; (d) 0.1 μl Ab AJ2; (e) 15 μl CBF 1 anti-human bladder cancer (RT-4) serum; (f) 3 μl CBF 1 anti-human ovarian cancer (SK-OV-3) serum.
FIG. 4. Proposed relationship between astrocyte differentiation and phenotypic characteristics of cultured astrocytomas based on serological typing for AJ8, A010 and GFA.
DESCRIPTION
Tissue Culture
Astrocytoma and other human tumor cell lines and short-term cultures of normal human skin fibroblasts and kidney epithelial cells have been described (3,4,5).
Serological Procedures
Direct serological tests were performed using an anti-mouse Ig mixed hemadsorption assay (1). Direct test conditions and absorption procedures were identical to those previously described for the protein A-mixed hemadsorption assay (4). Heat stability of the antigenic determinants was assessed by heating the cell suspension to 100° C. for 5 minutes and then testing for residual antigenic activity in absorption tests. Glial fibrillary acidic protein (GFA) was demonstrated by indirect immunofluorescence using monospecific rabbit antiserum provided by Dr. L. F. Eng.
Immunizations
BALB/c mice were immunized with either the GFA-negative astrocytoma line SK-MG-1 [designated AJ in a previous publication (3)] or the GFA-positive astrocytoma line SK-A02 (established by J. R. Shapiro and W. R. Shapiro, Laboratory of Neuro-Oncology, Sloan-Kettering Institute). For the initial immunization, 1×10 7 astrocytoma cells were injected subcutaneously with Freund's complete adjuvant. Five to ten subsequent immunizations were carried out at 2-week intervals by intraperitoneal inoculation of 1×10 7 tumor cells in the absence of adjuvant. Immunized mice were sacrificed 3 days after the last injection.
Production of Mouse Monoclonal Antibodies
The fusion of immune spleen cells with mouse myeloma MOPC-21 NS/1 ATCC #T1B 18 cells (ratio 5:1) was performed as described (1,2). Fused cells were grown in selective medium and subcloned by limiting dilution as previously described (1,2). For initial screening, supernatants were tested for antibody activity on a panel of cultured cells consisting of 3 astrocytoma cell lines (including the immunizing line), 2 melanomas, 5 carcinomas and adult and fetal skin fibroblasts.
ATCC designations of screening cell lines are
HT-29 (HTB 38) (colon)
SK-MEL-28 (HTB 72) (melanoma)
SK-MEL-31 (HTB 73) (melanoma)
SK-ME-180 (HTB 33) (cervix)
T-24 (HTB 4) (bladder)
SK-N-SH (HTB 11) (neuroblastoma)
SK-N-MC (HTB 10) (neuroblastoma)
U-373 MG (HTB 17) (astrocytoma)
BT-20 (HTB 19) (breast)
MCF-7 (HTB 22) (breast)
SK-BR-3 (HTB 30) (breast).
Antibody subclass was determined by double diffusion in agar with anti-Ig heavy-chain-specific reagents (Bionetics, Kensington, MD). Cultures of cloned hybridomas were injected subcutaneously into nu/nu mice (NIH Swiss Background). Sera from mice with progressively growing tumors were used for serological and biochemical characterization.
Immunoprecipitation Procedures
Antibodies were tested for precipitating activity using radiolabelled antigen from detergent solubilized extracts of the immunizing cell line. Three different labelling procedures were used. Labelling with [ 3 H]glucosamine (New England Nuclear, 30-60 Ci/mmole) or with [ 35 S]methionine (New England Nuclear, 1000 Ci/mmole) and extraction with Nonidet P40 (NP-40) buffer were carried out as described previously (1,2). In some experiments the [ 35 S]methionine-labelled extract was fractionated on a 1 ml concanavalin A (conA)-Sepharose (Pharmacia, Piscattaway, NJ) column, using 0.15M NaCl, 0.01M Tris HCl pH 7.3, 0.1% NP-40 as column buffer, and eluting with 0.2M α-methyl D-mannoside. 125 I-labelling of solubilized membrane preparations followed Brown et al (6), except that the gel filtration step before iodination was omitted. Membrane preparation was carried out according to Natori et al (7), except that the buffer during disruption was supplemented with 10 mM MgCl 2 and 2 mM phenylmethylsulfonylfluoride (PMSF). Protein-conjugated 125 I was estimated by counting samples precipitated with cold 10% (w/v) trichloroacetic acid and then washed with ethanol and acetone.
Radioimmunoprecipitation procedures with [ 3 H]glucosamine- and [ 35 S]methionine-labelled samples were carried out as described (1,2). For 125 I-labelled samples, aliquots (200 μl) were first precleared of non-specific binding material by treating with nu/nu mouse serum (1 μl), rabbit anti-mouse I gG (15 μl) (Cappel Laboratories, Cochranville, Pa) and Staphylococcus aureus (15 μl) (Bethesda Research Laboratories, Bethesda, Md). To aliquots (200 μl) of the precleared supernatant solution (5×10 5 cpm 125 I-protein), 0.1 or 1 μl antibody and 15 μl rabbit anti-mouse IgG were added. Immune complexes were isolated with S. aureus as described (6), except that 0.1 ml of normal rabbit serum was added to the second wash buffer to reduce background binding. Labelled antigen was eluted from the pellet and analyzed by NaDodSO 4 /polyacrylamide gel electrophoresis (PAGE) and two-dimensional (2-D) electrophoresis as described previously (8,9), except that iodoacetamide (14 mg/ml) was added to the sample buffer when non-reduced samples were analyzed.
RESULTS
From 4 fusions of NS/1 myeloma with spleen cells from mice immunized with SK-MG-1 (3 fusions) or SK-A02 (1 fusion), 12 antibody-producing clones were selected for detailed analysis (Table 1). The serological specificity of these antibodies was tested on a panel of 49 established human cell lines (Table 2). The antibodies were also tested on short-term cultures of human adult and fetal skin fibroblasts, kidney epithelial cells and melanocytes. In most cases, serological analysis consisted of both direct and absorption tests. Melanocytes were studied only by direct test, and lymphoblastoid lines, erythrocytes, adult brain and fetal brain were analyzed only by absorption tests.
Monoclonal antibodies Ab AJ225, Ab A010, Ab AJ8, Ab A0122, Ab AJ10, Ab AJ9, Ab AJ17, Ab AJ425 and Ab AJ2 defined 9 distinct cell surface antigenic systems. They have been selected for detailed presentation (Table 2). [Of the remaining 3 monoclonal antibodies listed in Table 1, Ab A050 and Ab A092 were serologically related to Ab A0122, and Ab AJ60 was similar to Ab AJ10].
The above hybridoma cell lines are maintained and are available on deposit at Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, N.Y. 10022 under designations corresponding to the monoclonal antibodies produced by each hybridomas as follows:
AJ225
AJ8
A0122
AJ10
AJ9
AJ17
AJ425
AJ2
A010
A050
A092
AJ60
Upon granting of the patent, said hybridoma cell lines will be permanently available from the deposit with the American Type Culture Collection under ATCC designations corresponding to the above Sloan-Kettering designations as follows:
______________________________________ SKI ATCC______________________________________ AJ225 HB8344 AJ8 HB8339 A0122 HB8349 AJ10 HB8341 AJ9 HB8340 AJ17 HB8342 AJ425 HB8345 AJ2 HB8338 A010 HB8346 AJ60 HB8343 A050 HB8347 A092 HB8348______________________________________
AJ225 Antigenic System
Direct tests and absorption analysis with Ab AJ225 indicated that the determinant detected by this antibody was largely restricted to astrocytoma cell lines (Table 2). Although all astrocytoma lines absorbed Ab AJ225 reactivity, the titers in direct serological tests permitted a division of cultured astrocytomas into two groups based upon quantitative differences in antigen expression; 12/16 tumors were high expressors and 4/16 low expressors. The only other tumor lines expressing high levels of AJ225 were 1/10 melanomas and 1/17 epithelial cancers; 2/4 renal carcinomas expressed low levels of the antigen demonstrable by absorption tests. In addition, a T-cell leukemia (MOLT-4) absorbed Ab AJ225 reactivity. EBV-transformed B-cells, adult and fetal skin fibroblasts, kidney epithelial cells, and homogenates of adult and fetal brain did not absorb. The results of direct serological tests on melanocytes suggest low levels of AJ225 expression on this normal cell type.
Ab AJ225 identified a heat-labile determinant and immunoprecipitated a protein with M r 145,000 from 125 I-labelled SK-MG-1 (FIG. 1). This band was not detected in precipitates from cells labelled with [ 3 H]glucosamine or [ 35 S]methionine. In some experiments, this antigen appeared as a closely spaced doublet. The pI of the 145,000 M r component was 4.8. Without reduction a single band with M r 150,000 was identified relative to reduced standards. The inability to precipitate the AJ225 antigen after metabolic labeling raised the possibility that this determinant was a fetal calf serum component adsorbed to the cell surface. However, the highly restricted distribution of this antigen, the failure of fetal calf serum to inhibit Ab AJ225, and the ability of fresh astrocytoma tissue to absorb Ab AJ225 reactivity speak strongly against this possibility.
A010 and AJ8 Antigenic Systems
The A010 and AJ8 antigenic systems are described together because, with two exceptions, they subdivided 16 cultured astrocytomas into mutually exclusive A010-positive and AJ8-positive subsets. The exceptions were SK-MG-10 which expressed neither antigen and SK-MG-12 which expressed both.
The A010 antigen was identified on 7/16 astrocytoma lines. As shown in Table 2, 4/7 A010-positive astrocytomas were GFA-positive. The antigen was also demonstrated on 3/10 melanomas, 2/2 neuroblastomas, and a T-cell leukemia. Direct serological tests failed to demonstrate the A010 determinant on epithelial cancers; however, absorption of Ab A010 reactivity indicated low levels of antigen expression on 2/17 of these lines. EBV-transformed B-cells did not absorb Ab A010 reactivity. The A010 determinant was detected in adult and fetal brain but not identified on adult and fetal skin fibroblasts, kidney epithelial cells or melanocytes.
The AJ8 antigen was detected on 9/16 actrocytoma lines. All AJ8-positive astrocytomas were GFA-negative (Table 2). The AJ8 antigen was also demonstrated on 4/10 melanomas. Direct serological tests failed to demonstrate the AJ8 determinant on epithelial cancers; however, absorption analysis detected low levels of antigen expression on 4/17 cell lines. Neuroblastomas (0/2), EBV-transformed B-cells and a T-cell leukemia did not absorb Ab AJ8 reactivity. AJ8 was detected on adult and fetal skin fibroblasts and melanocytes, but not on cultured kidney epithelial cells or in adult or fetal brain.
The A010 determinant was heat-labile, suggesting that it resided on a protein, but Ab A010 did not precipitate a detectable component from [ 3 H]glucosamine-, [ 35 S]methionine-, or 125 I-labelled SK-A02 cells. The AJ8 determinant was also heat-labile and could not be precipitated from [ 3 H]glucosamine-, [ 35 S]methionine-, or 125 I-labelled SK-MG-1 cells.
A0122 Antigenic System
The A0122 antigen was found on 9/16 astrocytoma lines (Table 2). The pattern of expression on astrocytomas clearly distinguished the A0122 system from the AJ225, AJ8 or A010 systems. A0122 was strongly represented on 8/10 melanomas. Neuroblastomas (0/2), epithelial cancers (0/17), EBV-transformed B-cells, and a T-cell leukemia did not express A0122. Melanocytes and adult and fetal skin fibroblasts were highly reactive with Ab A0122, and homogenates of adult and fetal brain absorbed Ab A0122 reactivity. A0122 was not detected on kidney epithelial cells or erythrocytes.
Ab A0122 identified a heat-labile determinant and immunoprecipitated a protein complex from 125 I-labelled SK-A02 cells. Four major proteins with M r s 265,000, 195,000, 180,000 and 140,000 were identified in reduced preparations (FIG. 1). Without reduction, 4 components with M r s 255,000, 150,000, 135,000 and 115,000 were seen. Only the 265,000 M r band was detected after labelling with [ 35 S]methionine. Ab A0122 did not precipitate a detectable component from [ 3 H]glucosamine labelled SK-A02 cells. Two other monoclonal antibodies, Ab A050 and Ab A092, appeared to recognize the A0122 determinant. The pattern of Ab A050 reactivity was identical to Ab A0122, but Ab A050 did not precipitate any components from 125 I-labelled SK-A02 cells. Ab A092 precipitated the same protein complex as Ab A0122, although minor differences were found in the serological reactivity of the two antibodies.
AJ10 Antigenic System
The AJ10 determinant was found to be widely distributed on normal and malignant cells (Table 2). Despite this broad representation, the AJ10 antigen was not detected on any of the breat or colon cancer cell lines.
Ab AJ10 identified a heat-labile determinant and immunoprecipitated two clearly indentifiable proteins with M r s 195,000 and 165,000 from reduced extracts of [ 35 S]methionine- or 125 I-labelled SK-MG-1 cells (FIG. 1). Unreduced samples migrated as two bands corresponding to M r S 135,000 and 110,000. Ab AJ10 did not precipitate a detectable component from [ 3 H]glucosamine-labelled cells. A second monoclonal antibody, Ab AJ60, demonstrated identical serological reactivity to Ab AJ10 but did not precipitate the 195,000/165,000 M r complex.
AJ2 Antigenic System
AJ2 was demonstrated on all nucleated human cells examined, both normal and malignant (Table 2). Ab AJ2 identified a heat-labile determinant and immunoprecipitated a glycoprotein complex from [ 3 H]glucosamine-, [ 35 S]methionine- and 125 I-labelled SK-MG-1 cells. With 125 I-labelling and under reduced conditions 3 components were identified by NaDodSO 4 /PAGE: 2 heavy chains with M r s 170,000 and 140,000 and one light chain with M r 28,000 (FIG. 1). Under non-reduced conditions, the 2 high molecular weight components migrated in a similar fashion, but the light chain was not identified (FIG. 1). 2-D electrophoresis resolved the 140,000 M r band into two distinct bands with slightly different molecular weights (FIG. 2). The 170,000 M r component had a pI of 5.2; the two 140,000 M r chains had isoelectric points of 5.5 and 4.7. The 28,000 M r light chain focused in 3 major spots at pH 6.2, 5.9 and 5.7 (FIG. 2A). The light chain was disulfide-linked to only one of the heavy chains. This was demonstrated in two ways. 2-D electrophoresis without reduction resulted in the disappearance of the light chain components and a shift upward of the 140,000 M r chain with pI 5.5 (FIG. 2C). Reduction after isoelectric focusing and before NaDodSO 4 /PAGE demonstrated the light chain beneath the 140,000 M r chain with pI 5.5 (FIG. 2B). [ 35 S]methionine labelled the 4 submits, but the light chain very weakly. With [ 3 H]glucosamine-labelling, only the heavy chains were labelled. The [ 35 S]methionine-labelled SK-MG-1 membrane preparation was fractionated on a conA-Sepharose column; Ab AJ2 precipitated the 170,000/140,000/140,000/28,000 M r s complex from the bound and eluted glycoprotein fraction.
Our experience suggests that AJ2 is highly immunogenic in mice. A range of antisera from mice hyperimmunized with different human cell lines immunoprecipitated a 140,000 M r component from [ 35 S]methionine-labelled cells (FIG. 3). Preclearing with Ab AJ2 removed this M r 140,000 component; preclearing with monoclonal antibodies of the same Ig subclass as Ab AJ2 but directed against other determinants did not remove the 140,000 M r band. In view of the strong immunogenicity of the AJ2 determinant, preclearing of AJ2 from cell extracts before immunizations may be advisable when antibodies to less immunogenic components are sought.
AJ9, AJ17 and AJ425 Antigenic Systems
Ab AJ9, Ab AJ17 and Ab AJ425 recognized heat-labile determinants on most normal and malignant cells. Differences in serological reactivity with specific cell lines suggest that they identify different antigenic systems. These antibodies have not precipitated detectable components from [ 3 H]glucosamine-, [ 35 S]methionine-, or 125 I-labelled SK-MG-1 cells.
DISCUSSION
This study of human malignant astrocytoma has generated a series of mouse monoclonal antibodies that define nine distinct cell surface antigenic systems. These cell surface determinants have been characterized as restricted or widely distributed based on their distribution on a large panel of cultured tumor cell types. The restricted antigens (AJ225, A010, AJ8, A0122) are preferentially expressed on tumors of neuroectodermal origin. The non-restricted antigens (AJ10, AJ9, AJ17, AJ425, AJ2) are found on virtually all malignant cells. Cell surface determinants present only on tumor cells have not been detected in this analysis; the antigens described here have been identified as normal cell surface components by their expression on at least one normal cell type. The non-restricted antigenic systems are expressed on most normal cell types and are found in brain. The restricted systems, on the other hand, have a restricted distribution on normal cells as well. A010 and A0122 are detected in brain, AJ225 and AJ8 are not. The failure to identify the AJ225 and AJ8 determinants in brain suggests that within the context of normal neural cells AJ225 and AJ8 represent "tumor" antigens. However, end-point absorptions with homogenates of brain may not be sufficiently sensitive to detect antigens restricted to a small subpopulation of neural cells. Extending the serological analysis to sections of normal brain and astrocytomas will be important in assessing the significance of antigens detected on tumor cells in culture but not demonstrable in normal brain by absorption techniques or binding assays.
In this study, subsets of cultured astrocytomas have been identified. The biological significance of grouping astrocytomas on the basis of cell surface characteristics is unknown. Observations in other tumor systems suggest that the surface phenotype of transformed cells reflects both the cell of origin and the state of differentiation of the normal counterpart at the time of malignant change (10). Phenotypic differences among astrocytoma lines may be explained in one of three ways. Astrocytoma subsets may point to transformation in one of several developmentally and phenotypically distinct astrocyte lineages. Alternatively, tumor subsets may indicate that transformation has occurred at different points in a single lineage of astrocyte differentiation. Lastly, tumor subsets may reflect the random loss or random expression of astrocyte differentiation antigens.
The division of cultured astrocytomas into mutually exclusive A010-positive and AJ8-positive subsets and the relationship between the A010/AJ8 surface phenotype and GFA expression provide an opportunity to speculate on the biological significance of these cell surface markers and of the subsets they define. The intriguing feature of A010 and AJ8 expression is the essentially non-overlapping distribution on cultured astrocytomas. It is unlikely that subsetting of this kind is explained by a random expression or loss of the A010 and AJ8 determinants. However, this reciprocal relationship could be taken as evidence for the existence of two antigenically distinct astrocyte lineages or two antigenically distinct phases in a single lineage. Past studies of GFA have indicated that GFA is absent in pleuripotential neuroglial stem cells and immature astrocyte precursors but is detectable in all mature astrocytes (11). The observation that A010 is present on GFA-positive tumors and that AJ8-positive tumors are GFA-negative, suggests that these cell surface markers reflect the state of differentiation of astrocytomas in culture and lends support to the latter view that transformation has occurred in astrocytes at different points in a single developmental lineage.
Serological typing for AJ8, A010 and GFA suggests that cultured astrocytomas can be divided into three groups on the basis of differentiation-related phenotypic characteristics. Cultured astrocytomas which are AJ8 - /A010 + /GFA + represent more differentiated cell lines; those which are AJ8 + /A010 - /GFA - represent less differentiated cell lines; and those which are AJ8 - /A010 + /GFA - , AJ8 - /A010 - /GFA - or AJ8 + /A010 + /GFA - represent groups at intermediate stages in differentiation. These relationships are illustrated in FIG. 4. It will now be important to determine whether this grouping of cultured astrocytomas on the basis of differentiation characteristics can be shown with tumors in vivo. Antigens AJ225 and A0122 also subset cultured astrocytomas, but the relationship between their expression and other biological properties of normal and malignant astrocytes is uncertain.
The reciprocal expression of A010 and AJ8 also extends to normal cells of neuroectodermal origin. Brain, for example, is A010+/AJ8-; melanocytes are A010-/AJ8+. Preliminary observations with other neuroectodermal tumors, including neuroblastoma and melanoma, indicate a similar pattern of reciprocal antigen expression. Also noteworthy is the detection of A010 on a T-cell leukemia (MOLT 4), a pattern reminiscent of that observed with other antigens, such as Thy-1, that are shared by T-cells and brain (12).
Because of differential serological methods, the use of different cell panels and the limited biochemical characterization of many determinants, especially those that do not precipitate, it is not possible to make direct comparisons between the antigens defined in this report and those described by other investigators in studies of malignant astrocytoma (13). Such comparisons await an exchange of reagents. However, serological differences on a uniform panel of cell lines together with immunochemical differences clearly distinguish the determinants described here from the 12 antigenic systems (gp 150, gp 95, M 19 , R 8 , O 5 , R 24 , gp160, S 25 , gp120r, gp120nr, gp115, V 1 ) previously defined in our laboratory by mouse monoclonal antibodies to human malignant melanoma and human renal cancer (1,2,14).
It will be understood that the specification and examples are illustrative but not limitative of the present invention and that other embodiments and functional equivalents within the spirit and scope of the invention or by following the procedures outlined in the specification of this application will suggest themselves to, or be made by, those skilled in the art.
REFERENCES
1. Dippold, W. G., Lloyd, K. O., Li, L. T. C., Ikeda, H., Oettgen, H. F. and Old, L. J. (1980) Proc. Natl. Acad. Sci. USA 77, 6114-6118.
2. Ueda, R., Ogata, S-I., Morrissey, D. M., Finstad, C. L., Szkudlarek, J., Whitmore, W. F., Oettgen, H. F., Lloyd, K. O. and Old, L. J. (1981) Proc. Natl. Acad. Sci. USA 78, 5122-5126.
3. Pfreundschuh, M., Shiku, H., Takahashi, T., Ueda, R., Ransohoff, J., Oettgen, H. F. and Old, L. J. (1978) Proc. Natl. Acad. Sci. USA 75, 5122-5126.
4. Carey, T. E., Takahashi, T., Resnick, L. A., Oettgen, H. F. and Old, L. J. (1976) Proc. Natl. Acad. Sci. USA 73, 3278-3282.
5. Ueda, R., Shiku, H., Pfreundschuh, M., Takahashi, T., Li, L. T. C., Whitmore, W. F., Oettgen, H. F. and Old, L. J. (1979) J. Exp. Med. 150, 564-579.
6. Brown, J. P., Wright, P. W., Hart, C. E., Woodbury, R. G., Hellstrom, K. E. and Hellstrom, I. (1977) J. Biol. Chem. 255, 4980-4983.
7. Natori, T., Law, L. W. and Appella, E. (1977) Cancer Res. 37, 3406-3413.
8. O'Farrell, P. H. (1975) J. Biol. Chem. 250, 4007-4021.
9. Ogata S., Ueda, R. and Lloyd, K. O. (1981) Proc. Natl. Acad. Sci. USA 78, 770-774.
10. Magrath, I. T. (1981) J. Nat. Cancer Inst. 67, 501-514.
11. Juurlink, B. H. J., Fedoroff, S., Hall, C. and Nathaniel, E. J. H. (1981 ) J. Comp. Neurol. 200, 375-391.
12. Barclay, A. N., Letarte-Muirhead, M. and Williams, A. F. (1976) Nature 263, 563-567.
13. Schnegg, J. F., Diserens, A. C., Carrel, S., Accolla, R. S. and de Tribolet, N. (1981) Cancer Res. 41, 1209-1213.
14. Pukel, C. S., Lloyd, K. O., Travassos, L. R., Dippold, W. G., Oettgen, H. F. and Old, L. J. (1982) J. Exp. Med. 155, 1133-1147.
TABLE 1__________________________________________________________________________DERIVATION OF MOUSE HYBRIDOMAS PRODUCING MONOCLONAL ANTIBODIESREACTING WITH SURFACE ANTIGENS OF HUMAN MALIGNANTASTROCYTOMA CELLS Astrocytoma cell No. of positive No. of clonesFusion line used for No. of wells/Total no. isolated and AntibodiesNo. immunizations Immunizations of wells analyzed Characterized__________________________________________________________________________1 SK-MG-1 6 17/480 4 AJ2 (1)*, AJ8 (1)*, AJ9 (1)*, AJ17 (1)*2 SK-MG-1 6 10/480 3 AJ60 (1), AJ225 (μ)* AJ425 (1)*3 SK-MG-1 8 59/360 1 AJ10 (1)*4 SK-A02 10 20/360 4 A010 (1)*, A050 (1), A092 (1), A0122 (1)*__________________________________________________________________________ *Prototype antibodies (see Table 2)
TABLE 2 SEROLOGICAL CHARACTERIZATION OF NINE PROTOTYPE MOUSE MONOCLONAL ANTIBODIES DETECTING CELL SURFACE ANTIGENS ON HUMAN MALIGNANT ASTROCYTOMA CELLS Ab AJ225 Ab A010 Ab AJ8 Ab A0122 Ab AJ10 Ab AJ9 Ab AJ17 Ab AJ425 Ab AJ2 Titer* Titer Titer Titer Titer Titer Titer Titer Titer Cells × 10.sup.-3 Abs** × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs × 10.sup.-3 Abs Astrocytomas (GFA)*** SK-MG-1 (-) 100 + - - 10 + - - 100 + 100 + 100 + 100 + 10000 + SK-MG-2 (+) - + 10 + - - 100 + 100 + 1000 + 10 + - + 1000 + SK-MG-3 (-) 10 + - - - + 1000 + 100 + 1000 + 100 + 100 + 10000 + SK-MG-4 (-) 100 + 100 + - - 1000 + 10 + 1000 + 10 + 10 + 1000 + SK-MG-7 (-) 100 + - - - + 100 + 10 + 1000 + 10 + 1 + 1000 + SK-MG-9 (-) - + 100 + - - 1 + 1 + 100 + 1 + 1 + 1000 + SK-MG-10 (-) 10 + - - - - - - 100 + 100 + 1 + - + 1000 + SK-MG-11 (-) 10 + - - 10 + 1000 + 1 + 1 + 1 + 1 + 1000 + SK-MG-12 (-) 10 + 10 + 100 + - - 10 + 1000 + 100 + 100 + 1000 + SK-MG-13 (-) 10 + - - 100 + 10 + - + 100 + 1 + 100 + 10000 + SK-MS (-) - + - - 100 + 1 + 100 + 100 + 10 + 10 + 1000 + SK-A02 (+) - + 1000 + - - 1000 + - + 1 + 1 + 10 + 1000 + T98 (-) 1 + - - - + - - 10 + 10 + 10 + 100 + 1000 + U178MG (-) 100 + - - 10 + - - 100 + 1000 + 1 + 1 + 1000 + U251MG (+) 1 + 1000 + - - - - 100 + 1000 + 10 + 100 + 1000 + U373MG (+) 100 + 1000 + - - - - 100 + 100 + 100 + 100 + 1000 + Neuroblastoma SK NMC - + 1000 + - - - - - - 1000 + 100 + 100 + 1000 + SK NSH - - 100 + - - - - - - 1000 + - - - + 10000 + Melanoma SK-MEL-13 - - - - 1000 + 100 + 100 + 100 + - + 100 + 1000 + SK-MEL-28 - - - - 1000 + 100 + 10 + 100 + 100 + 100 + 1000 + SK-MEL-29 - - - - - - - - 1000 + 1000 + 100 + 100 + 10000 + SK-MEL-31 - - - + - - 1000 + 100 + 100 + 1 + 10 + 1000 + SK-MEL-33 - - - + - - - - 100 + 100 + 100 + 100 + 100 + SK-MEL-37 - - 10 + - - 100 + 10 + 100 + 10 + 10 + 1000 + SK-MEL-44 100 + - - - - 100 + 100 + 10 + - + 1 + 100 + SK-MEL-93 - - - - 1000 + 100 + 1000 + 100 + 1 + 100 + 1000 + SK-MEL-124 - - - - - - 100 + 100 + 100 + 100 + 100 + 100 + MeWo - - - - 10000 + 100 + - - 1000 + 10 + 10 + 1000 + EPITHELIAL CANCERS Lung SK-LL-LC - - - - - - - - - - 1 + 1 + - + 100 + SK-LC-6 10 + - - - - - - 100 + 10 + 10 + 100 + 10000 + Breast A1Ab - - - - - - - - - - 1000 + 10 + 100 + 1000 + BT-20 - - - - - - - - - - 1000 + 10 + 1 + 1000 + CAMA - - - - - - - - - - - - 100 + 100 + 1000 + MCF-7 - - - - - - - - - - 100 + 10 + 100 + 1000 + SK-BR-3 - - - - - - - - - - 100 + 10 + 100 + 1000 + Colon HT-29 - - - - - - - - - - 100 + 1 + - + 1000 + SW-1116 - - - - - + - - - - 100 + 1 + - + 1000 + SW-1222 - - - - - + - - - - 100 + 1 + - + 1000 + Renal SK-RC-1 - + - - - + - - 100 + 100 + 10 + 100 + 1000 + SK-RC-6 - - - + - - - - 100 + 100 + 10 + 100 + 10000 + SK-RC-7 - - - - - - - - 100 + 100 + 10 + 100 + 1000 + SK-RC-9 - + - - - + - - 1000 + 100 + 10 + 100 + 1000 + Bladder RT-4 - - - + - - - - - - - + - - - + 10 + T-24 - - - - - - - - 100 + 1000 + 1000 + 1000 + 10000 + Cervix ME-180 - - - - - - - - - - 100 + - - - + 100 + LYMPHOBLASTOID CELLS EBV B-cells AH - - - - - + + BT - - - - - + + BD - - T-cells MOLT-4 + + - - - - - + + NORMAL HUMAN CELLS Main Adult - + - + + + + + + Fetal - + - + + + + + + Adult skin - - - - - + 100 + - + - + 1 + - + 10 + fibroblasts Fetal skin - - - - - + 10 + - + - + 100 + 1 + 1000 + fibroblasts Adult kidney - - - - - - - - 100 + 100 + 10 + 100 + 1000 + epithelium lanocytes 1 - 10 100 1000 100 10 100 1000 erythrocytes - - - - - - - - - *Titer: - indicates no reaction in direct tests at a dilution of 1:100. **Abs: absorption tests. Sera (diluted to end point) were absorbed with the indicated cell type and tested for residual activity for SKMG-1 (Ab AJ225, Ab AJ10, Ab AJ9, Ab AJ17, Ab AJ425, Ab AJ2), U25IMG (Ab A010), or SKMEL-28 (Ab AJ8, Ab A0122); + , complete absorption; -, no absorption. ***GFA: Glial fibrillary acidic protein expression was determined by reactivity of cultured astrocytoma cells (formaldehyde/acetone fixed) wit rabbit antiGFA antiserum (Dilution: 1/500) in indirect immunofluorescence tests. | Method of forming an antibody producing hybridoma cell line by fusing a myeloma cell line with splenocytes derived from BALB/c mice immunized with human astrocytoma tumor cells, the hybridoma cell line formed, and the monoclonal antibodies generated by said hybridoma cell line. A method of phenotyping astrocytoma tumor cells comprising determining the reaction of said cells to various monoclonal antibodies to astrocytoma tumor cells is also provided. | 8 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to pictorial and text scanning apparatus, and more particularly to a method of compensating for non-uniformity in sensors in image scanning.
2. Description of the Prior Art
Historically, copies of document originals have been produced by a xerographic process wherein the document original to be copied is placed on a transparent platen, either by hand or automatically through the use of a document handler, and the document original illuminated by a relatively high intensity light. Image rays reflected from the illuminated document original are focused by a suitable optical system into a previously charged photoconductor, the image light rays functioning to discharge the photoconductor in accordance with the image content of the original to produce a latent electrostatic image of the original on the photoconductor. The latent electrostatic image so produced is thereafter developed by a suitable developer material commonly referred to as toner, and the developed image transferred to a sheet of copy paper brought forward by a suitable feeder. The transferred image is thereafter fixed as by fusing to provide a permanent copy while the photoconductor is cleaned of residual developer preparatory to recharging.
More recently, interest has arisen in electronic imaging where in contrast to the above described xerographic system, the image of the document original is converted to electrical signals or pixels and these signals, which may be processed, transmitted over long distances, and/or stored, are used to produce copies. In such an electronic imaging system, rather than focusing the light image onto a photoreceptor for purposes of discharging a charged surface prior to xerographic development, the optical system focuses the image rays reflected from the document original onto the image reading array which serves to convert the image rays to electrical signals. These signals could be used to create an image by some means such as operating a laser beam to discharge a xerographic photoreceptor, or by operating some direct marking system such as an ink jet or thermal transfer printing system.
The prior art related to these types of systems includes:
U.S. Pat. No. 4,602,293 to Sekine discloses an apparatus having a shading correction reference surface which is scanned prior to scanning a manuscript. The output of a photoelectric converter (i.e., an image sensor array) produced while scanning the shading correction reference surface is converted to a digital signal and stored in a memory as a reference. Subsequently, while the manuscript is scanned, the output of each cell of the photoelectric converter is supplied to a comparator along with an analog version of the corresponding reference signal in the memory to effect shading correction of the output.
U.S. Pat. No. 4,383,275 to Sasaki et al. discloses a system for providing read-out level compensation in an optical reader system. In operation, the system first reads a white background to obtain a reference output. The reference output is reversed and stored in a memory. The actual sensor output derived from an original sheet is multiplied by the memorized, reversed reference output to get a compensated video signal.
U.S. Pat. No. 4,520,395 to Abe discloses a system for correcting shading or non-uniformity in a photosensitive element array due to light source, lens, optical transmission, and sensor characteristics. The system employs a memory having a number of cells corresponding to the number of photoelements positioned along a linear photosensitive array. The sensor output of each respective element is successively compared with data value stored in a corresponding memory cell in the memory. With each successive output of the linear array, the data stored in the memory is updated by determining the larger data value signal and then storing that signal in the corresponding memory cell. The stored data for each line is converted with a weighting factor and multiplied by the sensor output to produce a compensated output.
A difficulty with these prior art systems is often the difference in the sensors or reading elements themselves causing non-uniformity in response, as well as the varying effect on each sensor caused by variations in illumination level caused by optics and lamp degradation. In addition, prior art calibration systems are often limited to manuscript or text applications rather than halftone applications. It would be desirable, therefore, to be able to compensate for the above identified non-uniformities and also be able to provide halftone calibration in addition to text calibration.
It is an object of the present invention, therefore, to provide a new and improved scanner calibration system. It is another object of the present invention to provide an image scanner that calibrates itself by scanning a patch whose density defines the threshold level between black and white. It is another object of the present invention to provide a circuit architecture which gives both thresholding and halftone image processing without a central processing unit. Other advantages of the present invention will become apparent as the following description proceeds, and the features characterizing the invention will be pointed out with particularity in the claims annexed to and forming a part of this specification.
SUMMARY OF THE INVENTION
In a scanning system having an array of image reading elements, the method of scanning a document by providing a test patch to be scanned, initially scanning the test patch and storing the signal response of each reading element to the test patch in a pixel threshold table, providing a document to be scanned, scanning the document and comparing the signal response of each reading element with the corresponding signal response in the pixel threshold table, and printing a mark or not printing a mark in response to the comparison for each reading element. The method includes an extended threshold table to cover halftone cells.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the present invention, reference may be had to the accompanying drawings wherein the same reference numerals have been applied to like parts and wherein:
FIG. 1 is a schematic illustration of a machine incorporating a calibration control in accordance with the present invention;
FIG. 2 is a block diagram of text only circuitry in accordance with the present invention;
FIG. 3 is a schematic illustration of the calibration patch in the pictorial mode;
FIG. 4 is a block diagram of text/pictorial circuitry in accordance with the present invention;
FIG. 5A-5D are illustrations of the technique of pictorial calibration in accordance with the present invention;
FIGS. 6 and 7 are block diagrams of alternative embodiments of text and pictorial circuitry in accordance with the present invention; and
FIGS. 8 and 9 illustrate flow charts of the text and pictorial techniques in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1 of the drawings, there is shown a combined input/output scanner, designated generally by the numeral 10. With reference to FIG. 1, there is illustrated a typical scanner printer that might incorporate the present invention. There is generally shown a carriage assembly at 12 mounted on a lead screw 14 for reciprocal motion as illustrated by the carriage motion arrows 15 in relation to the machine frame 16. An array of light emitting diodes 18 project light upwardly, line 19, to be reflected down to the 45 degree mirror 20, in turn reflecting the light to the lens 22. The light is projected from the lens 22 to an array of image sensors 24. The array of light of image sensors 24 is suitably secured to the sub assembly 26 along with a suitable printing device such as an ink jet head 28. In operation, for scanning a stationery document illustrated at 30, the carriage assembly 12 moves from right to left to a start of scan position to suitably position the LED's 18 and mirror 20 at the right edge 31 of the document 30 to be scanned. As the carriage moves further to the left, the LED's project light to the document 30 and the document reflects the light to the mirror 20 to the lens 22 on to the array of image sensors 24 to sense the degree of reflected light from the document image. Similarly, in printing an object onto the stationery copy paper 32, the carriage 12 is moved to a start of print position and the ink jet print head 28 moves across the copy paper 32 to suitably project black and white dots onto the paper representative of the scanned image.
In accordance with the present invention, a calibration strip illustrated at 34 is suitably mounted on the underside of a contrast control 36 with projecting knob 38 for movement of the calibration strip to the right or left as illustrated by the arrows 40. As illustrated, the carriage assembly is in a home position, immediately underneath the contrast control 36 with calibration strip 34. The calibration strip contains a plurality of patches with predetermined densities. Thus, patch 42A is a very light density, 42B a darker density, 42C an even darker density, and 42D a very dark density. In operation, an operator moves the contrast control 36 to locate the desired density patch 42A-42D directly above the LED array 18 and the mirror 20. Thus, an operator can calibrate or set the threshold level of the machine to a desired density level by shifting the calibration strip 34 in a manner to position the desired density patch immediately above the imaging system. Each individual sensor of the image sensor array 24 will respond to the particular density patch, and this response is recorded in a pixel threshold table 44 as shown in FIG. 2.
With reference to FIG. 2, there is illustrated the calibration circuitry in accordance with the present invention. Assuming 200 sensors in the sensor array 23, each of the sensors receives a reflected signal from a particular patch of the calibration strip as illustrated at 46. This signal for each of the sensors is amplified as shown at 48 conveyed to sample and hold circuitry 50 and converted to digital form by the analog to digital circuitry 52 before input to the pixel threshold table 44, each pixel signal response being represented by an 8 bit byte. Modular 200 counter 54 maintains the count of the 200 sensors and the calibrate signal 56 which causes the system to enter the calibration mode.
In the copy mode, as a document is being scanned by the carriage assembly 12 for printing, the response of each sensor of the sensor array 24 is amplified at 48, conveyed to sample and hold circuitry 50 and to the analog to digital converter 52 and then conveyed to the threshold comparator 58 on line 59 where the response of a particular sensor is compared to the calibrated response of that same sensor provided by the pixel threshold table 44 on line 60. If the document signal is darker then the calibration data at that particular sensor, then a drop of ink is printed. If the document signal is lighter, then a drop of ink is not printed. Thus, the calibration patch defines the threshold between black and white in the machine. By designing a calibration strip with several different target patches and allowing the operator to slide the strip back and forth at the reference station, several different threshold settings are provided. This allows the operator to adjust for documents with high back ground levels or for documents printed on non white paper. The contrast or lighter or darker control adjustment can also be used to remove pencil markings from a document or to even enhance markings.
In accordance with another feature of the present invention, calibration settings can be provided for the copying or printing of pictorial images rather than text images. A series of gray or pictorial stripes 62 are printed at one end of the calibration strip as illustrated in FIG. 3. The density of each stripe corresponds to the density of one pixel in a half tone cell, for example, for a 4×4 half tone cell, there are 16 strips. FIG. 4 is an illustration of the expansion of the block diagram of FIG. 2 to accommodate the calibration of pictorial images as well as text images. As illustrated at 64 in FIG. 4, the pixel threshold table is extended to 200×4 bytes and the pixel address counter 66 indexes in both x and y directions. The x component of the pixel address is the sensor number from modulo 200 counter 68 and the y component is a row in the half tone cell determined by modulo 4 counter 70.
Calibration consists of reading the first strip 72 and recording the response of every fourth sensor element, that is, sensors 1, 5, 9 etc. in the first row of the pixel threshold table as shown in FIG. 5A. Next the carriage indexes to a position under strip 74 and the responses of sensors 2, 6, 10 etc. are recorded as shown in FIG. 5D. The process repeats for strips 76 and 78 at which time the first row of the table is completely filled as shown in FIG. 5C. In a similar manner rows 2 through 4 are filled with data obtained by scanning the remaining strips illustrated in FIG. 5D. The copy mode functions as before except that the pixel address counter 66 increments modulo 4 in the scan direction. Note that the expanded circuit will operate in the text mode if a wide gray patch is positioned over the calibration station. During calibration, the gray patch will be scanned 16 times as above. However, all rows of the pixel threshold table will contain the same data. Thus, in text mode, the threshold level for each pixel is fixed whereas in pictorial mode the threshold level for a pixel is dependent upon its spatial position in a half tone cell.
With reference to FIG. 6, there is an alternate embodiment of the text only calibration circuitry. In this particular embodiment, there are 384 sensor elements 80 receiving calibration signals from the predetermined calibration strip. The output of each of these sensors is amplified as shown at 82 and conveyed to an analog comparator 84, along line 86. The second input to the comparator 84, is from line 88, the output of the digital to analog converter 90. The input to the digital analog converter 90 is from the pixel threshold table 92, the output of the pixel threshold table 92 being a digital representation of a density level. The input to the threshold table 92 is the identification of the particular sensor being calibrated provided by modular 384 counter 94.
There is also a calibration signal 96 and a continually cycling density level illustrated by modular 256 counter 98. The modular 256 counter 98 represents density threshold levels provided by the delta threshold logic 100 to provide the appropriate output of the converter 90 to compare with the analog signal from the selected sensor on line 86. Upon comparison, the output of the comparator 84 is the reference signal that is stored in the threshold table representing that particular sensor FIG. 7, represents similar circuitry for threshold values for pictorial images and includes the modular 4 counter 102 and the modular 384 counter 104 to provide the sixteen threshold values for a complete half tone cell as previously described.
With reference to FIG. 8, there is illustrated a flow chart of the calibration procedure for text images. In particular, block 108, illustrates the positioning of the image sensor array under the calibration strip. The block 110 illustrates the particular pixel element that is being calibrated beginning with the first pixel or sensor element. The sensor is read as shown at 112 and the value of the sensor stored in the threshold table illustrated at 114. Block 116 illustrates shifting to the next sensor element and the decision is made at block 118 whether or not the last or maximum pixel number has been reached. If not, the system cycles back to read the next pixel element. If the pixel element or sensor being read is the final or maximum sensor, then the calibration is completed as shown at block 120.
With reference to FIG. 9, there is illustrated a flow chart of the pictorial mode calibration wherein capital M is the X dimension of a half tone cell and N is the Y dimension of a half tone cell, X is the horizontal position within the half tone cell, and Y is the vertical position within the half tone cell. As with the text mode, block 122 represents the positioning of the sensor array under the pictorial calibration strip. Blocks 124 and 126 represent the initialization of the half tone cell at the position zero, and block 128 is the current sensor or pixel element being calibrated. Block 130 represents the pointer to the data and the look up table, and block 132 is essentially the reading of each sensor element to provide the appropriate calibration signal in the look up table as illustrated at 134. Block 136 illustrates the reading of a first sensor and the offsetting the dimension of the half tone cell to read the next sensor. In other words, as illustrated in FIG. 5, initially, sensor or pixel #1 is read then sensor 5 and then sensor 9 and so on as set forth in block 138. At block 140, the decision is made whether or not the pixel being read is the maximum pixel. If so, there is an index as illustrated in block 142 and 144 to the next pictorial calibration strip. If the pixel is not the maximum pixel, then as illustrated at B, the sequence loops to read the next sensor element shown at 132. If however the system indexes to the next pictorial calibration strip, a decision is made at 146 whether or not the horizontal position within the half tone cell has reached the dimension M of the half tone cell. If not, the system loops to block 128 to read that particular pixel. If yes, the vertical position of the half tone cell is indexed as shown at block 148 until the vertical position within the half tone cell reaches the Y dimension of the half tone cell as shown at decision block 150. If the vertical position has reached the maximum then the calibration sequence is completed. If not, as illustrated at D, the system loops back to block 126.
While there has been illustrated and described what is at present considered to be a preferred embodiment of the present invention, it will be appreciated that numerous changes and modifications are likely to occur to those skilled in the art, and it is intended to cover in the appended claims all those changes and modifications which fall within the true spirit and scope of the present invention. | The method of scanning a document by providing a test patch to be scanned, initially scanning the test patch and storing the signal response of each reading element to the test patch in a pixel threshold table, providing a document to be scanned, scanning the document and comparing the signal response of each reading element with the corresponding signal response in the pixel threshold table, and printing a mark or not printing a mark in response to the comparison for each reading element. The method includes an extended threshold table to cover halftone cells. | 7 |
This is a division of application Ser. No. 482,711 filed June 24, 1974, now U.S. Pat. No. 3,984,473, which in turn is a division of application Ser. No. 765,023 filed Oct. 4, 1968, now U.S. Pat. No. 3,897,460.
BACKGROUND OF THE INVENTION
In recent years, much effort has been devoted to the total synthesis of steroids. The present invention relates to certain polycyclic compounds and processes for their synthesis. The novel intermediates and processes of this invention provide a new synthetic route for the preparation of pharmaceutically valuable steroids.
SUMMARY OF THE INVENTION
In one aspect, this invention relates to a process for preparing intermediates useful in the preparation of tricyclic compounds of the formula ##STR4## wherein R 1 is hydrogen or lower alkyl; R 4 is hydrogen or lower alkyl; Z is defined hereinafter; m is an integer having the value of 1 or 2.
Another aspect of this invention relates to a process for preparing intermediates which enable the direct preparation of steriods of the formulae ##STR5## wherein R 1 , R 4 and m are as defined above; Z is defined hereinafter; R 11 is hydrogen or lower alkyl and R 25 and R 20 are independently selected from the group consisting of lower alkyl, hydrogen and hydroxyl.
In accordance with this invention, it has been discovered that compounds of the formulae I, II and III above, can be synthesized depending on the particular starting reactants selected by employing as intermediates bicyclic compounds of the formula ##STR6## wherein m is an integer having a value of 1 or 2; R 4 is hydrogen or lower alkyl; Z is lower alkylenedioxy, CH(OR 2 ) and carbonyl; R 8 when taken alone is hydrogen; R 9 when taken alone is lower alkoxycarbonyl, aryloxy-carbonyl, lower cycloalkyloxycarbonyl, carbonyl-halide, hydrogen, carboxy, formyl and methylene-X, where X is a leaving group and when taken together are methylene; with the proviso that when Z is carbonyl, R 8 when alone is hydrogen; R 8 when taken alone is carbonyl halide, hydrogen, carboxy, formyl and methylene-X where X is a leaving group and when taken together are methylene and R 2 is hydrogen, lower alkyl, lower alkoxy-lower alkyl, phenyl-lower alkyl, tetrahydropyranyl, lower alkanoyl, benzoyl, nitrobenzoyl, carboxy-lower alkanoyl, carboxybenzoyl, trifluoroacety and camphorsulfonyl and reacting them in the care where R 8 and R 9 taken together are methylene or R 8 is hydrogen and R 9 is methylene-X with β-keto esters and other analogs of the formula ##STR7## wherein R 6 is selected from the group consisting of ##STR8## and lower alkyl; R 7 is lower alkyl; R 15 is selected from the group consisting of oxo, lower alkylenedioxy or (hydrogen and lower alkoxy); B is selected from the group consisting of lower alkoxy-carbonyl-methylene, lower-aryloxy-carbonyl-methylene, cyanomethylene, lower alkyl sulfinyl-methylene, lower alkyl, sulfonyl-methylene, and R 25 and R 26 are independently selected from the group consisting of hydrogen, hydroxyl and lower alkyl.
In still another aspect, this invention relates to the preparation of the compounds of formula III above wherein R 11 is hydrogen, by reacting the compounds of formulae IV-a and IV-c with a vinylogous cyclic-beta-keto compound of the formula: ##STR9## wherein B' is selected from the group consisting of lower alkoxy carbonyl-methylene, lower aryloxy carbonyl-methylene, lower alkyl sulfinyl-methylene and lower alkyl sulfonyl-methylene.
Structure III can also be obtained starting with a compound of the formula V, in which R 15 has been chosen to be oxo by reaction with compounds of the formulae IV-a and IV-c.
A further aspect of this invention relates to novel intermediates of the formula IV. Subgeneric to the bicyclic compound of formula IV above are compounds of the formulae: ##STR10## wherein R 4 , Z, m and X are as defined aforesaid; X is selected from the group consisting of fluorine, chlorine, bromine and iodine and R's is selected from the group consisting of lower alkyl, lower cycloalkyl and aryl.
DETAILED DESCRIPTION OF THE INVENTION
In one aspect, this invention is concerned with novel indanones of the formulae IV, IV-a, IV-b, IV-c, IV-d, IV-e and IV-f which are useful as chemical intermediates as described herein. Also, certain of the keto compounds of formula V are novel and are also considered within the scope of this invention. For purposes of convenience, the rings in formulae I and IV have been numbered. Throughout this specification, in the formulae of compounds containing asymmetric centers or in the designation of such compounds by chemical nomenclature, the desired enantiomeric form is shown or designated. However, unless explicitly indicated otherwise, such illustration and designation should be taken as comprehending the enantiomer shown or designated, as well as its optical antipode or their corresponding racemate. In the formulae presented herein, the various substitute on cyclic compounds are joined to the cyclic nucleus by one of two notations, a solid line (--) indicating a substituent which is in the β-orientation (i.e., above the plane of the paper), or a dotted line (-----) indicating a substituent which is in the α-orientation (below the plane of the paper). As used herein, the term "lower alkyl" comprehends both side and branched chain hydrocarbon moieties such as methyl, ethyl, isopropyl, n-propyl, t-butyl, and the like, having 1 to 7 carbon atoms in the chain. The preferred compounds are those derivatives wherein R 4 is methyl, ethyl and propyl which can be converted into steroids which exhibit exceptionally active pharmacological properties as hereinafter described. The formative "lower-alkyl"when used in expressions such as lower alkoxy-lower alkyl have the same significance. Thus, exemplary of the expression lower alkoxy-lower alkyl is α-ethoxy-ethyl and 3-propoxy-propyl. Exemplary of lower alkanoyl are acetyl and propionyl or other residues derived from lower alkane carboxylic acids of 1 to 6 carbon atoms; lower alkylenedioxy is understood to mean alkylene of 1 to 6 carbon atoms exemplary of which is ethylenedioxy. The term "nitrobenzoyl" as used herein comprehends benzo moieties containing one or more aromatic nitrile substituents, for example, nitrobenzoyl moieties such as 4-nitrobenzoyl and di-nitrobenzoyl moieties such as 3,5-dinitrobenzoyl. The expression carboxy-lower alkanoyl comprehends di-basic aliphatic acids of 1 to 7 carbon atoms absent one OH moiety. Similarly, the expression "carboxy-benzoyl" denotes, for example, phthalic acids absent one OH moiety. The expression "halide" or "halogen" comprehends chlorine, fluorine, bromine and iodine. The expression "lower alkoxy" as utilized herein designates a lower alkyl ether group such as methoxy, ethoxyand the like, wherein the alkyl group is an defined above. The term "lower alkoxy carbonyl methylene" includes for example. ethoxy carbonyl-methylene, The term "lower aryloxy carbonyl methylene" includes for example, phenylexy carbonyl methylene. The term "aryl" comprehends phenyl or phenyl having one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, nitro, amine and halogen. The expression "lower alkylaryl" comprehends, for example, tolyl and ethylphenyl. The term cycloalkyl includes rings containing from 1 to 6 atoms, for example, cycloalkyl and cyclopentyl. Especially preferred compounds of formula IV are those wherein "Z" is lower alkoxy, especially t-butoxy although the other derivatives defined hereinabove such as, tetrahydropyranyloxy can be suitably employed in accordance with the process of this invention.
The following schematic flow sheet entitled "Reaction Scheme A", exemplifies the process routes employed in accordance with the teachings of this invention for preparation via process routes (1), (2), (3), (4), (5), (6), (7), (8), (9) and (10), the key intermediates of the formulae IV-c and IV-a, each of which can independently be reacted with the β-keto esters and other analogs thereof of formula V to yield the end-products of formulae I, II and III as hereinafter detailed.
Thus, in one aspect of the process of this invention, comprises preparing compounds of the formula IV-a by the general reaction steps (1), (2) and (4) of Reaction Scheme A to which the numerals and letters in parenthesis are referenced in the following descriptions.
Many of the indanone starting reactants of formula VII wherein "Z" is carbonyl are known. They may be conveniently synthesized by methods known in the art, for example, by the Michael Addition of methyl-vinyl-ketone to 2-lower alkyl-cyclopentane-1,3-dione. The cyclization can be effected using pyrrolidine in a benzene solvent under reflux reaction conditions (ef., U.S. Pat. No. 3,321,488). If desired, other derivatives of formula VII may be prepared. For example, in order to prepare the derivatives wherein Z is hydroxy, the corresponding oxo group can be selectively reduced with lithium aluminum tri-(lower alkoxy)-hydride or sodium borohydride at low temperatures. Derivatives wherein Z is lower alkoxy, for example, tertiarybutoxy, can be obtained from the corresponding hydroxy derivative by reaction under acid conditions with isobutylene by means known in the art. 1-Carboxy-lower alkanoyl derivatives of formula VII can be conveniently obtained by reacting dibasic lower alkanoic acids such as, succinic acid and phthalic acid and the like, with corresponding compounds containing the hydroxy-methylene moiety. Other derivatives in accordance with the definition of "Z" can be obtained by methods known to those skilled in the art. ##STR11## wherein R 4 , Z, m, R's, X and Y are as defined aforesaid.
The bicyclic ketone of formula VII can be converted to acid compounds of formula VIII by reaction in accordance with Step (1) of Reaction Scheme A with a base sufficiently strong to afford the corresponding anion of the bicyclic compound via conjugate cnolate formation. Exemplary of the suitable bases for this reaction are alkali metal amides such as sodium amide and the like; alkali metal alkoxides such as lithium methoxide and the like and alkali metal hydrides such as sodium hydride. Generally, it is preferred to conduct this reaction at room temperature although temperatures from about -40° C. to the boiling point of the reaction mixture can be utilized. The reaction is conveniently carried out in liquid ammonia or in the presence of an organic solvent inert to the reactants such as dimethylsulfoxide, dimethylformamide; hydrocarbons, e.g., benzene and toluene; and ethers, e.g., diethylether and tetrahydrofuran. A preferred solvent for this reaction is dimethylsulfoxide. This intermediate enolate bicyclic reaction product can be isolated by conventional techniques such as, for example, by removal of the solvent using vacuum distillation.
The anion which is thus obtained as a residue can be carboxylated by reaction with excess carbon dioxide to afford the 4-indane carbocyclic acid of the formula VIII. The carboxylation can be suitably effected by employing solid carbon dioxide in the form of dry ice or passing gaseous carbon dioxide into the reaction medium. Exemplary of the desirable solvents for this reaction are any of the aforementioned listed solvents which can be employed to prepare the anion with the exception of liquid ammonia, which is basic and dimethylsulfoxide, which tends to promote decarboxylation. In cases wherein liquid ammonia or dimethylsulfoxide is employed to prepare the anion, an inert solvent should be substituted when conducting the carbonation reaction. Suitable reaction temperatures are in the range of -60° C and about 40° C. A preferred operating temperature range is 15° C-25° C. Separation of the desired reaction product from the reaction medium can be effected by extraction. The extraction is suitably conducted in a hydrocarbon solvent in the presence of a dilute base such as sodium hydroxide or lithium carbonate to form the corresponding water soluble salt of the acid. Base extraction is employed so as to remove the desired product from the starting material. The aqueous layer is separated and carefully acidified to a pH of between 2.5 and 4.5 with dilute mineral acid and the desired product is then obtained by conventional techniques. Although the reaction can be suitably conducted at atmospheric pressure, increased yields can be obtained by conducting the reaction under higher pressures, e.g., in the range of 450 to 550 psi. Carboxylation takes place only at C-4 position on the indane nucleus in agreement with the preference for heteroannular conjugate anion formation with compound VII.
Inasmuch as the ultimate goal of this invention is to produce a compound of the formula I containing a 9bα-configuration, it is clear that the hydrogenation of the compound of formula VIII in accordance with Step (2) of Reaction Scheme A must predominantly proceed so as to yield a trans-hydrogenation product with respect to the two rings of the 5-indanone or the corresponding 2-naphthalenone compounds. A feature of this invention is that the desired hydrogenation to yield a transfused bicyclic structure can be effected in extremely high yields. The hydrogenation is conducted in the presence of a catalyst preferably a noble metal catalyst, such as palladium, rhodium, irridium, platinum and the like. Especially preferred is the palladium catalyst. The noble metal catalyst can be utilized with or without a carrier and if a carrier is used, conventional carriers are suitable. It is preferred to use palladium on barium or calcium sulfate. Especially preferred is 10 percent Pd/BaSo 4 . The ratio of catalyst to substrate is not critical and can be varied. However, it has been found advantageous to use a weight ratio of catalyst to substrate from about 1:1 to about 1:10. Especially preferred is a ratio of 1:3. The hydrogenation is suitably effected in the presence of an inert organic solvent for the particular compound of formula VII being hydrogenated, for example, a lower alkanol, such as methanol, isopropanol or octanol; ketones for example, lower alkyl ketones such as acetone or methylethyl ketone; lower alkyl esters of lower alkanoic acids such as ethyl acetate; lower alkyl ethers such as diethyl ether to tetrahydrofuran; aromatic hydrocarbons such as toluene or benzene and the like. It is especially preferred to conduct the hydrogenation using a lower alkanol as the solvent and it is preferably conducted under non-acidic conditions. Suitably, the hydrogenation is conducted under neutral conditions. It can be conducted at atmospheric pressure or below or above atmospheric pressure, for example, at pressures of as high as about 50 atmosphere. Also, the hydrogenation can be conducted at room temperature or temperatures above or below room temperature. As a matter of convenience, it is preferred to conduct the hydrogenation at room temperature. The hydrogenation is effected by utilizing conventional techniques, for example, the hydrogenation should be stopped after the uptake of the equivalent of hydrogen or if the absorption of hydrogen ceases before the uptake of an equivalent of hydrogen, it is advantageous to then add more catalyst and further hydrogenate. It will be appreciated that another significant aspect of this hydrogenation step lies in that the hydrogenation of the compound of formula VIII to afford the compound of formula IV-f proceeds without substantial decarboxylation of the substituted indane of formula VIII. Depending on the hydrogenation conditions used, the group represented by "Z" in formula VIII can be modified during the hydrogenation. For example, under the above-described hydrogenation conditions, when Z is OR 2 and R 2 is a group such as alkoxy-lower alkyl or tetrahydropyranyl, such group can be split off during the hydrogenation procedure. A preferred group for R 2 in which to conduct the hydrogenation and many of the subsequent other reactions is alkyl, especially, t-butyl.
The thus obtained saturated compound of formula IV-f can be converted to the 4-methylene-trans-fused compounds of formula IV-a by employing a modified Mannich-type reaction in accordance with Step (4) of Reaction Scheme A. The conversion can be effected using formaldehyde in the presence of a primary or secondary amine salts. Suitable salts which may be employed are those derived from strong mineral or organic acids such as for example, hydrogen halides, preferably as the chloride, sulfuric acid, oxalic acid and the like, such as for example, piperadine hydrochloride. The reaction can be suitably carried out at a temperature range of from 0° C to about 80° C. A preferred temperature range for this reaction is 15° C-40° C. While the ratio of reactants used for the reaction is not critical, it has been found advantageous to use approximately a 10:1 molar ratio of formaldehyde to keto acid and a 0.1:1 to 1:1 molar ratio of amine to keto acid.
The reaction is best effected in a dimethylsulfoxide solvent which functions both as a solvent for the reaction and also as a decarboxylating agent. Most advantageous results are obtained by allowing the compound of formula IV-f to decarboxylate in the dimethylsulfoxide solvent so as to form the corresponding anion and quench it immediately with the Mannich System formed by the addition of formaldehyde and primary or secondary amine salt. Aqueous formalin (37 percent - 40 percent) is a generally satisfactory source of formaldehyde for this reaction. Exemplary of the amines suitable for this reaction include heterocyclic amines such as morpholine, piperidine and pyrrolidine; monoamines such as methylamine, butylamine and benzylamine. An especially preferred amine for this reaction is piperidine. Other polar solvents such as, for example, dimethylformamide and hexamethylphosphoramide which are inert to the reactants may be employed in conjunction with the dimethylsulfoxide. The dimethylsulfoxide solvent promotes decarboxylation and anion formation at the bicyclic C-4 position notwithstanding the known preferential tendency of these compounds to enolize in the direction of the bicyclic C-6 position.
In another aspect of this invention in accordance with Reaction Scheme A, compounds of Formula IV-c may be prepared by alternate process routes (3→9), (5→7→9), (5→10) and (5→6→8).
Thus, the compounds of formula IV-e can be prepared in accordance with Step (5) from the β-keto acids of formula IV-f in excellent yields employing an organic or inorganic acyl halide preferably thionyl halide, e.g., thionyl chloride; phosphorous trihalide, preferably phosphorous trichloride and phosphorous pentahalide, preferably phosphorous pentachloride. Thionyl chloride is particularly convenient since the by-products formed are gases and can be easily separated from the acid chloride. Any excess of the low boiling thionyl chloride can be easily removed by distillation. This substitution reaction was successfully effected notwithstanding the known prior art [cf., C. B. Hurd et al., J. Am. Chem. Soc. 62, 1548, (1940)] which teaches the inability to prepare β-keto acyl halides by conventional reaction techniques from the corresponding β-keto acids. The reaction is suitably conducted at a temperature of from 0° C to the boiling point of the solvent. Suitable solvents for the conversion are thionyl chloride (neat) or in an inert organic solvent such as, for example, benzene, toluene, hexane, cyclohexane and the like.
4-Carbonyl halide indanone compounds of formula IV-e, can be converted to the corresponding esters of formula IV-d by means known in the art. Preferred esters are those wherein R'3 is lower alkyl, especially methyl and ethyl. The esters can be conveniently obtained by reacting the halide with an alkali alkoxide, e.g., sodium methoxide in a solvent such as, for example, lower alcohol, e.g., methanol and the like. Alternatively, the esters of formula IV-d may be obtained by reacting the halide with carbonyl diimidazolide in tetrahydrofuran solvent, then further reacting the thus obtained product with the desired aliphatic or aryl alcohol, e.g., phenol, methanol, ethanol and the like at room temperature to the reflux temperature of the solvent in, for example, tetrahydrofuran to obtain the desired ester.
As a further alternate wherein it is desired to prepare 4-alkoxy carbonyl indanones of formula IV-d, the conversion can be effected by treatment of the acids of formula IV-f with an ethereal solution of a diazoalkane such as diazomethane by known means. The reagent is a yellow gas and small quantities can be prepared conveniently prior to use in the form of a solution in ether. When the yellow ethereal solution is added in portions to a solution or suspension of the acid in ether at room temperature, nitrogen is evolved at once and the yellow color is discharged. When the yellow color persists, which is an indication that excess diazomethane has been added, the solution can be heated, e.g., on a steam bath to expel excess reagent. Since the only by-product is a gas, a solution of the desired ester in ether results.
The esters of formula IV-d can also be prepared by first esterifying the unsaturated acid compounds of formula VIII to compounds of formula VIII-a in accordance with Reaction Scheme A by the aforementioned methods and then catalytically hydrogenating this unsaturated ester. The steric course of this hydrogenation proceeds so as to yield the C/D-trans-hydrogenated product. Thus, an identical product of the structure of formula IV-d with C/D-trans-ring-fusion is obtained in a similar manner to the case wherein the acid of formula VIII is employed directly as the starting reactant for the hydrogenation step. The bicyclic C/D-trans-structure obtained by the catalytic hydrogenation of the ester may be explained (although applicant is not bound by this theory) by postulating a chelated dienol ester intermediate formed from the non-enolic unsaturated β-keto ester on the surface of the catalyst. However, it should be noted that the rate of catalytic hydrogenation of the β-keto acid of formula VIII was approximately four times as rapid as was the case when the corresponding β-keto ester was employed as the reactant. However, hydrogenation of the ester employing approximately three times the amount of catalyst employed in the case of the acid under identical reaction conditions resulted in an approximately equal hydrogenation rate.
The β-keto aldehydes of formula IV-b can be prepared from the acid halides of formula IV-e in accordance with step (6) of Reaction Scheme A employing a reducing agent such as, lithium aluminum tritertiarybutoxyhydride. The reaction can be carried out in an inert aprotic organic solvent such as, ethers, e.g., tetrahydrofuran and hydrocarbons, e.g. toluene and hexane at a temperature range of -10° C. to -60° C., preferably between the temperature range of -20° C. and -40° C. When the reaction is carried out within the aforesaid defined temperature ranges, selective reduction of the acid halide can be effected without attacking the free keto group on the 5-position of the indane of formula IV-e. An alternative method of transforming the acid halide to the corresponding aldehydes can be accomplished by the catalytic hydrogenation of the acid chloride by the Rosenmund Reaction. The technique introduced by Rosenmund consists in adding a small amount of a poisoning agent containing sulfur to the hydrogen catalyst system.
The indanones of formula IV-e wherein R 4 , Z and m are as defined as aforesaid can be conveniently prepared in accordance with Steps (8), (9) and (10) of Reaction Scheme A depending upon the nature of "X", from the esters of formula IV-d, the acid halides of formula IV-e or the aldehydes of formula IV-b.
Suitable requirements for the leaving group as defined by "X" in the compounds of formula IV-e are that it should function efficaciously in this process aspect, that is, that it be a suitable leaving group for the process of the present invention. Suitable groups which may be employed to form leaving groups are lower alkyl-aryl sulfonyloxy groups such as, for example, tosyloxy; arylsulfonyloxy groups such as, for example, benzene sulfonyloxy; lower alkyl sulfonyloxy groups such as, for example, mesyloxy (methane sulfonyl); lower alkyl sulfinyloxy; halogen; an acyloxy radical derived from an organic carboxylic acid having 1 to 7 carbon atoms such as lower alkanoic acid, e.g., acetic acid and butyric acid; aryl carboxylic acids such as p-phenylbenzoic acid and benzoic acid and cycloalkyl carboxylic acids such as cyclopentyl carboxylic acids. Other suitable leaving groups may be selected from the group consisting of ##STR12## wherein each of R 20 and R 21 is independently selected from the group consisting of lower alkyl, aryl and hydrogen, and R 20 and R 21 when taken together to the nitrogen atom to which they are joined, form a 5- or 6-membered heterocyclic ring structure. Thus, the ##STR13## amine grouping represents secondary and tertiaryamino radicals. It includes monoalkylamino radicals, such as, for example, methyleneamino and butylamino; dialkylamino radicals such as, for example, dimethylamino and dipropylamino, heterocyclic amino radicals, such as, for example, pyrolidino, piperidino, morpholino and 4-methyl-piperizino. The amino radical ##STR14## may also be employed as a leaving group in a modified form by alkylation by known means with a suitable organic ester such as, for example, lower alkyl halide, e.g., methyl chloride or a hydrohalic acid such as, for example, hydrogen chloride to form the corresponding quaternary ammonium salt of the formula ##STR15## wherein R 20 , R 21 and Y are as defined aforesaid and R 22 is a cation from the organic ester.
Generically, the preferred leaving groups are tosyloxy and mesyloxy although depending on the steroidal end products being prepared, other leaving groups as exemplified above may be more preferable.
The compounds of formula IV-e wherein the leaving group "X" is lower alkyl-sulfonyloxy, e.g., mesyloxy or lower alkyl aryl-sulfonyloxy, e.g., tosyloxy may be conveniently prepared from the esters of formula IV-d in accordance with Step (9) of Reaction Scheme A by a reaction sequence which comprises first protecting the 5-oxo moiety on the indanone, reducing the ester group to the corresponding 4-hydroxy methylene derivative, removing the protecting group before or after conversion to the desired derivative of formula IV-e. Protection can be effected by converting the free oxo group to a cyclic ketal, e.g., a dioxolane ring system by reaction with a suitable lower alkylenedioxy containing compound, e.g., ethylene glycol or to an open ketal with for example, tri-lower alkyl orthoformates. The free oxo moiety can be regenerated after reduction of the 4-ester compounds of formula IV-d to the corresponding 4-hydroxy methylene compounds. A preferred protecting group is the dimethoxy derivative which can suitably be obtained by etherification with trimethyl orthoformate. The thus protected 4α-ester can be reduced employing for example, a suitable reducing agent such as, diisobutyl aluminum hydride to yield the 4-hydroxy methylene compound of the formula ##STR16## wherein R 4 , Z and m are as defind aforesaid.
Alternatively, the ester of formula IV-d in the protected form obtained as described above may be reduced to the alcohol of formula IV-c-1 using an alkali metal reducing agent such as sodium metal and lower alcohol or lithium aluminum hydride. Compounds of formula IV-c wherein the leaving group "X" is lower alkyl sulfonyloxy or lower alkyl-arylsulfonyloxy can be prepared by esterification with an organic sulfonylhalide such as, for example, toluenesulfonyl halide, especially, p-toluenesulfonyl chloride to prepare the tosyloxy derivative or lower alkyl sulfonyl halides, especially methane sulfonyl chloride to prepare the mesyloxy derivative. The above reactions can be suitably conducted at a temperature range of -10° C to +10° C in the presence of an organic base such as, for example, pyridine by methods known in the art. The corresponding sulfonic acids may also suitably be employed to effect the esterification in lieu of the sulfony halide. Leaving groups wherein "X" is lower alkyl sulfinyloxy may be obtained in an analogous manner to that above by employing the corresponding sulfinyl halides.
Leaving groups wherein "X" is defined by the grouping ##STR17## wherein R 20 and R 21 are defined as aforesaid can be conveniently obtained from the acid halides of formula IV-e in accordance with process route (10) of Reaction Scheme A by a reaction sequence which comprises the steps of (a) reacting the compounds of formula IV-e with a primary or secondary aliphatic or aromatic amine of the formula ##STR18## by known means to form the corresponding amide of the formula ##STR19## wherein R 4 , Z, m and R 20 and R 21 are as defined aforesaid; (b) protecting the 5-oxo group of the compounds of formula IV-c-2 by forming the 5-ketal analog in a manner similar to that previously described; (c) reducing the amide with a suitable reducing agent such as, for example, diborane or lithium aluminum hydride in an ether solvent such as, for example, tetrahydrofuran which upon removal of the protecting group by means of dilute mineral acid yields a compound of the formula: ##STR20## wherein R 4 , Z, m, R 20 and R 21 are as defined aforesaid. The compounds of formula IV-c-3 can be converted to their quaternary salt adducts by alkylation with for example, a lower alkyl halide such as methyl chloride.
Leaving groups wherein "X" is defined by the grouping ##STR21## wherein at least either R 20 and R 21 is hydrogen, may also be prepared from the aldehydes of formula IV-b in accordance with process route (8) of Reaction Scheme A by selective combination with a primary amine of the formula --H 2 NR 20 to form by known means the novel imino Shiff Base intermediate of the formula ##STR22## wherein R 4 , Z, m and R 20 are as defined aforesaid.
The ald-imines of formula IV-e-4 can be conveniently reduced with hydrogen and Raney Nickel to the desired secondary amines.
Leaving groups wherein "X" is defined as halogen may be conveniently obtained from the alcohols of formula IV-e-1 by reaction with for example, hydrogen halides, e.g., hydrogen chloride, phosphorous halides or thionyl chloride by means known in the art. Leaving groups wherein "X" is acyloxy as defined aforesaid may be suitably obtained from the compounds of formula IV-c-1 by reaction with the desired organic carboxylic acid in the presence of a mineral acid such as sulfuric acid or hydrochloric acid at reflux temperature by means known in the art.
In another aspect, the process of this invention relates to the preparation of compounds of the formulae I, II and III by reaction of a β-keto ester or other analog of formula V with compounds of formulae IV-c and IV-a in accordance with Reaction Scheme B. It should be appreciated that compounds of the formulae IV-a and IV-c can be used interchangeably in all of the hereinafter process reactions. ##STR23##
The process of this invention in this aspect, comprises employing the bicyclic indanone derivatives of formulae IV-a and IV-e prepared as aforesaid and reacting them with certain subgeneric compounds encompassed by generic compounds of the formula V-b in accordance with process route (11) of Reaction Scheme B to prepare the benz[e]indene compounds of formula I. Alternatively, for other subgeneric compounds encompassed by generic formula V-a in accordance with process routes (12) and (13) of Reaction Scheme B, the steroids of formulae II and III may be prepared. Thus, for certain compounds subgeneric to formula V, viz - formula V-b as defined below, the tricyclic benz[e]indenes of formula I may be prepared by means of the building in an annulation reaction steroidal ring B. Alternatively, for certain other compounds subgeneric to formula V-a as defined hereinafter, the steroids of formula II and III may be prepared by building by means of compounds of formula V-a, steroidal rings A and B. Thus, the keto compounds of formula V are employed as one of the starting reactants for the preparation of the tricyclic compounds of the formula I or the tetracyclic compounds of formulae II and III. However, it will be appreciated that the length of the carbon chain varies as exemplified by formula V-a and V-b below, depending on which class of end products are sought to be prepared. Thus, the β-keto esters and analogs thereof of formula V-a below, are employed wherein it is desired to prepare the tetracyclic steroids of formula II and III. ##STR24## wherein R 7 , R 15 , B, R 25 and R 26 are defined as aforesaid. ##STR25## wherein R 15 , R 25 , R 26 , and R' 3 are defined as aforesaid and R 5 is lower alkyl or aryl.
The β-keto esters and other analogs of formula V-a can be prepared in accordance with Reaction Scheme C below in which a specific embodiment is illustrated. The β-keto esters of formula V-a-1 can be prepared from the hexanoic esters of formula X via process route (a) by reaction with base, preferably, lithium hydroxide in a lower alcohol solvent, e.g., ethyl alcohol at the reflux temperature of the solvent to form the salt of the acid by saponification of the ester. Subsequent reaction of the thus obtained salt with equimolar quantity of an organo metallic compound, preferably, methyl lithium in tetrahydrofuran in the presence of a minute amount of triphenylmethane yields the compounds of formula XII. In effecting the conversion, R 15 should be in a protected keto form, e.g., ketal, the conversion to which has been herein before described. Alternatively, the compounds of formula XII can be prepared in accordance with Reaction Scheme C, via process routes (b) and (c) by reacting the compounds of formula X with a lower alkyl sulfonyl methylene compound, e.g., methyl sulfinyl carbanion [cf., E. J. Corey and M. Chaykovsky, M. Am. Chem. Soc. 86, 1639 (1964)] to yield intermediates of formula XI. The compounds of formula XI can if desired, be oxidized to the sulfonyl derivatives with an oxidizing agent such as, for example, potassium permanganate. Reduction of the thus obtained sulfoxides of formula XI with a reducing agent, preferably, aluminum amalgam, yields compounds of formula XII. The compounds of formula XII can be converted to the β-keto esters of formula V-a-1 via a Claisen Condensation with a carbonate of the formula
(R.sub.5).sub.2 CO.sub.3
wherein R 5 is aryl or lower alkyl
in accordance with process route (e). The preferred condensing agent is sodium hydride although alkali lower alkoxides, e.g., sodium alkoxide may also be suitably employed. The reaction is conveniently conducted in an ether solvent such as, for example, diethylether or tetrahydrofuran, the former being preferred at the reflux temperature of the solvent.
Illustrative of the β-keto ester and other analog compounds of formula V-a which may be employed as starting reactants wherein it is desired to prepare the steroids of formulae II or III include 6-(2-methyl-1,3-dioxolan-2-yl)-3-oxohexanoic acid ethyl ester; 6-(2-ethyl-1,3-dioxolan-2-yl)-3-oxohexanoic acid ethyl ester; 3,7-dioxo-octanoic acid methyl ester; 6-(2-methyl-1,3-dioxolan-2-yl)-3-oxohexanoic acid propyl ester; 3,7-dioxodecanoic acid ethyl ester; 1-methylsulfinyl-5-(2-methyl-1,3-dioxolan-2-yl)-2-pentanone and the like. By referring to the general formula IV, it can be thus appreciated that when it is desired to prepare the steroids of formula XVII, the selections of the variables of formula V should be as follows: R 6 is ##STR26## and R 25 , R 26 , R 15 and B are defined aforesaid.
The β-keto esters and other analogs of formula V-b below, are employed wherein it is desired to prepare the tricyclic compounds of formula I ##STR27## wherein R 6 and B are defined as aforesaid.
The compounds of formula V-b, for example, ethyl propionyl acetate, may be prepared in a similar manner to the compounds of formula V-a in accordance with process step (e) by employing in Reaction Scheme C (the Claisen Condensation Step) butanone in lieu of the compounds of formula XII.
Exemplary of the β-keto ester and other analogs of formula V-b which may be employed as starting reactants wherein it is desired to prepare the tricyclic compounds of formula I include ethyl propionyl acetate, methyl propionyl acetate, ethyl aceto acetate, ethyl butyro acetate, butyro acetonitrile, aceto-acetonitrile, 1-methyl-sulfinyl-2-butanone and 1-methyl-sulfonyl-2-pentanone.
While certain groups exemplified by the definition of the term "B" have been illustrated in the β-keto ester and other analogs of formulae V-a and V-b, it is to be understood that any other equivalent electron withdrawing group or groups of electrophilic nature can function as well. All that is required for the "B" segments of the molecule for the process of the reaction of the compounds of formula IV with the compounds of formula V is that it function efficaciously in this process aspect, that is, that it be a suitable electron withdrawing group so as to activate the hydrogen atom on the methylene group next adjacent to the carbonyl group. Preferred electron withdrawing groups are the alkoxy carbonyl esters, especially ethoxy carbonyl. The β-keto nitriles, e.g., aceto-acetonitrile of formula IV-b may be prepared by reaction of acetonitrile phenyllithium and diethylamine at a temperature range of -10° C to +10° C and hydrolyzing in dilute acid the thus obtained imine intermediate to the desired product [cf., Ann. 504, 94 (1933)]. The compounds of formula V-a and V-b wherein "B" is defined as lower alkyl sulfinyl methylene and lower alkyl sulfonyl methylene can be readily prepared from the esters of formula V-a-1 in a similar manner to that employed in process step (b) of Reaction Scheme C.
In a further aspect, the synthesis of the present invention relates to the preparation of steroids of the formulae II and III in accordance with Reaction Scheme B by means of reacting a carbon chain of the formula V-a with a bicyclic compound of the formulae IV-a or IV-c. In Reaction Scheme D, the numbers are assigned to Roman numerals for identification. Schematically, the sequence of reactions involved in the synthesis of a specific embodiment, namely, 19-nortestosterone is illustrated. ##STR28##
In the Michael addition, process step (a) of Reaction Scheme D, the precursors to the steroidal A and B rings are built up in a single annulation reaction. The reaction is conducted in the presence of a base sufficiently strong to form the anion of the β-keto ester. Exemplary bases are for example, alkali metal lower alkoxides such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium tertiary butoxide and the like; alkali metal hydroxides such as sodium hydroxide and the like; alkali metal hydrides such as sodium hydride, lithium hydride and the like; alkali metal amides such as lithium amide, sodium amide and the like; methyl sulfinyl carbanion (i.e., the anion from dimethyl sulfoxide). Especially preferred are the alkali metal lower alkoxides. The reaction can be conducted at a temperature range of from about -5° C to about 100° C. However, it is especially advantageous to conduct a reaction within a temperature range of from 0° C to 25° C. Moreover, the reaction is suitably conducted in the absence of oxygen for example, in an atmosphere of inert gas such as nitrogen or argon. It is convenient to conduct the reaction in the presence of an organic solvent inert to the reactants as well as the intermediates of formula XVI. Such solvents are for example, dimethylformamide, dimethylsulfoxide and aromatic hydrocarbons, such as, for example, benzene, toluene and xylene. Other suitable solvents include the ethers such as diethylether, tetrahydrofuran and the like and lower alkanols such as methanol, ethanol and the like. The concentration of reactants is not critical but it is preferred to use a 1:1 molar ratio of reactants of formulae IV-a-1 and V-a-3. One may add the reactant of formula V-a-3 to a reaction mixture already containing the bicyclic indanone of formula IV-a-1. However, the reaction can also be effected by placing all the reactants substantially together or preferentially the reactants of formula IV-a-1 can be added to a mixture containing the reactants of formula V-a-3. When employing as a starting reactant, the compounds of formula IV-a in lieu of the reactants of formula IV-c-1, the same process conditions are employed and products obtained although the reaction does not necessarily have to proceed by way of a Michael addition mechanism. The sidechain of the reaction intermediate XVI assumes the thermodynamically favorable equatorial configuration under the equilibrating reaction conditions. The alpha orientation of the sidechain is extremely important for the construction of ring B with the proper stereochemistry. No ring closure occurred at this stage because of the preferred enolization of the keto group towards the ester function. Following the Michael addition of the β-keto ester of formula V-a-3 to the bicyclic C/D-trans-indanone of formula IV-b-1, the thus obtained compound of formula XVI is saponified to remove the ester group and cyclized in accordance with process step (b) of Reaction Scheme D. The cyclization should be effected under reaction conditions which do not cleave the cyclic ketal protecting group. Exemplary basic cyclization reagents are for example, a dilute aqueous solution of alkali or alkaline metal hydroxides such as for example, sodium hydroxide, lithium hydroxide, calcium hydroxide and the like. The cyclization is suitably conducted in an inert organic solvent such as for example, hydrocarbons, e.g., benzene, toluene and ethers, e.g., tetrahydrofuran. The cyclization can be conducted at room temperature or above room temperature but as a matter of convenience, it is preferable to conduct the reaction at about room temperature. The ester group of the bicyclic intermediate of formula XVI can be removed by saponification of the ester in accordance with Step (b) of Reaction Scheme D to afford the corresponding acid of the formula XVII (after acidification) and decarboxylation to compounds of the formula XVII-1 for example, in refluxing toluene under an inert atmosphere such as for example, nitrogen in accordance with Step (c) of Reaction Scheme D. For other cases wherein the electron withdrawing group of formula V ("B") is other than ester, e.g., for example, lower alkyl sulfinyl methylene or lower alkyl sulfonyl methylene, the removal of the grouping can be effected by reduction with a reducing agent such as, for example, aluminum amalgam. For cases wherein the electron withdrawing group is nitrile, the reaction can be suitably conducted in an analogous manner to that wherein the electron withdrawing group is an ester as discussed above.
The hydrogenation of the Δ 9 (10) -double bond of the compounds of formula XVII-a to the compounds of formula XVIII can be effected in accordance with Step (d) of Reaction Scheme D in a lower alcohol solvent such as, for example, ethyl alcohol in the presence of a base, preferably, triethylamine. 19-Nortestosterone can be obtained from the compounds of formula XVIII by hydrolysis of the tertiarybutyl ether cyclization by refluxing in a mineral acid such as, hydrochloric acid or sulfuric acid in a lower alkanol solvent such as methanol in accordance with Step (e) of Reaction Scheme D.
It should be noted that the process steps exemplified in Reaction Scheme D can be utilized to prepare norgestrel. This can be effected by preparing the 7aβ-ethyl analogs of formula IV-a-1 as described on page 9 of the instant specification employing the reaction steps (a), (b), (c), (d) and (e) of Reaction Scheme D followed by oxidation utilizing for example, Jones Reagent and ethinylation in accordance with procedures described on page 49 of the instant application. It will be further appreciated that by employing the optically active 7aβ-ethylenantiomer of formula IV-a-1 of Reaction Scheme D, one can prepare optically active norgestrel.
It will be appreciated that this aspect of the process of the invention for the synthesis of steroids of the formula II of which 19-nortestosterone is a specific exemplar as set forth in Reaction Scheme D, can be modified so as to yield other pharmaceutically valuable steroids of formula II, well known in the art, wherein R 1 is other than hydrogen, e.g., lower alkyl by selectively alkylating the Δ 9 (10) -compounds of formula XVII-1 with a lower alkyl halide in the presence of a strong base, preferably lithium in liquid ammonia at temperatures in the order of -40° C in an inert solvent such as, for example, diethyl ether by means known in the art.
Moreover, when R 15 of the β-keto ester or other analogs thereof of the formula IV-a is oxo and not in a protected ketal form, Δ 4 , Δ 9 (10) -steroids of formula III in lieu of the steroids of formula II will be produced in accordance with Reaction Scheme E. Thus, in a specific embodiment exemplified in Reaction Scheme E, steroids encompassed by the genus of the formula III are prepared. The dione ester of the formula V-a-4 is reacted with the methylene ketal of formula IV-a-1 in accordance with Step (a) in the presence of an alkali alkoxide such as 0.1 N sodium methoxide in a methanol solvent using a temperature range of 0° C-20° C to yield the substituted trione of formula XVI-a. The compound of formula XVII-a in accordance with Step (b) of Reaction Scheme E can be hydrolyzed and ring closed using a hydrogen halide acid such as hydrogen bromide in an acetone solvent at a temperature of approximately 20° C to yield the acid compound XVII-a. Decarboxylation of compound XVII-a in refluxing toluene in accordance with Step (c) yields compound XVII-1-a. The diene steroids of the formula III-a can be obtained in accordance with Step (d) of Reaction Scheme E by cyclizing the compound of formula XVII-1-a using an alkali alkoxide preferably potassium t-butoxide in benzene. The 17-hydroxy diene steroids of formula III-b are obtained in accordance with Step (e) of Reaction Scheme E by refluxing in methanol in the presence of acid, preferably hydrogen chloride. ##STR29##
The keto compound XVII-1 of Reaction Scheme D can also be converted to steroids of the formula XVII-1-a via mild hydrolysis of the ketal moiety employing 0.1 N hydrochloric acid in a solvent such as tetrahydrofuran at a temperature of approximately 20° C in accordance with Step (f) of Reaction Scheme E. Steroids of Formula III can be converted to pharmaceutically valuable estrogens by known means (cf. Velluz et al., Angewandte Chemic 72, 725 (1960).
In a further aspect, the present invention relates to the preparation of Δ 4 , Δ 9 (10) -steroids of the formula III by reacting a vinylogous beta keto ester or other analogs of the formula ##STR30## wherein B' is defined as aforesaid with compounds of the formula IV-a and IV-c.
A preferred value of B' is lower alkoxy carbonyl. Especially preferred is methoxy carbonyl and ethoxy carbonyl. Thus, in a specific embodiment exemplified in Reaction Scheme F, diene steroids of the formula III-b are prepared. The vinylogous beta keto ester of formula VI-a is reacted with the methylene ketone of formula IV-a-1 in accordance with Step (a) of Reaction Scheme F in the presence of an alkali lower alkoxide, preferably 0.1 N sodium methoxide in a lower alcohol solvent, preferably, methanol or ethanol, at a temperature range of 0° C to 20° C yielding the dione of formula XXIII. The dione steroid of formula III-b can be conveniently obtained from the compound of formula XXIII by cyclization using refluxing mineral acid, preferably, 1-N-hydrochloric acid in a lower alcohol solvent, preferably methanol. ##STR31##
In still another aspect of this invention, compounds of the formula IV-f, in Reaction Scheme A, can be converted to compounds of the formula XXIII below, which are subgeneric to the compounds of formula IV ##STR32## wherein R 4 , Z and m are as defined aforesaid by decarboxylation in a refluxing solvent such as, for example, tetrahydrofuran or toluene with or without a strong mineral acid, e.g., hydrochloric acid. The novel C/D-trans bicyclic indanone of compounds of formula XXIII are themselves useful intermediates in a total steroidal synthesis by employing, e.g. the methods described by R. E. Ireland and M. Chaykovsky, J. Org. Chem. 28, 748 (1963) the compounds of formula XXIII can be converted to their Δ.sup.α acid analogs by a bromination-dehydrobromination procedure. The Δ.sup.α -C/D trans indanones can be converted by methods described in the above cited reference to the tricyclic compounds of the formula I which in turn can be converted to pharmaceutically valuable steroids by procedures hereinafter described.
In a further aspect, the synthesis of the present invention relates in accordance with Step (11) of Reaction Scheme B to the preparation of 2,3,3a,4,5,7,8,9,9a,9b-decahydro-3a-alkyl-7-oxo-1H-benz[e]indenes and 4,4aβ,4bα,5,6,7,8,8a,9,10-decahydro-8aβ-alkyl-3H-phenanthrene-3-ones which contain in the 3-position and 8-position, respectively, an oxo substituent or a β-OR 2 moiety wherein R 2 has the meaning given in the text accompanying formula I. Many members of this class of known compounds which are valuable intermediates in the synthesis of steroids, for example, benz[e]indene derivatives contain asymmetric centers at positions-9a,9b,3a and also at the 3-position if the substituent thereat is other than oxo. Thus, of the 3-oxo compounds, there are eight possible different stereoisomers, whereas of the compounds containing a 3-OR 2 substituent, there are possible sixteen stereoisomers.
In a preferred embodiment of this aspect, the synthesis relates to the preparation of the 9aβ,9bα,3aβ-stereoisomers of the benz[e]indene series, its optical antipode and racemate thereof and in the case where the 3-substituent is other than oxo, the 9aβ,9bα,3aβ,3β-stereoisomer, its optical antipode and the racemate thereof. The corresponding phenanthrene-2-ones, i.e., 4aβ,4bα,8aβ-stereoisomers may also be prepared. The especially desired end-products of the synthesis of this invention are the (-)-enantiomers of the formula ##STR33## wherein R 1 , R 4 , Z and m are as defined aforesaid.
The compounds of formula I can be obtained by commencing the synthesis of this invention with an optically pure starting material of formula IV or by commencing the synthesis of this invention with a racemic (i.e., dl) starting material of the formula IV and effecting resolution at any intermediate stage or after the desired end-product of formula I has been obtained as the racemate.
Referring to Reaction Scheme G, wherein the compounds are assigned Roman numerals for identification schematically, the sequence of reactions involved in the synthesis of a specific embodiment, namely, the benz[e]indenes of formula-I-a are illustrated. Thus, ethylpropionylacetate is reacted with a compound of formula IV-c-1 wherein the leaving group "X" exemplified is mesyloxy (compounds of formula IV-a-1 can also suitably be employed) to yield compounds of formula XV in accordance with Step (a). Reaction conditions employed for this conversion are identical with that exemplified hereinabove in process step (a) of Reaction Scheme E for the preparation of compound XVI. Compound of formula I-a is obtained in accordance with process step (b) via cyclization which includes an internal aldol condensation and dehydration using a strong mineral acid, e.g., 2N-hydrochloric acid in a lower alcohol solvent, e.g., methanol, at the reflux temperature of the solvent. The conversion of compounds of the formula XV of Reaction Scheme G to compounds of the formula I-a can also be conducted under reaction conditions employed in Steps (b), (c) and (e) of Reaction Scheme D.
__________________________________________________________________________REACTION SCHEME GPreparation of the tricyclic Compounds of Formula I__________________________________________________________________________ ##STR34## ##STR35## ##STR36## ##STR37##__________________________________________________________________________
As indicated above, the 2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3aβ-alkyl-7-oxo-1H-benz[e]indenes and the 4,4aβ,4bα,5,6,7,8,8a,9,10-decahydro-8aβ-alkyl-3H-phenanthren-2-ones of formula I obtained by the process of this invention are useful as intermediates in the formation of the tetracyclic steroid nucleus in accordance with Reaction Scheme F. The benz[e]indenes and the phenanthren-2-ones are a known class of compounds. The benz[e]indenes, for example, can be converted into the tetracyclic steroid nucleus by condensing the 7-oxo-benz[e]indene with for example, methyl-vinyl ketone or 1,3-dichloro-2-butene according to methods known per se. The patent literature contains many references which are illustrative of methods to effect conversion of the tricyclics of formula I to known steroids of which U.S. Pat. Nos. 3,115,507; 3,120,544; 3,128,591; 3,150,152 and 3,168,530 are exemplary.
The ultimate utility of the tricyclic intermediates depends on the nature of R 1 and R 4 . For example, compounds wherein R 1 is hydrogen may lead to either 19-nor steroids (Velluz et al., Angewandte Chemie 72, 725, (1960); or alternatively to 10α-19-nor-steroids (French Pat. No. 1,360,55) depending upon the reaction conditions. Further, the tricyclics wherein R 1 is hydrogen may be converted into 19-nor-retro(9β,10α)-steroids (Velluz et al., Tetrahedron Suppl. 8, Part II, 495 (1966) and estrogens, viz -- compounds having an aromatic "A" ring -- e.g., estradiol (Velluz et al., Angewandte Chemie 72, 725 (1960). On the other hand, compounds wherein R 1 is alkyl may lead to compounds of the 9α,10α-series (Velluz et al., Angewandte Chemie 77, 185, (1960) or alternatively to compounds of the retrosteroid series vis -- those having inverted centers of asymmetry at positions C 9 and C 10 , i.e., the 9β,10α -steroids (Belgium Pat. No. 663,193). Compounds wherein R 1 is lower alkyl may be obtained wherein R 6 of the compounds of formula V-b is lower alkyl (other than methyl).
As illustrated by the following Reaction Scheme H, in the first step of this reaction, the cyclo-olefin I may be hydrogenated to the tricyclic compound XIX. The reaction is preferably effected with a noble metal catalyst, e.g., a palladium-charcoal or a lower-rhodium charcoal catalyst. In formula XIX, R 1 represents hydrogen or lower alkyl. Thus, compounds of formula I wherein R 1 represents hydrogen or alkyl can be hydrogenated to the compounds of formula XIX. The conversion of compounds of formula I to compounds of formula XIX and of the latter to compounds of formula XXII are described in greater detail in Belgium Pat. No. 663,197. ##STR38##
Tricyclic compounds of formula I for values wherein R 1 is hydrogen may be converted by means known in the art to compounds of formula XXI wherein R 1 is hydrogen viz -- steroids of the 19-nor-10α-series. Further, the tricyclic compounds of formula I wherein R 1 is hydrogen may be alternatively converted to compounds of formula II viz -- the normal steroids of the 9α,10β-(normal-19-nor series). This is described more fully in Angewandte Chemie 77, 185 (1965), Velluz, Valls and Nomine and Angewandte Chemie 72, 725 (1960), Velluz et al.
A preferred procedure for converting tricyclic compounds of formula I wherein R 1 is hydrogen to normal steroids of the 9α-19-nor series of formula II can be effected by reacting the tricyclic compounds with 4-halo-2-alkoxy butane wherein the halogen is preferably selected from the group consisting of chlorine, bromine or iodine. For example, a tricyclic compound of formula I such as 2,3,3a,4,5,7,8,9aβ,9bα-decahydro-3aβ-ethyl-3-oxo-7-oxo-1H-benz[e]indene may be reacted with for example, 4-chloro-2-tertiarybutoxy-butane in a suitable solvent such as, for example, dimethylformamide or dimethylsulfoxide under a nitrogen atmosphere in the presence of a base such as, for example, sodium hydride or potassium tertiarybutoxide at a temperature range of between 15° and 100° to yield the intermediate 10-[3-tertiarybutoxy-butyl]-13-ethyl-19-nor-desA-androst-9-ene-5,17-dione. This latter compound can be converted to norgestrel by procedures described more fully in U.S. Pat. Application of Gabriel Sauey, Ser. No. 679,989, filed on Nov. 2, 1967.
4-Halo-2-tertiarybutoxy may be prepared from 4-halo-2-butanol by reaction of the latter compound with isobutylene in the presence of a mineral acid such as sulfuric acid or hydrochloric acid at room temperature.
The tricyclic compounds of formula I for values wherein R 1 is alkyl may be converted by methods known in the art to compounds of formula XXII viz -- steroids of the "retro" series via catalytic hydrogenation compounds of the formula XIX and base catalyzed reaction with for example, methyl vinyl ketone.
Compounds of formula I can also be directly reacted with for example, methyl vinyl ketone yielding a 5-hydroxy-tetracyclic compound of formula XX. These latter compounds can then be subjected to dehydration followed by hydrogenation or to hydrogenation followed by dehydration to yield a 9β,10α- or 10α-steroids of formulae XXI and XXII. These procedures are described in greater detail in Netherlands Octrooiaanvrage No. 6,412,939. Still other methods of utilizing compounds of formula I are described in the literature or in the patents.
Compounds of formula I when converted into compounds of formula II wherein R 4 is ethyl and R 1 is hydrogen and Z is carbonyl can be selectively alkynylated by a suitable organic metallic acetylide affording norgestrel (13β-ethyl-17α-ethinyl-17-hydroxy-gon-4-ene-3-one). The latter compound can also be prepared according to Reaction Scheme D (cf. Page 39 herein). Exemplary of the suitable alkynylating agents to effect conversion to norgestrel are the alkali acetylides such as lithium acetylide, potassium acetylide, sodium acetylide, etc. The reaction is carried out in the presence of liquid ammonia in suitable solvent systems such as benzene or toluene. The alkynylation is effected preferably at the reflux temperature of the reaction medium although temperatures from -60° to -30° are suitable. Exemplary of other suitable reagents to effect the acetylenic addition are ethylaminediamine complex in dimethylformamide solvent and Grignard analogs such as mono and bis acetylene-magnesium halides by means known in the art.
Further, the 19-nor-compounds of formula II, wherein R 4 is propyl are ovulatory inhibitors (cf., Tetrahedron Letters 127 (1961), Velluz, Romine et al.). Additionally, compounds of formula I wherein R 4 is methyl and R 1 is hydrogen have been converted to the series of formula II, specifically, 19-nortestosterone acetate, J. Org. Chem., 26, 3904 (1961), L. J. Chinn and H. L. Dryden.
Moreover, compounds of formula I wherein R 4 is ethyl and R 1 is methyl and "m" is equal to 2 can be converted to compounds of formula XXII, i.e., 18-homo-retrosteroids, specifically the acetyl derivatives of the pregnane series, which are progestational agents and are thus useful in the treatment of fertility disorders. The 18-homo-retroandrostanes of this series have both anti-estrogenic and anti-androgenic activity effecting the secretion of gonadotropic hormones. Hence, these compounds can be used for example, in the treatment of gynecological disorders and as contraceptive agents.
The methods of this invention, as indicated above, result in the preparation either of the desired optical enantiomer illustrated by formulae I and II or the racemate thereof. The optical antipode illustrated by formulae I and II can be obtained either by resolution of the corresponding racemic end product or by resolution of racemic starting material or, if racemic starting material is directly subjected to the methods of this invention, resolution of any intermediate racemate. The present invention provides a facile synthesis for optically active end products as a result of the fact that optical specificity is preserved throughout the synthesis as a result of the stereo selectivity of the individual process conversions exemplified in Reaction Schemes A, B, C, D, E and F. Resolution can be effects by conventional resolution means known per se. For example, compounds in which the moiety represented by the symbol "Z" is hydroxy-methylene, or a group convertible into hydroxy-methylene such as carbonyl (convertible by reduction to hydroxy-methylene) or an ether or ester of hydroxy-methylene (convertible by hydrolysis to hydroxy-methylene), can be resolved by reacting the compound containing the hydroxy-methylene moiety with a dibasic acid to form a half-acid ester. If the dibasic acids are, for example, dibasic-lower alkanoic acids such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid or the like, or an aromatic dibasic acid such as phthalic acid, the so-formed half-acid ester is then reacted to form a salt with an optically active base such as brucine, ephedrine or quinine and the resulting diastereoisomeric products are separated. Alternatively, the hydroxy-methylene moiety can be esterified with an optically active acid such as camphorsulfonic acid and the resulting diastereoisomeric esters can be separated. The optical antipodes can be regenerated from the separated diastereoisomeric salts and esters by conventional means.
The following examples are illustrative but not limitative of the invention. All temperatures are stated in degrees Centigrade. Infrared, ultraviolet and nuclear magnetic resonance spectra where taken were consistent with stated structures. IR spectra where indicated were taken in chloroform. UV spectra where indicated were taken in ethyl alcohol.
EXAMPLE 1
A 0.5 weight percent solution of 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-indane in absolute ethanol was hydrogenated at atmospheric pressure and room temperature using a ten percent palladium/CaCO 3 catalyst. Hydrogenation was stopped after the uptake of 1 mole of hydrogen. The solution was then filtered and evaporated in vacuo to give a crude hydrogenation product. This crude product was then subjected to hydrolysis by stirring and refluxing for six hours with a 1:1 mixture of tetrahydrofuran and 2 N hydrochloric acid under a nitrogen atmosphere. The solution was then cooled by means of an ice bath and neutralized with 5 N sodium hydroxide. The solvent was then evaporated in vacuo and the residue was extracted sequentially with ethyl acetate and then ether. The extract was washed with a saturated sodium chloride solution and then dried over sodium sulfate. Evaporation of the solvent in vacuo afforded a mixture of cis and trans reduction products -- 3aβ,4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone and 3aα,4,7,7 a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone which was analyzed by vapor phase chromatography and NMR. The vapor phase chromatography consisting of repeatedly subjecting the crude mixture of 3aβ,4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone and 3aα,4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone to vapor phase chromatography in 40 milligram portions on a Barber-Coleman Model 5072 equipped with flame detection and a split ratio of 5:95. By this technique, 3aα,4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone was obtained as an oil. γ max 3620, 3300-3550 and 1715 cm -1 in the infrared spectrum.
EXAMPLE 2
110 Mg. of purified trans alcohol 3aα,4,7,7a-tetrahydro-1β-hydroxy-3aβ-methyl-5(6H)indanone was oxidized by reacting with 0.175 ml. of 8 N chromium trioxide in sulfuric acid in a medium of 5 ml. of acetone under a nitrogen atmosphere at 10° C over approximately a five minute period. The reaction mixture was quenched by the addition of 5.0 ml. of ice water and the organic solvent was removed in vacuo. The aqueous solution was then extracted with a mixture of ethyl acetate and ether. The organic phase was washed with sodium bicarbonate and a saturated sodium chloride solution. The extract was dried over sodium sulfate and evaporated in vacuo to give the crude oxidation product 3aα,4,7,7a-tetrahydro-7aβ-methyl-1,5-(6H)indanedione, as an oil. 68 Mg. of the crude oxidation product, 3aα,4,7,7a-tetrahydro-7aβ-methyl-1,5-(6H)indanedione was subjected to vapor phase chromatography in 14 mg. aliquots on a Barber-Coleman Model 5072 equipped with flame detection at a split ration of 5:95. Fractionation gave pure 3aα,4,7,7a-tetrahydro-7aβ-methyl-1,5-(6H)-indanedione, as an oil; γ max 1740 and 1712 cm -1 in the infrared spectrum. A sample was crystallized from ether-petroleum ether, m.p. 52°-53° C.
EXAMPLE 3
45 Ml. of dimethylsulfoxide distilled from calcium hydride was added to a 53 percent dispersion of 1.03 g. of sodium hydride in mineral oil which had been previously washed with anhydrous ether and dried under a nitrogen atmosphere. The mixture was stirred at 20° C, and a solution of 5.0 grams of 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-indane in 45 ml. of dimethylsulfoxide was added at once. The reaction mixture was agitated until hydrogen evolution ceased, approximately four hours thereafter. The dimethylsulfoxide was then distilled off under high vacuo utilizing a bath kept at a temperature of 75° C. The residue (conjugate anion of 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-indane) was dissolved in 90 ml. of anhydrous ether and added as rapidly as possible (approximately 2 minutes) to a one liter flask containing a thick slurry of anhydrous solid carbon dioxide in 225 ml. of anhydrous ether. The reaction mixture was stirred vigorously. The slurry was formed by cooling 2-3 ml. of anhydrous ether with a dry ice-methanol cooling mixture and then permitting anhydrous solid carbon dioxide from an inverted tank of ∓bone dry" carbon dioxide to enter. The tank was connected to the flask with rubber pressure tubing. Two outlets were connected to two drying towers filled with anhydrous calcium sulfate. As the slurry formed and thickened, dry ether was added gradually from an addition funnel until a total of 225 ml. had been added. The reaction mixture was stirred for six hours in a dry ice-methanol cooling bath and allowed to stand at 20° C for 16 hours. 200 Ml. of water containing 50 ml. of 0.1 N sodium hydroxide was added to the ether solution and it was agitated under a nitrogen atmosphere for one hour. The ether and water layers were separated and the ether layer was washed twice with water. The combined aqueous fractions were extracted with ether. The combined ether extracts were dried over sodium sulfate and evaporated in vacuo yielding starting material 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-indane. The aqueous solution was filtered and carefully acidified with 2 N hydrochloric acid to a pH of 2.5 at approximately 0° C. The mixture was extracted twice with benzene and then with ether, washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to yield a dry solid the β-keto acid, 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane-carbocyclic acid, m.p. 153°-160° C. Trituration with ether yielded 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane-carbocyclic acid, m.p. 156° C. An analytically pure sample of 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane-carbocyclic acid was obtained by recrystallization from acetone, m.p. 159.5° C. Analysis calculated for C 15 H 22 O 4 : C, 67.64; H, 8,33. Found: C, 67.63; H, 8.62.
EXAMPLE 4
1.84 Grams of unsaturated β-keto-acid 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane-carbocyclic acid was dissolved in 92 ml. of absolute ethyl alcohol and hydrogenated in the presence of 184 mg. of 10 percent by weight palladium on barium sulfate catalyst at atmospheric temperature and room temperature. The theoretical amount of hydrogen was consummed in 20 minutes. The solution was filtered and evaporated in vacuo, affording 1β-tertiarybutoxy-3aβ-4β-5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indane-carboxylic acid, m.p. 107.5°-109° C. An analytically pure sample of 1β-tertiarybutoxy-3aα-4β-5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indane-carbocyclic acid was obtained by recrystallization from ether, m.p. 114°-114.5° C. Analysis calculated for C 15 H 24 O 4 : C, 67.13; H, 9.02. Found: C, 66.95; H, 9.09.
EXAMPLE 5
30.7 Mg. of the β-keto acid 1β-tertiary-butoxy-3aα-4β-5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indane carbocyclic acid was dissolved in 2.5 ml. of tetrahydrofuran to which 2.5 ml. of 2 N hydrochloric acid was added. The reaction mixture was refluxed under a nitrogen atmosphere for approximately six hours. It was then neutralized with 2 N sodium hydroxide and evaporated in vacuo. The residue was extracted with ether and the extract was washed with a small amount of saturated sodium chloride solution, dried over sodium sulfate and evaporated in vacuo to give bicyclic keto alcohol 3aα-4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone as a waxy solid, m.p. 41°-42°. NMR spectra superimposable to that of 3aα-4,7,7a-tetrahydro-1β-hydroxy-7aβ-methyl-5(6H)indanone, as prepared in Example 1. Analysis calculated for C 10 H 10 O 2 : C, 71.39; H, 9.59. Found: C, 71.11; H, 9.32.
EXAMPLE 5a
246 Mg. of (±)-1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7a.beta.-methyl-5-oxo-4α-indanecarboxylic acid was suspended in 6 ml. of concentrated hydrochloric acid and stirred under a nitrogen atmosphere for 2.5 hours at room temperature until the compound had thoroughly dissolved. The flask was sealed under a nitrogen atmosphere and permitted to stand for approximately 20 hours. The solution was then evaporated in vacuo at 30° C. to give a mixture that crystallized to yield a tacky crystalline-type solid upon treatment with acetone. The solid was ground up in 1 ml. of ether and the supernatant decanted to give a crude product, melting point 102°-104° C. (dec.). Recrystallization from ether gave pure (±)-3aα,4β,5,6,7,7a-hexahydro-1β-hydroxy-7aβ-methyl-5-oxo-4α-indanecarboxylic acid, melting point 123° C. (dec.).
EXAMPLE 6
2.95 G. of 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indane-carbocyclic acid was dissolved in a mixture of 22 ml. of dimethylsulfoxide and 12.2 ml. of 36-38 percent aqueous formaldehyde solution. 1.35 G. of piperidine hydrochloride was added and it was stirred under nitrogen for three hours. 9.35 Mg. of sodium bicarbonate in water (100 ml.) was added to the above reaction mixture. It was then extracted three times with benzene. The extract was washed with water and with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and then evaporated in vacuo to give a crude1β-tertiarybutoxy-3aα-6,7,7a-tetrahydro-7aβ-methyl-4-methylene-indan-5(4H)-one, as an oil. The crude methylene ketone 1β-tertiarybutoxy-3aα-6,7,7a-tetrahydro7aβ-methyl-4-methylene-indan-5(4H)-one was purified by preparative thin layer chromatography on silica gel with a fluorescent indicator. The sample was applied at the rate of 30 mg. per plate which measured 8 ×8 inches × 1 mm. thick. The development was carried out with a mixture of 92.5 percent benzene and 7.5 percent ethyl acetate. The area corresponding to the major component was mechanically removed from the plate and the adsorbent was suspended in ethyl acetate. Filtration through Celite was followed by evaporation in vacuo to afford pure 1β-tertiarybutoxy-3aα-6,7,7a-tetrahydro-7aβ-methyl-4-methylene-indan-5(4H)-one, as an oil which crystallized upon standing in a container filled with dry-ice, m.p. 42.5°-44° C. Analysis calculated for C 15 H 24 O 2 : C, 76.22; H, 10.24 Found: C, 75.32; H, 10.25.
EXAMPLE 7
410 Mg. of freshly distilled ethyl propionyl acetate was added to 115.2 mg. of the crude methylene ketone 1β-tertiarybutoxy-3aα, 6,7,7a-tetrahydro-7aβ-methyl-4-methyleneindan-5(4H)-one. The reaction mixture was cooled to 0° C and 0.87 ml of 0.1 N sodium methoxide in methanol was added while agitating under a nitrogen atmosphere. The reaction mixture was allowed to stand for approximately 18 hours at 0° C and for an additional 4 hours at 20° C. The mixture was cooled by employing an ice bath and neutralizing with 0.87 ml. of 0.1 N hydrochloric acid. The solvent was then removed in vacuo and the residue was extracted with methylene chloride. The extract was sequentially washed with water and with a saturated sodium chloride solution, dried with sodium sulfate, filtered and evaporated in vacuo to yield crude diketoester 2-(1β-tertiarybutoxy-3aβ-4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indanylmethyl)-3-oxo valeric acid ethyl ester. 220 Mg. of the β-diketoester 2-(1β-tertiarybutoxy-3aβ,4β, 5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indanylmethyl)-3-oxo-valeric acid ethyl ester was dissolved in 4 ml. of methanol to which 4 ml. of 2 N hydrochloric acid was added. The reaction mixture was stirred and refluxed under a nitrogen atmosphere for approximately six hours. The reaction mixture was then cooled by use of an ice bath and neutralized sequentially with 0.4 ml. of 19.5 H sodium hydroxide solution and then with 0.4 ml. of 0.1 N sodium hydroxide solution. The solvent was evaporated in vacuo and the residue was extracted two times with ethyl acetate and once with ether. The combined extract was washed once with water and then two times with a saturated sodium chloride solution. The combined extract was then dried over sodium sulfate, filtered and evaporated in vacuo to give crude 2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3β-hydroxy-3aβ-6-dimethyl-1H-benz[e]indan-7-one, an oil that could be crystallized by seeding with an authentic sample. 109 Mg. of the crude BCD-tricyclic compound 2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3β-hydroxy-3aβ,6-dimethyl-1H-benz[e]indan-7-one was purified by preparative thin layer chromatography on silica gel with fluorescent indicator. Filtration through Celite followed by evaporation in vacuo gave an oil which crystallized upon seeing with an authentic sample; trituration with a 2:1 mixture of ether gave pure 2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3β-hydroxy-3aβ,6-dimethyl-1H-benz[e]indan-7-one, m.p. 131°-133° C.
EXAMPLE 8
134 Mg. of the unsaturated β-keto acid, 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane carboxylic acid was suspended in 5 ml. of ether. The suspension was cooled to 0° C and 7.6 ml. of a solution of diazomethane in ether (0.076 mmoles/m.) was added dropwise while stirring. After approximately 10 minutes of stirring, the solution was then evaporated in vacuo to yield the methyl ester, 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane carboxylic acid ethyl ester, m.p. 73°-76° C. Recrystallization from petroleum ether (boiling point 30° C-60° C) gave analytically pure 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane carboxylic acid ethyl ester, m.p. 76.5° C-77° C. Analysis calculated for C 16 R 24 O 4 : C, 68.54; H, 8.63. Found C, 68.41; H, 8.92.
EXAMPLE 9
50 Mg. of the acid, 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indane carboxylic acid was dissolved in 1.0 ml. of ether. The solution was cooled to 0° C and 1.05 ml. of a solution of diazomethane in ether (0.19 mmoles ml.) was added dropwise while stirring. After 15 minutes of stirring, the solution was evaporated to dryness to give the β-keto ester 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indane carboxylic acid methyl ester, m.p. 112.5° C-113.5° C. Recrystallization from petroleum ether (boiling point 30° C.-60° C.) gave analytically pure 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indane carboxylic acid methyl ester, m.p. 113.0° C.-113.5° C. Analysis calculated for C 16 H 26 O 4 C, 68.05; H, 9.28. Found: C, 68.09; H, 9.49.
EXAMPLE 10
54.4 Mg. of the unsaturated β-keto ester, 1β-tertiarybutoxy-5,6,7,7a-tetrahydro-7aβ-methyl-5-oxo-4-indane carboxylic acid ethyl ester, was dissolved in 2.7 ml. absolute ethyl alcohol and hydrogenated in the presence of 18.2 mg. of 10 percent palladium on barium sulfate catalyst at atmospheric pressure and room temperature. Hydrogen uptake ceased after 15 minutes. The solution was filtered and evaporated in vacuo to give crude 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indane carboxylic acid methyl ester.
EXAMPLE 11
41 Mg. of the β-keto ester, 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indane carboxylic acid methyl ester was dissolved in a mixture of 1.25 ml. of methanol and 0.55 ml. of trimethyl orthoformate. The solution was cooled with an ice bath at 0° C and 0.26 ml. of 2N methyl sulfuric acid was added while stirring under nitrogen. After five minutes at 0° C, the mixture was allowed to stand at 20° C for 16 hours. It was cooled with an ice bath and neutralized with 1 N sodium methoxide and methanol. The solvent was evaporated in vacuo and the residue was extracted with ether. The extract was washed with aqueous sodium bicarbonate and with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to give 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-5,5-dimethoxy-7aβ-methyl-4α-indancarboxylic methyl ester, an oil; γ max 1728 -1 in the infrared spectrum.
EXAMPLE 12
160 Mg. of the ketal ester, 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-5,5-dimethoxy-7aβ-methyl-4α-indancarboxylic methyl ester was dissolved in 3.5 ml. of dry toluene. The solution was cooled to 0° C and 4.5 ml. of a 20 percent solution of diisobutyl aluminum hydride in toluene was added over a 5 minute period while stirring under nitrogen. After an additional 30 minutes at 0° C, the mixture was allowed to stand at 20° C for 16 hours. It was then cooled with an ice bath and 3.0 ml. of methanol was added carefully while stirring. After 10 minutes at 0° C, it was stirred at 20° C for one hour. The crystalline precipitate was filtered through a pad of "Celite" and it was washed and extracted thoroughly with ethyl acetate. The filtrate was washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to give 1β-tertiarybutoxy- 3aα,4β,5,6,7,7a-hexahydro-5,5-dimethoxy-7aβ-methyl-4.alpha.-indanmethanol, an oil; γ max 3575 cm -1 in the infrared spectrum.
EXAMPLE 13
31.6 Mg. of the ketal alcohol, 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-5,5-dimethoxy-7aβ-methyl-4α-indanmethanol was dissolved in 1.8 ml. of acetone. The solution was cooled to 5° C and 0.2 ml. of distilled water and 0.03 ml. of 2 N hydrochloric acid was added while stirring. After 20 minutes, the reaction mixture was neutralized with 0.65 ml. of a saturated sodium bicarbonate solution. The acetone was evaporated in vacuo and the residue was extracted with ether. The extract was washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to give 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indanmethanol, an oil; γ max 3580 and 1695 cm -1 in the infrared spectrum.
EXAMPLE 14
17.4 Mg. of the β-keto alcohol, 3β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indanmethanol was dissolved in 0.25 ml. of dry pyridine and cooled to 0° C. 8.0 Mg. of methane sulfonyl chloride was added while stirring to 0.56 ml. of dry pyridine. The reaction mixture was then allowed to stand at 20° C for 1.5 hours. It was evaporated to dryness in vacuo and the residue was dissolved in chloroform. The solution was then washed with water and a saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to give 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indanmethanol methanesulfonate, as an oil; γ max 1705, 1353 and 1175 cm -1 in the infrared spectrum.
EXAMPLE 15
22.9 Mg. of the β-keto mesylate, 1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indanmethanol methanesulfonate was dissolved in a mixture of 0.3 ml. of methanol and 0.3 ml. of anhydrous benzene. 59.5 Mg. of ethyl propionyl acetate and 0.7 ml. of 1.0 Mg. of ethyl propionyl acetate and 0.7 ml. of 1.0 N sodium methoxide was added and the reaction mixture was stirred at 0° C under nitrogen for two hours and at 20° C for 16 hours. The reaction mixture was neutralized with 0.1 N hydrochloric acid and evaporated to dryness in vacuo. The mixture was then treated twice with toluene and taken to dryness under high vacuo to yield the diketo ester, 2-(1β-tertiarybutoxy-3aα, 4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4-indanylmethyl)-3-oxo-valeric acid ethyl ester, as an oil.
EXAMPLE 16
23.8 Mg. of the crude diketo ester, 2-(1β-tertiarybutoxy-3aα,4β,5,6,7,7a-hexahydro-7aβ-methyl-5-oxo-4α-indanylmethyl)-3-oxo-valeric acid ethyl ester was dissolved in 0.5 ml. of tetrahydrofuran, and 0.5 ml. of 0.2 N sodium hydroxide was added while stirring at 20° C. under nitrogen. The reaction mixture was allowed to stand at room temperature for 16 hours. The solvent was then evaporated in vacuo, the residue was dissolved in water and extracted with chloroform to remove neutral material. The water solution was carefully acidifed with 2 N hydrochloric acid and extracted with chloroform. The extract was washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated in vacuo to give the crude β-keto acid, 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3a.beta., 6-dimethyl-7-oxo-1H-benz[e]inden-8α-carboxylic acid. 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-3a.beta.,6-dimethyl-1H-benz[e]inden-7-one was obtained from the above produced product by refluxing in toluene for 1 hour under a nitrogen atmosphere.
EXAMPLE 17
348 Mg. of the lithium salt of the ketal acid, 4-(2-methyl-1,3-dioxolan-2-yl)butanoic acid was dissolved in 5 ml. anhydrous tetrahydrofuran. The solution was cooled to 0° C and 1.25 ml. of a 1.6 molar solution of methyllithium in diethylether was added dropwise over a period of one hour while stirring under a nitrogen atmosphere. The solution was allowed to rise approximately to 20° C and kept at this temperature over a period of two hours. The reaction mixture was added to crushed ice and the organic solvents were removed in vacuo. The residue was extracted with ether, the extract was washed with a saturated sodium chloride solution, dried with magnesium sulfate, filtered and evaporated in vacuo to give crude 5-(2-methyl-1,3-dioxolan-2-yl)-2-pentanone.
EXAMPLE 18
378 Ml. of dimethylsulfoxide which was distilled from calcium hydride was added to a 53 per cent dispersion of sodium hydride (29.2 g.) in mineral oil which had been washed with anhydrous hexane and dried under nitrogen. The mixture was stirred under nitrogen and heated slowly to 68°-71° C. After 1.5 hours, the evolution of hydrogen ceased and a turbid grey solution of the sodium salt of the metal sulfinyl carbanion had formed. The solution was cooled to 18° C and 60.6 g. of the ketal ester 4-(2-methyl-1,3-dioxolan-2-yl)-butanoic acid ethyl ester was added over a 40 minute period to the stirred solution at a rate such as to maintain the exothermic reaction temperature at 18°-20° C for one hour. The solution was poured on ice, neutralized with cold 1 N hydrochloric acid and extracted with chloroform. The extract was washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated in vacuo to give an oil. Volatile impurities were then removed under high vacuo, bath temperature maintained at 80° C to give the β-keto sulfoxide, 1-methyl-sulfinyl-5-(2-methyl-1,3-dioxolan-2-yl)-2-pentanone. Analysis calculated for C 10 H 10 O 4 S: C, 51.26; H, 7.74; S, 13.68. Found: C, 50.96; H, 7.55; S, 13.81.
EXAMPLE 19
46.2 Grams of aluminum foil was cut into approximately 3 qt. inch square pieces and placed into a 5 lit. three necked flask, fitted with a nitrogen inlet and held on a shaker in a fume hood. The aluminum cuttings were shaken with a solution of 2 lit. of 1 N aqueous sodium hydroxide for 1-2 minutes, and the alkali was siphoned; the metal was washed two times with 2 lit. of water in an analogous manner. The metal was then amalgamated by shaking for 15 seconds with 2 lit. of a two percent mercuric chloride solution in water. The mercuric chloride solution was then siphoned off and the amalgam was washed twice with 1 lit. of ethyl alcohol and once with ether. All operations were conducted under a nitrogen atmosphere. 40.0 G. of the β-keto sulfoxide, 1-methyl-sulfinyl-5-(2-methyl-1,3-dioxolan-2-yl)-2-heptanone was dissolved in a mixture of 2160 ml. of tetrahydrofuran, 240 ml. of water and 4 ml. of 1 H sodium hydroxide. The solution was added at once to the 1 aluminum amalgam and was shaken under a rapid stream of nitrogen for two hours to entrain the methyl mercaptan formed. The reaction mixture was filtered through a pad of Cellic on a sintered glass funnel, and the gelatinous precipitate was washed thoroughly with ether. The mixture was concentrated in vacuo to a volume comprising 50 ml. and extracted with ether. The extract was washed with a sodium chloride solution, dried over sodium sulfate, charcoaled with Norit A, filtered and evaporated in vacuo to yield the cetal ketone, 5-(2-methyl-1,3-dioxolan-2-yl)-2-pentanone. Analysis calculated for C 9 H 16 O 3 : C, 62.76; H, 9.36. Found: C, 63.09; H, 9.42.
EXAMPLE 20
11.8 Grams (0.1 moles) of diethyl carbonate in 12.5 ml. of anhydrous ether was added to 4.55 g. (0.1 moles) of a 53 percent dispersion of sodium hydride in mineral oil which was washed with anhydrous hexane and dried under nitrogen. This mixture was stirred under nitrogen and 8.6 g. (0.05 mole) of the ketal ketone, 5-(2-methyl-1,3-dioxolan-2-yl)-2-pentanone was added dropwise over a period of two hours. A gentle reflux was maintained throughout the addition and the refluxing was continued for an additional period of approximately 1 1/2 hours. The solution was then cooled with an ice bath, 20 ml. of anhydrous ether and 2 ml. of absolute ethyl alcohol was added and it was stirred for 45 minutes to destroy any unreacted sodium hydride. The suspension was diluted with an equal volume of ether and the ice cold suspension was then added to a rapidly agitated mixture of 6 ml. of glacial acetic acid and 200 ml. of ice water. The etheral layer was separated, and the aqueous layer was additionally extracted twice with ether. The extract was washed with saturated sodium bicarbonate and with a saturated sodium chloride, dried with sodium sulfate, filtered and evaporated in vacuo to give the crude β-keto ester, 6-(2-methyl-1,3-dioxolan-2-yl)-3-oxo-hexanoic acid ethyl ester, b.p. 110°-112° C at 0.2 mm., Analysis calculated for C 12 H 20 O 5 : C, 59.00; H, 8.25. Found: C, 58.92; H, 8.38.
EXAMPLE 21
A mixture of 2.36 g. (0.01 moles) of freshly prepared crude methylene ketone, 1β-tertiarybutoxy-3aα,6,7,7a-tetrahydro-7aα-methyl-4-methyleneindan-5(4H)-one and 2.68 g. (0.11 moles) of β-keto ester 6-(2-methyl-1,3-dioxolan-2-yl)-3-oxo-hexanoic acid ethyl ester was cooled in an ice bath. 20 Ml. of an 0.1 normal sodium methoxide solution in methanol was added to the above reaction mixture and the solution was allowed to stand at 0° C for approximately 64 hours and at 20° C for about four hours. The pH of the solution was then adjusted to 7.5 by means of 0.5 N hydrochloric acid and the methanol was evaporated in vacuo. The oily residue was dissolved in 77.5 ml. of tetrahydrofuran to which 77.5 ml. of 0.2 N aqueous sodium hydroxide was added. The reaction mixture was stirred at 20° C under a nitrogen atmosphere for six hours. The tetrahydrofuran was evaporated in vacuo and the basic solution extracted with ether. The ether extract was then washed with water and a saturated sodium chloride solution, dried with sodium sulfate, filtered and evaporated in vacuo to give a neutral impurity. 42.5 Ml. of an aliquot of the aqueous basic solution was carefully acidified at 0° C with 5.1 ml. of 0.5 N hydrochloric acid so as to attain a pH of 3.5. The reaction mixture was then immediately extracted with ethyl acetate and with ether. The combined extract was washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo to give the crude unsaturated β-keto acid, 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7-oxo-1H-benz[e]inden-8.alpha.-carboxylic acid, an amorphous solid. A few drops of ether were added to the crude solid 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7-oxo-1H-benz[e]-inden-8α-carboxylic acid and it was kept at -10° C for 72 hours. A large crystalline crop was formed, which could be purified by trituration at room temperature with petroleum ether (b.p. 30°-60° C). Recrystallization from ether gave analytically pure 3β-tertiary-butoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7-oxo-1H-benz[e]inden-8α-carboxylic acid, m.p. 129° C. Analysis calculated for C 25 H 38 O 6 : C, 69.09, H, 8.81. Found: C, 68.84; H, 8.70.
EXAMPLE 22
Crude unsaturated β-keto acid, 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7-oxo-1H-benz[e]inden-8.alpha.-carboxylic acid was dissolved in 50 ml. of toluene. The solution was stirred and refluxed under nitrogen for 30 minutes. It was then cooled to room temperature and extracted with 0.5 N sodium bicarbonate solution and then with a saturated sodium chloride solution. The toluene solution was dried over sodium sulfate and evaporated in vacuo to give the unsaturated keto compound 3β-tertiary-butoxy-1,2,3,3a,4,5,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7H-benz[e]inden-7-one as an oil. Similar treatment of pure β-keto acid 3β-tertiarybutoxy-2,3,3a,4,5,7,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7-oxo-1H-benz[e]inden-8.alpha.-carboxylic acid gave analytically pure 3β-tertiarybutoxy-1,2,3,3a,4,5,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)-ethyl]-3aβ-methyl-7H-benz[e]inden-7-one, m.p. 85.5°-86° C. (petroleum ether, b.p. 30°-60° C.); Analysis calculated for C 24 H 38 O 4 : C, 73.80; H, 9.81. Found: C, 73.77; H, 10.13. The compound can also exist in a dimorphic modification, m.p. 103.5°-104° C.
EXAMPLE 23
414.7 Mg. of the crude unsaturated keto compound, 3β-tertiarybutoxy-1,2,3,3a,4,5,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7H-benz[e]inden-7-one was dissolved in 20.75 ml. of absolute ethyl alcohol containing 0.5 percent by volume of triethylamine. The reaction mixture was hydrogenated in the presence of 145 mg. of a 5 percent palladium on carbon catalyst at 20° C. at atmospheric pressure to give the saturated keto compound, 3β-tertiarybutoxy-1,2,3,3a,4,5,5aα,6,8,9,9aβ,9bα-dodecahydro-6α-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7H-benz[e]inden-7-one as an oil. Catalytic hydrogenation of a pure crystalline sample of the unsaturated keto compound, 3β-tertiarybutoxy-1,2,3,3a,4,5,8,9,9aβ,9bα-decahydro-6-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7H-benz[e]inden-7-one under analogous reaction conditions to that previously described yields analytically pure 3β-tertiarybutoxy-1,2,3,3a,4,5,5aα,6,8,9,9aβ,9bα-dodecahydro-6α-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-3aβ-methyl-7H-benz[e]inden-7-one, m.p. 94.5°-96.0° C (petroleum ether, b.p. 30°-60° C.). Analysis calculated for C 24 H 40 O 4 ; C, 73.43; H, 10.27. Found: C, 73.35; H, 10.52.
EXAMPLE 24
407.2 Mg. of crude 3β-tertiarybutoxy-1,2,3,3a,4,5,5aα,6,8,9,9aβ,9bα-dodecahydro-6α-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl)-3aβ-methyl-7H-benz[e]inden-7-one was dissolved in 15 ml. of methanol. 15 Ml. of 2 N hydrochloric acid were added to the stirred solution and it was refluxed under nitrogen for four hours. The reaction mixture was neutralized with 3 N sodium hydroxide and evaporated to a small volume in vacuo. The residue was extracted with ethyl acetate. The extract was then washed with saturated sodium chloride solution, dried over sodium sulfate, charcoaled with Norite A, filtered and evaporated in vacuo to give a crude amorphous solid. Trituration with petroleum ether (b.p. 30°-60° C) and finally with 0.3 ml. of ether gave racemic 19-nortestosterone, m.p. 106°-115° C. The non-crystalline material from the mother liquors was purified by preparative thin layer chromatography on silica gel with a fluorescent indicator. A sample was applied to a single plate measuring 8 by 8 inches by 1 mm. thick. The development was carried out with a 50 percent benzene-ethyl acetate mixture and the solvent front was permitted to travel to the top of the plate. The areas corresponding to the product were mechanically removed from the plate and the adsorbent was suspended in ethyl acetate. Filtration through Celite, evaporation in vacuo, purification by trituration with petroleum ether (b.p. 30°-60° C) and ether gave racemic 19-nortestosterone, m.p. 112°-113° C. When using the reverse addition technique, racemic 19-nor-testosterone is obtained with m.p. 126°-127° C. | Total synthesis of known progestationally active steroidal materials. The steroids can be synthesized depending on the particular starting reactants selected by employing as intermediates bicyclic compounds of the formula ##STR1## wherein m is an integer having a value of 1 or 2; R 4 is hydrogen or lower alkyl; Z is lower alkylenedioxy, CH(OR 2 ) and carbonyl; R 8 when taken alone is hydrogen; R 9 when taken alone is lower alkoxycarbonyl, aryloxy-carbonyl, lower cycloalkyloxycarbonyl, carbonyl-halide, hydrogen, carboxy, formyl and methylene-X, where X is a leaving group and when taken together are methylene; with the proviso that when Z is carbonyl R 8 when taken alone is hydrogen; R 9 when taken alone is carbonyl halide, hydrogen, carboxy, formyl and methylene-X where X is a leaving group and when taken together are methylene and R 2 is hydrogen, lower alkyl, lower alkoxy-lower alkyl, phenyl-lower alkyl, tetrahydropyranyl, lower alkanoyl, benzoyl, nitrobenzoyl, carboxy-lower alkanoyl, carboxybenzoyl, trifluoroacetyl and camphorsulfonyl
And reacting then in the case where R 8 and R 9 taken together are methylene or R 8 is hydrogen and R 9 is methylene-X with β-keto esters and other analogs of the formula ##STR2## wherein R 6 is selected from the group consisting of ##STR3## lower alkyl; R 7 is lower alkyl; R 15 is selected from the group consisting of oxo, lower alkylenedioxy or (hydrogen and lower alkoxy); B is selected from the group consisting of lower alkoxy-carbonylmethylene, lower-aryloxy-carbonyl-methylene, cyanomethylene, lower alkyl sulfinyl-methylene, lower alkyl sulfonyl-methylene, and R 25 and R 26 are independently selected from the group consisting of hydrogen, hydroxyl and lower alkyl. | 2 |
FIELD OF THE INVENTION
The invention relates to a semiconductor device having a relatively low dielectric constant film and a manufacturing method for a semiconductor device having a relatively low dielectric constant film.
BACKGROUND OF THE INVENTION
With the increasing miniaturization of semiconductor elements in recent years, a demand has risen for technologies to achieve the following: reduction of the gate length of the transistor, reduction of the thickness of the gate oxide film, reduction of the film thickness of the electrode side wall spacer, and shallowing of junctions. However, it has also been desirable for basic device properties such as diffusion resistance, electrode resistance, and parasitic capacitance to be reduced or held at the level of the current generation.
Regarding processes currently under development, 0.13-μm processes require diffusion layers of depths from 45 to 90 nm and 0.1 μm processes require diffusion layers of depths from 35 to 70 nm. Meanwhile, the resistance required for the diffusion layer and gate wiring is 4 to 6 Ω. Currently, the most widely used silicide in 0.13-μm processes is CoSi 2 and the specific resistance is from 18 to 28 μΩ-cm.
Consequently, a CoSi 2 film thickness of approximately 36 nm is required to obtain a sheet resistance of 5 Ω, and the corresponding reaction quantity of Si is 130 nm. Even if Ni, having a resistance of 12 to 15 μΩ-cm, which is a lower specific resistance than Co, is used, 24 nm of Ni silicide is required, and thus 44 nm of Si is required for the reaction (IEDM 84 P110)
As a result, the distance between the junction surface of the diffusion layer and the bottom surface of the silicide layer decreases and leads to degradation of the junction properties (increased junction leakage current). The distance between the junction and the bottom surface of the silicide maintains the junction properties, and based on experience it is generally determined that a distance of approximately 50 nm is required. On the other hand, it is desirable to make the diffusion layer shallower in order to miniaturize the transistor. Thus, the objectives of maintaining the silicide resistance value and developing a more miniature transistor have a reached an impasse where they contradict each other.
One means of solving this problem was to use stacked diffusion layer technology as discussed in Laid-Open Japanese Patent Publication No. 7-22338. Using such technology, Si is stacked onto a diffusion layer region, high-concentration ion implantation is conducted, and then a silicide is formed. This conventional art manufacturing method will be further described with regard to FIGS. 16–19 .
FIG. 16 depicts the formation of an isolation region 102 on a silicon substrate 101 . Impurities are implanted into the substrate 101 as necessary. Gate oxide film 103 and gate electrode 104 are deposited, and patterning is conducted. Next, as shown in FIG. 17 , a drain extension region 106 is formed by conducting drain extension, pocket implantation, etc. Then a side wall spacer 105 is formed by depositing an insulating film on the entire surface and conducting an anisotropic etch. Next, as shown in FIG. 18 , a silicon film 107 is epitaxially grown on silicon substrate 101 using an epitaxial method such as the load-lock type silicon CVD device described in Laid-Open Japanese Patent Publication No. 7-22338. Thereafter, ion implantation is conducted to form a high-concentration region.
In conventional processes having no epitaxial region, it was necessary to conduct extremely shallow implantation in order to improve the transistor characteristics. However, when there is an epitaxially grown region on the silicon substrate as shown in FIG. 18 , a higher implantation energy could be used and a heat treatment with sufficient activation could be conducted. In short, as shown in FIG. 19 , a sufficiently deep junction 108 could be made and the transistor characteristics could be improved.
However, these stacked diffusion layer technologies, like those presented in Laid-Open Japanese Patent Publication No. 7-22338, increase the parasitic capacitance between the gate electrode and the diffusion layer, and have an enormous effect on the speed of the circuit itself. Also, it is necessary to lower the resistance of the drain extension in order to raise the drive current of the transistor. As a result, it is necessary to make the side wall spacer of the gate electrode thinner, which causes the parasitic capacitance to increase even further.
The parasitic capacitance of the gate side wall can be calculated as indicated below. Assuming the width of the transistor channel is Wch, the width of the side wall is Wsw, the side wall material is Si 3 N 4 , and the height of the stacked diffusion layer is d, then the parasitic capacitance CSW generated in one transistor is given by
CSW=∈ 0*∈SiN* d*Wch/Wsw.
Here, ∈0 is the relative dielectric constant in a vacuum (8.85×10 −12 F/m) and ∈ SiN is the relative dielectric constant (7.5) of the nitride film. It is clear that the parasitic capacitance increases when the width of the side wall is made thinner and when the stacked diffusion layer is made thicker.
The dielectric constant of SiO 2 is lower than that of Si 3 N 4 . SiO 2 has a dielectric constant of 3.9, but Si 3 N 4 has a dielectric constant of 7.5. See S. M. Sze, Physics of Semiconductor Devices, 2nd Ed., page 852. Silicon oxynitrides have dielectric constants ranging between about 4 and 7. In contrast, other nitrides have higher dielectric constants, where GaN has a dielectric constant of about 8.9, AlN has a dielectric constant of about 8.5 and InN has a dielectric constant of about 15.3. Also, the dielectric constants of metal oxides can be considered, where Al 2 O 3 has a dielectric constant of about 9, Ta 2 O 5 has a dielectric constant of about 25, ZrO 2 has a dielectric constant of about 25, HfO 2 has a dielectric constant of about 40 and TiO 2 has a dielectric constant of about 50.
As has been noted, conventional technology for the manufacture of thin film transistors has disadvantages when applied to further miniaturization.
SUMMARY OF THE INVENTION
The invention, in part, pertains to a semiconductor device having a structure which reduces the parasitic capacitance by using a film with a low relative dielectric constant as the side wall material. The material with a low relative dielectric constant is preferably a material whose relative dielectric constant is less than the relative dielectric constant of an oxide film (i.e., less than about 3.9). In this case the parasitic capacitance of the device is lower than that of a SiO 2 sidewall device.
The invention, in part, pertains to a semiconductor device having a structure that reduces the parasitic capacitance by using multi-layer side wall of a material including at least one of a low relative dielectric constant film or an oxynitride film. In this case, the parasitic capacitance of the device is lower than that of a SiN sidewall device.
The invetnion, in part, pertains to a semiconductor device having a structure that reduces the parasitic capacitance by using multi-layer side wall of a material including at least one of a low relative dielectric constant dilm or an oxynitrided film. In this case, the parasitic capacitance of the device is lower than that of a SiN sidewall devce.
The invention, in part, pertains to a semiconductor device that is a field effect transistor with at least one side wall spacer, the side wall spacer including a film with dielectric constant relatively lower than that of an oxide film, or an oxynitrided film. The field effect rransistor can be formed on the semiconductor substrate using a stacked diffusion layer.
The invention, in part, pertains to a semiconductor device that is a field effect transistor with at least one side wall spacer, the sidewall spacer including a film with dielectric constant relatively lower than that of an oxide film, or an oxynitrided film. Additionally, the field effect transistor includes a diffusion layer surface at a relatively higher position than a channel surface of the field effect transistor on a semiconductor substrate.
The invention, in part, also provides a method of forming a semiconductor device with a relatively low dielectric constant side wall film. In this method, a trench separation region, gate oxide film, and gate electrode are formed on a semiconductor substrate. Then, a film having a relatively low dielectric constant is deposited and the side wall spacer of the gate electrode is formed, preferably using anisotropic etching. The relatively low dielectric constant can be relative to the oxide film. Next, an Si film is epitaxially grown on the Si surface, high-concentration ion implantation is conducted, and an activation heat treatment is conducted to form a silicide. Afterwards, interlayer insulating films, contacts, and metal wirings are formed using existing technologies. Accordingly, with the present invention, the parasitic capacitance of the side faces of the gate electrode can be reduced in an element having a stacked diffusion layer structure.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1–5 illustrate a semiconductor device and method of forming the device of a first embodiment of the present invention;
FIGS. 6–10 illustrate a semiconductor device and method of forming the device of a second embodiment of the present invention;
FIGS. 11–15 illustrate a semiconductor device and method of forming the device of a third embodiment of the present invention; and
FIGS. 16–19 illustrate a conventional semiconductor and manufacturing method.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Advantages of the present invention will become more apparent from the detailed description given herein after. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
To reduce the size of a transistor, one must reduce the size of the gate to reduce the chip size. As the size of the gate becomes smaller, a field in a horizontal direction interferes with a field in the vertical direction. To reduce this interference, the diffusion layer must be made shallower. As the diffusion layer becomes shallower, the electric resistance becomes greater. This electric resistance needs to also be reduced. In order to accomplish this, a silicide technique has been developed. The electric resistance of the silicide is about one tenth of that of the diffusion layer. This permits the 0.13 μm line width of the current generation of semiconductor devices.
However, the silicide also needs some thickness to reduce resistance, and the diffusion layer must be thin. When the bottom of the diffusion layer and the silicide layer become close, current tends to leak. In order to avoid this current leakage, a structure having two diffusion layers has been developed: one layer being shallow and the other layer being deep. First, the shallow layer is formed, and silicon is grown over it using epitaxial growth. Then the high density region is provided. Thus, the resistance, as a whole, is reduced as if only a shallow connection is made. Since there is plenty of silicon on top, a thick silicide layer can be formed to reduce resistance. This is called the“raised source drain formation.”
In a polysilicon gate terminal, a dielectric film is provided as an insulator, and parasitic capacitance results. The parasitic capacitance reduces the circuit operation speed. Therefore, the capacitance needs to be reduced. Conventionally, an SiO 2 film or Si 3 N 4 film was used. SiO 2 has a dielectric constant of 3.9, but Si 3 N 4 has a dielectric constant of 7.5. Therefore, if Si 3 N 4 is used, the capacitance increases. This needs to be reduced, and conventionally SiO 2 is used. In the invention, a dopant is used to reduce the capacitance.
A method of forming a semiconductor isolation region in a field effect transistor that is a negative channel metal-oxide semiconductor (NMOS) is illustrated in FIGS. 1–5 . This method and the resulting apparatus are merely exemplary and the present application is not so limited to what is described hereinafter.
As shown in FIG. 1 , an isolation region 2 is first formed on semiconductor surface 1 . Next, ion implantation is required for adjusting a threshold voltage of the transistor and forming a well are introduced into the substrate using an existing implantation method to form the channel formation region of the transistor. Next a gate oxide film 3 (such as a thermal oxide film of 3 to 10 nm, or even more preferably about 5 nm) and a poly-Si film (using, for example, LP-CVD) of 100 to 400 nm, or even more preferably about 225 nm are deposited. A gate electrode 4 is formed on the gate oxide film 3 using conventional lithography and processing technologies. An antireflective film may also be deposited on the poly-Si film before electrode patterning in order to increase exposure precision.
Next, as shown in FIG. 2 , an oxide film 1 a (formed, for example, by dry oxidization at about 700 to 800° C.) for ion implantation protection is formed, and drain extension and pocket implantation for improving the short channel characteristics are provided to form drain extension 5 of the transistor. Although these implantation conditions depend on the generation of the transistor, the following conditions are desirable for a drain extension in a 0.13-μm process: arsenic implantation at an energy of 1 to 10 key (preferably about 5 keV) and a dose of 1×10 14 to 1×10 15 /cm 2 (preferably about 5×10 14 /cm 2 ) and pocket implantation using an angled implantation at approximately 15 to 30 degrees and a dose of 2×10 13 to 1×10 14 /cm 2 using step implantation.
Next, a film having a low dielectric constant (preferably a film made of the fluorine-containing SiOF and having a relative dielectric constant of 3.5 to 3.6) is deposited to a thickness of about 50 to 150 nm (preferably about 100 nm) using, for example, a CVD method. A side wall spacer 6 is formed by etching back using, for example, anisotropic etching, as shown in FIG. 3 . Reactive ion etch (RIE) is one method that can be used for anisotropic etching. It is also possible to deposit, for example, an oxide film and/or a nitride film as a buffer film before depositing the SiOF film.
The film having a low dielectric constant can have a dielectric constant relatively lower than that of an oxide film. This low dielectric constant film can include at least one of: an oxide film doped with fluorine, an oxide film doped with carbon, an oxynitrided film, an amorphous carbon film, an inorganic SOG film, an organic SOG film, Allied Signal's FLARE™ and HOSP™, Dow Chemical's SiLK™, Dow Corning's HSQ™, Catalysts and Chemicals' IPS™, and Applied Materials' BLACK DIAMOND™. Combinations of these materials can also be used to form the film with the relatively low dielectric constant. The film with the relatively low dielectric constant can be deposited using one of a CVD or a SOG method, without being restricted to these methods.
Next, all oxide films are removed from the Si surface and about 10 to 100 nm (preferably about 50 nm) of Si are epitaxially grown on the Si substrate using a load-lock type vertical furnace. It is also acceptable to use an existing epitaxial device to accomplish the epitaxial growth, such as by L/L Poly CVD. Non-crystalline Si is deposited on the gate electrode and the element separation isolation region, but it is removed selectively using a liquid mixture of hydrofluoric acid, acetic acid, nitric acid, or the like as shown in FIG. 4 .
Next, high-concentration ion implantation (using, for example, arsenic at 30 to 200 keV and a dose of about 2×10 15 to 1×10 16 /cm 2 for example, even more preferably about 120 keV and about 5×10 15 /cm 2 ) for forming the source and drain is performed. Then, an activation heat treatment at about 900° C. to about 1100° C. is conducted for approximately 5 to 30 seconds (preferably about 10 seconds at about 1000° C.) to form source-drain region 8 as shown in FIG. 5 . Finally, a semiconductor element with a small parasitic capacitance is completed by forming a silicide, depositing interlayer films, forming contacts, and patterning wiring using conventional technologies.
Although this embodiment of the present application presents the fabrication of an NMOS, the invention can also be applied to other semiconductors and field effect transistors, including but not limited to, positive channel metal oxide semiconductor (PMOS), complementary metal oxide semiconductor (CMOS), and silicon on insulator (SOI).
A second alternative method of forming a semiconductor element separation region in a semiconductor device (a negative channel metal-oxide semiconductor (NMOS) is illustrated in FIGS. 1–5 , but this is merely exemplary and the present application is not so limited) in accordance with the invention is described hereinafter.
As shown in FIG. 6 , an element separation region 22 is first formed on semiconductor surface 21 . Next, ions required for adjusting a threshold value of the transistor and forming a well are introduced into the substrate using a conventional implantation method to form the channel formation region of the transistor. Next, a gate oxide film 23 (such as a thermal oxide film of about 1 to 10 nm, or even more preferably about 2 nm) and a poly-Si film (using, for example, LP-CVD) of about 100 to 400 nm, or even more preferably about 225 nm are deposited. A gate electrode 24 is formed on the gate oxide film 23 using conventional lithography and processing technologies. An antireflective film may also be deposited on the poly-Si film before electrode patterning in order to increase exposure precision.
Next, as shown in FIG. 7 , an oxide film 1 a (formed for example by dry oxidization at about 700 to 800° C.) for ion implantation protection is formed. Then, drain extension and pocket implantation for improving the short channel characteristics are conducted to form drain extension 25 of the transistor. Although these implantation conditions depend on the generation of the transistor, the following conditions are desirable for an extension in a 0.13-micron process: arsenic implantation at energy of about 1 to 10 keV (preferably about 5 keV) and a dose of 1×10 14 to 1×10 15 /cm 2 (preferably about 5×10 14 /cm 2 ) and pocket implantation using an angled implantation at approximately 15 to 30 degrees and a dose of about 2×10 13 to 1×10 14 /cm 2 using step implantation such as 4-direction or 8-direction step implantation (preferably a 20-degree angle implantation and total implantation dose of about 4×10 13 /cm 2 are accomplished by conducting step implantation four times).
Next, an oxide film having a thickness of about 5 to 20 nm (preferably about 10 nm), a nitride film having a thickness of about 5 to 50 nm (preferably about 20 nm), and a film having a low dielectric constant (preferably a film made of the fluorine-containing oxide SiOF and having a relative dielectric constant of 3.5 to 3.6) are deposited to a thickness of about 800 nm and side wall spacer 26 is formed by etching back using, for example, anisotropic etching, as shown in FIG. 8 . An anisotropic etch technique such as reactive ion etch (RIE) can be used. FIG. 8 a shows a detail of the side wall spacer 26 indicating the oxide film 26 a , the nitride film 26 b and the film having the relatively low dielectric constant 26 c.
Next, all oxide films are removed from the Si surface and about 50 nm of Si 27 are epitaxially grown on the Si substrate using a load-lock type vertical furnace. It is also acceptable to use an existing epitaxial device to accomplish the epitaxial growth. Non-crystalline Si is deposited on the gate electrode and the element separation region, but it is removed selectively using a liquid mixture of hydrofluoric acid, acetic acid, nitric acid, or the like as shown in FIG. 9 .
Next, high-concentration implantation (using, for example, arsenic at about 30 to 200 keV and a dose of about 2×10 15 to 1×10 16 /cm 2 for example, even more preferably about 120 keV and about 5×10 15 /cm 2 ) for forming the source and drain is conducted and an activation heat treatment at about 900° C. to 1100° C. is conducted for approximately 5 to 30 seconds (preferably about 10 seconds at about 1000° C.) to form source-drain region 28 as shown in FIG. 10 .
Finally, a semiconductor element with a small parasitic capacitance is completed by forming a silicide, depositing interlayer films, forming contacts, and patterning wiring using conventional technologies.
Although this embodiment of the present application presents the fabrication of an NMOS, the invention can also be applied to other semiconductors and field effect transistors, including but not limited to, positive channel metal oxide semiconductor (PMOS), complementary metal oxide semiconductor (CMOS), and silicon on insulator (SOI).
A third alternative method of forming a semiconductor element separation region in a semiconductor device in a semiconductor device (a negative channel metal-oxide semiconductor (NMOS) is illustrated in FIGS. 1–5 , but this is merely exemplary and the present application is not so limited) in accordance with the present invention is described hereinafter.
As shown in FIG. 11 , an element separation region 32 is first formed on semiconductor surface 31 . Next, ions required for adjusting a threshold value of the transistor and forming a well are introduced into the substrate using a conventional implantation method to form the channel formation region of the transistor. Next, a gate oxide film 33 (such as a thermal oxide film of about 3 to 10 nm, or even more preferably about 5 nm) and a poly-Si film (such as LP-CVD 100 to 400 nm, or even more preferably about 25 nm) are deposited and a gate electrode 34 is formed on the gate oxide film 33 using conventional lithography and processing technologies. An antireflective film may also be deposited on the poly-Si film before electrode patterning in order to increase exposure precision.
Next, as shown in FIG. 12 , an oxide film 1 a (formed for example by dry oxidization at 700 to 800° C.) for ion implantation protection is formed. Then, drain extension and pocket implantation for improving the short channel characteristics are conducted to form a drain extension 35 . Although these implantation conditions depend on the generation of the transistor, the following conditions are desirable for a drain extension in a 0.13-micron process: arsenic implantation at energy of about 1 to 10 keV (preferably about 5 keV) and a dose of about 1×10 14 to 1×10 15 /cm 2 (preferably about 5×10 14 /cm 2 ) and pocket implantation using an angled implantation at approximately 15 to 30 degrees and a dose of 2×10 13 to 1×10 14 /cm 2 using step implantation such as 4-direction or 8-direction step implantation (preferably a 20-degree angle implantation and total implantation dose of 4×10 13 /cm 2 are accomplished by conducting step implantation four times).
Next, a film having a relatively low dielectric constant (a film made of the oxynitride SiON and having a relative dielectric constant of about 3.9 to about 7.5) is deposited at a thickness of about 50 to 150 nm (preferably about 100 nm) using a CVD method and side wall spacer 36 is formed by etching back using, for example, anisotropic etching, as shown in FIG. 13 . It is also acceptable to deposit an oxide film as a buffer film before depositing the SiON film.
Next, all oxide films are removed from the Si surface and about 10 to 100 nm (preferably about 50 nm) of Si 37 are epitaxially grown on the Si substrate using a load-lock type vertical furnace, as is shown in FIG. 14 . It is also acceptable to use a conventional epitaxial device to accomplish the epitaxial growth.
As shown in FIG. 15 , non-crystalline Si is deposited on the gate electrode and the element separation region, but it is removed selectively using a liquid mixture of fluoric acid, acetic acid, etc. Next, high-concentration implantation (using for example, arsenic at 30 to 200 keV from about 2×10 15 to 1×10 16 /cm 2 for example, even more preferably about 120 keV and about 5×10 15 /cm 2 ) for forming the source and drain is conducted and an activation heat treatment at about 900° C. to 1100° C. is conducted for approximately 5 to 30 seconds (preferably about 10 seconds at 1000° C.) to form source-drain region 38 as shown in FIG. 15 .
Finally, a semiconductor element with a small parasitic capacitance is completed by forming a silicide, depositing interlayer films, forming contacts, and patterning wirings using existing technologies.
Although this embodiment of the present application presents the fabrication of an NMOS, the invention can also be applied to other semiconductors, including but not limited to, positive channel metal oxide semiconductor (PMOS), complementary metal oxide semiconductor (CMOS), and silicon on insulator (SOI).
Although this embodiment of the present application presents the fabrication of an NMOS, the invention can also be applied to other semiconductors, including but not limited to positive channel metal oxide semiconductor (PMOS), complementary metal oxide semiconductor (CMOS), and silicon on insulator (SOI).
The present invention makes it possible to, among other features, reduce the parasitic resistance between the electrodes and diffusion layer of a semiconductor element having a stacked diffusion layer structure.
The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications, as would be obvious to one skilled in the art, are intended to be included within the scope of the following claims. | A semiconductor device has a structure that reduces the parasitic capacitance by using a film with a low relative dielectric constant as the side wall material of the gate. The material with a low relative dielectric constant is preferably a material whose relative dielectric constant is less than the relative dielectric constant of an oxide film, i.e., less than about 3.9. | 7 |
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to vacuum chambers or systems. More particularly, the present invention relates to a removable door for a vacuum chamber.
2. Description of the Prior Art
In high-vacuum instrumentation, it is necessary to provide demountable seals to access instrument components housed within the vacuum system. These components must be accessed, for example, for servicing, cleaning, or for periodic exchange.
In the prior art, high-vacuum flanges or plates are sealed to the vacuum chamber using elastomeric "O-rings", gaskets, or other "soft-metal" type seals. Such flanges or plates may also provide the mounting for various components, such as a mass spectrometer analyzer. FIG. 1 is an isometric view of a vacuum chamber (10) having high-vacuum plates, according to the prior art. Such plates are typically shaped to seal round (12) or substantially rectangular (14) openings.
The O-ring (16) fits into a groove (18) that may be formed either in the plate or in the chamber itself. The plate (19) is installed over the opening and compressively held in place by fasteners such as bolts (20) or clamps. The O-ring seal material is thereby compressed between the vacuum plates or flanges and the vacuum chamber.
It is known in the prior art to use the pressure differential between the inside of the pumped-down chamber and atmospheric pressure to seal the plate to the opening. However, such pressure sealing has heretofore required the substantial weight of the plate to initially seal the opening under the weight of gravity prior to vacuum initiation. The prior art pressure seal is thus not usable for vertical openings in the side (22), or openings in the bottom (24) of a vacuum chamber, without the additional use of clamps or bolts.
FIG. 2 is a side sectional view of a bolted plate, according to the prior art. A flange (26) surrounds an opening (28) in the vacuum chamber (30). The O-ring (32) fits within the groove (34) formed in the flange. The plate (36) is placed over the opening. Bolts (38) are then inserted through apertures (40) formed in the plate and flange. Finally, nuts (42) are mated to the bolts to compressively seal the plate to the chamber.
These prior art seals do not provide quick and convenient access to the inside of the vacuum chamber. The bolted plate requires use of a tool to remove or install the bolts. The plate must be entirely removed from the vacuum chamber. Thus, any components mounted on the plate must also be removed. When the removed plate is then placed on a surface or a rack for storage, the user must be careful not to damage the mounted components.
It would be an advantage to provide a demountable sealing plate that may be used on all sides of a vacuum chamber. It would be a further advantage if this demountable sealing plate provided access to the interior of a vacuum chamber without requiring complete plate removal.
SUMMARY OF THE INVENTION
The invention provides a detachable, vacuum-sealing plate assembly for vacuum chamber access. The assembly has a demountable hinge, thereby permitting the plate to be swung open or closed, or completely removed from the chamber. A hinge assembly allows the hinge to move, permitting a seal such as an O-ring to be compressed, thereby sealing the opening. The swung-closed plate is pressure-sealed to the chamber during vacuum pump-down by the pressure differential between the interior of the chamber and the outside atmosphere. The plate is released upon vacuum venting, thereby providing swing-open access to the chamber.
Functional components may be mounted to the plate. The plate may also have associated high-vacuum electrical or physical component feed-throughs.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an isometric view of a vacuum chamber having high-vacuum plates, according to the prior art;
FIG. 2 is a side sectional view of a bolted plate, according to the prior art;
FIG. 3 is an isometric view of a demountable, high-vacuum plate assembly, according to a preferred embodiment of the invention;
FIG. 4 is an isometric view of a vacuum chamber, according to the invention;
FIG. 5 is an isometric view of a vacuum chamber having a sealing groove formed therein, according to the invention;
FIGS. 6a and 6b show bottom and top partial sectional views of the demountable vacuum-sealing plate assembly hinged end, according to the invention; and
FIG. 7 shows the demountable vacuum-sealing plate apparatus according to the invention incorporated into a gas chromatograph/mass spectrometer system.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a novel demountable high-vacuum sealing plate assembly for a vacuum chamber.
FIG. 3 is an isometric view of a demountable, high-vacuum plate assembly 44, according to a preferred embodiment of the invention. Functional components, such as a mass spectrometer analyzer 46 with an ion source 48, quadrupole ion mass filter 50, and ion detector 52 are mounted to the inner (vacuum chamber) side 54 of the plate 56. It is readily apparent to one skilled in the art that alternate embodiments of the invention may have different or no components mounted to the assembly. In yet another embodiment, functional components, such as a wafer loading mechanism, are mounted to the atmospheric side 58 of the plate.
High-vacuum feed-throughs 60 may be provided through the plate. Such feed-throughs include electrical connections for applying a voltage or conducting current, as well as devices for gas or liquid transfer, such as a gas sample port or a plasma supply line.
A hinge movably connects the plate in the region of the chamber wall. The hinge pin 64 is affixed to the plate. In alternate embodiments of the invention, the plate is vertically, horizontally, or angularly hinged. More than one hinge and plate may be provided.
FIG. 4 is an isometric view of a vacuum chamber, according to the invention.
The chamber 66 has a hinge assembly 68 formed as an integral part of the chamber at each port, or opening 70, to be sealed by such invention. The hinge assembly includes a lower aperture 72 dimensioned to receive and secure an end of the hinge pin 64. Although not shown in FIG. 4, a hinge pin bushing may be inserted into this lower aperture. The opposite end of the hinge pin is removably inserted into an upper slot 74. Such hinge assembly facilitates the separation or removal of the plate assembly from the mating vacuum chamber. Although not required, hinge bushings or bearings may be included as working parts of either the hinge pin or the hinge assembly.
The hinge permits swing-open access to the chamber upon vacuum venting.
The plate is swung closed to seal the vacuum chamber at pump-down. The opening and closing may be manually or automatically performed. In the preferred embodiment of the invention, the hinge is formed of stainless steel.
However, in alternate embodiments, the hinge is formed of any material having the requisite structural strength. In this example, the hinge pin and plate are made of stainless steel, and the integral hinge assembly and chamber is made of aluminum. The vacuum plate preferably incorporates a single-axis integral hinge pin.
However, in other embodiments of the invention, a plurality of hinge pins may be used. In yet another embodiment, the hinge pin is not formed as an integral part of the assembly. Rather, the hinge pin is formed separately and subsequently attached to the assembly.
In alternate equally preferred embodiments of the invention, a seal such as an O-ring is fit into a groove formed in the plate or in the chamber itself. FIG. 5 is an isometric view of a vacuum chamber having a sealing groove formed therein, according to the invention. In the figure, the vacuum chamber 66 has a vertical opening 70 formed therein. The O-ring 76 is fitted into a groove 78 formed in the chamber wall. The hinge assembly 68 is provided at one end of the opening.
The O-ring is preferably formed of an elastomeric, compressible material. It will be appreciated by those skilled in the art that although O-rings are described herein in connection with the presently preferred embodiment of the invention, other seals may be used to practice the invention. Upon pump-down, the O-ring seal is automatically compressed and held in place by the pressure differential. Thus, no bolts, clamps or fasteners are required.
However, in alternate embodiments of the invention, such fastening means may be provided in addition to the atmospheric-pressure sealing. Upon venting, the internal and external pressures equilibrate, and the seal is released. The door then swings open.
The hinge assembly is dimensioned to securely retain the hinge pin, while permitting the plate to be radially pivoted. However, the hinge assembly does provide sufficient space for the hinge pin to move slightly when vacuum pressure is initiated or released within the chamber. Thus, the plate may be drawn towards the chamber during pump-down, to compress the O-ring and seal the chamber. Similarly, when the chamber is vented, the plate separates from the chamber, and the O-ring is de-compressed.
FIGS. 6a and 6b show top and bottom partial sectional views of the demountable vacuum-sealing plate assembly. The O-ring 76 is fitted within a groove 78 formed in the chamber wall 80. This groove cross-section is typically trapezoidal in shape, to retain the O-ring securely therein. The hinge pin 64 rests within the lower aperture 72 and upper slot 74. Prior to pump-down, the plate 56 is positioned such that the un-compressed O-ring touches the plate as shown in position 81. After pump-down has commenced, the plate is urged towards the vacuum chamber to provide O-ring compression to affect the vacuum seal. In this sealed position 82, the hinge pin moves within the spaces 84 and 85 provided in the lower aperture and upper slot, respectively, to permit full compression of the O-ring between the plate and grooved chamber wall.
Although dependent on the size of vacuum chamber and vacuum pumps, experimental testing has indicated that the plate is pressure-sealed to the chamber, preferably within 10-20 seconds, and more preferably within approximately 3-5 seconds of commencing the pump-down. Since the rate of venting is controlled by the user, the time for releasing the plate varies accordingly.
The demountable vacuum-sealing plate assembly may be disassembled by hand, and without requiring the use of tools or fasteners. Alternately, the chamber may be quickly accessed using the hinged vacuum door function without removing the plate. Handling of components mounted on the plate is thereby reduced, minimizing the likelihood of damage to delicate devices, and support for components being accessed is provided.
Although the invention is described herein with reference to the preferred embodiment, one skilled in the art will readily appreciate that other applications and equivalents may be substituted for those set forth herein without departing from the spirit and scope of the present invention. For example, a variety of devices, including electron microscopes, mass spectrometer analyzers, sample handlers for electron microscopes, surface science equipment, and wafer loaders may be mounted to the plate. Electronic subassemblies may also be mounted on the plate, if desired.
FIG. 7 shows one embodiment of the invention in which the demountable vacuum-sealing plate apparatus according to the invention is incorporated into a gas chromatograph/mass spectrometer system. The invention may also be applied to such systems as liquid chromatograph/mass spectrometer systems. In the system shown in FIG. 7, a gas sample to be tested flows from the gas chromatograph 88 and into the ion source of the mass spectrometer 90, mounted to the inside of the plate and within the vacuum chamber 66. The mass spectrometer drive electronics 92 are mounted to the outside of the plate. The vacuum pump 96 is located at any appropriate position proximate to the chamber, and is connected thereto.
In this embodiment, the hinged vacuum plate function permits engagement of the ion source, mounted to the vacuum plate 64, to the sample transfer line 94, or column, connection with the gas chromatograph. This provides automatic engagement/disengagement of the ion source with the gas chromatograph transfer line or column upon closing/opening.
In a preferred embodiment, an entrance port 98 better illustrated in FIG. 3 attached to the ion source slides over the gas chromatograph column exit-end tubulation (see FIGS. 3 and 7) within the vacuum chamber to effect a gas-tight sleeve seal upon door closure. Similarly, the sleeve seal disengages upon door opening.
While the invention does not require the use of additional fasteners, such fastener devices may also be provided. For example, a clamp may be provided to hold the plate shut during shipping and transport.
Accordingly, the invention should only be limited by the claims included below. | A detachable, vacuum-sealing plate assembly is provided for vacuum chamber access. The assembly has a demountable hinge, thereby permitting the plate to be swung open or closed, or completely removed from the chamber. The swung-closed plate is automatically pressure-sealed to the chamber during vacuum pump-down by the pressure differential between the interior of the chamber and the outside atmosphere. The plate is released upon vacuum venting, thereby providing swing-open access to the chamber. Functional components may be mounted to the plate. The plate may also have associated high-vacuum electrical fluid flowpath transfer or physical component feed-throughs. | 5 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to and the benefit of Korean Patent Application No. 10-2008-0024563, filed Mar. 17, 2008, the disclosure of which is incorporated herein by reference in its entirety.
BACKGROUND
[0002] 1. Field
[0003] The present disclosure relates to a floating system having propulsive devices, and more particularly, to a floating system having propellers for used in moving the ship while sailing and mooring.
[0004] 2. Discussion of the Related Technology
[0005] Natural gas which is in a gas state is transported through a gas pipe line installed on the land or in the sea, or natural gas which is in a liquefied natural gas (LNG) state is transported by an LNG carrier (LNG transport vessel) to distant markets while the liquefied natural gas is stored in the LNG carrier. Liquefied natural gas is produced by cooling natural gas at an extremely low temperature of approximately −163° C., and a volume of the liquefied natural gas is approximately 1/600 of a volume of natural gas which is in a gas state, so that marine transportation is suitable for a long-distance transportation of liquefied natural gas.
[0006] In recent, besides an LNG transport vessel employed for loading LNG, sailing on the sea and unloading LNG to a land market, an LNG regasification vessel (RV), which is loaded with LNG, sails on the sea, and re-gasifies the stored LNG to unload the regasified LNG in a natural gas state after arriving a land market, has been employed. Such an LNG RV is equipped with a storage tank for storing LNG and facilities such as an apparatus for re-gasifying LNG and the like.
[0007] In addition, recently, a demand for a floating marine structure such as an LNG floating production storage and offloading (FPSO) or an LNG floating storage and regasification unit (FRSU) also has been increased gradually. Such a floating marine structure is also equipped with the storage tank, which is installed to the LNG transport vessel or the LNG RV, and mounted with an apparatus for liquefying natural gas or re-gasifying LNG, if necessary.
[0008] The LNG FPSO is the floating type maritime structure used for liquefying the produced natural gas directly on the sea, storing it in a storage tank, and delivering the LNG stored in the storage tank to an LNG transport vessel when necessary. In addition, the LNG FSRU is a floating type maritime structure, which stores LNG, which is unloaded from the LNG transport vessel, in a storage tank on the sea far away from the land and then gasifies the LNG, if necessary, and supplies the gasified natural gas to a market on the land.
[0009] The foregoing discussion in the background section is to provide general background information, and does not constitute an admission of prior art.
SUMMARY
[0010] One aspect of the invention provides a ship. The ship comprises a hull having a length in a longitudinal direction and a width in a lateral direction perpendicular to the longitudinal direction; a first propeller secured to the hull and configured to propel the ship; and a second propeller secured to the hull and configured to propel the ship, wherein the second propeller is distanced from the first propeller both in the longitudinal and lateral directions.
[0011] In the foregoing ship, at least one of the first and second propellers may be configured to pivotally rotate while secured to the hull. The first and second propellers may be closer to a rear end of the ship than to a front end of the ship. A first distance from the first propeller to a rear end of the ship may be smaller than a second distance from the second propeller to the rear end of the ship. The hull may comprise a center line extending in the longitudinal direction between front and rear ends thereof, wherein the first propeller may be on one side of the center line and the second propeller is on the other side of the center line. The center line may be closer to the second propeller than to the first propeller. The first and second propellers may be arranged along an imaginary straight line which is substantially tilted from the longitudinal direction. The imaginary line may be tilted from the longitudinal direction forming an angle therebetween from about 10° to about 80°.
[0012] Another aspect of the invention provides a floating system. The floating system comprises: a floating body; a first propeller pivotally secured to the floating body; and a second propeller pivotally secured to the floating body and distanced from the first propeller in a first direction and in a second direction perpendicular to the first direction, wherein the first and second directions are generally parallel to a surface of water on which the floating system floats.
[0013] In the foregoing floating system, the floating body may comprise a stem and a stem, wherein the first and second propellers are located closer to the stem than to the stem. The floating body may comprise a stem and a stem, wherein the floating body generally may extend in the first direction from the stem and the stem. The first and second propellers may be arranged along an imaginary line which is slanted with respect to the first direction. The imaginary line and the first direction may define an angle from about 10° to about 80°. The angle may be from about 30° to about 60°.
[0014] Still in the foregoing system, the floating system may further comprise a mooring structure configured to be fixed to a seabed or land, wherein the floating body is pivotally connected to the mooring structure. The first and second propellers may be configured to, in combination or alone, apply a propulsive force to the floating body so as to move around the mooring structure. The first propeller may be configured to pivot with respect to the floating body between a first sailing position and a first mooring position, wherein the second propeller may be configured to pivot with respect to the floating body between a second sailing position and a second mooring position.
[0015] Further in the foregoing system, the floating body may be configured to sail substantially straight when the first and second propellers are set in the first and second sailing positions. The floating body may be configured to move around the mooring structure when the first and second propellers are set in the first and second mooring positions. The first propeller may be configured to apply a first propulsive force to the floating body at the first sailing position generally in a fourth direction, wherein the second propeller may be configured to apply a second propulsive force to the floating body at the second sailing position generally in a fifth direction, wherein the floating body may further comprise a rudder configured to control sailing of the floating body in the first direction. The fourth and fifth directions may be substantially parallel to the first direction. The first propeller may be configured to apply a first propulsive force to the floating body at the first sailing position generally in a fourth direction, wherein the second propeller may be configured to apply a second propulsive force to the floating body at the second sailing position generally in a fifth direction, wherein the fourth and fifth directions may be substantially nonparallel. The floating body may be selected from the group consisting of an LNG tank ship, an LNG RV, an LNG FPSO and an LNG FSRU.
[0016] Still another aspect of the invention provides a method of operating a floating system. The method comprises: providing the foregoing floating system; engaging the floating body with a mooring structure fixed to a seabed; and running the first and second propellers so as to rotate the floating body around the mooring structure while the floating body s engaged with the mooring structure.
[0017] In the foregoing method, the method may further comprise disengaging the floating body from the mooring structure; and running the first and second propellers so as to sail the floating body away from the mooring structure. The method may further comprise: pivoting the first propeller with respect to the floating body to a first sailing position; and pivoting the second propeller with respect to the floating body to a second sailing position, wherein running the first and second propellers so as to sail the floating body comprises operating the first propeller to apply a first propulsive force to the floating body at the first sailing position generally in a fourth direction; and operating the second propeller to apply a second propulsive force to the floating body at the second sailing position generally in a fifth direction, wherein the fourth and fifth directions are substantially parallel to the first direction.
[0018] Still in the foregoing method, the method may further comprise pivoting the first propeller with respect to the floating body to a first sailing position; and pivoting the second propeller with respect to the floating body to a second sailing position, wherein running the first and second propellers so as to sail the floating body comprises operating the first propeller to apply a first propulsive force to the floating body at the first sailing position generally in a fourth direction; and operating the second propeller to apply a second propulsive force to the floating body at the second sailing position generally in a fifth direction, wherein the fourth and fifth directions are substantially nonparallel.
[0019] Further in the forgoing method, the floating system may comprise a LNG tank configured to contain LNG, wherein the method may further comprise loading or unloading LNG into or from the LNG tank while the floating system moors. The floating system may comprise a LNG tank containing LNG and a LNG vaporizer, wherein the method may further comprise vaporizing the LNG and transmitting the vaporized LNG to a valve port connected to an onshore LNG supplying system.
[0020] An aspect of the present invention is to provide a floating structure having a pair of thrusters, acting as propulsive devices, installed to a stem bottom thereof slantingly with respect to each other to enable the pair of thrusters to control both propulsion and heading angle thereof.
[0021] According to an aspect of the present invention, there is provided a floating structure sailing or moored on the sea, which comprises a plurality of propulsive devices rotatably installed to a stem bottom of the floating structure, wherein the propulsive devices are disposed on the stem bottom slantingly with respect to each other, thereby preventing the propulsive devices from interfering with each other when they operate.
[0022] The plurality of propulsive devices may be arranged in a longitudinal direction of the floating structure to generate propulsive force when the floating structure sails, and the plurality of propulsive devices may be arranged in a right or left side direction of the floating structure to control a heading angle when the floating structure is moored, thereby performing the propulsion and the heading angle control of the floating structure when it sails and is moored, respectively.
[0023] The plurality of propulsive devices are preferably a pair of azimuth type thrusters capable of changing a propelling direction while rotating in its origin place.
[0024] A pair of the propulsive devices are preferably installed to the stem bottom of the floating structure slantingly at an angle θ with respect to each other, the angle θ being in a range of 10 to 80°.
[0025] The floating structure may further comprise an automatic control system for correcting an advance direction of the floating structure by utilizing a rudder, by adjusting directions of the pair of propulsive devices, or by adjusting a propulsive force ratio of the pair of propulsive devices to correct an error caused by a difference in moment when the floating structure sails by the pair of propulsive devices slantingly installed.
[0026] The floating structure may be any one selected from an LNG transport vessel, an LNG RV, an LNG FPSO and an LNG FSRU.
[0027] According to another aspect of the present invention, there is provided a method of controlling a heading angle of a moored floating structure using a plurality of propulsive devices rotatably installed to a stem bottom thereof, wherein a heading angle of the moored floating structure is controlled using the plurality of propulsive devices disposed on a stem bottom of the floating structure slantingly with respect to each other to prevent the propulsive devices from interfering with each other when the propulsive devices operate.
[0028] The method of controlling a heading angle of a moored floating structure may comprise the step of generating propulsive force in a state where the propulsive devices are rotated to be directed to a right or left side of the floating structure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 is a plan view schematically showing a floating structure according to one embodiment of the present invention; and
[0030] FIG. 2 is a side view schematically showing the floating structure according to one embodiment of the present invention.
DETAILED DESCRIPTION OF EMBODIMENTS
[0031] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.
[0032] The floating structures, such as an LNG regasification vessel, an LNG FPSO, an LNG FRSU and the like, for transporting and storing liquid cargo such as LNG on the sea can be used in a state where the floating structure is moored by a single point mooring system such as a turret or yoke mooring system. Such a single point mooring system is mainly applied to a floating structure for operating on a sea area in which a direction of environmental force such as wind, tide and wave is frequently changed.
[0033] According to the single point mooring system, a mooring rope used for mooring a floating structure is fixed to a device such as a turret, so that the mooring rope serves to maintain a location of the floating structure. At this time, the floating structure can freely turn about the turret, so that a direction of the floating structure can be converged to minimize external force exerted on the floating structure.
[0034] Various external forces are exerted on the floating structure according to external environmental conditions. Wind, tide and wave as external force may be applied to the floating structure. A heading angle of the floating structure moored in the single point mooring system is naturally stabilized to minimize magnitudes of the various external forces caused by an environment.
[0035] However, in a case where a direction of wind and tide applied to the floating structure differs from a direction of wave applied thereto, wave is frequently applied to not a front of the hull but a side thereof in a state where a heading angle is stable. At this time, if the wave is high, a motion of the hull, in particular a roll motion of a stem wherein the hull rolls from side to side, becomes large.
[0036] If the roll motion of the stem becomes excessively large, it is difficult to operate various kinds of facilities provided in the floating structure or a severe sloshing phenomenon can be caused in the storage tank, so that there is need to control intentionally a heading angle of the floating structure according to the circumstances. The sloshing phenomenon means that a liquid state material, i.e., LNG, stored in the storage tank flows when a floating body such as a vessel moves under various marine conditions, and causes a wall surface of the storage tank to be severely damaged.
[0037] In a floating structure, accordingly, in addition to a propulsive device provided at the stern and used for sailing (or moving, coming back to harbor), other propulsive devices are additionally mounted to left and right surfaces of the stern for intentionally controlling a heading angle when the floating structure is moored in a single point, as described above.
[0038] In the floating structure as described above, a propulsive device for sailing the floating structure and propulsive devices for controlling a heading angle are separately provided. Thus, the cost required for installing the propulsive devices is increased and a control system used for controlling a plurality of propulsive devices becomes complicated.
[0039] FIG. 1 is a plan view schematically showing a floating structure according to one embodiment of the present invention; and FIG. 2 is a side view schematically showing the floating structure according to one embodiment of the present invention.
[0040] In certain embodiments, a floating structure mentioned herein is a concept including a structure or a vessel, which floats on the sea on which flows occur. In one embodiment, the structure or vessel has a storage tank for storing liquid cargo such as LNG loaded at an extremely low temperature, LNG re-gasification facilities or LNG liquefaction facilities. For example, the floating structure includes a marine structure, such as an LNG FPSO or an LNG FSRU, as well as a vessel, such as an LNG transport vessel or an LNG RV. The floating structure can be utilized while being moored by a single point mooring system such a turret or yoke mooring system. As an example, FIGS. 1 and 2 show that a floating structure 1 is single-point-moored by a turret 2 provided at a stem portion of the floating structure 1 . However, the present invention is not limited thereto. The floating structure of one embodiment of the present invention can be moored by any known system in addition to the turret.
[0041] In one embodiment, propulsive devices 4 and 6 are installed to a stem bottom of the floating structure 1 . Although azimuth type thrusters capable of changing the propelling direction while rotating in its origin place are used as these propulsive devices 4 and 6 in one embodiment, a variety of propulsive devices may be employed if they are rotatable or pivotable with respect to the hull.
[0042] As shown in FIG. 1 , the propulsive devices 4 and 6 are installed to the stem bottom of the floating structure 1 along a line L 2 extending in a direction slanted with respect to a line L 2 at a certain angle θ.
[0043] Assuming that an imaginary line L 1 passes the first propulsive device 4 installed to a stern side of the floating structure 1 and is perpendicular to a line L 3 extending along the longitudinal direction of the floating structure 1 , and that an imaginary line L 2 passes the first propulsive device 4 and the second propulsive device 6 installed to be closer to a stem side than the first propulsive device 4 , the lines L 1 and L 2 define a certain angle θ. The lines L 2 and L 3 define an angle α.
[0044] In one embodiment, the angle α is about 10° to about 80°. In certain embodiments, the angle α is one of about 20°, about 30°, about 35°, about 37°, about 40°, about 42°, about 44°, about 45°, about 46°, about 48°, about 50°, about 52°, about 54°, about 56°, about 58°, about 60°, about 62°, about 65°, about 68°, about 70° and about 75°. In some embodiments, the angle α may be within a range defined by two of the foregoing angles. In an embodiment, the angle α is determined such that the first and second propulsive devices 4 and 6 avoid undesirably interfering with each other when the floating structure 1 sails (or moves, comes to the harbor). In addition, the angle α is determined such that the first and second propulsive devices 4 and 6 avoid undesirably interfering with each other when the floating structure 1 turns in a moored state.
[0045] In a case where the floating structure 1 sails using the first and second propulsive devices 4 and 6 disposed slantingly with respect to each other as described above, they generate propulsive force in a state where the first and second propulsive devices 4 and 6 are directed to the rear, i.e., in a state where the first and second propulsive devices are arranged in the longitudinal direction of the floating structure 1 to be directed to the rear.
[0046] At this time, since the first propulsive device 4 is positioned to be closer to the stern than the second propulsive device 6 , it is concerned that an advance direction of the floating structure 1 can be changed due to a difference in moment generated by the first and second propulsive devices.
[0047] Thus, in order to accurately control the advance direction of the floating structure 1 , it is preferable that the advance direction should be corrected by utilizing a rudder 10 , by adjusting the directions of the first and second propulsive devices 4 and 6 , by adjusting a propulsive force ratio of the first and second propulsive devices 4 and 6 .
[0048] The correction of the advance direction of the floating structure 1 as described above can be controlled precisely by an automatic control system (not shown) mounted in the floating structure 1 .
[0049] In addition, when the moored floating structure 1 turns using the first and second propulsive devices 4 and 6 arranged as described above, the first and second propulsive devices 4 and 6 generate the propulsive force in a state where both the first and second propulsive devices 4 and 6 rotate to the right by about 90° or to the left by 90°, i.e., arranged to be directed to the right or left side of the floating structure 1 .
[0050] At this time, since the first and second propulsive devices 4 and 6 arranged along the line L 2 , it is possible to turn the moored floating structure to control the heading angle thereof without interference between the two propulsive devices.
[0051] Referring to FIG. 1 , in one embodiment, the first propulsive device 4 , which is positioned to be closer to the stern than the second propulsive device 6 , is provided on the portside of the floating structure 1 , and the second propulsive device 6 , which is positioned to be closer to the stem than the first propulsive device 4 , is provided on the starboard thereof. According to one embodiment of the present invention, however, the first propulsive device 4 is positioned to be closer to the stem than the second propulsive device 6 .
[0052] As described above, according to one embodiment of the present invention, there is provided a floating structure having a pair of thrusters, acting as propulsive devices, installed to a stem bottom thereof to enable the pair of thrusters to both propel the structure to sail or navigate and control heading angle thereof.
[0053] Accordingly, it is advantageous that the number of propulsive devices to be installed can be decreased to save the cost and the number of the propulsive devices to be controlled can also be decreased to simplify the control system.
[0054] Although embodiments of the present invention have been described, it will be apparent to those skilled in the art that various modifications, changes and variations can be made thereto within the scope of the present invention and the appended claims. Therefore, the aforementioned descriptions and the accompanying drawings should be construed as not limiting the spirit or scope of the present invention but illustrating the present invention. | Disclosed is a floating system. The floating system comprises a floating body, a first propeller and a second propeller. The first propeller is pivotally secured to the floating body. The second propeller is pivotally secured to the floating body and distanced from the first propeller in a first direction and in a second direction perpendicular to the first direction. The first and second directions are generally parallel to a surface of water on which the floating system floats. | 1 |
This application claims benefit of U.S. Provisional Application No. 60/163,016 filed Nov. 2, 1999.
FIELD OF THE INVENTION
The present invention is directed towards a leader used to pull a seamable papermaker's fabric onto a paper machine particularly one that is durable and allows its reuse.
BACKGROUND OF THE INVENTION
Fabrics in modern papermaking machines may have a width of from 5 to over 33 feet, a length of from 40 to over 400 feet and weigh from approximately 100 to over 3,000 pounds. These fabrics wear out and require replacement. Replacement of fabrics often involves taking the machine out of service, removing the worn fabric, setting up to install a fabric and installing the new fabric. While many fabrics are endless, about half of those used in press sections of the paper machines today are on machine seamable. All dryer fabrics used all have a seam of some type. Some Paper Industry Process Belts (PIPBs) are contemplated to have an on machine seam capability, such as some transfer belts, known as Transbelt®. Installation of the fabric includes pulling the fabric body onto a machine and joining the fabric ends to form an endless belt.
An important aspect of loading a fabric body onto a paper machine is that there be uniform tension across the fabric. If uniform tension is not achieved and one section of the fabric pulls more than another, then the fabric can bubble or ridge across the fabric width.
Another aspect of loading a fabric body is preventing damage to the fabric body seam. In order to avoid or minimize the chance of damage to the seam during installation, tension, weight and pressure must be avoided on the seam itself.
A further aspect of loading a fabric, especially very long ones is properly aligning the fabric body in the machine so the fabric guides true in the machine direction (MD) and does not oscillate or track to one side of the machine. If the fabric guides or tracks poorly it can make contact with the paper machine support frame and cause fabric damage.
For fabrics and belts with seams that can be joined together on the paper machine, various types of leaders have been tried to assist installation. In order to avoid or minimize the potential for damaging the fabric body and the machine during installation and operation, the leader should be designed so there is uniform tension across the fabric body. There have been several attempts to design such leaders.
U.S. Pat. Nos. 5,306,393 and 5,429,719 both to Rhyne describe a device and method for installing a fabric body onto a paper machine. The method includes providing a self-aligning fabric loading harness having a leading edge and a plurality of spaced empty grommets disposed adjacent to the leading edge, to which multiple ropes are attached, securing a pull rope through loading harness and a line receiving device, pulling the pull rope, and automatically readjusting the pull rope through the loading harness to attempt to achieve uniform tension across the fabric.
Some leaders are square or rectangular, with the long dimension to either the MD or CD. Multiple ropes or straps are attached to the leader at evenly spaced apart locations across the width of the leader, and the leader with the attached papermaker's fabric or belt is pulled through the fabric run, and the ends of the papermaker's fabric or belt are brought together and joined by a seam to make the fabric endless. The leader is removed and the fabric is ready for use. However, the multiple ropes or straps can get hung up on the stationary equipment in the fabric run, causing difficult and time consuming installation, if not tearing and damage of the fabric.
There are also leaders currently used in the industry which are shaped like an isosceles triangle, having the apex removed to form a trapezoid. The leaders are fabricated from a woven material. The material can also be a nonwoven from which the leader is fabricated. The base of a leader has a zipper, which is used to attach the leader to an end of the fabric being installed on the paper machine. Such a design is preferred because only one rope is attached near the apex to pull the fabric onto the machine. When the triangle is cut from woven material, one of the yarn systems in the weave goes straight from the base to the apex and the other is at a 90° angle thereto.
FIG. 1 shows a top view of a prior art leader 10 . Leader 10 is shaped like an isosceles triangle and is fabricated from a woven material. The base 12 of leader 10 has a one half a zipper edge 12 , which is used to attach leader 10 to an end of the fabric being installed on the paper machine to which the other half of the zipper edge is attached to the fabric or belt. Papermill personnel can attach a rope near the apex which is provided with a hole 14 and pull the fabric onto the machine. When the triangle is cut from woven material, one of the yarn systems in the weave goes straight from the base to the apex and the other is at a 90° angle thereto. When the rope is pulled as shown in FIG. 1 a , the force is unevenly distributed across the leader as well as the attached fabric body which causes fabric body to bunch up on the sides.
Full width steel bars may be inserted at the base of the leader for better weight/tension distribution. However, the bars are heavy, thick and sometimes difficult to pass through the nip formed by two press rolls, or a shoe and opposing roll.
With a leader of this type, even with a 4 foot wide (in the cross machine direction or CD) steel reinforcing bar at the apex of the triangle/trapezoid, when the rope is pulled the force is unevenly distributed about the leader and across the attached fabric body. When the apex above is pulled, most of the force is distributed over four feet in the CD at the center of the leader. This causes the center of the fabric to bunch up, making it more difficult to seam, and often causes the edges of the fabric or belt 16 and leader 10 to droop 18 and 20 while it is being pulled onto the paper machine.
The drawback of this type of leader is that the load is always concentrated down its center. This causes both the center of the leader and the fabric attached to it, to lead the edges and form waves in the center while pulling through the machine, making it more difficult to seam as well as guide the fabric through the run during installation. This often causes the edges of the fabric to droop while it is being pulled through the fabric run. Any fabric edge droop or bunching/waviness (any departure from a relatively flat fabric profile) can cause the fabric to become hung up on stationary equipment, or to not easily pass through the gap formed between two press rolls. Attempts to correct both the fabric and leader edges from drooping by inserting ropes down the edges, usually results in the edges curling up and folding over, which is also not desirable.
While the types of methods and devices for installing an on machine seamable fabric or belt aforementioned have particular advantages, they also have attendant disadvantages discussed above.
SUMMARY OF THE INVENTION
It is therefore a principal object of the invention to overcome the shortcomings of the devices heretofore mentioned.
It is a further object of the invention to provide a device and method for installing a fabric in a paper machine which evenly distributes the load on the fabric making for easier installation and seaming.
It is a further object of the invention to provide a device for installing a fabric in a paper machine which is durable and allows for repeated use.
To solve this problem, a leader has been fashioned from at least one section of a polymeric material to form a triangle with a tapered apex. The triangle is preferably isosceles with the total leader length equivalent to the base of the leader width divided by 1.5. In preferred embodiments the leader comprises polymeric PVC (poly-vinyl-chloride) coated woven coarse fabrics woven of polyamide or polyester yarns, usually monofilaments, which are assembled together by a high frequency (H.F.) welding system. In a more preferred embodiment, additional melted strips of PVC are placed at regular intervals to reinforce the leader structure. There is a loop formed of folded over material provided at the tapered apex so that a metal bar may be placed therein with an access hold cut around a portion of the bar in the center to allow a rope or other means to be affixed to pull the leader. Depending on the fabric weight, load distribution achieved, and strength of the leader material itself, more than one rope might be attached at the apex.
The leader is attached to the fabric by an attachment means at its base. In a preferred embodiment, the leader is attached to the fabric by a zipper, one half of which zipper edge is attached to the base of the leader. Another half of the zipper is attached to the fabric. Other means suitable for this purpose might be used to attach the leader to the fabric.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a top view of a prior art leader.
FIG. 1 a shows a side view of fabric attached to the leader of FIG. 1 after it has been pulled.
FIG. 2 shows a side view illustrating a press section used in papermaking.
FIG. 3 shows a side view illustrating a dryer section used in papermaking.
FIG. 4 shows a top view of a preferred embodiment of the present invention.
FIG. 5 is a side sectional view taken along line 5 — 5 of FIG. 4 .
FIG. 6 shows a picture of the top view of the preferred embodiment of FIG. 4 attached to fabric.
FIG. 7 shows a detailed view of a partial top view of the preferred embodiment of FIG. 4 showing the apex of the leader.
FIG. 8 shows a detailed view of a second partial top view of the preferred embodiment of FIG. 4 showing the additional melted/fused MD strips and edge strips.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Initially, FIG. 2 shows a side view of the press section of a papermaking machine. FIG. 3 shows a side view of the drying section of a typical papermaking machine. The path of the fabric used in these sections is illustrated therein.
FIGS. 4 and 5 show an embodiment of the present inventive leader 110 . Leader 110 is shaped like a triangle with a tapered apex 112 and a base 114 . The triangle is preferably isosceles. The leader substrate 115 may be made from a polyester material or other material suitable for purpose. In preferred embodiments the leader substrate 115 comprises PVC coated woven coarse fabrics which are assembled together by H.F. welding system or other means suitable for purpose. Preferably approximately 900 g/m 2 of PVC coating 117 is applied. To reinforce the structure melted strips 116 of PVC may be placed at regular intervals on one or both surfaces of the coated leader substrate. For example, the strips may be 2 cm wide and placed about every 15 to 20 cm apart. Strips are also folded about the sides and the base of the triangle. There is a loop 118 made by a flap 119 of folded over leader material provided at tapered apex 112 so that a metal bar 120 may be inserted through loop 118 across apex 112 . The loop 118 preferably measures 10 cm in the machine direction (MD). Lateral PVC strips 121 may be positioned over the flap 118 for reinforcing purposes. An access hole 122 is cut around a portion of bar 120 in the center so that a rope 124 or other attachment means may be affixed to pull leader 110 . Depending on the fabric weight, load distribution achieved, and strength of the leader material itself, more than one rope can be wrapped around the bar at the apex 112 , although a single rope is preferred.
The leader is attached to the fabric by an attachment means at its base 114 . In a preferred embodiment, the leader 110 is attached to the fabric by a zipper 126 , one half of which zipper edge is attached to the base 114 of the leader. Another half of the zipper is attached to the fabric. Other means suitable for purpose may also be employed.
When the fabric 128 is to be installed on a paper machine, the rope is attached to the bar 120 though access hole 122 and pulled to draw the fabric 128 through and around the components of the machine. The load applied to the leader is evenly distributed across it. The edges do not droop and the load distribution is very uniform. Furthermore, the rugged design of the leader allows for its repeated use with relatively heavy loads. The leader design may be further enhanced by use of a different layer of stronger material, or by using more than one layer of material such as sheets of woven polypropylene yarns or tapes, properly oriented with respect to one another to maximize load distribution, forming a reinforced multilayer structure. In another alternative, different polymeric coatings can be used such polyurethane, or coatings that are biodegradable in some manner once the leader has reached its useful life.
In addition, while a woven coarse fabric has been referred to, non-woven materials, including reinforced and non-reinforced spunbonds might also be used. Knitted material can also be used. Also, the cost may also be reduced by reducing overall leader length (height of triangle) for some leaders, either for heavy fabrics or very wide fabrics. Triaxial woven material can also be used.
Leader design distributes the load in an even manner allowing easier seaming since the fabric is flat. The leader also pulls the fabric onto the machine uniformly due to the load distribution which keeps the fabric flat and prevents contact with stationary elements such as suction boxes or showers.
Furthermore, the design does not usually require the use of multiple ropes across the width which is commercially undesirable. Nor does the design require multiple straps or thick, heavy, full width metal bars which have known disadvantages.
Thus by the present invention its advantages will be realized and preferred embodiments have been disclosed and described herein. | A leader having a shape substantially that of a triangle which is used to pull a seamable papermaker's fabric onto a paper machine comprising a plastic coated substrate having plastic reinforcing strips thereon. | 3 |
FIELD OF THE INVENTION
[0001] The present invention relates to a method for reliably manufacturing stampers/imprinters utilized for rapid, cost-effective patterning of a layer or body of a recording medium. The invention has particular utility in the formation of patterns, e.g., servo patterns, in the surfaces of recording layers of data/information storage and retrieval media, e.g., hard disks.
BACKGROUND OF THE INVENTION
[0002] Recording media of various types, e.g., magnetic, optical, magneto-optical (“MO”), read-only memory (“ROM”), readable compact disks (“CD-R”), and readable-writable compact disks (“CD-RW”) are widely used in various applications, e.g., in hard disk form, particularly in the computer industry for storage and retrieval of large amounts of data/information. Typically, such media types require pattern formation in the major surface(s) thereof for facilitating operation thereof. For example, magnetic and magneto-optical (MO) recording disks require formation of servo patterns for positioning the read-write transducer over a particular band or region of the media; ROM disks require formation of memory patterns therein; and CD-R and CD-RW disks require formation of wobble groove patterns therein.
[0003] Magnetic and magneto-optical (MO) recording media are conventionally fabricated in thin film form; the former are generally classified as “longitudinal” or “perpendicular”, depending upon the orientation (i.e., parallel or perpendicular) of the magnetic domains of the grains of the magnetic material constituting the active magnetic recording layer, relative to the surface of the layer.
[0004] In operation of magnetic media, the magnetic layer is locally magnetized by a write transducer or write head to record and store data/information. The write transducer creates a highly concentrated magnetic field which alternates direction based on the bits of information being stored. When the local magnetic field applied by the write transducer is greater than the coercivity of the recording medium layer, then the grains of the polycrystalline magnetic layer at that location are magnetized. The grains retain their magnetization after the magnetic field applied by the write transducer is removed. The direction of the magnetization matches the direction of the applied magnetic field. The pattern of magnetization of the recording medium can subsequently produce an electrical response in a read transducer, allowing the stored medium to be read.
[0005] A typical contact start/stop (CSS) method employed during use of disk-shaped recording media, such as the above-described thin-film magnetic recording media, involves a floating transducer head gliding at a predetermined distance from the surface of the disk due to dynamic pressure effects caused by air flow generated between mutually sliding surfaces of the transducer head and the disk. During reading and recording (writing) operations, the transducer head is maintained at a controlled distance from the recording surface, supported on a bearing of air as the disk rotates, such that the transducer head is freely movable in both the circumferential and radial directions, thereby allowing data to be recorded and retrieved from the disk at a desired position in a data zone.
[0006] Adverting to FIG. 1 , shown therein, in simplified, schematic plan view, is a magnetic recording disk 30 (of either longitudinal or perpendicular type) having a data zone 34 including a plurality of servo tracks, and a contact start/stop (CSS) zone 32 . A servo pattern 40 is formed within the data zone 34 , and includes a number of data track zones 38 separated by servo tracking zones 36 . The data storage function of disk 30 is confined to the data track zones 38 , while servo tracking zones 36 provide information to the disk drive which allows a read/write head to maintain alignment on the individual, tightly-spaced data tracks.
[0007] Although only a relatively few of the servo tracking zones are shown in FIG. 1 for illustrative simplicity, it should be recognized that the track patterns of the media contemplated herein may include several hundreds of servo zones to improve head tracking during each rotation of the disk. In addition, the servo tracking zones need not be straight radial zones as shown in the figure, but may instead comprise arcs, intermittent zones, partial spirals, or irregularly-shaped zones separating individual data tracks.
[0008] In conventional hard disk drives, data is stored in terms of bits along the data tracks. In operation, the disk is rotated at a relatively high speed, and the magnetic head assembly is mounted on the end of a support or actuator arm, which radially positions the head on the disk surface. If the actuator arm is held stationary, the magnetic head assembly will pass over a circular path on the disk, i.e., over a data track, and information can be read from or written to that track. Each concentric track has a unique radius, and reading and writing information from or to a specific track requires the magnetic head to be located above that track. By moving the actuator arm, the magnetic head assembly is moved radially on the disk surface between tracks. Many actuator arms are rotatable, wherein the magnetic head assembly is moved between tracks by activating a servomotor which pivots the actuator arm about an axis of rotation. Alternatively, a linear actuator may be used to move a magnetic head assembly radially inwardly or outwardly along a straight line.
[0009] As has been stated above, to record information on the disk, the transducer creates and applies a highly concentrated magnetic field in close proximity to the magnetic recording medium. During writing, the strength of the concentrated magnetic field directly under the write transducer is greater than the coercivity of the recording medium, and grains of the recording medium at that location are magnetized in a direction which matches the direction of the applied magnetic field. The grains of the recording medium retain their magnetization after the magnetic field is removed. As the disk rotates, the direction of the writing magnetic field is alternated, based on bits of the information being stored, thereby recording a magnetic pattern on the track directly under the write transducer.
[0010] On each track, eight “bits” typically form one “byte” and bytes of data are grouped as sectors. Reading or writing a sector requires knowledge of the physical location of the data in the data zone so that the servo-controller of the disk drive can accurately position the read/write head in the correct location at the correct time. Most disk drives use disks with embedded “servo patterns” of magnetically readable information. The servo patterns are read by the magnetic head assembly to inform the disk drive of track location. In conventional disk drives, tracks typically include both data sectors and servo patterns and each servo pattern typically includes radial indexing information, as well as a “servo burst”. A servo burst is a centering pattern to precisely position the head over the center of the track. Because of the locational precision needed, writing of servo patterns requires expensive servo-pattern writing equipment and is a time consuming process.
[0011] Commonly assigned, co-pending U.S. patent application Ser. No. 10/082,178, filed Feb. 26, 2002 (Attorney Docket No. 50103-401), the entire disclosure of which is incorporated herein by reference, discloses an improvement over the invention disclosed in commonly assigned U.S. Pat. No. 5,991,104, and is based upon the finding that very sharply defined magnetic transition patterns can be reliably, rapidly, and cost-effectively formed in a magnetic medium containing a longitudinal or perpendicular type magnetic recording layer without requiring expensive, complicated fabrication of a master disk.
[0012] Specifically, the invention disclosed in U.S. patent application Ser. No. 10/082,178 is based upon recognition that a stamper/imprinter (analogous to the aforementioned “master”) comprised of a magnetic material having a high saturation magnetization, B sat , i.e., B sat ≧about 0.5 Tesla, and a high permeability, μ, i.e., μ≧about 5, e.g., selected from Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV, can be effectively utilized as a contact “stamper/imprinter” for contact “imprinting” of a magnetic transition pattern, e.g., a servo pattern, in the surface of a magnetic recording layer of a magnetic medium (“workpiece”), whether of longitudinal or perpendicular type. A key feature of this invention is the use of a stamper/imprinter having an imprinting surface including a topographical pattern, i.e., comprised of projections and depressions, corresponding to a desired magnetic transition pattern, e.g., a servo pattern, to be formed in the magnetic recording layer. An advantage afforded by the invention is the ability to fabricate the topographically patterned imprinting surface of the stamper/imprinter, as well as the substrate or body therefor, of a single material, as by use of well-known and economical electroforming techniques (described below in more detail).
[0013] According to this invention, the magnetic domains of the magnetic recording layer of the workpiece are first unidirectionally aligned (i.e., “erased” or “initialized”), as by application of a first external, unidirectional magnetic field H initial of first direction and high strength greater than the saturation field of the magnetic recording layer, typically ≧2,000 and up to about 20,000 Oe. The imprinting surface of the stamper/imprinter is then brought into intimate (i.e., touching) contact with the surface of the magnetic recording layer. With the assistance of a second externally applied magnetic field of second, opposite direction and lower but appropriate strength H re-align , determined by B sat /μ of the stamper material (typically ≧100 Oe, e.g., from about 2,000 to about 4,500 Oe), the alignment of the magnetic domains at the areas of contact between the projections of the imprinting surface of the stamper/imprinter (in the case of perpendicular recording media, as schematically illustrated in FIG. 2 ) or at the areas facing the depressions of the imprinting surface of the stamper/imprinter (in the case of longitudinal recording media, as schematically illustrated in FIG. 3 ) and the magnetic recording layer of the workpiece is selectively reversed, while the alignment of the magnetic domains at the non-contacting areas (defined by the depressions in the imprinting surface of the stamper/imprinter) or at the contacting areas, respectively, is unaffected, whereby a sharply defined magnetic transition pattern is created within the magnetic recording layer of the workpiece to be patterned which essentially mimics the topographical pattern of projections and depressions of the imprinting surface. According to the invention, high B sat and high μ materials are preferred for use as the stamper/imprinter in order to: (1) avoid early magnetic saturation of the stamper/imprinter at the contact points between the projections of the imprinting surface and the magnetic recording layer, and (2) provide an easy path for the magnetic flux lines which enter and/or exit at the side edges of the projections.
[0014] Another process which has been recently studied and developed as a low cost alternative technique for fine dimension pattern/feature formation in a substrate surface is thermal imprint lithography. A typical thermal imprint lithographic process for forming nano-dimensioned patterns/features in a substrate surface is illustrated with reference to the schematic, cross-sectional views of FIGS. 4 (A)- 4 (D).
[0015] Referring to FIG. 4 (A), shown therein is a stamper/imprinter 10 including a main (or support) body 12 having upper and lower opposed surfaces, with an imprinting layer 14 formed on the lower opposed surface. As illustrated, stamper/imprinter 14 includes a plurality of features 16 having a desired shape or surface contour. A workpiece 18 carrying a thin film layer 20 on an upper surface thereof is positioned below, and in facing relation to the molding layer 14 . Thin film layer 20 , e.g., of polymethylmethacrylate (PMMA), may be formed on the substrate/workpiece surface by any appropriate technique, e.g., spin coating.
[0016] Adverting to FIG. 4 (B), shown therein is a compressive molding step, wherein stamper/imprinter 10 is pressed into the thin film layer 20 in the direction shown by arrow 22 , so as to form depressed, i.e., compressed, regions 24 . In the illustrated embodiment, features 16 of the imprinting layer 14 are not pressed all of the way into the thin film layer 20 and thus do not contact the surface of the underlying substrate 18 . However, the top surface portions 24 a of thin film 20 may contact depressed surface portions 16 a of imprinting layer 14 . As a consequence, the top surface portions 24 a substantially conform to the shape of the depressed surface portions 16 a , for example, flat. When contact between the depressed surface portions 16 a of imprinting layer 14 and thin film layer 20 occurs, further movement of the imprinting layer 14 into the thin film layer 20 stops, due to the sudden increase in contact area, leading to a decrease in compressive pressure when the compressive force is constant.
[0017] FIG. 4 (C) shows the cross-sectional surface contour of the thin film layer 20 following removal of stamper/imprinter 10 . The imprinted thin film layer 20 includes a plurality of recesses formed at compressed regions 24 which generally conform to the shape or surface contour of features 16 of the molding layer 14 . Referring to FIG. 4 (D), in a next step, the surface-imprinted workpiece is subjected to processing to remove the compressed portions 24 of thin film 20 to selectively expose portions 28 of the underlying substrate 18 separated by raised features 26 . Selective removal of the compressed portions 24 may be accomplished by any appropriate process, e.g., reactive ion etching (RIE) or wet chemical etching.
[0018] The above-described imprint lithographic processing is capable of providing sub-micron-dimensioned features, as by utilizing a stamper/imprinter 10 provided with patterned features 16 comprising pillars, holes, trenches, etc., by means of e-beam lithography, RIE, or other appropriate patterning method. Typical depths of features 16 range from about 5 to about 200 nm, depending upon the desired lateral dimension. The material of the imprinting layer 14 is typically selected to be hard relative to the thin film layer 20 , the latter comprising a thermoplastic material which is softened when heated. Thus, suitable materials for use as the imprinting layer 14 include metals, dielectrics, semiconductors, ceramics, and composite materials. Suitable materials for use as thin film layer 20 include thermoplastic polymers which can be heated to above their glass temperature, T g , such that the material exhibits low viscosity and enhanced flow.
[0019] Referring now to FIG. 5 , schematically illustrated therein, in simplified cross-sectional view, is a sequence of processing steps for performing nano-imprint lithography of a metal-based workpiece, e.g., a disk-shaped substrate for a hard disk recording medium, utilizing a stamper/imprinter with a lubricated imprinting surface, as disclosed in commonly assigned, co-pending U.S. patent application Ser. No. 09/946,939, filed Sep. 5, 2001 (Attorney Docket No. 50103-381), the entire disclosure of which is incorporated herein by reference.
[0020] In a preliminary step according to the method, a thin film of a thermoplastic polymer, e.g., polymethylmethacrylate (PMMA), is spin-coated on the substrate surface. In another preliminary step, a stamper/imprinter, e.g., formed of Ni, having an imprinting surface with a negative image of servo pattern features having a lateral dimension of about 600 nm and a height of 170 nm is fabricated by conventional optical lithographic patterning/etching techniques and provided with a thin layer of an anti-sticking or release agent. In the next steps according to the disclosed invention, the system of substrate/workpiece and Ni-based stamper/imprinter is heated to above the glass transition temperature (T g ) of the PMMA, i.e., above about 105° C., and the negative image of the desired pattern on the imprinting surface of the stamper/imprinter is embossed into the surface of the thermoplastic PMMA layer at a pressure of about 10 MPa. The stamper/imprinter is then maintained in contact with the PMMA layer and under pressure until the system cools down to about 70° C., and then removed from the substrate/workpiece to leave replicated features of the imprinting surface in the surface of the PMMA layer. Subsequent processing of the imprinted substrate/workpiece involves selective removal of substrate material utilizing the imprinted layer of thermoplastic material as a pattern defining (etching) mask, followed by removal of the imprinted layer of thermoplastic material.
[0021] Still another process which has been recently studied and developed as a low cost alternative technique for fine dimension pattern/feature formation in a substrate surface is imprinting of a sol-gel layer on a substrate surface, as for example, disclosed in commonly assigned, co-pending U.S. patent application Ser. No. 09/852,084, filed May 10, 2001 (Attorney Docket No. 50103-377), the entire disclosure of which is incorporated herein by reference.
[0022] According to the process disclosed therein, problems attendant upon the use of very hard surfaced, high modulus materials, e.g., of glass, ceramics, or glass-ceramic composites, as substrates in the manufacture of hard disk recording media are addressed, and the invention is based upon the discovery that the surfaces of such materials may be modified, i.e., reduced in hardness, so as to facilitate formation of servo patterns therein, as by a simple and conveniently performed embossing process. According to the invention, modification (i.e., reduction) of surface hardness of high modulus substrates for use in the manufacture of thin film recording media is obtained by first forming a relatively soft sol-gel coating layer on the substrate surface, embossing the desired servo pattern in the exposed upper surface of the relatively soft sol-gel layer utilizing a stamper/imprinter with an appropriately patterned imprinting surface comprising a patterned plurality of depressions and protrusions having a negative image of the desired servo pattern, and then converting the embossed, relatively soft sol-gel layer to a relatively hard glass-like layer while retaining the embossed servo pattern therein. The thus-formed substrate with embossed servo pattern in the exposed surface thereof is then subjected to thin film deposition thereon for forming the layer stack constituting the magnetic recording medium. The inventive methodology advantageously provides servo-patterned recording media without requiring servo-writing subsequent to media fabrication.
[0023] Stampers/imprinters for use in a typical application, e.g., servo pattern formation in the recording layer of a disk-shaped, thin film, longitudinal or perpendicular magnetic recording medium, comprise an imprinting surface having topographical features consisting of larger area data zones separated by smaller areas with well-defined patterns of projections and depressions corresponding to conventionally configured servo sectors, as for example, disclosed in the aforementioned commonly assigned U.S. Pat. No. 5,991,104. For example, a suitable topography for forming the servo sectors may comprise a plurality of projections having a height in the range from about 20 to about 500 nm, a width in the range from about 0.01 to about 1 μm, and a spacing of at least about 0.01 μm.
[0024] Stampers/imprinters suitable for use in performing the foregoing patterning processes may be manufactured by a sequence of steps as schematically illustrated in FIG. 6 , which steps include providing a “master” comprised of a substantially rigid substrate with a patterned layer of a resist material thereon, the pattern, which is formed in the resist layer by conventional lithographic techniques, including, e.g., e-beam or laser beam exposure of selected areas of the resist, comprising a plurality of projections and depressions corresponding (in positive or negative image form, as necessary) to the desired pattern, e.g., a servo pattern, to be formed in the surface of the stamper/imprinter. Stampers/imprinters are made from the “master” by initially forming a thin, conformal layer of an electrically conductive material (e.g., Ni) over the patterned resist layer and then electroforming a substantially thicker (“blanket”) metal layer (e.g., Ni in the case of magnetic stampers/imprinters) on the thin layer of electrically conductive material, which electroformed blanket layer replicates the surface topography of the resist layer. Upon completion of the electroforming process, the stamper/imprinter is separated from the “master”.
[0025] In practice, however, since the “master” with fragile resist layer thereon is effectively destroyed upon separation of the stamper/imprinter from the “master”, a process has been developed involving forming a “family” of stampers/imprinters, as schematically illustrated in FIG. 7 . As shown in the figure, the stamper/imprinter formed directly from the “master” is termed a “father” and has a reverse (i.e., negative) replica of the topographical pattern of the “master”. The “father” is then utilized for forming several (illustratively two) “mothers” therefrom (e.g., as by a process comprising electroforming, as described above), and each “mother” is in turn utilized for forming several (illustratively two, for a total of four) “sons” therefrom (also by a process comprising electroforming). The “sons” are positive replicas of the “father” and are utilized as the stampers/imprinters for media patterning. Since, as described above, the “master” is effectively destroyed in the process of making the “father” therefrom, the “family” making process avoids the need for repeatedly manufacturing “master” stampers/imprinters by preserving the “father” and utilizing the “sons”. Therefore, process time and cost of making “masters” is substantially reduced by means of the “family” making process.
[0026] The thus-formed “sons” are then subjected to further processing for forming stampers/imprinters with a desired dimension (i.e., size) and geometrical shape or contour, e.g., an annular disk-shaped stamper/imprinter for use in patterning of annular disk-shaped media such as hard disks, which stampers/imprinters necessarily include a circularly-shaped central aperture defining an inner diameter (“ID”) and a circularly-shaped periphery defining an outer diameter (“OD”).
[0027] The “family” making process, as described supra, is made possible/practical only if the “mothers” are readily separated from the “father” without incurring damage to the patterned surface(s), and the “sons” are similarly readily separated from the “mothers” without incurring damage to the patterned surface(s). As a consequence, the patterned surfaces of the “father” and the “mothers” are each provided with a coating layer of a material, termed a “release” layer and typically comprised of a passivating material, prior to formation of the respective “mothers” and “sons”, for facilitating separation, i.e., “release”, of the “mothers” from the “father” and the “sons” from the “mothers”.
[0028] A typical method for forming the release layer, such as when at least the imprinting surface of the stamper/imprinter is comprised of a metal or alloy, e.g., a magnetic metal or alloy, such as Ni or a Ni-based alloy, involves formation of a thin layer of a passivating oxide of the metal or metal alloy on the imprinting surface of the “father” and the “mothers” by means of a “wet” process, such as, for example, electrochemical anodization or application of an oxidizing solution. Electrochemical anodization of the Ni or Ni-based alloys utilized in the formation of magnetic stampers/imprinters is typically performed utilizing an alkaline aqueous solution of tri-sodium phosphate (Na 3 PO 4 ). However, the “wet” process of electrochemical anodization for forming passivating oxides for use as release layers is disadvantageous in that it: (1) is a source of defect generation in the topographical pattern of the imprinting surface; and (2) is incompatible with the other, i.e., “dry”, processes utilized for manufacture of the stampers/imprinters, such as the sputtering processing utilized for forming thin metal layers on the patterned surfaces prior to the electroforming step.
[0029] In view of the foregoing problems, drawbacks, and disadvantages attendant upon the use of conventional “wet” processing techniques, e.g., electrochemical anodization, for forming passivation layers on the imprinting surfaces of the “father” and “mothers” to facilitate separation of the respective “mothers” and “sons” therefrom in a “family” making process for manufacturing stampers/imprinters for use in patterning of recording media, there exists a need for methodologies for manufacturing a “family” of starnpers/imprinters which are free of the above-described problems, drawbacks, and disadvantages associated with the use of wet techniques for the formation of passivation layers utilized for facilitating release or separation of the “mothers” and “sons” from the respective “father” and “mothers”. Moreover, there exists a need for methodologies which facilitate rapid, reliable, and cost-effective manufacture of “families” of stampers/imprinters for use in rapid, reliable, accurate, and cost-effective patterning of a variety of types of recording media including, but not limited to, formation of servo patterns in magnetic and magneto-optical (MO) recording media.
[0030] The present invention addresses and solves the aforementioned problems, drawbacks, and disadvantages associated with the use of conventional wet techniques for the formation of passivation layers utilized for facilitating release or separation of the “mothers” and “sons” from the respective “father” and “mothers”, while maintaining full compatibility with the requirements of automated manufacturing technology.
DISCLOSURE OF THE INVENTION
[0031] An advantage of the present invention is an improved method of manufacturing a stamper/imprinter for use in patterning of a recording medium.
[0032] Another advantage of the present invention is an improved method of manufacturing a plurality of stampers/imprinters for use in contact patterning of a magnetic recording medium.
[0033] Additional advantages and other features of the present invention will be set forth in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from the practice of the present invention. The advantages of the present invention may be realized as particularly pointed out in the appended claims.
[0034] According to an aspect of the present invention, the foregoing and other advantages are obtained in part by an improved method of manufacturing a stamper/imprinter for use in patterning of a recording medium, comprising sequential steps of:
(a) providing a substrate/workpiece comprising a topographically patterned surface including a plurality of projections and depressions corresponding to a pattern to be formed in a surface of a recording medium; (b) forming a thin release layer in conformal contact with the topographically patterned surface by means of a dry process; (c) forming (e.g., by electroforming) a thicker layer of a material in conformal contact with the thin release layer on the topographically patterned surface; and (d) separating the thicker layer of material from the topographically patterned surface to form therefrom a stamper/imprinter including an imprinting surface having a negative image replica of the topographically patterned surface, separation of the thicker layer of material from the topographically patterned surface being facilitated by the thin release layer formed by the dry process.
[0039] According to embodiments of the present invention, step (a) comprises providing a substrate/workpiece wherein the topographical pattern corresponds to a magnetic pattern including a servo pattern for a magnetic or magneto-optical (MO) recording medium, a read-only memory (ROM) pattern, or a wobble groove pattern for a readable compact disk (CD-R) or a readable-writable compact disk (CD-RW).
[0040] Preferred embodiments of the invention include those wherein step (a) comprises providing a substrate/workpiece wherein the topographical pattern corresponds to a magnetic pattern including a servo pattern for a magnetic or magneto-optical (MO) recording medium, in which instance step (a) comprises providing a substrate/workpiece wherein at least the topographically patterned surface is comprised of at least one magnetic material having a high saturation magnetization B sat ≧0.5 Tesla and a high permeability μ≧˜5; step (b) comprises forming at least one passivating oxide of the at least one magnetic material as said the release layer, e.g., step (b) comprises forming at least one passivating oxide as a thin release layer from about 50 to about 200 Å thick; and step (c) comprises forming a layer of at least one magnetic material having a high saturation magnetization B sat ≧0.5 Tesla and a high permeability μ≧˜5 as the thicker layer.
[0041] According to embodiments of the present invention, step (b) comprises forming the at least one passivating oxide by thermal oxidation of the at least one magnetic material in an O 2 -containing atmosphere.
[0042] Preferred embodiments of the present invention include those wherein step (b) comprises forming the at least one passivating oxide by means of a plasma; as when step (b) comprises treating the topographically patterned surface with an oxygen (O 2 ) plasma under conditions selected for minimizing deformation and/or degradation of the pattern and for an interval sufficient for facilitating release of the thicker layer of at least one magnetic material therefrom in step (d).
[0043] According to alternative preferred embodiments of the present invention, step (b) comprises forming the at least one passivating oxide by means of a DC, RF, or microwave plasma, or a combination thereof; e.g., step (b) comprises exposing the topographically patterned surface to an oxygen (O 2 ) plasma, under conditions selected for minimizing deformation and/or degradation of the pattern and for an interval sufficient for facilitating release of the thicker layer of at least one magnetic material therefrom.
[0044] In accordance with particularly preferred embodiments of the present invention, step (a) comprises providing a substrate/workpiece comprising at least one magnetic material selected from the group consisting of: Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV; step (b) comprises forming the thin release layer as comprising at least one passivating oxide of at least one magnetic material selected from the group consisting of Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV; step (c) comprises forming a layer comprising at least one magnetic material selected from the group consisting of: Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV as the thicker layer; and step (d) comprises separating the thicker layer of at least one magnetic material from the topographically patterned surface to form therefrom a magnetic stamper/imprinter including an imprinting surface having a negative image replica of the topographically patterned surface, the magnetic stamper/imprinter being usable for contact patterning of magnetic recording media; wherein step (b) comprises treating said topographically patterned surface of said substrate/workpiece with an oxygen (O 2 ) plasma under conditions selected for minimizing deformation and/or degradation of said pattern and for an interval sufficient for facilitating release of said thicker layer of at least one magnetic material therefrom.
[0045] Further preferred embodiments of the present invention include those wherein the method further comprises repeating steps (a)-(d) at least once, utilizing the same substrate/workpiece provided in step (a), to form at least one additional stamper/imprinter therefrom, or utilizing the stamper/imprinter formed in step (d) as the substrate/workpiece for performing a sequence of steps (a)-(d) for manufacturing at least one additional stamper/imprinter therefrom.
[0046] Another aspect of the present invention is a method of manufacturing a plurality of stampers/imprinters for use in contact patterning of a magnetic recording medium, comprising sequential steps of:
(a) providing a first stamper/imprinter comprising a topographically patterned surface including a plurality of projections and depressions corresponding to a magnetic pattern including a servo pattern to be formed in a surface of a recording medium, the topographically patterned surface comprised of at least one magnetic material having a high saturation magnetization B sat ≧0.5 Tesla and a high permeability μ≧˜5, selected from the group consisting of: Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV; (b) forming a thin release layer, from about 50 to about 200 Å thick, in conformal contact with the topographically patterned surface by means of a dry process, said thin release layer comprising at least one passivating oxide of at least one magnetic material selected from the group consisting of Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV; and (c) forming a thicker layer of at least one magnetic material in conformal contact with the thin release layer, the thicker layer comprised of at least one magnetic material having a high saturation magnetization B sat ≧0.5 Tesla and a high permeability μ≧˜5, selected from the group consisting of: Ni, NiFe, CoNiFe, CoSiFe, CoFe, and CoFeV; (d) separating the thicker layer of at least one magnetic material from the topographically patterned surface to form therefrom a second stamper/imprinter including an imprinting surface having a negative image replica of the topographically patterned surface, separation of the thicker layer of at least one magnetic material from the topographically patterned surface being facilitated by the thin release layer formed by the dry process, wherein: the first stamper/imprinter is a “father” and the second stamper/imprinter is a “mother”, or the first stamper/imprinter is a “mother” and the second stamper/imprinter is a “son”.
[0052] According to preferred embodiments of the invention, step (b) comprises treating the topographically patterned surface with an oxygen (O 2 ) plasma to form the thin release layer under conditions selected for minimizing deformation and/or degradation of the pattern and for an interval sufficient for facilitating release of the thicker layer of material therefrom in step (d); and the method further comprises repeating steps (a)-(d) at least once, utilizing the “father” or “mother” provided in step (a) as the first stamper/imprinter, to form at least one additional “mother” or “son” therefrom, or utilizing a “mother” stamper/imprinter formed in step (d) as the first stamper/imprinter for performing a sequence of steps (a)-(d) for manufacturing at least one “son” stamper/imprinter therefrom.
[0053] Additional advantages and aspects of the present invention will become readily apparent to those skilled in the art from the following detailed description, wherein embodiments of the present invention are shown and described, simply by way of illustration of the best mode contemplated for practicing the present invention. As will be described, the present invention is capable of other and different embodiments, and its several details are susceptible of modification in various obvious respects, all without departing from the spirit of the present invention. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as limitative.
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] The following detailed description of the embodiments of the present invention can best be understood when read in conjunction with the following drawings, in which the various features are not necessarily drawn to scale but rather are drawn as to best illustrate the pertinent features, wherein:
[0055] FIG. 1 illustrates, in simplified, schematic plan view, a magnetic recording disk designating the data, servo pattern, and CSS zones thereof;
[0056] FIG. 2 illustrates, in schematic, simplified cross-sectional view, a sequence of process steps for contact printing a magnetic transition pattern in the surface of a perpendicular magnetic recording layer, utilizing a stamper/imprinter formed of a high saturation magnetization, high permeability magnetic material having an imprinting surface with a surface topography corresponding to the desired magnetic transition pattern;
[0057] FIG. 3 illustrates, in schematic, simplified cross-sectional view, a similar sequence of process steps for contact printing a magnetic transition pattern in the surface of a longitudinal magnetic recording layer;
[0058] FIGS. 4 (A)- 4 (D) illustrate, in simplified cross-sectional view, a process sequence for performing thermal imprint lithography of a thin resist film on a substrate (workpiece), according to the conventional art;
[0059] FIG. 5 schematically illustrates, in simplified cross-sectional view, another sequence of steps for performing imprint lithography of a resist film;
[0060] FIG. 6 schematically illustrates, in simplified cross-sectional view, a sequence of steps for forming a stamper/imprinter for recording media patterning;
[0061] FIG. 7 is a schematic flow chart for illustrating a sequence of process steps for manufacturing a plurality of stampers/imprinters from a single “master”; and
[0062] FIG. 8 schematically illustrates, in simplified cross-sectional view, a sequence of steps for forming a magnetic stamper/imprinter for use in contact patterning of magnetic recording media, according to the methodology of the present invention.
DESCRIPTION OF THE INVENTION
[0063] The present invention addresses and solves problems, disadvantages, and drawbacks attendant upon the formation of “families” of stampers/imprinters, e.g., magnetic stampers/imprinters for use in rapidly and cost-effectively performing servo patterning of magnetic recording media (e.g., hard disks) by contact patterning, by means of a fabrication process sequence wherein a “mother” stamper/imprinter is initially formed with a topographically patterned imprinting surface in conformal contact with a similarly topographically patterned surface of a “father” stamper/imprinter and subsequently separated therefrom, or a “son” stamper/imprinter is initially formed with a topographically patterned imprinting surface in conformal contact with a similarly topographically patterned surface of a “mother” stamper/imprinter and subsequently separated therefrom, followed by utilization of the resultant stampers/imprinters for forming servo patterns in the surfaces of magnetic recording media by contact patterning, as described supra.
[0064] Specifically, the present invention eliminates problems, disadvantages, and drawbacks associated with the use of “wet” processing techniques, such as electrochemical anodization or treatment with an oxidizing solution, for forming thin, metal oxide passivation/release coating layers on the topographically patterned imprinting surfaces of the “father” or “mother” stampers/imprinters prior to formation of the respective “mother” or “son” stampers/imprinters in conformal contact therewith, which release layers facilitate separation and multiple re-use of the “father” and “mother” stampers/imprinters.
[0065] As indicated above, electrochemical anodization of the Ni or Ni-based alloys utilized in the formation of magnetic stampers/imprinters is typically performed utilizing an alkaline aqueous solution of tri-sodium phosphate (Na 3 PO 4 ). However, the “wet” process of electrochemical anodization for forming passivating oxides for use as release layers is disadvantageous in that it: (1) is a source of defect generation in the topographical pattern of the imprinting surface; and (2) is incompatible with the other, i.e., “dry”, processes utilized for manufacture of the stampers/imprinters, such as the sputtering processing utilized for forming thin metal layers on the patterned surfaces prior to the electroforming step.
[0066] According to preferred embodiments of the present, therefore, formation of the release layer on the topographically patterned (e.g., servo patterned) imprinting surfaces of stampers/imprinters, e.g., magnetic stampers/imprinters comprised of at least one magnetic metal or alloy (as enumerated above), is accomplished by means of a plasma, e.g., plasma oxidation utilizing an oxygen (O 2 ) plasma for forming a thin passivating oxide layer which functions as a release layer facilitating separation of the stampers/imprinters. Since a principal feature of the invention is oxidation of the topographically patterned imprinting surface of the stamper/imprinter, e.g., a Ni or Ni alloy surface, to form a Ni oxide or an oxide of the Ni alloy, an O 2 plasma process which differs from the O 2 plasma treatments typically utilized for material removal (i.e., etching) and cleaning, is utilized. More specifically, according to the inventive methodology, the O 2 plasma is very “soft” and gentle compared to the conventional O 2 plasmas, e.g., wherein the pressure ≧200 mTorr and the power ≦100 W, in order to avoid exposing the topographically patterned imprinting surfaces to a harsh environment capable of disadvantageously resulting in deformation and/or degradation of the pattern features.
[0067] According to the invention, after a “father” stamper/imprinter is separated from a “master”, as at the beginning of a “family” making process, e.g., as schematically illustrated in FIG. 7 and described above, the topographically patterned imprinting surface of the “father” stamper/imprinter comprising a negative image replica of the topographically patterned surface of the “master” stamper/imprinter is subjected to a preliminary treatment with ozone (O 3 ) and UV irradiation for removing any resist residue from the “master”.
[0068] Referring to FIG. 8 , which schematically illustrates, in simplified cross-sectional view, a sequence of steps for forming a magnetic stamper/imprinter for use in contact patterning of magnetic recording media, according to the inventive methodology, the O 3 /UV treated “father” stamper/imprinter is then immediately treated with a soft and gentle O 2 plasma (wherein, as previously indicated, the pressure ≧200 mTorr and the power ≦100 W)), e.g., a DC, RF, or microwave plasma, or a combination thereof, for forming a thin (e.g., from about 50 to about 200 Å thick) layer of a passivating oxide as a release layer facilitating separation therefrom of a subsequently electroformed “mother” stamper/imprinter having an imprinting surface which is a negative image replica of the imprinting surface of the “father” stamper/imprinter. A similar O 2 plasma process, not necessarily requiring the preliminary O 3 /UV treatment for residual resist removal, is performed on the “mother” stampers/imprinters prior to their use in fabricating “son” stampers/imprinters, as illustrated in FIG. 7 . According to the invention, the topographically patterned imprinting surface of the stamper/imprinter is treated with the O 2 plasma under conditions selected for minimizing deformation and/or degradation of the pattern (e.g., a servo pattern) and for an interval sufficient for facilitating release of the “mother” or “son” from the respective “father” or “mother”.
[0069] The O 2 plasma-treated imprinting surface of the stamper/imprinter is then subjected to sputtering of a thin, electrically conductive layer thereon, e.g., a Ni or Ni alloy layer, which thin, electrically conductive layer is necessary for effecting subsequent formation, by an electroforming process, of a thicker, mechanically robust “blanket” layer of a magnetic material, e.g., Ni or a Ni alloy, in conformal contact with the release layer-coated imprinting surface of the stamper/imprinter. After the “mother” or “son” is electroformed on the respective “father” or “mother”, the “father”/“mother” or “mother”/“son” pair is removed from the electroforming bath, rinsed, and thoroughly dried before separation. The “mother” is then separated from the “father”, or the “son” is separated from the “mother”, utilizing the passivating oxide as a release layer for facilitating separation of the pairs of stampers/imprinters. In cases where the “father” or the “mother” stamper/imprinter is to be re-used for forming additional “mothers” and “sons”, it is then immediately placed back into the apparatus (comprising interconnected vacuum chambers) for re-formation of the thin passivation/release layer on the topographically patterned imprinting surface by means of O 2 plasma treatment, followed by sputtering of the thin, electrically conductive layer and electroforming of the “blanket” layer. In this way, liquid contamination and defect generation of the O 3 /UV and O 2 plasma-treated imprinting surfaces is effectively minimized.
[0070] The advantageous nature, features, and capabilities of the invention will now be illustrated by reference to the following non-limitative examples, wherein an Oxford RIE “Plasmalab 80 plus” apparatus was utilized for performing the O 2 plasma oxidation/passivation process for forming release layers. A pair of topographically patterned Ni-based “mother” stampers/imprinters (i.e., Nos. 1 and 2) and a Ni-based mirror-finished “mother” stamper/imprinter were treated with a soft and gentle O 2 plasma for different intervals to form a passivating oxide layer thereon for use as a release layer during subsequent formation of a “son” stamper/imprinter therefrom. A separation test was performed on each of the “mother”/“son” pairs after electroforming of the “blanket” layer. the results are given in Table I below.
TABLE I “Son” stamper “Mother” stamper O 2 plasma treatment separation Patterned No. 1 2 min., 100 W, 200 mTorr, O 2 Failed flow 50 sccm Mirror-finished 10 min., 100 W, 200 mTorr, O 2 Successful flow 50 sccm Patterned No. 2 10 min., 100 W, 200 mTorr, O 2 Successful flow 50 sccm
[0071] As is evident from the results presented in Table I, successful separation of the “son” stamper/imprinter from the “mother” stamper/imprinter (i.e., No. 2) occurred when the O 2 plasma treatment was of sufficient duration, i.e., ˜10 min., as to cause formation of an effective oxide passivation/release layer.
[0072] Microscopic inspection of the imprinting surface of patterned “mother” stamper/imprinter No. 2 after separation therefrom of the “son” stamper/imprinter indicated essentially complete absence of pattern deformation, tearing, or debris formation. Results of Atomic Force Microscopy (“AFM”) measurements of the topographically patterned imprinting surface of the “mother” stamper/imprinter No. 2 after the 10 min. O 2 plasma treatment are given in Table II below, which results indicate that the pattern features are very well preserved upon separation and no significant changes in the pattern occur as a result of the dry (O 2 ) plasma passivation process.
TABLE II Before O 2 plasma After O 2 plasma treatment treatment Average depth 97 nm 97 nm Average width 159 nm 156 nm Average wall angle 72° 74°
[0073] The present invention thus affords a number of significant advantages over previous processes for forming stampers/imprinters utilized for patterning various types of recording media, including, but not limited to, formation of servo patterns in magnetic recording layers, including the ability to form stampers/imprinters from larger-sized substrates/workpieces without damaging or otherwise compromising the quality of the topographical pattern.
[0074] It should be apparent to one of ordinary skill in the art that the present invention provides a significant improvement over the conventional art such as has been described above, particularly with respect to the ease and simplicity of manufacturing high replication fidelity stampers/imprinters for use in various types of media patterning processes. Further, the imprinting surface of the stampers/imprinters according to the invention can be formed with a wide variety of topographical patterns, whereby the inventive methodology can be rapidly, easily, and cost-effectively implemented in the automated manufacture of a number of articles, devices, etc., requiring patterning, of which servo patterning of longitudinal and perpendicular magnetic recording media merely constitute examples of the versatility and utility of the invention.
[0075] In the previous description, numerous specific details are set forth, such as specific materials, structures, processes, etc., in order to provide a better understanding of the present invention. However, the present invention can be practiced without resorting to the details specifically set forth. In other instances, well-known processing materials and techniques have not been described in detail in order not to unnecessarily obscure the present invention.
[0076] Only the preferred embodiments of the present invention and but a few examples of its versatility are shown and described in the present disclosure. It is to be understood that the present invention is capable of use in other combinations and environments and is susceptible of changes and/or modifications within the scope of the inventive concept as expressed herein. | A method of manufacturing a stamper/imprinter for use in patterning of a recording medium comprises sequential steps of: (a) providing a substrate/workpiece comprising a topographically patterned surface including a plurality of projections and depressions corresponding to a pattern to be formed in a surface of the recording medium; (b) forming a thin release layer in conformal contact with the topographically patterned surface by means of a dry process; (c) forming a thicker layer of a material in conformal contact with the thin passivation layer on the topographically patterned surface; and (d) separating the thicker layer of material from the topographically patterned surface to form therefrom a stamper/imprinter including an imprinting surface having a negative image replica of the topographically patterned surface, separation of the thicker layer of material from the topographically patterned surface being facilitated by the thin release layer formed by the dry process. | 2 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims an invention which was disclosed in a provisional application filed Jan. 20, 2006, entitled “Low Voltage Ultraviolet Light Apparatus and Packing” and assigned Ser. No. 60/760,470. The benefit under 35 USC §119(e) of the U.S. provisional application is hereby claimed, and the aforementioned application is hereby incorporated herein by reference.
BACKGROUND AND SUMMARY
The present invention relates to a low voltage ultraviolet light apparatus for application into typical centralized air heating, ventilating and air conditioning (HVAC) systems. The device is intended for the reduction and control of organic contamination that can occur within confines of these central air handling units (AHU's).
Organic contamination such as algal, fungal, bacterial, and viral contamination of central air handling units (AHU's) components is a widespread indoor air related problem in homes and buildings with centralized heating, ventilation, and air-conditioning (HVAC) systems and is a potential source of contamination of the occupied air space. Organic growth has been found growing on air filters, insulation, internal wires, blower wheels and motors, cooling coils, and drain pans as well as in ducts of these systems. This contamination if un-checked can contribute to building-related illnesses and diseases, including both infectious diseases and hypersensitivity diseases.
By applying the present inventions ultraviolet light apparatus into typical central air handling units (AHU's), it can help to maintain components that are susceptible to organic growth and fouling through the use of the germicidal ultraviolet light, which can prevent the organic fouling from occurring and spreading.
The present invention includes a low voltage ultraviolet light apparatus (including its means for attachment) and it's related packaging for marketing. As discussed in more detail below, the ultraviolet light apparatus also involves an extended operating range low voltage power supply, weather resistant lamp cable, weather resistant lamp and related mounting hardware. Further, as also discussed in more detail below, the packing of the ultraviolet light for transport and marketing involves a tube that contains two end caps to contain the product within the tube's interior, a paper insert that contains marketing and technical information on the UV apparatus and two round foam inserts that pad and contain the UV apparatus components on either end, with the UV light source aligned with and within the tube's center.
The low voltage power supply of my invention is intended to receive it's power source from the 24 VAC low voltage source that is commonly found within residential air and light commercial air handling units (AHU's). This power source is typically the source that powers the thermostat and controls of the air handling unit. However, its use is difficult in this application both because it must be made compatible with the normal demand for 60 VAC used to power the UV light source and because the low voltage source for thermostat power is itself subject to great variation in terms of output, often ranging from 18 to 32 VAC.
A weather resistant lamp cable is attached to the low voltage power supply. This cable is intended to supply power to the ultraviolet light source and is weather resistant due to the inherent moist nature found within typical air handling units.
The weather resistant ultraviolet light source is intended to be applied to various configurations of air handling units for the purpose of disinfection and sterilization of internal components that are prone to grow organic microbial contaminates.
The present invention also involves a method for the reduction of typical indoor odors through a combination of ultraviolet light spectrums emitted by the UV light source. The combination of UV spectrums produces a UV oxidative effect that increases the UV's reactivity with odors and other volatile organic compounds (VOC's).
The present invention likewise involves an installation hardware kit for mounting the ultraviolet light apparatus within typical air handling units. The installation hardware kit includes a specially designed magnetic “Z” bracket for the purpose of mounting the ultraviolet light source above the components of the air handling unit.
Finally, The present invention involves special packaging and display innovations. These relate to case packing of the product for display and marketing of a bulk quantity of the product. The case packaging involves a cardboard case box for boxing multiples of the product, such as a case containing 15 pieces. In addition the case packaging involves a marketing display such as a poster attached to the outside of the case box. Further, a lighted counter display unit allows visual display and marketing of the product. The counter display involves a working and lighted sample of the UV apparatus and it's related packaging that is attached to a flat counter mountable base. Additionally, a retail brochure holder can be attached to this base for the purpose of displaying the sales and marketing credentials of the UV apparatus.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 provides a first perspective view of the ultraviolet light apparatus and the related transparent packaging cylinder or tube of my invention.
FIGS. 2A through 2C provide illustrations of the low voltage power supply of my invention and its related wire harnesses.
FIGS. 3A through 3C provide perspective views of the weather resistant ultraviolet light source of my invention, including its base and installation variations.
FIG. 4 provides a more detailed perspective view of the UV/Oxidation tip of the ultraviolet light source, which assists in the reduction of odors.
FIGS. 5A and 5B provide views of the installation hardware kit of my invention, with FIG. 5A providing separate perspective views of the “Z” shaped mounting bracket of the invention.
FIG. 6 provides a perspective view of the case box packaging of the invention.
FIG. 7 provides a perspective view of the counter display of the invention.
DESCRIPTION
FIG. 1 provides an illustration of the UV apparatus and related packing. The UV apparatus 1 , 2 , 3 has been placed inside of a clear tubular package 4 for the intention of display and marketing. The clear packaging 4 serves two main purposes for the invention. First, it serves as a means to quickly and easily display the UV apparatus for marketing and sale. Second, it serves as a means to transport the UV apparatus prior to installation. The tube contains two end caps 5 to contain the product within the tube's interior, a paper insert 6 that contains marketing and technical information on the UV apparatus and two round foam inserts 7 that contain the UV apparatus components on either end 1 and 3 , and the UV light source 2 within the tube's center.
FIGS. 2A through 2C illustrate the low voltage power supply 8 and it's related wire harnesses 9 and 10 . The power supply 8 is comprised of a low voltage electronic circuit 11 designed to operate the UV light source 2 . The circuit 11 has been specially designed to except an extended range of low voltage supply voltages that range from eighteen (18) volts of alternating current (VAC) up to thirty-two (32) volts (VAC). The extended range low voltage power supply 8 is intended to receive it's power source from the twenty-four (24) VAC low voltage source found within typical residential air and light commercial air handling units (AHU's). This power source is typically the source that powers the thermostat and controls of the air handling unit and is fed from a low voltage transformer that takes the high voltage from the main power supply of the air handling unit and transformers it to a low voltage range for this purpose. It is not uncommon for this source of power to be inconsistent and not exactly at twenty-four VAC. In fact, it is made even more difficult to use for the purposes of this invention as it is typical to find this voltage source to have varying degrees of voltages within the eighteen to thirty-two VAC range. Moreover, the UV light source 2 requires approximately 60 VAC.
However, subject to overcoming these problems, this voltage source is an attractive source of power to be used for this invention and for the purpose of powering this type of UV light apparatus 1 , 2 , 3 because it is a common source of power found throughout the air conditioning industry, regardless of manufacturer of AHU. Therefore, in the case of this invention, it has been a particular point of non-obvious innovation to include and use a circuit 11 designed to accept these low and varying voltages. The principle behind circuit 11 is known generally to those in the electronic arts as the Villard's cascade and, in addition to a band pass filter, provides the foundation for the design of Circuit 11 .
The usual power conditioning method for using a low voltage source in an operation of this type would be to incorporate a voltage doubler circuit on the incoming power in the circuit design. This would seem to be an acceptable method as the UV light source will typically operate between 40 and 60 volts of operating voltage. Thus, a typical voltage doubler circuit could take the incoming power source of 24 VAC and double it to 48 VAC. However, when the incoming power is inconsistent (as in the current application) then the doubling effect can magnify the power problems associated with it and give inconsistent operating voltages which can cause increased operating heat loads on circuit components and potential product failure.
Thus, I use a full wave voltage multiplier circuit with a band pass filter which actually involves multiple voltage doublers and band pass filters that allow the inconsistent power to be multiplied and then filtered several times to provide a stabilized operating voltage at a more normalized level. In my invention, circuit 11 first doubles the input voltage from 24 to 48 VAC and then filters it within an acceptable operating range. It then takes another input voltage of 24 VAC, doubles it again, filters it again, and averages the two values together with a capacitor to provide a more stabilized averaged value.
From review of the foregoing, it is clear that circuit 11 has been designed to optimize operation of the UV light source 2 for it's maximum efficiency under these low voltage and varying conditions. Also, the circuit 11 is intended to be used in damp environments that can damage the circuit if not protected. For this reason, the circuit 11 is encased in a “potted” enclosure 12 where the circuit board is placed inside of a plastic case 12 and coated and secured within the inside of the case with a weather resistant “potting” material.
The power supply 8 contains a pair of incoming power leads 9 , one red and one black for connection to the low voltage supply source. Also, the power supply 8 contains a weather resistant lamp supply cable 10 for connection to the UV light source 2 . This supply cable 10 is designed to be weather resistant because the operating conditions in which the UV apparatus 1 , 2 , 3 is applied is often times in highly wet or damp conditions found within the interior of air handling units that could damage the cables operation otherwise.
FIGS. 3A through 3C provide further illustrations of the weather resistant ultraviolet light source 2 of my invention. The ultraviolet light source (UV Lamp) 2 is a mercury vapor style of light source of such design as to produce light in the UV-C germicidal spectrums such as 254 nM. This spectrum is well documented for it's effectiveness in sterilizing microbial contaminates and is commonly used for this type of UV light source 2 . Other frequencies, such as 185 nM can be incorporated into the lamp also to produce additional benefits such as odor control and are discussed with reference to FIG. 4 .
The UV Lamp 2 contains a specially designed base 14 that allows for the UV lamp 2 to be applied in a number of different installation configurations. The large flat circular ring (or annular flange) 15 found around the mid point of the base 14 provides a stable surface for mounting the lamp 2 . This affords the opportunity for the lamp 2 to be mounted to flat surfaces using a through hole mounting technique as illustrated in FIG. 3C or mounted to the specially designed magnetic “Z” mounting bracket of the invention (as discussed in detail with reference to FIG. 5 ). The base ring 15 has two U shaped cut-outs 16 that allow for mounting screws or studs to pass within the circumference area of the base ring for securing it to these surfaces.
The UV lamp 2 also contains a 12″ long lamp cable “pigtail” 17 which is intended to provide a means of connecting the lamp 2 remotely from the power supply 1 of FIG. 2 . This cable is designed to be weather resistant because the operating conditions in which the UV apparatus 1 , 2 , 3 is applied is often times in highly wet or damp conditions found within the interior of air handling units that could damage the cables operation otherwise. The particular design intention of the 12″ lamp cable “pigtail” 17 is such that the lamp 2 can be connected and disconnected in the immediate location where the lamp 2 is placed. The connectors of the power supply cable 18 and lamp “pigtail” 19 are of such design as that manufactured by PEI Genesis for application in wet environments.
FIG. 4 provides a more detailed illustration of the ultraviolet light source 2 with the UV/Oxidation tip 20 for reduction of odors. As outlined in the discussion of FIGS. 3A through 3C , it is the intention of the UV light source 2 to produce light in the UV-C spectrum for the purpose of sterilization of microbial contamination. But, in addition, this UV-C light can be combined with a small segment of the lamp body to contain a “splice” 20 of the lamp to produce light in a different spectrum such as that at 185 nM in the UV-O spectrum range.
This “splice” provides additional benefits to the design of the lamp 2 such as for odor control or the reduction of volatile organic compounds (VOC's), which are chemical or organic compounds found in the air that can potentially pose health risks. The light produced in the UV-O range and particularly at 185 nM has been shown to react with oxygen and humidity in the air to produce ozone and hydroxyl radicals (OH ions), which are recognized as an oxidizing agents that can destroy odor molecules and VOC molecules. It is of particular embodiment and design of this lamp 2 to contain only a small portion of this light spectrum so therefore the lamp 2 is constructed such that no more than 10% of the lamps length is of this spectrum. And the term “splice” comes from the fact that these two sections of the lamp are “spliced” 20 or fused together at this point.
FIGS. 5A and 5B provide several illustrations of the installation hardware kit 22 and specially designed “Z” lamp mounting bracket 21 . As mentioned previously, the UV apparatus 1 , 2 , 3 of this invention entails a extended range low voltage power supply 1 and UV light source 2 that is intended to be installed within the confines of centralized air handling units. As these air handling units (AHU's) come in many different varieties and the range of configurations of the internal components is numerous, it is important to provide the necessary hardware to properly implement the UV apparatus 1 , 2 , 3 for the purpose of preventing microbial contamination growth from inside of these AHU's and on all of it's internal components contained within. Of particular embodiment to this invention is the design of the “Z” mounting bracket 21 , which is intended to provide a variety of mounting options for the UV lamp 2 .
The “Z” mounting bracket 21 contains a magnet 23 attached to it's base such that the “Z” bracket 21 can be magnetically fixed to an interior surface of these AHU's, which are typically constructed of ferrous metal that will afford the opportunity for the magnet to become affixed to the interior metal panels of the AHU. If this is not the case, the magnet 23 can be removed from the “Z” bracket 21 and the hardware kit 22 contains self tapping sheet metal screws 24 that can be used to affix the bracket 21 to these surfaces or other internal surfaces or components of the AHU.
In addition, the “Z” bracket 21 is constructed of bendable aluminum to allow the bracket 21 to be bent to any degree of angles to allow the opportunity for the UV lamp 2 to be positioned in a varying degree of angles for optimum exposure of the UV light to the surfaces intended for exposure. In essence, the “Z” mounting bracket 21 is a universal mounting apparatus intended to give the maximum amount of mounting opportunities to the installer to achieve the optimum exposure potential of the UV light source 2 .
If it is not feasible to use the “Z” mounting bracket 21 then the particular design of the lamps base (as described with reference to FIG. 3B ) is utilized. In this case, a 1″ hole can be drilled into any flat surface of the AHU such as the A-plate of the AHU's coil or one of the exterior panels of the AHU. The lamp is then secured using a set of the included self tapping sheet metal screws 24 of the hardware kit 22 . Additionally, the hardware kit 22 contains wire attachments that allow for the low voltage power supplies 1 power input wires 9 to be connected to the low voltage wires found inside of the AHU.
FIG. 6 provides an illustration of the case packing of the present invention. As the design of the UV apparatus's packing of FIG. 1 is for a point of sale display marketing concept, the apparatus 1 , 2 , 3 when displayed in bulk is intended to also convey the point of sale approach. Therefore, the case packaging 26 is design to hold a bulk quantity of fifteen units and has been designed to hold the packages in a vertical arrangement such that the bar code and model number of the UV apparatus's package of FIG. 1 can be displayed. Additionally, the outer face of the case packaging contains a marketing point of sales poster 27 that explains the UV apparatus and it's features and benefits.
FIG. 7 provides an illustration of the counter display of the present invention. As the design of the UV apparatus's packing of FIG. 1 is for a point of sale display marketing concept, the apparatus itself when displayed can also convey the point of sale approach. In this case, a sample of the UV apparatus and it's related packaging of FIG. 1 can be attached to a flat counter mountable base 28 that can be modified to light up non UV-C producing light source for display purposes only for the purpose of drawing attention to the product for point of sales marketing purposes. Additionally, a retail brochure holder 29 can be attached to this base for the purpose of displaying the sales credentials of the UV apparatus.
Thus, as should be clear from the foregoing, my invention includes any or all of the foregoing features, either alone or in combination:
(a) A UV apparatus designed to operate off of the low voltage (24 VAC) control circuit power supply of typical centralized air handling units.
(b) A UV light power supply designed to operate within an extended range of low voltage supply voltages that range from eighteen (18) volts of alternating current (VAC) up to thirty-two (32) volts (VAC).
(c) A UV light power supply circuit designed to optimize the operation of the UV light source for it's maximum efficiency under these low voltage and varying conditions.
(d) A UV power supply circuit intended to be used in damp environments that can damage the circuit if not protected, therefore the circuit is encased in a “potted” enclosure where the circuit board is placed inside of a plastic case and coated and secured within the inside of the case with a weather resistant “potting” material.
(e) A UV power supply containing a pair of incoming power leads, one red and one black for connection to the low voltage supply source.
(f) A UV power supply containing a weather resistant lamp supply cable for connection to the UV light source.
(g) An ultraviolet light source to be applied to the interior of central air handling units for the control of surface and airborne microbial contamination from within the interior components of these units.
(h) An ultraviolet light source (UV Lamp) of mercury vapor type of light source of such design as to produce light in the UV-C germicidal spectrums such as 254 nM.
(i) An ultraviolet light source (UV Lamp) of mercury vapor type of light source of such design as to produce light in the 185 nM to produce additional benefits such as odor control.
(j) A ultraviolet light source with the UV/Oxidation tip for reduction of odors.
(k) A UV light source that contains a “splice” of the lamp to produce light in a different spectrum such as that at 185 nM in the UV-O spectrum range.
(l) A UV light source that contains only a small portion of this light spectrum so therefore the lamp is constructed such that no more than 10% of the lamps length is of this spectrum.
(m). An ultraviolet light source that contains a specially designed base that allows for the UV lamp to be applied in a number of different installation configurations.
(n) A UV lamp mounting base that contains a large flat circular ring (or annular flange) found around the mid point of the base that provides a stable surface for mounting the lamp.
(o) A UV lamp that contains a 12″ long lamp cable “pigtail” which is intended to provide a means of connecting the lamp remotely from the power supply.
(p) A specially designed “Z” mounting bracket intended to provide a variety of mounting options for the UV light source of this invention.
(q) A “Z” mounting bracket that contains a magnet attached to it's base such that the “Z” bracket can be magnetically fixed to interior wall surfaces of AHU's, which are typically constructed of ferrous metal that will afford the opportunity for the magnet to become affixed to the interior metal panels of the AHU.
(r) A “Z” mounting bracket that, when the magnet is removed from the bracket, can be secured to interior wall surfaces of AHU's or other internal surfaces or components of the AHU with self tapping sheet metal screws.
(s) A “Z” mounting bracket constructed of bendable aluminum to allow the bracket to be bent to any degree of angles to allow the opportunity for the UV lamp to be positioned in a varying degree of angles for optimum exposure of the UV light to the surfaces intended for exposure.
(t) A “Z” mounting bracket that is a universal mounting apparatus intended to give the maximum amount of mounting opportunities to the installer to achieve the optimum exposure potential of the UV light source.
(u) If it is not feasible to use the “Z” mounting bracket than the particular design of the lamps base as described in FIG. 3B is utilized. In this case, a 1″ hole can be drilled into any flat surface of the AHU such as the A-plate of the AHU's coil or one of the exterior panels of the AHU. The lamp is then secured using a set of the included self tapping sheet metal screws of the hardware kit.
(v) A UV apparatus that is placed inside of a clear tubular package for the intention of display and marketing.
(w) A UV apparatus that is placed inside of a clear tubular package as a means to quickly and easily display the UV apparatus for marketing and sale.
(x) A UV apparatus that is placed inside of a clear tubular package as a means to transport the UV apparatus prior to installation.
(y) A UV apparatus that is placed inside of a clear tubular package that contains two end caps to contain the product within the tubes interior.
(z) A UV apparatus that is placed inside of a clear tubular package that contains a paper insert that contains marketing and technical information on the UV apparatus.
(aa) A UV apparatus that is placed inside of a clear tubular package that contains two round foam inserts that contain the UV apparatus components on either end and the UV light source within the tubes center.
(bb) A UV apparatus that is placed inside of a clear tubular package that when displayed in bulk is intended to also convey the point of sale approach.
(cc) A case packaging of the UV apparatus which is design to hold a bulk quantity of fifteen units designed to hold the packages in a vertical arrangement such that the barcode and model number of the UV apparatus's package can be displayed.
(dd) A case packaging of the UV apparatus such that the outer face of the case packaging contains a marketing point of sales poster that explains the UV apparatus and it's features and benefits.
(ee) A sample of the UV apparatus and it's related packaging that is attached to a flat counter mountable base that is lite up with a non UV-C producing light source for display purposes only for the purpose of drawing attention to the product for point of sales marketing purposes.
However, it will be appreciated that various of the above-disclosed and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. Also that various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the following claims. | This UV light system for use in a central air handling unit of a heating or air conditioning system includes a UV light source and is adapted for operation on, and receives power from, an approximately 24VAC low voltage power supply for a thermostat of the heating or air conditioning system. In its preferred embodiments it is provided with a mounting system including a bendable “Z” shaped mounting bracket, which bracket can be bent to multiple angles allowing the UV light source to be positioned in numerous ways within the central air handling unit. It is preferably packaged in a cylindrical packing case where the elongate cylindrical emitter portion of the UV light source is aligned with the axis of the case. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates to a leveling device.
Leveling devices are known in the art. One of such devices is disclosed for example in the U.S. Pat. No. 5,519,942. The leveling device of this patent has a housing, a support surface which is fixed to the housing, an adjusting device. The adjusting device has at least one adjusting screw which can be displaced so that it extends outwardly beyond the support surface. For this purpose the adjusting screw is provided with an adjusting thread which engages with a counter thread in the housing. The adjusting device with the adjusting screw serves for adjusting the leveling device to the desired leveling plane, which is adjustable by means of a water balance formed on the leveling device. This construction however has a substantial disadvantage that the adjusting screw must be screwed back when it must be again returned into the housing so that it no longer extends outwardly beyond the support surface. In the practice, the return points for the operators of the leveling device are frequently omitted, since it is too time consuming and complicated. When the adjusting screw after the use of the leveling device must again extend outwardly beyond the support plane of the support surface, the adjusting screw can be easily damaged. Moreover the leveling device with the extended adjusting screw can not be used as a water balance.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a leveling device of the above mentioned type which avoids the disadvantages of the prior art.
In keeping with these objects and with others which will become apparent hereinafter, one feature of present invention resides, briefly stated in a leveling device, in which the counter thread engaging with an adjusting thread of the adjusting screw extending beyond the abutment surface is formed as a partial thread on a slider which is displaceable transversely to the longitudinal section of the adjusting screw and is bringable outside of engagement with the adjusting thread.
When the leveling device is designed in accordance with the present invention, it has the advantage that the adjusting screw can be returned in each arbitrary position in a simple manner in the housing of the leveling device, so that every time without great expenses the operation of a water balance is available.
In accordance with a further advantageous feature of the present invention, the adjusting screw after actuation of a releasing key is displaceable back by the spring force. Thereby the one-hand operability of the leveling device remains guaranteed.
The novel features which are considered as characteristic for the present invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a leveling device in accordance with the present invention;
FIG. 2 is a longitudinal section through the inventive leveling device;
FIG. 3 is a partial section through the inventive leveling device on an enlarged scale when compared with FIG. 2;
FIG. 4 is a cross-section through the inventive leveling device; and
FIG. 5 is a view of the leveling device in accordance with the present invention as seen from the front.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A leveling device in accordance with the present invention is identified with reference numeral 10 in FIG. 1 . It has a housing 11 which forms a support surface 13 on a lower side 12 .
The leveling device 10 has a level element 14 oriented parallel to the support surface 13 . Moreover, the leveling device 10 has a light indicating device 15 , which can produce a bundled light beam oriented parallel to the support surface 13 . Furthermore, an adjusting device 16 is provided for orienting the support surface 13 relative to the respective substrate, in particular horizontally.
The adjusting device 16 is further provided with two support legs 17 a and 17 b . They are arranged laterally on the housing and turnable so that they can extend outwardly beyond the support surface 13 as shown in FIG. 5 . In FIG. 1 the support legs 17 a , 17 b are shown in their folded back position. The abutment legs 17 a , 17 b are substantially plate-shaped and have outwardly curved support edges 57 a and 57 b.
In the leveling device 10 shown in FIG. 2 level element 14 extends parallel to the support surface 13 . In the front region 18 the leveling device has a light indicating device 15 . The light indicating device includes a laser diode 20 , a collimation lens 21 and a light outlet passage 22 . The path of rays of a light beam produced by the light indicating device 15 is oriented parallel to a longitudinal axis 23 of the leveling device 10 , to which also the support surface 13 is oriented parallel.
A battery compartment 26 is located substantially centrally in the housing 11 of the leveling device 10 . A battery 27 for the current supply of the light indicating device 15 is accommodated in the battery department 26 . The adjusting device 16 is accommodated in a rear region 19 of the leveling device 10 and has an adjusting screw 30 which is arranged substantially transversely to the longitudinal axis 23 . In FIG. 2 it is shown in a base position at the housing 11 , displaced back behind the support surface 13 .
The adjusting screw 30 has a cylindrical shaft part 31 which is provided on the outer periphery with an adjusting thread 36 , and also a multi-edge drive part 32 . The adjusting screw is form-lockingly coupled via the drive part 32 with an adjusting wheel 34 . The adjusting wheel 34 engages partially in the window retained laterally in the housing 11 through the housing 11 and therefore is available for actuation of the adjusting screw 30 by the operator from outside. At the end located near the support surface 13 , the adjusting screw 30 forms an adjusting mandrel 33 .
A slider 37 is supported displaceable transversely to the displacing direction of the adjusting screw 30 in the housing 11 . The slider 37 has a throughgoing opening 38 , through which the adjusting screw 30 engages with its shaft part 31 . The throughgoing opening 38 is wider than the diameter of the shaft part 31 of the adjusting screw 30 , so that the slider 37 is displaceable within certain limits. An inner thread 39 is formed on a wall of the throughgoing opening 38 . It is bringable in engagement with the adjusting thread 36 . The inner thread 39 is substantially semi circular and forms a partial thread. The slider 37 is pre-tensioned by a pressure spring 40 in the direction toward the engaging position of the inner thread 39 and the adjusting thread 36 .
In the arresting position shown in FIG. 2, the slider 37 is blocked by an arresting pin 41 which in this position serves as an abutment for the pretensioning force of the pressure spring 40 . The arresting pin 41 engages with its end 42 facing the support surface 13 , into the arresting opening 43 in the slider 37 . The arresting opening 43 has substantially the same diameter as the slider 37 , so that the slider 37 is blocked form-lockingly in the arresting position. In this position the inner thread 39 and the adjusting thread 36 are not in engagement with one another. Simultaneously the adjusting screw 30 is forced by a return spring 44 to a base position in which it is completely withdrawn into the housing. In this base position the support surface 13 is available for the support purposes.
A push button 48 is located in a rear region 19 of the leveling device 10 , in an extension of the arresting pin 41 . The arresting pin 41 is displaceable by the push button 48 from the base position relative to the slider 37 . Near a support-side end 42 , the arresting pin 41 is provided with a narrowing 49 which is displaceable by the pressing in of the push button 48 at the height of the arresting opening 43 . When the narrowing 49 and the slider 37 are in alignment with one another, the slider 37 is released axially, so that the slider 37 is displaced by the force of the spring 40 , until the inner thread 39 and the adjusting thread 36 are engaged with one another as shown in FIG. 3 . Simultaneously, a first spring 50 is pre-tensioned and loads the push button 48 . After releasing of the push button 48 , the first spring 50 forces the push button 48 again back to its initial position, and the projections 52 , 53 of the push button 48 come to abutment against the corresponding projections on the housing 13 . A second spring 51 loads the arresting pin 41 with its return force.
FIG. 3 shows the rear region 19 of the adjusting device 16 in its adjusting position, on a scale which is enlarged when compared with FIG. 2 . In this position the thread 36 on the shaft part 11 of the adjusting screw 30 is in engagement with the inner thread 39 on the slider 37 . The slider 37 engages on the one hand in the narrowing 49 in the arresting pin 41 . In this engaging position, the adjusting screw 30 by turning of the adjusting wheel 34 displaces as a result the thread connection 36 / 39 against the restoring spring 44 , and the abutment mandrel 33 then extends outwardly of the housing 11 and is displaceable outwardly over the support surface 13 .
On its end which faces away from the slider 37 , its pressure spring 40 has a T-shaped actuation button 54 which extends outwardly of the housing 11 . Therefore, the actuation button 54 is accessible for the operator of the inventive machine 10 . By pressing the actuating button 54 , the operator can displace the slider 37 against the pretensioning force of the pressure spring 40 , and the slider is moved back from the narrowing 49 and releases in this way the arresting pin 41 . The arresting pin 41 is displaced again to its initial position shown in FIG. 2 . The inner thread 39 and the adjusting thread 36 then again engage one another. The return spring 44 forces the adjusting screw 30 automatically back to its base position in the housing 11 .
FIG. 4 shows a cross-section through the leveling device 10 in the region of the support leg 17 a , 17 b . There are total two support legs 17 a , 17 b on the opposite sides of the housing 11 . They are coupled with one another through a toothed gear transmission 55 . Each support leg 17 a , 17 b is non-rotatably connected with a toothed gear 56 a , 56 b . Thus, by turning a first support leg 17 a , 17 b the corresponding another abutment leg 17 a , 17 b is also turned.
FIG. 5 shows the leveling device 10 with the unfolded support legs 17 a , 17 b which, because of the coupling through the toothed gear transmission 55 , are turned always uniformly. The abutment legs 17 a , 17 b extend outwardly through the support surface 13 , so that the leveling device 10 can be placed on any substrate, independently from the support surface 13 . This is usable especially in the event of uneven substrates. The adjusting screw 30 which is extended outwardly beyond the support surface 13 is recognizable between both support legs 17 a , 17 b with the support mandrel 33 . Because of the curved support edges 57 a , 57 b of the support legs 17 a , 17 b , the leveling device 10 with the turned out abutment legs 17 a , 17 b is easily adjustable via the adjusting screw 30 .
It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of constructions differing from the types described above.
While the invention has been illustrated and described as embodied in leveling device, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention.
What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims: | A leveling device has a housing, a support surface which is fixed with the housing, an adjusting device including at least one adjusting screw which is displaceable outwardly and has an adjusting thread which is engageable with a counter thread for adjusting the adjusting screw, the counter thread being formed as a partially side of a slider which is displaceable transversely to a longitudinal axis of the adjusting screw and disengageable from the adjusting thread. | 8 |
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application contains subject matter related to commonly assigned U.S. Pat. No. 5,358,508, incorporated herein by reference.
BACKGROUND OF THE INVENTION
The present invention relates to a laparoscopic instrument, and more particularly to a laparoscopic instrument having a disposable or replaceable, manually operable tip, such as cutting blades, forceps, or the like.
A wide variety of medical instruments for laparoscopic surgery are presently known. Such instruments are used to access, e.g., the peritoneal cavity of a patient through a small incision in the abdominal wall. An endoscope normally is inserted into the cavity through a second incision in the abdominal wall for viewing of the operation of the instrument by the surgeon. Typical of such laparoscopic instruments are those having a tip end including, e.g., cutting blades, forceps, or other surgical device to be inserted into the cavity to perform the surgery, an external end from which the surgeon may manually manipulate the tip device from a position external to the abdominal wall, and an elongated shaft operably connecting the tip end and the external end.
Many such laparoscopic instruments have permanently attached tips. However, a significant advance has been made in the last few years, in that instruments have been developed having disposable tips. Thus, a worn cutting blade may be replaced or one type of tip may be replaced with another, interchangeable type.
Because of the high cost of such laparoscopic instruments, reuse of each instrument would be advantageous in controlling the cost of laparoscopic surgery. However, such reuse requires instruments of rugged construction which may be readily cleaned and sterilized. Known laparoscopic instruments, even those with removable tips, can be difficult to clean due to their length and complex internal structure.
Accordingly, it is an object of the present invention to provide a laparoscopic instrument which overcomes the disadvantages of the prior art.
It is another object of the invention to provide a laparoscopic instrument assembly which is more easily and thoroughly cleaned by normal hospital equipment and procedures.
It is yet another object of the invention to provide a laparoscopic instrument assembly in which the shaft and handle portions of the instrument are readily disassembled for cleaning and reassembled for reuse.
It is still another object of the invention to provide a laparoscopic instrument assembly which includes a disposable shaft, with or without a permanently attached tip.
It is a further object of the invention to provide a laparoscopic instrument assembly in which the tip, shaft, and handle portions of the instrument are readily disassembled and reassembled or replaced for reuse of the instrument.
SUMMARY OF THE INVENTION
In accordance with these objects, the invention is a laparoscopic instrument assembly including a tip having a surgical device or, alternatively, for use with a removable tip. The shaft between the tip and the external, body or handle portion of the instrument includes a rod moving axially within a sheath to transmit the manipulation of the handle portion to actuate the tip. Both the sheath and the rod are removable from the handle for cleaning of the instrument. Thus, after use, the shaft may be readily disassembled from the handle, the shaft and handle portion sterilized, and the shaft and handle readily reassembled for reuse of the instrument. Alternatively, the shaft may be disposed of and the handle portion reassembled with a fresh shaft. The assembly may be used with a removable tip provided separately, or a removable or non-removable tip may be provided as part of the assembly. The removable tip may be cleaned or replaced with a substitute during or after use, or a non-removable tip may be provided as part of a shaft-tip unit.
In one aspect the invention is a laparoscopic instrument assembly. In another aspect, the invention is a laparoscopic instrument assembly for use with a removable tip. The assembly includes a shaft, a manually controllable handle member, and, optionally, a removable or non-removable tip. The shaft includes a tubular sheath and a first rod disposed for axial movement within the sheath. The shaft, the sheath, and the first rod each have a proximal end and a distal end. In one embodiment, the shaft distal end in cludes means for operably and removably attaching a replaceable tip including a surgical device to the shaft for actuation of the surgical device. In another embodiment, the tip is permanently attached to the shaft. The handle member includes a casing having a first axial bore therein and a second rod disposed for axial movement within the first axial bore.
The assembly also includes means for removably attaching the sheath to the casing to extend from the casing with the sheath coaxial with the first axial bore, as well as means for operably and removably attaching the first rod to the second rod for axial movement of the first rod within the sheath in response to movement of the second rod within the first axial bore. On attachment of the removable tip to the shaft distal end, if required, actuation of the surgical device is effected by movement of the second rod within the first axial bore and movement of the first rod within the sheath in response to the movement of the second rod. The shaft and the handle member may readily be disassembled and reassembled for disposal of the shaft and tip or for cleaning and reuse of the laparoscopic instrument assembly.
In a narrower embodiment, the means for operably and removably attaching the first rod to the second rod includes threads on the first rod proximal end and a threaded axial bore in the second rod distal end for mating engagement with one another to removably attach the first rod to the second rod. A pin is inserted through a radial bore in the casing and fits within a slot in the second rod for preventing rotational movement of the second rod while permitting free axial movement of the second rod within a range sufficient to manipulate the tip. The pin is inserted in the casing before actuation of the removable tip, preventing rotational movement of the second rod relative to the first rod, and permitting removal of the first rod from the second rod.
In another narrower embodiment, the first axial bore has a first, larger diameter portion near the first axial bore distal end and a second, smaller diameter portion proximally of the first diameter. The diameter of the second portion is selected for close sliding fit of the second rod therewithin. The first rod proximal end includes an annular groove formed therein. The second rod distal end includes an inwardly extending, second axial bore and one or more radial bores extending from an outer surface thereof to be open to the second axial bore. Each radial bores is of a first, larger diameter at the outer surface and a second, smaller diameter at the second axial bore. The assembly further includes a detent member, e.g., a ball, disposed in each radial bore and engageable with the groove. Each detent member is shaped and sized (a) to permit only partial entry of the detent member into the second axial bore, (b) to be freely movable radially within the radial bore in response to urging from a wall of the first axial bore second portion or from a wall of the groove, and (c) to extend beyond the radial bore either into the second axial bore to engage the groove or into the first axial bore first portion but not into both. Each detent member engages the groove during actuation of the removable tip, preventing removal of the first rod from the second rod. Each detent member is disengageable from the groove when the tip is not actuated, permitting removal of the first rod from the second rod.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the present invention, together with other objects, features, advantages, and capabilities thereof, reference is made to the following Description and appended Claims, together with the Drawings in which:
FIG. 1 is an exploded elevation view, partly in section, of a laparoscopic instrument assembly in accordance with one embodiment of the present invention;
FIGS. 2A and 2B are an elevation views, partly in section, of portions of the shaft and handle member of the assembly of FIG. 1, showing the locking or detent mechanism in further detail;
FIG. 3 is an elevation view, partly in section, of the shaft and tip portions of a laparoscopic instrument assembly in accordance with another embodiment of the invention;
FIG. 4 is an exploded elevation view, partly in section, of portions of the shaft and handle member of a laparoscopic instrument assembly in accordance with yet another embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The laparoscopic instrument assembly described herein includes a handle member and a shaft operably interconnecting the handle member and a removable or stationary, non-removable tip. The shaft includes a tubular sheath and a rod movable within the sheath. The distal end of the shaft may be operably connected to the tip for actuation of a surgical device on the tip. The proximal end of the shaft is removably and operably connected to the handle member for transmission to the tip surgical device of manipulation by the surgeon of the handle member.
The description below of various embodiments shown in the Drawings refers to laparoscopic instruments in accordance with the invention. However, this description is not intended to limit the scope of the present invention, but merely to be illustrative and representative thereof.
Referring now to FIG. 1, laparoscopic instrument assembly 10 in accordance with one embodiment of the present invention includes handle member 12 and shaft 14 operably interconnecting handle member 12 and removable tip 16. Removable tip 16 may be provided as part of assembly 10 or, alternatively, may be obtained separately. Shaft 14 includes tubular sheath 18 and rod 20 movable within sheath 18. Distal end 22 of shaft 14 is operably connected to tip 16 for actuation of surgical device 24 on tip 16. Handle member 12 includes body, or casing, 26, stationary handle 28, finger-operable, movable handle 30 pivotally linked to stationary handle 28, and rod 32 linked to moveable handle 30 for sliding axial movement within axial bore 34 through casing 26 in response to pivotal movement of movable handle 30. Conveniently, stationary handle 28 and movable handle 30 include openings 36a and 36b shaped to receive fingers and thumb, respectively, of the surgeon for scissors-like manipulation of the instrument.
As shown in FIG. 2A, sheath 18 is attached to casing 26 in a conventional manner using collet 38, collet closer 40 including ring knob 42, and knob 44. Sheath 18 extends distally from casing 26 to be coaxial with bore 34. Rod 20 is operably and removably attached to rod 32 for axial movement of rod 20 within sheath 18 in response to movement of rod 32 within bore 34 in a manner illustrated in further detail in FIGS. 2A and 2B.
FIGS. 2A and 2B show proximal end 51 of shaft 14 removably and operably connected to handle member 12 for transmission to the tip surgical device of manipulation by the surgeon of handle member 12. Axial bore 34 includes larger diameter portion 46 near the bore distal end and smaller diameter portion 48 proximally of the larger diameter portion. The diameter of narrower portion 48 is selected for close sliding fit of rod 32.
As part of the detent mechanism for attaching rod 20 to rod 32, an annular groove 50 is formed in proximal end 51 of rod 20. Distal end 33 of rod 32 includes axial bore 52 extending inwardly from distal end 33 and sized for close sliding fit of rod 20. Radial bores 54 are also formed in distal end 33 to extend from the outer surface of rod 50 into and open to axial bore 52. The axial position of radial bores 54 is selected for registry of radial bores 54 with groove 50. A radial bore is provided for each detent member, described below. Each radial bore 54 has a larger diameter at the rod outer surface and a smaller diameter where it enters axial bore 52.
Each radial bore 54 contains a detent member 56 therein for mating engagement of detent members 56 with groove 50. The number of detent members 56 is selected to optimize the gripping power of the detent members on rod 20. Typically, from one to six detent members and radial bores are provided, with three the preferred number. Each detent member 56 is shown in the Figures as a ball. However, detent members 56 may be any shape and size which will (a) permit only partial entry of each detent member 56 into axial bore 52; (b) to be freely movable radially within its radial bore 54 in response to urging from the wall of narrow portion 48 of axial bore 34 or from side wall 58 of groove 50; and (c) to extend beyond its radial bore 54 either into axial bore 52 to engage groove 50 or into narrow portion 48 of axial bore 34, but not into both.
Each detent member 56 engages groove 50 during actuation of tip surgical device 24, preventing removal of rod 20 from axial bore 52. However, sheath 18 may be released from casing 26 in a conventional manner, and detent members 56 may be disengaged from groove 50 by separating handles 28 and 30 (FIG. 1) sufficiently wide apart to drive rod 32 distally beyond its operating position, bringing radial bores 54 and detent members 56 in registry with larger portion 46 of axial bore 34. In this position, pulling of shaft 14 forces side wall 58 of groove 50 against detent members 56, forcing the detent members out of groove 50 and into larger portion 46 of axial bore 34, permitting removal of rod 20 from rod 32 and separation of shaft 14 from handle member 12.
For reassembly, e.g., after cleaning, the steps are reversed. With rod 32 in its far distal position, shaft 14 is inserted into handle member 12 with sheath 18 in position within axial bore 34 and rod 20 inserted into axial bore 52 with groove 50 in registry with radial bores 54. Handles 28 and 30 then may be brought closer together, drawing rod 32 in a proximal direction. Wall 60 between larger portion 46 and narrower portion 48 of axial bore 34 then forces detent members 56 out of larger portion 46 of axial bore 34 and into groove 50, locking rod 20 to rod 32. Detent members are held in groove 50 by the close sliding fit of rod 32 within narrower portion 48 of axial bore 34. Ring knob 42 is used in a conventional manner to tighten collet 38 against sheath 18.
For use, removable tip 16 is attached to distal end 22 of shaft 18 in known manner, and surgical device 24, e.g., cutting means or forceps, is actuated by scissor-like movement of handles 28 and 30, which effects axial movement of rod 32 within axial bore 34. Axial movement of rod 32 effects axial movement of rod 20 within and relative to sheath 18, which actuates surgical device 24 in known manner.
FIG. 3 shows an embodiment in which the laparoscopic instrument assembly has a disposable shaft and tip, not intended for reuse. Like features to those shown in FIGS. 1 and 2 are indicated by the same reference numerals. In this embodiment, tip 16a and its surgical device 24a are permanently attached to sheath 18a and rod 20a of shaft 14a in a conventional manner, and are not removable. After use, shaft 14a may be removed from handle member 12, as described above, and disposed of. After cleaning of the handle member, a new shaft with tip may be attached to the handle member, also as described above.
FIG. 4 shows in detail an alternate detent mechanism for operably and removably attaching the shaft to the handle member. Like features to those shown in FIGS. 1, 2, and 3 are indicated by the same reference numerals. Sheath 18b of shaft 14b is attached to casing 26a as described above. Proximal end 51b of rod 20b includes external threads 70 for mating engagement with internal threads 72 in axial bore 52a in rod 32a. Thus, proximal end 51b of rod 20b may be attached to distal end 50a of rod 32a by screwing threads 70 into threads 72.
To permit rotation of rod 20b relative to rod 32a for separation of rods 20b and 32a, while permitting axial movement of rod 32a, rod 32a is provided with slot 74. Radial bore 76 and opposing radial bore 78 are provided in casing 26a to receive and hold in place pin 80. The relative sizes of slot 74 and pin 80 are selected to permit free axial movement of rod 32a within a range sufficient to manipulate a surgical device of a tip attached to shaft 14b. Rotational movement of rod 32a, however, is prevented by pin 80.
Conveniently, as shown in FIGS. 1, 2A, 2B, and 4, casing 26 (FIGS. 2A and 2B) or 26a (FIG. 4) may include ratchet 82 and bearing 84 or 84a, respectively, coaxial with knob 44, to provide axial bore 34 or 34a, respectively. During fabrication of the instrument assembly shown in FIG. 4, pin 80 is inserted into slot 74 of bearing 84, then bearing 84 and pin 80 are inserted into ratchet 82.
Pin 80 remains in place within slot 74 during actuation of a tip surgical device (not shown), preventing rotational movement of rod 32a within bore 34a. The tip and its surgical device may be removable or non-removable from shaft 14b, as described above. Preferably, pin 80 is not fixed within bores 76 and 78, but is retained in place by ratchet 82.
The invention described herein presents to the art a novel, improved laparoscopic instrument assembly having a removable and replaceable or disposable shaft, with or without a permanently attached tip. The replaceable assembly is more easily and thoroughly cleaned by normal hospital equipment and procedures. Alternatively, the shaft may be disposable and readily replaced by a new shaft for reuse of the handle member of the assembly.
While there has been shown and described what are at present considered the preferred embodiments of the invention, it will be apparent to those skilled in the art that modifications and changes can be made therein without departing from the scope of the present invention as defined by the appended Claims. | A laparoscopic instrument assembly for use with a removable tip. The shaft between the removable tip and the external, body or handle portion of the instrument includes a rod moving axially within a sheath to transmit the manipulation of the handle portion to actuate the tip. Both the sheath and the rod are removable from the handle for cleaning of the instrument. Thus, after use, the shaft may be readily disassembled from the handle, the shaft and handle portion sterilized, and the shaft and handle readily reassembled for reuse of the instrument. Alternatively, a non-removable tip may be provided as part of a shaft-tip unit. | 0 |
FIELD
[0001] The disclosure is related to reducing aerodynamic drag of an airplane and, more particularly, to flight control surface seals that reduce aerodynamic drag.
BACKGROUND
[0002] An airplane includes flight control surfaces that a pilot can adjust to control the aircraft's flight attitude. Airplane design determines what flight control surfaces are available on a particular airplane. Typical flight control surfaces include the wing's slats, flaps, spoilers, and ailerons; vertical and horizontal stabilizers; rudders, and elevators.
[0003] A horizontal stabilizer is a horizontal wing attached to the aft end of the fuselage of an airplane to trim the airplane about the longitudinal axis by providing a stabilizing force to the aft end of the airplane. While some horizontal stabilizers are fixed, others can be moved during flight. These movable horizontal stabilizers, which may be referred to as variable incidence horizontal stabilizers, allow the pilot to adjust the angle of the horizontal stabilizer based on the aircraft's longitudinal stability parameters, such as center of gravity location.
[0004] Elevators are flight control surfaces that control the aircraft's longitudinal attitude by changing the vertical loads on the aft end of the fuselage. Elevators are usually hinged to the aft end of the horizontal stabilizer.
[0005] Since these movable horizontal stabilizers and elevators move relative to the fuselage, a gap exists between these flight control surfaces and the fuselage except at the point where the surface is attached to the fuselage (i.e., the pivot point of the surface). Since most aft fuselages are convex curved about the longitudinal axis of the airplane, the gap between the movable horizontal stabilizer inboard edge and the fuselage is not constant. This gap normally increases as the stabilizer is moved more from its neutral position. This is also true of the elevator. As the size of the gap increases, so too does the aerodynamic drag of the airplane, which impacts the performance of the airplane.
SUMMARY
[0006] A system and method for reducing aerodynamic drag of an airplane is disclosed. The system includes a flight control surface of an airplane and a seal connected to the flight control surface. The seal blocks airflow through a gap located between the flight control surface and a fixed structure of the airplane. In a preferred embodiment, the flight control surface is a horizontal stabilizer or an elevator, the fixed structure is a fuselage, and the seal is a bulb seal.
[0007] The method includes placing an exterior surface of a seal adjacent to an inboard edge of a flight control surface of an airplane, positioning a fastener adjacent to an opposite exterior surface of the seal, and attaching the seal to the flight control surface with the fastener. The seal fills a gap located between the flight control surface and a fixed structure of the airplane. The method further includes applying a low friction coating, such as Teflon® paint, on the fixed structure.
[0008] The features, functions, and advantages that have been discussed can be achieved independently in various embodiments or may be combined in yet other embodiments further details of which can be seen with reference to the following description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Presently preferred embodiments are described below in conjunction with the appended drawing figures, wherein like reference numerals refer to like elements in the various figures, and wherein:
[0010] FIG. 1 is an illustration of an empennage of an airplane, according to an example;
[0011] FIG. 2 is an illustration of an isometric view of a horizontal stabilizer and an elevator, according to an example;
[0012] FIG. 3 is an illustration of a cross-sectional view of a seal, according to an example;
[0013] FIG. 4 is an illustration of a cross-sectional view of a fastener for attaching the seal to the horizontal stabilizer and the elevator, according to an example;
[0014] FIG. 5 is an illustration of a view looking down on the stabilizer and elevator identifying a location for attaching the seal, according to an example; and
[0015] FIG. 6 is an illustration of a view looking up on the stabilizer and elevator identifying a location for attaching the seal, according to an example.
[0016] The drawings are for the purpose of illustrating example embodiments, but it is understood that the inventions are not limited to the arrangements and instrumentality shown in the drawings.
DETAILED DESCRIPTION
[0017] FIG. 1 is an illustration of an empennage 100 of an airplane. The empennage 100 , also known as the tail or tail assembly, contributes to the stability and the control of the airplane. The empennage 100 includes a horizontal stabilizer 102 with elevators 104 . The empennage 100 also includes a vertical stabilizer 106 with a rudder 108 . The horizontal stabilizer 102 and vertical stabilizer 104 are connected to a fuselage 110 of the airplane.
[0018] As the horizontal stabilizer 102 and the elevators 104 move relative to the fuselage 110 , a gap between the fuselage 110 and either the horizontal stabilizer 102 or elevators 104 changes size. To reduce aerodynamic drag, a seal is attached to inboard edges 112 of the horizontal stabilizer 102 and inboard edges 114 of the elevators 104 . The seal expands and compresses as the gap changes size to block airflow between these flight control surfaces 102 , 104 and the fuselage 110 .
[0019] FIG. 2 is an isometric view 200 of the horizontal stabilizer 102 and the elevator 104 . The view 200 depicts trailing edge panels 206 a and 206 b of the horizontal stabilizer 102 and an elevator panel 208 of the elevator 104 . Seals 210 a and 210 b are attached to each of the panels 206 a and 206 b, respectively. A seal 210 c is also attached to the elevator panel 208 .
[0020] FIG. 3 is a cross-sectional view of a seal 300 that may be used for the seals 210 a , 210 b, and 210 c. The seal 300 is a compression seal and is depicted in FIG. 3 as a bulb seal and, in particular, a P-bulb seal. The bulb seal is flexible and changes shape as pressures are exerted on the exterior of the seal 300 . The flexible nature of the seal 300 allows it to expand and contract to fill the variability of the gap throughout the normal range of the horizontal stabilizer 102 and elevator 104 . Other flexible seal types may also be used.
[0021] The dimensions of the seal 300 depend on the design of the airplane and, more specifically, the size of the gap between the flight control surfaces 102 , 104 and the fuselage 110 as the flight control surfaces 102 , 104 move. As the elevator 104 typically has a greater range of motion than the horizontal stabilizer 102 , different seal dimensions may be used for the different panels 206 a, 206 b, and 208 . For example, the diameter of the bulb may be larger for the seal 210 c attached to the elevator panel 208 than the seals 210 a and 210 b attached to the trailing edge panels 206 a and 206 b.
[0022] In one example, the diameter (d) of the bulb from the exterior edges of the bulb may be approximately 1.8″ and the thickness of the bulb wall (t) may be approximately 0.08″ when not subjected to external forces. In other examples, the diameter (d) may be between 1″ and 3″ and the bulb wall thickness (t) may be between 0.5″ and 1.5″. In other examples, the diameter (d) may be between 0.5″ and 5″ and the bulb thickness (t) may be between 0.1″ and 2″.
[0023] The P-bulb seal includes an attachment surface 302 , sometimes referred to as a handle or lip. The attachment surface 302 facilitates attachment of the seal 300 to the panels 206 a, 206 b , and 208 . While other mechanisms and surfaces may be used to attach the seal 300 to the panels 206 a, 206 b, and 208 , P-bulb seals are readily available and convenient to use.
[0024] The seal 300 is composed of a non-metallic material, preferably, silicone. In a preferred embodiment, the seal is composed of BMS 1-57 Type 2 silicone. Other non-metallic materials, such as rubber, may also be used.
[0025] The seal 300 may also be covered with an external covering 304 , such as a polyester fabric or other protective material. For example, the external covering 304 may include one or more layers of Mohawk D2000 Dacron® fabric or HT 2002 Nomex® fabric. Preferably, the external covering 304 has two reinforced plies of one of these two fabrics. In this example, the thickness of the external covering 304 is approximately 0.12″. In other examples, the thickness of the external covering 304 may be between 0.05″ and 0.25″.
[0026] The bulb seal 300 is attached to the panels 206 , 208 with a row of fasteners. In one example, the fasteners are spaced 1.875″ apart. In other examples, the fasteners are spaced between 1.5″ and 2″ apart. In other examples, the fasteners are spaced between 1″ and 3″ apart.
[0027] FIG. 4 is a cross-sectional view of a fastener 400 . The fastener 400 includes a seal retainer 402 , a nut plate retainer strip 404 , a nut plate 406 , and a bolt 408 . A slotted hole 410 is located in the seal 300 and the seal retainer 402 . While FIG. 4 depicts a typical slotted hole, other dimensions are suitable.
[0028] The seal retainer 402 provides support to the seal 300 as external pressures from the fuselage 110 deform the seal 300 . In one example, the seal retainer 402 is formed using one or more layers of carbon or carbon composite fabric. Preferably, the seal retainer 402 is formed from four plies of carbon composite fabric (e.g., BMS 8-256) having a thickness of approximately 0.034″. In other examples, the thickness of the seal retainer 402 may be between 0.02″ and 0.05″ or between 0.01″ and 0.1″. Additionally, in other examples, the seal retainer 402 may be formed using one or more layers of fiberglass fabric, such as 4-ply 181 fiberglass fabric, or other suitable materials.
[0029] The nut plate retainer strip 404 is located between the seal retainer 402 and the nut plate 406 . A bolt 408 attaches the seal retainer 402 to the panels 206 , 208 . The size of the bolt depends on the type of nut plate 406 selected. Preferably, the bolt is a 3/16″ bolt, but other bolt types may also be used. In one example, a 3/16″ titanium BACB30VF bolt is used in a BACN11G nut plate. The slotted holes 410 in the seal 300 and the seal retainer 402 allow the bolt 408 to slide left and right as the bolt 408 is installed. While a slotted hole is not necessary, it is easier to install the bolt 408 with this ability to adjust the location of the bolt 408 within the slotted holes 410 .
[0030] To attach the seal 300 to the panels 206 , 208 , an installer places an exterior surface of the attachment surface 302 adjacent to the inboard edges 112 , 114 of the panels 206 , 208 such that the seal 300 extends from the panels 206 , 208 and contacts the fuselage 110 . During installation, the seal 300 is compressed against the fuselage 210 . The amount of compression is based on the range of motion of the flight control surfaces 102 , 104 and the maximum width of the gap expected.
[0031] The installer positions the fastener 400 adjacent to an opposite side of the exterior of the attachment surface 302 aligning the slotted holes 410 in the seal 300 and the seal retainer 402 . The installer then positions the nut plate strip 404 and the nut plate 406 on the seal retainer 402 . The installer then installs bolts 408 through the nut plate 406 , the nut plate strip 404 , the seal retainer 402 , and the panels 206 , 208 .
[0032] While FIG. 4 depicts a particular fastener design, it is understood that other attachment mechanisms may be used. It is also understood that the fastener 400 may be modified to include more or less components. The fastener 400 may also use different materials and dimensions than described herein.
[0033] FIG. 4 also depicts how the seal 300 changes shape based on external pressures. As the seal 300 is pressed against the side of the fuselage 110 when the panels 206 , 208 move closer to the fuselage 110 , the seal 300 deforms as shown by the dotted deformation line 412 . For example, the diameter (d′) of the bulb from the exterior edges of the bulb may be reduced from 1.8″ to 1.5″. While this is only one example, it shows how the seal 300 is able to block the airflow between the fuselage 110 and the panels 206 , 208 as the gap size changes.
[0034] In addition to the contact pressure from the fuselage 110 , the seal 300 is also subjected to friction as it moves along the fuselage 110 . To reduce friction, a low friction coating may be applied to the fuselage 110 . For example, a polytetrafluoroethylene (PTFE) (i.e., Teflon®) coating or paint may be applied to the fuselage.
[0035] The seal 300 was flight tested on an on a Boeing 787-9 airplane. FIG. 5 depicts where the seal 210 a was attached to the trailing edge panel 206 a of the horizontal stabilizer 102 and the seal 210 c was attached to the elevator panel 208 of the elevator 104 . FIG. 6 depicts where the seal 210 b was attached to the trailing edge panel 206 b of the horizontal stabilizer 102 . Flight test data confirms that the seal 300 reduces aerodynamic drag. Test results showed that the seal 300 improved drag by an equivalent of 600 pounds of airplane weight. This improvement results in a more fuel efficient operation of the airplane.
[0036] While the seal was tested on a Boeing 787-9 airplane, the use of the seal 300 is not limited to any particular type of airplane. For example, the seal 300 may be used on private airplanes and military airplanes, e.g., tanker aircraft, in addition to commercial airplanes. Moreover, the seal 300 can be retrofitted onto older airplanes that are currently operating without the seal 300 .
[0037] While the seal 300 was described with respect to the horizontal stabilizer 102 and the elevators 104 , the seal 300 may be useful for reducing drag between a fixed structure of the airplane (e.g., the fuselage 110 , fixed wing portions) and other control surfaces. For example, the seal 300 may be attached to flight control surfaces associated with the wing (e.g., slats, flaps, spoilers, and ailerons) or the vertical stabilizer 106 (e.g., the rudder 108 ). As another example, the seal 300 may be useful for reducing drag between two control surfaces, such as between the horizontal stabilizer 102 and the elevators 104 .
[0038] By reducing aerodynamic drag through the use of the seal 300 , the airplane becomes more fuel efficient. Moreover, the fuel savings obtained from use of the seal 300 are much greater than the cost of adding the seal 300 to the airplane. As a result, the cost of operating the airplane and the impact to the environment is reduced.
[0039] It is intended that the foregoing detailed description be regarded as illustrative rather than limiting and that it is understood that the following claims including all equivalents are intended to define the scope of the invention. The claims should not be read as limited to the described order or elements unless stated to that effect. Therefore, all embodiments that come within the scope and spirit of the following claims and equivalents thereto are claimed as the invention. | A system and method for reducing aerodynamic drag is disclosed. A compression seal is attached to the inboard edges of the stabilizer and elevators of an airplane. The seal blocks airflow in a gap located between these inboard edges and a fuselage. The shape of the compression seal changes as the shape of the gap changes due to movement of the stabilizer and elevators during flight to effectively block airflow through the gap during flight. By blocking the airflow, the seal reduces the aerodynamic drag of the airplane. | 8 |
BACKGROUND OF THE INVENTION
The present invention relates to a miniature continuous magnetic tape loop cartridge suitable for use in compact devices such as point of sales displays, or spot announcements in super markets, or in stuffed animals, such as talking teddy bears.
It is known in the prior art to use continuous tape loops in eight track tape music cartridges and in modified cassette tape cartridges. The eight track is often too large for compact applications and the cassette models are often too complicated and unreliable when modified to play continuous tape loops.
In prior art cartridge attempts to miniaturize the cartridge tapes have often had a tendency to feed out of the cartridge. The tape loops are difficult to restore without disassembling and damaging the cartridge case.
Microchips have entered the market for short audio messages but cannot match the economy and convenience of on-the-spot recording of messages by erasing and reusing the same tape.
SUMMARY OF THE INVENTION
The present development for an improved miniature, endless tape cartridge, provides advanced features to avoid tape "feed out" and internal tape tangles. It also provides a means for fast and automatic loading, tape splicing and editing, after loading, without opening the cartridge.
For example, tape feed-out is limited by a stripper post at the pressure roller as the tape is moved forward into a "spill chamber".
Inner tape tangles are avoided by recessing the tape disk into the cartridge base so as be flush with the tape spill chambers. An additional guard against tape tangles is a plastic ring protruding from the cover into the cone top to prevent tape loops from working their way across the cone top. A tapered bearing seat on the tape disk provides a self seating action for smooth rotation to held avoid flutter and wow.
The cartridge provides a press fit on four corner posts for assembly and a self tapping screw through the base to the cover. This permits opening the cartridge without destroying the cover label recessed on the top. A "key-flange" is molded on one side of the cartridge to insure proper placement into the player. Finger grip notches are molded on the back edges that also serve for stacking cartridges on a rail for automatic players.
A top and bottom groove is provided at the front of the cartridge to receive a protective tape guard for shipping and storage. These grooves also serve for numerical storage in shelf racks designed with numbered storage cells. A ramp notch is provided at the outside edge of said grooves to serve as index notches to hold the cartridge into play position. The front cavity for a tape head is provided with a leaf-spring mounted felt pressure pad and a groove to hold a MU-METAL shield.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 and 2 are exploded views of the tape cartridge, according to the present invention;
FIG. 1 is a perspective view of the inside cartridge base;
FIG. 2 is a top view of the tape disk showing the relationship between the cartridge base and disk;
FIG. 3 is a perspective view of the cover inside showing the relationship to the disk and base;
FIG. 4 is a perspective view of a tape loading spindle which engages holes in the disk for the tape winding operation;
FIG. 5 is a perspective view of the disk when positioned upon the loading spindle and showing the tape loading spindle fingers in proper relationship to the disk cone;
FIG. 6 is a cross section of the assembled cartridge showing the relationship of the components and the assembly screw; and
FIG. 7 is a top view of the assembled cartridge showing, in phantom, the tape path and also showing the editing slot and a shipping shield.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The principal components and design of this tape cartridge invention are shown in FIGS. 1, 2 and 3 while the assembled views are shown in FIGS. 6 and 7.
Referring to FIG. 1, a cartridge base 1 has four corner tape guide posts 2 which also serve as press fit assembly posts when pressed into four cover index flanges 33 (see FIG. 3). When the cartridge is assembled, base flanges 3 (FIG. 1) and the cover flanges 33 are slightly over 150 mills apart to form a guide channel for 150 mill magnetic tape. A center post 4 on the cartridge base 1 mounts a tape disk 27 (FIG. 2). A tape disk cone 29 at the center of the tape disk 27 has a taper at the base of a hub 28 to conform to a taper 6 on the lower end of the post 4, to insure a smooth self-centering disk 27 rotation slightly above a bearing flange 5 defined in the center of the base 1. A hole 7 in the post 4 receives a center 35 depending from a cover 44 (FIG. 3). The center post 35 has a hole 34 to receive a self tapping screw 22 (FIG. 1) to firmly lock the assembled cartridge. This arrangement permits for opening the cartridge without defacing any label on the cover top (See FIG. 3).
Referring to FIGS. 1 and 7, "spill-chambers" 8 are provided to accommodate the natural irregularity of slack tape loops that form when the outer strand does not return to the mass as fast as the center strand emerges from adjacent the center disk cone 29.
Other design features to avoid tape tangles include a circular flange 9 in FIG. 1 that forms a guard rail slightly higher than the adjacent tape disk 27. This prevents the tape from winding under the disk 27. Also a guard rail 36 in the cover 44 (FIG. 3) protrudes downwardly into the cone 29. In the event of a tape loop feed out, in prior art continuous loop cartridges, there often was no convenient method to retrieve the loop for normal operation. Corrections in such prior art cartridges requires complete disassembly of the cartridge to rewind the tape. This is not a simple task and results in many discarded cartridges.
The present invention provides a solution. By placing the tip of a tooth pick or a paper clip in a rear cover slot 46 (See FIG. 7), the tape can be pulled outwardly through an editing window 21 (FIG. 1). The feed out loop at the front is thus pulled back into normal play position and the rear tape loop 47 feeds back into the mass at the tape periphery 50 (FIG. 7) when the cartridge is returned to "play".
The same operation of loop retrieval serves as a unique method to splice and edit a continuous loop without removal from the loaded cartridge. For example, a continuous loop is often used for a series of short messages with timing controlled by a short conductive or reflective tape applied at the desired intervals. These spot signals can be applied or removed by use of the editing or rear cover slot 46.
Still another feature to avoid "tape tangles" is shown in FIG. 1 where a stripper post 12 is mounted close to a pressure roller 10, at the point where the "peel-off" from the roller continues to flow into the front channel and around one of the posts 2 into the spill chamber 8. A recess slot 14 allows for proper alignment of the tape as it passes across a head recess chamber 13 (FIG. 1). The recess chamber 13 is provided with tape guide posts 17 and recess slots 15 for a "Mu-metal" shield and pressure pad assembly 24 shown in FIG. 7.
Referring to the inside cover view shown (FIG. 3), it can be seen that cover front flanges 30 extend downward so as to cover the entire front tape channel of the base when assembled. This simplifies the tape loading operation by gentle alignment of the tape into position with the front channel.
Index circular flanges 31, 33 and holes 32 in the cover 44 (FIG. 3) serve to engage their counterparts in the base 1 to maintain assembled alignment. The final assembly self tapping screw 22 (FIG. 1) can be removed without disturbing any top label on the cover of the cartridge.
Referring to FIGS. 4 and 5, holes 26 are provided in the tape disk 27 for automatic loading operations. One of the most costly and time consuming problems in standard tape loading is the tight binding of the starting tape strands around the center cone 29. To permit the tape to emerge freely from the mass, while in operation, there is provided a "free loop gap" at point 45, FIG. 7. The size of this "gap" varies in direct relation to the tape footage in the mass.
To perform the loading operation manually, in prior art devices, the center strand must be pulled firmly from the cone. This causes distortion of the emerging strand which must be cut away and discarded. This must then be followed by pulling on tape ends to establish the desired "free-loop" length and for final splicing.
To automatically perform the above costly operation, the present invention utilizes a tape loading jig spindle 38 (FIG. 4) which has a centering indexing shaft 39. A plurality of indexing fingers 41 extend upwardly and engage the tape disk holes 26. The fingers 41 come to rest just under the outer perimeter of cone 29 (FIG. 5). Upon removing the disk 27 from the loading spindle 38 (FIG. 4) the center strand 45 (See FIG. 7) can be removed freely without distorting the tape. The size of the tape gap left around the cone 29 determines the length of the "free-loop" after the ends are spliced. An assortment of loading spindles provides the desired "tape-gap" required for any given length of tape mass.
Loading spindles with removable or revolving oblong fingers also serve for the fine adjustments required to provide the proper "tape-gap" for any given size of tape footage on a given production run.
Referring to FIG. 7, a groove 48 is provided in parallel relationship on the top and bottom of the cartridge to provide a guide channel for the shipping and storage clip 34. The clip 34 is generally U-shaped. The groove 49 also serves as a manual retainer guide in a numbered storage rack, such as used in a broadcast station, to provide quick selection for spot announcements or music selections.
Additional selection is provided for automatic program retrieval by using "finger notches" 19 (FIG. 7) as a means for mounting cartridges between two parallel tracks. Preprogrammed selections can then be made for automatic handling.
Various modifications and revisions may be made to the above described embodiments without departing from the scope of the following claims. | A miniature continuous magnetic tape loop cartridge designed for heavy duty "fool proof" usage in message repeaters. It embodies a loading spindle for fast production loading, and spill chambers and a stripping post for protection against tape tangles and feed out. An editing slot is provided for tape loop retrieval, fast editing for tape messages and stop intervals. | 6 |
FIELD OF THE INVENTION
[0001] The disclosure relates to the optic transport network technology in the field of optical communication, and in particular to a method and a system for implementing automatic protection switching for transmission equipment.
BACKGROUND OF THE INVENTION
[0002] Optical Transport Network (OTN) is a transport network in the optical layer network based on Wavelength Division Multiplexing (WDM) technology. The OTN is a backbone network of the next generation, and it is a digital transport system and optical transport system of new generation regulated by recommendations of a series of InterNational Telegraph Union Telecommunication Standardization Sector (ITU-T), such as G.872, G.709 and G.798. OTN solves problems such as weak service scheduling capability, weak networking capability and weak protection capability regarding the transparent wavelength or sub-wavelength services of the traditional WDM network. OTN mainly defines an OTUk frame structure. By defining the OTUk frame structure, the user signal adaptation problem and the transparent wavelength or sub-wavelength services scheduling problem of the WDM network can be solved. Also, as the OTUk frame structure has plenty overhead, reliable transmission of the optical layer can be guaranteed, and the problems such as weak protection capability of the traditional WDM network are solved. Through the OTN technology, service scheduling can be achieved more flexibly, the reliability of transmission can be improved, the protection capability of network can be enhanced, and the network can be monitored.
[0003] Defined according to recommendations of ITU-T, Synchronous Digital Hierarchy (SDH) is a technical system formed by multiplexing method, mapping method and related synchronization method. The SDH is an information structure in which the corresponding level is provided for the transmission of digital signals at different speed. It can achieve various functions such as effective network management, real-time service monitoring, dynamic network maintenance and intercommunication between equipments from different manufacturers. It greatly improves the utilization of network resources, reduces the management and maintenance expenses, and achieves flexible, reliable and highly efficient network operation and maintenance. Therefore, nowadays the SDH becomes a development and application hotspot of the transmission technology of the information field in the world, and attracts extensive attention. In the related optical communication technologies, network protection switching is executed based on SDH, but there is no method supporting protection switching in OTN.
SUMMARY OF THE INVENTION
[0004] Therefore, the main purpose of the disclosure is to provide a method and a system for implementing automatic protection switching for transmission equipment, to implement automatic protection switching for transmission equipment in OTN.
[0005] To achieve the above purpose, the technical solutions of the disclosure are implemented as follows.
[0006] The disclosure provides a method for implementing automatic protection switching for transmission equipment, comprising:
[0007] a control sub-card determining to execute protection switching according to a received automatic protection switching trigger condition and received information of each line sub-card which are transferred by a cross sub-card via Time Division Multiplexing Fabric to Framer Interface (TFI5) frames, and sending a protection switching command to the cross sub-card; and
[0008] the cross sub-card completing the protection switching action.
[0009] In the method, before determining to execute protection switching, the method further comprises:
[0010] reporting the information of the each line sub-card to the control sub-card.
[0011] In the method, the automatic protection switching trigger condition is transferred to the control sub-card by the cross sub-card via fixed overhead locations of a TFI5 frame.
[0012] In the method, before reporting information of each line sub-card to the control sub-card, the method further comprises:
[0013] a user setting the automatic protection switching trigger condition in the each line sub-card according to the state of a signal received at a line side and configuration of a Optical Transport Network (OTN).
[0014] In the method, setting the automatic protection switching trigger condition comprises:
[0015] setting the automatic protection switching trigger condition by means of writing a program via a software interface according to a fiber interface alarm or an Optical Data Unit k (ODUk) service alarm.
[0016] In the method, the method further comprises:
[0017] according to the received automatic protection switching trigger condition and received information of the each line sub-card, the control sub-card determining that a line sub-card has an abnormity but protection switching is not to be executed, and prompting that the line sub-card has an abnormity.
[0018] In the method, the control sub-card determining to execute protection switching according to the received automatic protection switching trigger condition and the received information of the each line sub-card comprises:
[0019] the control sub-card judging whether the each line sub-card has any abnormity according to information reported by the each line sub-card, and if a line sub-card has an abnormity, executing protection switching when the abnormity on the line sub-card is consistent with the automatic protection switching trigger condition set on the line sub-card.
[0020] The disclosure also provides a system for implementing automatic protection switching for transmission equipment, comprising:
[0021] a plurality of line sub-cards, configured to report an automatic protection switching trigger condition and information of the plurality of line sub-cards to a control sub-card by a cross sub-card via Time Division Multiplexing Fabric to Framer Interface (TFI5) frames;
[0022] the cross sub-card, configured to transfer the automatic protection switching trigger condition and the information of the plurality of line sub-cards to a control sub-card, receive a protection switching command sent by the control sub-card, and complete the protection switching action; and
[0023] the control sub-card, configured to determine to execute protection switching according to the received automatic protection switching trigger condition and the received information of the plurality of line sub-cards which are transmitted by the cross sub-card via the TFI5 frames, and send the protection switching command to the cross sub-card.
[0024] In the system, each of the plurality of line sub-cards further comprises:
[0025] a setting module, configured to set the automatic protection switching trigger condition and send the automatic protection switching trigger condition to a TFI5 frame module; and
[0026] the TFI5 frame module, configured to define the fixed overhead locations of the TFI5 frames, insert the automatic protection switching trigger condition into the fixed overhead locations of a TFI5 frame, and transfer the automatic protection switching trigger condition and the information of the plurality of line sub-cards to the cross sub-card.
[0027] According to the method and the system for implementing automatic protection switching for transmission equipment in the disclosure, the control sub-card can automatically judge whether protection switching is needed. When the protection switching is needed, the control sub-card sends a command and the cross sub-card switches the line sub-card. Thus, when the transmission equipment has any abnormity, the automatic protection switching for transmission equipment in OTN can be implemented conveniently to ensure that the transmission service will not be interrupted. In the disclosure, the fixed overhead locations of the TFI5 frame are also defined. The user can set the automatic protection switching trigger condition by writing a program via the software interface. Therefore the solution of the disclosure has great flexibility, and the implementation of the solution is simple and reliable.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 is a flow chart of a method for implementing automatic protection switching for transmission equipment according to the disclosure; and
[0029] FIG. 2 is a structure diagram of a system for implementing automatic protection switching for transmission equipment according to the disclosure.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0030] The disclosure proposes a method for implementing automatic protection switching for transmission equipment in OTN. The basic concept of the disclosure is that: a control sub-card determines to execute protection switching according to a received automatic protection switching trigger condition and information of each line sub-card, and sends a protection switching command to the cross sub-card; and the cross sub-card completes the protection switching action.
[0031] The disclosure will be described below in detail with reference to drawings and specific embodiments.
[0032] In the embodiments of the disclosure, the transmission equipment includes: a plurality of line sub-cards, a cross sub-card and a control sub-card, wherein the plurality of line sub-cards are configured to transmit services, and the cross sub-card is configured to transfer information of the plurality of line sub-cards to the control sub-card.
[0033] FIG. 1 is a flow chart of a method for implementing automatic protection switching for transmission equipment according to the disclosure. As shown in FIG. 1 , the method comprises the following steps.
[0034] Step 101 : setting the automatic protection switching trigger condition. Specifically, the user can set the automatic protection switching trigger condition on the setting module of each line sub-card according to the state of signals received at the line side and the configuration of the OTN. The automatic protection switching trigger conditions can be classified into two types. One is the protection switching trigger condition generated according to an alarm from a fiber interface, such as Lose of Signal (LOS), Signal Fail (SF) and Signal Degraded (SD) or the like from an Optical Transform Unit (OTU) fiber interface in OTN. The other type is the protection switching trigger condition generated according to an ODUk service alarm, such as Lose of Frame (LOF), Lose of Multiplex Frame (LOM) or the like.
[0035] The user can set an automatic protection switching trigger condition by writing a program via the software interface.
[0036] Step 102 : transferring the automatic protection switching trigger condition to the control sub-card by the cross sub-card via a TFI5 frame.
[0037] Specifically, line sub-card inserts the automatic protection switching trigger condition into fixed overhead locations of TFI5 frame. Insertion method may be: loading information carrying the automatic protection switching trigger condition into bit information of TFI5 frame. TFI5 refers to implementation agreement from Time Division Multiplex and Multiplexer (TDM) bus matrix to framer interface, and is used for defining data exchange of interface between the TDM cross matrix and the TDM framer, as shown in Table 1:
[0000]
TABLE 1
17 . . .
21 . . .
25 . . .
29 . . .
33 . . .
20
24
28
32
48
49 . . .
144
1
A1
A1
A2
2
Fiber
inter-
face
SD/SF
3
ODUk
SD/SF
4
5
6
7
8
9
[0038] Table 1 shows all overhead locations in the TFI frame. The fixed overhead locations of the TFI5 frame are the overhead locations that are not used in all overhead locations in the TFI5 frame. For instance, the 17th column to the 20th column in the 2nd line or the 17th column to the 32nd column in the 3rd line can be used as the fixed overhead locations of the TFI5 frame. The fixed overhead locations of the TFI5 frame are used for transferring the automatic protection switching trigger condition to the cross sub-card. The cross sub-card transfers the automatic protection switching trigger condition to the control sub-card. And the control sub-card extracts the automatic protection switching trigger condition from the fixed overhead locations of the received TFI5 frame and saves it.
[0039] Step 103 : reporting information of each line sub-card to the control sub-card.
[0040] Specifically, each line sub-card periodically inserts information of the line sub-card to the fixed overhead locations of the TFI5 frame. Information of each line sub-card is transferred to the cross sub-card via the TFI5 frame and then transferred to the control sub-card by the cross sub-card. The control sub-card receives and saves information of each line sub-card. The information is the line state of each line sub-card, such as the strength of signals in the line and the transfer state of the frame or the like. If the report period is the period of the TFI5 frame and the frequency is 2.5 GHZ, the period is 1/2.5 GHZ. As the report period is extremely short, the line sub-card reports information of the line sub-card substantially in real-time.
[0041] Step 104 : The control sub-card judges whether to execute protection switching; and if no, execute Step 105 ; if yes, execute Step 106 .
[0042] Specifically, the control sub-card judges whether each line sub-card has any abnormity according to the information reported by each line sub-card. If a line sub-card has an abnormity, the control sub-card judges whether the abnormity on the line sub-card is consistent with the automatic protection switching trigger condition set on the line sub-card, for example whether there is any phenomenon of the automatic protection switching trigger condition LOS, LOF or LOM on the line sub-card. If it is not consistent, protection switching will not be executed and Step 105 is to be executed; and if it is consistent, protection switching will be executed and Step 106 is executed. If there is no abnormity, no action will be performed.
[0043] Step 105 : The control sub-card prompts that the line sub-card has an abnormity.
[0044] Specifically, the control sub-card prompts the user that the line sub-card has an abnormity. The prompting manner may be that: the control sub-card writes a historic document via software. Such manner is helpful to save information related to the abnormity in the line sub-card for future enquiry. And the prompting manner also may be prompt by material objects, such as indicator light, sound or the like.
[0045] Step 106 : The control sub-card sends a protection switching command to the cross sub-card.
[0046] Step 107 : The cross sub-card completes the protection switching action. Specifically, after receiving the protection switching command sent by the control sub-card, the cross sub-card switches services transferred on the abnormal line sub-card to a line sub-card selected by the control sub-card from spare line sub-cards on which abnormity is never happened. The control sub-card selects one line sub-card from spare line sub-cards on which abnormity is never happened, to transfer services according to the information reported by each line sub-card and the state of the links between transmission equipment. And the cross sub-card completes the protection switching action. The control sub-card can obtain the state of the links between transmission equipment by receiving information of the line sub-card transferred by each line sub-card. If the abnormal line sub-card is recovered, services are still transferred on the original line sub-card, and no switching is executed. The recovered line sub-card may serve as a spare line sub-card when other line sub-cards have an abnormity.
[0047] To implement the above method, the disclosure also provides a system for implementing automatic protection switching for transmission equipment. As shown in FIG. 2 , the system comprises: a line sub-card 21 , a cross sub-card 22 and a control sub-card 23 , wherein
[0048] the line sub-card 21 is configured to report an automatic protection switching trigger condition and information of the line sub-card to the control sub-card 23 by the cross sub-card 22 via TFI5 frames, wherein there may be a plurality of line sub-cards;
[0049] the cross sub-card 22 is configured to transfer the automatic protection switching trigger condition and information of the line sub-card to the control sub-card, receive a protection switching command sent by the control sub-card 23 , and complete the protection switching action; and
[0050] the control sub-card 23 is configured to determine to execute protection switching according to the received automatic protection switching trigger condition and the received information of the line sub-card, which are transmitted by the cross sub-card via the TFI5 frames, and send the protection switching command to the cross sub-card 22 .
[0051] The line sub-card 21 further comprises:
[0052] a setting module 211 , configured to set the automatic protection switching trigger condition and send the automatic protection switching trigger condition to a TFI5 frame module 212 ; and
[0053] the TFI5 frame module 212 , configured to define the fixed overhead locations of the TFI5 frames, insert the automatic protection switching trigger condition into the fixed overhead locations of a TFI5 frame, and transfer the automatic protection switching trigger condition and the information of the line sub-card to the cross sub-card.
[0054] The cross sub-card 22 is further configured to receive the automatic protection switching trigger condition and the information of the line sub-card sent by the TFI5 frame module 212 in the line sub-card 21 , and send the same to the control sub-card 23 .
[0055] The control sub-card 23 is further configured to determine that a line sub-card has an abnormity and protection switching is not to be executed, according to the received automatic protection switching trigger condition and the received information of each line sub-card, and prompt that the line sub-card has an abnormity. Specifically, the control sub-card extracts the automatic protection switching trigger condition from the fixed overhead locations of the received TF15 frame and saves it.
[0056] The automatic protection switching trigger condition is transferred to the control sub-card 23 by the cross sub-card 22 via the fixed overhead locations of a TF15 frame.
[0057] The step that the setting module 211 sets the automatic protection switching trigger condition comprises: according to a fiber interface alarm or an ODUk service alarm, setting the automatic protection switching trigger condition by means of writing a program via a software interface.
[0058] The step that the control sub-card 23 determines to execute protection switching according to the received automatic protection switching trigger condition and the received information of each line sub-card comprises: the control sub-card 23 judging whether each line sub-card has any abnormity according to the information reported by each line sub-card; and if there is some abnormity on a line sub-card, executing protection switching when the abnormity on the line sub-card is consistent with the automatic protection switching trigger condition set on the line sub-card.
[0059] The above contents are only preferred embodiments of the disclosure and are not intended for limiting the disclosure. Any modifications, equivalent replacements and improvements within the spirit and principle of the disclosure should be within the protection scope of the disclosure. | A method for realizing an automatic protection switching of a transmission device is provided, and the method includes that: according to a received automatic protection switching trigger condition and information of each line sub-card, which are transmitted by a cross sub-card via a Time Division Multiplexing Fabric to Framer Interface (TFI5) frame, a control sub-card determines to execute protection switching, and sends a protection switching command to the cross sub-card; and the cross sub-card completes the protection switching action. A system for realizing an automatic protection switching of a transmission device is also provided. According to the technical solution of the present invention, the automatic protection switching of the transmission device in an Optical Transport Network (OTN) is achieved conveniently. | 7 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation-in-Part Application of U.S. Non-Provisional application Ser. No. 13/096,221, filed Apr. 28, 2011, which is incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
[0002] This invention pertains to betaine esters and processes for the preparation and use thereof.
BACKGROUND OF THE INVENTION
[0003] There is an increasing industrial and societal need for the preparation of ingredients that reduce or eliminate organic solvents and irritants, employ reagents that are themselves biocompatible and that optimally use starting materials derived from a natural source or are “nature-equivalent.” This is of urgent interest in consumer-facing industries such as personal and household care. One class of materials that might be approached in a “greener” manner is surfactants. In particular, there is a need for new betaines that are made in a more environmentally-friendly manner. Betaines are zwitterionic surfactants used in the personal care, household care, and other industries. They are classified as specialty co-surfactants that complement the performance of the primary surfactants. These co-surfactants also increase the mildness of the formulation by reducing irritation associated with purely ionic surfactants.
[0004] Betaines are commonly produced by a multi-step process based on coconut or palm kernel oil. For example, one process for the preparation of a prototypical betaine, fatty acid amidopropyl betaine, involves the amidation of fatty acids with 3-dimethylaminopropylamine (DMAPA) at high temperatures (150-175° C.). The intermediate fatty aminoamide is then reacted with sodium chloroacetate to afford the final product. The amidation requires high temperatures for conversion and distillation to remove unreacted starting materials. These high reaction temperatures can generate by-products and impart color to the products, requiring additional steps to remove the by-products and the color. DMAPA is also a known sensitizer and is found in trace quantities in the final formulation. Thus, betaines prepared under mild conditions without the use of DMAPA would be of great interest.
[0005] It would be highly desirable for the production of the betaines to occur under mild conditions and in high yield. Such a process would take place at lower temperatures, with fewer processing steps and by-products and it would lessen environmental impacts. These objectives can be met, for example, by the transesterification process disclosed below, beginning with the first step of converting the fatty acid to its methyl ester. It would further be highly desirable for the production of the betaines to occur directly from the fatty acids, avoiding a process step and eliminating the use of an alcohol such as methanol and its required recycle.
BRIEF SUMMARY OF THE INVENTION
[0006] A first embodiment of the present invention concerns a compound represented by the general formula 1:
[0000]
[0007] wherein R is selected from the group consisting of C 5 -C 17 alkyl and mixtures thereof;
[0008] R 1 is methyl and R 2 is selected from the group consisting of C 1 -C 5 alkyl; and
[0009] A is selected from the group consisting of C 3 -C 10 alkylene and C 3 -C 10 alkenylene.
[0010] Another embodiment concerns a surfactant comprising the compound described above.
[0011] Yet another embodiment concerns a formulated product comprising the compound described above.
[0012] Still another embodiment concerns a transesterification process for the preparation of betaine, represented by the general formula 1,
[0000]
[0000] comprising:
a) producing an ester of formula 2:
[0000]
wherein R is selected from the group consisting of C 5 -C 17 alkyl, C 5 -C 17 alkenyl, C 5 -C 17 dienyl, C 5 -C 17 trienyl, and mixtures thereof, and
[0015] R 6 is selected from the group consisting of C 1 -C 6 alkyl;
b) reacting a dialkylamino alcohol 3:
[0000]
[0000] with ester 2 in the presence of an enzyme to form an intermediate 4:
[0000]
wherein R 1 is methyl and R 2 is selected from the group consisting of C 1 -C 5 alkyl;
A is selected from the group consisting of C 3 -C 10 alkylene and C 3 -C 10 alkenylene, and
c) reacting intermediate 4 with sodium chloroacetate to produce a betaine.
[0020] Still another embodiment concerns a direct esterification process for the preparation of betaine, represented by the general formula 1,
[0000]
[0000] comprising:
a) reacting a carboxylic acid
[0000]
wherein R selected from the group consisting of C 5 -C 17 alkyl, C 5 -C 17 alkenyl, C 5 -C 17 dienyl, C 5 -C 17 trienyl, and mixtures thereof, and R 6 is a C 1 -C 6 alkyl;
with a dialkylamino alcohol 3:
[0000]
[0000] in the presence of an enzyme to form an intermediate 4:
[0000]
wherein R 1 is methyl and R 2 is selected from the group consisting of C 1 -C 5 alkyl;
A is selected from the group consisting of C 3 -C 10 alkylene and C 3 -C 10 alkenylene; and
b) reacting intermediate 4 with sodium chloroacetate to produce a betaine.
DETAILED DESCRIPTION
[0026] The present invention comprises a series of betaine compounds represented by the general formula 1:
[0000]
[0000] wherein R is selected from substituted and unsubstituted, branched- and straight-chain, saturated, unsaturated, and polyunsaturated C 1 -C 22 hydrocarbyl, substituted and unsubstituted C 3 -C 8 cycloalkyl, substituted and unsubstituted C 6 -C 20 carbocyclic aryl, and substituted and unsubstituted C 4 -C 20 heterocyclic wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen, or mixtures thereof, and R 1 and R 2 may be the same or may be independently chosen from substituted or unsubstituted straight- or branched-chain C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 4 -C 6 dienyl, and C 3 -C 8 cycloalkyl groups wherein the branching and/or substitution of R 1 and R 2 may connect to form a ring, and A is selected from substituted and unsubstituted, branched- and straight-chain, saturated, unsaturated, and polyunsaturated C 1 -C 10 divalent hydrocarbyl, substituted and unsubstituted C 3 -C 8 cycloalkylene, substituted and unsubstituted C 6 -C 10 carbocyclic arylene, and substituted and unsubstituted C 4 -C 10 divalent heterocyclic wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen.
[0027] According to an embodiment, the betaine compounds are denoted by structure 1 wherein R is selected from substituted and unsubstituted, branched- and straight-chain saturated C 1 -C 22 , C 5 -C 17 , C 9 -C 17 , and C 5 -C 18 alkyl, substituted and unsubstituted, branched- and straight-chain C 2 -C 22 , C 5 -C 17 , C 9 -C 17 , and C 5 -C 18 alkenyl, substituted and unsubstituted, branched- and straight-chain C 4 -C 22 , C 5 -C 17 , C 9 -C 17 , and C 5 -C 18 dienyl, substituted and unsubstituted, branched- and straight-chain C 6 -C 22 , C 5 -C 17 , C 9 -C 17 , and C 5 -C 18 trienyl, substituted and unsubstituted C 3 -C 8 cycloalkyl, substituted and unsubstituted C 6 -C 20 carbocyclic aryl, substituted and unsubstituted C 4 -C 20 heteroaryl, R 1 and R 2 are selected from straight or branched chain C 1 -C 6 and C 1 -C 5 alkyl, C 2 -C 6 alkenyl or C 4 -C 6 dienyl, and A is selected from branched and straight chain C 1 -C 8 , C 3 -C 10 , and C 3 -C 8 , alkylene, branched- and straight-chain C 2 -C 8 , C 3 -C 10 , and C 3 -C 8 alkenylene, substituted and unsubstituted C 3 -C 8 cycloalkylene, substituted and unsubstituted C 6 -C 10 carbocyclic arylene, substituted and unsubstituted C 4 -C 12 divalent heterocyclic, or mixtures thereof.
[0028] The saturated, unsaturated, and polyunsaturated alkyl groups which may be represented by R may be straight- or branched-chain hydrocarbon radicals containing up to about 22 carbon atoms and may be substituted, for example, with one to five groups selected from C 1 -C 6 -alkoxy, carboxyl, amino, C 2 -C 16 aminocarbonyl, C 2 -C 16 amido, cyano, C 2 -C 7 -alkoxycarbonyl, C 2 -C 7 -alkanoyloxy, hydroxy, aryl, heteroaryl, thiol, thioether, C 2 -C 10 dialkylamino, C 3 -C 15 trialkylammonium and halogen. The terms “C 1 -C 6 -alkoxy”, “C 2 -C 7 -alkoxycarbonyl”, and “C 2 -C 7 -alkanoyloxy” are used to denote radicals corresponding to the structures —OR 3 , —CO 2 R 3 , and —OCOR 3 , respectively, wherein R 3 is C 1 -C 6 -alkyl or substituted C 1 -C 6 -alkyl. The terms “C 2 -C 16 aminocarbonyl” and “C 2 -C 16 amido” are used to denote radicals corresponding to the structures —NHCOR 4 , —CONHR 4 , respectively, wherein R 4 is C 1 -C 15 -alkyl or substituted C 1 -C 15 -alkyl. The term “C 3 -C 8 -cycloalkyl” is used to denote a saturated, carbocyclic hydrocarbon radical having three to eight carbon atoms.
[0029] The alkyl, alkenyl and dienyl groups which may be represented by R 1 and R 2 may be straight- or branched-chain hydrocarbon radicals containing up to about 6 carbon atoms and may be substituted, for example, with one to three groups selected from C 1 -C 6 -alkoxy, carboxyl, amino, C 2 -C 16 aminocarbonyl, C 2 -C 16 amido, cyano, C 2 -C 7 -alkoxycarbonyl, C 2 -C 7 -alkanoyloxy, hydroxy, aryl, heteroaryl, thiol, thioether, C 2 -C 10 dialkylamino, C 3 -C 15 trialkylammonium and halogen. The terms “C 1 -C 6 -alkoxy”, “C 2 -C 7 -alkoxycarbonyl”, and “C 2 -C 7 -alkanoyloxy” are used to denote radicals corresponding to the structures —OR 3 , —CO 2 R 3 , and —OCOR 3 , respectively, wherein R 3 is C 1 -C 6 -alkyl or substituted C 1 -C 6 -alkyl. The terms “C 2 -C 16 aminocarbonyl” and “C 2 -C 16 amido” are used to denote radicals corresponding to the structures —NHCOR 4 , —CONHR 4 , respectively, wherein R 4 is C 1 -C 15 -alkyl or substituted C 1 -C 15 -alkyl. The term “C 3 -C 8 -cycloalkyl” is used to denote a saturated, carbocyclic hydrocarbon radical having three to eight carbon atoms.
[0030] The divalent hydrocarbyl radicals which may be represented by A may be straight- or branched-chain saturated, unsaturated, and polyunsaturated alkylene and cycloalkylene groups containing up to about 10 carbon atoms and may be substituted, for example, with one to five groups selected from C 1 -C 6 -alkoxy, carboxyl, amino, C 2 -C 16 aminocarbonyl, C 2 -C 16 amido, cyano, C 2 -C 7 -alkoxycarbonyl, C 2 -C 7 -alkanoyloxy, hydroxy, aryl, heteroaryl, thiol, thioether, C 2 -C 10 dialkylamino, C 3 -C 15 trialkylammonium and halogen. The terms “C 1 -C 6 -alkoxy”, “C 2 -C 7 -alkoxycarbonyl”, and “C 2 -C 7 -alkanoyloxy” are used to denote radicals corresponding to the structures —OR 3 , —CO 2 R 3 , and —OCOR 3 , respectively, wherein R 3 is C 1 -C 6 -alkyl or substituted C 1 -C 6 -alkyl. The terms “C 2 -C 16 aminocarbonyl” and “C 2 -C 16 amido” are used to denote radicals corresponding to the structures —NHCOR 4 , —CONHR 4 , respectively, wherein R 4 is C 1 -C 15 -alkyl or substituted C 1 -C 15 -alkyl.
[0031] The aryl groups which R may represent (or any aryl substituents) may include phenyl, naphthyl, or anthracenyl and phenyl, naphthyl, or anthracenyl substituted with one to five substituents selected from C 1 -C 6 -alkyl, substituted C 1 -C 6 -alkyl, C 6 -C 10 aryl, substituted C 6 -C 10 aryl, C 1 -C 6 -alkoxy, halogen, carboxy, cyano, C 2 -C 7 -alkanoyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfonyl, trifluoromethyl, hydroxy, C 2 -C 7 -alkoxycarbonyl, C 2 -C 7 -alkanoylamino and —OR 5 , —S—R 5 , —SO 2 —R 5 , —NHSO 2 R 5 and —NHCO 2 R 5 , wherein R 5 is phenyl, naphthyl, or phenyl or naphthyl substituted with one to three groups selected from C 1 -C 6 -alkyl, C 6 -C 10 aryl, C 1 -C 6 -alkoxy and halogen.
[0032] The arylene groups which A may represent may include phenylene, naphthylene, or anthracenylene and phenylene, naphthylene, or anthracenylene substituted with one to five substituents selected from C 1 -C 6 -alkyl, substituted C 1 -C 6 -alkyl, C 6 -C 10 aryl, substituted C 6 -C 10 aryl, C 1 -C 6 -alkoxy, halogen, carboxy, cyano, C 2 -C 7 -alkanoyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfonyl, trifluoromethyl, hydroxy, C 2 -C 7 -alkoxycarbonyl, C 2 -C 7 -alkanoylamino and —OR 5 , —S—R 5 , —SO 2 —R 5 , —NHSO 2 R 5 and —NHCO 2 R 5 , wherein R 5 is phenyl, naphthyl, or phenyl or naphthyl substituted with one to three groups selected from C 1 -C 6 -alkyl, C 6 -C 10 aryl, C 1 -C 6 -alkoxy and halogen.
[0033] The heterocyclic groups which R may represent (or any heteroaryl substituents) include 5- or 6-membered ring containing one to three heteroatoms selected from oxygen, sulfur and nitrogen. Examples of such heterocyclic groups are pyranyl, oxopyranyl, dihydropyranyl, oxodihydropyranyl, tetrahydropyranyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, pyridyl, pyrimidyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl and the like. The heterocyclic radicals may be substituted, for example, with up to three groups such as C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, substituted C 1 -C 6 -alkyl, halogen, C 1 -C 6 -alkylthio, aryl, arylthio, aryloxy, C 2 -C 7 -alkoxycarbonyl and C 2 -C 7 -alkanoylamino. The heterocyclic radicals also may be substituted with a fused ring system, e.g., a benzo or naphtho residue, which may be unsubstituted or substituted, for example, with up to three of the groups set forth in the preceding sentence.
[0034] The divalent heterocyclic groups which A may represent include 5- or 6-membered ring containing one to three heteroatoms selected from oxygen, sulfur and nitrogen. Examples of such heterocyclic groups are pyranyl, oxopyranyl, dihydropyranyl, oxodihydropyranyl, tetrahydropyranyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, pyridyl, pyrimidyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl and the like. The heterocyclic radicals may be substituted, for example, with up to three groups such as C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, substituted C 1 -C 6 -alkyl, halogen, C 1 -C 6 -alkylthio, aryl, arylthio, aryloxy, C 2 -C 7 -alkoxycarbonyl and C 2 -C 7 -alkanoylamino. The heterocyclic radicals also may be substituted with a fused ring system, e.g., a benzo or naphtho residue, which may be unsubstituted or substituted, for example, with up to three of the groups set forth in the preceding sentence.
[0035] The term “halogen” is used to include fluorine, chlorine, bromine, and iodine.
[0036] Examples of the compounds of the invention include those represented by formula 1 wherein R is a mixture of C 5 to C 17 hydrocarbyl radicals (derived from coconut oil), R 1 and R 2 are methyl and A is 1,3-propylene. In another aspect R is a mixture of C 9 to C 17 hydrocarbyl radicals (derived from stripped coconut oil), R 1 and R 2 are methyl and A is 1,3-propylene
[0037] In an embodiment, the compound of the invention includes a compound represented by the general formula 1 wherein R is selected from the group consisting of C 5 -C 17 alkyl and mixtures thereof; R 1 is methyl and R 2 is selected from the group consisting of C 1 -C 5 alkyl; and A is selected from the group consisting of C 3 -C 10 alkylene and C 3 -C 10 alkenylene. In one aspect A is selected from the group consisting of C 3 -C 8 alkylene and C 3 -C 8 alkenylene. In one aspect R 2 is methyl. In yet another aspect, R is selected from the group consisting of C 5 -C 17 alkyl and mixtures thereof, R 2 is methyl, and A is 1,3-propylene.
[0038] Specific examples of our inventive compound include 3-dimethylaminopropyl hydrogenated cocoate (R is a mixture of C 5 -C 17 ) betaine, 3-dimethylaminopropyl hydrogenated stripped cocoate (R is a mixture of C 9 -C 17 ) betaine, 3-dimethylaminopropyl laurate betaine, 3-dimethylaminopropyl myristate betaine, and 3-dimethylaminopropyl palmitate betaine.
[0039] Another embodiment concerns a transesterification process for the preparation of betaines represented by general formula 1. The first step of the transesterification process is the production of esters of the general formula 2:
[0000]
[0000] wherein R is defined above and R 6 may be C 1 -C 6 straight or branched chain alkyl.
[0040] Short chain esters 2 can be produced by any practical method, including the solvolysis of non-hydrogenated or hydrogenated triglycerides in the presence of a lower alcohol and a base, acid or enzyme catalyst as is known in the art. Examples of lower alcohols include C 1 -C 4 alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, and isobutanol. The short-chain esters 2 may contain from 0-20% of residual lower alcohol.
[0041] The second step of the transesterification process comprises the enzymatic reaction of a dialkylamino alcohol 3:
[0000]
[0000] with ester 2 in the presence of an enzyme with or without methods for the removal of the alcohol by-product to form the desired intermediate 4, wherein R, R 1 , R 2 and A are defined above.
[0000]
[0042] In one aspect of the transesterification process, R is selected from C 5 -C 17 alkyl, C 5 -C 17 alkenyl, C 5 -C 17 dienyl, C 5 -C 17 trienyl, and mixtures thereof; R 6 is a C 1 -C 6 alkyl; R 1 is methyl and R 2 is selected from the group consisting of C 1 -C 5 alkyl; and A is selected from C 3 -C 10 alkylene and C 3 -C 10 alkenylene. In another aspect, R is selected from C 5 -C 17 alkyl and mixtures thereof; R 1 is methyl and R 2 is selected from C 1 -C 5 alkyl, and A is selected from C 3 -C 8 alkylene and C 3 -C 8 alkenylene. In another aspect, the lower alcohol is a C 1 -C 4 alcohol, R 2 is methyl, and A is selected from C 3 -C 8 alkylene and C 3 -C 8 alkenylene. In yet another aspect, the lower alcohol is selected from methanol, ethanol, 1-propanol, and 2-propanol, and A is 1,3-propylene.
[0043] The second step of the transesterification process is carried out without solvent or in an inert solvent chosen from cyclic or acyclic ether solvents such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, or tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, or xylene, aliphatic or alicyclic saturated or unsaturated hydrocarbons such as hexane, heptane, cyclohexane, or limonene, halogenated hydrocarbons such as dichloromethane, dichloroethane, dibromoethane, tetrachloroethylene, or chlorobenzene, polar aprotic solvents such as acetonitrile, dimethyl formamide, or dimethyl sulfoxide, or mixtures thereof. In one aspect, no solvent is used. In another aspect, heptane is used as the solvent. In one aspect, the solvent forms an azeotrope with the C 1 -C 4 alcohol facilitating removal of the alcohol from the reaction mixture and driving the reaction to higher conversions.
[0044] The second step of the transesterification process may be carried out at a temperature from about −100° C. to about the boiling point of the solvent, from about 20 to about 80° C., or from about 50 to about 70° C. The amount of alcohol 3 may be from about 0.85 to about 20 equivalents based on the ester 2, or can be from about 1 to about 10 equivalents, or even from about 1 to about 1.5 equivalents. The use of short chain alcohol esters of carboxylic acids is beneficial to the success of the enzymatic esterification of the amino alcohol.
[0045] The enzyme used in the second step of the transesterification process is chosen from a protease, a lipase, or an esterase. Moreover, lipases may be in the form of whole cells, isolated native enzymes, or immobilized on supports. Examples of these lipases include but are not limited to Lipase PS (from Pseudomonas sp), Lipase PS-C (from Psuedomonas sp immobilized on ceramic), Lipase PS-D (from Pseudomonas sp immobilized on diatomaceous earth), Lipoprime 50T, Lipozyme TL IM, Novozym 435 ( Candida antarctica lipase B immobilized on acrylic resin) or Candida antarctica lipase B immobilized on a porous fluoropolymer support as described in US Patent Pub. 20120040395.
[0046] Removal of the alcohol byproducts can be done chemically via an alcohol absorbent (e.g., molecular sieves) or by physical removal of the alcohol. According to an embodiment, this by-product removal can be done by evaporation, either by purging the reaction mixture with an inert gas such as nitrogen, argon, or helium, or by performing the reaction at reduced pressures, or both, as these conditions can afford >98% conversion of ester 2 to intermediate 4. According to an embodiment, pressure for the reaction is from about 1 torr to about ambient pressure, or from about 50 torr to about ambient pressure. Any organic solvent that is included in this process may or may not be removed along with the alcohol. In one aspect, the organic solvent also functions to assist in removal of the alcohol byproduct by azeotropic distillation. Examples of dialkylamino alcohol 3 include dimethylaminoethanol and dimethylaminopropanol.
[0047] The third step of the transesterification process to generate the final product 1 comprises the reaction of intermediate 4 with sodium chloroacetate. The third step of the transesterification process can be carried out without solvent or in an inert solvent chosen from water, cyclic or acyclic alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, ethylene glycol, 1,2-propanediol, or 1,3-propanediol, cyclic or acyclic ether solvents such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, or tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, or xylene, aliphatic or alicyclic saturated or unsaturated hydrocarbons such as hexane, heptane, cyclohexane, or limonene, halogenated hydrocarbons such as dichloromethane, dichloroethane, dibromoethane, tetrachloroethylene, or chlorobenzene, polar aprotic solvents such as acetonitrile, dimethyl formamide, or dimethyl sulfoxide, or mixtures thereof.
[0048] The third step of transesterfication process may be carried out at a temperature of from about −100° C. to about the boiling point of the solvent, from about 25 to about 150° C., or from about 50 to about 100° C. The amount of sodium chloroacetate may be from about 0.75 to about 20 equivalents based on the amount of intermediate 4, from about 1 to about 10 equivalents, or from about 1 to about 1.5 equivalents. If included, a base is chosen from metal hydroxides, metal carbonates, or metal bicarbonates. According to an embodiment, bases can be sodium hydroxide, potassium hydroxide, sodium bicarbonate, and potassium bicarbonate. The amount of base can be from about 0 molar equivalents to about 1 molar equivalent based on intermediate 4 or in an amount high enough to keep the reaction mixture basic, for example at about pH 8-9.
[0049] The intermediate 4 and the product 1 of the process may be isolated using methods known to those of skill in the art, e.g., extraction, filtration, or crystallization.
[0050] Another embodiment concerns a direct esterification process for the preparation of betaines represented by general formula 1. The first step of the esterification process comprises the reaction of a carboxylic acid
[0000]
[0000] wherein R selected from C 5 -C 17 alkyl, C 5 -C 17 alkenyl, C 5 -C 17 dienyl, C 5 -C 17 trienyl, and mixtures thereof, with a dialkylamino alcohol 3:
[0000]
[0000] in the presence of an enzyme to form an intermediate 4:
[0000]
[0051] wherein R 1 is methyl and R 2 is selected from C 1 -C 5 alkyl; and A is selected from C 3 -C 10 alkylene and C 3 -C 10 alkenylene. The second step of the direct esterification process comprises reacting intermediate 4 with sodium chloroacetate to produce a betaine.
[0052] In one aspect of the direct esterification process, R is selected from C 5 -C 17 alkyl and mixtures thereof; R 1 is methyl and R 2 is selected from C 1 -C 5 alkyl, and A is selected from C 3 -C 8 alkylene and C 3 -C 8 alkenylene. In another aspect, R 2 is methyl, and A is selected from C 3 -C 8 alkylene and C 3 -C 8 alkenylene. In yet another aspect, R 2 is methyl and A is 1,3-propylene.
[0053] The first step of the direct esterification process can be carried out without solvent or in an inert solvent chosen from cyclic or acyclic ether solvents such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, or tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, or xylene, aliphatic or alicyclic saturated or unsaturated hydrocarbons such as hexane, heptane, cyclohexane, or limonene, halogenated hydrocarbons such as dichloromethane, dichloroethane, dibromoethane, tetrachloroethylene, or chlorobenzene, polar aprotic solvents such as acetonitrile, dimethyl formamide, or dimethyl sulfoxide, or mixtures thereof. In one aspect, no solvent is used. In one aspect, heptane is used as the solvent. In one aspect, the solvent serves as an agent coping agent with water facilitating removal of water from the reaction mixture and driving the reaction to higher conversions.
[0054] The first step of the direct esterification process may be carried out at a temperature from about −100° C. to about the boiling point of the solvent, from about 20 to about 80° C., or from about 50 to about 70° C. The amount of dialkylamino alcohol 3 may be from about 0.85 to about 20 equivalents based on the carboxylic acid, or can be from about 1 to about 10 equivalents, or even from about 1 to about 1.5 equivalents.
[0055] The enzyme used in the first step of the direct esterification process is chosen from a protease, a lipase, or an esterase. Moreover, lipases may be in the form of whole cells, isolated native enzymes, or immobilized on supports. Examples of these lipases include but are not limited to Lipase PS (from Pseudomonas sp), Lipase PS-C (from Psuedomonas sp immobilized on ceramic), Lipase PS-D (from Pseudomonas sp immobilized on diatomaceous earth), Lipoprime 50T, Lipozyme TL IM, Novozym 435 ( Candida antarctica lipase B immobilized on acrylic resin) or Candida antarctica lipase B immobilized on a porous fluoropolymer support as described in US Patent Pub. 20120040395.
[0056] Removal of the water byproducts can be done chemically via a water absorbent (e.g., molecular sieves) or by physical removal of the water. According to an embodiment, this by-product removal can be done by evaporation, either by purging the reaction mixture with an inert gas such as nitrogen, argon, or helium, or by performing the reaction at reduced pressures, or both, as these conditions can afford >98% conversion of the carboxylic acid to intermediate 4. According to an embodiment, pressure for the reaction is from about 1 torr to about ambient pressure, or from about 50 torr to about ambient pressure. Any organic solvent that is included in this process may or may not be removed along with the water. In one aspect, the organic solvent also functions to assist in removal of the water byproduct by azeotropic distillation. Examples of dialkylamino alcohol 3 include dimethylaminopropanol.
[0057] The second step of the direct esterification process to generate the final product 1 comprises the reaction of intermediate 4 with sodium chloroacetate. The second step of the direct esterification process can be carried out without solvent or in an inert solvent chosen from water, cyclic or acyclic alcohol solvents such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, ethylene glycol, 1,2-propanediol, or 1,3-propanediol, cyclic or acyclic ether solvents such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, or tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, or xylene, aliphatic or alicyclic saturated or unsaturated hydrocarbons such as hexane, heptane, cyclohexane, or limonene, halogenated hydrocarbons such as dichloromethane, dichloroethane, dibromoethane, tetrachloroethylene, or chlorobenzene, polar aprotic solvents such as acetonitrile, dimethyl formamide, or dimethyl sulfoxide, or mixtures thereof.
[0058] The second step of direct esterification process may be carried out at a temperature of from about −100° C. to about the boiling point of the solvent, from about 25 to about 150° C., or from about 50 to about 100° C. The amount of sodium chloroacetate may be from about 0.75 to about 20 equivalents based on the amount of intermediate 4, from about 1 to about 10 equivalents, or from about 1 to about 1.5 equivalents. If included, a base is chosen from metal hydroxides, metal carbonates, or metal bicarbonates. According to an embodiment, bases can be sodium hydroxide, potassium hydroxide, sodium bicarbonate, and potassium bicarbonate. The amount of base can be from about 0 molar equivalents to about 1 molar equivalent based on intermediate 4 or in an amount high enough to keep the reaction mixture basic, for example at about pH 8-9.
[0059] The intermediate 4 and the product 1 of the process may be isolated using methods known to those of skill in the art, e.g., extraction, filtration, or crystallization.
[0060] Another embodiment of the invention is the use of the betaine esters 1 as surfactants. The surfactant properties of the betaine esters 1 can be determined by a number of tests including an ASTM foam height test and a test for critical micelle concentration.
[0061] The Standard Test Method for Foaming Properties of Surface-Active Agents (ASTM 1173-07) was used to determine the foaming properties of the betaine esters 1 described herein. This method generates foam under low-agitation conditions and is generally used for moderate- and high-foam surfactants. This test gathers data on initial foam height and foam decay. Foam decay provides information on foam stability.
[0062] The apparatus for carrying out this test includes a jacketed column and a pipet. The jacketed column serves as a receiver, while the pipet delivers the surface-active solution. Solutions of each surface-active agent were prepared. The betaine solution to be tested was added to the receiver (50 mL) and to the pipet (200 mL). The pipet was positioned above the receiver and opened. As the solution fell and made contact with the solution in the receiver, foam was generated. When the pipet was empty, the time was noted and an initial foam height was recorded. The foam height was recorded each minute for five minutes. Exact size specifications for the glassware can be found in ASTM 1173-07.
[0000]
TABLE 1
Foam height (cm) at time t (min)
1 g/L (0.1 weight %)
10 g/L (1.0 weight %)
t = 0
1
2
3
4
5
t = 0
1
2
3
4
5
Example
No.
4
9.0
9.0
9.0
9.0
9.0
9.0
16.5
16.5
16.0
16.0
16.0
16.0
5
15.0
14.0
14.0
13.5
13.5
13.5
17.0
16.5
16.0
15.5
15.5
15.0
6
16.0
15.5
15.5
15.5
15.5
15.5
15.0
15.0
15.0
15.0
15.0
15.0
8
14.0
13.5
13.5
13.5
13.0
13.0
17.0
16.0
15.5
15.5
15.0
15.0
9
15.5
15.0
15.0
14.5
14.5
14.0
17.0
16.0
15.5
15.5
15.5
15.0
11
10.0
10.0
10.0
10.0
9.5
9.5
21.0
19.5
19.0
19.0
18.5
18.5
14
16.5
16.0
16.0
15.5
15.5
15.5
16.0
15.5
15.5
15.0
15.0
15.0
16
17.0
16.5
15.5
15.5
15.0
13.5
17.5
17.0
17.0
17.0
16.5
16.5
18
17.0
16.5
16.5
16.5
16.5
16.5
18.0
17.0
17.0
16.5
16.5
16.5
20
17.0
16.0
15.5
15.5
15.0
15.0
19.0
16.5
16.5
15.5
15.5
15.5
22
4.0
3.5
3.5
3.0
2.5
2.5
ND
ND
ND
ND
ND
ND
Comparative
example no.
2
17.0
16.5
16.5
16.0
16.0
16.0
17.5
17.0
17.0
16.5
16.5
16.5
4
15.5
15.5
15.5
15.5
15.5
15.5
16.5
16.0
15.5
15.5
15.5
15.5
6
16.5
16.0
15.5
15.5
15.5
15.5
17.5
17.0
16.5
16.5
16.0
15.5
8
16.0
15.0
15.0
14.0
12.0
5.0
17.0
15.5
14.0
13.0
7.0
5.0
[0063] Data from the foam height test can be found in Table 1. Examples 4-6, 8, 9, 11, 14, 16, 18, 20, and 22 are betaine esters, while Comparative Examples 2, 4, 6 and 8 are betaine amides for comparison. These compounds were prepared at 1 g/L and 10 g/L solutions. As the data in Table 1 indicate, solutions of the betaine esters generate large amounts of foam. Examples in which foam height does not decrease over time indicate good foam stability. Comparative Example 2 is a useful standard, in that this compound is used commercially as a betaine surfactant.
[0064] The critical micelle concentration (CMC) was also determined for each compound. The CMC is the concentration of surfactants above which micelles spontaneously form. CMC is an important characteristic of a surfactant. At surfactant concentrations below the CMC, surface tension varies widely with surfactant concentration. At concentrations above the CMC, surface tension remains fairly constant. A lower CMC indicates less surfactant is needed to saturate interfaces and form micelles. Typical CMC values for surface-active agents are less than 1 weight %.
[0065] The fluorimetric determination of CMC described by Chattopadhyay and London ( Analytical Biochemistry, 139, 408-412, 1984) was used to obtain the critical micelle concentrations found in Table 2. This method employs the fluorescent dye 1,6-diphenyl-1,3,5-hexatriene (DPH) in a solution of the surface-active agent. The analysis is based on differences in fluorescence upon incorporation of the dye into the interior of the micelles. As the solution exceeds CMC, a large increase in fluorescence intensity is observed. This method has been found to be sensitive and reliable, and has been demonstrated on zwitterionic, anionic, cationic and uncharged surface-active agents.
[0000]
TABLE 2
CMC
(weight %)
Example
No.
4
0.0050
5
0.0053
6
0.0007
8
0.0045
9
0.0023
11
0.0004
14
0.0042
16
0.0026
18
0.0092
20
0.0020
22
0.0006
Comparative
Example No.
2
0.0029
4
0.0041
6
0.0025
8
0.0027
[0066] The data in Table 2 indicate that very low concentrations of the betaine esters are needed to reach CMC. Again, Examples 4-6, 8, 9, 11, 14, 16, 18, 20, and 22 are betaine esters, while Comparative Examples 2, 4, 6 and 8 are betaine amides for comparison. As with foam height, all of these compounds appear similar. These values fall in the range of being useful as surface-active agents. As noted above, Comparative Example 2 is used commercially as a betaine surfactant and provides a reference point by which to compare values for the betaine esters of general formula 1.
[0067] The betaine esters are molecules possessing both hydrophilic and hydrophobic regions, making them useful as surfactants in a number of formulated product applications, including personal care products such as skin care, hair care or other cosmetic products, household and industrial surface cleaners, disinfectants, metal working, rust inhibitors, lubricants, agrochemicals, dye dispersions, oil field additives, and oil dispersants. Betaines can also be used as emulsifiers and thickening agents in emulsions. Betaines are often formulated into products as secondary surface-active agents. Although a primary use is as humectants and foaming agents, betaines are also used for their anti-static and viscosity-controlling properties.
[0068] Such product formulations can contain from about 0.001 weight % to about 20 weight %, from about 0.01 weight % to about 15 weight %, or even from about 0.1 weight % to about 10 weight % of the betaine esters.
[0069] Product formulations of the invention may include other surfactants in addition to the betaine esters. These surfactants can include anionic surfactants (such as alcohol ether sulfates, linear alkylbenzene sulfonates, acyl isethionates), cationic surfactants (such as quaternary ammonium salts, fatty amine oxides, and ester quats), and non-ionic surfactants (such as alky polyglycosides, alcohol ethoxylates, and fatty alcanol amides). Such ingredients are known to those of skill in the art.
[0070] The cosmetic, skin, and hair care compositions of the invention may also contain other skin conditioning ingredients or cosmetically acceptable carriers in addition to the betaine esters.
[0071] Such formulations may also contain skin care ingredients/carriers such as retinol, retinyl esters, tetronic acid, tetronic acid derivatives, hydroquinone, kojic acid, gallic acid, arbutin, α-hydroxy acids, niacinamide, pyridoxine, ascorbic acid, vitamin E and derivatives, aloe, salicylic acid, benzoyl peroxide, witch hazel, caffeine, zinc pyrithione, and fatty acid esters of ascorbic acid. Such other ingredients are known to those of skill in the art.
[0072] Other ingredients that may be included in these formulations include conditioning agents (such as polyquaterniums and panthenol), pearlizing agents (such as glycol distearate, distearyl ether, and mica), UV filters (such as octocrylene, octyl methoxycinnamate, benzophenone-4, titanium dioxide, and zinc oxide), exfoliation additives (such as apricot seeds, walnut shells, polymer beads, and pumice), silicones (such as dimethicone cyclomethicone, and amodimethicone), moisturizing agents (such as petrolatum, sunflower oil, fatty alcohols, and shea butter), foam stabilizers (such as cocamide MEA and cocamide DEA), anti-bacterial agents such as triclosan, humectants such as glycerin, thickening agents (such as guar, sodium chloride, and carbomer), hair and skin damage repair agents (such as proteins, hydrolyzed proteins, and hydrolyzed collagen), and foam boosters such as cocamide MIPA. Such other ingredients are known to those of skill in the art.
[0073] Many preparations are known in the art, and include formulations containing acceptable carriers such as water, oils and/or alcohols and emollients such as olive oil, hydrocarbon oils and waxes, silicone oils, other vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lecithin, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like. These same general ingredients can be formulated into liquids (such as liquid soaps, shampoos, or body washes), creams, lotions, gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophilic colloids.
EXAMPLE
[0074] The processes and compounds provided by the present invention are further illustrated by the following examples.
Example 1
[0075] Preparation of Methyl Cocoate
[0076] To a jar was added potassium hydroxide (1 g) and methanol (25 g). The solution was stirred for 1 hour. To a separate jar was added coconut oil (100 g). The solid was heated to a melt and the KOH/MeOH solution was added and the mixture was stirred overnight. The mixture was transferred to a separatory funnel and allowed to separate. The bottom (glycerol) layer was removed. The top layer was filtered to afford a pale yellow oil (100 g). 1 H NMR (300 MHz, CDCl 3 ) δ 3.65 (s, 3H), 2.28 (t, 2H), 1.60 (m, 2H), 1.24 (s, 16H), 0.86 (t, 3H).
Example 2
[0077] Preparation of Ethyl Cocoate
[0078] To a jar was added potassium hydroxide (2 g) and ethanol (72 g). The solution was stirred for 1 hour. To a separate jar was added coconut oil (200 g). The solid was heated to a melt and the KOH/EtOH solution was added and the mixture was stirred overnight. The mixture was transferred to a separatory funnel and allowed to separate. The bottom (glycerol) layer was removed. The top layer was filtered to afford a pale yellow oil (227 g). 1 H NMR (300 MHz, CDCl 3 ) δ 4.09 (t, 3H), 3.68 (q, 2H), 2.27 (t, 2H), 1.60 (m, 2H), 1.24 (s, 16H), 0.86 (t, 3H).
Example 3
[0079] Preparation of Dimethylaminoethyl Cocoate
[0080] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), dimethylaminoethanol (5.09 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (8 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 4.15 (t, 2H), 2.54 (t, 2H), 2.31 (t, 2H), 2.26 (s, 6H), 1.60 (m, 2H), 1.24 (s, 16H), 0.86 (t, 3H).
Example 4
[0081] Preparation of Dimethylaminoethyl Cocoate Betaine
[0082] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminoethyl cocoate (10 g, 35.3 mmol), sodium chloroacetate (4.11 g, 35.3 mmol, 1 eq) and water (32.9 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 30% aqueous solution (43 g). 1 H NMR (300 MHz, DMSO d-6) δ 3.89 (t, 2H), 3.78 (t, 2H), 3.66 (s, 2H), 3.17 (s, 6H), 2.27 (t, 2H), 1.51 (m, 2H), 1.23 (s, 16H), 0.85 (t, 3H).
Example 5
[0083] Preparation of Dimethylaminoethyl Cocoate Betaine
[0084] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminoethyl cocoate (10 g, 35.3 mmol), sodium chloroacetate (4.11 g, 35.3 mmol, 1 eq) and 1,3-propanediol (4.7 g). The reaction mixture was heated at 98° C. for 8 hours. When the reaction was complete by NMR, the mixture was allowed to cool. The mixture was filtered to afford the product as a viscous, 75% solution in 1,3-propanediol (14 g). 1 H NMR (300 MHz, DMSO d-6) δ 3.89 (t, 2H), 3.78 (t, 2H), 3.66 (s, 2H), 3.17 (s, 6H), 2.27 (t, 2H), 1.51 (m, 2H), 1.23 (s, 16H), 0.85 (t, 3H).
Example 6
[0085] Preparation of Dimethylaminoethyl Cocoate Betaine
[0086] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminoethyl cocoate (10 g, 35.3 mmol), sodium chloroacetate (4.11 g, 35.3 mmol, 1 eq) and isopropanol (15 mL). The reaction mixture was heated at reflux for 8 hours. When the reaction was complete by NMR, the mixture was allowed to cool. The mixture was filtered and isopropanol was removed in vacuo to afford the product as a viscous, semi-solid (13 g). 1 H NMR (300 MHz, DMSO d-6) δ 3.89 (t, 2H), 3.78 (t, 2H), 3.66 (s, 2H), 3.17 (s, 6H), 2.27 (t, 2H), 1.51 (m, 2H), 1.23 (s, 16H), 0.85 (t, 3H).
Example 7
[0087] Preparation of Dimethylaminopropyl Cocoate
[0088] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), dimethylaminopropanol (4.76 g, 46.2 mmol, 1.2 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (9.2 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 4.10 (t, 2H), 2.30 (m, 4H), 2.21 (s, 6H), 1.78 (t, 2H), 1.60 (m, 2H), 1.24 (s, 16H), 0.86 (t, 3H).
Example 8
[0089] Preparation of Dimethylaminopropyl Cocoate Betaine
[0090] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminopropyl cocoate (10 g, 35 mmol), sodium chloroacetate (4.1 g, 35 mmol, 1 eq) and 1,3-propanediol (14.1 g). The reaction mixture was heated at 98° C. for 8 hours. When the reaction was complete by NMR, the mixture was allowed to cool. The mixture was filtered to afford the product as a 50% solution in 1,3-propanediol (27 g). 1 H NMR (300 MHz, CDCl 3 ) δ 4.16 (t, 2H), 3.92 (t, 2H), 3.67 (t, 2H), 3.28 (s, 6H), 2.34 (q, 2H), 2.10 (t, 2H), 1.60 (m, 2H), 1.26 (s, 16H), 0.88 (t, 3H).
Example 9
[0091] Preparation of Dimethylaminopropyl Cocoate Betaine
[0092] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminopropyl cocoate (10 g, 35.3 mmol, 1 eq), sodium chloroacetate (4.11 g, 35.3 mmol, 1 eq) and isopropanol (15 mL). The reaction mixture was heated at reflux for 8 hours. When the reaction was complete by NMR, the mixture was allowed to cool. The mixture was filtered and isopropanol was removed in vacuo to afford the product as a viscous, semi-solid (14 g). 1 H NMR (300 MHz, CDCl 3 ) δ 4.16 (t, 2H), 3.92 (t, 2H), 3.67 (t, 2H), 3.28 (s, 6H), 2.34 (q, 2H), 2.10 (t, 2H), 1.60 (m, 2H), 1.26 (s, 16H), 0.88 (t, 3H).
Example 10
[0093] Preparation of Dimethylamino-2-Methylethyl Cocoate
[0094] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), dimethylamino-2-methylpropanol (5.95 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (7 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 5.01 (m, 1H), 2.61 (t, 2H), 2.31 (t, 2H), 2.29 (m, 7H), 1.60 (m, 2H), 1.24 (m, 19H), 0.86 (t, 3H).
Example 11
[0095] Preparation of Dimethylamino-2-Methylethyl Cocoate Betaine
[0096] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylamino-2-methylethyl cocoate (5.6 g, 18.8 mmol), sodium chloroacetate (2.18 g, 18.8 mmol, 1 eq) and water (7.8 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 50% solution in water (14 g). 1 H NMR (300 MHz, DMSO d-6) δ 4.96 (m, 1 H), 3.89 (t, 2H), 3.66 (s, 2H), 3.17 (s, 6H), 2.27 (t, 2H), 1.51 (m, 2H), 1.23 (m, 19H), 0.85 (t, 3H).
Example 12
[0097] Preparation of Hydrogenated Coconut Oil Methyl Esters
[0098] Hydrogenated coconut oil (C 6 -C 18 saturated fatty acid triglyceride) (501 g; 0.767 mol) was combined with methanol (123 g; 3.84 mol; 5 equiv) and 25% sodium methoxide in methanol (25 wt %; 19.90 g; 0.092 mol; 0.12 equiv). The mixture was stirred at ambient temperature for 3 hours to afford 99.4% conversion. The stirring was stopped and the lower glycerol layer was decanted. The top layer was concentrated and the crude product was treated with magnesol and filtered to afford the methyl esters of hydrogenated coconut oil fatty acids (476 g; 91%). 1 H NMR (300 MHz, CDCl 3 ) δ 3.64 (s, 3H), 2.28 (t, 2H), 1.59 (m, 2H), 1.24 (m, 16H), 0.85 (t, 3H).
Example 13
[0099] Preparation of 3-Dimethylaminopropyl Hydrogenated Cocoate
[0100] Hydrogenated coconut oil fatty acid methyl esters (100 g; 0.44 mol), 3-dimethylaminopropanol (54.5 g; 0.529 mol; 1.2 equiv), Novozym 435 (17 g), and heptane (45 mL) were combined and heated to 65° C. The heptane azeotrope was utilized to remove methanol by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. After 8 h GC analysis indicated 99.2% conversion to the 3-dimethylaminopropyl ester of hydrogenated coconut oil fatty acids. The enzyme was removed by filtration and the filtrate was concentrated to afford 131.6 g (92%) of the product. 1 H NMR (300 MHz, CDCl 3 ) δ 4.09 (t, 2H), 2.31 (t, 2H), 2.27 (t, 2H); 2.20 (s, 6H); 1.77 (m(5), 2H); 1.59 (m, 2H), 1.26 (m, 16H), 0.85 (t, 3H).
Example 14
[0101] Preparation of 3-Dimethylaminopropyl Hydrogenated Cocoate Betaine
[0102] Sodium chloroacetate (291 g; 2.5 mol; 1.15 equiv) and sodium bicarbonate (36.5 g; 0.435 mol; 0.2 equiv) were added to a jacketed 3-L reactor with a mechanical stirrer and a condenser. Water (1470 mL) and 3-dimethylaminopropyl hydrogenated cocoate (650 g; 2.17 mol) were added and the mixture was stirred and the jacket was heated at 84° C. After 24 h, HPLC analysis indicated 99.0% conversion to product. The mixture was cooled to ambient temperature and the pH of the mixture was adjusted to 6.75 by the addition of 3 M HCl. The resulting mixture was clarified through a scintered glass funnel to afford 2376 g of a 31.8 wt % (by HPLC) solution of 3-dimethylaminopropyl hydrogenated cocoate betaine in water (97% yield). 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.03 (t, 2H), 3.59 (s, 2H); 3.45 (m, 2H); 3.07 (s, 6H), 2.28 (t, 2H), 1.97 (m, 2H), 1.49 (m, 2H), 1.22 (m, 16H), 0.83 (t, 3H).
Example 15
[0103] Preparation of 3-Dimethylaminopropyl Hydrogenated Stripped Cocoate
[0104] Hydrogenated and stripped coconut fatty acids (C 10 -C 18 saturated fatty acid mixture) (375 g; 1.69 mol), 3-dimethylaminopropanol (209 g; 2.03 mol; 1.2 equiv), Novozym 435 (20 g), and heptane (173 mL) were combined and heated to 65° C. The heptane azeotrope was utilized to remove water by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. The reaction was allowed to proceed for 8 h at which point GC analysis indicated 99.6% conversion of the hydrogenated stripped coconut fatty acids to the 3-dimethylaminopropyl esters. The enzyme was removed by filtration and the filtrate was concentrated, and the concentrate was purged with nitrogen overnight at 60° C. to remove excess 3-dimethylaminopropanol, 99% yield. 1 H NMR (300 MHz, CDCl 3 ) δ 4.10 (t, 2H), 2.33 (t, 2H), 2.28 (t, 2H); 2.20 (s, 6H); 1.79 (m(5), 2H); 1.60 (m, 2H), 1.24 (m, 16H), 0.86 (t, 3H).
Example 16
[0105] Preparation of 3-Dimethylaminopropyl Hydrogenated Stripped Cocoate Betaine
[0106] Sodium chloroacetate (6.53 g; 56.0 mmol; 1.15 equiv), sodium bicarbonate (0.81 g; 9.6 mmol; 0.2 equiv) and 3-dimethylaminopropyl hydrogenated stripped cocoate (15 g; 48.6 mol) were combined in a 100-mL round bottom flask with 33.8 g of water. The mixture was stirred and heated to at 80° C. for 13 h, at which point HPLC analysis indicated 99.3% conversion to product. The mixture was cooled to ambient temperature and filtered to afford 55.88 g of a 32 wt % (by HPLC) solution of 3-dimethylaminopropyl hydrogenated stripped cocoate betaine in water (99% yield). 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.03 (t, 2H), 3.58 (s, 2H); 3.10 (s, 6H), 2.27 (t, 2H), 1.96 (m, 2H), 1.49 (m, 2H), 1.22 (m, 16H), 0.83 (t, 3H).
Example 17
[0107] Preparation of 3-Dimethylaminopropyl Laurate
[0108] Lauric acid (600 g; 3.0 mol), 3-dimethylaminopropanol (371 g; 3.59 mol; 1.2 equiv), Novozym 435 (30 g), and heptane (267 mL) were combined and heated to 65° C. The heptane azeotrope was utilized to remove water by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. The reaction was allowed to proceed for 12 h at which point GC analysis indicated 99.3% conversion of lauric acid to the 3-dimethylaminopropyl ester. The enzyme was removed by filtration and the filtrate was concentrated, and the concentrate was purged with nitrogen overnight at 60° C. to remove excess 3-dimethylaminopropanol. 1 H NMR (300 MHz, CDCl 3 ) δ 4.09 (t, 2H), 2.32 (t, 2H), 2.27 (t, 2H); 2.20 (s, 6H); 1.78 (m(5), 2H); 1.59 (m, 2H), 1.26 (m, 16H), 0.86 (t, 3H).
Example 18
[0109] Preparation of 3-Dimethylaminopropyl Laurate Betaine
[0110] Sodium chloroacetate (292 g; 2.5 mol; 1.1 equiv) and sodium bicarbonate (38.3 g; 0.455 mol; 0.2 equiv) were added to a jacketed 3-L reactor with a mechanical stirrer and a condenser. Water (219 mL), isopropanol (876 mL), and 3-dimethylaminopropyl laurate (650 g; 2.28 mol) were added and the mixture was stirred and the jacket was heated at 81° C. overnight, at which point HPLC analysis indicated 99.6% conversion to product. The mixture was cooled to ambient temperature and 876 mL of isopropanol was added to afford a precipitate. The mixture was filtered and the filtrate was concentrated at reduced pressure. Water (1000 mL) was added, and the mixture was heated to 80° C. with a headspace nitrogen purge with periodic addition of water to remove residual isopropanol. Once the isopropanol had been evaporated ( 1 H NMR analysis), the mixture was cooled to ambient temperature and the pH was adjusted to 6.75 by the addition of 3 M HCl. The resulting mixture was clarified through a scintered glass funnel to afford 2100 g of a 33.0 wt % (by wt % 1 H NMR) solution of 3-dimethylaminopropyl laurate betaine in water (89% yield). 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.03 (t, 2H), 3.58 (s, 2H); 3.10 (s, 6H), 2.27 (t, 2H), 1.96 (m, 2H), 1.49 (m, 2H), 1.22 (m, 16H), 0.83 (t, 3H).
Example 19
[0111] Preparation of 3-Dimethylaminopropyl Myristate
[0112] Myristic acid (10 g; 43.8 mmol), 3-dimethylaminopropanol (5.87 g; 56.9 mmol; 1.3 equiv), and Novozym 435 (2 g) were combined and heated to 65° C. with nitrogen sparging at 100 mL/min. After 12 h, GC analysis indicated 93.7% conversion of myrstic acid to the ester. The enzyme was removed by filtration and the filter cake was washed with heptane. The filtrate was washed with 1:1 methanol:10% aqueous potassium carbonate (30 mL), then with 5% sodium bicarbonate (15 mL), dried with sodium sulfate, and concentrated to afford 12.09 g (88%) of 3-dimethylaminopropyl myristate. 1 H NMR (300 MHz, CDCl 3 ) δ 4.11 (t, 2H), 2.33 (t, 2H), 2.29 (t, 2H); 2.22 (s, 6H); 1.79 (m(5), 2H); 1.61 (m, 2H), 1.25 (m, 20H), 0.88 (t, 3H).
Example 20
[0113] Preparation of 3-Dimethylaminopropyl Myristate Betaine
[0114] 3-Dimethylaminopropyl myristate (5.0; g; 15.95 mmol), sodium chloroacetate (2.04 g; 17.54 mmol; 1.1 equiv) and sodium bicarbonate (268 mg; 3.19 mol; 0.2 equiv) were added to a 100-mL round bottom flask. Water (5 mL) and isopropanol (5 mL) were added, and the mixture was stirred and heated to 80° C. for 16 h, at which point HPLC analysis indicated 99.1% conversion. The mixture was cooled to ambient temperature to afford a total solution weight of 15.18 g, indicating approximately 37 wt % 3-dimethylaminopropyl myristate betaine in isopropanol/water. 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.02 (t, 2H), 3.59 (s, 2H); 3.08 (s, 6H), 2.26 (t, 2H), 1.95 (m, 2H), 1.47 (m, 2H), 1.22 (m, 20H), 0.81 (t, 3H).
Example 21
[0115] Preparation of 3-Dimethylaminopropyl Palmitate
[0116] Methyl palmitate (10 g; 37.0 mol), 3-dimethylaminopropanol (4.96 g; 48.1 mol; 1.3 equiv), and Novozym 435 (2 g) were combined and heated to 65° C. with nitrogen sparging at 100 mL/min. After 12 h, 98.9% conversion of methyl palmitate to 3-dimethylaminopropyl palmitate was observed along with a little palmitic acid according to GC analysis. The enzyme was removed by filtration and the filter cake was washed with heptane. The filtrate was washed with 1:1 methanol:10% aqueous potassium carbonate (30 mL), then with 5% sodium bicarbonate (15 mL), dried with sodium sulfate, and concentrated to afford 10.00 g (79%) of 3-dimethylaminopropyl palmitate. 1 H NMR (300 MHz, CDCl 3 ) δ 4.11 (t, 2H), 2.33 (t, 2H), 2.29 (t, 2H); 2.22 (s, 6H); 1.80 (m(5), 2H); 1.61 (m, 2H), 1.25 (m, 24H), 0.88 (t, 3H).
Example 22
[0117] Preparation of 3-Dimethylaminopropyl Palmitate Betaine
[0118] 3-Dimethylaminopropyl palmitate (5.0; g; 14.64 mmol), sodium chloroacetate (1.88 g; 16.1 mmol; 1.1 equiv) and sodium bicarbonate (246 mg; 2.93 mol; 0.2 equiv) were added to a 100-mL round bottom flask. Water (5 mL) and isopropanol (5 mL) were added, and the mixture was stirred and heated to 80° C. for 15 h, at which point HPLC analysis indicated 99.3% conversion. The mixture was cooled to ambient temperature to afford a total solution weight of 13.75 g, indicating approximately 40 wt % 3-dimethylaminopropyl palmitate betaine in isopropanol/water. 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.02 (t, 2H), 3.59 (s, 2H); 3.09 (s, 6H), 2.26 (t, 2H), 1.95 (m, 2H), 1.48 (m, 2H), 1.20 (m, 24H), 0.81 (t, 3H).
Example 23
[0119] Preparation of 3-Dimethylaminopropyl Cocoate
[0120] Coconut fatty acid (32.8 g; 0.154 mol), 3-dimethylaminopropanol (18.15 g; 0.176 mol; 1.14 equiv), Novozym 435 (2.62 g), and heptane (15.3 mL) were combined and heated to 50° C. The heptane azeotrope was utilized to remove water by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. After 6 h GC analysis indicated 99.0% conversion to the 3-dimethylaminopropyl ester of coconut oil fatty acids. The enzyme was removed by filtration and the filtrate was concentrated to afford 41.64 g (90%) of 3-dimethylaminopropyl cocoate.
Example 24
[0121] Preparation of Dimethylaminopropyl Cocoate Betaine
[0122] To a 40 mL vial with a magnetic stir bar and a condenser was added 3-dimethylaminopropyl cocoate prepared in example 23 (3 g, 10.0 mmol), sodium chloroacetate (1.35 g, 11.6 mmol, 1.15 eq) and sodium bicarbonate (169 mg; 2.0 mmol; 0.2 equiv). Water (6.82 g) was added and the reaction mixture was heated at 80° C. for 20 hours at which point HPLC analysis indicated 99.0% conversion to the betaine. The reaction mixture was cooled to afford 10.77g of the product as a 33% solution in water. 1 H NMR (300 MHz, CDCl 3 ) δ 4.16 (t, 2H), 3.92 (t, 2H), 3.67 (t, 2H), 3.28 (s, 6H), 2.34 (q, 2H), 2.10 (t, 2H), 1.60 (m, 2H), 1.26 (s, 16H), 0.88 (t, 3H). HPLC (150×4.6 mm Zorbax SB-C8 column, 80:20 methanol:water (containing 0.1% trifluoroacetic acid) for 10 min, gradient to 100% methanol over 1 min, held at 100% methanol for 9 min, ELSD detection): t R (laurate ester) 3.4 min.
Example 25
[0123] Preparation of 3-Dimethylaminopropyl Cocoate
[0124] Coconut fatty acid (32.8 g; 0.154 mol), 3-dimethylaminopropanol (18.15 g; 0.176 mol; 1.14 equiv), were added to 1080 cm 2 of Candida antarctica lipase B immobilized on a porous fluoropolymer support as described in US Patent Pub. 20120040395. Heptane (30 mL) was added and the mixture was heated to 50° C. The heptane azeotrope was utilized to remove water by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. After 6.5 h GC analysis indicated 99.9% conversion to the 3-dimethylaminopropyl ester of coconut oil fatty acids. The product solution was decanted and the enzyme was washed with heptane. The combined organic solution was concentrated to remove volatiles and afford 43.49 g (94%) of 3-dimethylaminopropyl cocoate.
Example 26
[0125] Preparation of Dimethylaminopropyl Cocoate Betaine
[0126] To a 40 mL vial with a magnetic stir bar and a condenser was added 3-dimethylaminopropyl cocoate prepared in example 25 (3 g, 10.0 mmol), sodium chloroacetate (1.35 g, 11.6 mmol, 1.15 eq) and sodium bicarbonate (169 mg; 2.0 mmol; 0.2 equiv). Water (6.82 g) was added and the reaction mixture was heated at 80° C. for 20 hours at which point HPLC analysis indicated 99.2% conversion to the betaine. The reaction mixture was cooled to afford 10.97 of the product as a 32% solution in water. 1 H NMR (300 MHz, CDCl 3 ) δ 4.16 (t, 2H), 3.92 (t, 2H), 3.67 (t, 2H), 3.28 (s, 6H), 2.34 (q, 2H), 2.10 (t, 2H), 1.60 (m, 2H), 1.26 (s, 16H), 0.88 (t, 3H). HPLC (150×4.6 mm Zorbax SB-C8 column, 80:20 methanol:water (containing 0.1% trifluoroacetic acid) for 10 min, gradient to 100% methanol over 1 min, held at 100% methanol for 9 min, ELSD detection): t R (laurate ester) 3.4 min.
Example 27
[0127] Preparation of 3-Dimethylaminopropyl Cocoate
[0128] Methyl cocoate (50.0 g; 0.221 mol) and 3-dimethylaminopropanol (28.3 g; 0.274 mol; 1.24 equiv), were added to 150 cm 2 of Candida antarctica lipase B immobilized on a porous fluoropolymer support as described in US Patent Pub. 20120040395. The mixture was heated to 65° C. and sparged with 100 mL/min of nitrogen to remove the methanol by-product. After 20 h GC analysis indicated 98.7% conversion to the 3-dimethylaminopropyl cocoate.
Example 28
[0129] Preparation of Dimethylaminopropyl Myristate
[0130] Myristic acid (35.17g; 0.154 mol), 3-dimethylaminopropanol (18.15 g; 0.176 mol; 1.14 equiv), Novozym 435 (2.62 g), and heptane (15.3 mL) were combined and heated to 50° C. The heptane azeotrope was utilized to remove water by reducing the pressure until the azeotrope distilled overhead into a Dean-Stark trap to return the heptane to the reaction vessel. After 8 h GC analysis indicated 98.5% conversion to 3-dimethylaminopropyl myristate.
Example 29
[0131] Preparation of 3-Dimethylaminopropyl Cocoate
[0132] Coconut fatty acid (32.8 g; 0.154 mol), 3-dimethylaminopropanol (18.15 g; 0.176 mol; 1.14 equiv), Novozym 435 (2.62 g), were combined and heated to 50° C. Stirring was started and a nitrogen sparge (500 mL/min) was started. After 8 h GC analysis indicated 91.2% conversion to the 3-dimethylaminopropyl ester of coconut oil fatty acids with 3-dimethylaminopropanol still remaining. An additional 0.25 equiv of 3-dimethylaminopropanol (4.0 g; 0.039 mmol) was added and the reaction was continued for an additional 8 h, at which point GC analysis indicated 95.8% conversion. An additional 0.25 equiv of 3-dimethylaminopropanol (4.0 g; 0.039 mmol) was added and the reaction was continued for an additional 6 h, at which point GC analysis indicated 96.7% conversion. The enzyme was removed by filtration and the filtrate was washed with heptane. The combined organic solution was washed with a mixture of 10% aqueous potassium carbonate (25 mL), methanol (25 mL), and water (20 mL). The layers were separated and the top organic layer was concentrated. The residue was dissolved in heptane, dried with sodium sulfate and the volatiles were removed to afford 40.30 g (87%) of 3-dimethylaminopropyl cocoate.
[0133] Comparing Examples 28 to 19 and Examples 29 to 23 show the improvement achieved using an azeotroping agent to remove water. In Example 19, without a solvent, conversion of myristic acid to 3-Dimethylaminopropyl Myristate after 12 hours was 93.7%. In Example 28, with a solvent, conversion after 8 hours was 98.5%. Likewise, in Example 29, without a solvent, conversion to 3-Dimethylaminopropyl Cocoate after 8 hours was 91.2% while in Example 23, with solvent, the conversion after 6 hours was 99.0%
Comparative Example 1
[0134] Preparation of Dimethylaminopropyl Cocoamide
[0135] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), dimethylaminopropylamine (5.9 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (8.9 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 7.02 (s, 1 H), 3.28 (m, 2H), 2.32 (m, 2H), 2.18 (s, 6H), 2.10 (t, 2H), 1.59 (m, 4H), 1.21 (s, 16H), 0.84 (t, 3H).
Comparative Example 2
[0136] Preparation of Dimethylaminopropyl Cocoamide Betaine
[0137] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminopropyl cocoamide (10 g, 35 mmol), sodium chloroacetate (4.1 g, 35 mmol, 1 eq) and water (14.7 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 45% solution in water (33 g). 1 H NMR (300 MHz, DMSO d-6) δ 8.07 (s, 1 H), 3.59 (s, 2H), 3.45 (m, 2H), 3.08 (s, 6H), 3.05 (m, 2H), 2.04 (t, 2H), 1.76 (m, 2H), 1.44 (m, 2H), 1.19 (s, 16H), 0.81 (t, 3H).
Comparative Example 3
[0138] Preparation of Diethylaminopropyl Cocoamide
[0139] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), diethylaminopropylamine (7.52 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (11 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 7.45 (s, 1 H), 3.29 (m, 2H), 2.47 (m, 6H), 2.08 (m, 2H), 1.58 (m, 4H), 1.23 (s, 16H), 0.99 (m, 6H), 0.84 (t, 3H).
Comparative Example 4
[0140] Preparation of Diethylaminopropyl Cocoamide Betaine
[0141] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added diethylaminopropyl cocoamide (5 g, 16 mmol), sodium chloroacetate (1.85 g, 16 mmol, 1 eq) and water (5.85 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 38% solution in water (11 g). 1 H NMR (300 MHz, DMSO d-6) δ 8.05 (s, 1 H), 3.58 (s, 2H), 3.06 (q, 2H), 2.86 (m, 6H), 2.04 (t, 2H), 1.68 (m, 2H), 1.44 (m, 2H), 1.20 (s, 16H), 1.10 (t, 6H), 0.82 (t, 3H).
Comparative Example 5
[0142] Preparation of Dimethylaminoethyl Cocoamide
[0143] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), dimethylaminoethylamine (5.09 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (8.6 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 6.25 (s, 1 H), 3.25 (m, 2H), 2.34 (t, 2H), 2.16 (s, 6H), 2.10 (t, 2H), 1.54 (m, 2H), 1.18 (s, 16H), 0.80 (t, 3H).
Comparative Example 6
[0144] Preparation of Dimethylaminoethyl Cocoamide Betaine
[0145] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added dimethylaminoethyl cocoamide (8 g, 28.3 mmol), sodium chloroacetate (3.3 g, 28.3 mmol, 1 eq) and water (11 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 50% solution in water (21 g). 1 H NMR (300 MHz, DMSO d-6) δ 8.33 (t, 1H), 3.65 (s, 2H), 3.61 (m, 2H), 3.42 (q, 2H), 3.14 (s, 6H), 2.06 (t, 2H), 1.45 (m, 2H), 1.20 (s, 16H), 0.83 (t, 3H).
Comparative Example 7
[0146] Preparation of Diethylaminoethyl Cocoamide
[0147] To a 50 mL conical bottom plastic vial was added ethyl cocoate (10 g, 38.5 mmol), diethylaminoethylamine (6.71 g, 57.7 mmol, 1.5 eq) and Novozym 435 (400 mg). A syringe was inserted through the cap and two additional holes were punched for gas to exit. Nitrogen was bubbled at a rate sufficient to mix the contents. The vial was placed in a heating block set to 65° C. The reaction was monitored by GC/MS to observe the disappearance of starting material. The reaction was complete after approximately 24 hours. The reaction mixture was allowed to cool. The Novozym 435 was removed by filtration to afford the product as a pale yellow oil (10.2 g) without further purification. 1 H NMR (300 MHz, CDCl 3 ) δ 6.21 (s, 1 H), 3.32 (m, 2H), 2.56 (m, 6H), 2.21 (m, 2H), 1.65 (m, 2H), 1.29 (s, 16H), 1.04 (m, 6H), 0.92 (t, 3H).
Comparative Example 8
[0148] Preparation of Diethylaminoethyl Cocoamide Betaine
[0149] To a 100 mL round bottom flask with a magnetic stir bar and a condenser was added diethylaminoethyl cocoamide (5 g, 16.7 mmol), sodium chloroacetate (1.94 g, 16.7 mmol, 1 eq) and water (14.7 g). The reaction mixture was heated at 98° C. for 8 hours. The pH was kept basic by the addition of 50% NaOH. When the reaction was complete, the mixture was neutralized with 1 M HCl and allowed to cool. The reaction mixture was filtered to afford the product as a 38% solution in water (18 g). 1 H NMR (300 MHz, DMSO d-6) δ 8.01 (s, 1 H), 3.54 (s, 2H), 3.20 (q, 2H), 2.70 (m, 6H), 2.04 (t, 2H), 1.45 (t, 2H), 1.21 (s, 16H), 1.03 (t, 6H), 0.83 (t, 3H).
Comparative Example 9
[0150] Preparation of Dimethylaminopropyl Cocoate (Transesterification)
[0151] To a 100 mL flask fitted with a distillation head and condenser was added methyl cocoate (10 g, 0.0467 mol) and dimethylaminopropanol (5.77 g, 0.0561 mol, 1.2 eq). To the mixture was added stannous oxalate (0.103 g, 1 mol %). The flask was heated to 100° C. slowly over 1 hour. Over several hours the temperature was increased to 130° C. The reaction was monitored by GC/MS. Methanol was collected in the receiver (ca. 1 mL). The reaction was allowed to cool to room temperature. The mixture was filtered to afford the product as a golden oil (10 g). 1 H NMR (300 MHz, CDCl 3 ) δ 7.02 (s, 1H), 3.28 (m, 2H), 2.32 (m, 2H), 2.18 (s, 6H), 2.10 (t, 2H), 1.59 (m, 2H), 1.21 (s, 16H), 0.84 (t, 3H).
Comparative Example 10
[0152] Preparation of Coconut Fatty Acid
[0153] To a 2 L flask was added coconut oil (100 g), methanol (435 mL) and water (307 mL). To this mixture was added 45% potassium hydroxide (88 g). The solution was heated at 45° C. overnight. The reaction was monitored by GC/MS. When the reaction was complete, the mixture was allowed to come to room temperature. To the flask was added methanol (275 mL) and heptane (200 mL). The mixture was stirred and transferred to a separatory funnel. The aqueous layer was returned to the 2 L flask. The organic layer was discarded. To the flask was added water (50 mL). The pH was brought to 1 with the addition of concentrated HCl (ca. 70 mL). The mixture was stirred well and transferred to a separatory funnel. The aqueous layer was removed. The organic layer was dried over MgSO 4 and concentrated in vacuo to afford the product as a yellow oil (80 g). 1 H NMR (300 MHz, CDCl 3 ) δ 11.68 (s, 1 H), 2.36 (t, 2H), 1.65 (m, 2H), 1.28 (s, 16H), 0.90 (t, 3H).
Comparative Example 11
[0154] Preparation of Dimethylaminopropyl Cocoate (Direct Esterification)
[0155] To a 100 mL flask fitted with a distillation head and condenser was added coconut fatty acid (10 g, 0.05 mol,) and dimethylaminopropanol (6.18 g, 0.06 mol, 1.2 eq). The flask was heated to 40° C. (under nitrogen) to melt the fatty acid. To the molten mixture was added stannous oxalate (0.103 g, 1 mol %). The flask was heated to 100° C. slowly over 1 hour. Over several hours the temperature was increased to 150° C. The reaction was monitored by GC/MS. Water was collected in the receiver (ca. 1 mL). The reaction mixture was allowed to cool to room temperature. The mixture was diluted with diethyl ether and washed with saturated sodium bicarbonate solution. The organic layer was dried and concentrated in vacuo to afford the product as a yellow oil (2.6 g). 1 H NMR (300 MHz, CDCl 3 ) δ 7.02 (s, 1 H), 3.28 (m, 2H), 2.32 (m, 2H), 2.18 (s, 6H), 2.10 (t, 2H), 1.59 (m, 2H), 1.21 (s, 16H), 0.84 (t, 3H).
Comparative Example 28
[0156] Preparation of Dimethylaminoethyl Laurate
[0157] Lauric acid (4.66 g; 23.3 mol), dimethylaminoethanol (1.04 g, 11.6 mmol; 0.5 equiv) and Candida antarctica lipase B immobilized on an acrylic resin particle (230 mg) (made in the laboratory whereas in other examples purchased Novozym 435 was used) were combined and heated to 65° C. with a nitrogen sparge to remove the water byproduct. At 2 h, 4 h, and 6 h each an additional 0.50 equiv of dimethylaminoethanol (0.52 g; 5.8 mmol) was added, to afford a total of 2.0 equivalents of dimethylaminoethanol. The reaction was allowed to proceed for a total of 23 h at which point GC analysis indicated 84.9% conversion of lauric acid to the dimethylaminoethyl ester. An additional 0.5 equiv of dimethylaminoethanol was added (0.52g; 5.8 mmol) and heating was continued. After 5 additional hours (total 29 h) the conversion was 85.8%, indicating that the reaction had stalled.
[0158] Comparative Example 12 illustrates a conversion 85.8% after a total of 29 hours when chemical moiety A of formula 1 has only 2 carbon atoms.
[0159] The invention has been described in detail with particular reference to preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the invention. | A variety of betaine esters, including dialkylaminoalkyl cocoate betaines and dialkylaminoalkyl hydrogenated cocoate betaines are disclosed. These betaines can be advantageously prepared in high yield and purity by a three-step transiterification chemoenzymatic process or a two-step direct esterficiation chemoenzymatic process. These betaine esters have excellent surfactant properties. | 2 |
BACKGROUND OF THE INVENTION
The present invention is directed to a polarized magnetic relay having a base body; a coil being secured in the base body and having a coil body with an axially extending passage, a first end flange, a second end flange and a winding on the coil between the flanges; a bar-shaped armature being received inside of the passage of the coil body on an axis thereof with one end being pivotally mounted adjacent the first flange so that the armature can pivotably move in the coil body, a permanent magnet arrangement having two pole plates which are on a common plane extending parallel to the coil axis, each pole plate adjacent the second flange having end portions extending at right angles to the common plane to provide spaced surfaces forming an air gap therebetween with a free end of the armature extending therethrough, said magnet arrangement including a flux plate having a portion extending perpendicular to the coil axis and having at least one segment extending parallel to the pole plates and coacting with the pole plates to form a space for receiving each magnet of the arrangement; at least one stationary contact element anchored in the base body and at least one movable contact element being moved by the armature between a position out of engagement with the associated stationary contact and a position engaging the stationary contact.
A relay of the above known type is disclosed in U.S. patent application Ser. No. 401,235, filed July 23, 1982, which application was based on German Letters Patent No. 31 32 244. The disclosure of this copending application was issued on April 2, 1985 as U.S. Pat. No. 4,509,025 and is incorporated by reference thereto. As disclosed in this patent application, the relay system is very sensitive and has a particular advantage that both a monostable as well as a bistable switching characteristic can be achieved without structural modifications by means of corresponding adaptation of the quadripole permanent magnet system whereby a response value can be obtained in a very tight tolerance range.
The system described in the patent application is particularly suited for very small relays having more than one changeover contact so that a very compact structure is possible. The arrangement of the quadripole permanent magnet over the coil given simultaneous coverage of the contact elements by the pole plates or, respectively, yokes, is very meaningful to design this relay for a compact structure. This design, however, involves problems when such a system is to be utilized for switching high currents because an insulating path required between the contact elements and the magnet system necessitates additional measures. Further, without increasing the overall height, the flat magnet arrangement employed therein can be practically executed only with a ceramic magnet whose response to temperatures will lead to a great reduction of the contact force given uses under high ambient temperatures.
SUMMARY OF THE INVENTION
The present invention is directed to providing a modified and perfected polarized magnetic relay of the type initially cited which relay retains the advantageous properties of the known magnet system in such a fashion that particularly high contact forces for switching high currents can also be achieved given a high ambient temperature. In addition, the relay structure is a simple assembly that has a compact format and simultaneously provides large insulating paths between the magnet system and the contact elements.
To accomplish these goals, the present invention is directed to an improvement in a polarized magnetic relay having a base body; a coil being secured in the base body and having a coil body with an axially extending passage, a first end flange, a second end flange and a winding on the coil body between the flanges; a bar-shaped armature being received inside of the passage of the coil body on an axis thereof with one end of the armature being pivotably mounted adjacent the first flange; a permanent magnet arrangement having two pole plates which are on a common plane extending parallel to the coil axis, each pole plate adjacent the second flange having an end portion extending at right angles to the common plane to provide spaced surfaces with an air gap therebetween for a free end of the armature to extend into said magnet arrangement including a flux plate having a portion extending perpendicular to the coil axis and having a segment extending parallel to the pole plates and coacting with the pole plates to form a space for receiving each magnet of the arrangement; at least one stationary contact element anchored in the base body; and at least one movable contact being moved by the armature between a position out of engagement with the associated stationary contact and a position engaging the stationary contact. The improvements comprise the magnet arrangement having a portion on both sides of the coil, each portion of the arrangement including one pole piece and a narrow segment of the flux plate extending parallel thereto to form a space for receiving a double pole permanent magnet, at least one permanent magnet being provided in one of the two spaces, said one end of the armature being mounted for pivotal movement in a recess in the portion of the flux plate, actuating means for transferring movement of the armature to the movable contact element and wherein said base body having recesses for receiving each of the parts of the relay including the coil body, the contact elements, said flux plate, each permanent magnet and the two pole plates so that during assembly of the relay, the elements, body, plates and magnets are easily plugged into the base body.
Given the inventive relay, the magnetic circuit is improved on the one hand in that the armature is seated directly in the flux plate so that the air gap between the magnet and parts is reduced to a minimum. High contact forces for high-voltage current contacts can thereby be achieved. On the other hand, the magnet system or arrangement is structurally modified over the known magnet system in such a fashion that the permanent magnet arrangement is displaced into the base body at both sides of the coil so as to enable a plug-type fastening of the individual parts into the base body to facilitate a good insulation by means of corresponding design of the base body and therefore a compact overall design of the relay becomes possible.
A permanent magnet arrangement has hereby been subdivided into two parts at both sides of the coil. A relatively great magnet length is thus respectively available for the two permanent magnets next to the coil. Thus, alnico magnets (magnets of aluminum-nickel-cobalt alloys) can be employed. These types of magnets, in fact, require a greater length in the polarization direction than the ceramic magnets but are significantly less temperature-dependent. A relay therefore still retains high contact forces even given utilization under high ambient temperature on the order of 125° C. The pole plates are indeed disposed in the same manner as in the known system and angled down and inwardly toward the armature. However, differing therefrom, the two permanent magnets are not disposed at the outside of the pole plate or yokes as seen from the coil but at the side facing the coil so that the coil lies between two stratas of pole plates, permanent magnets and flux plate sections.
The two permanent magnets, which are polarized in mutually opposite directions, can be balanced independently of one another so that both a bistable switching behavior as well as a monostable switching behavior--as a result of asymmetrical balancing--can be achieved. Also, it is conceivable in a specific embodiment wherein the permanent magnets at one side of the coil is completely demagnetized or is omitted altogether. In this case, the space between the pole plate and the flux plate section can be ferromagnetically bridged or connected so that the relay is lent a monostable switching behavior.
As mentioned, both the coil body as well as the permanent magnets, the pole plates and the flux plate are respectively secured next to one another in the base body by means of plugging the members, bodies or elements into recesses in the base body. Since this design is to be specifically suitable for switching high currents, it is expedient to design the base body as a housing which encloses the magnetic system both at the bottom side as well as with the four lateral walls so that only a passage for the armature or, respectively for a contact slide actuatable via the armature is left open. Moreover, the bottom side or base is necessarily recessed in the region of the coil so that the entire depth of the base body within an inverted protective cap is available for the coil winding. The contact elements are thereby likewise disposed in the base body but separated from the housing surrounding the magnetic system. To this end, the base body expediently forms a second or additional chamber surrounding the contact elements. This additional chamber comprises lateral slots for the insertion of the contact terminal elements.
The relay possesses at least one stationary contact element and one movable contact element. A changeover contact is also possible as is the provision of more than one contact pair or changeover contact, for example, by means of disposing respectively one contact pair at each side of the magnet system. In this latter instance, a contact actuating slide could, for example, be hinged to the armature with its central part and actuated respectively movable contact elements with its two ends. In an embodiment of the inventive relay, the movable contact element in the form of a contact spring is secured to a rigid terminal element anchored in the base body. The neutral position of such a contact spring can be determined by a detent fashioned in the housing or also by an adjustable continuation of the appertaining terminal element. In another embodiment, the movable contact spring can also be secured to a continuation of the armature. In this case, the contact spring is designed as a contact bridge or is connected to a terminal element via a flexible lead.
In one embodiment of the invention, a contact actuation member is coupled to the free end of the armature, for example, to that end lying opposite to the bearing thereof. The magnet system, however, can also be disposed such that the armature penetrates the flux plate with its seated end and comprises an angle of continuation in extension of this end which indirectly or directly actuates the contact spring.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a fundamental illustration of the magnet system for the relay in accordance with the present invention;
FIG. 2 is a cross-sectional view with portions in elevation taken along line II--II of FIG. 3 of the relay in accordance with the present invention;
FIG. 3 is a cross-sectional view with portions in elevation taken along line III--III of FIG. 2;
FIG. 4 is a side view taken in the direction of arrow IV of FIG. 2;
FIG. 5 is a cross-sectional view taken along line V--V of FIG. 2;
FIG. 6 is a partial cross-sectional view similar to FIG. 2 of a modification or embodiment of the contacts in accordance with the present invention;
FIG. 7 is a cross-sectional view similar to FIG. 2 of an embodiment of the relay;
FIG. 8 is a cross-sectional view similar to FIG. 2 of another embodiment of the present invention;
FIG. 9 is a cross-sectional view of a still further embodiment in accordance with the present invention; and
FIG. 10 is a cross-sectional view similar to FIG. 2 of yet another embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The principles of the present invention are particularly useful in a relay such as illustrated in FIG. 2 which utilizes a magnetic system best illustrated in FIG. 1. As illustrated in FIG. 1, an elongated, bar-shaped armature 2 is disposed in a coil 1 that is only schematically illustrated. On both sides of the coil 1 are respective permanent magnets 3 and 4. The magnet 3 is positioned between a pole plate or piece 5 and a narrow section 7a of the flux plate 7. In a similar manner, the magnet 4 is positioned between a pole plate or piece 6 and a narrow section 7b of the flux plate 7. The two magnets have opposite polarization directions. At their mutual facing edges, the two pole plates 5 and 6 have sections or portions 5a and 6a which are bent roughly at right angles to a common plane of the plates 5 and 6. As illustrated, these portions 5a and 6a are angled inwardly down and form mutually opposed pole faces that are parallel to one another. A free end 2a of the armature 2 is switchable in a working air gap between the faces of the portions 5a and 6a. The opposite end 2b of the armature 2 is seated in a portion 7c of the flux plate 7 which section or portion is perpendicular to the coil axis. As illustrated, the armature end 2b is received in a recess or aperture 7d so that a good transfer of the magnetic flux between the flux plate 7 and the armature 2 is assured. The permanent magnets 3 and 4 as well as flux plate segments 7a and 7b are thus disposed at both sides of the coil and are respectively laterally attached to the pole plates 5 and 6, respectively, at the side towards which the pole plate sections 6a and 6b are also angled. A flat format of the magnetic system or arrangement is thus achieved so that this can be used in a base body in a compact form.
An actual relay in accordance with the present invention is illustrated in FIGS. 2-5. In this relay, a base body 11 has a bottom portion 11a which has a recess 11b that receives a coil body 12 with a winding 13. The coil body 12 has a spool shape and has an axially extending passage 12a, a first end flange 12c and a second end flange 12b. A bar-shaped armature 14 having ends 14a and 14b is disposed in the passage 12a roughly on the axis of the coil body 12. A permanent magnet 15 is positioned above the coil body 12 and a permanent magnet 16 is positioned below the coil body 12. A pole plate or piece 17 engages one side of the permanent magnet 15 while a pole plate or piece 18 engages one side of the permanent magnet 16 and the two pole pieces basically lie in a common plane which extends parallel to the axis of the coil body 12 (see FIG.3). Each of the pole plates 17 and 18 adjacent one end have sections or portions 17a and 18a which extend at right angles to the common plane and provide parallel faces on opposite sides of the axis of the coil, which faces surround a free end 14a of the armature. Thus, the faces of the sections or portions 17a and 18a form a working air gap 19 in which the armature is moved back and forth. The pole faces of the two magnets 15 and 16 which are opposite to the pole faces engaged by the plates 17 and 18 are covered with respective sections 20a and 20b of a flux plate 20 which has a major portion 20c that extends perpendicular to the coil axis and which has an opening or recess 21 in which an end 14b of the armature 14 is received to form a pivotable mounting of the armature. As illustrated, the armature preferably has shoulders such as 22 adjacent the end 14b to limit the movement of the armature into the aperture 21 and to insure good contact between the armature and the flux plate portion 20c.
As illustrated in the drawings, the coil body 12 with the windings 13 and the armature 14, the permanent magnets 15 and 16, the pole plates 17, 18 and the flux plate 20 are all surrounded on all sides by lateral wall portions 23, 23a, 24 and 44 of the base body 11. As mentioned hereinbefore, these wall portions form a recess 11b in the low region 11a of the body 11 for receiving the coil body so that the bottom 11a of the base body 11 need not be wider than the diameter of the coil winding. In addition, the base body forms respective seating surfaces for the plug-type fastening and positioning of the individual parts. For example, the flux plate 20 has a segment 20a received in a recess 25 formed between the lateral wall portions 23 and 23a. In a similar manner, the segment 20b is received in the recess 26 which is formed between the segment 24 and 23a (FIG. 3). These recesses 25 and 26 also receive the permanent magnets and the recess 25 is spaced from the recess 11b by a wall or portion 27 while the recess 11b is spaced from the recess 26 by a wall portion such as 28. The wall portion 27 has a recess 27a which helps receive and hold the magnet 15 in the desired position and the wall portion 28 (FIG. 2) has a recess 28a for receiving and holding the magnet 16 in the desired position. The pole plates 17 and 18 are likewise laterally supported against the walls 23 and 24 whereas their angled sections 17a and 18a lie between the seating surfaces 29 and 30 of the second flange 12b and are supported at the inside by a nose-like elevation or projection 31 of the base body 11 as well as the nose or portion 32 on the coil body 12 (see FIG. 3). Thus, each of these parts is plugged into its position in the base body 11 and the desired air gap is defined.
The wall portion or partition 23 also forms an insulation between the magnetic system or arrangement and a contact chamber 33 in an upper portion of the base body 11. In the contact chamber 33, a stationary contact element element such as 34 with a terminal element 35 as well as a contact spring element 36 with a terminal element 37 are mounted. The two contact terminals 35 and 37 are secured by being plugged into grooves or recesses on the coil body 11 from opposite sides. They form respective terminal pins 38 in the grid with the coil terminal pins 39 as well as plug receptacle terminals (fast-on plugs) such as 40 (FIG. 2). The contact element 36 is actuated by a slide 41 which has a recess or aperture 42 that is received on the free end 14a of the armature. The free end of the contact spring 36 is received in an aperture opening 43 at the opposite end of the slide 41. The slide 41 slides along a glide face of a channel 44 (FIG. 5) which is formed in the end of the body 11. The slide is secured in the channel 44 by a pair of projections 45 which are provided on an inner surface of a protective cap 46 of insulating material that is slipped over the body 11. Due to utilizing insulating material for both the body 11 and the cap 46, a large insulating path can be obtained between the magnet system in the lower portion of the body and the contact elements which are in the upper portion with only a passage 47 for the armature which passage is formed in a side wall 48 of the base body 11.
The assembly of the various parts of the relay is obtained in a simple fashion by means of a plug-in technique. First of all, the wound coil body 12 is assembled with the flux plate 20 whereby insulated bushings 49 of the terminal pins 39 extend through a recess or slots 50 of the flux plate section or portion 20c. Subsequently, the flux plate with the coil body is inserted into the base body 11 and the permanent magnets 15 and 16 as well as the pole plates 17 and 18 are then assembled in the respective recesses by a plug-in manner. The terminal element 35 with contact element 34 is likewise introduced from the same side whereas the contact terminal 37 is introduced into and secured in the base body from an opposite side. The armature 14 is introduced into the passage 12a of the coil body with its fixed end assembled with the flux plate portion 20c. Then the contact slide 41 is plugged onto the armature and onto the contact spring 36. The parts are secured in the insulated base body 11 by means of assembling the protective cap 46 thereon.
As shown in FIG. 2, the contact 51 of the movable contact spring 36 rests on a seat 52 when in a neutral condition. This seat 52 has been designed by a crimped extension of the terminal element 37. The neutral position of the contact spring can be adjusted by means of bending this seat 52.
In an embodiment or modification illustrated in FIG. 6, the contact 51 is supported against a detent or rib 53 which is formed in the insulating material of the body 11. Otherwise, the relay illustrated in FIG. 6 is exactly like the relays of FIGS. 2-5.
In FIGS. 7-10, four modifications or embodiments of the relay of the present invention are illustrated. For example, in FIG. 7, a relay has a base body 61 for receiving a coil body 62 with a winding 63. An armature 64 as well as permanent magnets 65 and 66 are positioned with the armature 64 extending into the passage of the coil body and the magnets being on opposite sides thereof. Pole plates 67 and 68 are disposed as described above as well as the flux plate 69. Two stationary contact elements 70 and 71 are mounted in the body 61 with a movable contact element or contact spring 72 anchored therebetween. To actuate the movable contact, the armature 64 has a bent or crimped continuation 73 on which a slide or element 74 of insulating material has been formed or extruded thereon. Thus, actuation of the relay from the position illustrated to an upper position causes the movable contact 72 to move from contact with the stationary contact 71 to the stationary contact 70.
In the embodiment illustrated in FIG. 8, the relay has a base body 81, a coil body 82 with a winding 83, an armature 84 and permanent magnets 85 and 86. Two pole plates 87 and 88 as well as a flux plate 89 are disposed in the base body 81 but are disposed at the opposite ends from the positions illustrated in FIG. 7. In a fashion similar to that above, the armature 84 is seated in a passage in the flux plate 89, however, the armature has a portion that extends past the seated end and is provided with an angled or bent continuation 90 which has a portion extending parallel to the armature and then has a U shape. The end of the continuation is connected by a slide 91 of insulating material to the movable contact spring 92. A stationary contact element 93 is anchored in the base body 81 with its terminal element as is the terminal element for the contact spring or element 92.
Another embodiment of the relay is illustrated in FIG. 9. In this embodiment, which is similar to the embodiment of FIG. 8, the two stationary contact elements 94 and 95 are anchored in the base body 81 and a movable contact spring or element 96 is switchable therebetween. This movable contact spring 96 is rigidly connected to an armature continuation 90 by an insulating block 97 so that it is a loosely mobile slide and any friction is eliminated. It should be noted that the electrical contact to the movable contact spring 97 is attained via a wire which extends into the relay.
A final embodiment is shown in FIG. 10. In this embodiment, a magnetic system with a coil body 102 with a winding 103 and an armature 104 is shown as being disposed in a base body 101. In addition, a permanent magnet 105 is disposed at one side of the coil body whereas the two pole plates 107 and 108 as well as a flux plate 109 are symmetrically provided in accordance with the preceding illustrative embodiments. The base body 101 has a guide strip 110 which forms a guide channel with the protective cap 111. Balls 112 for contact actuation are movably arranged in this guide channel. These balls 112 consist of insulating material and are dimensioned in sizes and numbers such that they precisely fill out the distance between the armature 104 and a contact spring 113 in order to switch this contact spring between the two cooperating contact elements 114 and 115. The actuation balls 112 can, for example, by provided in two slightly different sizes so that a different combination and thus different actuation units can be formed by means of corresponding selection from these two sizes. Thus, during the assembly of the relay, a precise distance between the armature 104 and the contact spring 113 is first determined and the required combination of balls with slightly different diameters is correspondingly selected. As mentioned hereinabove, due to the presence of only a single permanent magnet 105, the pole piece such as 108 is ferromagnetically connected to the flux plate 109.
Although various minor modifications may be suggested by those versed in the art, it should be understood that I wish to embody within the scope of the patent granted hereon, all such modifications as reasonably and properly come within the scope of my contribution to the art. | An improved polarized relay characterized by a coil body being received in a recess of a base body along with a permanent magnet arrangement which has a pair of pole plates extending in a common plane with portions bent to form an air gap for receiving a free end of an armature, a flux plate extending perpendicular to the axis of the coil and having a recess to mount the armature and segments extending parallel to the pole plates to form spaces for receiving at least one permanent magnet with the recess being entirely closed by a protective covering so that the only exposure of the magnet arrangement and coil to the contacts is through an opening in which the armature extends to actuate the movable contact element. The polarized relay due to the insulation of the magnet arrangement and the coil is particularly adapted for contacts handling high currents at high ambient temperatures. | 7 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This utility patent application claims the benefit of the filing of U.S. Provisional Patent Application No. 60/424,159, entitled “Commercial External Re-Entry Testing from Orbit,” filed on Nov. 6, 2002 and the specification thereof is incorporated herein by reference.
[0002] This utility patent application also claims the benefit of the filing of U.S. Disclosure Document No. 521688, entitled “Commercial External Re-entry Testing from Orbit (IDF063) and Secondary Internal Payloads (IDF039),” filed on Nov. 15, 2002 and the specification thereof is incorporated herein by reference.
NO GOVERNMENT RIGHTS
[0003] No government funding, no government support or government contract or clause is related to this invention.
COPYRIGHTED MATERIAL
[0004] A portion of the disclosure of this patent document contains material that is subject to copyright protection. The owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyrights whatsoever.
BACKGROUND OF THE INVENTION
[0005] 1. Field of the Invention (Technical Field)
[0006] The present invention relates to transporting external test experiments to and from orbit on the exterior of a reusable launch vehicle. More particularly, the present invention relates generally to external vehicle experiments, integration, transport to orbit, exposure in orbit, exposure to the external re-entry environment from orbit including instrumentation and testing apparatus and the return of various support hardware and experiment sample services used on reusable space transportation vehicles.
[0007] 2. Description of the Related Art
[0008] Note that the following discussion refers to a number of publications by author(s) and year of publication, and that due to recent publication dates certain publications are not to be considered as prior art vis-à-vis the present invention. Discussion of such publications herein is given for more complete background and is not to be construed as an admission that such publications are prior art for patentability determination purposes.
[0009] The transportation of cargo to space is expensive. The secondary payload hardware has mass and minimum volume. Transporting the internal secondary payload hardware to and from orbit in an affordable manner is a goal consistent with life cycle costs and efficient logistics operations. The problem is the cost of the individual operations required to transport cargo to orbit. The part of the transportation operation can be addressed by the emerging reusable launch vehicles. Kistler Aerospace's secondary payload hardware research and development has proposed various additional aerospace structures and opened a new area of technology and commercial secondary payload hardware accommodation. Secondary payload hardware structures are a refined technology within the aerospace community. Unmanned activities in space are less expensive than manned activities. The unmanned aerospace reusable launch vehicle (RLV) can provide the secondary payload hardware technologies to smooth this process.
[0010] The traditional approach to manifesting of space launch systems has been hardware intensive, safety driven and long duration scheduling activities. The emerging commercial technologies point another way and attempt to be sensitive to commercial customer's launch on demand requirements.
[0011] Many previous space launch patents in prior art discuss reusable features, but none talk about external payloads designed to permit the testing of the materials required. The heating on the surfaces of the reusable launch vehicle are significant and require testing to develop a reliable reusable material and the testing environments for development. A typical simulation procedure requires several wind and arc jet wind tunnels to simulate, on the earth's surface, part of the re-entry environment experienced in an actual orbital re-entry.
[0012] U.S. Pat. No. 4,884,770 to Martin, issued on Dec. 5, 1989, describes a earth to orbit turbojet vehicle, but no mention of testing external surfaces on the exterior. U.S. Pat. No. 4,796,839 to Davis, issued on Jan. 10, 1989, describes an earth to orbit vehicle with recovery aspects, but no mention of testing external surfaces on the exterior. U.S. Pat. No. 4,265,416 to Jackson of NASA, issued on May 5, 19819, describes a earth to orbit reusable vehicles, but no mention of testing external surfaces on the exterior. U.S. Pat. No. 5,568,901 to Stiennon, issued on Oct. 29, 1996, describes a two stage earth to orbit reusable vehicle, but no mention of testing external surfaces on the exterior surfaces. Even U.S. Pat. No. 4,802,639 to Hardy, issued on Dec. 5, 1989, describes an earth to orbit turbojet vehicle, but no mention of testing external surfaces on the exterior.
[0013] U.S. Pat. No. 5,133,517 to Ware, issued on Jul. 28, 1992, uses an access door on the external tank, but fails to associate it to any exterior tests designed to provide samples for thermal protection system (TPS) analysis in the patent.
[0014] U.S. Pat. No. 4,650,139 to Taylor, issued on Mar. 17, 1987, attempts to alter the TPS on a partly reusable space launch vehicle, but enhance the aerodynamic flow by changing the re-attach point and injecting fluids into the slip stream, but no mention of returning sample for analysis or removing samples from the vehicle after re-entry. U.S. Pat. No. 4,790,499 to Taylor, issued on Dec. 13, 1988, expands the original patent, but fails to return any external samples.
[0015] The exterior sample return from the external tank (ET) of the space shuttle has been studied by NASA and their manufacturers in the 1980's, but the sample return from the ET requires removal of the samples from the ET after it has been taken to orbit. This involves altering the space shuttle mission trajectory, the salvage of the ET in orbit, a space walk by an astronaut for removal of the TPS samples from the ET, the restowing of the samples aboard a reusable segment of the vehicle and the proper disposal of the ET, which involves significant additional effort and expense.
[0016] Project Re-Entry II: Returning samples from Earth orbit at www.gvsp.usra.edu steps around the issue, but discusses low-cost sample return missions and has held two workshops, but doesn't mention using the return capsule and a test article for future mission for exterior materials or future samples for development by analysis of re-entry materials. The Ariane vehicle by the European Space Agency creates an Ariane Re-entry Demonstrator (ARD) testbed to re-enter from earth orbit, but is separate hardware and appears to have no exterior re-entry samples in the literature or pictures. Again it is the microgravity that is the focus of ARD rather than the phased testing approach with incremental development advances in materials technology based on systematic analysis of re-entry sample materials from actual re-entry missions.
[0017] Even the Orbital Science Corporation Pegasus alludes to leading edge research into thermal protection systems on www.orbital.com and some of their technical papers and literature details missions for spaceplanes, but all seem to cost an entire mission instead of the full instrumentation tests with sample back for analysis in an incremental development manner. Prior art uncovered to date is not directly germane to the present invention.
[0018] The space station attempts to address the exposure of experiments to the space environment, see Brian Berger's article, “NASA Aims to Finish Express Pallet As Costs Stiffe Brazil's Plans,” SPACENEWS Aug. 26, 2002, 1p, Springfield, Va., USA. The Express Pallet does not address either cycle through the atmosphere, however. Astrocourier (USA) addresses a similar commercial market, but also does not offer either cycle through the atmosphere, however.
[0019] Accordingly, it can be appreciated that there is a great need for a cost effective, reliable, efficient, and safe hardware systems using integrated technologies containing subsystems common with the reduced cost hardware solutions. The present invention provides this and other advantages, as will be apparent from the following detailed description and accompanying figures.
SUMMARY OF THE INVENTION
[0020] The techniques described herein comprise, in an exemplary embodiment, a system for introducing payloads into earth orbit. The system comprises a reusable orbital vehicle capable of being placed in earth orbit and having an outer skin surface. The vehicle has plurality of attachment positions located on the outer skin surface of the orbital vehicle. The system further comprises a first experimental package affixed to the orbital vehicle at a first one of the plurality of attachment positions wherein the first experimental package is exposed to the external atmosphere during launch and reentry phases of a space mission and is further exposed to the environment of space while in orbit.
[0021] In an alternative embodiment, the system may further comprise a second experimental package affixed to the orbital vehicle at a second one of the plurality of attachment positions such that the second experimental package is exposed to the external atmosphere during launch and reentry phases of the space mission and is further exposed to the environment of space while in orbit.
[0022] In one embodiment, the system further comprises an access panel on the outer skin surface of the reusable orbital vehicle wherein at least one of the plurality of attachment positions is located on the access panel. The access panels may be removable from the reusable orbital vehicle.
[0023] The experimental package may comprise a thermal protection system. In one embodiment, a carrier plate is configured for attachment at the first one of the plurality of attachment positions and further configured for attachment to the first experimental package wherein the carrier plate is intermediate the outer skin surface of the orbital vehicle and the first experimental package. Alternatively, the system may further comprise a thermal protection system affixed to the orbital vehicle to form the outer skin surface thereof. The thermal protection system at at least one of the plurality of attachment positions being configured for attachment to the first experimental package.
[0024] The plurality of attachment positions may be in a variety of different locations on the orbital vehicle. The orbital vehicle has an elongated shape with first and second ends and a rocket engine positioned proximate the second end. The first of the plurality of attachment positions is on the exterior skin of the orbital vehicle substantially at the first end. Alternatively, a first of the plurality of attachment positions may be on the exterior skin of the orbital vehicle forward of a midpoint between the first and second end. In yet another alternative embodiment, the first of the plurality of attachment positions may be on the exterior skin of the orbital vehicle rearward of a midpoint between the first and second end. In yet another alternative embodiment, the orbital vehicle also has an aft skirt proximate the second end wherein a first of the plurality of attachment positions is on an exterior skin portion of the aft skirt.
[0025] In yet another alternative embodiment, the orbital vehicle has an aft skirt and a protected attachment position on an interior portion of the aft skirt. The system may further comprise an aft skirt with an attachment member mounted to an interior portion of the aft skirt. In this embodiment, the attachment member may be rotatably mounted to the interior portion of the aft skirt.
[0026] A second experimental package may be coupled to the attachment member and, the system may further comprise a control system to control movement of the attachment member and thereby position a second experimental package outside the interior portion of the aft skirt.
[0027] In yet another embodiment, the system further comprises a sensor associated with the first experimental package, the sensor generating sensor data. The system may further comprise an experiment management unit electrically coupled to the orbital vehicle and electrically coupled to the sensor wherein the experiment management unit receives and stores the generated sensor data. The system may also be used with an avionics data bus on the orbital vehicle used to monitor operation of the orbital vehicle. In this embodiment, the experiment management unit is coupled to the avionics data bus to monitor the operation of the orbital vehicle and to store data related to the operation of the orbital vehicle in association with the generated sensor data. The sensor may be used with the first experimental package wherein the first experimental package comprises a thermal protection system.
[0028] In yet another embodiment, a system for introducing payloads into earth orbit comprises a reusable orbital vehicle having an elongated body portion with first and second ends with a rocket engine positioned proximate the second end of the orbital vehicle and an aft skirt coupled to the body portion proximate the second end and extending circumferentially around the rocket engine. The system further comprises an attachment member mounted to an interior portion of the aft skirt and configured to receive an experiment.
[0029] In one embodiment, the attachment member is rotatably mounted to the interior portion of the aft skirt. In another embodiment, the attachment member is movably mounted to the interior portion of the aft skirt and the system further comprises a control system to control movement of the attachment member to move the attachment member and thereby position the experiment outside the interior portion of the aft skirt.
[0030] In one embodiment, the experiment may be an experimental control surface. In this embodiment, the control system provides steering control of the attachment to thereby steer the experiment while positioned outside the interior portion of the aft skirt. In this embodiment, the system may also comprise a sensor associated with the experiment to generate sensor data and a data storage unit to store the generated sensor data.
[0031] Other objects, advantages and novel features, and further scope of applicability of the present invention will be set forth in part in the detailed description to follow, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] The accompanying drawings, which are incorporated into and form a part of the specification, illustrate several embodiments of the present invention and, together with the description, serve to explain the principles of the invention. The drawings are only for the purpose of illustrating a preferred embodiment of the invention and are not to be construed as limiting the invention. In the drawings:
[0033] [0033]FIG. 1 is the exterior secondary payload hardware locations possible on a reusable launch vehicle (RLV).
[0034] [0034]FIG. 2 is a fragmentary cross-section of the RLV of FIG. 1 and an external payload illustrating an example mounting of a standard exterior secondary payload hardware system.
[0035] [0035]FIG. 3 illustrates an example of exterior secondary payload hardware attachment.
[0036] [0036]FIG. 4 is the aft skirt launch vehicle location for the exterior secondary payload hardware deployed while in flight;
[0037] [0037]FIG. 5 illustrates the secondary aft skirt payload hardware of FIG. 4 in a retracted condition.
[0038] [0038]FIG. 6 illustrates the secondary aft skirt payload hardware of FIG. 4 in a deployed condition.
[0039] [0039]FIG. 7 illustrates the exterior secondary payload environment during a flight of the RLV of FIG. 1.
[0040] [0040]FIG. 8 is a functional block diagram of an experiment management unit to control experiments and record data.
DETAILED DESCRIPTION OF THE INVENTION
[0041] In contrast to high cost current technology, the present invention uses the emerging technologies to create hardware and procedures of a commercial nature. These secondary payload hardware systems and environments that start the process of lowering the cost of space activities by creating a commercial system using space for commercial gain and supported by affordable transportation.
[0042] As will be discussed in detail below, the exterior secondary payload hardware invention provides support for the exterior experiments and other experiment accommodation hardware and eventually integrating/delivering/servicing experiment payloads to low earth in a cost effective manner and return through the re-entry environment. The hardware of the invention is a reusable launch vehicle (RLV) supporting a series of exterior secondary payloads using hardware solutions to create a commercial service enterprise providing access to the ascent and re-entry environments for customers.
[0043] The accommodation of external secondary payload hardware on the launch vehicles uses various methods to provide a commercial service to the customer. A primary advantage of the techniques described herein is to reduce costs. This advantage includes the cost effective combination of a reusable launch vehicle, with both the ascent and re-entry environment, an affordable subsystem hardware concept for the commercial attachment of external experiments, the processing of the experiments within the integration or refurbishment between flights, the use of the reusable launch vehicle's avionics, power, communications and other capabilities and other technologies to reduce the costs for testing.
[0044] The exterior secondary payload hardware on a reusable launch vehicle advantageously provides an opportunity for commonality with existing subsystems already used on the launch vehicle and/or secondary payload hardware providing cost effective common subsystems through commonality in design, procurement, testing and secondary payload hardware attachment.
[0045] The common ground handling techniques, launch on demand manifesting, technical maintenance, financing and ownership of the exterior secondary payload hardware, launch vehicle, and payloads all serve to reduce costs and increase efficiency to the point where commercialization is feasible.
[0046] Another advantage of the secondary payload hardware is an integrated design, flexible enough to be capable of accommodating, on an RLV, a number of different payloads from numerous organizations with varying requirements, different weights, different processing requirements, and varying financial needs. The RLV provides its vehicle capabilities as a testbed for the full cycle to and from orbit and ground services supporting the exterior secondary payload hardware payloads in orbit.
[0047] Within structured safety and aerodynamic limits, the invention includes the various exterior payloads with different shapes that can be attached to the exterior surface using adaptable structural interfaces. As will be described in greater detail below, the exterior secondary payload hardware placed in different locations on the host launch vehicle with the flexibility, common subsystems, multiple attachment locations and launch on demand capabilities of the exterior secondary payload hardware and RLV combination.
[0048] The exterior secondary payload hardware can be configured in various sized packages and placed as different sizes in both high and low heating areas on the host launch vehicle. This second stage of the RLV is cost effective, because it combines the advantages of a reusable launch vehicle including the ability to examine the materials used that is not available with expendable vehicles.
[0049] Another feature described herein includes the stowage of an experiment within the aft flare volume of the launch vehicle out of the slip stream. The mounting apparatus has a rotating arm to introduce this arm tip into the slip stream during the re-entry phase of the re-entry trajectory.
[0050] In a nominal mission, the exterior secondary payload hardware is mated with the customer's experiment. The launch vehicle powers the payload on the full transportation cycle. The current experimental timeline includes the full ascent exposure, 22 hours of the space environment in orbit and the re-entry environment to full landing.
[0051] The exterior secondary payload hardware relates to introducing a full service all in one testing environment, which can only be simulated on the Earth with a series of wind and arc jet tunnels to an existing customer base. The new interfaces and support structure technologies, reusable launch vehicle (RLV) technology and its use in the space environment of orbit offers a new avenue of testing that makes many expensive alternatives nearly obsolete. The present invention provides a more cost-effective integration, ascent transportation to orbit, 22 hour exposure in orbit and return through the re-entry environment. The customer system is capable of placing test samples and experiments into orbits beyond the capability of sounding rockets, sub-orbital air launch systems, arc jet/wind tunnels and other current development methods.
[0052] One example of a fully reusable launch vehicle is the Kistler Aerospace Reusable Launch Vehicle called the K-1. The present description illustrates the operation of the invention on the K-1 reusable launch vehicle. However, the present invention relates generally to the access to space ascent and re-entry environments plus hardware innovation and testing locations with supporting repeatable transportation cycles or missions, the transfer and attachment of payloads to a variety of space transportation vehicles for the research, testing and the exposure of experiments in orbital re-entry environments including the return of experiment samples to earth for analysis and profit.
[0053] The present invention hardware is capable of providing more than just the transportation service to orbit like all other expendable launch vehicles. The experiments, when carried to orbit and during re-entry from orbit, provide the services such as power, data recording, sensors, communications and different structural attachments using the existing Development Flight Instrumentation (DFI) System on the launch vehicle.
[0054] The development of thermal protection systems (TPS) for space launch vehicles requires a phased testing and development process of trial and error on various systems and materials that are tested and documented afterward. An expendable launch vehicle limits the analysis afterward, because the hardware and the exterior samples including the entire stage or vehicle are discarded in the launch process.
[0055] The K-1 is a reusable launch vehicle and offers the advantage of exposing the external experiments to the entire transportation cycle envelope and the opportunity to examine the experiment samples afterward. To obtain similar conditions from Mach zero to Mach 25, atmospheric pressures from 14.7 psi to zero and the thermal environments involved; required previous researchers and manufacturers to use a series of different wind tunnel and arc jet tunnels to attempt to duplicate the ascent, orbital and re-entry environments. This was time consuming, expensive, labor intensive and less effective than the present invention.
[0056] Experiment Accommodations
[0057] Ordinary expendable launch and re-entry vehicles have a variety of different environments on the exterior of the vehicle, but it generally requires two vehicles, one for launch and one for re-entry to provide the full testing environment. The reusable launch vehicle can provide the same environment on one reusable vehicle and repeat the identical experiment in both directions again on the next mission using a new test experiment.
[0058] The example K-1 vehicle can accommodate three basically different environment locations with different types of experiments in both directions of travel on the same vehicle. This is the subject of this patent application. Externally mounted experiments are mounted on fail-safe test panels and would include advanced materials and TPS experiments. Internally mounted experiment support hardware to support the exterior experiment is accommodated inside the reusable launch vehicle in a variety of locations on the vehicle. The third type of experiment is the replacement of an existing K-1 subsystem or component with one using advanced technology.
[0059] Externally Mounted Experiment Accommodations
[0060] The RLV can place experiments on the outside of the vehicle to demonstrate the operation of thermal protection systems and other exterior technologies in an actual launch, orbital, and reentry environment. While the space shuttle has a full transportation range of complete ascent and re-entry cycles on the same vehicle, it does not have the provisions for exterior test locations or the support hardware to support the testing or the provisions for supporting the experiments with power, communications and other services during the experiment phase. The reusable launch vehicle described herein provides exterior experiment locations in both directions.
[0061] The Kistler K-1 reusable launch vehicle (RLV) is one example of such a reusable launch vehicle. The K-1 RLV comprises a booster stage or launch assist platform (LAP) 58 (see FIG. 7) and an orbital vehicle (OV) 20 (see FIG. 1). Exterior experiments are mounted in Kistler supplied hardware of various sizes for use in various locations. The Kistler-supplied Experiment Containment hardware can also be used for government and commercial experiments. Experiments can be placed at locations on the OV nose, OV Mid-Body, and OV Aft Flare within regions of two different types of existing thermal protection system (TPS) on the Kistler vehicle. The repeatable experiments are designed to provide a standard mechanical and electrical interface for a wide variety of experiments.
[0062] Reference is now made to FIG. 1, which illustrates an exemplary embodiment of the invention. FIG. 1 is a side view of exterior secondary payload hardware locations offering the full range of re-entry heating environments on reusable orbital vehicle (OV) 20 , which may typically be the second stage of a two-stage launch vehicle. The initial booster stage, sometimes referred to as a launch assist platform (LAP), is shown diagrammatically as the LAP 58 in FIG. 7.
[0063] The OV 22 includes a number of suitable locations where external payloads may be attached. FIG. 1 illustrates six possible mounting locations for external payloads on the OV 22 ranging from a nose 22 location in a high heat area with surrounding thermal protection system tile to a less severe locations including one low heat aft skirt 24 location.
[0064] [0064]FIG. 1 illustrates an exterior nose experiment footprint 26 (identified as experiment number 1 footprint) at the forward end of the OV 22 at the opposite end from a launch vehicle engine 28 . Exterior experiment number 2 footprint 30 and exterior experiment number 3 footprint 32 are approximately 12 feet aft of the nose 22 and use carrier plate 46 footprint experiment hardware. Details of the carrier plate 46 are provided below.
[0065] Exterior experiment number 4 footprint 34 is at midbody region of the OV 20 and also uses carrier plate 46 footprint experiment hardware. Exterior experiment number 5 footprint 36 is on aft skirt 24 location and includes a tile substitution experiment location. Exterior experiment number 6 footprint 38 uses carrier plate 46 footprint experiment hardware and is on aft flare skirt 24 location.
[0066] The experiments on the K-1 RLV are located in areas where additional TPS material is located to protect the K-1 RLV from damage if an experiment breaks or fails. At each of the external mounting locations, backup insulation, in the form of bordering blankets and an ablator, is bonded to the K-1 structure to maintain thermal integrity of the host vehicle (i.e., the OV 20 ). In addition to the use of additional thermal material to protect the OV 20 , the experiment footprints may be conveniently located at hatchways, doors or access panels 39 . If a customer experiment fails, damage would be limited to the access panel 39 . The access panel 39 is removable and can thus be readily replaced if damaged.
[0067] The mounting footprints described above experience a range of different heat loads. For the high heat exposure, experiments can be mounted at experiment number 1 footprint 26 and experiment number 5 footprint 36 . The experimenter will either bond their tile onto the carrier plate 46 , which is then mechanically fastened to the K-1. Alternatively, the carrier plate can be bonded directly to the OV 20 .
[0068] The footprint of each experiment depends on the mounting location and the specific reusable launch vehicle. To provide the necessary thermal protection, the height of each experiment is generally limited to the TPS Outer Mold Line (OML), which is approximately 2.0 inches. The OML outline is shown in FIG. 2 by the cross-section of the TPS 40 of the OV 20 .
[0069] For safety reasons, the RLV has certain limitations, such as no experiments at the experiment number 1 footprint can exceed the local TPS thickness. The experiment thickness can possibly exceed the OML by more than 2 inches at experiment number 2-6 footprints 30 - 38 , but will require additional aerodynamic analysis and verification. The OV 22 can provide data recording to sensors mounted on or around the experiment, such as thermocouples and strain gauges, using its existing DFI system and passing insulated wire through the vehicle structure, ablator, and carrier plate. The DFI system monitors numerous parameters of the LAP 58 and the OV 20 using conventional technology. Data related to the operation of the OV 20 is made available on a standard 1553B data bus. The various experiments can make use of this system data by monitoring the 1553B data bus. As will be described in greater detail below, operational parameters that may be related to an experiment may be monitored and stored for further analysis by a customer/owner of the experiment. Details of the DFI system are also provided below.
[0070] Using the K-1 RLV as an example, the footprint for each experiment depends on the specific mounting location. Table 1 below provides example sizes for the experimental footprints 1-6.
TABLE 1 Passive Experiment Footprint Dimensions Foot- print # Location Type A (in.) B (in.) 1 Nosecap Tile 9.00 × 9.00 9.16 × 9.16 Substitution 2 Payload Module Carrier Plate 7.50 × 4.25 10.50 × 7.25 3 Payload Module Carrier Plate 7.50 × 4.25 10.50 × 7.25 4 Mid Body Carrier Plate 24.00 × 24.00 27.00 × 27.00 5 Aft Flare Tile 9.00 × 9.00 9.16 × 9.16 Substitution 6 Aft Flare Carrier Plate 6.00 × 14.00 9.00 × 17.00
[0071] In addition, the experiments must meet certain mass limitations, which are also dependent on the specific RLV and the specific mounting location. Again, using the K-1 RLV as the example, Table 2 provides maximum mass values (in pound-mass units) for each of the exterior experiment footprints 1-6:
TABLE 2 Passive Experiment Maximum Mass Footprint # Mass (lbm) 1 12.0 2 5.0 3 5.0 4 20.0 5 12.0 6 12.0
[0072] [0072]FIG. 2 is a cross section depicting an example of a customer thermal protection system (TPS) experiment 42 and thermal protection system 40 on the OV 20 with an example of carrier plate 46 experiment. The carrier plate 46 provides an optional mounting method for the customer's TPS experiment 42 . The carrier plate is provided to the customer and the customer's TPS experiment 42 is bonded to the carrier plate 46 . Thus, the customer has the responsibility of adequately bonding the customer's TPS experiment 42 to the carrier plate 46 . The carrier plate 46 has mounting holes 48 , which may be best seen in FIG. 3, to permit mounting of the carrier plate 46 to the OV 20 . Thus, the carrier plate 46 , with the customer TPS experiment 42 mounted by the customer, is bolted to the OV 20 at one of the attachment locations (i.e., the exterior experiment footprint numbers 1-6). For added protection, an ablator bonding layer 44 may be inserted beneath the carrier plate 46 to provide additional protection of the OV 20 in the event of a failure of the customer's TPS experiment 42 . The space surrounding the customer's TPS experiment 42 and the TPS 40 on the OV 20 is protected by a border blanket 47 . Thus, the customer's TPS experiment 42 is bonded to the carrier plate 46 and surrounded by the thermal border blanket 47 such that no gaps are permitted that might adversely affect the customer's experiment. Those skilled in the art will appreciate that protection of the customer's TPS experiment 42 also serves to provide additional thermal protection for the OV 20 .
[0073] [0073]FIG. 3 depicts the customer TPS experiment 42 ablator bonded to carrier plate 46 with multiple bolt holes 48 positioned around the peripheral edge of the carrier plate plus an instrumentation wire pass-thru hole 50 . The carrier plate 46 illustrated in FIG. 3 may be suitable for mounting in attachment positions such as the exterior experiment number 2 footprint 30 and the exterior experiment number 3 footprint 32 . Those skilled in the art will recognize that the shape of the carrier plate 46 and the position of the bolt holes 48 will vary depending on the footprint outline (see Table 1 above). However, the arrangement of FIG. 3 illustrates the use of the carrier plate 46 to receive the customer's TPS experiment 42 and the arrangement for attaching the carrier plate 46 to the OV 20 .
[0074] Sensors 43 , such as pressure transducers, strain gauges, thermocouples and the like may be part of the experiment 42 . The sensor 43 has sensor wires 43 w which are routed through the pass-thru hole 50 for connection to electronics, such as a data recorder, within the OV 20 . As will be described in greater detail below, an experiment management unit (EMU) 100 (see FIG. 8) has data processing capabilities to monitor and record data from the experiment 42 . Connections between the data sensors and the EMU 100 are provided by the sensor wires 43 w via the pass-thru hole 50 .
[0075] [0075]FIG. 4 depicts the OV 20 with aft flare skirt 24 region containing exterior experiment number 5 footprint 36 and exterior experiment number 6 footprint 38 . Exterior experiment number 5 footprint 36 located on a lower region of the aft flare skirt 24 bottom and is thus in a high heat region on the bottom of the OV 20 . Due to the high temperatures expected in the attachment area of the exterior experiment number 5 footprint 36 , the customer's TPS experiment 42 may be directly bonded to the TPS 40 of the aft flare skirt 24 . In applications in this region, the carrier plate 46 (see FIG. 3) may be eliminated. Border blanket 47 with through holes (see FIG. 2) can be used around tile substitution customer's TPS experiment 42 to provide additional thermal protection for the OV 20 . Further up on the side of the OV 20 aft flare skirt 24 is a lower heat area and the location of exterior experiment number 6 footprint 38 . A lower expected temperature range associated with the exterior experiment number 6 footprint 38 permits the use of the carrier plate 46 for ease in mounting the customer's TPS experiment 42 . The carrier plate arrangement, such as illustrated in FIG. 3, may be readily adapted for use at the exterior experiment number 6 footprint 38 .
[0076] Also located inside aft flare skirt 24 is an installable base unit 52 anchoring a deployment arm 54 . The deployment arm 54 comprises a base portion 54 b , an intermediate portion 54 i and a terminal portion 54 t . The deployment arm base portion 54 b is moveably coupled to the base unit 52 . The deployment arm base portion 54 b can rotate on an axis of rotation 53 to permit the deployment arm terminal portion 54 t to move into the slip stream surrounding the OV 20 as it moves in environments with some atmosphere at high speed. The deployment arm terminal portion 54 t is moveably coupled to the deployment arm intermediate portion 54 i and is capable of rotation in along three different and substantially orthogonal axes. As illustrated in FIG. 4, the deployment arm terminal portion 54 t can rotate about an axis of rotation 55 , an axis of rotation 57 and an axis of rotation 59 .
[0077] The movement of the deployment arm 54 may be electrically controlled by motors, gears, pulleys and the like. Alternatively, the deployment arm 54 may be hydraulically controlled. The EMU 100 (see FIG. 8) provides the necessary signals to control movement of the deployment arm 54 .
[0078] The deployment arm 54 is particularly useful for testing leading edges and control surfaces of space craft and the associated TPS used thereon. When the deployment arm 54 is activated and moved into the slipstream, the high speed creates friction and heat on leading edge TPS experiment 56 and acts through controllable rotation of the deployment arm 54 as a method of diverting the slip stream for purposes of steering reusable orbital vehicle 20 . Those skilled in the art will appreciate that the term “leading edge” refers to the edge of a wing or other re-entering object. The leading edge encounters significant heating and is generally the most difficult area of a space craft to test under simulated conditions. The present invention advantageously provides a technique for testing leading edge experiments under actual operating conditions. The leading edge TPS experiment 56 my be bolted or pinned to the deployment arm terminal portion 54 t . Alternatively, the leading edge TPS experiment 56 may be slipped on in a shoe arrangement. In yet another alternative embodiment, the leading edge TPS experiment 56 may be coupled to the deployment arm 54 all the way back inside the aft flare skirt 24 so that the actual connection is inside the protected volume and not in the slipstream itself.
[0079] The leading edge TPS experiment 56 may be used to test steering elements of a space craft. Steering elements, such as ailerons on a wing or tail rudder steering elements, which are used to steer a re-entering space craft may be tested as the leading edge TPS experiment 56 . In yet another alternative embodiment, the leading edge TPS experiment 56 may be used as a steering element itself. Some theorists have suggested that a single “foot” dangling behind a re-entering space vehicle in the slipstream can be mechanically turned to function like a canoe paddle and thus divert the vehicle back and forth to permit the “S” turns used by the space shuttle to dissipate the energy of reentry. The leading edge TPS experiment 56 may be repositioned using the mechanical, electrical or hydraulic steering subsystem to demonstrate the efficacy of a single dangling foot used to control S turns.
[0080] Such an approach to experimental design points out another advantage of the reusable system of the present invention. A space craft designer can test the testing steering elements on a craft, such as the OV 20 for several million dollars rather than risking several billion dollars on a new vehicle with no prior testing of such steering elements. Utilization of the deployment arm 54 on the OV 20 allows testing under actual conditions prior to the commitment of billions of dollars to the development of a new craft.
[0081] Those skilled in the art will appreciate that use of the leading edge TPS experiment 56 may alter the steering of the OV 20 in actual operation. Accordingly, the experimental protocol must take into account the effects of the experiment on the actual operation of the OV 20 . Furthermore, the OV 20 may use the steering element for non-experimental purposes to control re-entry, as described above.
[0082] [0082]FIG. 5 depicts aft flare skirt 24 region with one retracted position for deployment unit 52 with one retracted position for deployment arm 54 capable of rotating into the slip stream surrounding the OV 20 as it moves in environments with some atmosphere at high speed. This high speed creates friction and heat on leading edge TPS experiment 56 for testing and other purposes.
[0083] [0083]FIG. 6 depicts aft flare skirt 24 region for deployment unit 52 with one deployed position for deployment arm 54 capable of rotating into the slip stream surrounding the OV 20 as it moves in environments with some atmosphere at high speed. This high speed creates friction and heat on leading edge TPS experiment 56 for testing and other purposes. Ground level after landing 92 is far enough to allow protecting of leading edge TPS experiment 56 for testing and reuse purposes.
[0084] [0084]FIG. 7 depicts the OV 20 launch and re-entry environments from launch to reuse. The OV 20 launches with the assistance of launch assist platform 58 and is part of a complete transportation cycle from launch site landing 80 with experiment recovery 81 to next launch site landing 80 at ground level after landing 92 .
[0085] Carrier plate type customer's TPS experiment 42 and/or tile substitution type customer's TPS experiment 42 are attached to the OV 20 and carried with the LAP 58 from near landing area 80 upwards toward orbit. As the OV 20 moves along an ascent trajectory 88 , it experiences some heating and some re-entry heating and other environments after stage separation 84 at approximately Mach 4.4 at approximately 135,000 feet altitude.
[0086] Stage separation occurs at a point 84 along an ascent trajectory 88 . At stage separation 84 , the OV 20 separates from the LAP 58 . Following stage separation 84 , the LAP 58 changes direction 180 degrees. The center engine on the LAP 58 relights and propels the nearly empty 1st stage back toward landing 80 area for recovery and reuse. The LAP 58 experiences some re-entry heating and some other environments on LAP re-entry phase 86 moving toward landing 80 area.
[0087] Following stage separation 84 , the OV 20 continues on the ascent OV trajectory 88 into orbit and experiences some additional ascent heating and other environments. The OV 20 reaches orbit, delivers payload and orbits for approximately 22 hours for the earth to spin under it and position the OV 20 for re-entry OV trajectory 82 .
[0088] Those skilled in the art will appreciate that the OV 20 may carry a number of payloads into orbit. These payloads may include the exterior experiments attached to the OV 20 at the exterior attachment locations (i.e., the exterior experiment footprint numbers 1-6 or attached to the deployment arm 54 ), experiments contained within the interior of the OV 20 and satellites carried aboard the OV to be dispensed in orbit. The interior experiments are discussed in co-pending U.S. Patent Application Number (not yet assigned, Express Mail No. ER495032228), entitled COMMERCIAL EXPERIMENT SYSTEM IN ORBIT, filed on Oct. 9, 2003, which is assigned to the assignee of the present invention and which is incorporated herein in its entirety. The use of an active satellite dispenser to insert one or more satellites into orbit is discussed, for example, in co-pending U.S. patent application Ser. No. 10/132,083, entitled ACTIVE SATELLITE DISPENSER FOR REUSEABLE LAUNCH VEHICLE, filed on Apr. 23, 2002, which is assigned to the assignee of the present invention and which is incorporated herein in its entirety.
[0089] Moving along re-entry OV trajectory 82 , the OV 20 continues to entry interface 89 and starts pre-entry phase 60 with open loop bank command at approximately 400,000 feet or 76 miles above the earth. The OV 20 continues to entry phase 62 with 0.1 gravity encountered at a point 90 along the re-entry OV trajectory 82 . After continuing along re-entry OV trajectory 82 , the OV 20 initiates bank reversal 70 and enters a bank reversal phase 64 . The bank reversal phase 64 refers to a process in which the re-entering OV 20 performs a series of gentle S turns, such as used by the shuttle, to dissipate energy and to slow down. The wide gentle banking in alternating directions (i.e., S turns) allows the OV to dissipate a significant amount of the energy of re-entry and to reduce speed. At the end of the bank reversal 72 , the OV 20 continues to terminal phase 66 of along the re-entry OV trajectory 82 .
[0090] Moving along re-entry OV trajectory 82 , the OV 20 deploys a stabilization chute at a point 74 . This starts chute phase 68 and stabilization chute deployed 74 , drogue chute deployed 76 and finally main chute deployed 78 . This chute phase 68 sequence starts approximately 70,000 feet above the surface.
[0091] The OV 20 continues under parachute to launch site landing 80 . Customer's TPS experiment 42 is part of the OV 20 processing for reuse, which includes experiment recovery 81 . Data from sensors 43 is stored on-board the OV 20 and is recovered and returned to the customer for analysis.
[0092] The OV 20 contains an Experiment Management Unit (EMU) 100 , which provides each experiment with power, if necessary, data recording for analog sensors, digital data recording, if required, for example through an RS-422 interface, TTL-compatible digital discrete control lines, and access to the K-11553B avionics databus in a shadow or monitor mode.
[0093] [0093]FIG. 8 depicts the EMU 100 attached to OV 20 . The EMU 100 serves as the interface between various experiments (i.e., the customer's TPS experiment 42 of FIG. 3) and the OV 20 support services available from the OV 20 including power, communications, the 1553B data bus, control and other services including transportation.
[0094] Actual avionics flight data from the OV 20 is available via the 1553B data bus monitoring 102 through the connection of a multi-pin vehicle side electrical connector 104 to a mating tray side connector 106 for the actual flight of the experiment (i.e., the customer's TPS experiment 42 ).
[0095] Communications data from the OV 20 is available via an RS-422 communications link 108 through the connection of the vehicle side connector 104 coupled to the sensor wires 43 w via an experiment connector 110 for the actual flight of the experiment.
[0096] Discrete communications data or separate status information from the OV 20 is available via discrete commands in 5 standard wires 112 through the vehicle side connector 104 to the experiment connector 110 for the actual flight of the experiment.
[0097] Data recording to and from OV 20 is available via data recorder 114 through analog in 8 standard wires 116 via the vehicle side connector 104 to the experiment connector 110 for the actual flight of the experiment.
[0098] Power from the OV 20 is available via power conditioning 118 from an experiment battery 120 in the EMU 100 . The experiment connector 110 on the EMU 100 is shown with experiment support structure, such as the carrier plate 46 for the actual flight of the experiment on the OV 20 . A power inhibit circuit 128 further provides control to turn power on and off in 28 volt 2 standard wire power circuit 130 .
[0099] The EMU 100 may include conventional components such as an analog to digital converter (ADC) 122 to provide digitized signals 124 to the data recorder 114 , a digital to analog converter (not shown) and relay drivers 126 to control the discrete lines, and the like. The operation of these components is well known in the art and need not be described herein. The operation of the EMU 100 is controlled by a control system 132 , to provide the necessary timing for experiments, power control, signal buffering data storage and the like. The control system 132 may be a microprocessor, digital signal processor, microcontroller, programmable gate array, discrete component circuit or the like.
[0100] Well in advance of launch, Kistler K-1 staff delivers each experimenter an Interface Kit containing the requisite number of experiment size and thickness details, fasteners, electrical connectors, and an EMU simulator to verify the electrical interfaces. The box contains a standard attachment method to mount experiments. Prior to launch, the experimenters deliver their experiments mounted on furnished hardware to Kistler; who in turn, installs the hardware onto the K-1 vehicle. Multiple experiments from different customers may be placed on the same vehicle, or experiments may be separated into different locations, depending on compatibility, temperature or due to other issues. After the flight, Kistler returns the experiments and data to the experimenters, and delivers a Post-Flight Report documenting flight parameters.
[0101] If required, processing areas, office space, and storage areas at the launch site for the experimenter are available to support pre-launch checkout and testing. Selected operating parameters for the OV 20 may be used to assist in designing the customer experiments. Some of these parameters are provided below. Other parameters have already been discussed or are within the design skills of a person of ordinary skill in the art utilizing the disclosure contained herein.
[0102] External Experiments
[0103] Kistler's approach to externally mounted experiments is to replace existing K-1 hardware (access panels, doors, tile, or blanket parts) with technology experiments on fail-safe test panels. Panels will be designed with backup insulation and structure to maintain thermal integrity in the event of an experiment failure. Data recording will be made available through the existing developmental flight instrumentation (DFI) system on the K-1 vehicle.
[0104] External Experiment Environments
[0105] Material experiments will be exposed to the ambient air at Kistler's launch site in Woomera, South Australia.
[0106] Thermal Environment
[0107] Heat loads during reentry drive the design of materials and TPS experiments externally mounted to the orbital vehicle OV vary with the specific vehicle used. The example K-1 vehicle has specific predicted heat environment at each identified mounting location on K-1 Orbital Vehicle locations as shown in table 3 below:
TABLE 3 Heating Environment in K-1 OV External Footprints Peak Heating Integrated Rate Heat Load Radiation Eq. Footprint # (BTU/ft 2 /sec) (BTU/ft 2 ) Temp. (F.) 1 65.0 14,350 3,060 2 9.5 1,830 1,716 3 7.6 1,300 1,598 4 2.2 450 1,050 5 33.0 5,940 2,511 6 12.4 2,435 1,866
[0108] Acoustic Environment
[0109] Acoustic loads during reentry drive the design of materials and TPS experiments externally mounted to the orbital vehicle OV vary with the specific vehicle used. The example K-1 maximum predicted noise is 148 to 160 overall sound pressure level (in dB) at each external mounting location depending on the location, including the phase of flight the maximum environment occurs. If Kistler and the experimenter determine acoustic testing is required, Kistler will provide sound pressure spectrums for verification testing.
[0110] Design Limit Load Factors
[0111] An example K-1 design limit load factor of 35 g encompasses both predicted static and dynamic loads for externally mounted TPS experiments. This load factor applies to each axis (one at a time).
[0112] Subsystem Replacement Experiments
[0113] Reusable launch vehicles can substitute a test subsystem for an existing subsystem on the vehicle. An expendable launch vehicle can also substitute a test subsystem for an existing working subsystem, but the test subsystem never comes back for testing and evaluation. Each type of vehicle could also substitute a test subsystem and have a back up working subsystem to take over, if the test subsystem fails. The expendable vehicle would return only one half of the trips test data and no test system for testing and evaluation on the ground. The reusable launch vehicle can provide the full trip cycle of test data. The final category of experiment open to experimenters is replacement of an existing K-1 subsystem with one utilizing advanced technology. As an example of this options is the Space Launch Initiative (SLI) experiments on the K-1 vehicle. Existing interfaces will be maintained between the experiment and the vehicle. Examples of this type of experiment on the example K-1 vehicle include:
[0114] Replacement of a K-1 TPS material and joint details with another;
[0115] Replacement of one or more of the K-1's main engines with upgraded engine(s) utilizing advanced materials, mechanical subsystems, and IVHM;
[0116] Replacement of one of the K-1's batteries with higher energy density storage devices;
[0117] Replacement of one of the K-1's structural elements, such as propellant tanks, with elements utilizing advanced materials.
[0118] K-1 Development Flight Instrumentation (DFI) System
[0119] Data recording for an example K-1 vehicle is available to all categories of Space Launch Initiative (SLI) experiments (externally mounted, internally mounted, and subsystem replacement) through the K-1's existing DFI system. The DFI system was designed to provide a modular, tailorable system for measurement of data required for final verification of the K-1 RLV. Approximately 270 parameters will be measured using the system on the first four K-1 flights. Data measurement instruments in the basic DFI system include thermocouples, strain gauges, accelerometers, pressure transducers, temperature gas probes, Resistance Temperature Devices (RTDs), and microphones.
[0120] The example Kistler K-1 can leave all or part of the Development Flight Instrumentation (DFI) system in the K-1 vehicle to support NASA and other customer Add-on Technology Experiment flights, and can reconfigure and expand the DFI system over 50% to meet mission needs. The Kistler K-1 baseline DFI system is a distributed data acquisition system with data nodes located in all launch assist platform (LAP) and orbiter vehicle (OV) compartments. There are four OV nodes. Each node is capable of supporting up to 31 channels of analog/digital signal processing. The number of measurements that a channel can handle is dependent upon the type of signal being processed. For example:
[0121] A thermocouple channel (card) can process 8 thermocouples
[0122] An accelerometer channel (card) can process 2 accelerometers
[0123] A bridge circuit channel (card) can process 4 bridge circuits. Each node is capable of streaming 10 Mbps. The baseline DFI system does not send DFI data to the ground. Real time data is collected and recorded in a solid-state recorder [one each on the launch assist platform (LAP) and orbiter vehicle (OV) stages]. Each recorder is capable of recording four 10 Mbps channels.
[0124] Data from the DFI system is available for use in customer experiments using the 1553B data bus in monitoring only mode. For example, the EMU 100 may monitor data to determine flight status information. This flight status information can be stored in the data recorder 114 in association with data from the sensors 43 . Upon completion of the mission, the experiment owner may use the data for analysis of the experiment. The DFI system data may also be used by the EMU 100 to trigger certain events. For example, an experiment involving the deployment arm 54 may require deployment of the deployment arm at a certain phase of the mission (e.g., the re-entry phase 62 in FIG. 7). The EMU 100 monitors the 1553B data bus to determine the start of the re-entry phase 62 and triggers the activity of the deployment arm 54 .
[0125] Experiment Integration Facilities
[0126] Integration facilities required by experiment support crews vary on a case-by-case basis on other reusable launch vehicles. As a baseline approach, the example Kistler K-1 will set aside space in its vehicle processing facility (VPF) for use by the experiment's support crew as required. Kistler's K-1 example approach to SLI experiments is to integrate them as part of the normal maintenance and refurbishment process of the K-1 stages.
[0127] Therefore, placing the experimenter's support facilities in the Vehicle Processing Facility (VPF) will facilitate experiment integration into the K-1, which is refurbished and maintained in the same room. If required, Kistler can segregate the experimenter's area within the VPF, or provide a separate facility outside the VPF for use by experimenters. If clean facilities are required, Kistler can also provide the experiment support crew with a payload station in its PPF. The availability of the payload station is subject to coordination with Kistler's payload customers. The Payload Processing Facility (PPF) is designed to support satellite processing, test, and integration. The PPF includes two highbay payload processing work areas, two processing control rooms, a highbay payload module processing and hazardous operations area, a master airlock, a support equipment storage area, and the necessary office and personnel facilities. The Kistler Mission Control Center is also located in the PPF. Processing areas in the PPF are Class 100,000 clean facilities. Ultimately, experiments in the clean facility must be moved into the VPF for integration into the K-1.
[0128] Other objects, advantages and novel features, and further scope of applicability will be set forth in part in the detailed description to follow including drawings taken in conjunction with the accompanying drawings FIG. 1 through FIG. 7, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the new testing opportunities process instrumentation and combinations particularly pointed out in the appended claims.
[0129] Although the invention has been described in detail with particular reference to these preferred embodiments, other embodiments can achieve the same results. Variations and modifications of the present invention will be obvious to those skilled in the art and it is intended to cover all such modifications and equivalents.
INDUSTRIAL APPLICABILITY
[0130] The invention is further illustrated by the following non-limiting examples.
EXAMPLE 1
Passive Experiment Mounting Footprints
[0131] Six footprints are available to mount Passive Experiments on the outside of the K-1 Orbital Vehicle (OV). These footprints are attached to the exterior of the vehicle. Kistler's approach for passive experiments is to replace existing K-1 hardware (access panels, doors, tile, or blanket parts) with experiments mounted on Carrier Plates or bonded directly to the K-1 structure.
EXAMPLE 2
Passive Stowage with Active Re-Entry Environment Exposure
[0132] Commercial service includes the stowage of an experiment in the aft flare volume of the launch vehicle out of the re-entry slip stream and the ability to introduce the movable arm tip upon command or other control into the re-entry slip stream during the re-entry phase of the re-entry trajectory.
[0133] The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
[0134] Although the invention has been described in detail with particular reference to these preferred embodiments, other embodiments can achieve the same results. Variations and modifications of the present invention will be obvious to those skilled in the art and it is intended to cover in the appended claims all such modifications and equivalents. The entire disclosures of all references, applications, patents, and publications cited above are hereby incorporated by reference. | An experiment system with six different re-entry experiment locations for testing high temperature re-entry materials, creating new thermal protection systems, proving innovative new concepts for spacecraft exterior surfaces and the incremental development of next generation aerospace materials. A commercial transportation system to and from orbit provides a 24-hour return cycle for the experiments on a surface actually re-entering the earth's atmosphere. Now using existing doors, hatches and other points on the reusable launch vehicle's exterior, the actual re-entry environment is experienced by test specimens with quick turn around for a wide variety of different re-entry temperatures ranges for broad testing and development purposes. The reusable launch vehicle launches, remains in orbit for 24 hours and returns to provide an actual test environment for the exterior experiment system. | 1 |
This application is a continuation of application Ser. No. 947,502 Filed Dec. 29, 1986, abandoned.
The invention relates to a machine tool having a work spindle that can be made to revolve, and an electrical clamping drive associated with it. The clamping drive includes a threephase motor and a trigger unit for the motor. A machine of this kind is disclosed in U.S. Pat. No. 4,567,794 issued to Bald.
The machine may be a lathe or a milling machine with an electrical tool clamp or chuck, or a drilling or grinding machine, and the like.
Background
From a brochure of the Siemens company entitled "Elektromechanischer Antrieb fur Reitstockpinolen" [Electromechanical Drive for Tailstock Spindles], undated, an apparatus is known which can be flanged to the tailstock of lathes and includes a three-phase asynchronous motor, which is pole-changeable to alternate between virtually load-free fast speed and loaded creep speed. A strain gauge device detects the clamping force built up after meeting the workpiece, in order to adjust the clamping force in accordance with a predetermined value.
The pressing force is stored in a cup spring assembly.
The Invention
It is the object of the present invention to improve the machine tool of the generic type and embody it such that the clamping operation takes less time, the structural size is smaller, the machine as a whole is easier to operate, and overall production costs of the machine are reduced.
Briefly, the machine tool is provided with at least one further three-phase motor for a machine unit that is operated only in alternation with the clamping drive, and a continuously regulating trigger unit that operates on the principle of frequency conversion is provided for the motors. To trigger the motors in alternation, the outputs on the take-off side of the trigger unit are reversible, and at the same time there is alternating access to the motor parameters that are definitive for the particular motor to be triggered, and/or to algorithms, as well as to the associated actual and set-point values for the motor.
The invention is based on the following considerations:
The motor provided for the clamping drive must be able to meet rather extreme conditions. At least its rotor should have small axial and especially radial dimensions, so that the moment of inertia remains low. Nevertheless, it should develop an extremely high torque--even if only briefly--especially at low rpm, but should also be possible to drive it at high maximum rpm, so that both high clamping forces and short positioning times can be attained. Furthermore, the motor must be controllable with high dynamics, so that during the buildup of clamping force, which should be completed within only about two motor revolutions, beginning with a prior maximum rpm, a regulated motor shutdown is attained.
When a pole changeable motor is used, none of these conditions can be realized together, or they can be realized only very incompletely.
However, triggering units having an integrated microcomputer are known, which operate by the principle of frequency conversion (brochure by the AMK Company entitled "PUMASYN Drehstromregelantriebe" [PUMASYN Three-phase Control Drive Mechanisms]) and enable meeting the above-described requirements, with adaptation to a suitable clamping drive motor. Accordingly, the invention preferably provides for the use of such control units, so as to be able to exploit the thereby available possibility for the clamping motor of combining both extremely high torque in the low rpm range and very high maximum rpm. The attainment of the very high torques at low rpm--with respect to the structural size--is due to the fact that with the current imposed upon the motor, the values for the magnetizing current component and the values for the torque-forming current component can be optimally apportioned by the microcomputer in a constant adaptation to the operating state of the motor.
On these conditions, with the same structural size and the same electrical output supplied to the motor stator, when the provided trigger unit is used for the clamping motor, a run-up torque can for instance be attained which is greater by a factor of 8-10 than with a kind of triggering which does not provide this apportioning of the current component, for example triggering by means of a contactor or by means of a trigger unit having phase control.
The high regulating dynamics required--especially with regulated buildup of the clamping force with the participation of a spring clamping force storage means--is also attained by the computer-controlled current component apportioning. For practical use, however, the system comprising a three-phase motor and computer-controlled trigger unit proves to be much too expensive in comparison with the conventional hydraulic clamping system.
Therefore the fact is taken into account that as a rule the clamping operations of the machine tools in question are accomplished during the shutdown of at least the spindle drive motor, and possibly the additional feed motor also provided, and that these motors in any case are driven with a convenient trigger unit. If at least one further motor is now used as this trigger motor, then it can make "joint use" of the same trigger unit, in alternation, as the clamping motor.
The trigger unit should be modified for this purpose, however. Its outputs are alternatingly connected to one or the other motor, and the same applies to its inputs, to which the actual signal from the motors is supplied; in the simplest case, this involves the output signal of an angle transducer provided on the motor. Furthermore, the two motors to be triggered will have entirely the same parameters only in exceptional cases; yet such parameters are to be taken into account for the operation of the trigger unit, and the situation is exactly the same for the regulating characteristics, which should for instance be different for a lathe spindle drive than for the clamping drive. When switching over the outputs and inputs of the trigger unit, a switchover is also made to the particular parameters and regulating algorithms applicable to the particular motor; the same is also true for the set-point and actual values of the motors.
This conception is much less complicated and expensive than if each individual motor were assigned its own trigger unit, because the expensive components, and in particular the power stage, do not need to be modified and only a single one needs to be provided.
However, this also makes the entire machine tool easier to operate. Since fewer components are involved, there is less likelihood of malfunctions.
The concept according to the invention also has an effect on the embodiment of the mechanical parts of the clamping unit. According to the teaching of the above-mentioned German patent DE-PS No. 33 14 629, the stator of the clamping drive motor is disposed stationary, while the rotor rotates with the spindle, and its drive moment is converted by means of a rolling screw drive into an axial motion for driving clamping jaws. Because this system is very low in friction, with suitable triggering of the clamping drive motor it also permits accurate apportioning of the clamping forces.
A further conventional type of clamping units having an electrical drive motor is described in the company publication of the Paul Forkardt GmbH & Co. KG#500.01.7 D/1979 entitled "Elektrospanner" [Electric Clamping Tools].
These electric clamping tools include an electric motor, which for clamping tools, for instance in milling machines, may be stationary and may be coupled only for the clamping operation, but may also be embodied such that in lathes it rotates with the spindle. The drive moment of the motor is transmitted via a step-down gear and a torque limiter to the nut of a sliding screw drive, which cooperates with a tension/compression tube. The torque limiter is embodied as a so-called click and rachet wheel, in which the radial serration disposed on two different parts can unlatch after overcoming an adjustable spring force. By varying the spring force, the clamping force introduced to the tension/compression tube can thus be varied. Because after the torque limit is reached the click and rachet wheel can be latched and unlatched via a plurality of teeth, the torque continuously produced by the electric motor is converted into a train of torque pulses, which also increases the spanning force generated by the sliding screw drive.
In order to realize a clamping force storage means, which is always recommended at the high machine tool work spindle speeds typical at present, a spring element made up of cup springs is interposed in the work spindle bore between the tension/compression tube and the clamping means (such as lathe chucks). The disadvantages of the construction having the sliding screw drive are the following:
It is relatively inaccurate and difficult to adjust the clamping force at the mechanical torque limiter, and it must be done by hand and is therefore relatively time-consuming and can virtually not be automated. In addition to the imprecision of the clamping force, dictated by the kind of adjustment, there is a further and even greater component of imprecision. This is due to the wide range of possible coefficients of friction that are operative in the sliding screw drive. The coefficient of friction may range from μ=0.1, for a well-lubricated and clean sliding screw drive, to more than μ=0.2 where there is not enough lubricant and there is insufficient maintenance. Even with a limit torque that remains constant, this means a possible fluctuation of 100% in the clamping force.
The stroke speeds attainable are too low and should be at least 20 mm per second. The opening and closing times that are dependent thereon in fact contribute directly to the unproductive standby periods. The low stroke speeds are caused by the fact that the asynchronous three-phase motors triggered by reversing contacts put out a relatively low torque, so that to attain the necessary clamping forces a relatively high gear reduction becomes necessary. Increasing the engine speed beyond 3000 rpm is impossible in principle with a mains frequency of 50 Hz, and increasing the motor output is prohibited because of the structural volume that would necessarily have to be increased, and in particular the volume of the motor stator that revolves with the spindle, the centrifugal moment of which would be increased considerably thereby. Finally still another disadvantage has to do with this last situation mentioned.
In modern lathes of the present day, speeds of 6500 rpm and higher are typical. When electric clamping tools are used with a revolving motor stator, then because of the extremely high centrifugal forces at these rpm, the limits for strength of the motor components would rapidly be reached.
The functional superiority of the clamping unit having a rolling screw drive must, however, be bought at the expense of considerably higher production cost, which result above all from the necessarily more-complex trigger unit for the electric motor and from the rolling screw drive.
The higher production costs of the electric clamping tool with a rolling screw drive are certainly justifiable if all the functional advantages can be made use of in a practical application.
In many applications, however, even in modern lathes the advantages resulting from a rolling screw drive are not exploited fully. This is particularly true when a through bore for the passage through it of rod work is not required on the electric clamping tool and when the considerably lower number of clamping operations possible with the sliding screw drive until reaching the wear limit as compared with a rolling screw drive are still acceptable.
The disadvantage of the sliding screw drive can be lessened, however, if the threaded faces of the nut and/or the spindle meshing with one another are subjected to a surface treatment that reduces drive friction. It is possible even after the conventional metallurgical tempering operations to apply firmly adhering, very thin layers of extremely hard and friction-reducing material, which are preferrably to be precipitated out of the gas phase using the CVD method. Among the coating materials that may be suitable are titanium nitride, for example, but a diamondlike carbon is particularly suitable, such as that described in the publication entitled "Battelle aktuell" ]Battelle Update] dated Sept. 2, 1986, or the publication entitled "Ion Beam Deposition of Thin Films of Diamondlike Carbon", by Aisenberg and Chabot in J. Appl. Phys., 42/1971, pages 2953-2958.
A sliding screw drive improved in this way in terms of the friction conditions can then be made with a larger diameter, and possibly even hollow, without requiring a higher-power clamping drive motor. Conversly, with a smaller diameter of the drive, a smaller motor could be selected, or a reducing gear could be dispensed with. Finally, it is also possible to combine these provisions with one another.
In order to use this kind of clamping unit with high-speed lathes, it is recommended that not only the stator but the rotor of the clamping drive motor as well be disposed stationary with respect to the work spindle revolution and for the clamping/unclamping operation to couple it with the drive; this coupling is preferrably electrically switchable.
The invention will be described in greater detail below, referring to the accompanying drawings.
Drawing
FIG. 1 is a block circuit diagram of a machine tool;
FIG. 2 shows a vertical section taken through a spindle stock of a lathe according to the invention;
FIG. 3 is an axial section taken through the clamping drive motor of FIG. 2;
FIG. 4 is an axial section taken through the tension/compression tube of FIG. 2;
FIG. 5 is a fragmentary axial section taken through the spindle stock of a lathe in a second embodiment of the invention;
FIG. 6 shows a diagram in which the clamping force and the angular velocity of the speed are plotted as a function of the rotor angle for one clamping operation; and
FIG. 7, in a longitudinal section, shows the tailstock of a lathe according to the invention.
DETAILED DESCRIPTION
The principle of the invention will first be described, referring to the accompanying block circuit diagram of FIG. 1.
As an example, a lathe having a motor MI for the clamping drive and a motor MII for the work spindle drive is assumed. Each motor is equipped with an angle transducer, which for example furnishes one output pulse per degree of rotational angle. By differentiation in accordance with time, the rotary speed is obtained, and by differentiation a further time, the rotational acceleration is obtained. The motor parameters required (such as moment of inertia of a rotor and other fixed data) are stored in associated memories 410 for the motor MI, and 412 for the motor MII.
The corresponding regulating algorithms are similarly stored in memories 411 (for the motor MI) and 413 (for motor MII). The actual values and the outputs of the memories--for the sake of simplicity, the connections are shown as buses--reach a reversing switch 414, so that only the data belonging together can be supplied to the regulator 415 at a given time. The actual values are also sent to an interface 416, which communicates via a bus 417 with a conventional CNC machine control. The positioning signals of the regulator 415 reach a control variable converter or end stage 418, which converts the supplied mains power, in this case 380V mains voltage, threephase, into the particular set stator currents required for the two motors, which are switched depending on the position of the switch 419 to one of the motors MI or MII. The CNC control also furnishes the set-point values via the interface, and the setpoint values are also switched over by means of the switch 420. All three switches are controlled from the CNC control via the interface. The switches shown, but especially the switches 414 and 420, can in practice naturally be embodied as semiconductor switches.
It is assumed that one workpiece has just been completely finished and has been unclamped. The switches are located in the positions shown, because with the work spindle stopped the clamping chuck of the motor MI was the last to be actuated in the unclamping direction. After a new blank has been inserted into the chuck, the motor MI is supplied with current such that it runs up with maximum rotary acceleration up to a set-point rpm, which is monitored by comparison of the actual and set-point values. Because of the tolerances of the blank, it cannot be predicted how many revolutions the clamping motor can execute. When the clamping means driven by the motor MI (for example the clamping jaws of a chuck) meet the workpiece, a signal is generated by means of a clamping force sensor, and this brings about a continuous reduction of the rotary frequency with a simultaneous increase in the clamping force, such that precisely when the intended clamping force value is attained, the rotational speed of the clamping motor assumes a certain predetermined residual value, in this case the value of zero.
Depending on the design of the trigger unit, there are two further possibilities for obtaining a trigger signal when the clamping means meet a workpiece, for example: If the trigger unit is designed such that it regulates the rpm of the motor to a constant value, then the sudden high load causes a sharp increase in the required current, which can be detected and evaluated. Contrarily, if the trigger unit is designed such that regulation to a constant output torque is performed, then the sudden load increase causes a drop in the rpm, which can be detected and evaluated via the corresponding transducer (for the actual value). In the drawing, the latter case has been assumed for the sake of simplicity; for one skilled in the art it is understood that the regulator 415 must also be supplied via interface 416 with the output signal of the clamping force sensor, if such a sensor is used (this is suggested with the dashed line). If a clamping force sensor is not used, the regulation is done by using a torque signal.
Once the clamping operations has ended, a switchover to the motor MII can be made for performing the machining operations. The commands required for this are furnished in the usual manner by the CNC control. Once the machining program has run its course, the switches are switched back again, and the operations take place in the reverse sequence for unclamping the workpiece.
It should be noted that the power requirement for a work spindle drive of a lathe and that for its clamping chuck drive are at least of somewhat comparable magnitude, so that the dimensioning of the end stage is appropriate for both. It should also be pointed out that instead of the clamping chuck drive, or alternatively with it, the drive for the tailstock spindle can also be actuated with the main spindle drive trigger unit. The adoption of the invention to other types of machines will be readily accomplished by one skilled in the art from the above teaching.
The ON duration of the clamping drive motor is generally at maximum 2%, with the maximum output having to be brought to bear only for a fraction of this time. Thus the motor can be embodied as very small, without the danger of thermal overload. Contrarily, the spindle drive should be designed for an ON duration of 100%, so that the motor MII is substantially larger than the motor MI. This can be taken into account, however, by means of the different parameters supplied to the regulator, and the same applies for the resultant different regulating algorithms.
In the block circuit diagram of FIG. 1, the reverse switching operations and the corresponding alternating access to the motor parameters, regulating algorithms, actual values and set-point values are associated with the internal computer of the trigger unit; alternatively, the computer of a higher-level CNC control of the entire machine can be used.
The three-phase motor is preferrably embodied as a shortcircuit rotor motor, preferrably an asynchronous motor, because this has advantages in terms of price and construction, especially if the stator of the clamping drive motor is stationary but it rotor rotates with the spindle.
Because clamping units having sliding screw drive are naturally preferred for reasons of cost, clamping units of this type will be primarily described below.
In order to clearly explain the demands made of the motor trigger unit, some relationships and facts will first be described in detail below. Some concrete dimensioning data will be used, such as may be applied to the clamping unit shown in FIG. 3 and to be described in detail later.
The clamping force F A amounts to 70,000N. For the sake of minimum wear, the thread diameter D of the sliding screw drive becomes larger than would actually be necessary from the standpoint of material strength, and in fact it is designed for D=40 mm. The thread pitch is assumed to be p=2 mm. The theoretically necessary torque M ds for operation without any friction at all at the sliding screw drive is, using a simplified formula, M ds =F A ·p/2π≈22 Nm. With an assumed upper value of μ=0.2 for the coefficient of friction, the friction torque becomes M dR =F A D/2μ=180 Nm. This shows that the friction may be approximately 12 times larger than the useful torque.
In order to be able to attain a stroke speed of v=20 mm/s, the maximum rotational speed at the sliding screw drive must be n=10 rps, or n=600 rpm. Assuming that with a clamping unit for F A =70,000N, the rotor diameter logically must not exceed the value of 160 mm and the rotor width must not exceed the value of 50 mm, then with the above-described trigger unit being used, the maximal torque becomes 110 Nm up to a motor speed of 180 rpm.
If the torque to be brought to bear, with a cofficient of friction of μ=0.2, also taking into consideration the axial roller bearing involved, is estimated to be Md,ges*≈320 Nm, then it becomes clear that the reduction gear ratio i of the planetary gear must be on the order of i≈1:3. From this resultant gear reduction ratio, it is clear that to establish a stroke speed of v=20 mm/s in fast speed--however with a low torque requirement--the motor must attain a maximum rpm of Nmax*=1800 rpm. For the sake of lower production costs, a smaller structural size with a motor rotor and the desired freedom from wear, the only type of motor to be considered can be a threephase motor.
One skilled in the art of motors will recognize that to meet both demands, namely first an extremely high torque with a small structural size and low rpm, and on the other hand a very high rpm in view of the multipolarity of the stator to be provided, while simultaneously meeting the requirement for good regulating dynamics, a high-grade trigger unit, such as the PUMASYN unit mentioned above, is necessary.
Changing the gear reduction ratio i of the planetary gear in one or the other direction while simulataneously maintaining the maximum stroke speed will hardly lessen the demands made on the motor and trigger unit, because with the mode of operation under discussion here, when the maximum rpm is increased the maximum torque is decreased--and vice versa.
The mode of operation that must necessarily be performed when building up the clamping force magnitude, when a sliding screw drive is used, cannot be precisely adjusted via the motor torque, because the coefficient of friction varies so widely.
Instead, the influence on the motor must be effected by using a sensor for continuous detection of the actual value of the clamping force. Furthermore, shutting down the clamping motor cannot be effected such that the engine rpm is regulated downward continuously to the value of zero until the predetermined clamping force is attained. To lessen the "stick-slip effect" that arises with sliding screw drives, it must instead be driven until the end at a predetermined minimum rotary speed, and then the motor must be shut down abruptly when the predetermined clamping force is attained. This requires great regulating dynamics on the part of the electrical drive as provided by the high-grade triggering unit.
Following these more theoretical considerations, the exemplary embodiment shown in FIGS. 2-7 will now be described.
In FIG. 2, the spindle box 10 is shown with the spindle 14 supported in roller bearings 12. At one free end of the spindle, there is a clamping chuck body 16, which axially displaceably receives a clamping piston 18, which via wedge guides 20 actuates the clamping jaws 22 in a manner known per se. The spindle drive is effected via a gear 24, which is for example connected via a toothed belt (not shown) with a spindle drive motor (not shown, but marked MII in FIG. 1).
At the other free end of the spindle 14, the spindle carries the rotor 26 of a clamping motor 25, the stator 41 (see FIG. 3) of which is housed in a housing 28 flanged to the spindle box 10 (see motor MI in FIG. 1).
Extending through the hollow spindle 14 is a tension/compression tube 30, which on the chuck end is joined to the clamping piston 18 and on the clamping motor end is connected to screw drive 29, the nut of which is rotatable by the clamping motor 25 relative to the spindle 14. The terminal box for the supply of current to the stator is shown at 32.
In FIG. 3, the housing 28 is shown with the stator 41 of the clamping motor, including the yoke 40 with the winding 42. The rotor embodied as a short-circuit rotor surrounds the core 44 with the short-circuit rings 46. It is clamped firmly to a sleeve 48, the end flange 50 of which has a radial serration 52, which rotates before a stationary inductive transducer 128, which furnishes one pulse per unit of rotary angle; the use of these pulses will be described later. The end flange 50 is screwed together with an inner tube 54 coaxial with the sleeve 48; the inner tube 54 is supported in roller bearings 56, 58 and has an outer serration 60 on its free end.
A sleeve 62 is screwed onto the free end of the spindle 14 and a pipe section 64 is connected to the sleeve; the pipe section has an inner serration 66 at the level of the serration 60. On its end remote from the spindle, a bushing 68 is screwed on, and the outer rings of the roller bearings 56, 58 are fixed in this bushing.
In the annular space between the serration 60 and 66, there is a sun wheel 70 with planet pinions 72, which mesh with the serrations 60 and 66; the sun wheel 70 is screwed to the threaded drive nut 74 and is supported axially on the pipe section 64 by means of a face bearing 76.
Accordingly, the sleeve 62, the pipe section 64 and the bushing 68 are joined to the spindle 14 in a rotationally fixed manner. The components connected to the rotor 26 of the clamping motor are rotatable relative to this above assembly and to the stationary housing 28, these components being the sleeve 48, the end flange 50 and the inner tube 54. Upon a rotation of this latter group relative to the spindle 14, the sun wheel accordingly will travel through an angle that depends on the gear reduction ratio of the planetary gear, embodied by the serrations 60, 66 and the pinions 72. This rotation of the sun wheel is transmitted to the nut 74 and converted by means of the thread 77 into an axial displacement of the driving screw 78 and the components joined to it.
These components include, on the side remote from the spindle 14, a guide tube 80, the free end of which is coupled via a roller bearing 82 to a carriage 84 in such a manner that the carriage--which is secured against rotation by means of a screwed-in cam 86, which moves in an oblong slot 88 of the housing attachment 90--is moved in a coupled manner by the driving screw 78. The carriage 84 has a measuring head 92 which will be described in detail later.
On the side of the driving screw 78 oriented toward the spindle 14, the driving screw is joined in a rotationally and axially fixed manner with the tension/compression tube 30 via the tubular connection piece 94. The structure of the tension/compression tube 30 is shown in FIG. 4, which will now be described in detail.
The tension/compression tube 30 includes an outer tube 100, which is rotationally and axially fixedly connected to a stop sleeve 102, into which the clamping piston 18 is coaxially screwed. The rod 104, on the chuck-side end of which the coupler bushing 106 is located, is located in the outer tube 100; cup spring assemblies 108 are disposed between the outer tube and the rod. These assemblies are supported on the chuck-side on the sleeve 102 via a pressure ring 110, which can however be shifted by the coupler bushing 106 in the direction of the clamping motor in response to compression of the cup springs, when the rod 104 is pulled out of the outer tube (toward the left in FIG. 4).
On the side remote from the chuck, the cup spring assemblies 108 are supported on a shoulder of the outer tube 100 via a second pressure ring 112. This pressure ring is once again shiftable into the outer tube 100, however, which compresses the cup springs, whenever the rod 104 is pushed into the outer tube 100 (toward the right in FIG. 4).
The connection piece 94 has a wedge 114, which engages axial grooves 116 of the outer tube 100 and thus joins the connection piece 94 and the outer tube 100 to one another in a rotationally fixed manner, yet permits relative shifting of the tube in both axial directions, in each case in response to compression of the cup springs, as explained above.
Extending through oblong slits 118 of the connection piece 94 in a radial direction is a pin 120, which is joined in a rotationally fixed manner to a sliding block 122, which is guided in an axially shiftable manner in a bore of the connection piece 94. One end of a sensor rod 124 is screwed into the sliding block, extending through the driving screw 78 of the guide tube 30 as far as the other side of the roller bearing 82, where it has a sensor head 126. Upon a relative axial shifting of the outer tube 100 and rod 104, a relative shifting of the sensor head 126 to the measuring head 92 accordingly takes place as well. The sensor head 126 and the measuring head 92 cooperate in such a way that in accordance with the spacing between them an electrical signal (analog or digital) is generated in the measuring head, which is representative of this distance between them and thus representative of the amount of compression of the cup spring assemblies 108, which serve as storage means for clamping force.
The cooperation of the embodiment as described so far with the trigger unit will now be explained, referring to FIGS. 1 and 6; FIG. 1 has already been explained above.
Because of the fact that the sliding screw drive operates by the so-called stick-slip mode, the regulating algorithm is laid out in accordance with FIG. 6. The lower curve shows the course of the output signal of the sensor 92/126 as a function of the rotational angle of the clamping motor rotor, which is marked β. During the idle stroke β L , only a very slight force is measured, corresponding to the friction in the chuck. As soon as the chuck jaws meet the workpiece, the force increases, and as soon as a predetermined value F S is attained--which is higher only by a certain safety margin than the force value of β L --the rotational speed dβ/dt (upper portion of the diagram of FIG. 6) is reduced, for example linearly as shown, while at the same time the clamping force F A rises. The rotational speed must not fall below a minimum value dβ/dt min, however, so that the "slip" operation continues to be maintained. Only once a predetermined clamping force value of F E is attained, is the rotational speed of the motor abruptly dropped to 0.
Now that the clamping operation has thus been ended, a switchover to the motor MII can be made to perform the machining steps. The commands required for this are furnished in the usual manner by the CNC control. After the machining program has been completed, the switches are switched back again, and for unclamping the workpiece, the operations logically take place in reverse order.
For the case where, in a drilling and milling machine, for example, the clamping means serves to receive interchangeable tools each having the same shaft diameter, then a sensor for ascertaining the actual value of the clamping force can be dispensed with. Because in the clamping operation in this case--beginning at a predetermined angular position of the clamping motor rotor in the opened state of the clamping means--a predetermined clamping force, with a deformation derived from it of a clamping force storage spring, is established once an associated constant rotational angle has been traversed, the control of the clamping motor can be accomplished using only the measured actual value for the rotational angle.
It should be noted that the power requirement for a work spindle drive of a lathe and for its clamping chuck drive are at least approximately of the same magnitude, so that the dimensioning of the end stage is suitable for both. It should also be noted that instead of the clamping chuck drive, or in alternation with it, the drive for the tailstock spindle can also be actuated with the main spindle drive trigger unit. The adoption of the invention to other types of machines, such as for clamping tools, is well within the competence of one skilled in the art, using the above descriptions.
The ON duration of the clamping drive motor is generally at maximum 2%, with the maximum output having to be brought to bear only for a fraction of this time. Thus the motor can be embodied as very small, without the danger of thermal overload. Contrarily, the spindle drive should be designed for an ON duration of 100%, so that the motor MII is substantially larger than the motor MI. This can be taken into account, however, by means of the different parameters supplied to the regulator, and the same applies for the resultant different regulating algorithms.
If the spindle 14 were not braked during the shutoff of its drive motor and the switching on of the clamping motor, then the clamping motor could turn the spindle, instead of shifting the driving screw, or could do both. However, it can be presumed that the spindle drive motor has a brake that locks it when the spindle drive is shut off. However, the danger still exists that in the event of a braking moment acting suddenly upon the revolving spindle, the rotor of the clamping motor will contnue to run at least briefly with its former speed, and depending on conditions may make the clamping force impermissibly great or even, in the opposite situation, unclamp the workpiece. For this reason, care is taken to couple the rotor mechanically to the spindle when the clamping motor is shut off.
To this end, as shown in FIG. 3, the stator core 40 of the clamping motor is axially lengthened with respect to the rotor core toward the spindle, and in the face region of the stator core, a coupling ring 130 having a radial serration is seated on the rotor in alignment with a counterpart serration 132 on the bushing 68. The coupling ring is mounted on bolts 134, which are biased by springs 136 in the direction of the tooth meshing.
The trigger unit in its preferred embodiment enables the separate imposition of the field-generating current components and of the torque-generating current components upon the stator winding 42. The regulating algorithm is accordingly laid out such that the field-generating component is always switched on first, and as a result the coupling ring--acting as the armature of the stator core, which then functions as a magnet--is released from the serration, and only then is the torque generated. In the shutoff process, naturally the procedure takes place in reverse order.
The parallel detection of rotational angle, clamping force and braking moment (via the operating parameters of the trigger unit) makes it possible to provide various monitoring functions. For instance, the play between the driving nut and the driving screw upon the reversal of rotational direction makes itself felt in a sharp drop of braking torque, and the associated rotational angle is then a standard for the "looseness" in the sliding thread drive and thus a standard for wear, so that for example if a predetermined threshold value is exceeded a warning signal can be emitted.
The level of the braking moment during the idle stroke β L is also a standard for the lubricant status of the threaded drive, and here again a warning signal can be generated if a predetermined threshhold value is exceeded.
In the exemplary second embodiment of FIG. 5, once again a sliding thread drive is provided in which however the friction-reducing coating mentioned initially is provided and the thread courses can therefore be located on a larger diameter, so the spindle can be embodied as hollow. The clamping motor is stationary with respect to the spindle rotation, and its rotor is coupled to the spindle only for the clamping or unclamping operation.
The general structure of the spindle stock need not be described again here; in this connection, see FIG. 2.
The tension/compression tube 152 is located inside the spindle 150, revolving with the spindle and being axially shiftable relative to the spindle for the sake of actuating clamping jaws. Screwed to the spindle is a flange 154, which via screws 156 carries a force storing assembly 158.
This assembly surrounds a supporting sleeve 160, in which an inner ring 162 is seated. A first cup spring 166 is axially supported on the end flange 164 of the inner ring, and on its other end this cup spring is clamped in place by a first intermediate ring 168. On its other side, a second cup spring 170 follows, clamped by a second intermediate ring 172. The supporting sleeve is fixed between this second inner ring and an annular nut 173, which is screwed onto the inner ring 162. The radially outer circumferences of the cup springs 166, 170 are fixed on an outer ring 174 by means of a further clamping ring 176 and an annular screw 178, which is screwed into the outer ring 174. From the outer ring 174, pins 180 extend into a slit 182 of the supporting sleeve 160, so that the two are coupled to one another in a rotationally fixed but axially displaceable manner.
The particular axial position of the outer ring 174 relative to the spindle and thus relative to the spindle box 184 is detected by means of a sensor 186, which is built into the spindle box.
The outer ring 174 is also joined via a crosswise roller bearing 188 to the nut 190 of a sliding thread drive, the hollow screw 192 of which is screwed to the tension/compression tube 152. Axial wedge grooves 194 on the outside of the screw 192 couple this screw in a rotationally fixed but axially displaceable manner to the inner ring 162 of the force storing assembly.
Upon rotation of the nut 190 relative to the screw 192--which when the spindle is at a standstill does not revolve either--the tension/compression tube 152 is accordingly axially shifted, until it is sharply braked, for example by the meeting of the clamping jaws with a workpiece; from then on, further rotation of the nut causes the nut to be axially screwed along the screw 192, axially shifting the outer ring 174, causing elastic deformation of the cup springs 166, 170, so that they store the clamping force.
The rotational movements required for clamping and unclamping are trasmitted by the nut 190 in the following manner:
In the spindle box 184, a coupling ring 198 is supported by means of roller bearings 196 and coupled via wedge grooves 200 in a rotationally fixed but axially displaceable manner to the nut 190. The coupling ring 198 has a radial serration 202.
A motor housing 204 is flanged to the spindle box, receiving the stator 206 of a clamping drive motor, and a sleeve 208 is screwed to the motor housing, extending inward from an end flange 210. Supported on the sleeve 208, by means of ball bearings 212, 214, is the rotor 216 of the motor, which is firmly connected to the coupling tube 218. The ball bearing 212 is displaceably seated on the sleeve 208, and the ball bearing 214 is displaceably seated in the coupling 218. Between the bearings 212 and 214, a restoring spring 220 is fastened, and during spindle rotation, or in other words when the clamping drive motor is without current, the restoring spring 220 keeps the rotor of the clamping drive motor in the axial position shown, which is defined by the stop ring 222.
The coupling tube 218 has a radial serration 224 on its inner end face, which can be made to mesh with the radial serration 202 of the coupling ring by means of axial shifting of the coupling tube 218, with compression of the spring 220. This is done by switching on the motor current, which causes retraction of the rotor into the stator. The two parts that couple with one another have circumferential teeth, which in cooperation with sensors 226 and 228, respectively, enable recognition of the angular location, so that the radial serrations are not damaged when the coupling is effected.
The entire apparatus is designed centrally symetrical with respect to the spindle axis, so that only the upper half needs to be shown in section.
FIG. 7 schematically shows an axial fragmentary section of the tail stock region of a lathe. The machine bed 330 has the linear guide 332 for the tailstock carriage 334 and spindle 336, in the usual manner, the end of the tailstock spindle 336 remote from the spindle stock being supported on a compression spring assembly 338. Shifting of the tailstock carriage is effected by means of a rolling thread drive, the nut 342 of which is retained at 340 and cooperates with the spindle 344 that can be driven for rotation. An axial bearing 346 absorbs the forces of reaction. Via a coupling 348, a servomotor 350, secured to the bed 330 by means of retaining brackets 352 (with screws 360), drives the spindle 344 for rotation and in so doing shifts the tailstock carriage 334. The motor is connected via a multiple conductor cable 354 to a trigger unit, preferrably the same trigger unit that is also associated with the clamping drive and the spindle drive. In addition to the output signal of a spring force sensor 356, which represents the pressing force exterted by the tip 358 of the tailstock spindle, a travel sensor 362 is also provided. This makes it possible to selectively attain a predetermined clamping force or predetermined adjusting distance. It will be understood that other servomechanisms of the same trigger unit can be operated by this same manner, on the condition that they do not have to be controlled simultaneously. Similarly, instead of the rolling thread drive 342/344 a sliding thread drive coated for friction reduction can be provided. | A machine tool having a work spindle with an electrically actuated clamping unit including a three-phase motor with a stationary stator. The motor is supplied with electricity from a control unit operating with frequency conversion, and the control unit is alternatingly also used for triggering a spindle drive motor. A sensor detects clamping force applied to a workpiece, and produces a signal used to reduce motor speed of the three-phase motor until a predetermined clamping force is achieved. | 8 |
BACKGROUND AND SUMMARY OF THE INVENTION
This is a continuation of Ser. No. 898,217 (filed 8/20/86), now abandoned which is a continuation of application Ser. No. 669,357, filed Nov. 8, 1984, now U.S. Pat No. 4,625,245 which is a continuation-in-part of application Ser. No. 560,103 filed Dec. 12, 1983, now abandoned.
The present invention relates to magnetic recording, wherein a magnetization continuum is recorded on a magnetic recording medium by means of a transducer (record head) driven by electrical signal currents having an active duty cycle which is lower than that of the recorded magnetizations or of the analogous electrical signals reproducable from them. The invention provides continuous recording with only intermittent power consumption and low heat dissipation, an advantage which favors selection of low cost circuits as record head drivers. Other advantages of the invention will be apparent from the further description herein.
The present invention is generally applicable to various forms of magnetic recording, but is described herein for purpose of illustration in its application to digital recording on a variety of media, e.g., magnetic disks, tapes, drums and cards. Although the invention is described, at times herein, in terms most applicable to fixed, ring head, longitudinal recording on magnetic tape, it is understood that it is not limited thereto.
In accordance with the present invention, a magnetic record medium, such as a tape, is continuously driven across, or traverses, the record gap of a magnetic record head to record a continuum of data or intelligence thereon. In conventional magnetic recording, the intelligence is embodied in a continuum of electrical signals that are transduced continuously by the record head to effect a continuous magnetic recording action on the record tape. Pursuant to the present invention, the continuum of electrical signals are sampled and applied to the record head as discrete and discontinuous impulses of very short duration. The time duration of each impulse is a fraction of the time interval required for a point on the record medium to traverse the effective record gap of the record head or transducer. Also, the time spacing between successive record impulses is approximately equal to the aforesaid time interval of traverse.
The present invention takes advantage of the fact that upon the application to the record head of a record current impulse, the value of that impulse is immediately recorded over the entire extent of record medium spanning the effective recording gap or effetive recording field of the record head. Each succeeding record impulse is applied to the head preferably at the instant that each preceding recorded increment has completed its traverse across the effective recording field. Thus, although the electrical record impulses are applied discontinuously, the magnetic recording is in fact substantially a continuum and will be transduced by a play back head into an electrical continuum corresponding to the original electrical signal continuum from which the record impulses are sampled.
In order to appreciate fully the significance and advantages of the present invention, a summary description and analysis is provided of magnetic recording principles and their application in accordance with the standard practices of the prior art.
MAGNETIC RECORDING PRINCIPLES AND PRIOR ART PRACTICES
The ensuing summary description of the principles of magnetic recording and their application in prior art magnetic recording practices is had in conjunction with the accompanying FIGS. 1-11, which are described in sequence in the following description.
Digital record and reproduce systems, well known and broadly applied in the art, provide an output electrical signal conveying binary intelligence by means of two signal levels, e.g., positive and negative, or by means of a transition sequence between levels. Numerous digital encoding methods are practiced and their selection depends upon factors such as application, need to conform to data interchange standards, bit pattern sensitivity or frequency spectrum restrictions of a digital system and the preference of the system designer.
In digital magnetic recording systems which do not have intra-system code conversion, the reproduced electrical signal continuum is analogous to a magnetic flux continuum recorded on a medium. The output electrical signal level corresponds to the sense, i.e. direction, of a recorded magnetization, and a transition in output electrical signal level corresponds to a transition from one magnetization sense to another. The recording transducer (record head) signal current continuum producing the recording relates to the magnetic flux continuum in the same manner.
It is common practice to use record current levels sufficient to produce near saturation remanence in the medium; higher current levels are used if there is a need to reliably record new data over prerecorded data (overwrite) without benefit of an erase cycle.
FIG. 1 illustrates a record current waveform with the corresponding reproduce system voltage waveform and the corresponding remanent magnetization pattern. The magnetization pattern is represented by a simple planar (parallel to plane of medium) vector model. This illustration is typical of a non-return-to-zero-level (NRZ-L) digital system. The planar vector model disregards any normal (perpendicular) components of magnetization which exist in regions of flux transitions in the medium.
FIG. 2 illustrates an elementary ring record head which converts record signal current from a head driver (generator) to a fringing magnetic recording field which penetrates into the magnetic layer of a recording medium.
Record head structures of a type widely applied in the current art are usually more complex than that depicted in FIG. 2, but the essential principles are the same; signal current through the core windings produces magnetic flux within the material of the head core, some of which emanates from the region of a non-magnetic gap to form the recording field.
A more detailed illustration of the magnetic field in the region of a record head gap is given in FIG. 3.
As a medium is being recorded the instantaneous magnetization of each of its particles or domains is determined by the magnetic susceptibility of the particle and the intensity and direction of the recording field at the particle site. The susceptibility of a particle may vary with its orientation. The particles of typical commercial recording media are capable of being switched to a new state of magnetization within 3 nanoseconds of a change in the recording field.
During recording, the magnetization of a particle changes as a function of field direction and intensity attributable to position change or record signal change while the particle moves through the entire recording gap region; but, the final determinant of remanent magnetization is the direction and intensity of the field near the trailing edge of the recording gap. Therefore, the recording zone of a head is generally considered to exist along contours emanating from the trailing edge in which the field intensity approximately equals the coercivity of the medium. FIG. 4 illustrates such a recording zone. The contours shown depict contours of constant magnetic field intensity as opposed to filed lines. The numerals 1, 0.9, 0.8, etc. indicate field strength relative to the strength in the center of the deep gap field. The gap length of a record head is usually designed to produce a desired record zone penetration depth into a medium. Gap length values ranging from one to two times the minimum wavelength to be recorded are typical.
Another factor affecting remanence is demagnetization. Demagnetization occurs when fields emanating from a magnetization return to oppose the sense of adjacent magnetizations. If the geometry of a magnetized region is such that its field generally emanates and returns externally, the demagnetization factor will be low; if its field generally returns internally through the region of the magnetization, the demagnetization factor will be high.
FIG. 5 illustrates the demagnetization effect for a thin, flat sheet whose length and width dimensions are very large with respect to thickness. When most of the field returns externally, as in FIG. 5a, the demagnetization factor is nearly zero and remanence is high; when most of the field returns internally, as in FIG. 5b, the demagnetization factor is nearly unity and remanence is low.
Similarly, for a continuum of recorded planar magnetizations, long compared to their depth (magnetic layer thickness), the demagnetization factor is low. As the recorded wavelength of such planar magnetizations decreases, the demagnetization factor increases, i.e., for purely planar magnetizations, remanence decreases with recorded wavelength.
If a long array of normal magnetizations of like sense is recorded, the situation is similar to that depicted in FIG. 5b, and the demagnetization factor is high. However, if the normal magnetizations alternate in sense over closely spaced intervals, as occurs in short wavelength recording, then their fields are mutually supportive and the demagnetization is low. For purely normal components of magnetization, remanence increases as the recorded wavelength decreases.
Table 1 is presented as FIG. 6A, and it qualitatively summarizes demagnetization effects for long and short wavelength planar and normal magnetizations.
As a region of a medium moves through an active recording zone, the shape of that zone (FIG. 4) produces both planar and normal magnetization components, instant by instant; these components are then subject to modification by demagnetization effects.
FIG. 6B shows a record current transition and a model of the resulting magnetization pattern before and after demagnetization. The long planar component array is essentially unchanged by demagnetization. However, the normal components are diminished by demagnetization with the exception of those located in the region corresponding to the transition. These transition region normal components are less affected by demagnetization because of a supporting field from the planar continuum which they terminate.
In general, the longitudinal recording of a digital data signal continuum produces a magnetization pattern of normal components marking transition regions which are supported (flux linked) by planar components. The longer the recorded half-wavelength, i.e., the longer the recording signal remains at one polarity, the longer will be the continuum of planar components, the deeper will be its penetration into the medium, and the longer will be the region of possible interaction between normal components terminating adjacent, opposite sense, half-wavelengths. Such interaction is a cause of pulse crowding which contributes to pattern sensitivity. FIG. 7 illustrates a simplified planar and normal component model associated with a record current waveform having various single polarity time intervals.
Compensating pattern sensitivity by means of advancing or delaying record current transitions is known in the art. Some effects contributing to pattern sensitivity can be minimized by means of thin magnetic medium coatings, record heads having short gap lengths to limit fringing flux penetration and to improve the record field gradient, and by means of reduced record current to limit flux penetration and to improve the field gradient. The latter means, of course, compromises overwrite performance.
When a recording current changes polarity rapidly, as in the recording of a square wave, a subsequent cycle partial erasure occurs. FIG. 8 illustrates this effect. As the polarity of the record current changes, previously recorded magnetizations leave the record zone to be affected by a weaker field of opposite sense, i.e. partially erased. Thus, output levels are reduced for signals having closely spaced reversals of polarity.
The more abruptly the field strength decreases with distance from the trailing edge of the record gap, i.e. the higher the recording field gradient, the less will be the effects of subsequent cycle erasure. In general, increasing record current, which may be done to assure adequate overwrite levels in a digital system, decreases the recording field gradient and increases the effects of subsequent cycle erasure.
Opposite sense normal magnetizations in close proximity may have a mutual flux circuit of such low reluctance as to preclude their flux contribution being sampled by a reproduce head circuit, as is illustrated in FIG. 9. This proximity mutual flux "loss" can reduce signal output and shift the point at which a transition is sensed in the medium by the reproduce circuit.
FIG. 10 illustrates a typical digital data record current waveform. Current is maintained in one direction or the other through a record head winding. Heat energy dissipated by a head and head driver is a function of the shaded area of the waveform shown. The sustained heating effect of the relatively high currents required in some digital systems precludes use of low power rated and inexpensive components in head driver circuits, particularly for multi-track systems.
The remanent flux produced by sustained currents through the record head can be modulated at any time a medium is being recorded by variation in head to medium contact, thereby producing noise. This noise modulation is caused by random irregularities in surface quality of the medium.
Some digital recording systems utilize a read-after-write protocol and, to accomodate it, very closely spaced write (record) and read (reproduce) head gaps, e.g., 0.150 inch. In such systems, crossfeed, the transformer coupling of write head energy to read circuits, is a major design consideration. Crossfeed can interfere with the data being reproduced from the recording medium. Transformer coupling of write energy generally increases with frequency, however, frequencies higher than the fundamental frequency of the highest data rate are of less concern because the reproduce head circuit can include low pass filter elements to reject them.
FIG. 11 shows a square wave which might represent the highest data rate record current waveform of a digital record/reproduce system. The relative amplitudes of the fundamental frequency, the third harmonic, and the fifth harmonic comprising part of the frequency spectrum of this waveform are also shown. The harmonics can, of course, be filtered by the system; but the fundamental frequency which has a higher peak value than the recording waveform can crossfeed to the reproduce circuit. Design elements of the read/write head assembly and its shielding are dictated by crossfeed performance versus cost considerations.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a chart illustrating conventional continuous magnetic recording;
FIG. 2 illustrates a conventional magnetic record head and media;
FIG. 3 is an enlarged detail of FIG. 2;
FIG. 4 further illustrates a recording zone;
FIGS. 5A and 5B illustrate the demagnetization effect in a thin, flat recording sheet;
FIG. 6A is a table summarizing demagnetization effects;
FIG. 6B shows a magnetization model for a record current transition;
FIG. 7 shows a magnetization model for a particular record current transition;
FIG. 8 shows a subsequent cycle partial erasure for a record current rapid change in polarity;
FIG. 9 shows proximity mutual flux loss;
FIG. 10 shows one typical data record current waveform;
FIG. 11 shows a square wave with its fundamental frequency, and third and fifth harmonics;
FIG. 12 is a block diagram of a recording system of the present invention;
FIGS. 13 and 14 are time, waveforms and magnetic vector charts;
FIG. 15 is a diagram of the record circuit;
FIGS. 16 and 17 shows magnetic vector components.
DESCRIPTION OF THE INVENTION
In accordance with the present invention, a magnetic flux continuum analogous to a digital information signal continuum is recorded as a sequence of end-to-end juxtaposed magnetized increments. The sequence of magnetized increments is recorded along a track of a recording medium as the medium moves at constant speed relative to a record transducer (head). Each magnetized increment comprising the 14 magnetic flux continuum is produced by an instantaneous magnetic recording field. This instantaneous recording field results from the record head being driven by a current impulse. The current impulse is of short duration compared to the time required for a point on the track to traverse the length of the recording field which it produces. The length of each magnetized increment so produced includes the length along the track penetrated by the recording field; for a ring head, this length is the entire gap leading edge to gap trailing edge penetrating field length which includes all contours of sufficient intensity to produce a recording effect. The length of each magnetized increment also includes the relatively small distance traversed by a point on the track during application of the current impulse. The timing of the sequence of current impulses which produce the sequence of magnetic increments is such that the end of one magnetized increment on the medium is made to approximately coincide with the beginning of the next magnetized increment, in sequence, along the track. Of course, the timing is a function of the speed of the record medium relative to the record head.
Thus, a magnetic flux continuum is produced by a sequence of current impulses having a low active duty cycle.
In one embodiment of the present invention, the aforesaid magnetized increment length (determined, in part, by the record head gap length) is made to coincide with the length of an NRZ-L bit cell recorded on magnetic tape. Thus, it can be appreciated that a sequence of bits can be recorded on tape by means of uniformly time-separated, short duration, current impulses of appropriate sense, one current impulse corresponding to one recorded bit; and that the magnetization pattern thus produced will be similar to that produced by systems which apply current of one sense or the other to the record head continuously (continuous current systems); and that the heating effect (average power consumption) of such current impulses in head driver electronic components can be low, and that media surface modulation noise can be statistically limited during recording by the short duration of the active current impulse.
It can also be appreciated that the sequential current impulse waveforms are not characterized by instantaneous reversals of polarity, as are continuous current system waveforms. Therefore, there are minimal subsequent cycle erasure effects and proximity mutual flux loss effects. In consequence, peak record currents can be made relatively high to achieve good overwrite performance without causing a significant loss of output for high transition rate signals and without causing at least one transition shifting mechanism.
An additional factor to be appreciated is that the sequential current impulse waveform spectrum includes a fundamental frequency of lower peak value than the impulse itself, and use of sequential current impulse recording can result in low crossfeed interference by the fundamental frequency component.
Therefore, the objects of the present invention are:
To provide for sequential impulse magnetic recording of information on a magnetic medium in a manner which can be compatible with the reproduce techniques of continuous current recording systems, which systems are widely known and applied in the art.
To provide for magnetically recording information in a manner which requires less energy and dissipates less heat than do continuous recording systems.
To provide for magnetically recording information in a manner less affected by media surface modulation noise.
To provide for magnetically recording information in a manner which can simultaneously achieve less interference from overwritten data, higher output of high transition rate data signals, and fewer transition shifting mechanisms than can simultaneously be achieved by continuous current recording systems.
To provide for magnetically recording digital information in a manner which can produce less fundamental frequency crossfeed interference energy than is produced by continuous current recording systems.
Other objects and advantages of the invention will be apparent to those skilled in the art from the foregoing general description of the invention, and from the following description of one embodiment of the invention. This embodiment is presented only as illustrative of the invention in order to facilitate a complete understanding thereof by those skilled in the art, and to facilitate their making and using the invention. This embodiment represents the best mode contemplated at this time for practicing the invention, although it is obvious that other modes are possible and might indeed ultimately prove more practical.
The following description is had in conjunction primarily with FIGS. 12-17 of the accompanying drawings, wherein like reference characters refer to like or corresponding parts, and wherein:
FIG. 12 is a block diagram of a recording system for practicing the present invention, with associated schematic waveform diagrams for explaining the operation;
FIGS. 13 and 14 are time, waveform and magnetic vector charts showing the details of impulse recording in accordance with the present invention;
FIG. 15 is a schematic diagram of the record circuit used in the present embodiment of the invention;
FIG. 16 depicts the magnetic vector components wherein the present invention is practiced with a small overlap in recording increments; and
FIG. 17 depicts the magnetic vector components wherein the present invention is practiced with perpendicular field recording.
In one single channel (track) embodiment of the present invention, digital information is recorded on magnetic tape by means of sequential recording current impulses. The magnetization patterns created on magnetic tape by this embodiment are similar to the patterns created by continuous current recording systems in all characteristics essential to their being reproduceable as electrical signals by reproduce systems of types known in the art and widely used in conjunction with continuous current recorders.
FIG. 12 shows a functional block diagram of the present embodiment of the invention, and of a reproduce system. Waveforms associated with the NRZ-L code used, are also shown.
A data signal conveying each bit (level) to be recorded and a clock signal defining each bit period (cell) are applied to their respective record logic circuit inputs 101 and 102. The record logic circuit 103 processes the clock and data to produce dual polarity voltage impulses. The voltage impulses are converted to current impulses of appropriate amplitude and sense by a head driver 104 having an input level control. The head driver, in turn, drives the record head 105. The record head creates an instantaneous magnetic recording field and a magnetically recorded increment in the tape 106, for each intermittent current impulse. The length of each increment thus recorded is related to the record head gap length. The spacing of these recorded increments is defined by the timing of current impulses and the speed of the magnetic tape, which speed is well regulated by means known in the art.
For this embodiment, design parameters such as record head gap length, current impulse timing, and tape speed are chosen to produce closely spaced recorded increments on tape, each of which corresponds to a bit cell. A tape thus produced can then be reproduced by a system functionally equivalent to that shown in FIG. 12 and described herein, in general terms, for benefit of an example.
The reproduce head 107 generates a voltage proportional to the rate of change of flux sensed across its gap as the tape moves over it at a uniform speed. The reproduce head signal is amplified by a preamplifier 108, then equalized at 109 to compensate for the non-constant amplitude versus frequency (data level change rate) transfer characteristic of the rate-responsive reproduce head. Phase equalization to compensate for pattern sensitivity or for phase erros introduced by amplitude equalization may also be employed. The equalized reproduce signal is then processed by the reproduce logic circuit 110 which detects and shapes the output data signal, synthesizes a stable clock signal, and accurately synchronizes the data signal to the clock signal, at output terminals 111 and 112.
A dimensioned timing diagram and vector magnetization model for the recording of a 1-0 bit sequence by the subject emobidment is shown in FIG. 13. The timing of the reproduce waveform for that sequence is also shown.
The data rate of this embodiment is 250,000 bits per second (BPS) recorded (and reproduced) at a tape speed of 71/2 inches per second (IPS) to produce a bit packing density on tape of 33,333 bits per inch (BPI). For the NRZ-L code used, 33,333 is also the maximum number of flux changes per inch (FCI), i.e. the maximum number of sense reversed, adjacent increments (half-cycles) recorded per inch of tape. Each bit cell corresponds to a time interval of 4 microseconds and a recorded length of tape of 30 microinches. The upper frequency of the record/reproduce channel pass band need only be 125,000 Hertz for 250,000 BPS at the Nyquist rate of 2 bits per Hertz.
The clock period is 4 microseconds to provide a positive-going voltage transition at the beginning of each bit cell as shown. The 50 percent duty cycle clock waveform also provides a negative-going transition at the center of each bit cell. Each negative-going transition of the clock is used to trigger a recording current impulse. The duration of each current impulse is 400 nanoseconds and its sense is defined by the data level of the cell to which it corresponds.
In the vector magnetization model of FIG. 13, vectors marked "1" represent components recorded at the leading edge of a current impulse; those marked "t" represent components recorded 400 nanoseconds later at the trailing edge of the current impulse. The length, L A , is the distance traveled by the tape during an active current impulse (3 microinches). The shaded area of FIG. 13 represents the effective recording field penetration into the tape, and the length L E , the length of that penetration. The length of each recorded increment, L I , is 30 microinches, the sum of a field penetration length (L E ) of 27 microinches plus the 3 microinches traveled during its recording current impulse. The length of the record head gap, L G , producing the desired penetration length is approximately 20 microinches.
FIG. 14 illustrates waveforms and a planar/normal vector magnetization model associated with the subject embodiment and a random bit sequence. The long sequence of identical bits, e.g., 0--0--0, are recorded as identical increments having adjacent terminations of opposite sense components. These components, shown circled in FIG. 14, have energy stable, proximity, mutual fields which cannot be sensed by a reproduce circuit. Therefore, the effective component pattern is similar to one produced by continuous current recording.
FIG. 15 is schematic diagram of the record circuit used for the subject embodiment. Dual polarity, positive logic is used, i.e. a positive voltage signifies a logic "1", a negative voltage signifies a logic "0". U1 and U2 are non-inverting buffers for the clock and data signal respectively. The clock buffer U1 drives the inverting trigger input of a monostable multivibrator, U3. U3 generates a positive pulse at its Q output for each negative-going clock transition. R1 and C1 are timing components which determine the duration of each positive pulse (400 nanoseconds). The Q output of U3 is applied to the control input C of a bilateral switch, U4. The output of U2 is connected to the data input I of U4. When the control input of U4 is negative, it is in a high impedance state and its output at 0 is held to ground potential (0 volts) by R2. When the control input is positive, during the 400 nanosecond pulses, the output of U4 is of the same polarity as the data signal. The dual polarity voltage impulses thus derived are divided by level control potentiometer, R2. The R2 signal is connected to a transconductance head driver consisting of Q1 through Q4 and R3 through R7. The head driver converts voltage impulses to current impulses and presents a high source impedance to the record head, L1. The driver, acting as a current source, provides a small L/R time constant in conjunction with record head inductance and results in a broad range of inductances possible in a record head designed to be driven by short duration current impulses. When the input to the bases of Q1 and Q2 is grounded (the quiescent state), Q1 through Q4 are not conducting and no current is supplied to the head. When the input is positive, Q2 and Q4 are not conducting, but Q1 does conduct. The current of Q1 is determined by the value of R5 and the input voltage. Q1 current causes a voltage drop across Q1 collector resistor, R3. The R3 voltage and the value of R6 determine the collector current of Q3. The collector of Q3 drives the record head during positive sense impulses. When the input to the bases of Q1 and Q2 is negative, Q1 and Q3 are not conducting, while Q2 conducts current in an amount determined by the input voltage and the value of R5. Q2 current then causes a voltage drop across R4 which, in conjunction with the value of R7, determines the collector current of Q4. The collector of Q4 drives the record head during negative sense impulses.
Thus, the data signal and clock signal are processed to provide 400 nanosecond current impulses of dual sense for recording.
In summary, the subject embodiment records bits as 30 microinch magnetized increments on tape: the length of each increment is largely determined by head design, not tape motion; and the field energy of each increment is derived from a current impulse having a tape motion related, half-wavelength of only 3 microinches, one tenth of the recorded increment length. Expressed in terms of frequency, the 400 nanosecond recording current impulse relates to the half-wave period of 1.25 megaHertz signal, a frequency ten times higher than the pass band required for the subject embodiment data channel. It is significant that, in comparison to the heat dissipated by elements (e.g. transistor junctions) of comparable continuous current head drivers, the heat dissipated by the impulse current head driver of this embodiment is reduced by 90 percent. A further 90 percent reduction in heat could easily be achieved by reducing the 400 nanosecond current impulses (10 percent duty cycle) to 40 nanoseconds (1 percent duty cycle), an entirely practical value considering that less than 3 nanoseconds is required to switch the particles of the magnetic tape and that any active record current duty cycle including current impulses of at least 3 nanoseconds will, in theory, be sufficient. As a practical matter, the minimum active record current duty cycle acceptable for a given application will be determined by the minimum pulse width handling capacity of components selected for other considerations such as cost. At the other extreme, determining the maximum duty cycle acceptable for a given application requires a more complex analysis of the effects of increased duty on the various benefits expected. In practice, it has been found that substantial benefits of sequential current impulse recording over continuous current recording are obtained by using an active record current duty cycle of 50 percent or less. The vector magnetization resulting from the subject embodiment is effectively the same as that from its continuous current counterpart; but, the magnetizations are produced without the need to continuously record and thereby overwrite record head leading edge components; in fact, it is inefficient to do so.
In the magnetic tape recorder embodiment described herein, the shortest recorded half-wavelength was determined by the data rate and the tape speed, both of which were constant. However, in typical magnetic disk applications, data rate and angular velocity are constant; track (cylinder) speed varies with circumference as does bit packing density and recorded half-wavelength. If, in a disk embodiment of the present invention, design parameters are chosen to yield a recording increment length corresponding to the minimum half-wavelength to be recorded on the outer track, then these recording increments will overlap on inner tracks. Impulse recording with overlapped increments is modeled in FIG. 16. The bold vectors are shown to have overwritten the "over-length" components (shown dashed) of the previously recorded half-wavelength. This increment overlap is similar to overwriting which occurs in continuous current recording systems, except that some benefits of the current impulse recording technique are retained, which benefits are generally associated with the nature of the recording waveform.
The benefit of compatibility with reproduce systems of continuous current recorders is obviously retained regardless of the degree of overlap (or increase in active record current duty cycle caused by overlap) for continuous current recording could be regarded as an infinite sequence of overlaps. The benefits of reduced modulation noise and reduced heat dissipation are inversely related to the active duty cycle of the sequential current impulse recording waveform. The benefits of improved overwrite performance without loss of output for high transition rate signals depends on maintaining a recording medium motion related distance separating the occurrence of opposite sense record current impulses, which distance is at least equal to the length of the record zone located at the trailing edge of the record head gap (refer to FIG. 8.) Of course, the record zone length increases with peak record current but the condition of separation of opposite sense recording impulses is generally met so long as the combination of the impulse duration and the overlap provides an inactive time interval between impulses which allows this distance to traverse the head. The benefit of reduced crossfeed interference depends on the degree of reduction of the fundamental frequency energy for the impulse current waveform compared to that of a continuous recording current waveform. In summary, the overall benefits of sequential current impluse recording are retained substantially for moderately overlapped increments. This fact permits application of reasonable gap length tolerances in the manufacture of current impulse record heads for all applications. Operation with overlapped recording increments also permits use of the current impulse recording method with codes having possible transitions at sites other than those defined by integer multiples of the minimum half-wavelength increment.
In an embodiment of the present invention which utilizes perpendicular field recording, the length of the effective field region (L E ) is defined by head pole geometry rather than record head gap length. Purely normal magnetization components of one sense are recorded in each increment length as shown in FIG. 17. Each recorded increment is produced by a single, low duty cycle, current impulse of appropriate sense in a manner similar to that described herein for the longitudinal recording embodiment.
Restating the invention in light of all the foregoing description and analysis, in reference to the embodiment utilizing the linear traverse of a magnetic record head relative to the surface of a magnetic record medium, the following terms are defined:
L E is the length along said line of traverse of the effective recording field of the record head (see FIG. 13);
L A is the length of said linear traverse during the time of application of an active record current impulse to said record head (see FIG. 13);
L I is the length of a recorded increment resulting from the application of a record current impulse to said record head (see FIG. 13);
S T is the speed of said traverse;
T A is the period of an active recording current impulse (see FIG. 13); and
T R is the period between initiation of successive recording current impulses (see FIG. 13).
In accordance with the present invention the relationships among the terms defined above are expressed by the following equations:
1. L A =S T ×T A ;
2. L I =L E +L A ; and
3. L A <L E
In the referenced embodiment of the invention, T A /T R is the active record current duty cycle, it may conveniently equal about 1/4, or 1/10, or can be made as small as is practical for the minimum pulse width capacity of the components selected for the recording circuit. Of course, the recording current impulse must be of sufficient duration to accomplish switching of the magnetic particles. Also, ideally, L E =S T (T R -T A ) and T R =L I /S T as this would mean that the effective length of the recording field (L E , determined by record head design and magnitude of record current) exactly corresponded to the length of traverse of the magnetic medium during the inactive time interval between successive, active recording current impulses; in consequence, a continuous magnetic recording without overlap or separation of successive increments of recording would be provided. However, the advantages of the present invention are still obtained with some measure of overlap or separation of the successive increments of recording.
The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. | Magnetic recording of a data continuum is effected by means of sequential impulses of recording current. The impulses occur at regular intervals providing samples of the data continuum. The impulses are of very short time duration, in that each impulse extends for only a small fraction of the time interval that is required for a point on the record medium to traverse the effective recording field of the record head. The time spacing between impulses is approximately equal to said time interval, thereby providing a magnetic recording continuum corresponding to said data continuum. | 6 |
BACKGROUND OF THE INVENTION
The present invention relates to an appliance spin control and method adaptable to floor structure.
Washing machine appliances include washing baskets that spin about a basket axis during one or more washing machine cycles. Weak, unstable or unlevel supporting floors often cause a washing machine to become unbalanced, and therefore it is necessary to provide a system which compensates for a lack of rigidity, stability, or levelness of the floor below the machine. Because the floor condition will vary from one washing machine installation to another, it is desired in accordance with the present invention to have the machine automatically adjust the rotational speed of the basket in relation to the characteristics of the supporting floor.
Therefore a primary object of the present invention is the provision of an improved appliance spin control and method which automatically adjusts the spin of the washing basket in response to the particular characteristics of the supporting floor structure.
A further object of the present invention is the provision of a spin balance control that utilizes a vibration sensor attached to the washing machine cabinet for sensing the vibration of the cabinet during rotation of the washing machine basket.
A further object of the present invention is the provision of a spin control which adjusts the rotational speed of the basket to prevent unbalance vibration for each variation of supporting floor structure.
A further object of the present invention is the provision of an improved appliance spin control and method which are economical in manufacture, durable in use, and efficient in operation.
BRIEF SUMMARY OF THE INVENTION
The foregoing objects may be achieved by a washing machine spin balancing system comprising in combination a support floor and a washing machine cabinet supported on the support floor. A washing machine basket is mounted within the cabinet for rotation about a basket axis. A drive is connected to the basket for causing rotation of the basket. The drive is capable of rotating the basket at a high rotational speed or alternative at one or more low rotational speeds slower than the high rotational speed. A vibration sensor is attached to the cabinet for sensing the vibration of the cabinet. A controller is connected to the sensor and to the drive. The controller is adapted to cause the drive to rotate the basket at the high rotation speed in response to the vibration sensor sensing less than a predetermined amount of vibration of the cabinet. The controller is adapted to cause the drive to rotate the basket at a low rotational speed in response to the vibration sensor sensing more than the predetermined amount of vibration of the cabinet.
According to one feature of the invention the vibration sensor comprises an accelerometer. However, the particular structure of the accelerometer or vibration sensor may vary without detracting from the invention. All that is required is that the vibration sensor be capable of sensing the vibration of the washing machine cabinet.
According to another feature of the invention, the slower rotational speed is approximately 67% of the higher rotational speed.
The foregoing control system permits the reduction of the rotational speed of the basket in response to various types of floors. A floor with imperfections causes the threshold unbalance vibration to be reached more easily at the higher rotational speed than would be the case if the floor were without these imperfections.
According to another feature of the invention, the method comprises placing the washing machine cabinet on a floor having unique characteristics of stability, strength, and levelness which affect the magnitude of vibration of the washing machine cabinet in response to rotation of the basket within the washing machine cabinet. A drive is used to rotate the washing machine basket at a first rotational speed. During rotation a sensor senses the magnitude of vibration of the washing machine cabinet. A controller connected to the vibration sensor and to the drive causes the drive to reduce the rotational speed of the basket to a second rotational speed slower than the first rotational speed in response to the sensed magnitude of vibration of the washing machine basket exceeding a predetermined magnitude of vibration.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic pictorial view of a washing machine having a rotatable washing machine basket therein.
FIG. 2 is a pictorial view of an example of an accelerometer that may be used with the present invention.
FIG. 3 is a block diagram showing the interrelationship of the sensor, the controller and the drive motor.
FIG. 4 is a flow diagram showing the method for controlling rotational speed of the basket.
DETAILED DESCRIPTION OF THE INVENTION
Referring to the drawings the numeral 10 designates a washing machine cabinet. Cabinet 10 includes cabinet feet 12 which are shown schematically, and which support the cabinet 10 on a supporting floor 14 . The structure of the feet 12 is intended to be shown only in a schematic sense, and various types of supporting legs, feet or devices are used with washing machines to support the washing machine cabinet on a supporting floor.
Many supporting floors differ in their characteristics. Some floors are not level. Others are weak and likely to vibrate in response to vibration of the cabinet. Others may have depressions or other weak parts which cause the cabinet 10 to vibrate more easily than would be the case if the cabinet were supported on a level sturdy floor.
A basket 16 is rotatably mounted with the cabinet 10 and is driven by a drive motor 18 shown schematically in FIG. 1 . Mounted on the cabinet 10 is a controller 20 for controlling the drive motor. Also mounted on the cabinet 10 is a sensor box 22 . Within sensor box 22 is a sensor 24 which is adapted to sense the vibration of the cabinet 10 .
The preferred vibration sensor 24 is an accelerometer such as shown in FIG. 2 . The accelerometer 24 in FIG. 2 is electronically connected to the controller 20 and is mounted on cabinet 10 to sense machine vibration. Although the accelerometer can be positioned in a variety of different locations about the washing machine cabinet 10 , mounting the accelerometer 24 toward the top of the washing machine cabinet 10 has been found to produce the most reliable results. The accelerometer includes a piezoelectric film 26 with a mass 28 attached to the end of the film 26 . Leads 30 are also attached to the film 26 . The accelerometer 24 is well suited for measuring vibration because acceleration of the mass 28 and the vibration of the cabinet 10 are proportional. The accelerometer 24 shown in FIG. 2 is only an example, and other forms of accelerometers or vibration sensors may be used without detracting from the invention.
Referring to FIG. 3 the sensor or accelerometer 24 is connected electrically to the controller 20 , and the controller 20 is also connected to the drive motor 18 . Drive motor 18 is adapted to rotate the basket 16 at two or more different speeds. The normal speed is the fastest, but if an unbalance situation arises where the vibration of cabinet 10 is too great then the motor 18 is capable of reducing the rotational speed of the basket to one or more lesser speeds.
FIG. 4 shows a flow diagram of the method of the present invention. The numeral 32 refers to the start of the method. After the start the motor 18 rotates the basket 16 at its normal high speed. This step is identified by the numeral 34 .
The numeral 36 refers to the sensing of the vibration of the cabinet 10 by means of the accelerometer 24 . The numeral 38 refers to the analysis done by the controller 20 to determine whether or not the sensed vibration exceeds a predetermined magnitude representing undesirable unbalance situations. The numeral 40 represents a “no” analysis that the vibration is below the unbalance condition. In that situation the controller 20 causes the motor 18 to continue rotating the basket 16 at its highest speed.
However, if an unbalance condition is sensed at any time during the rotation of the device, as represented by the numeral 42 , the controller automatically causes the drive 18 to reduce the rotational speed of the basket to a slower rotating speed. There may be only a single slower rotating speed, or there may be multiple rotating speeds in descending order, all less than the initial rotating speed represented by the numeral 34 .
During the rotation at the slower speed, the accelerometer continues to sense the vibration of the machine, and if the vibration ceases, the controller can again initiate the rotation of the basket 16 at the faster speed.
The controller may set so that it continues at the slower speed, or it can be set so that after a pre-determined time frame it could retry to attain the faster speed. As it accelerates from the slower speed to the faster speed, the sensor may sense the vibration and switch back to the slower speed. It is not required that the faster speed be used for adequate performance.
The advantage of the present invention is that the controller automatically adjusts the rotational speed of the basket 16 in relation to the type of floor 14 upon which the cabinet 10 is supported. If the floor is weak or not level, the vibration sensed by the sensor 24 reaches the predetermined unbalance condition very easily, thereby causing the controller to reduce the speed of the basket. On other floors that provide a better supporting surface, there may be little or no sensing of an unbalance condition, and the basket continues to rotate at its higher speed. Furthermore, if at some time during the spin cycle the contents of the basket 16 become unevenly distributed, an unbalance condition may arise, and the controller will automatically reduce the speed of the basket during this temporary unbalance condition.
In the drawings and specification there has been set forth a preferred embodiment of the invention, and although specific terms are employed, these are used in a generic and descriptive sense only and not for purposes of limitation. Changes in the form and the proportion of parts as well as in the substitution of equivalents are contemplated as circumstances may suggest or render expedient without departing from the spirit or scope of the invention as further defined in the following claims. | A washing machine spin balancing control includes a sensor for sensing vibration of the washing machine cabinet. The floor permits the cabinet to vibrate during the rotation of the basket, the controller senses this vibration and reduces the speed of the basket in response to the vibration caused by imperfections in the floor. | 3 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a case for storing medical instruments and apparatuses, for strong medical denistry, for example, dental burs, dental cutters, ratchets, screwdrivers, and devices such as endodontic aids.
2. Description of the Prior Art
With the prior art, dental instruments are stored in trays, either individually in bores, or together in larger bores. Dental apparatuses are also stored in special boxes.
The cases commonly used at present are of a design which is unfavorable from the application point of view. Thus, the stability and the clear arrangement of the instruments stored therein are for the most part very unsatisfactory. At the same time, it is often not possible to remove the instruments easily and safely using one hand. In addition, the risk of the cutting edges and bur points breaking upon contact with one another, with the case walls or with external objects is not generally prevented.
The dental material into which the instruments, such as burs and cutters, have to penetrate during working on the tooth is known to be hard and abrasive. Burs and milling cutters which are used on this material have to be very hard in order to guarantee an acceptable service life. These hard and wear-resistant bur and cutter materials are known to be brittle and friable. The cutting edges and points of such cutters and burs are therefore very susceptible to abrasion and breakage of the cutting edges, if they are carelessly handled, and they have to be stored safely without any wall contact whatsoever.
In addition to the abovementioned requirements, a case for medical instruments and apparatuses should also facilitate the repeatedly necessary cleaning and disinfection of the instruments and devices used in the field of dentistry. To this end, the case itself must not only be able to be cleaned thoroughly in a simple and hygienic manner, but must at the same time be capable of being used directly as a container for the instruments and devices which are to be sterilized in the steam bath, at a maximum of 135° C.
Cases for application in dentistry, which satisfy all the abovementioned requirements simultaneously, are not as yet known.
A transport container for spiral burs is disclosed in the PCT patent specification WO 92/15502, a variable number of spiral burs being held immobile in order to prevent any damaging contact of the bur points within the inner walls of the container. For this purpose the container has a bottom part which is joined by means of a hinge to a lid part, which is designed such that it can be swivelled downward to make contact with the bottom part. A plurality of rectangular receiving holders for spiral burs are secured on the bottom part. Receiver openings for spiral burs in each receiving holder are designed for receiving one or more spiral burs, each of which is equipped with a limit ring around it for the purpose of limiting the depth of insertion. A plurality of holding plates extend downward from the lid part. With the lid part closed, a separate holding plate is thus arranged between two adjacent receiver openings for spiral burs in such a way that the lower surface of the holding plate is arranged above the upper limit ring surfaces which are formed on the spiral burs introduced into the receiver openings. This ensures that each upward movement of the rings arranged on the spiral burs is limited. However, this design of the case has the disadvantage that with the lid part opened, a spiral bur can fall out from the receiver opening. In addition, each spiral bur has to be equipped with a limit ring, which is expensive.
A case for storing elongate instruments, such as spiral burs, thread-cutting taps and the like, is known from the patent specification DE 3500569 C1. The case has a lid part, and a bottom part attached to the latter, as well as a holder part, arranged on the bottom part, with guide holders for the instruments, which are aligned essentially perpendicular to the swivel axis of the bottom part. Each guide holder has two guide recesses, of which the first forms a central mounting, essentially free of play, for the instrument, and of which the second has a shape which permits a swivel movement of the instrument about the first guide recess in a plane perpendicular to the hinge axis of the bottom part. The disadvantage of this embodiment lies in the fact that the case has only a moderate stability, the instruments can fall out when the lid part is opened, and the movable parts and the guide holders cannot be reliably cleaned.
3. Objects of the Invention
For cases of the abovementioned type, the invention achieves the object of securing the instruments against any damage, be it during transportation, during opening or closing of the case, or in the event of hocks or movements during sterilization. The case according to the invention should in this respect not only offer a reliable solution preventing the instruments from inadvertently falling out, but should also reduce to a minimum any risk of injury to the user during removal or introduction of the instruments and apparatuses.
It should also be possible, for instance when making the case ready for introduction or removal of the instruments, for the case itself, and also for the parts of the case which have been opened up, to be positioned securely and be swivelled into a position facilitating removal. It would at the same time be expedient if the instruments which are to be stored were arranged in a line so that they could be seen clearly at all times. The individual parts of the case according to the invention should be of a straightforward and robust design. The novel case should be safe to handle and as easy as possible to clean. It should also be capable of being used directly for disinfection of the instruments and devices, which are stored therein, in the liquid and steam baths which it is desired to use in each case. Finally, it should be possible for the novel case to be used as a complete treatment unit with all instruments and apparatuses necessary for the dental treatment envisaged.
SUMMARY OF THE INVENTION
The above-discussed objects of the present invention are achieved by providing a case for dental instruments and apparatuses in which a container and an associated lid are provided with at least one tray, and at least one insert, extending alongside the tray, is arrange in the container, with the insert including a unit for receiving the instruments. The unit consists of a holder and a carrier. The unit can be folded about swivel axle elements into a folded down position parallel with the bottom of the case and into an opened, vertical position. The unit in the folded down position provides for play in the axle bearings and can be removed from the insert without auxiliary means. In the opened position the unit is immovably fixed in the axle glide, and is held releasably in this position by bulge means. The carrier has insert openings for receiving the instruments, with each insert opening having a shape which interacts with a stop arm on the holder in such a way that the instrument located in the insert opening is secured against positional displacement by the contact pressure of the respective stop arm. It is further provided a grip projecting above the instruments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows an opened case for instruments and apparatuses in a plan view, with an insert arranged therein, together with holder and support, and also a tray;
FIG. 2 shows a section through the case along the line A--A in FIG. 1, the holder and support being represented in a position in which they are opened up;
FIG. 3 shows a partial section along the line B--B in FIG. 2 through the mounting and the fixing means for an instrument, on an enlarged scale;
FIG. 4 shows a partial section along the line C--C in FIG. 2, with the unit in the closed position, on an enlarged scale;
FIG. 5 shows a partial section along the line C--C in FIG. 2, with the unit in the opened position, on an enlarged scale;
FIG. 6 shows a partial section along the line D--D in FIG. 1, with the unit in the closed position, on an enlarged scale;
FIG. 7 shows a partial section along the line D--D in FIG. 1, with the unit in the opened position, on an enlarged scale.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The case 1 represented in FIGS. 1, 2 and 3 consists of a container 2, and of a lid 3 which can be placed on top. Both parts 2, 3 are preferably made of aluminum, which is surface-treated. The container 2 has a bottom 21 with hollows, and support feet 22. The lid 3 similarly has a cover 31 with hollows.
In the container 2 there is at least one tray 4 for receiving apparatuses 81-83, and at least one insert 5 for receiving instruments 80. Both parts 4 and 5 are made of stainless steel, for example.
The tray 4 has a bottom 41 with hollows. End walls 42, 43 with support strips 46, 47 issue from the narrow edges of said bottom 41, while side walls 44, 45 without support strips issue from its long edges. The end walls 42, 43 and side walls 44, 45 are designed widening upward, and the support strips 46, 47 are preferably bent inward.
The insert 5 has a bottom 51 with hollows. End walls 52, 53 issue from the narrow edges of said bottom 51, while side walls 54, 55 issue from its long edges. Here, the end walls 52, 53 each have a support strip, and one of the side walls 54, 55 has a third support strip, the three support strips being contiguous. Swivel journal guides 56, 57 are formed in the end walls 52, 53 for the purpose of receiving swivel journals 71, 72 of a carrier 7.
The carrier 7 is essentially rectangular in cross section. As a body, it has the shape of an elongate parallelepiped. The latter has, on its upper, narrow cover surface, insert openings 73 which are arranged in a straight line and are spaced apart uniformly from each other. These insert openings 73 extend from the upper cover surface of the carrier 7 almost to its bottom surface, maintaining a residual wall thickness. The insert openings 73 receive instruments 80 secure against tilting and with play. The carrier 7 moreover has a swivel axle 78, for which purpose it has, on its end walls 74, 75, the swivel journals 71, 72 which have already been mentioned. The carrier 7 can be folded down into a horizontal position parallel with the bottom, and can be opened up into a vertical position.
The carrier 7 is pushed into a holder 6 which is essentially U-shaped in cross section. A bead 61 in the one leg 62 of the holder 6 engages into a recess 76 of the carrier 7 and thus fixes, in conjunction with the other leg 65 of the holder 6, the position of the carrier 7 in the holder 6 in two of three directions. The one leg 62 of the holder 6 moreover lies opposite the insert openings 73 of the carrier 7.
Each insert opening 73 has an essentially cylindrical shape. It also has an open side surface 77 toward the one leg 62 of the holder 6. Taking this open side surface 77 of the insert openings 73 into account, the cross sectional areas of the insert openings 73 have the shape of a circle, from which one segment has been removed. The ratio of the curve height h of the removed circle segment to the circle radius r of the residual circle area preferably amounts here to 2/5, but can lie between 1/5 and 4/5 depending on the concrete example of application. The radius r* of the individual instrument shaft located in the insert opening 73 is in each instance slightly smaller than the circle radius r of the associated insert opening 73, but greater than the curve height h of the removed circle segment (written as a formula: h<r*<r), so that a part of the instrument shaft 80 protrudes outward through the open side surface 77 of the insert opening 73. The respective size of the circle radius r of the insert openings 73 in the carrier 7 must of course be adapted to the predetermined, standardized measurements of the individual instrument shaft.
Stop arms 63 are arranged on the one leg 62 of the holder 6 at a short distance from the front long wall of the carrier 7. Each insert opening 73 is assigned, at its open side surface 77, such a stop arm 63. Each stop arm 63 is in this instance designed with a bulge 64 in order, in conjunction with the insert opening 73, to hold the instruments 80 immobile by contact pressure, i.e. to secure them against moving in their insert openings 73. This securing of the instruments is guaranteed both when the unit 6, 7 is in the opened position and in the folded down position, and also when the unit 6, 7 is being removed from the insert 5. The stop arms 63 issue from, and are made of the same material as, the holder 6, i.e. the design is cost-effective and of simple technological concept.
Since the insert openings 73 are arranged in a line and in the longitudinal direction of the carrier 7, there is a clear view of the instruments 80 when the carrier 7 is in the opened position. That part of the instrument shaft in each instance protruding from the carrier 7 can be easily gripped with the pincers. The instrument 80 which is wanted can thus be removed from the carrier 7 easily, safely and in a perfectly hygienic manner.
The following statements are evident in conjunction with FIGS. 1, 4, 5, 6 and 7.
The other leg 65 of the holder 6 has, at its free end, a rim 66 which is L-shaped in cross section. When the unit 6, 7 is folded down, the rim 66 can be used as a grip for opening the unit 6, 7, i.e. for moving it from its horizontal position in the container 5 into its vertical position by turning the whole unit 6, 7 through approximately 90° about the swivel axle 78 extending through the swivel journals 71, 72. The unit 6, 7 is in this instance held in bearings by means of the swivel journals 71, 72 interacting with the swivel journal guides 56, 57 of the insert 5, as shown in FIG. 7. A locking is obtained by virtue of the fact that two bulges 58, 59 in the rear side wall 55 of the insert 5 interact with two resilient beads 68, 69 at the lower corners of the leg 65 of the holder 6, since the resilient beads 68, 69 have to be bent back slightly under application of force when the unit 6, 7 is turned into the vertical position. In this way the unit 6, 7 locks in the opened position free of play, the movements of the swivel journals 71, 72 additionally being guided and limited by the one side wall 55 and the bottom 51 of the insert 5.
In order to remove the unit consisting of holder 6 and carrier 7 from the insert 5, see FIG. 6, the unit 6, 7 is brought into the horizontal position. In this position, it can be lifted in the vertical direction and removed from the insert 5, the swivel journals 71, 72 fitting the gap between the swivel journal guide 56 or 57 and the one side wall 55.
The turning or folding of the unit 6, 7, consisting of holder 6 and carrier 7 in the insert 5, about the swivel axle 78 into the horizontal or vertical position, respectively, and the locking are made possible solely by the interaction of the resilient beads 68, 69 on the holder 6 and of the bulges 58, 59 on the insert 5 with the integrally formed swivel journals 71, 72 on the carrier 7 and the side wall 55 and bottom 51. No welding, soldering, screwing, riveting or other connections are used which have surfaces which are difficult to clean and sterilize. As will be readily appreciated by the specialist, the case can also be dismantled immediately into its individual parts in a few maneuvers. The fact that it can be dismantled into a small number of simple individual parts means that the case can be cleaned perfectly hygienically in a simple manner. | A case for dental instrument including a container, a lid for closing the container, a tray, and an insert arranged alongside of the container and including an instrument-receiving unit having a holder and a carrier and pivotable between a folded down position and an opened, vertical position, axle elements for supporting the instrument-receiving unit for pivotal movement, and elements for releasably holding the instrument-receiving unit in the opened position, with the carrier being provided with instrument-receiving insert openings and the holder being provided with stop arms for retaining the instruments in the insert openings. | 0 |
CROSS-REFERENCE TO OTHER APPLICATIONS
[0001] This is a nonprovisional of the following U.S. Provisional Applications, all of which are hereby incorporated by reference herein in their entireties: U.S. Provisional Application No. 60/866,532, entitled, “A METHOD FOR PACKET AGGREGATION IN A COORDINATED HOME NETWORK”, filed on Nov. 20, 2006, U.S. Provisional Application No. 60/866,527, entitled, “RETRANSMISSION IN COORDINATED HOME NETWORK” filed on Nov. 20, 2006, U.S. Provisional Application No. 60/866,519, entitled, “IQ IMBALANCE CORRECTION USING 2-TONE SIGNAL IN MULTI-CARRIER RECEIVERS”, filed on Nov. 20, 2006, U.S. Provisional Application No. 60/907,111, “SYSTEM AND METHOD FOR AGGREGATION OF PACKETS FOR TRANSMISSION THROUGH A COMMUNICATIONS NETWORK” filed on Mar. 21, 2007, U.S. Provisional Application No. 60/907,126, entitled, “MAC TO PHY INTERFACE APPARATUS AND METHODS FOR TRANSMISSION OF PACKETS THROUGH A COMMUNICATIONS NETWORK”, filed on Mar. 22, 2007, U.S. Provisional Application No. 60/907,819, entitled “SYSTEMS AND METHODS FOR RETRANSMITTING PACKETS OVER A NETWORK OF COMMUNICATION CHANNELS”, filed on Mar. 25, 2007, and U.S. Provisional Application No. 60/940,998, entitled “MOCA AGGREGATION”, filed on May 31, 2007.
FIELD OF THE INVENTION
[0002] The present invention relates generally to information networks and specifically to transmitting information such as media information over communication lines such as coax, thereby to form a communications network.
BACKGROUND OF THE INVENTION
[0003] Many structures, including homes, have networks based on coaxial cable (“coax”).
[0004] The Multimedia over Coax Alliance (“MoCA™”), provides at its website (www.mocalliance.org) an example of a specification (viz., that available under the trademark MoCA 1.0, which is hereby incorporated herein by reference in its entirety) for networking of digital video and entertainment information through coaxial cable. The specification has been distributed to an open membership.
[0005] Technologies available under the trademark MoCA, other specifications and related technologies (“the existing technologies”) tap into the vast amounts of unused bandwidth available on the coax. For example, coax has been installed in more than 70% of homes in the United States. Some homes have existing coax in one or more primary entertainment consumption locations such as family rooms, media rooms and master bedrooms. MoCA™ technology allows homeowners to utilize installed coax as a networking system and to deliver entertainment and information programming with high quality of service (“QoS”).
[0006] The existing technologies provide high speed (270 mbps), high QoS, and the innate security of a shielded, wired connection combined with state of the art packet-level encryption. Coax is designed for carrying high bandwidth video. Today, it is regularly used to securely deliver millions of dollars of pay per view and premium video content on a daily basis. Networks based on the existing technologies can be used as a backbone for multiple wireless access points to extend the reach of wireless service in the structure.
[0007] Existing technologies provide a consistent, high throughput, high quality connection through the existing coaxial cables to the places where the video devices currently reside in the home without affecting other service signals that may be present on the cable. The existing technologies provide a link for digital entertainment, and may act in concert with other wired and wireless networks to extend entertainment throughout the structure.
[0008] The existing technologies work with access technologies such as asymmetric digital subscriber lines (“ADSL”), very high speed digital subscriber lines (“VDSL”), and Fiber to the Home (“FTTH”), which provide signals that typically enter the structure on a twisted pair or on an optical fiber, operating in a frequency band from a few hundred kilohertz to 8.5 MHz for ADSL and 12 MHZ for VDSL. As services reach such a structure via any type of digital subscriber line (“xDSL”) or FTTH, they may be routed via the existing technologies and the coax to the video devices. Cable functionalities, such as video, voice and Internet access, may be provided to the structure, via coax, by cable operators, and use coax running within the structure to reach individual cable service consuming devices in the structure. Typically, functionalities of the existing technologies run along with cable functionalities, but on different frequencies.
[0009] The coax infrastructure inside the structure typically includes coax, splitters and outlets. Splitters typically have one input and two or more outputs and are designed to transmit signals in the forward direction (input to output), in the backward direction (output to input), and to isolate outputs from different splitters, thus preventing signals from flowing from one coax outlet to another. Isolation is useful in order to a) reduce interference from other devices and b) maximize power transfer from Point Of Entry (“POE”) to outlets for best TV reception.
[0010] Elements of the existing technologies, such as that available under the trademark MoCA, are specifically designed to propagate backward through splitters (“insertion”) and from output to output (“isolation”). One outlet in a structure can be reached from another by a single “isolation jump” and a number of “insertion jumps.” Typically isolation jumps have an attenuation of 5 to 40 dB and each insertion jump attenuates approximately 3 dB. MoCA™ technology has a dynamic range in excess of 55 dB while supporting 200 Mbps throughput. Therefore MoCA™ technology can work effectively through a significant number of splitters.
[0011] Managed network schemes, such as MoCA™ technology, are specifically designed to support streaming video without packet loss providing very high video quality between outlets.
[0012] Because digital cable programming is delivered to a structure with a threshold Packet Error Rate (“PER”) below 1 per million, programming transmitted from outlet to outlet within the structure should have a similar or better error rate so as to provide similar viewability. It would therefore be desirable to provide systems and methods for communicating information over the coax in structure networks.
SUMMARY
[0013] There is thus provided, in accordance with the principles of the invention, a system servicing an individual node in a shared communication network having a MAC layer and a PHY layer, the system being operative to interface between the MAC layer and the PHY layer, the system comprising a first physical channel transferring at least one packet between the layers, a second physical channel transferring at least one burst parameter between the layers, and a third physical channel transferring at least one timing signal, for a burst characterized by the at least one burst parameter and comprising the at least one packet, between the layers.
[0014] Further in accordance with a preferred embodiment of the present invention, the timing signal comprises an indication, provided by the MAC layer to the PHY layer, of a time at which to transmit at least one burst.
[0015] Still further in accordance with a preferred embodiment of the present invention, the timing signal comprises an indication, provided by the MAC layer to the PHY layer, of a time at which to receive at least one burst.
[0016] Additionally in accordance with a preferred embodiment of the present invention, the at least one burst parameter is transferred before the burst, from the MAC layer to the PHY layer.
[0017] Further in accordance with a preferred embodiment of the present invention, at least one burst parameter comprises at least one status parameter of the burst transferred after the burst, from the PHY layer to the MAC layer.
[0018] Additionally, in accordance with a preferred embodiment of the present invention, at least one burst parameter comprises at least one reception configuration attribute of the burst.
[0019] Further in accordance with a preferred embodiment of the present invention, at least one burst parameter comprises at least one transmission configuration attribute of the burst.
[0020] Still further in accordance with a preferred embodiment of the present invention, the second physical channel is operative to transfer, from the PHY layer to the MAC layer, an indication of the PHY layer's extent of interest in different types of status parameters.
[0021] Additionally in accordance with a preferred embodiment of the present invention, the second physical channel comprises a multi-standard pre-processor operative to pre-process, for transfer from layer to layer, at least one burst parameter formatted in accordance with any of a plurality of access mode-defining standards.
[0022] According to some communication standards, transmission of information between the PHY layers of various nodes in a network, which may include, say, up to dozens of nodes, is multitone. Some of these standards include, for each individual node N 1 in the network, and for each node with which the individual node N wishes to interact (receive (“RX” from or transmit (“TX”) to) Tx and Rx bit loading tables. Node N i 's TX bit loading table for a particular node N n defines for each of a plurality of tones such as 256 or 512 tones, the number of bits to be loaded on that tone when transmitting to node N n . Node N i 's RX bit loading table for a particular node N n defines for each of a plurality of tones such as 256 or 512 tones, the number of bits loaded on that tone when receiving from node N n . The key accessing these tables is present in the MAC layer.
[0023] Further in accordance with a preferred embodiment of the present invention, the system also comprises at least one bit-loading table stored externally to the PHY layer.
[0024] Still further in accordance with a preferred embodiment of the present invention, the second physical channel is operative to transfer an individual bit-loading table, characterizing a pair of nodes including a Tx node and an Rx node, to a PHY layer of at least one of the Tx node and the Rx node when the nodes are preparing to communicate with one another.
[0025] Further in accordance with a preferred embodiment of the present invention, the second physical channel is operative to transfer at least one item of information regarding a burst, other than contents of packets included in the burst and other than an indication of a time at which to transmit the burst.
[0026] Still further in accordance with a preferred embodiment of the present invention, the timing signal comprises an alert, provided by the PHY layer to the MAC layer, that a burst has been received.
[0027] Further in accordance with a preferred embodiment of the present invention, the system also comprises at least one gain-per-tone table stored externally to the PHY layer.
[0028] According to some communication standards, transmission of information between the PHY layers of various nodes in a network, which may include, say, up to dozens of nodes, is multitone. Some of these standards include, for each individual node N in the network, a gain-per-tone table defining the transmission power for each of a plurality of tones such as 256 or 512 tones when node N transmits to other nodes. The key accessing these tables is present in the MAC layer.
[0029] Further in accordance with a preferred embodiment of the present invention, the second physical channel is operative to transfer an individual gain-per-tone table, characterizing an individual Tx node, to the PHY layer of the Tx node.
[0030] Still further in accordance with a preferred embodiment of the present invention, at least one status parameter transferred after the burst may include at least one of the following: SNR information characterizing the burst; and channel response information characterizing the burst.
[0031] Further in accordance with a preferred embodiment of the present invention, the second physical channel transfers information characterizing a configuration of an individual burst while at least one packets of a burst previous to the individual burst are still traversing the first physical channel, thereby to shorten an inter-frame gap defined between the individual burst and the previous burst.
[0032] Also provided, in accordance with the principles of the invention, is a method for operating an individual node in a shared communication network having a MAC layer and a PHY layer, the method being operative to interface between the MAC layer and the PHY layer, the method comprising transferring at least one packet between the layers over a first physical channel, transferring at least one burst parameter between the layers over a second physical channel; and transferring at least one timing signal, for a burst characterized by the at least one burst parameter and comprising the at least one packet, between the layers over a third physical channel.
[0033] Further in accordance with a preferred embodiment of the present invention, the burst, au be transmitted from the individual node to another node.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] The above and other features of the present invention, its nature and various advantages will be more apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings, and in which:
[0035] FIG. 1 is a simplified functional block diagram of a MAC-PHY interface, constructed and operative in accordance with principles of the invention, in a single device configuration;
[0036] FIG. 2A-2B , taken together, form a table describing the signals of FIG. 1 from the PHY's point of view in accordance with principles of the invention;
[0037] FIG. 3 is a MAC to PHY Timing Diagram describing preferred timing from the MAC of FIG. 1 to the PHY of FIG. 1 in accordance with principles of the invention;
[0038] FIG. 4 is a diagram of several operation states for the PHY of FIG. 1 in accordance with principles of the invention;
[0039] FIG. 5 is a table of parameters for the PHY layer of FIG. 1 in accordance with principles of the invention;
[0040] FIG. 6 is a diagram showing a preferred structure for data passing between the MAC and PHY over the MAC Protocol Data (“MPD”) interface in FIG. 1 ;
[0041] FIG. 7 is a diagram of a burst initialization parameters structure in accordance with principles of the invention;
[0042] FIG. 8 is a preferred timing diagram for a preferred mode of operation for the interface apparatus of FIG. 1 ;
[0043] FIG. 9 is a timing diagram for a burst initialization in accordance with principles of the invention;
[0044] FIG. 10 is a diagram of receive (“RX”) burst result timing in accordance with principles of the invention;
[0045] FIG. 11 is a diagram of RX result budget time in accordance with principles of the invention;
[0046] FIG. 12 is a timing diagram of a burst initialization interrupting an RX burst result, in a system constructed and operative in accordance with principles of the invention;
[0047] FIGS. 13-16 are tables and timing diagrams which together illustrate features of exemplary embodiments of a portion of the interface of FIG. 1 in accordance with principles of the invention;
[0048] FIGS. 17-20 are timing diagrams which together illustrate one implementation of a portion of the interface of FIG. 1 in accordance with principles of the invention; and
[0049] FIG. 21 shows a schematic diagram of an illustrative single or multi-chip device that may be used in connection with the interface of FIG. 1 in accordance with principles of the invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0050] FIG. 1 shows illustrative MAC-PHY interface 1 , constructed and operative in accordance with principles of the invention, in a single device configuration. Interface 1 may be a MoCA™ technology MAC-PHY Interface (“MPI”), which is typically built in a modular way to support communication between PHY layer 10 and MAC layer 20 , which are in communication with different devices.
[0051] Interface 1 includes MAC Protocol Data (“MPD”) interface 110 , which may include 8-bit data bus 112 , management interface 120 , which may include 4-bit data bus 122 , control interface 130 and configuration interface 140 . Interface 110 may be used to transfer data from and to MAC 20 . Management interface 120 may be used to transmit burst initial parameters and to receive RX burst result parameters. Control interface 130 may be used for PHY operations and for burst arrival time. Interface 140 may be used to configure PHY layer 10 .
[0052] FIGS. 2A-2B , taken together, form a table showing attributes of illustrative signals that may be communicated by interface 1 (see FIG. 1 ) from the point of view of PHY layer 10 (i.e., signals designated as input (“I”) are sourced in MAC layer 20 and are inputs with respect to PHY layer 10 .
[0053] A CPU in communication with MAC layer 20 may use interface 1 to accesses PHY layer 10 through MAC layer 20 (see FIG. 1 ). The CPU may do so via a serial interface for configuration, initialization and debug. A configuration port may use the PHY_CLK 134 (see FIG. 1 ) signal as a serial clock. A protocol is typically defined in connection with the serial interface to allow read and write access.
[0054] Management interface 120 is a channel through which MAC layer 20 may configure PHY layer 10 , typically with MoCA™ burst parameters, and receive from PHY layer 10 burst results and status.
[0055] FIG. 3 shows a MAC to PHY Timing Diagram showing timing from MAC layer 20 to PHY layer 10 . MNG_DIR signal 124 may be used to set the direction of data transfer.
[0056] MPD interface 110 may be used to transfer RX/TX data.
[0057] FIG. 4 shows several operation states, such as Reset, Standby and Active in which PHY layer 10 may operate. In Reset, PHY layer 10 and MAC layer 20 typically drive their signals to inactive values. The Reset signal is not part of the MAC-PHY interface apparatus shown and described herein. Standby is the state of the PHY layer 10 when PHY layer 10 is not active in either RX or TX. In Standby, PHY layer 10 reduces power consumption by turning unnecessary functions off. However, the parameters registers are typically left active for read and write. PHY layer 10 enters the Active state upon PHY_STRT 132 (see FIG. 1 ) assertion and remains in that state until the burst process ends. In Active, paths MPD_TX 116 and/or MPD_RX 118 (see interface 110 in FIG. 1 ) may be active. Both MPD_TX 116 and MPD_RX 118 could be active if and when TX follows RX and RX is still not finished when TX starts. In Active, the only active path is on. The other path should be off.
[0058] FIG. 5 shows illustrative parameters, which may include both capability and dynamic parameters, of PHY layer 10 (see FIG. 1 ). The parameters may be based on a vendor specific implementation. PHY layer 10 dynamic parameters are preferably separate from burst parameters and configuration parameters. The burst parameters may be changed in connection with every burst and the configuration parameters may be changed during the operation of interface 1 (see FIG. 1 ) and may affect the operation of PHY layer 10 . Burst parameters may be accessed via management interface 120 and configuration parameters via the configuration interface 140 .
[0059] FIG. 6 shows that data passing between MAC layer 20 and PHY layer 10 over MPD interface 140 may comprise illustrative MAC frame 200 , which may include CRCs 210 and 214 for header 218 and payload 222 , respectively. Forward error correction (“FEC”) padding 230 is typically added by PHY layer 10 . In MoCA™ RX (PHY to MAC), typically, a FEC pad such as 230 is transferred over an MPD interface such as 140 and a MAC layer such as 20 de-pads the FEC pad.
[0060] FIG. 7 shows an illustrative format for passing data over management interface 120 (see FIG. 1 ). The format typically includes a variable parameters list. Different parameters are typically initiated according to TX, RX and the burst type. The data may start with a 32-bit section length and a list of parameters, e.g. as shown in FIG. 7 .
[0061] FIG. 8 shows an illustrative mode of operation for interface 1 (see FIG. 1 ). Before each RX or TX burst, MAC layer 20 typically sends to PHY layer 10 , via MNG_DATA bus 122 , parameters that are to be used by PHY layer 10 for transmitting or receiving. After the RX burst, PHY layer 10 typically sends to MAC layer 20 RX burst parameters that typically include receive burst status, RX learning parameters and, in the probe, the probe result.
[0062] FIG. 9 shows an illustrative burst initialization (“burst init”). PHY_STRT 132 is typically asserted at Burst Delay time before the first symbol of the preamble present at the coax. A first part of the Burst Delay time may be used by MAC layer 20 to send burst init parameters. A second part of the Burst Delay Time may be used for PHY layer 10 delay from the burst init end to the first symbol of the preamble being present at the coax. In the RX burst, PHY layer 10 typically starts acquisition at the end of the Burst Delay. Upon PHY_STRT 132 assertion, PHY layer 10 may start reading burst parameters from MAC layer 20 even while RX results are being sent. Burst init time typically allows 400 bytes of burst parameters to be sent to PHY layer 10 before the burst. The PHY layer 10 start delay may be 5 microseconds (“uS” or “μS”) so as to provide increased pre-burst preparation time.
[0063] FIG. 10 shows that PHY layer 10 may begin sending RX burst results after an RX process delay end time. RX Process Delay time is typically measured from the end of the last symbol on the coax to the maximum delay to process the RX burst. FIG. 11 shows that the maximum time for sending RX result parameters may be 33.8 μS (845 B). FIG. 12 shows that RX burst results may be interrupted by burst init.
[0064] FIGS. 13-16 show illustrative features of an illustrative data interface such as MPD interface 110 (see FIG. 1 ).
[0065] The MPD interface 110 of FIG. 1 typically comprises a data bus such as MPD_DATA bus 112 , a data enable signal such as MPD_DATA EN signal 114 , and TX/RX signals such as MPD_TX signal 116 and MPD_RX signal 118 . Signals 116 and 118 typically define the direction of data bus 112 and typically are not active together. MPD_RX signal 118 typically finishes transferring to MAC layer 20 before MPD_TX 116 is sent. The tail of MPD_RX signal 118 may be transmitted over the MPD_DATA 112 during the preamble of the next TX burst start transmit.
[0066] A medium data gap (“MDG”) is defined herein as the time, as measured at the coax, between the end of an RX last symbol and a first symbol of the TX payload. During the gap, all RX data is typically transferred to MAC layer 20 and enough data is read for transmission after the preamble ends. In some embodiments, the MDG may be 21.52 us in 50 MHz bandwidth, but any suitable MDG may be used. In some embodiments, the MDG may be 14.66 in turbo mode (100 MHz), but any suitable MDG may be used. The MDG typically comprises the minimum inter-frame gap (“IFG”) of 7.8 us (10 us-2.2 us) and minimum preamble time. In some embodiments, at 50 MHz bandwidth, the minimum preamble time (the minimal-size preamble, “P 4 ,” size with the minimum allowed cyclic prefix, “CP,” size of 10 samples) may be 13.72 us, but any suitable minimum preamble time may be used. In some embodiments, in turbo mode the time may be 6.86 us, but any suitable minimum preamble time may be used.
[0067] A medium symbol gap (“MSG”) is defined as the time, as measured at the coax, between the end of an RX last symbol and a first symbol from a device (e.g., a consumer electronics (“CE”) device). During the gap, a FFT machine typically finishes processing the last RX symbol, an IFFT typically finishes the CE symbol processing and the first CE sample is typically present on the medium at the end of the preamble. In some embodiments, at 50 MHz bandwidth, the MSG may be 9.08 us, but any suitable MSG may be used. In some embodiments, in turbo mode (100 MHz), the MSG may be 8.44, but any suitable MSG may be used. The MSG typically comprises the minimum IFG of 7.8 us (10 us-2.2 us) and a short preamble time. In some embodiments, at, 50 MHz bandwidth, the short preamble time may be 1.28 us (L 2 ), but any short preamble time may be used. In some embodiments, in turbo mode the time may be 0.64 us, but any short preamble time may be used.
[0068] IFG (see FIGS. 11 and 12 ) is the gap time on MPD_DATA bus 112 between two bursts of data transferring on the MPD_DATA bus 112 . IFG is typically the MAC time for internal delay. The time is typically 0.5 us (25 cycles of PHY_CLK).
[0069] PHY layer 10 timing is now described. There are typically two time-critical paths between the RX burst to the TX burst in the PHY:
[0070] Path A: FFT to IFFT. The time between the FFT end processing the last symbol of the RX burst to starting IFFT for the first symbol (CE) of the TX burst; and
[0071] Path B: RX data to TX data. The time between the last byte of the RX burst passing over interface 1 (see FIG. 1 ) to the first byte of the TX burst start transmitted over interface 1 .
[0000] For Path A, time from the RX path through the FFT in addition to time from the IFFT to the TX path are typically accumulated. For Path B, all RX and TX path time in addition to the MPD_IFG are typically accumulated.
[0072] FIGS. 13 and 14 show examples of the RX path delay and TX path delay, respectively.
[0073] Referring again to the two data bursts that transfer on MPD_DATA bus 112 , and as shown in FIG. 15 , MPD_TX signal 116 is typically asserted by PHY layer 10 when the first data byte of TX burst TX( 1 ) has been transferred over MPD_DATA bus 112 until the last byte of the burst.
[0074] FIG. 16 shows that MPD_RX signal 118 is typically asserted from the start of the first data symbol (e.g., an Adaptive Constellation Multitone (“ACMT”) symbol) received on the coax medium and until the transmission of the last byte of the RX burst on the MPD_DATA bus 112 . MAC layer 20 typically detects the assertion of MPD_RX signal 118 and latches a Network Timer (“NT”) for an Arrival Time Stamp (“ATS”). The ATS is typically used for comparing with a Transmit Start Time for synchronization of the NT to a Network Controller NT. MPD_RX signal 118 is typically de-asserted when the acquisition is finished and the two CE symbols have arrived within a tolerance defined by a predetermined number of samples. The time between the start preamble presented on the medium to the assertion of MPD_RX signal 118 typically depends on the preamble type and the CP.
[0075] FIGS. 17-20 show features of an illustrative embodiment of configuration interface 140 (see FIG. 1 ). FIG. 17 illustrates a serial read operation in which MAC layer 20 drives the first part of the transaction, which includes a PHY register address. PHY layer 10 drives the second part of the transaction, which includes requested data. Whether MAC layer 20 or PHY layer 10 drives management interface 120 , every bit driven on CNFG_SERIAL_DATA line 142 is always synchronized with PHY_CLK 134 (see FIG. 1 ). MAC layer 20 may drive a “1” as the first bit on CNFG_SERIAL_DATA line 142 . The second bit is a “1”, which indicates a read operation. MAC layer 20 may drive the next 16 bits, which store the PHY register address. After the 16-bit address, MAC layer 20 typically drives a ‘0’ bit to place the CNFG_SERIAL_DATA line 142 in a known state.
[0076] PHY layer 10 may drive from 0 to 32 ‘0’ bits on CNFG_SERIAL_DATA line 142 beginning on the second PHY_CLK 134 after MAC layer 20 stops driving interface 1 (see FIG. 1 ). PHY layer 10 may drive a ‘1’ bit to indicate start of data followed by 32 data bits. The transaction is typically completed by driving a terminating ‘0’ bit to place CNFG_SERIAL_DATA line 142 in a known state before releasing the line to be driven by MAC layer 20 .
[0077] FIG. 18 shows typical timing for the fastest PHY layer 10 response to a read operation. An implementer may use internal or external pull-down resistors to set the CNFG_SERIAL_DATA line 142 to 0 when MAC layer 20 is no longer driving the signal. CNFG_SERIAL_DATA pin 142 typically continues to be controlled by MAC layer 20 .
[0078] FIG. 19 shows an illustrative serial write operation. For a serial write operation, MAC layer 20 typically drives the entire transaction. Each bit that MAC layer 20 drives on the CNFG_SERIAL_DATA line 142 is typically synchronized with PHY_CLK signal 134 . MAC layer 20 typically drives a “1” as the first bit on CNFG_SERIAL_DATA line 142 . The second bit is a “0”, which indicates a write operation. The next 16 bits are typically the PHY layer 10 address location. The next 32 bits are typically the data to be written to the addressed PHY layer 10 register. At the end of 32-bits of data, MAC layer 20 typically drives a terminating “0.” Once the transaction is complete MAC layer 20 typically stops driving management interface 120 . An implementer can use, e.g., internal or external pull-down resistors to set the CNFG_SERIAL_DATA line 142 to 0 when MAC layer 20 is no longer driving the signal. CNFG_SERIAL_DATA line 142 typically continues to be controlled by MAC layer 20 .
[0079] FIG. 20 shows the fastest timing for a read operation followed immediately by a write operation.
[0080] FIG. 21 shows a single or multi-chip module 2102 according to the invention, which can be one or more integrated circuits, in an illustrative data processing system 2100 according to the invention. Data processing system 2100 may include one or more of the following components: I/O circuitry 2104 , peripheral devices 2106 , processor 2108 and memory 2110 . These components may be coupled together by a system bus or other interconnections 2112 and are disposed on a circuit board 2120 in an end-user system 2130 that may be in communication with a coax medium via an interface such as interface 1 (see FIG. 1 ).
[0081] For the sake of clarity, the foregoing description, including specific examples of parameter values provided, is sometimes specific to certain protocols such as those identified with the name MoCA™ and/or Ethernet protocols. However, this is not intended to be limiting and the invention may be suitably generalized to other protocols and/or other packet protocols. The use of terms that may be specific to a particular protocol such as that identified by the name MoCA™ or Ethernet to describe a particular feature or embodiment is not intended to limit the scope of that feature or embodiment to that protocol specifically; instead the terms are used generally and are each intended to include parallel and similar terms defined under other protocols.
[0082] It is appreciated that software components of the present invention including programs and data may, if desired, be implemented in ROM (read only memory) form, including CD-ROMs, EPROMs and EEPROMs, or may be stored in any other suitable computer-readable medium such as but not limited to disks of various kinds, cards of various kinds and RAMs. Components described herein as software may, alternatively, be implemented wholly or partly in hardware, if desired, using conventional techniques.
[0083] Features of the present invention which are described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, features of the invention which are described for brevity in the context of a single embodiment may be provided separately or in any suitable subcombination. | A system for serving an individual node in a shared communication network having a MAC layer and a PHY layer, the system being operative to interface between the MAC layer and the PHY layer. The system may include a first physical channel transferring at least one packet between the layers, a second physical channel transferring at least one burst parameter between the layers, and a third physical channel transferring at least one timing signal, for a burst characterized by the at least one burst parameter and comprising the at least one packet, between the layers. | 7 |
FIELD
[0001] The invention is related to a device and a procedure which enables treatment of presbyopia in human eyes
BACKGROUND
[0002] Cataract surgery of the human eye lens is the most commonly performed operation world-wide, with about 20 million procedures performed a year. Cataract numbers increase more and more with aging society. Because of age as well as other factors such as UV radiation, the human lens becomes increasingly opaque until the patient becomes blind. Well-established cataract surgery, which is mostly done by phacoemulsification of the natural lens within the capsular bag and implantation of a new artificial intraocular lens, can avoid blindness and give patients clear vision again.
[0003] Before the onset of cataract, on-going growth and hardening of the natural human lens over time can reduce the ability of the lens to accommodate or change shape in order to see both distant and near objects. By the age of 40, the accommodation range can become less than 3 D, which strongly influences near vision in emmetropic eyes. This is called presbyopia. Reading glasses are helpful to overcome the effects of presbyopia, but don't address the root cause. Other approaches like multifocal intraocular lenses, multifocal corneal laser ablation profiles in LASIK (laser in situ keratomileusis) procedures, intracorneal inlays, Femtosecond (or other) laser incisions inside the corneal stroma like INTRACOR® or photothermal keratoplasty can regain near vision. These surgical treatment options are based on using multifocality to extend the depth of focus, but at a cost of contrast sensitivity or also requiring a monovision or micro-monovision.
[0004] Accommodating artificial intraocular lenses like AT-45 CrystaLens, Human Optics 1CU and others have been developed as a potential solution to recreate the accommodative response artificially, however, studies have shown that there is negligible forward movement of the lens and so any increase in near vision with these lenses comes from a small depth of field increase due to the asphericity in the lenses. Certainly, accommodative lenses have been unable to give the patient the 3 D of accommodative range that is required.
[0005] Lens capsule refill technologies are under development to bring a gel into the capsular bag after phacoemulsification of the natural lens. However, these lens capsule refill technologies cannot currently adjust the refractive power or the dimensions of this gel IOL accurately enough during the refilling process. There are also serious problems with posterior lens capsule opacification.
[0006] Over the last 10 years, femtosecond (or other) laser surgery of the human cornea has been introduced into clinical practice. Femtosecond (or other) laser technology uses the phenomenon of photodisruption to create microbubbles within the cornea to separate tissue. By scanning the laser spot, 3-dimensional cuts can be performed to create a flap as part of a LASIK procedure (U.S. Pat. No. 5,984,916) or also to cut out a precise intra-stromal lenticule, which can then be extracted through a small incision to correct the manifest refraction with the VisuMax femtosecond (or other) laser system (US 2008/0275433).
[0007] Femtosecond (or other) laser cataract surgery has also been successfully introduced in recent years. In this procedure, a femtosecond (or other) laser is used to open the anterior capsular bag by creating a centred, round, custom-designed anterior capsulotomy. Using a femtosecond (or other) laser has advantages over manual capsulotomy as the cut is more accurate. The femtosecond (or other) laser is then used to break up the cataract lens by making a crossed cut or by chopping the lens into tiny parts which can then be easily removed from the capsular bag (U.S. Pat. No. 7,351,241).
[0008] Femtosecond (or other) laser surgery for the treatment of presbyopia has also been proposed in the past. The main approach was to soften the natural human lens with theory that the lens would regain elasticity and accommodative amplitude. The lens softening can be done by cutting gliding planes or producing microbubbles in order to produce a more elastic sponge-like structure. (See: EP 1212022 B 1). This approach is mainly based on the Helmholtz model of accommodation where the stiffness of the lens material plays the most important role.
SUMMARY
[0009] In an embodiment, the present invention provides a treatment apparatus for surgical correction of presbyopia or defective eyesight in an eye of a patient. The treatment apparatus includes a laser device configured to treat lens tissue of the eye by irradiation of pulsed laser radiation with the laser radiation being focused on target points arranged in a pattern within the lens. An interface supplies measurement data on parameters of the eye and/or defective-eyesight data on the eyesight defect to be corrected in the eye, and defines a volume located within the lens using the supplied measurement data and/or defective-eyesight data, the volume being defined so as to achieve the desired correction of presbyopia or defective eyesight when removed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The present invention will be described in even greater detail below based on the exemplary figures. The invention is not limited to the exemplary embodiments. All features described and/or illustrated herein can be used alone or combined in different combinations in embodiments of the invention. The features and advantages of various embodiments of the present invention will become apparent by reading the following detailed description with reference to the attached drawings which illustrate the following:
[0011] FIG. 1A shows a peripheral laser treatment zone outside an optical zone of the lens;
[0012] FIG. 1B shows an outside lens shape change after shrinking of the lens due to laser treatment of FIG. 1A ;
[0013] FIG. 2A shows a cylindrical laser treatment zone outside an optical zone of the lens;
[0014] FIG. 2B shows an internal gliding cylinder, due to tissue softening, that results in improved central forward movement of lens tissue because of vitreous pressure, which causes improved accommodation in presbyopic lenses due to the treatment of FIG. 2A ;
[0015] FIG. 3A shows a conical laser treatment zone outside of the optical zone of the lens;
[0016] FIG. 3B shows an internal gliding cylinder, due to tissue softening, that results in improved central forward movement of lens tissue because of vitreous pressure, which causes improved accommodation in presbyopic lenses due to the treatment of FIG. 3A
DETAILED DESCRIPTION
[0017] An aspect of the present invention is to provide a method, a device and arrangement to treat presbyopia of the human eye lens using a minimally invasive procedure using femtosecond (or other) laser technologies. Thereby the basis of the proposed treatment may be the Coleman catenary theory of accommodation and presbyopia, as described in:
Coleman, D J, Unified model for accommodative mechanism. Am. J. Ophthalmol, 1970, 69(6): 1063-79; Coleman, D J, On the hydraulic suspension theory of accommodation , Trans Am. Ophthalmol Soc., 1986, 84: 846-68; Coleman D J, Fish S K, Presbyopia, accommodation, and the mature catenary , Ophthalmology, 2001, 108(9): 1544-51.
This theory of accommodation holds that the lens shape change is caused by vitreous support pushing the lens forward into a conoid or catenary-like shape supported by the anterior zonules, rather than capsular force rounding up the natural lens. This theory claims that the loss of accommodation is caused by an increase in the volume of the lens with age, such that the vitreous support of the lens can no longer produce a steep anterior radius of curvature due to the ocular anterior segment dimension restrictions. Reduction of peripheral lens volume would re-establish the catenary potential of a steep central optical curvature and restore the natural accommodative mechanism.
[0021] The aim of the minimally invasive femtosecond (or other) laser treatment is to shrink the peripheral circle of the lens outside the optical zone to reduce the lens volume, so that hydraulic lens movement can take place and contribute in an improved manner to an increased accommodative amplitude of the eye.
[0022] Thereby the lens shrinkage treatment is foreseen to be minimally invasive, so that no cataract will be induced. It has been shown in animal and human studies, that femtosecond (or other) laser induced photodisruption can be applied without inducing cataract changes in the crystalline lens. Therefore a femtosecond (or other) laser can be used to place photodisruption bubbles in the periphery of the lens. This treatment will lead to gas production, but also a reduction of tissue because of the photodisruption process. The treatment can be applied symmetrically as shown in FIG. 1 , but also asymmetric treatment options are possible, that e.g. only a shrinking in the anterior part of the lens will occur. To reduce immediate over-production of gas bubbles and to ensure that this gas will be absorbed by the fluid of the eye and transported away, a special treatment protocol over time and space is proposed in embodiments of the invention.
[0023] This protocol includes several treatment sessions where spots at different spacing, in a navigated manner, will be applied into the circular periphery outside the optical zone of the lens. One example is to treat 3 times over the course of 4 weeks (i.e. 2 and 4 weeks after the first treatment) and use a spot separation of 10 times the spot diameter of minimal 5 nm and maximal 50 nm. Thereby the spot positioning will be shifted from one treatment session to the other with help of registration and recommended OCT navigation in between the earlier applied spot patterns in a well-defined manner as shown in FIG. 2 .
[0024] This step by step treatment procedure ensures that there is enough time between treatments and enough space between spots for the gas produced by the photodisruptive bubbles to be transported away without causing problems in the treatment zone.
[0025] As the laser induced shrinking of the peripheral lens volume will also lead to a change of the static refractive power of the lens, in a further extension of the invention an aberrometer is used to obtain a refractive or wavefront measurement during and/or after the laser treatment. With the help of this accurate measurement of refractive power, changes not only with regard to sphere and cylindrical values as well as higher order aberrations like spherical aberrations and coma will be possible, it also will become possible to tune the refractive power of the lens and the eye within some dioptre and sub-dioptre range to stay at emmetropia or also to become an emmetropic eye, if there is myopia or hyperopia. So this new method is also suited to treat static refractive errors within an eye. As the shrinking will lead to a desired shrinking in the anterior periphery of the lens, the radius of curvature of the anterior surface of the lens will become smaller and the refractive power higher. So one approach is to change the laser treatment zone (see FIG. 1 ) from a symmetrical ring with circular cross section into non circular cross section shapes which will induce a flatter shape of the posterior lens surface due to the shrinking, which can be e.g. a triangle shape with one corner at the outside of the laser treatment ring zone.
[0026] In order to place the laser treatment spots into planned positions within the lens tissue, the device may including a navigation, for example based on optical coherence tomography, confocal laser scanning or Scheimpflug imaging. As a further advantage, this imaging modality can also be used to track the geometrical shape changes of the lens geometry which will correspond to the change in refractive power measured with help of aberrometry.
[0027] A dynamic OCT imaging after laser treatment during the accommodation of the eye will be very helpful to understand the effect of laser shrinking of the lens with regard to increase of accommodative power. Instead of a dynamic OCT imaging also a dynamic high speed ultrasound imaging is also helpful in order to see the peripheral lens regions behind the iris during accommodation of the individual eye, This information can be used to plan the next treatment session to be individualized and optimized with regard to the unique geometries of each patient's eye.
[0028] In a further version of the invention not only photodisruption with nonthermal interaction with lens tissue by help of especially fs-laser pulses is used, but also longer pulse lengths from ps-, ns-, μs- and ms-range are intended, which have more thermal side effects but also a photodisruptive potential to create gas bubbles. These thermal side effects lead to thermally induced tissue shrinking in combination with the photodisruptive tissue elimination.
[0029] A further version of the invention is the use of cw (continuous wave)-laserradiation which only heats up the lens tissue without a generation of bubbles. So the heating will lead to a coagulation of the lens tissue with the effect of tissue shrinking. The application time will be in the ms-s-time range in this treatment version.
[0030] As it is known that thermally induced cataract can occur, the treatment parameter with all longer pulse as well as cw-laser treatment methods which use thermal coagulation to shrink the lens tissue have to be carefully adjusted.
[0031] So the wavelengths of the lasers used will be within the transmission range of the anterior chamber of the human eye (near UV, visible and near infrared region: 350-1300 nm). The laser powers which will be applied will be less than 1 W.
[0032] In an embodiment, the invention relates to a planning tool to calculate the laser treatment for the methods described above. This planning tool generates control data for such procedures based on input of measurement data of the eye and/or of the refractive error to be corrected, and defines a volume located within the lens which would achieve the desired refractive correction if removed.
[0033] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. It will be understood that changes and modifications may be made by those of ordinary skill within the scope of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.
[0034] The terms used in the claims should be construed to have the broadest reasonable interpretation consistent with the foregoing description. For example, the use of the article “a” or “the” in introducing an element should not be interpreted as being exclusive of a plurality of elements. Likewise, the recitation of “or” should be interpreted as being inclusive, such that the recitation of “A or B” is not exclusive of “A and B,” unless it is clear from the context or the foregoing description that only one of A and B is intended. Further, the recitation of “at least one of A, B and C” should be interpreted as one or more of a group of elements consisting of A, B and C, and should not be interpreted as requiring at least one of each of the listed elements A, B and C, regardless of whether A, B and C are related as categories or otherwise. Moreover, the recitation of “A, B and/or C” or “at least one of A, B or C” should be interpreted as including any singular entity from the listed elements, e.g., A, any subset from the listed elements, e.g., A and B, or the entire list of elements A, B and C. | A treatment apparatus for surgical correction of presbyopia or defective eyesight in an eye of a patient. The treatment apparatus includes a laser device configured to treat lens tissue of the eye by irradiation of pulsed laser radiation with the laser radiation being focused on target points arranged in a pattern within the lens. An interface supplies measurement data on parameters of the eye and/or defective-eyesight data on the eyesight defect to be corrected in the eye, and defines a volume located within the lens using the supplied measurement data and defective-eyesight data, the volume being defined so as to achieve the desired correction of presbyopia or defective eyesight when removed. | 0 |
BACKGROUND OF THE INVENTION
Recently considerable work has been directed to the operation of an induction machine as a self-excited generator. U.S. Pat. No. 3,829,758, entitled "AC-DC Generating System", which issued to the assignee of this application on August 13, 1974, teaches the use of an inverter-type circuit for exciting the generator. Since that time it has been found that the generator field can be modulated to provide a constant frequency a-c system. Such an arrangement is described and claimed in the application entitled "Modulated Induction Generator", filed Apr. 16, 1975, having Ser. No. 568,746, now U.S. Pat. No. 3,958,174 and is assigned to the assignee of this application. A subsequent step in the evolution of this technology was the provision of a controlled switching arrangement for both shorting the generator terminals to provide excitation for the induction generator field and periodically reversing the polarity of the voltage supplied to the load terminals, to provide a square wave alternating voltage from the same inverter-type circuit which excites the generator. This step is described and claimed in the application entitled "Variable Speed, Constant Frequency Induction Generator System", filed Nov. 28, 1975, Ser. No. 636,331, which issued as U.S. Pat. No. 3,982,170 on Sept. 21, 1976, and is assigned to the assignee of this application. This last-filed application pointed out that a generator having an unusual winding configuration, such as a plurality of closely-wound windings for each phase circuit, would be required to provide a constant-frequency, or controlled-frequency, quasi-square wave a-c voltage to energize a multi-phase load.
It is therefore a principal object of this invention to provide a switching system for both intermittently shorting the generator terminals to excite an induction generator and also to provide a constant (or controlled) frequency, quasi-square wave, three-phase a-c output voltage to a load, using only a conventional three-phase induction generator operating over a wide speed range.
A related and important object of this invention is to provide such a switching arrangement which is capable of full regeneration, and requires no large energy storage devices.
A corollary consideration of this invention is to provide such a power conversion system in which the frequency of the output voltage is independent of the generator frequency, and in fact may be either higher or lower than the frequency of the induction generator.
Another important object of the invention is to provide a nine-switch converter useful in direct ac-to-ac power conversion systems.
Still another important object of the invention is the provision of a power conversion system which receives a general quasi-square wave voltage at a given frequency, and converts it to another quasi-wave voltage at a different frequency.
SUMMARY OF THE INVENTION
A power conversion system constructed according to this invention has a converter, comprising nine power switches connected in a matrix such that the power switches can be closed in different combinations to supply different output potentials. Also included in a control means, coupled to the converter, for regulating turn-on and turn-off of the nine power switches to determine the output potentials.
In one embodiment the system of the invention includes three system input connections suitable for coupling to the output terminals of a three-phase induction generator, and also has three system output connections for providing three-phase quasi-square wave a-c energy to supply any suitable a-c load. The control means includes a combinational logic circuit with nine gates. Each gate has an output connection for applying a turn-on signal to one of the nine converter power switches, and each gate has two input connections. Also included is a first counter circuit, having three output connections, each of which is coupled to three different gate input connections in the combinational logic circuit. Likewise there is a second counter circuit, having three output connections, each of which is coupled to three different gate input connections in the combinational logic circuit. Some means, such as one or more oscillators, is coupled to both the first and second counter circuits, for supplying timing pulses to both counter circuits to regulate operation of the power switches and thus correspondingly regulate the frequency of the input QSW voltage (which controls the amplitude of the output voltage), and also regulate the frequency of the quasi-square wave, three-phase a-c output voltage.
THE DRAWINGS
In the several figures of the drawings, like reference numerals identify like components, and in those drawings:
FIG. 1 is a schematic diagram depicting a prior art variable speed, constant frequency generating system;
FIG. 1A is a graphical illustration of a QSW line-to-line voltage;
FIGS. 2, 3 and 4 are simplified schematic showings, and FIGS. 5 and 6 are vector diagrams, useful in understanding the present invention;
FIG. 7 is a block diagram of major components of the present invention;
FIG. 8 is a schematic diagram depicting certain components shown in FIG. 7 in greater detail; and
FIG. 9 is a system block diagram depicting an actual system connected and tested to prove the principles of the present invention.
GENERAL BACKGROUND DESCRIPTION
One system for providing a constant frequency a-c output voltage from a generator 10 driven over a shaft 11 at some variable frequency ω is shown in FIG. 1, providing three-phase energy at its output connections 30, 31, and 32. Such arrangements are generally termed VSCF (variable speed, constant frequency) systems. As there shown, an inverter-type circuit 12 comprising switches A-F is coupled to d-c bus conductors 13, 14. This inverter-type circuit not only supplies the field excitation for the generator 10 but also feeds d-c power to the bus conductors 13, 14, as taught in U.S. Pat. No. 3,829,758. A second inverter circuit 15, with switches G-L, is energized from the d-c power on bus conductors 13, 14, providing a controlled-frequency, three-phase output voltage on the output conductors 16, 17, and 18.
The first inverter 12 has the switches A-F controlled by a logic circuit 20, in turn regulated by a voltage-controlled oscillator (VCO) 21 which supplies timing pulses at a frequency determined by an input error signal supplied by a comparator 22. The comparator receives both a reference signal from a reference unit 23, which can be any suitable unit such as a potentiometer, and a feedback signal from a rectifier circuit 24 coupled to the output connections of the induction generator 10. Of course the feedback signal could also be derived from the bus conductors 13, 14, to obviate the need for a rectifier circuit. This arrangement, including components 20-23, forces the inverter 12 switching frequency to follow the induction machine speed very closely, as described in the above-identified patent. The power switches G-L in the second inverter circuit 15 are governed by a separate logic circuit 25, driven from a second oscillator 26. Knob 27 represents a means for adjusting the frequency of the timing signals supplied by oscillator 26 to the logic circuit 25. Thus the frequency of the output voltage on conductors 16-18 is independent of the speed of rotation of the generator 10 and of the switching frequency of the first inverter-type circuit 12.
After considerable analysis of the system shown in FIG. 1 it was discovered that it is possible to provide a matrix of power switches to effect an ac-to-ac transformation without the intermediate step of providing the d-c voltage on the bus 13, 14. Two conditions must be met to effect the transformation in the same manner as the two-inverter system of FIG. 1: (1) the input terminals must be selectively connected to the appropriate ones of the output terminals to provide the desired output potentials; and (2) the correct input terminals must be connected to each other, and the proper output terminals must be connected to each other, in the proper sequence. The basic generator excitation depends upon the periodic shorting of the generator terminals, as described in the above-identified application having Serial No. 636,331. These conditions can be met, making all the proper connections between all the terminals 16-18 and 30-32, using only nine power switches (such as P1-P9 in FIG. 2) instead of the 12 switches shown in FIG. 1. In general the term "converter", as used herein and in the appended claims, refers to a plurality of power switches connected in a matrix such that, with given potentials appearing on the input connections 30, 31 and 32, closure of the power switches in different combinations in effect applies different potentials, depending on the switches closed in a given combination, on the output conductors 16-18.
To avoid confusion as to what is meant by a quasi-square wave voltage waveform, FIG. 1A depicts a QSW line-to-line voltage. This could, by way of example, be the voltage viewed between output conductors 16 and 17 in FIG. 1. It is apparent that the line-to-line potential is positive for a 120° time interval, zero (terminals shorted) for the next 60° interval, negative for the next 120° interval, shorted for the next 60° , and so forth. It will become apparent from the subsequent explanation of the invention that the power converter must not only translate the appropriate potentials between the input connections and output connections of the complete system, but must also provide the short circuits between the proper terminals at the appropriate times to produce the QSW output voltage.
Another way of viewing a VSCF system is to consider the single phase arrangement shown in FIG. 3. Again the inverter-type circuit 12 is used to excite an induction generator by periodically closing the power switches A-F to produce quasi-square wave a-c energy at the generator output conductors 30-32, and a d-c voltage is produced on the bus conductors 13, 14. Considering a certain time when the switches A, D and F are closed and a potential represented by the polarity signs 33 is being provided, if A, D and F are suddenly opened and at the same time switches B, C, and E are closed, the inverter has been "turned up-side down" or "inverted" in an electrical sense. That is, the polarity of the voltage on the bus conductors is reversed, and is now represented by the polarity symbols 34. Thus by controlling the rate at which the inverter is itself "inverted", the frequency of the output voltage on the bus conductors can be controlled in the manner taught in the application having Ser. No. 636,331, filed Nov. 28, 1975.
In the system of FIG. 3 it is evident that the output is a square wave voltage, because the bus conductors cannot be shorted to produce a QSW voltage without shorting the generator terminals as well. It is desirable to utilize a QSW voltage waveform because of the harmonic content, as contrasted to other possible waveforms, and because the system is capable of handling a certain amount of reactive energy as a result of the circulation paths provided. Ordinary inverter switches, such as a thyristor in parallel with a diode, are not suitable for use as the switches A-F. Instead a switch which blocks current in both directions when open, and which passes current in both directions when turned on, is required. Such a switch, termed a "power switch" in this specification and in the appended claims, could be a pair of inverse-connected power transistors. If a thyristor is used as a power switch, then a commutation circuit must be provided, as is well known and understood in the art.
GENERAL DESCRIPTION OF THE INVENTION
FIG. 4 shows that by adding another output terminal and three additional switches P, Q, and R to the system of FIG. 3, a three-phase output voltage can be supplied on lines 16, 17 and 18. The additional switches allow the shorting of any two output terminals, to obtain a quasi-square wave output voltage, since the input terminls which are not to be shorted need not now be directly connected to the shorted output terminals.
In an ordinary inverter-drive system, the output terminals are periodically connected to either the positive or negative d-c bus. Gating signals from a logic circuit, such as a ring counter, determine which bus conductor should be connected to which terminal, and further determine which terminals should be shorted to sustain the generator field. For an explanation of the present system, it is helpful to assume that the power conversion system of this invention has an imaginary d-c bus, and two separate logic or ring counter circuits. The first logic circuit would normally connect the generator output terminals (or converter input terminals) to the imaginary bus, in a matter analogous to the connection of the output terminals 30-32 of generator 10 in FIG. 1 to the real bus 13, 14, and in so doing would provide the terminal to-terminal shorts to sustain the generator field. The second ring counter can be used to govern the connections of the system output terminals, such as conductors 16-18 in FIG. 1, to the imaginary bus. It will become apparent that an important component of the present invention is a combinational logic circuit which compares (1) the desired connections of the system input connections to the imaginary bus to (2) the desired connections between the system output terminals and the imaginary bus, closing only those a-c power switches between the terminals whose "bus" connections coincide.
FIGS. 5 and 6 show the generator output terminals 30, 31 and 32 and the load terminals 16, 17 and 18 of FIG. 4, without the converter power switches. FIG. 5 indicates the polarities at some instant in time when the potential on terminal 30 is positive with respect to the potentials at both terminals 31 and 32, which are then shorted together. Similarly the potential at output terminal 17 is positive with respect to the potentials then present at both terminals 16 and 18. To provide these output voltage polarities, the system power switches would connect terminal 30 to terminal 17 (A in FIG. 4 is closed), terminal 31 to terminals 16 and 18 (Q and D closed), and terminal 32 to terminals 16 and 18 (R and F closed), thus providing not only the appropriate input to output connections, but also the required short circuits (16 to 18 and 31 to 32). During the next polarity change of the generator, terminals 30 and 32 are positive with respect to terminal 31 as shown in FIG. 6, and it is assumed that the output voltage polarities on terminals 16-18 remain as they were in FIG. 5. FIG. 6 illustrates the new switch connections which would be required at this time. From the foregoing it is apparent that this is realized by closing the switches A, Q, D and E in FIG. 4. Those skilled in the art will not readily understand the switching sequence which must be implemented to effect the direct ac-to-ac power conversion without any solid d-c bus conductors such as used in the circuit of FIG. 1.
DETAILED DESCRIPTION OF THE INVENTION
The block diagram of FIG. 7 depicts salient components of the power conversion system of this invention. As there shown, a converter 40 provides the requisite switching between an induction generator 10 and the load to be supplied by a three-phase, quasi-square wave output voltage. Converter 40 may comprise nine switches such as those designated generally P1-P9 in FIG. 2. The combinational logic circuit 41 shown in FIG. 7 provides output signals over line 42 to regulate the converter operation to provide the requisite energy to the load when the induction generator is operating. Combinational logic circuit 41 provides the signals which close the switches P1-P9 to effect the desired circuit connections as described above in connection with FIGS. 5 and 6. To this end the combinational logic circuit receives a first series of control signals from a first counter 43, which in effect regulates the generator frequency by those signals passed over line 44 to the combinational logic circuit. Signals from the second counter 45 are passed over line 46 to the combinational logic circuit, and these signals in effect determine the frequency of the output voltage passed by the converter over the output conductors such as 16, 17 and 18 in FIG. 1 to any suitable a-c load.
The control signals provided by first counter 43 are in turn determined by timing signals issued by a first oscillator circuit 47, and the frequency of these timing signals is determined by some adjusting means, represented by adjustable knob 48. The output or timing signals from oscillator 47 are provided on line 50. The second oscillator 51 also includes some means designated 52 for adjusting the frequency of the timing signals provided on its output line 53. Those skilled in the art will appreciate that the output signals on lines 50, 53 could be applied directly to the counters 43, 45 or the timing signals could be provided by a single oscillator and passed over different circuits, one of which may include division and/or multiplication stages to supply the requisite timing signals. However in the preferred embodiment the separate oscillators were provided as shown, and a delay circuit 54 was coupled between the first oscillator and the first counter. In addition a latch circuit 55 was provided and connected as shown. That is, the delayed output signals from circuit 54 were provided over a first line 56 to a first counter 43. The signals on line 57, delayed longer than those on line 56, are then applied to the other input connection of latch circuit 55. The output signal from the latch circuit is passed over line 58 to the second counter 45. Those skilled in the art will recognize that the use of the longer delay and the latch circuit is one approach to preventing switching failure in the power switches which might otherwise be caused by the virtually simultaneous arrival of timing pulses on the lines 44 and 46. This will be better understood in connection with the more detailed showing in FIG. 8. For the present it is important to note that the converter, combinational logic circuit, and the first and second counter circuits are important components of the invention. The additional blocks representing the first and second oscillators, together with the delay and latch circuits, can together be considered as means for supplying timing pulses to both the counter circuits 43 and 45, thus to regulate the generator speed (hence output voltage amplitude) and the actual frequency of the quasi-square wave a-c output voltage.
The nine-switch converter is important in itself, as it can provide ac-to-ac power conversion at controlled frequency and regulated amplitude. Broadly then the other components (41, 43, 45, 47, 51, 54 and 55) can be collectively considered as a control means for regulating the turn-on and turn-off of the nine power switches in the converter.
FIG. 8 illustrates the details of the counter and combinational logic circuits. As there shown, timing signals provided by the first oscillator are received over line 50 and applied to both stages 60 and 61 within delay circuit 54. It is assumed that the power switches in converter 40 have a turn-off time T. Hence stage 60 provides a delay of twice that turn-off time, or 2T, and delay stage 61 provides a substantially longer delay, 4T. These delays insure that a power switch has sufficient time to turn off and completely recover before it is turned on again.
The output signal from stage 60 in delay circuit 54 is passed over line 56 to the input of first counter 43. This counter is a conventional logic or ring counter circuit, including three flip-flop stages 62, 63 and 64 connected to provide output signals on the conductors 65, 66 and 67 as a function of the basic timing signals received over line 50 from the first oscillator. In addition counter 43 includes NAND stages 68, 70 connected to provide proper starting of the first counter 43.
The longer-delayed signals from stage 61 within delay circuit 54 are passed over conductor 57 to the input side of latch circuit 55, which includes the conventionally connected logic stages 71, 72, 73 and 74. The other input signal for latch 55 is provided from the second oscillator over line 53, and a divide-by-two circuit 75 is interposed between the second oscillator and the latch circuit 55. This was done for convenience to provide the appropriate frequency of the signals to the latch circuit. A reset signal can be applied over line 76 to the divide-by-two circuit 75 when the system is started. The output signal from latch circuit 55 is passed over conductor 58 to the input side of second counter 45. As shown this is another conventional ring counter circuit, with a pair of NAND stages 77, 78 to provide for proper starting and three flip-flops 80, 81 and 82 connected to provide the sequential output signals on lines 83, 84 and 85 as a function of the timing signals received over line 58.
The signals from the first and second counters are applied to the input connections of the exclusive OR gates 91-99 in the combinational logic stage 41 as shown in FIG. 8. This provides the appropriate combination of turn-on signals on the output conductors 101-109 for application to the nine power switches (connected as shown in FIG. 2) within converter 40. Those skilled in the art will understand that the power switches can, by way of example, be comprised of nine inverse-parallel pairs of power transistors, which would not require any commutation or turn-off signal. If other units such as a triac or inverse-parallel thyristors are employed, then of course suitable commutation circuits must be supplied for turn-off in a manner well known and understood by those skilled in the art.
FIG. 9 is a block arrangement showing an actual system which was built and successfully operated to prove the principles on which the invention is based. A nine-switch converter 40 was utilized, with nine switches such as those designated P1-P9 shown in FIG. 2 connected between the system input and output connections. Induction generator 10 was a two horsepower unit and in one test arrangement, the load 110 was a two horse power induction motor. The delay and latch circuits are omitted from the showing of FIG. 9 for simplicity. In the test arrangement a bridge rectifier 111 was connected as shown to provide a signal on line 112 related to the amplitude of the three-phase output voltage provided to the load. Instead of the first oscillator 47 being a simple unit with a self-contained adjustment, the first oscillator was a voltage controlled oscillator (VCO) as shown, and received its controlling voltage input signal over line 113 from a comparator 114. The other input signal to the comparator was a reference signal provided over line 115. The comparator algebraically summed the rectified signal on line 112 with the reference voltage signal on line 115 provided by a reference unit 116, such as a potentiometer. Such arrangements are well known and understood for providing an output signal on line 113 which governs the operation of VCO 47. With this arrangement the two horsepower motor 110 was successfully and easily run over a frequency range from 30 hertz to 120 hertz. It was found that if the frequency of the output voltage supplied to the motor was very close to the input frequency supplied by the induction generator, or to a subharmonic of the input frequency, there was a noticeable torque pulsation of the induction motor 110 at the beat (difference) frequency. When the inertia of motor 110 was small, this pulsation was sufficiently severe to cause speed variations in excess of the normal slip range. The effect was most severe and objectionable when the output frequency was close to the input frequency, but was not noticed at higher speed ratios.
It is understood that some excitation must be supplied for the induction generator during system start-up. As taught in the above-identified patent, this can be done with a simple low-voltage battery connected to supply a small d-c potential during the initial energization of the induction generator. Alternatively the remanent magnetization of the rotor can be used, or some other supply used to "dump" a small amount of energy into the system at the time of starting.
TECHNICAL ADVANTAGES
A three-phase, quasi-square wave generating system has been explained. The frequency of the output voltage on conductors 16-18 can be regulated independently of the generator frequency, simply by regulating the frequency of the timing pulses supplied by the second oscillator. The system is capable of supplying a resistive load up to the rating of the induction generator, and can supply inductive loads of considerably greater magnitude. The simple switching system of the converter can use nine power switches, or force-commutated switches in a manner well known and understood by those skilled in this art.
It is important to note that the nine-switch converter 40 has significant utility in addition to its use with induction generator systems. For example, it can be used with any ac-to-ac conversion system, in lieu of known two-inverter systems (FIG. 1) or Cycloconverters and other similar arrangements. It is also important to note that the control means which regulates the converter is not limited to produce only a quasi-square wave output voltage. Instead pulse-width modulation techniques, which are well known and understood in this art, can be employed to control the waveform of the system output voltage.
In the appended claims the term "connected" means a d-c connection between two components with virtually zero d-c resistance between those components. The term "coupled" indicates there is a functional relationship between two components, with the possible interposition of other elements between the two components described as coupled or "intercoupled."
While only a particular embodiment of the invention has been described and claimed herein, it is apparent that various modifications and alterations may be made therein. It is therefore the intention in the appended claims to cover all such modifications and alterations as may fall within the true spirit and scope of the invention. | A plural switch matrix is connected as a direct ac-to-dc converter between an induction generator and an a-c load. The generator provides three-phase output energy which is switched and controlled by the converter, to supply a controlled three-phase quasi-square wave (QSW) voltage to a load. The converter switching provides periodic shorts across the generator terminals, translating some of the mechanical input energy into electrical energy to sustain the generator field. The converter is regulated by gating signals from a combinational logic circuit. | 7 |
FIELD OF THE INVENTION
The invention concerns a process and means for monitoring the position of changes in the position of the interface between two fluids of different densities.
More specifically, the invention relates to a process for installing the probe used to monitor the interface formed when excavating a salt cavity by means of leaching, with said cavity being at least partially filled with one or more of the abovementioned fluids.
BACKGROUND OF THE INVENTION
For such applications, it is essential to know the position or variation in position of the interface between the two fluids in order to be able to determine the depth the excavation has reached (the excavation generally proceeds from the bottom toward the surface) and so monitor the development of the cavity.
It will be noted that the fluids present in the cavity are often fuel oil (in the top portion) and brine (in the lower portion), with the brine formed from water injected under appropriate pressure.
Similar monitoring processes already exist in which the fluids in question move through one and/or another of two pipes leading to and/or from the cavity. The two pipes generally extend concentrically into the cavity, one inside the other.
The probe, in such known means, is usually connected to a stationary exterior point by a cable link from which it is suspended. Said probe generally comprises at least one signal-emitting source and at least one detector-receiver.
With such means, readings of the position of the interface are usually done by logging, which involves:
The use of a complete on-site logging unit (mobile laboratory and specialized team) for each movement in the position of the fluids if the probe is to be accurately positioned at the spot in which the measurements are to be made;
The permanent presence of probe and cable inside the center pipe.
In practice, such an arrangement of the probe within the central pipe may prove fatal. This is so particularly when one seeks to monitor a salt cavity formed by a technique known as reverse leaching, which is in itself known.
In such applications, saturated brine to be removed moves through the inner pipe. The presence of measuring instruments inside the pipe impedes proper flow. The resulting losses of head are too high. In addition, probe and cable tend to wear out prematurely because of the salt in the brine.
SUMMARY OF THE INVENTION
The invention resolves these problems by proposing to place the measuring probe and its cable in the intermediary space between the inner and outer pipes.
This provides a radical solution to the problems of head loss and corrosion.
It is worth noting in this regard that the substance that moves through the annular space separating the two pipes is generally the water being used to excavate the cavity.
In practice, the invention provides that the probe should be installed in said intermediary space in the following way:
the probe is essentially fastened against a portion of the outer wall of the inner pipe, following which
the section of the inner pipe carrying the probe is positioned near the spot at which one seeks to take measurements.
Probe and cable therefore form part of the stationary equipment. They can be positioned at the desired location for an indeterminate length of time. Furthermore, the services of a specialized team to maneuver the probe are no longer required.
The invention also concerns means for implementing the process that has just been presented.
In the particular application of the means to the excavation of cavities, notably salt cavities, the process of monitoring the progress of the work obviously requires that each borehole be equipped with the monitoring means of the invention.
The invention and more of its purposes, details, and advantages will appear more clearly and be better understood in light of the following explicative description, which is provided solely by way of example and with reference to the attached nonlimitative drawings.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a partially schematic cross-section of an underground cavity in the process of being excavated, showing the location of the monitoring means of the invention.
FIG. 2 is an axial schematic view, cut away to show the constituent parts of the monitoring means of the invention.
FIG. 3 is a cross-section along line III--III of FIG. 2, showing the position of the detector.
FIG. 4 is a cross-section along line IV--IV of FIG. 2, illustrating the position of the emitting source.
FIGS. 5A, 5B, and 5C illustrate the different relative positions that may be assumed by the monitoring probe and the interface.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows a salt cavity 8 for the surveillance of which the control means of the instant invention are particularly suited and necessary if one is to know the location or movement of the interface 6 between the nonmiscible fluids 30, 50 of different densities present in the cavity.
It should be noted at the outset that knowing the position of interface 6 enables the operators to monitor the excavation of cavity 8.
The leaching process used to form cavity 8 will not be described since it is not one of the objects of the invention and is furthermore in itself known.
It will be noted simply that FIG. 1 offers a schematic representation of two pipes--an inner pipe 3, and an outer pipe 4--which enter cavity 8 through access shaft 5. According to he excavation process adopted, pipe 3 contains freely circulating, unobstructed brine 30 in the process of being raised to the surface and evacuated at 13. The brine was drawn off from the cavity at a given depth. Outer pipe 4 handles water 40, moving it into cavity 8 from supply point 14. Said water is used for excavating the cavity and, after mixing with the salt elements of underground formation 7, forms brine 30.
As FIG. 1 clearly shows, the upper portion of the outer wall of pipe 4, i.e, that portion located substantially at the level of shaft 5, is bathed in a liquid 50 having a density lower than that of brine 30 and not miscible with it. Fluid 50 may be fuel oil, which is fed into and withdrawn from shaft 5 at 15.
In order to facilitate understanding of the manner in which the various fluids circulate through the pipes, their direction of flow is indicated by arrows in FIG. 1.
On one section of the outer wall of pipe 3 and in the proximity of interface 6 are fastened a source 10 and a detector 9. The detector is linked by cable 16 to a receiving/analyzing unit 17 on the surface.
Source 10 and detector 9 are the basic elements of the means 1 of the invention. Said means, which are particularly well suited for monitoring the movement or position of the interface 6 between two fluids 30, 50, are shown in detail in FIG. 2. They are composed primarily of a measuring probe, labeled 2, consisting essentially of emitting source 10 and detector-receiver 9. Detector 9 and source 10 are separated from each other by a set distance d. Advantageously, source 10 and detector-receiver 9 are offset vertically and aligned in a direction that is substantially parallel to the axes of pipes 3 and 4. Said axes 23, 24 are substantially parallel.
Between pipes 3 and 4 lies an annular space 19 that is wide enough to accommodate detector 9, source 10, and their fasteners. In the application selected, said fasteners are means that hold the probe in a fixed position, at least with respect to inner pipe 3. The probe is therefore fastened to outer wall 3a of said inner pipe.
In addition, probe assembly 2, composed of source, detector, and cable link 16, is separated from inner surface 4a of outer pipe 4 by spacers, labeled 12a and 12b, in the form of protective rails running substantially radially, as illustrated in FIGS. 2 through 4, over the entire length occupied by monitoring means 1. More specifically, spacers 12a form a first set of spacers consisting of two substantially rectilinear metal rails 121, 122 welded to a portion of outer wall 3a of inner pipe 3 and protruding into the annular space 19 between the pipes and into close proximity with the inner surface 4a of pipe 4. More or less diametrically opposed to the first set of spacers is a second set 12b consisting of one rail 123 welded to outer wall surface 3a and likewise extending into the proximity of inner wall surface 4a of pipe 4.
It will be noted that a small clearance has been left between the edge of the various spacers and the inner surface 4a of the outer pipe so as to allow for possible expansion of said spacers under stress.
Spacers 12a, of substantially equal width 1, are wider than the opposing spacer 12b, which has width 1'. The result is to offset the center of inner pipe 3 with respect to outer pipe 4. The axes 23 and 24 of pipes 3 and 4 respsectively are therefore separated by a distance d'. In other words, annular space 19 is made wider on the side accommodating the instruments 9, 10 that make up probe 2, whereas the space on the opposing side is reduced commensurately.
As FIGS. 3 and 4 clearly show, the detector 9, with its cable link 16, and source 10 are placed between rails 121 and 122.
Referring now to FIGS. 2 and 3, it can be seen that the detector, rendered schematically and labeled with numeral 9, is essentially held against outer surface 3a of inner pipe 3 by metal bands or hoops 18. The hoops encircle pipe 3 and detector 9, passing through openings 31, 31' in the various rails 121, 122, 123.
Advantageously, edge 32 of each opening 31 is bevelled so as to facilitate the passage of the band.
It wll be noted that in FIG. 2 only two hoops have been shown passing through the corresponding openings at two different levels along detector 9. However, the number of hoops may be adapted to the fastening strength required.
In order to prevent cable link 16 from becoming stuck between pipes 3 and 4, it may be useful to provide other fastening bands (not shown) at several points along the path of the cable from detector 9 to the receiving/analyzing unit 17 at the surface.
As shown in FIGS. 2 and 4, the rigidity and adherence of the rails, particularly rails 121 and 122, are enhanced through the use of reinforcers 33 welded to the rails and to the outer wall surface 3a of pipe 3. Said reinforcers are set at several points along the rails. They may be provided at the upper and lower ends of the rails and at the level of the probe and/or detector.
In the application shown, source 10 is a radioactive source. In itself known, it consists substantially of a radioactive pellet 22 emitting directed radiation, set within a holder 29. Said holder may be screwed into a case 25, with appropriate seals 35 to keep it leaktight. Case 25 is equipped with a radiation slot or window 28 and is itself screwed into a mounting bracket 26 that has been made integral with the outer surface 3a of pipe 3, e.g., by weld beads 36, 36'. Appropriate seals 35 and 27 ensure that the assembly thus constituted will be free of leaks (FIG. 4).
Window 28 is used first for the installation of pellet 22 and its holder 29, and second for focusing the radioactivity of the source onto fluids 30 and/or 50, which surround the outer surface 4b of pipe 4. We shall return to this characteristic in the source of explaining how the newly invented probe works. In any event, in order to prevent any unwanted direct radiation from source 10 from reaching detector 9 (i.e., radiation that has not been reflected by at least one of fluids 30, 50), a screen 34 has been placed between these two components. Screen 34 may consist of a sufficiently thick mass of metal, formed, for example, from a series of weld beads. Said mass extends transversely between rails 121 and 122, covering substantially their entire width 1.
In the example presented in FIGS. 2 through 4, it will be noted that the dimensions of source 10 are slightly larger in cross-section than those of detector 9. It will be understood that in this case, the radial extension of rails 121 and 122, between which source and detector are positioned, should be adapted to the respective dimensions of the latter. In particular, the two rails might spread out slightly below screen 34, i.e., between the screen and the lower end of the rails.
The structure of detector 9 will not be described, since it does not constitute one of the objects of the invention. It will simply be noted that the detector comprises a sensor or receiver (labeled with numeral 38 in FIG. 2) that picks up the signals emitted by the radioactive source, and a processing circuit, labeled 35, that sends the data received to receiving/analyzing unit 17 through cable link 16.
In one particular application, provided by way of nonlimitative example, monitoring means 1 as described above might have the dimensions set forth below.
It should first be noted, however, that pipes 3 and 4 are each formed from a series of pipes placed end to end and joined by any appropriate means, a fact that is in itself known.
It should also be noted that in order to facilitate the accommodation and installation of the instruments making up the means of the invention, inner pipe 3, particularly the section onto which the instruments are fastened (notably the source and detector), has a diameter D that is slightly less than the diameter D' of the adjacent sections of inner pipe 3 to which it is joined at its two ends 36 and 37.
Diameter D may be approximately 100 mm, and D' approximately 120 mm.
On the other hand, in this application the outer pipes all have the same diameter, which may be approximately 200 mm. The thickness of pipes 3 and 4 is approximately 10 mm.
It should also be noted that the offset d' between the centers of pipes 3 and 4 is advantageously on the order of 20 mm. The width 1 of the rails or spacers making up set 12a would therefore be approximately 50 mm overall, whereas the width of the opposing, complementary spares 12b would be approximately 20 mm overall. The length of pipe over which the rails extend is substantially 200 to 250 cm, and preferentially about 230 cm.
The operation and (briefly) the installation of the above newly invented monitoring means will now be described.
First to be discussed will be the installation of the means of the invention in the context of the particular application covered here, namely the process of monitoring an interface 6 between two liquids 30 and 50 in the course of forming a salt cavity by leaching, and particularly by reverse leaching.
First, at the beginning of the leaching operation, outer pipe 4 is put into place through shaft 5, by setting pipe sections of the same diameter end on end and sinking them in the direction of cavity 8.
Next, after having prepared the special inner pipe 3 that is to support the monitoring means, i.e., after having placed detector 9 and source 10 between rails 121 and 122, and fastening all of the latter by means of bands and welds respectively, a series of inner pipes 3 is sunk into pipe 4.
More specifically, a sequence of pipes 3 of diameter D' is set end to end. At a specific, predetermined point in this chain, special inner pipe 3, with diameter D, is inserted. It will be understood that special inner pipe 3 is inserted in such a way that, once in place underground, measuring probe 2 is positioned at the level of one and/or the other of fluids 30, 50 and near the point at which one seeks to monitor the position of interface 6.
Of course, cable link 16 has been sunk as well.
Understandably, the measuring probe is advantageously deployed at a predetermined and fixed depth throughout the excavation. Care should preferentially be taken to see that no two adjacent outer pipes 4 will be joined in the space between source and detector, since the joint might interfere with the propagation of the radiation or signals emitted by the source.
Once in place, monitoring probe 2 can be connected to station 17, the receiving and analyzing unit.
The monitoring means are now operational.
Readings are taken of the signals received by detector 9 after being emitted by source 10 and at least partially reflected by said fluids 30, 50. The position or position of interface 6 is computed from the signals received, which vary as a function of the relative position of interface 6 and measuring probe 2.
More specifically, care must be taken to maintain a vertical separation d between source 10 and detector 9. If cesium 137 were used as the radioactive source, said distance d might be between 40 and 60 cm, and preferentially about 50 cm. Thus, if the relative position of interface 6 and probe 2 is such that emitting source 10 and detector-receiver 9 are both located below the level of the interface, as in FIG. 5A, detector-receiver 9 will receive signals of a certain type, the product of at least partial reflection [of the signals proceeding from the source 10] by the elements making up fluid 30 only.
On the other hand, as shown clearly in FIG. 5C, if detector and source are both above the level of interface 6, the signals emitted by source 10 will be wholly or partially reflected solely by fluid 50, and detector-receiver 9 will therefore pick up signals of a type distinct from those registered in FIG. 5A.
FIG. 5B is an intermediate arrangement in which source 10 is located under interface 6, i.e., opposite fluid 30, whereas detector 9 lies above interface 6, opposite fluid 50. It will be understood that in this case, the signals picked up by receiver 9 will lie between the two extreme signal levels corresponding to FIGS. 5A and 5C, since in this case the signals will have been reflected through the constituents of both fluids 30 and 50.
The analysis of the signals received by detector 9 consists of counting the number of pulses received over a given period of time. In other words, the frequency of the reflected signals is measured as a function of time. It will therefore be understood that the measurement will vary depending on whether the emitted signals are reflected solely by liquid 30, in this case brine (FIG. 5A); solely by the fluid 50 that floats on the surface, i.e., fuel oil (figure 5C); or by both of the fluids, brine and fuel oil (FIG. 5B).
It is further noted that in intermediate FIG. 5B, the frequencies obtained are representative of the proportion of each of the two fluids 30, 50 present in the zone of measurement at a given moment.
The process described above therefore makes it possible to determine the position, or changes in the position, of an interface, enabling an operator to track the progress of an excavation. The interface rises toward the surface as the cavity develops.
Returning one last time to FIG. 2, it will be noted that offset d' between the centers of pipes 3 and 4 is useful particularly at the level of the special inner pipe 3 upon which the probe is mounted. Therefore, arrangements could be made for the complementary sections of pipe 3 on either side of special pipe 3 to have substantially the same axis as axis 24 of outer pipes 4. In such a case, as is known, ends 36 and 37 would be substantially conical in shape, allowing simultaneously for the eccentricity (at 23) of the special pipe 3 carrying the probe, and for the essential coaxiality (at 24) of outer pipe 4 and the rest of the sections of pipe 3. | This invention relates to a system for monitoring, in a cavity in the earth, the position of, or changes in the position of, an interface between two immiscible liquids of different densities. In accordance with the invention, two pipes, one positioned within the other to form a space between them, extends into the cavity in the earth. A probe is mounted on the outer wall of the inner pipe and is vertically positioned near the interface to be monitored. The probe includes an emitting source and a detector-receiver and readings are taken of signals received by the detector after emission by the source and at least partially reflected by at least one of the liquids. From the readings the position of or change in interface may be computed since the signal reading will vary as a function of the relative position of the probe and the interface. The invention may be applied to the monitoring of excavations of underground salt cavities. | 4 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to digital data processing apparatus in which two or more processes which have access to one or more serially reusable resources within the addressable storage of the apparatus are performed concurrently.
2. Description of the Prior Art
The invention is applicable to data processing systems in which any or all of the following conditions hold:
1. concurrent processes may be performed by one or by many computers having access to the same addressable storage;
2. a controlling process or processes allocates the use of the computer or computers in the system to some or all of the processes in the system according to some scheme of priorities;
3. a process may either temporarily or permanently and either in the course of its normal performance or in the event of interruption by some other process, including input and output operations and machine and program malfunction, either itself abandon or be forced to surrender the use of a computer which was performing it;
4. a process, when it has temporarily either abandoned or been forced to surrender the use of a computer, may be restarted using either the same or another computer and either at the point where use of the computer was lost or at another point in the program or programs being then executed;
5. a paging mechanism is implemented either by hardware or by both hardware and programming whereby,
some or all of the processes in the system may address not only data, including programs, in the main storage of the apparatus but also data held on peripheral storage including magnetic disks and drums, and
upon reference by a process to data within its addressable storage but not in the main storage of the apparatus that process may lose the use of the computer performing it until such time as the paging mechanism has copied the required data from the device on which it resided at the time of reference into the main storage of the apparatus.
Terms and Expressions
In this description the term, process, is defined as a unit of work requiring the use of a computer and therefore may denote what are variously called jobs or job steps, tasks, exit processes, program threads, or service requests. Processes may be identified by the extents of storage allocated to them. At an instant each computer in a data processing system may identify one process, termed the active process on that computer which is the process being performed by that computer at that instant. This identification of an active process is effected by the values held in one or more registers which are component parts of the computer performing the process. Processes may be said to compete for the use of the computers in a data processing system this competition entailing such effects as: interruption of one process by another, and selection of one process rather than another to become the active process. A scheme of process priorities in a data processing system may be defined to determine of each pair of processes which, if either, may interrupt the other, and which will be selected in preference to the other. A process which may interrupt or which will be selected is said to be of higher priority than another process which may be interrupted by it or which may not be selected before it.
A process is to be distinguished from an operation which is a significant modification of values held within a data processing system, and from a program which is the embodiment of an algorithm serving to instruct a computer to execute one or more operations for its active process.
The term, addressable storage, is defined as part or parts of a data processing system which contains data, including programs, accessible by a process without the process itself moving that data from one part or type of storage to another.
The term, paging mechanism, is defined as a part or parts of a data processing system which so manages the data held in the addressable storage of processes that when a process attempts to access the data held in its addressable storage but not in the main storage of the apparatus the mechanism interrupts the process, initiates the movement of the referenced data into the main storage of the apparatus, and permits the interrupted process to resume use of a computer only when the data has been moved.
The term, serially reusable resource, is defined as part or parts of a data processing system which may be required for use in any process. It may be used repeatedly either by one or by many processes but it may not be used concurrently by two or more processes. If two or more processes have access to a serially reusable resource, some mechanism is required to ensure their serial use of it. An otherwise serially reusable resource may be concurrently reusable with respect to certain operations in particular those operations which access but do not modify the resource.
Among the serially reusable resources in a data processing system are lists, queues, and chains, hereafter collectively termed lists. A list comprises one or more extents of addressable storage commonly accessible by two or more processes and containing such values than when a process has located one extent of storage, termed the anchor, it may by manipulating the values held in it and in the other extents of storage, hereafter termed elements, locate each element in series. Each element of a list, with the exception of one element called the tail, is succeeded by another, no two elements having the same successor. Each element of a list therefore, with the exception of one element called the head, is preceded by another. A list may be singulary when it has just one element which is both the head and the tail, or it may be empty when it has no elements.
By allowing some or all of the elements of a list to serve as anchors for other lists, more complex structures may be constituted out of lists and manipulated by similar algorithms.
A list may be said to be in normal form when it is not allocated to a process. When a list is in normal form, the values in its anchor and elements are such as to enable any process to locate each element as described above and then to manipulate the list. Once a process has started but has not completed an operation on a list it may be that modifications made by the process to the values in the anchor and elements would prevent any other process correctly locating each element or correctly manipulating the list: a list in such a state would not be in normal form.
Usage of Lists In Data Processing Apparatus
Resource management programs, including operating systems, data base control programs, and timesharing and data communication monitors, are largely occupied in manipulating lists in order to allocate resources of the system to processes, to mark the release of resources by processes, and to identify and control the processes holding resources. Many such lists not only are themselves serially reusable resources but are used in the control of serially reusable resources. For example, the IBM OS ENQUEUE (IBM is a Registered Trademark of International Business Machines Corporation) facility is used to ensure the serial use of data held on magnetic media and itself employs lists of names such that the presence of a name in a list indicates the allocation of the data associated with that name to some process. Clearly, such a mechanism for the control of serially reusable resources cannot upon pain of infinite regress be used for the control of lists themselves.
Frequently encountered types of lists include chains of main storage buffers either allocated to a process or available for such allocation, queues of requests for the use of some resource such as an output device, and chains or queues of processes using or waiting to use some resource such as a program or a computer.
Current List Protection Mechanisms
Among the current methods of ensuring the serial use of lists are programmed locking mechanisms, disabling, and serializing hardware instructions. Locking mechanisms are of two kinds: suspend locks, sometimes called latches or gates, and spin locks.
A lock is a switch indicating whether its associated serially reusable resource is allocated to some process and possibly to which process it is allocated. If its associated resource is allocated a lock is said to be held. A process attempting to obtain a resource and finding the associated lock held will, if it is a suspend lock, abandon its use of any computer until the resource becomes available and the lock is released, or, if it is a spin lock, continue to use the computer but in an unproductive way looping within a program that intermittently checks the lock until it is released.
Disabling is a hardware mechanism whereby a process prevents the computer it is using being seized by some other process. It may be used with the intention that a process running disabled should be the only process being performed in a system but this intention is not achieved if either there is more than one computer in the system or the process being performed references data in its addressable storage but not in main storage thereby permitting the paging mechanism and thereafter some other process to use the computer. In current systems therefore it is ensured that all storage reference by a process that is running disabled is main storage and in systems with more than one computer disabling is used only as an adjunct to other mechanisms.
Serializing hardware instructions effect the controlled modification of small extents of storage. During the execution of such an instruction for a process, no other process, even if it is being performed on another computer, can modify the same storage. A serializing hardware instruction effectively acquires, uses, and releases a small extent of serially reusable storage in the course of its execution. Such instructions are used by locking mechanisms to hold and release locks. A process executing a serializing hardware instruction will either succeed in effecting a modification of storage, or fail if some other process had modified the same storage at or about the time of execution of the instruction.
Disadvantages and Limitations of Current Mechanisms
Locks suffer from these disadvantages:
Suspend Locks
1. force a computer to idle or to perform work of a lower priority than that of the suspended process;
2. they require extra use of a computer to control the suspension and resumption of processes;
3. if a paging mechanism is implemented, a process suspended on requesting a held lock may have some of its data transferred from main storage to peripheral storage and thereafter incur extra use of a computer and delay in performance owing to the execution of the paging mechanism.
Spin locks avoid these disadvantages but at the cost of wasted computer use. Locks of both kinds suffer from these disadvantages:
4. a process holding a lock may be delayed in its performance by a variety of causes, including interruption by other processes and execution of a paging mechanism, so imposing these delays on any other processes obliged to be suspended or to spin on finding the lock held;
5. a process holding a lock may terminate abnormally without releasing the lock, therefore mechanisms must be created to release locks under these cirsumstances and extra use of the computer be incurred in executing these mechanisms.
Processes holding or attempting to hold locks may be forced to use disabling or other mechanisms in order to reduce the risk of suspension while holding a lock. Disabling reduces the responsiveness of a system, that is to say that when a process is running disabled no process of higher priority may seize the computer performing it, thus the intention of the priority scheme is thwarted.
Locking and disabling are not themselves list manipulation mechanisms; they are merely methods of serializing the use of lists. The actual list manipulation is performed by normal programming. For example, a list in normal form, and not allocated to a process, might have an anchor containing addresses of the head and the tail, and elements each containing the address of its successor except that the tail might contain the value zero. In adding a new element to the end of the list a process might:
1. place the value zero in the new element, thus preparing it to become the tail;
2. acquire the list by holding its associated lock;
3. place the address of the new element in the tail thereby making the new element the tail;
4. place the address of the new element in the anchor.
Between (3) and (4) the list is not in normal form because the anchor does not contain the address of the tail.
It is because during its manipulation a list is not in normal form that the list is not concurrently usable but only serially reusable. Moreover, should a process terminate while a list being manipulated by it is not in normal form a recovery mechanism must be executed in order to restore the list to normal form. One of the principal objectives in creating a list manipulation mechanism is therefore to minimize the time during which lists are not in normal form. This objective is achieved to a high degree but within strict limitations by the serializing hardware instructions.
Serializing hardware instructions, such as the IBM System/370 Compare and Swap (CS) and Compare Double and Swap (CDS) described in the "IBM System/370 Principles of Operation", pp. 310-314, effect the conditional modification of small contiguous extents of addressable storage. When a process employs such an instruction to modify an extent of storage no other process can modify the same storage during the execution of the instruction. Consequently, if some operation can be executed on a list using just one serializing hardware instruction, the list being in normal form both immediately before and immediately after the execution of that instruction, then with respect to that operation the list is effectively concurrently usable.
Characteristically lists consist of several extents of storage at different locations so that, in all but the simplest cases, two or more non-contiguous extents of storage must be modified in order to execute some operation and return the list to normal form, as in the example above. As the serializing hardware instructions manipulate only small extents of contiguous storage, operations on such lists are currently executed under the protection of such mechanisms as locking.
It may be noted that a lock itself may be regarded as a degenerate case of a list which can only be either empty or singulary, such a simple list being manipulable by the serializing hardware instructions.
The advantages of the serializing hardware instructions are then that no process can be delayed, thereby delaying other processes, nor terminated, thereby requiring list recovery, while allocated a list manipulated by these instructions.
The invention, by means of programming or the equivalent of such programming implemented in hardware, extends the use of serializing hardware instructions to manipulate complex lists with minimal cost in computer use and minimal loss of responsiveness. It permits temporary or permanent loss of a computer by a process at any time during list manipulation without requiring the list being manipulated either to be released from such a process or to be restored to normal form before being manipulated by some other process. It permits the performance of a process to be resumed either at the point where it lost the use of a computer or at some other point.
The invention allows for the use of indefinitely many computers in a system and for the execution of paging mechanisms. It never requires a process to abandon the use of a computer nor to spin unproductively nor to disable and it permits a process to suffer delay caused either by the intervention of other processes or by the execution of a paging mechanism while manipulating a list without imposing that delay on other processes requiring access to the same list.
In sum, the advantages of the invention are just those of the serializing hardware instructions, but it does not suffer their rigid limitations.
Analysis of Operations On Lists
In order to understand the invention, it is necessary to analyze the operations executed on a list, these operations being the insertion, removal, and modification of elements in the list.
The anchor and elements of a list are held in storage addressable by two or more processes. Each process may also address storage exclusive to itself. A process may be said to own both the storage exclusive to itself and any elements which it has removed from a list.
Any operation executed on a list involves one or more transformations, a transformation being the modification of the anchor or an element in a list, which, according to the invention, is performed by means of a serializing hardware instruction. An operation either about to be started by a process or already partially executed may therefore be defined by an agenda or ordered set of transformations.
At an instant a list is in some state in the sense that there are certain values in the anchor, that certain elements are in the list, and that these elements are in a given sequence and contain certain values.
The definition of an algorithm to execute a set of operations on a list requires for each operation to be executed when the list is in each state a specification of the change of state to be effected and therefore a specification of the transformations required to that end. In current list processing algorithms no such specification is available when a list is in certain states, namely those states when the list is not in normal form.
A list may at an instant be such that either no operation or some operation which may be termed an active operation is being executed on it. If an operation is permitted to be executed on a list before the previously started operation has been completed, that is to say, on a list with an active operation, the integrity of the list may be lost. For this reason lists are, in general, serially reusable. Current algorithms debar a process not merely from starting an operation on such a list but from modifying the list at all.
SUMMARY OF THE INVENTION
According to the invention there is provided a data processing system in which one or more processes may attempt to execute an operation on a list at a time when an active operation has been only partially executed on that list, characterized by a mechanism that operates to ensure only one active operation is permitted on a list at any instant, each process attempts to complete the active operation before starting any other operation, the active operation is executed by one or more of the processes attempting to execute it, and all operations on a list are executed serially irrespective of the number and priorities of processes starting those operations.
BRIEF DESCRIPTION OF THE DRAWINGS
In order that the invention may be fully understood embodiments of its principal concepts and some currently known mechanisms, and preferred embodiments of the invention will now be described with reference to the accompanying drawings, in which:
FIG. 1 is the key to the other figures.
FIGS. 2 and 3 illustrate possible formats for a First-In, First-Out Queue.
FIG. 4 illustrates formats for a currently implemented Last-In, First-Out Queue.
FIG. 5 illustrates formats for an embodiment of the invention, First-In, First-Out Queue,
FIGS. 6 to 8 illustrate formats for another embodiment of the invention, a Last-In, First-Out and Priority Queue.
DESCRIPTION OF PREFERRED EMBODIMENTS
Annex 1 describes the terms and expressions used in the formal definitions of algorithms.
Annex 2 formally defines an embodiment of a currently implemented algorithm.
Annex 3 formally defines an embodiment of the invention, the First-In, First-Out Queue whose formats are shown in FIG. 5.
Annex 4 formally defines an embodiment of the invention, the Last-In, First-Out and Priority Queue whose formats are shown in FIGS. 6 to 8.
Annex 5 formally defines a partial embodiment of the invention, illustrating a general algorithm, modifications of which could generate algorithms for other disciplines of list manipulation.
In FIG. 1, an Anchor 10 is shown on the left. Two fields of the Anchor 10 are shown: Head 11 and Tail 12. Head 11 points to an element 13, shown centre: the line 14 indicates this relationship. Tail 12 is null.
The centre element 13 points to (an element which points to . . . ), i.e. is chained to, the element 15 shown on the right: the line 16 indicates this relationship. Zero or more elements may lie within the chain. A single field is shown in the first element 13: Next.
In the element 15 on the right Next is undefined--it may have any value; this element also has a Priority value, marked as "t".
Serializing Hardware Instructions--Operation
A serializing hardware instruction is to be understood as operating in the following manner:
the instruction has three operands, each of which is an extent of storage; the first and second operands are private to the executing process, the third operand is accessible by all processes that may execute the instruction;
the values in the operands are called respectively the old, new and current values;
upon execution of the instruction, all processes accessing the third operand complete that access and are then not permitted to access that operand until the instruction is complete; the old value is compared with the current value, if not equal the instruction completes, otherwise the new value is placed in the third operand, becoming the current value and the instruction completes;
following the execution of the instruction, the process that executed it can test whether it succeeded on an equal comparison or failed on a not equal comparison and therefore whether it did or did not replace the current value.
In the IBM System/370 the first two operands are general purpose registers, the third is part of main storage; the Compare and Swap instruction accesses four, and the Compare Double and Swap accesses eight contiguous bytes (eight bit characters) in each operand. On a not equal comparison these instructions load the current value into the first operand but this feature is inessential and is ignored hereafter. The term SWAP is used hereafter in reference to a serializing hardware instruction as described above.
A SWAP is used in the following way: to update an extent of storage accessible by many processes, copy the contents of that extent of storage into storage private to the executing process thus establishing the old value; calculate the required new value and hold that also in storage private to the process--the extent of storage to be updated now contains the current value, which may be the old value; and SWAP the new value into the extent of storage to be updated, checking the old and current values and leaving the current value unchanged if they are unequal.
If the SWAP fails on a not equal comparison, restart the entire algorithm by again copying the contents of the extent of storage.
It will be seen that the essence of this method is to work on data in private storage, unaffected by other processes, and then to update commonly addressable storage just if the information on which the update is based is still valid.
List Formats
A list consists of one or more parts each of which is a block, i.e. contiguous extent of addressable storage namely an anchor and zero or more elements. Each block may be divided into fields.
Each part of a list contains at least one pointer. A pointer is a field used to contain either the address of another block, to which it is said to point, or a value from which such an address can be calculated, or it may for special purposes either point to the block in which it is itself contained or contain a nominated value, generally zero, indicating that it points nowhere: this nominated valud is called NULL and a pointer containing it is called a NULL pointer.
An anchor generally contains a pointer to the first element, or head, of the list and may contain a pointer to the last element, or tail, of the list. Characteristically, such pointers will be NULL if the list is empty. An anchor may contain other data such as a count of elements on the list or a value associated with the control of serial use of the list.
An element generally contains a pointer to its successor and may contain a pointer to its predecessor. Characteristically, such pointers in the tail and head respectively will be NULL. An element may contain other data such as priority values used in placing new elements in the list or a value associated with the control of serial use of the list.
Generally, each list in a system has just one anchor, and each anchor is associated with just one list. Elements however, may be moved from list to list.
The various states in which a list may be found can be classified into formats, thus a list which is singulary may be said to be in the Singulary Format, so that this one format comprises any one of a large number of states characterized by the list having just one element. The formats of a list may themselves be classified according to whether they comprise states which arise when no operation is active on the list or when an operation is active on the list: such formats may be respectively termed Basic Formats and Active Formats.
As provided in the invention, a list in an Active Format must indicate what agenda of transformations remain to be performed in order to complete the active operation. Such a list and its agenda may be said to be bound to each other. In practice, it is convenient to set a value in the anchor to show that a list has an active operation on it and therefore is bound to an agenda. Unless the final transformation of the bound agenda modifies the anchor such a switch may be left on when the operation is complete, and in consequence the list may appear from its anchor to be in an Active Format but examination of its elements may reveal that no further transformations are required: a list in such a state may be called pseudo-bound or bound to an empty agenda. Certain of the Active Formats of a list comprise one of these pseudo-bound states. It is therefore convenient to further classify list formats into those which are properly Active in that they comprise a state with a non-empty agenda, and those which are either Basic or comprise a pseudo-bound state: such formats may be respectively termed Routed Formats and Unrouted Formats.
List Operations
The principal operations executed by list manipulation algorithms are the placing of an element into a list hereafter called a PUT and the removal of an element from a list hereafter called a TAKE.
The PUT operations include (but are not exhausted by) the following:
PUT HEAD--place an element into a list as the first element of the list;
PUT TAIL--place an element into a list as the last element of the list;
PUT by Priority--place an element into a list at a position determined by priority values associated with it and with the other elements in the list.
The TAKE operations include (but are not exhausted by) the following:
TAKE HEAD--remove the first element from the list;
TAKE Specific--remove a given element from the list.
In addition to these operations, complementary operations may be defined. Certain processes, when they fail to remove an element from a list either because the list is empty or because there is no suitable element on the list, suspend their performance until an element is put into the list by another process. In order to facilitate the resumption of such a suspended process, a complementary element may be placed in the list when a TAKE fails. This complementary element indicates which process should be resumed when a normal element is placed in the list.
In an algorithm allowing complementary elements therefore a TAKE request may be either conditional or unconditional: the former will result in a take operation or a PUT Complement. A PUT request will result in either a PUT operation or, if there are complementary elements in the list, a TAKE Complement.
Generally, each list in a system is associated with a particular processing discipline which determines which operations may be performed on the list:
a list restricted to PUT Head and TAKE Head is called a Last-In, First-Out (LIFO) Queue;
a list restricted to PUT Tail and TAKE Head is called a First-In, First-Out (FIFO) Queue;
a list restricted to PUT by Priority and TAKE Head is called a Priority Queue.
Analysis of List Processing Operations--Current Limitations
Given the processing discipline to be applied to a list, the analysis of operations on the list requires definition of: the Formats of the list, the Changes Of Format effected by each operation, the agenda of Transformations which constitute each operation, each of which effects one Change of Format, and the Storage Accesses involved in each Transformation.
The limitations of current methods of list manipulation may be demonstrated by applying this method of analysis to a FIFO Queue. The Basic Formats of the list are shown in FIG. 2. In principle, indefinitely many formats could be defined for lists having zero, one, two and so on elements; in practice, because the list is modified only at its ends, only one format (FIG. 2C) is defined for lists having two or more elements.
This format is defined using the is chained to rather than the points to relationship: if an element, say E, either points to another element, say F, or points to an element which points to F, or points to an element which points to an element which points to F, and so on, then E is said to be chained to F. Formally, is chained to is the ancestral of points to.
The Active Formats of the list may be defined as shown either in FIG. 3A and B, or in FIG. 3C and D: the former pair of formats require that a PUT Tail first make the old Tail element point to the new element then make the anchor point to the new element, the latter pair require these transformations to be performed in the reverse sequence. Either method may be selected.
The Changes of Format may now be defined, that is to say for each format and each operation, if that operation is attempted on the list in that format, to which new format, or series of formats, will the list be set. These Changes of Format may be conveniently summarized in a table (here the Active Formats shown in FIGS. 3A and B have been selected):
______________________________________ In Format:Operation 2a 2b 2c 3a 3b______________________________________TAKE Head 2a 1 2a 2b or 2c2PUT Tail 2b 3a-2c 3b-2c 3______________________________________ Notes: 1 TAKE fails on empty list 2 Format with one less element 3 Format with one more element
In this table, formats are listed along the top line and operations down the leftmost column, entries in the table indicate the resultant format or sequence of formats. Notes show where an operation fails and where an element has been added or removed (where there might be ambiguity).
It will be observed that certain entries have been left blank: these represent the coincidences of formats and operations that a locking mechanism would be required to prevent by delaying the process attempting the operation. In effect a locking mechanism identifies normal form with Basic Format.
From the Changes of Format the required Transformations may be defined:
for TAKE Head,
if Empty--no change, TAKE fails,
if Singulary--Anchor Head and Tail pointers set to NULL,
if Multiple--Anchor Head pointer reset to value of Head element Next pointer,
if Post-singulary or Post-multiple--undefined;
for PUT Tail,
if Empty--Anchor Head and Tail pointers set to point to new element,
if Singulary or Multiple--Tail element Next pointer set to point to new element, then Anchor Tail pointer set to point to new element,
if Post-singulary or Post-multiple--undefined.
The Storage Accesses required by each Transformation, can be classified according to the addressability of the storage and the effect of the access.
Extents of storage used in list manipulation include those in storage addressable by only one process, hereafter termed private, and those in storage addressable by more than one process, hereafter termed public.
Lists are held in public storage--their elements may be termed listed elements. If a process executes a TAKE it thereby acquires an element which was, but is now not, part of a list: such an element may be termed an unlisted element. A process executing a PUT must have acquired the new element to be added to the list, probably by a previous TAKE: such an element will be an unlisted element before the execution of the PUT.
Each unlisted element therefore is owned by just one process but is in public storage so the list manipulation algorithm must ensure that processes other than the owning process do not modify an unlisted element. The principal obstacle to a process modifying an unlisted element that it does not own is that no pointer to the element is to be found in public storage. On a TAKE Head for example, the only pointer to the head element in public storage namely that in the anchor is overwritten in the performance of the TAKE. Of course, some process may have copied such a pointer into its private storage before the TAKE was performed: the list manipulation algorithm must ensure either that such a copy is not made or that if made it is not used to modify the now unlisted element. Generally, once a pointer to an unlisted element is placed into some part of a list, as by a PUT, that element becomes listed.
A Storage Access may either change, or simply reference the value held in the storage:
the term transaction may be applied to a change of public storage, either an anchor or a listed element, in any embodiment of the invention invariably effected by a SWAP,
the term preparation may be applied to a change of an unlisted element, generally in the course of a PUT,
the term examination may be applied to a reference (with no change) of public storage, either an anchor or listed element,
private storage accesses are of less significance and will not require separate designation.
As an example of this detailed level of analysis, the first transaction of the PUT Tail operation can be defined as:
the preparation of the new element (an unlisted element) by setting its Next pointer to NULL,
an examination of the Anchor to determine from its Tail pointer the location of the Tail element,
the examination of the Next pointer of that element: copying it into private storage as the old value for the next SWAP, and
the transaction of SWAPPing a pointer to the new element into the Tail element Next pointer.
The presence of two or more transformations in one operation may necessitate locking in current list processing algorithms, but even where each operation can be reduced to a single transformation, for example, by omitting the Tail pointer from the Anchor of a FIFO Queue and searching down the elements to find the last one, it may not be possible to avoid locking. Though only a single transformation is required, it contains multiple examinations. The information gained from those examinations may be incorrect by the time the final transaction is executed (the extreme case being where the list has been emptied by some other process). Thus, locking is currently required not only to protect lists in active formats from manipulation by processes other than the active process, but also to ensure the validity of information gleaned from the list by a process in the course of a single transformation.
Some currently available list processing algorithms do ensure serial use of lists by serializing hardware instructions alone but they impose one or more of the following restrictions:
each operation is to consist of just one transformation;
no operation is to include multiple examinations;
certain operations, such as PUT Tail, are to be performed by just one process on any given list;
each process is to be allocated a distinct priority and while a process is performing an operation on a list no other process of lower priority is to obtain the services of any computer in the system. This restriction can be enforced only in single computer systems and requires that no paging mechanism shall seize control of the computer from a process which is performing an operation on a list.
The invention removes all these restrictions.
List State Control
Certain information about the state of a list must be available to any process placing an element into or removing an element from that list. For example, a process removing an element from a LIFO queue needs to know the address of the first element in the queue and the address of the second element in the queue, which it will be making the new first element. This information is obtained by one or more examinations of a part or parts of the list, preparatory to a SWAP or SWAPs.
It will be recognized that a SWAP fails when the value of the third operand changes between the copying of the old value and the execution of the SWAP Instruction. If a part of the list such as the anchor is updated by a SWAP this update is performed conditionally upon the maintenance of the state of the list insofar as the state of the list is reflected in the part being updated. If a SWAP is used to manipulate a list, assuming that the algorithm is otherwise correctly coded, it is therefore a sufficient condition for the maintenance of integrity of the list that the checking in the SWAP detect any state change that has occurred in the list since the relevant part or parts of it were copied into private storage. Ensuring that this condition holds may be termed List State Concentration: the state of a list has been concentrated for a SWAP when that SWAP will fail if the information on which it relies has changed since it was obtained by examination of the list.
One mechanism which is currently used, and which is extensively employed in the invention, to detect state changes is the incrementation of a modulus in a part of a list, generally the anchor. A modulus is a number which can be incremented to some maximum value depending on the length of storage available for it and which returns to its minimum value when a process attempts to increment it past its maximum. The use of a modulus can best be seen by considering the following mistaken algorithm.
A LIFO Queue consists of an Anchor which contains just a Head pointer and elements which each contain just a Next pointer, the Tail element's Next pointer being NULL.
PUT Head is performed by:
pointing the New element's Next pointer to the Head element of the list, and
SWAPPing a pointer to the new element into the Anchor's Head pointer.
TAKE Head is performed by:
identifying the Head element from the Anchor's Head pointer,
SWAPPing the Head element's Next pointer into the Anchor's Head pointer.
Appropriate modifications of these operations are used for empty lists, but these are not relevant to the example.
The flaw in the algorthm can be seen by considering what might happen during a TAKE.
Let the list consist of the anchor (A) and two elements (E and F), this may be simply represented as:
A→E→F
the active process copies A so creating the old value namely a pointer to E. E is now located and copied so creating the new value namely a pointer to F. The process is now ready to SWAP the new value into A in order to create a list consisting of just A and F:
A→F
but let the process now be interrupted before it executes this SWAP, and let another process or processes become active and execute the following sequence of operations:
TAKE--element E leaves the list--
A→F
TAKE--element F leaves the list--
which is now empty,
PUT a new element (G) into the list--
A→G
PUT the element E into the list again--
A→E→G
Let the interrupted process now resume and attempt to SWAP the new value into the anchor. Despite the change of state of the list, the old and current values are equal, both being pointers to E: the SWAP therefore succeeds. The list should consist of A and G, E having been removed--
A→G
in fact consists of A, F, and those elements, if any, following F in whichever list F has been placed--
A→F→?
and the integrity of the list has been lost.
Clearly the contents of the anchor in such a list do not adequately reflect the state of the list.
If we also include in the anchor a field which can vary in value from zero to an indefinitely large number, and every time we SWAP the anchor in order to TAKE we increment the value in this field then such a SWAP as that described above will fail, for the new field which is included in the SWAP check will have been incremented by two since the anchor was copied to create the old value. In practice, such a field cannot be provided as it would be of indefinite length, however a modulus of reasonable length gives effectively the same protection; a sixteen bit modulus is a threat to list integrity only if while a process is executing one operation on the list about sixty thousand modulus incrementing operations are performed by other processes.
It should be noted that it is not the modulus alone but the total contents of a part of the list that provide an indication of state change. Not every operation therefore requires the modulus to be incremented, in fact the less frequently a modulus is incremented the better, that is either the more security is provided or conversely the smaller the modulus need be. In the example above for instance, it is not strictly necessary to increment the modulus on a TAKE from a singulary list.
Algorithms for such a LIFO Queue are defined in the IBM System/370 Principles of Operation, pp. 310-314 and in this specification--see FIG. 4 for the Formats and Annex 2 for definition of the Algorithm.
This algorithm is included to illustrate the current state of the art, to allow familiarization with the notation of the Figures of Formats and the definition language used in the Annexes, and to serve as an introduction to the LIFO and Priority Queue algorithm which is an extension of it. The Changes of Format of the LIFO Queue are given in the following table:
______________________________________ In Format;Operation 4a 4b 4c______________________________________TAKE Head 4a 1 4a *4b or *4c2PUT Head 4b 4c 4c3______________________________________ Notes: *Modulus in anchor incremented 1 TAKE fails on empty list 2 Format with one less element 3 Format with one more element
LIFO Queues have then been implemented using serializing hardware instructions alone, more complex lists--even the relatively simple FIFO Queue--cannot currently be so implemented without serious restrictions. The invention permits the implementation of algorithms that manipulate lists more complex than LIFO Queues without these restrictions and is in principle applicable to lists of much greater complexity than those currently implemented with restrictions.
Non-Serial State Verification
The introduction of a modulus into a part of a list is one method of ensuring that the value held in that part of the list shall adequately concentrate the state of the list for the purposes of the next SWAP to be executed on it. A second method used in the invention may be termed non-serial state verification. This is nothing more complex than a comparison performed between a field or fields in public storage and a previously copied value of the same field or fields in a private storage.
SWAPPing has been described above: a SWAP is serialized and includes a comparison which is a list state verification; non-serial state verification is a similar state verification but does not modify any value in storage and can be implemented by ordinary non-serialized comparison instructions.
A non-serial state verification is to be understood as operating in the following manner:
the instruction has two operands, each of which is an extent of storage; the first operand is storage private to the executing process, the second operand is storage accessible by all processes that may execute the instruction;
the values in the operands are called respectively the old and current values;
upon execution of the instruction, the old value is compared with the current value and the instruction completes;
following the execution of the instruction, the process that executed it can test whether it succeeded on an equal comparison or failed on a not equal comparison.
The term CHECK is used hereafter in reference to a non-serial state verification as described above.
In the invention only a successful SWAP constitutes a transaction, that is to say that any embodiment of the invention attempts to modify the values held in anchors and listed elements only by means of SWAPPing. An examination however may be constituted by a failed SWAP, or by a CHECK, or by copying the value of an anchor or listed element into private storage.
The Problems of List Manipulation and Their Solution
In order to understand the invention fully, it is necessary to have an explicit understanding of the two major problems of list manipulation, by serializing hardware instructions alone, that it solves, and the peculiar logic required to implement it. The two problems, which have already been adumbrated are:
to sever the connection between Basic formats and normal form by ensuring that a list is always in normal form, and
to ensure list state concentration before every SWAP.
If a list is always to be in normal form, it follows that any process attempting to manipulate a list in order to execute any operation must be able to manipulate that list forthwith; at the same time, if operations are to be serialized, it follows that if an operation is active on a list then a process cannot start another operation on the list. The conjunction of these two requirements entails that any process finding an operation active on a list can only attempt to complete that active operation. The special logic required to control a multiplicity of processes all attempting to execute the same operation may be called re-executable.
Maintenance of Normal Form By Serialization Of Operations
It is an essential principle of the invention that while it may be generally impossible for many processes to execute different operations on a list simultaneously, it is possible to create the re-executable algorithms that permit many processes to execute the same operation on a list. Thus, operations on a list may be serialized without serializing processes.
In manipulating a list therefore a process may be at any instant associated with two operations:
its own operation in order to execute which it has begun to perform the list manipulation algorithm on the list, and
the active operation on the list.
Any embodiment of the invention will generally ensure that:
if there is an active operation on the list, the agenda of transformations remaining to complete that operation is available to the process by examination of the state of the list,
the performance of the first transformation of that agenda will either complete the active operation leaving the list in an Unrouted format or will replace that agenda by a smaller agenda comprising just those transformations needed to complete the active operation,
if there is no active operation on the list, and the process has not initiated its own operation, then one part of the list, generally the anchor, will be designated as the next part to be SWAPped, such a SWAP constituting the initiation of the process own operation,
if the processes own operation comprises only one transformation, then its initiation will also be its completion,
otherwise its initiation will effect the binding to the list of the agenda of transformations required to complete the process own operation, which will thereby become the active operation,
the process will no longer manipulate the list when
1. it has initiated its own operation, and
2. that operation is no longer the active operation,
the process whenever it executes a CHECK or a SWAP which fails will re-examine the list and
if it has initiated its own operation but that operation is not the active operation, cease to manipulate the list,
if it has not initiated its own operation, then it will attempt to complete any active operation and initiate its own, as described above.
Nevertheless, there are certain circumstances where somewhat less rigidity than is here implied will be acceptable:
where a process requires no more information about its own operation than that its successful execution is ensured it may cease to manipulate the list as soon as it has initiated its own operation even if, in so doing, it leaves its own operation active on the list:
such an operation may be termed non-productive and is exemplified by a PUT Tail to a FIFO Queue,
other operations such as TAKE Head are productive in that the owning process needs to know not merely that the operation was successful but also which element was TAKEn,
where the final transformation of the agenda bound to a list, or the transformation which returns a pseudo-bound list to Basic Format, is a transformation of that part of the list, generally the anchor, designated as the part to be SWAPped to
initiate any operation, that transformation and the initiation of a process's own operation may be effected by the same SWAP, and
in the rare cases where two operations can be simultaneously executed on a list (i.e. where the list is concurrently reusable with respect to one of the operations) they need not be serialized: one example is that a discipline permitting TAKE head, PUT Head, and PUT Tail, will permit PUT Head to be performed safely irrespective of any other operation active on the list.
Achievement of List State Concentration
The problem of concentration is to so represent the state of the list being manipulated in the next part of the list to be SWAPped that the SWAP will fail if the list state changes. This problem can be illustrated by means of the FIFO Queue logic illustrated in FIGS. 2 and 3a and b and analyzed above. If a list is singulary, see FIG. 2B, two processes may attempt to manipulate it concurrently the one attempting a TAKE and the other a PUT. The TAKE process SWAPs the anchor to create an empty list, see FIG. 2a; the PUT process SWAPs the single element to create a postsingulary list, see Diagram 3a. If these SWAPs are executed either simultaneously or immediately consecutively the list is emptied and the TAKEn element is pointing to the newly PUT element. In effect the PUT process has modified an unlisted element. Neither the value in the anchor nor that in the single element gave an adequate representation of the state of the list.
In order to solve the problem of List State Concentration, it is assumed that serialization of operations has been achieved as described above. At any instant therefore the state of a list, in conjunction with the provisions of the list manipulation algorithm, indicates either
that there is an active operation on the list,
what part of the list is to be SWAPped in the next transformation, and
what change of state that transformation is to effect, or
that there is no active operation on the list and
what part of the list is to be SWAPped in the next transformation, this transformation constituting the initiation of the next operation to be executed on the list.
It follows that if a process has complete information about what the state of a list was at some instant then it can determine which part of the list was, or was to be, SWAPped next. An instant about which a process has determined such complete information may be termed an information point.
It may now be demonstrated that a process can obtain an information point, in the following laborious way if in no other: let the process be at a point where it has no information about the state of the list except the location of the anchor, we may term this the Retry point of the list manipulation algorithm.
Each part of a list incorporates a modulus which is changed on sufficient transformations of that part, if necessary on all transformations of it, to ensure that, within the period of time allowed by the size and frequency of change of the modulus, the total value held in the part, and compared on each SWAP or CHECK of it, will be different from one instant to another if any transformation of the part occurred between those two instants.
The following procedure is to be performed:
The anchor is copied into private storage; from each non-NULL pointer value in the copy of the anchor in turn an element is located and copied into private storage;
from each non-NULL pointer value in the copies of the elements in turn an element is located and copied into private storage, no element being copied more than once, this process being repeated until all parts of the list have been copied and the copies held in private storage.
During this procedure, after copying any element the copy of the anchor and the copies of all elements previously obtained are CHECKed against the current values of the parts of the list from which they were copied:
if any CHECK fails, some other process must have modified the list and the process restarts from the Retry point;
if no CHECK fails, the procedure continues.
When every part of the list has been copied, and the final CHECKs have been successfully performed, it has been established that the instant at which the last element was copied is an information point: the private storage of the process contains total information about the list at that instant. It may be noted that when the information point is obtained, it is in past time; the present instant is not an information point, for the value in any part of the list may have changed since it was last CHECKed.
The process can now determine the next SWAP to be executed after the information point and
the process attempts the SWAP.
As each part of the list is provided with a modulus it can be ensured that upon SWAPping it, its value will become different from what it was at any time close to the last information point, so
if the SWAP of the selected part of the list succeeds, no other process could have performed any transformation on the list between the information point and the SWAP, for any process was obliged to SWAP that part,
if the SWAP of the selected part fails then some other process must have succeeded in SWAPping the same part: the process restarts from the Retry point.
It can be seen that at the information point the state of the list has been concentrated into the value of the selected part of the list.
When a series of examinations as described above is followed by a successful SWAP, the time of the SWAP becomes an information point. The process having performed such a successful SWAP may therefore immediately determine whether, according to the provisions of the list manipulation algorithm, it has completed the procedure or must attempt the next SWAP in order either to complete the execution of the active operation or to initiate its own operation.
A process that has already initiated its own productive operation may discover during the examinations described above that its own operation is no longer the active operation and so complete the procedure without obtaining an information point, or without performing a SWAP. Such a process will have previously performed at least one successful SWAP, namely that initiating its own operation.
In practice, it is rarely necessary to copy and CHECK an entire list, sufficient indication of its state and bound agenda, if any, being given by a small number of its parts. The algorithms described below illustrate this limited examination.
Re-executable Algorithms
Embodiments of the invention therefore have this characteristic: within the algorithm there is a Retry point, as described above, from which point a, not necessarily exhaustive, series of examinations of a list are performed; any process executing the algorithm following the Retry point
completes its manipulation of the list, or
effects at least one transformation, or
detects that some other process has effected a transformation.
The algorithm, and in particular that part following the Retry point, may be described as reexecutable in that a process may execute it indefinitely many times but still achieve the same result with respect to its own operation as it would have achieved had it executed the algorithm just once with all SWAPS and CHECKS successful.
Looking at such an algorithm with respect to operations rather than processes, we may view it as a method whereby agendas are performed on a list by a mechanism which ensures that if at least one and optionally indefinitely many processes are manipulating a list one transformation after another will be performed but which process will perform any given transformation is undetermined, except that each process performs at least that transformation which initiates its own operation.
Because the invention divorces processes in this way from operations and because many processes have to a large extent the same effect as a single process, not only can a process manipulating a list lose control of a computer without ill effect but it is more efficient in computer use for a process so to lose control and permit other processes to manipulate the list with fewer failed SWAPs and CHECKs.
The only overheads of the invention are the manipulation wasted when SWAPs and CHECKs fail (and this overhead is reduced as the apparatus becomes busier with handling interrupts) and the ingenuity required in devising such algorithms.
DESCRIPTIONS OF EMBODIMENTS OF THE INVENTION
Two embodiments of the invention are described: for FIFO Queuing and for LIFO Queuing with Priority Queuing of Complementary Elements. The former represents a commonly used discipline for queuing of work to a serially reusable resource; the latter is appropriate for control of passive resources such as fixed length storage buffers for the use of processes of different priorities.
The Changes of Format defined for these algorithms are classified into changes of Routed Formats which are independent of the operation being attempted (the processes own operation), and changes of Unrouted Formats, which are dependent on the operation being attempted, and are effected after any changes of Routed Format have been effected (after the active operation has been completed). The changes of Routed Format are therefore repeatedly attempted until an Unrouted Format has been created.
A generalized, and ipso facto incomplete, algorithm is also described.
______________________________________FIFO Queue AlgorithmAlgorithm Name: FIFODefinition: Annex 3Formats: FIG. 5Format Changes: In Routed Format:Operation: 5d 5e______________________________________Any @5f @5f______________________________________ In Unrouted Format:Operation 5a 5b 5c 5f______________________________________TAKE Head 5a 1 5a *5b or *5b or *5c2 *5c2PUT Tail 5b 5d 5e 5e______________________________________ Notes: @Modulus in Element incremented *Modulus in Anchor incremented 1 TAKE fails on empty list 2 Format with one less element
The formats may be contrasted with those in FIGS. 2 and 3 a and b. In particular, it should be noted that the tail element does not necessarily contain a NULL pointer: the tail element is recognized as such because the tail pointer in the anchor points to it. FIG. 5 Formats d, e, and f illustrate Active Formats, their agendas are indicated by the Bound Flag, shown as an asterisk, the tail pointer in the anchor, and the pointers in the tail and old tail elements: Formats d and e have the same agenda, a single transaction to make the old tail point to the tail, so creating format f which has an empty agenda.
The format changes shown above indicate that formats d and e are Routed Formats: they are inevitably transformed to format f. Of the operations shown, the TAKE is a single transformation operation and the PUT a double transformation operation, the second transformation being the chaining of the old tail of a list in Routed Format. The PUT operation is non-productive, so leaves a list in Routed Format.
The algorithm defined in Annex 3 is described below:
at label Fifo
the parameters passed to the algorithm are a pointer to the anchor and a pointer which is NULL for a TAKE operation or points to the unlisted element to be PUT.
The anchor, and each of its copies in private storage when made, contains a pointer to the first element, a pointer to the last element, and a Bind Flag or Switch--these are shown in FIG. 5, and a modulus; the elements and any copies of them, each contain a pointer to their successor--also shown in FIG. 5, and modulus.
It should be noted that in formats d, e, and f the pointer in the tail element is used to point not to its successor but to its predecessor.
At label Retry, (this is the Retry point) the anchor is copied.
It will be noted that an empty list, see format a, cannot be bound to an agenda. The logic for a list in Basic Format, i.e. not Bound, may be considered first.
For a TAKE, control passes to label Take or if the list is empty to label Exit via label Void (failed TAKE).
The PUT logic depends on whether the list is empty or not: a PUT to an empty list is effected in one transformation, to a non-empty list in two, consequently when the list is not empty the Bind Switch is set to indicate that the partial agenda containing the second transformation is bound to the list.
This modification of the anchor is first made in the new anchor which is a copy of the anchor held in private storage, and this is the practice throughout all embodiments of the invention (see Serializing Hardware Instructions--Operation).
If a previous PUT has left the Bind switch on, the Unbind routine is invoked to complete the PUT before any other operation is initiated.
At label Void,
failed TAKE is detected.
A PUT to an empty list is commenced by setting the anchor's head pointer, see formats a and b.
(Thereafter the PUT operation is identical for both PUT to an empty list and PUT to a non-empty list, the Bind Switch having already been set in the latter case.)
At label Put,
the new (unlisted) element is about to become the tail element of the list in format b, d, or e.
The new element is made to point to the old tail, or if the list is empty is made NULL,
then the new anchor's tail pointer is made to point to the new element.
At this point, if the anchor has not been modified since the Retry point, the new anchor has the value which should be SWAPped into the anchor.
At label Take,
a singulary list, format b, is identified by the head and tail pointers having the same value, empty lists having already been excluded.
If the list is not singulary, the head pointer in the new anchor is made to point to the second element in the list and the modulus is incremented (just as in the LIFO logic).
At label Single,
the new anchor is made to represent an empty list.
At label Swap,
an attempt is made to initiate an operation, PUT or TAKE.
If it fails the algorithm is restarted.
If it succeeds either a double transformation PUT has been initiated, or a TAKE or a single transformation PUT to an empty list has been performed.
In either event, the algorithm ends at label Exit.
At label Exit,
the output parameters, relevant only for a TAKE, are described.
Control returns to the program that invoked the algorithm.
At label Unbind. The Unbind routine has three functions:
1. to identify the agenda as either empty, as in format f, or not, as in formats d and e,
2. in the latter case to effect the transformation to format f, and in any event,
3. to set off the Bind Switch in the new anchor. It may be noted that if the executing process own operation is a PUT, the Bind Switch will be set on again as described above.
The Bind Switch is set off.
The tail element is copied, this is of course the element being PUT in the active operation;
from its pointer the old tail element, called in the definition the Sacral Element, is located.
This element is also copied and then tested to see if it already points to the tail element, the condition called Chained and indicating an empty agenda as in format f.
If the agenda is empty than it is probable that another process is manipulating the list for format f is rarely found when no process is executing the algorithm, so
the anchor is CHECKed to ensure that it has not been modified since the Retry point, and
if it has not been modified execution continues from the instruction following the CALL of the Unbind Routine.
This CHECK is not strictly necessary as a similar test is implicit in the next anchor SWAP, but in practice it may be more efficient than a failed SWAP.
If this, or any, CHECK fails the algorithm is restarted from the Retry point. Format f having been eliminated
the algorithm prepares to SWAP the old tail element in order to
make it point to the tail element and to
increment its modulus,
the incrementation of the modulus being necessary for list state concentration.
Just before the SWAP the anchor is CHECKed, and this CHECK is necessary for list state concentration, although the exhaustive method described above is not.
The old tail element is then SWAPped.
If the SWAP fails of course the algorithm is restarted from the Retry point,
otherwise the agenda has been emptied and the Unbind routine returns control to the instruction following its CALL.
As the algorithm will then continue to SWAP the anchor, so creating format b, c, d, or e, it can be seen why format f is nearly always very transistory.
A non-transistory format f can be caused either by failure and termination of a process before it can SWAP the anchor or by the strange coincidence that the tail element of a list in format b or c points to an unlisted element which is PUT into the list so effecting a transformation from format b or c to format f: though odd, this is quite harmless and in fact saves a SWAP.
At label Check,
the anchor is CHECKed.
It should be noted that the RETURN is to the instruction following the CALL of Unbind after the first CHECK described above, but to the instruction following the CALL of Check after the second CHECK described above--in the former case CHECK was invoked by GO instead of CALL (see Annex 1 for Terms and Expressions used in Definitions of Algorithms).
The function of the Unbind routine can be summarized thus: it ensures that the list is in Unrouted Format, format f, and prepares to return the list to Basic Format, format c, by setting off the Bind Switch in the new anchor; consequently the logic for lists in Basic Formats is applicable after the invocation of Unbind.
______________________________________LIFO and Priority Queue AlgorithmLIFO Queue with Priority Queue of Complementary ElementsAlgorithm Name: ComplDefinition: Annex 4Formats: FIGS. 6, 7 and 8Format Changes: In Routed Format:Operation 7a 7b 7c 7d 8a 8b______________________________________Any @8a @8b @8c @8d <8e <8f______________________________________ Note: Routed formats 8c and 8d included below
In Unrouted Format: 6e8cOperation 6a 6b 6d 6d8d 8e8f______________________________________TAKE Head 7d 1 6a *6b or 7b or 7a or *6c2 7c 1,4 7b or 7c 1,4PUT by Prty 6b 6c 6c3 6a5 *6d or *6e 2,5,6______________________________________ Notes: @Modulus in Active Element incremented <Modulus in Previous Element incremented *Modulus in Anchor incremented 1 TAKE converted to PUT Complement 2 Format with one less element 3 Format with one more element 4 depending on Priority 5 PUT converted to TAKE Complement 6 Exception format 8e cannot change to format 6d
This algorithm may be compared with the LdFO Queue Algorithm of Annex 2, Formats shown in FIG. 4. In particular, in FIGS. 4 and 6, Formats a, b, and c are strictly equivalent, as are their associated changes in the leftmost three columns of the above table of Changes of Unrouted Formats, with the exception of TAKE from an empty list. The LIFO algorithm is incorporated almost unchanged--see Annex 4 from label Compl down to label Retry and label Normal down to label Exit.
In order to understand the algorithm it may be assumed that each process is a task having some priority associated with it, priorities being used in the allocation of resources to tasks. Each task marks the elements it owns with its priority. The list being manipulated is a list of resources, such as fixed length storage buffers, which when placed in the list are made available to any task. While there are sufficient resources the list is simply a LIFO Queue and any task requiring one of the resources just takes the first one on the queue.
When there are no resources on the queue any task requiring a resource must suspend execution until one becomes available. The task leaves a note on the queue that it is waiting for a resource. When a resource becomes available it is desired to allocate it to the highest priority waiting task (the highest priority task whose note is on the queue). The queuing of these notes or complementary elements must therefore be in priority order.
Such a list may clearly be in either of two conditions, normal when it has no complementary elements or complemented. In FIG. 6 the formats a, b, and c represent a list in normal condition--all these are Basic Formats; the Basic Formats in complemented condition are shown in formats d and e. The formats shown in FIGS. 7 and 8 are Active Formats.
It will be seen that PUT Complement is in essence a three transformation operation.
The first transformation is the initiation of the operation and consists of setting in the anchor a pointer to a new complementary element in the Next pointer of which points to itself. This generates one of the Initial Formats as shown in FIG. 7.
The second transformation requires that the list be searched in order to discover between which elements the new element should be placed: in the figures the parameters of priority which determine the sequencing of elements are shown as letters which should be arranged in alphabetic sequence. The elements involved in the insertion are called:
the Active Element--which is the element being inserted,
the Previous Element which is to become the predecessor of the Active Element, and
the Following Element which is to become the successor of the Active Element
The second transformation makes the Active element point to the Following Element. This generates one of the Insertable Formats as shown in FIG. 8a to d.
The final transformation completes the insertion of the Active Element by making the Previous Element point to it. When the new element should be inserted as the first element in the list the final transformation must be performed on the anchor and is therefore conveniently performed by the same SWAP that initiates the next operation (see the entries for Formats 8c and 8d in the Table above). This saving of a transaction is associated with the Condition Listart in the algorithm definition: in this condition, the Active Element lacks a predecessor (it is to become the head element); the Condition Listend in the algorithm definition applies when the Active Element lacks a successor (it is to become the tail element); when both Listart and Listend apply, the list is Singulary (the Active Element is the only element).
The other operations executed on the list - TAKE an element, normal or complementary, and PUT a normal element--are all single transformations. It may be noted that the multiple transformation PUT Complement is non-productive.
The algorithm defined in Annex 4 is described below:
at label Compl,
the parameters passed are similar to those for the FIFO Queue, but it should be noted that the Pointer Element is never NULL as even a TAKE request must pass an element which may be queued as a complementary element. A TAKE is therefore signalled by making this element's Next pointer point to the element itself.
The element contains a priority and the anchor indicates a relation related: this should be read as one of the following
less than
greater than
equal to
not equal to
not greater than
not less than
either equal to or not equal to (always true) both equal to and not equal to (always false).
This relation is used to end the search down the list on the condition:
Priority of the Active Element is related priority of the putative Following Element.
i.e. if this condition is true, the Following Element has been identified.
If no Following Element is identified, the element is inserted at the end of the list (condition Listend). It will be seen that
the always true relation creates a LIFO queue,
the always false relation creates a FIFO queue, and
the greater than relation creates a genuine Priority Queue with higher priority for a greater priority parameter (elements of the same priority being queued FIFO).
In FIGS. 6 to 8 it is assumed that alphabetically earlier letters are less than later letters and the relation related is
the less than relation, so the highest priority is represented by "a" and the lowest by "z".
At label Retry,
(this is the Retry point, all failed SWAPs and CHECKs cause a restart from here)
the anchor is copied.
The conditions Complemented and Bound are defined.
There is no Bind Switch as in the FIFO Algorithm, instead a Bind pointer takes the place of the Tail pointer which is not required. If this pointer is neither NULL nor pointing to the first element of the list then it is pointing to an element to be inserted into the list--this element must be a complementary element--and the list is bound to some, possibly empty, agenda. The definition from this point down to the label Normal is concerned with the processing of such lists, which have formats shown in FIGS. 7 and 8.
The Active Element, which is to be inserted, is located and copied.
Values are now set to begin a search of the list.
The search conceptually consists of placing the Active element between the anchor and the first element, between the first and second elements, between the second and third, and so on until it is placed between the penultimate and the last, testing the priority relation in each position and stopping when the appropriate position is found. If none is found, the Active Element is placed at the end of the list--condition Listend.
To begin the search, the condition Listart is set: the Pointer Previous which during the search will point to the putative Previous Element is made to point to the anchor.
The Pointer Following points to the putative Following Element so is first set to point to the first element in the list.
In formats 7d and 8d there is no first element in the list, consequently at this point both conditions Listart and Listend are in effect.
At label Search,
the search is iterated until the condition Listend is found, if not terminated earlier.
The putative Following Element is located and copied (this element is the one pointed by the Previous Element, or if Listart, the anchor head pointer).
A fairly extensive state verification is then performed by CHECKing the anchor, the Active Element, and (except when Listart) the Previous Element.
If this is successful the priority relation is tested and if found true the search is terminated--the Active Element has effectively been placed.
If the priority relation is found false the Active Element is conceptually moved on to the next position in the list: the Following Element is now regarded as the Previous Element and the pointer to the new Following Element is set.
On looping back to label Search, as described above, the new Following Element is located.
The search always completes by going to the label Found unless a CHECK fails.
At label Check,
the state verification is performed.
if unsuccessful control returns to the Retry point.
At label Found,
the conditions tested relate to the active format thus:
Initial holds for the formats shown in FIG. 7,
Pseudobound for the formats shown in FIG. 8e and f,
neither for the formats shown in FIG. 8a to d.
It may be noted that the condition Pseudobound is an alternation of two sentences: which of these two may hold is dependent on the relation related. If a list is pseudo-bound the search will stop either when the Active Element is the same element as the Previous Element or when it is the same element as the Following Element.
These are the two possibilities defined in the Pseudobound condition: the former holds when related is "less than", "greater than", "not equal to", or the always false relation, the latter holds for the other relations.
At label Juston,
the formats shown in FIG. 7 are converted to the similarly lettered formats (a to d) in FIG. 8.
When the Next pointer in the Active element is made to point to the Following Element (or to become NULL when Listend) the modulus in the Active element is simultaneously incremented.
At label Insert,
the Listart condition identifies formats 8c and 8d whose final transformation will be effected in the SWAP initiating the next operation on the list.
Formats 8a and 8b are converted to formats 8e and 8f respectively.
At label Unbind,
the pseudo-bound formats 8e and 8f cause the copy of the anchor called the New Anchor to be marked as not bound.
At label Sethead,
Formats 8c and 8d are handled by indicating in the New Anchor that the Active Element should be the new first element, and simultaneously unbinding the New Anchor.
At label Normal,
normal condition LIFO processing is performed.
At label Void,
what in normal LIFO processing would be a failed TAKE is changed into a PUT Complement.
At label Put,
normal LIFO processing continues.
At label Unbound,
no matter whether reached from Unbind, from Set head, or by bypassing all the search processing, the New Anchor has been marked as unbound. The next anchor SWAP after that point will, mark the anchor unbound unless it is bound by the next transformation, and effect the next transformation.
As the list is in complementary condition a TAKE is changed into a PUT Complement, and a PUT into a TAKE Complement.
The TAKE Complement processing is normal TAKE processing preceded by recording which complementary element is taken, and resetting the Bind pointer. It may be noted that if the list is singularly as in format 6d this reset of the Bind pointer, along with the reset of the Head pointer by the TAKE logic, will make it empty, so effecting the change shown in the second row and fourth column of the Table above.
If the list is not singulary this reset of the Bind pointer simply leaves the list complemented but unbound.
At label Take,
the common TAKE processing is performed (i.e. TAKE proper or PUT converted to TAKE Complement).
At label Putcomp,
a TAKE was intended, but the list was either empty or complemented.
As a TAKE is signalled by the Pointer Element pointing to an element which points to itself, by binding this element to the anchor one of the formats shown in FIG. 7 must be created.
This constitutes the initiation of the multiple transaction PUT Complement.
At label Swap,
common anchor SWAPping is performed.
At label Exit,
the Condition Fail indicates a failed, i.e. delayed, TAKE. The invoking program should cause the task to wait until restarted. Upon restart the desired element will be made available.
The Condition Schedule indicates a PUT has been converted to a TAKE Complement:
the desired element should be used to restart the waiting task that placed it on the queue,
the element that was to be put, i.e. the current processes own element should be made available to the restarted task.
The condition Taken indicates a successful TAKE.
If none of these conditions hold a normal PUT has been performed.
Clearly, this algorithm needs to be used with a suspend-resume mechanism and with another list processing algorithm that manages a list of free elements that tasks may acquire in order to invoke this algorithm and release after invoking this algorithm.
In practice, the algorithm as defined would not necessarily succeed perfectly in its objectives: a process having completed a PUT which was converted into a TAKE Complement might be interrupted before it had restarted the highest priority waiting process.
Another process might then perform another PUT and either succeed in putting a normal element into the list or perform a TAKE Complement and restart the second highest priority waiting process. The algorithm could be modified to prevent this possible failure in implementation of the priority scheme, but as this would involve placing the process resume logic within the algorithm itself it would complicate the exposition and has therefore not been described here.
A noteworthy characteristic of the algorithm is the amount of work done in the search and unbind logic. This could be reduced by having the initiating process of a PUT Complement perform a similar search before initiating its own operation, the element bound to the anchor could then be bound already having been set to point to the Following Element. Whether, and in what circumstances, this modification might give an improvement in performance has not been investigated. One consequence of the algorithm in its present form is that the agenda bound to a list consists in effect of all the information to be found in the list, but this is a theoretical effect which may have no practical implications.
General Algorithm
A schematic general algorithm is defined in Annex 5.
The algorithm is a framework incorporating the general principles of the invention; the following notes indicate the sort of logic which needs to be inserted into it.
Preface
Input definition,
location of the Current Anchor, definition of fields in Anchor and Element,
definition of conditions in particular:
Active--true when the executing processes own operation is the active operation, probably dependent on values in the New Anchor and the Input data;
Bindable--true when the executing processes own operation has an agenda of more than one transformation, dependent on the Input data and possibly on values in the New Anchor;
Nonproductive--true when the executing processes own operation is non-productive, dependent on the Input data.
Test New Anchor
Definition of conditions in particular:
Bound--true when the anchor is bound to a (possibly empty) agenda,
and possibly checking for and processing special conditions such as empty or singulary list.
Identify and Verify Next Transaction
Examination of the list,
identification of the first transformation of the agenda,
state verification using CHECK going to Retry,
definition of the condition:
Pseudobound--true when the bound agenda is empty, resetting the New Anchor to not Bound.
Perform Next Transaction
SWAPping the appropriate part of the list identified by the Identify and Verify next Transaction logic.
Perform Own Operation
Performing a single transformation operation using a SWAP.
Initiate Own Operation
Performing the first transformation of a multiple transformation operation so binding an agenda to the list and setting the Bound condition using a SWAP.
Exits
Output definitions and RETURN.
ANNEX 1--TERMS AND EXPRESSIONS
Terms Used in the Definitions of Algorithms
In the definition of algorithms, terms in lower case letters are used in three ways:
1. as connectives in instructions and definitions, as described under Commands:
2. as connectives in statements, as described under Statements;
3. as truth functional connectives of statements the following terms are used--
not not statement is the negation of statement;
and statement-1 and statement-2 is the conjunction of statement-1 and statement-2;
or statement-1 or statement-2 is the inclusive alternation of statement-1 and statement-2.
In the definition of algorithms terms with just their initial letters capitalized are used in five ways:
1. as labels
marking the commands which follow them, or
in GO, CALL, and RESTART commands indicating the transfer of execution to the commands preceded by the same lables;
2. as abbreviations for statements, as defined by the CONDITION command;
3. as field names. To avoid ambiguities and increase readability field names may be either
preceded by field types such as POINTER or
followed by an expression of the form:
of Blockname Blocktype;
4. as block names;
5. as block types. A block is
a part of a list,
a copy of a part of a list, or
such a copy with one or more fields modified subsequently to their being copied.
A block is named by a block description which is an expression of the form:
Blockname Blocktype
where Blockname is a block name and Blocktype is a block type.
In the definition of algorithms, terms in capitals are used in three ways:
1. as command identifiers occurring as the first term in an instruction or definition;
2. as field types. The following terms are used--
POINTER a pointer,
MODULUS a modulus,
SWITCH a field which can contain just one of two values ON and OFF,
PARAMETER a field containing a numeric value for comparison,
RELATION a field marking a relation for a comparison
3. as values. The following terms are used--
NULL the NULL value, set in pointers, ON and OFF the two values which can be set in a SWITCH
Statements
Statements are expressions which at any point in the execution of an algorithm are either true or false. A statement may be either simple or compound.
A simple statement is of the form:
field relation operand,
where field is a field descriptor, i.e., an expression of the form:
fieldtype fieldname
or of the form:
fieldname of blockname blocktype
as described above;
relation is an expression such as:
is greater than
and operand is either
a field descriptor
or
a value term such as NULL.
A simple statement is true when the relation expressed by relation holds between the value of the field named by field and the value of the field named by, or the value indicated by, operand.
When operand is a value term and relation expresses simple equality or inequality then relation is written as:
is
or
is not
rather than as:
is equal to
or
is not equal to.
A compound statement is formed by connecting simple statements by negation, conjunction, and alternation, as described above.
When defined by the CONDITION command a single term may serve thereafter as complete statement, either simple or compound.
Commands
Commands are either definitions or instructions. In a given implementation of an algorithm the instructions would be implemented as one or more machine instructions. The definitions serve to interpret the expressions used in the instructions. The definitions LOCATE and WHEN are related to instructions in certain implementations as described below.
Instructions that Transfer Control of Execution
GO to label. Execution continues at the point in the algorithm where label marks a command.
CALL label. The address of the point immediately following the CALL instruction is conceptually placed on a stack, the Return Stack, and execution continues at the point in the algorithm where label marks a command. The Return Stack is deemed to be empty on entry to the algorithm.
RETURN. If the Return Stack is empty execution of the algorithm is complete. Conceptually, control returns to the program which invoked the algorithm. If the Return Stack is not empty, the last address placed on the stack is removed from it and execution continues at the point indicated by that address.
RESTART from label. The return Stack is emptied and execution continues at the point in the algorithm where label marks a command.
Conditional Commands
IF Statement command. The truth of statement is tested: if it is true the command command is executed, otherwise execution continues following the IF instruction.
WHEN Statement command. The WHEN command is a definition which indicates how the program to which the algorithm passes control may process the information returned to it. This program may issue an IF instruction of the same form as the WHEN command, i.e., the instruction: IF statement command.
OTHERWISE command. The OTHERWISE instruction is written immediately following an IF instruction. If on execution of the IF statement instruction statement was true then the command command in the OTHERWISE instruction is not executed, but execution continues following the OTHERWISE instruction; if statement was false then command is executed.
IF FAILED command. The IF FAILED instruction is used following SWAPs and CHECKs. It may be read as an IF command in which FAILED is the statement that the just executed SWAP or CHECK discovered the inequality of the Old and Current Values.
SWAP (operand-1, operand-2, operand-3).
and
CHECK (operand-1, operand-2). The expressions operand-1 etc. are block descriptors of the form:
Blockname Blocktype
The execution of SWAP and CHECK is as defined respectively in Serializing Hardware Instructions--Operations and non-serial State Verification.
Non-serialized Data Modification Instructions
COPY operand-1 to operand-2, operand-3, . . . : The expressions operand-1 etc. are either all block descriptors or all field descriptors, in the latter case the values of operand-2, etc. are set to the value of operand-1; in the former case the values of all the fields in operand-2, etc. are set to the values of similarly named fields of operand-1, the block types of operand-1, etc. are identical.
SET field to value. The value of the field named by the field descriptor field is set to the value identified by value.
INCREMENT field. The modulus named by the field descriptor field is incremented, as described in List State Control.
Data Definitions
INPUT is field-1, field-2 . . . The expressions field-1, field-2, etc. are field descriptors naming the fields made available to the algorithm by the program that invoked it.
FIELDS of block are type-1 name-1, type-2 name-2, . . . . The expression block is a block type such as Element, the expressions type-1, type-2, etc. are field types such as POINTER, the expressions name-1, name-2, etc. are field names such as Next. Each block of type block is defined as comprising fields type-1 name-1, type-2 name-2, etc.
It should be noted that following a FIELDS definition, the fields of a block will be referred to as name of blockname block, for example:
Next of New Element
OUTPUT is field-1, field-2, . . . The expressions field-1, field-2, etc. are field descriptors naming the fields made available by the algorithm and containing information relevant to the program that invoked it.
Definitions of Synonomy
CONDITION name statement. The expression name is to be read as if it were (i.e. is to be treated as an abbreviation of) the expression statement.
LOCATE blockname blocktype from field. The expression field is a field descriptor of a pointer which points to the block named by blockname blocktype.
It should be noted that if the value in the pointer field is implemented as an address then it may be that no machine instruction will be required to implement this command. If however, pointers are implemented as displacements from a known address, this command may have to be implemented as the calculation of an address from such a displacement.
Definition and Mofidication of Storage Areas
Blocks in public storage are explicitly defined by the appearance of their descriptors in the first operand position of a LOCATE command.
Blocks in storage private to the executing process are implicitly defined by their block descriptor's appearing as the operand or part of an operand of an instruction.
All block types are explicitly defined in FIELDS commands.
Fields within blocks are defined by the definition of their containing blocks and the associated FIELDS commands.
Fields not in blocks, which are all private to the executing process, are either explicitly defined by the appearance of their descriptors in INPUT commands or implicitly defined by their descriptors appearing as the operand of an instruction.
It should be noted that when a field within a block is modified by an instruction such as COPY, SET or INCREMENT, the other fields in that block are unchanged.
ANNEX 2--LAST-IN-FIRST-OUT QUEUE PROGRAM
(for illustration--state of the art algorithm)
Lifo.
INPUT is POINTER Anchor, POINTER Element.
CONDITION Taking is POINTER Element is NULL.
LOCATE Current Anchor from POINTER Anchor.
FIELDS of Anchor are POINTER Head, MODULUS Amod.
FIELDS of Element are POINTER Next.
Retry.
COPY Current Anchor to Old Anchor, New Anchor.
CONDITION Empty is Head of New Anchor is NULL.
IF Empty GO to Void.
IF not Taking GO to Put.
LOCATE Desired Element from Head of Old Anchor.
COPY Next of Desired Element to Head of New Anchor.
IF not Empty INCREMENT Amod of New Anchor.
GO to Swap.
Void.
IF Taking GO to Exit.
PUT.
LOCATE New Element from POINTER Element.
COPY Head of Old Anchor to Next of New Element.
COPY POINTER Element to Head of New Anchor.
Swap.
SWAP (Old Anchor, New Anchor, Current Anchor).
IF FAILED GO to Retry.
EXIT.
OUTPUT IS Head of Old Anchor, POINTER Element.
CONDITION Fail is Taking and Head of Old Anchor is NULL.
WHEN Taking and not Fail
LOCATE Desired Element from Head of Old Anchor.
RETURN.
ANNEX 3--FIRST-IN-FIRST-OUT QUEUE PROGRAM
Fifo.
INPUT is POINTER Anchor, POINTER Element.
CONDITION Taking is POINTER Element is NULL.
LOCATE Current Anchor from POINTER Anchor.
FIELDS of Anchor are POINTER Head, POINTER Tail, MODULUS Amod, SWITCH Bind.
FIELDS of Element are POINTER Next, MODULUS Emod.
Retry.
COPY Current Anchor to Old Anchor, New Anchor.
CONDITION Empty is Head of New Anchor is NULL.
CONDITION Bound is Bind of New Anchor is ON.
IF Empty GO to Void.
IF Bound CALL Unbind.
IF Taking GO to Take.
SET Bind of New Anchor to ON.
GO to Put.
Void.
IF Taking GO to Exit.
COPY POINTER Element to Head of New Anchor.
Put.
LOCATE New Element from POINTER Element.
COPY Tail of New Anchor to Next of New Element.
COPY POINTER Element to Tail of New Anchor.
GO to Swap.
Take.
LOCATE Desired Element from Head of Old Anchor.
CONDITION Singulary is Head of Old Anchor is equal to Tail of Old Anchor.
IF Singulary GO to Single.
COPY Next of Desired Element to Head of New Anchor.
INCREMENT Amod of New Anchor.
GO to Swap.
Single.
SET Head of New Anchor to NULL.
SET Tail of New Anchor to NULL.
Swap.
SWAP (Old Anchor, New Anchor, Current Anchor).
IF FAILED GO to Retry.
Exit.
OUTPUT is Head of Old Anchor, POINTER Element.
CONDITION Fail is Taking and Head of Old Anchor is NULL.
WHEN Taking and not Fail
LOCATE Desired Element from Head of Old Anchor.
RETURN.
Unbind.
SET Bind of New Anchor to OFF.
LOCATE Tail Element from Tail of New Anchor.
COPY Tail Element to Work Element.
LOCATE Sacral Element from Next of Work Element.
COPY Sacral Element to Old Element, Chain Element.
CONDITION Chained is Next of Chain Element is equal to Tail of New Anchor.
IF Chained GO to Check.
COPY Tail of New Anchor to Next Of Chain Element.
INCREMENT Emod of Chain Element.
CALL Check.
SWAP (Old Element, Chain Element, Sacral Element).
IF FAILED RESTART from Retry.
RETURN.
Check.
Check (Old Anchor, Current Anchor).
IF FAILED RESTART from Retry.
RETURN.
ANNEX 4--LAST-IN-FIRST-OUT AND PEIORITY QUEUE PROGRAM
Compl.
INPUT is POINTER Anchor, POINTER Element.
LOCATE Current Anchor from POINTER Anchor.
LOCATE Own Element from POINTER Element.
FIELDS of Anchor are POINTER Head, POINTER Bind, MODULUS Emod, Relation related.
FIELDS of Element are POINTER Next, MODULUS
Emod, PARAMETER Priority.
Retry.
COPY Current Anchor to Old Anchor, New Anchor.
CONDITION Complemented is Bind of New Anchor is not NULL.
CONDITION Bound is Complemented and Bind of New Anchor is not equal to Head of New Anchor.
IF not complemented GO to Normal.
IF not Bound GO to Unbound.
LOCATE Active Element from Bind of New Anchor.
COPY Active Element to Moving Element.
COPY POINTER Anchor to POINTER Previous.
COPY Head of New Anchor to POINTER Following.
CONDITION Listart is POINTER Previous is equal to POINTER Anchor.
CONDITION Listend is POINTER Following is NULL.
Search.
IF Listend GO to Found.
LOCATE Following Element from POINTER Following.
COPY Following Element to Point-from Element.
CALL Check.
IF Priority of Moving Element is related Priority of Point-from Element GO to Found.
COPY Point-from Element to Point-to Element.
COPY POINTER Following to POINTER Previous.
COPY Next of Point-to Element to POINTER Following.
LOCATE Previous Element from POINTER Previous.
GO to Search.
Check.
CHECK (Old Anchor, Current Anchor).
IF FAILED RESTART from Retry.
CHECK (Moving Element, Active Element).
IF FAILED RESTART from Retry.
IF Listart RETURN.
CHECK (Point-to Element, Previous Element).
IF FAILED RESTART from Retry.
OTHERWISE RETURN.
Found.
CONDITION Initial is Next of Moving Element is equal to Bind of New Anchor.
CONDITION Pseudobound is Next of Moving Element is not equal to POINTER Following or Bind of New Anchor is equal to POINTER Previous.
IF Initial GO to Juston.
IF not Pseudobound GO to Insert.
OTHERWISE GO to Unbind.
Juston.
COPY Moving Element to New Element.
COPY POINTER Following to Next of New Element.
INCREMENT Emod of New Element.
SWAP (Moving Element, New Element, Active Element).
IF FAILED GO to Retry.
Insert.
IF Listart GO to Sethead.
COPY Point-to Element to New Element.
COPY Bind of New Anchor to Next of New Element.
INCREMENT Emod of New Element.
SWAP (Point-to Element, New Element, Previous Element).
IF FAILED GO to Retry.
Unbind.
COPY Head of New Anchor to Bind of New Anchor. GO to Unbound.
Sethead.
COPY Bind of New Anchor to Head of New Anchor.
GO to Unbound.
Normal.
CONDITION Empty is Head of New Anchor is NULL.
CONDITION Taking is Next of Own Element is equal to POINTER Element.
IF Empty GO to Void.
IF not Taking GO to Put.
LOCATE Desired Element from Head of Old Anchor.
GO to Take.
Void.
IF Taking GO to Putcomp.
Put.
COPY Head of Old Anchor to Next of Own Element.
COPY POINTER Element to Head of New Anchor.
GO to Swap.
Unbound.
IF Taking GO to Putcomp.
COPY Head of New Anchor to Next of Own Element.
LOCATE Desired Element from Next of Own Element.
COPY Next of Desired Element to Bind of New Anchor.
Take.
COPY Next of Desired Element to Head of New Anchor.
IF not Empty INCREMENT Amod of New Anchor.
GO to Swap.
Putcomp.
COPY POINTER Element to Bind of New Anchor.
Swap.
SWAP (Old Anchor, New Anchor, Current Anchor).
IF FAILED GO to Retry.
Exit.
OUTPUT IS Head of New Anchor, Bind of New Anchor, Bind of Old Anchor, POINTER Element, Next of own Element, Head of Old Anchor.
CONDITION Fail is Bound.
CONDITION Schedule is bind of Old Anchor is not NULL and not Bound.
CONDITION Taken is Head of New Anchor is not equal to POINTER Element. and not Bound and not Schedule.
WHEN Taken
LOCATE Desired Element from Head of Old Anchor.
WHEN Schedule
LOCATE Desired Element from Next of Own Element.
RETURN.
ANNEX 5--GENERAL ALGORITHM
General.
(Preface)
SET SWITCH Ownswitch to OFF.
CONDITION Initiated is SWITCH Ownswitch is ON.
Retry.
COPY Current Anchor to Old Anchor, New Anchor.
Own.
(Test New Anchor)
IF Initiated and not Active
GO to Exit.
IF Not Bound
GO to Unbound.
Clear.
(Identify and Verify next Transaction)
IF Pseudobound
GO to Own.
(Perform next Transaction)
IF FAILED GO to Retry
OTHERWISE GO to Clear.
Unbound.
IF Bindable
GO to Init.
(Perform Own Operation)
IF FAILED GO to Retry.
OTHERWISE GO to Exita.
Init.
(Initiate Own Operation)
IF FAILED GO to Retry.
IF Nonproductive GO to Exitb.
SET SWITCH Ownswitch to ON.
GO to Clear.
Exit.
Exita. Exitb. (Exits)
While the invention has been particularly shown and described with references to a preferred embodiment thereof, it will be understood by those skilled in the art that the foregoing and other changes in form and details may be made therein without departing from the spirit and scope of the invention. | A data processing system in which a process having a low priority may be interrupted by a process having a higher priority and in which an interrupted process ceases its current operation immediately the interrupt occurs, a mechanism by which the higher priority interrupting process finishes the interrupted operation of the lower priority process before commencing its own next operation. | 6 |
FIELD OF THE INVENTION
[0001] The present invention relates to a double-covered yarn having a sparkling effect, a process for making the same, and fabric comprising such a yarn. More specifically, the invention relates to a double covered sparkling yarn comprising a core yarn, a first flat bright polyamide sheath yarn and a second dyed polyamide sheath yarn, wherein the first and the second sheath yarn are wound around the core yarn in the same direction.
BACKGROUND OF THE INVENTION
[0002] Nowadays, numerous textile applications employ covered yarns, such as single covered yarns obtained by winding a sheath yarn around a core yarn, and double-covered yarns obtained by further winding around the single covered yarn a second sheath yarn. When an elastomeric core yarn is employed, the resulting covered yarn may be employed for manufacturing stretch fabrics for various applications, for instance in the field of hosiery, underwear, socks, upper wear, and sportswear. A process for the production of double covered elastomeric yarn is disclosed for instance in U.S. Pat. No. 6,240,716, wherein a spandex core is covered with a first sheath yarn to form a single covered yarn, and a second sheath yarn is wound around the single covered yarn.
[0003] However, in some textile applications such as hosiery, yarns having a sparkling effect may be of interest. In this case the air-jet entangling method is preferably used as it enables the production of yarns having a better luster. Air-jet entangling as a covering process for spandex elastomeric yarn is described for instance in U.S. Pat. No. 3,940,917. However, air-jet covered composite yarns present some drawbacks. Specifically, such composite yarns have loops extending from the covering component which partially obscure knitted stitch openings, resulting in a more opaque look to knitted hosiery. Further, in knitted hosiery the extending loops increase the likelihood that difficulties will be encountered during the knitting operation and when the finished hosiery is in use.
[0004] Therefore, there is a need for a simple and cost effective process for producing dyed yarns having a sparkling effect and which can be easily knitted.
[0005] It is thus an object of the invention to provide a yarn having both a homogeneous color and a sparkling effect all along the yarn.
[0006] It is another object of the invention to provide a dyed sparkling yarn for use in the textile industry, especially for hosiery and fashionable knitted garments.
[0007] It is still another object of the invention to provide a process for manufacturing a dyed sparkling yarn.
[0008] It is still another object of the invention to provide a fabric made of a dyed sparkling yarn.
[0009] Further purposes and advantages of this invention will appear as the description proceeds.
SUMMARY OF THE INVENTION
[0010] In a first aspect, the present invention provides a sparkling dyed double covered yarn comprising:
[0000] (i) a core yarn;
(ii) a first sheath yarn made of a bright polyamide yarn wound around the core yarn to form a single covered yarn; and
(iii) a second sheath yarn made of a dyed polyamide yarn wound around said single covered yarn to form a double covered yarn; wherein the first sheath yarn and the second sheath yarn are wound in the same direction.
[0011] In some specific embodiments of the double covered yarn of the invention, the core yarn is an elastomeric yarn, such as a spandex yarn.
[0012] In some specific embodiments of the double covered yarn of the invention, the first sheath yarn is a bright flat polyamide yarn, especially a bright flat fully drawn polyamide yarn (FDY). In some other embodiments, the first sheath yarn is a bright partially oriented polyamide yarn (POY) or a bright textured polyamide yarn.
[0013] In some specific embodiments of the double covered yarn of the invention, the second sheath yarn is a dyed textured polyamide yarn, a dyed flat polyamide yarn, or a dyed POY yarn.
[0014] In some specific embodiments of the double covered yarn of the invention, the number of turns per meter of the bright polyamide yarn is between 300 and 1800 turns per meter.
[0015] In some specific embodiments of the double covered yarn of the invention, the number of turns per meter of the dyed polyamide yarn is between 300 and 1800 turns per meter.
[0016] A particular embodiment of the sparkling dyed double covered yarn of the invention comprises:
[0000] (i) an elastomeric core yarn;
(ii) a first sheath yarn made of a bright flat fully drawn polyamide yarn wound around the core yarn to form a single covered yarn; and
(iii) a second sheath yarn made of a dyed textured polyamide yarn wound around said single covered yarn to form a double covered yarn; wherein the first sheath yarn and the second sheath yarn are wound in the same direction.
[0017] In a second aspect, the invention provides a process for manufacturing a sparkling dyed double covered yarn comprising the steps of:
[0000] (i) providing a core yarn;
(ii) winding a first sheath yarn made of a bright polyamide yarn around said core yarn to form a single covered yarn; and
(iii) winding a second sheath yarn made of a dyed polyamide yarn around said single covered yarn to form a double covered yarn; wherein the first and the second sheath yarn are wound in the same direction.
[0018] In some specific embodiments of the process of the invention, the core yarn is an elastomeric yarn, such as a spandex yarn.
[0019] In some specific embodiments of the process of the invention, the first sheath yarn is a bright flat polyamide yarn, especially a bright flat fully drawn polyamide yarn (FDY). In some other embodiments, the first sheath yarn is a bright partially oriented polyamide yarn (POY) or a bright textured polyamide yarn.
[0020] In some specific embodiments of the process of the invention, the second sheath yarn is a dyed textured polyamide yarn, a dyed flat polyamide yarn, or a dyed POY yarn.
[0021] In some specific embodiments of the process of the invention, the winding speed of the bright polyamide yarn is between 300 and 1800 turns per meter.
[0022] In some specific embodiments of the process of the invention, the winding speed of the dyed polyamide yarn is between 300 and 1800 turns per meter.
[0023] In a third aspect, the invention provides a fabric comprising a sparkling dyed double covered yarn as described above.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] The above and other characteristics and advantages of the invention will be more readily apparent through the following examples, and with reference to the appended drawings, wherein:
[0025] FIG. 1 is a drawing showing the structure of an embodiment of the double covered yarn of the invention ( 40 ): core yarn ( 10 ), bright yarn ( 20 ) and dyed yarn ( 30 ); and
[0026] FIG. 2 is a drawing showing an embodiment of the double cover process of the invention: core yarn feeding bobbin ( 1 ), core yarn ( 10 ), bright yarn bottom spool ( 2 ), bright yarn ( 20 ), dyed yarn upper spool ( 3 ), dyed yarn ( 30 ), double covered yarn ( 40 ), double covered yarn receiving bobbin ( 4 ).
DETAILED DESCRIPTION
[0027] It has been surprisingly found by the inventors that a sparkling colored yarn can be obtained by winding a first bright sheath yarn around a core yarn, and by further winding a second dyed sheath yarn around the first bright sheath yarn, the first and the second sheath yarn being wound in the same orientation. The resulting double covered yarn can be easily knitted into fabrics which show both a homogenous color and a uniformly distributed sparkling effect.
[0028] As used herein, the terms “core yarn” or “core fiber” refer to a central yarn around which a first and a second sheath yarns are wound. The core yarn may be elastomeric or non-elastomeric. In a specific embodiment of the invention, the core yarn is a spandex yarn.
[0029] The term “spandex” and “elastan” are used interchangeably and means a manufactured fiber in which the fiber-forming substance is a long chain synthetic elastomer comprised of a polyurethane-polyurea copolymer. Spandex in the range of about 11 to 350 decitex is suitable for use in making the double covered yarn of the present invention.
[0030] As used herein, the expression “sheath yarn” means a yarn comprising continuous filaments, bundled staple fibers, or spun staple fibers, or both filaments and staple fibers.
[0031] The “first sheath yarn” is the sheath yarn wound around the core yarn to form a single covered yarn. Suitable first sheath yarns for use in the present invention are bright flat yarns (especially fully drawn yarn FDY), bright partially oriented (POY) polyamide yarns or bright textured yarns. First sheath yarns may have a round, an oval or a trilobal cross-section. Examples of suitable first sheath bright yarns for use in the present invention are Nylon 6.6 FLAT 22/7 BR trilobal (Nilit®Fibers), Nylon 6.6 FLAT 17/4 BR oval (Nilit®Fibers), Nylon 6.6 FLAT 17/3 BR trilobal (Nilit®Fibers) and Nylon 6.6 FLAT 44/34 BR trilobal (Nilit®Fibers), Nylon 6.6 POY 27/7 BR trilobal (Nilit®Fibers), Nylon 6.6 POY 17/3 BR trilobal (Nilit®Fibers), Nylon 6.6 POY 22/7 BR trilobal (Nilit®Fibers) and Nylon 6.6 POY 27/12 BR trilobal (Nilit®Fibers).
[0032] The “second sheath yarn” is the sheath yarn wound around the single covered yarn to form a double covered yarn. Examples of suitable second sheath yarns for use in the present invention are made of natural or dyed polyamide (e.g. spin dyed polyamide), and can be either textured, flat or POY yarns. An example of a suitable second sheath yarn for use in the present invention is the Nylon 6.6 TEXTURED 44/34/1 BK (spin-dyed black yarn) from Nilit®Fibers.
[0033] The terms “bright”, “brilliant”, “shiny”, and “glossy” are used herein interchangeably and refer to the glossy effect of the first sheath yarn. The term “sparkling” is used herein to define the effect produced by the double covered yarn of the invention (which is comparable to the sparkling of a diamond), this effect resulting from the specific arrangement of the two sheath yarns (a dyed yarn and a bright yarn) around the core yarn.
[0034] The first and second sheath yarns of the sparkling double covered yarn of the present invention have an identical twist orientation, i.e. both in the z-direction or both in the s-direction ( FIG. 1 ). In the method of the invention the first sheath yarn wound around the core yarn is made of a bright polyamide yarn, whereas the second sheath yarn wound around the first sheath is made of a dyed polyamide yarn. This allows a uniform distribution of the color and the shining effect along the double-covered yarn and generates a uniform sparkling effect along the manufactured yarn. The number of twists (or turns) of each of the first sheath yarn and the second sheath yarn may be similar or different according to the intensity of the sparkling effect which is required (i.e. more or less shiny, more or less colored). For instance, if the number of twists of the bright sheath yarn is more important than the number of twists of the dyed sheath yarn, the resulting double covered yarn is shinier and less color effect is perceptible.
[0035] The sparkling double covered yarn of the invention may be manufactured with any standard double covering machine. A bright polyamide yarn is placed on a bottom spool and a dyed polyamide yarn is placed on an upper spool ( FIG. 2 ). The core yarn enters the machine from the bottom and is first covered with the flat bright sheath polyamide yarn at about 300-1800 turns per meter to form a single covered yarn. The single covered yarn is then covered with the second dyed sheath polyamide yarn, which is wound in the same direction is about 300-1800 turns per meter. The number of twists per meter and the winding speed of each of the bright yarn and the dyed yarn may be adjusted so as to obtain the desired sparkling effect.
[0000] The present invention is further described by the following examples which are not intended to limit the scope of the present invention, which scope is defined by the appended claims.
Example 1
[0036] In this example, production of a sparkling black double covered yarn was done on a double covering machine Menegatto model 1500, with the following covering settings and yarn properties:
[0000] Core Yarn First sheath yarn Second sheath yarn Reference PA 66 17Dtex Nylon 6.6 FLAT Nylon 6.6 TXT Mobilon ™ 22/7 BR 44/34/1 Black (Nisshinbo (Nilit ®Fibers) (Nilit ®Fibers) Chemical) Speed 1600 m/min 1600 m/min 1400 m/min Tension 4 g 4 g 8 g Turns per NA 800 800 meters (tpm)
The core yarn has the following characteristics: draw ratio of elastan 3.00, tenacity 3.9 cN/dtex, elongation 43.3%, and 1% oil. The Nylon 6.6 FLAT 22/7 BR is a fully drawn yarn (FDY).
As a result of the above process, a sparkling black double covered elastic yarn was produced according to the method above. This sparkling black double covered yarn glistens with a delicate, refined shine and may be further used for the manufacture of fashionable knitted stretch garments. | The present invention provides a sparkling dyed double covered yarn comprising: (i) a core yarn; (ii) a first sheath yarn made of a bright polyamide yarn wound around the core yarn to form a single covered yarn; and (iii) a second sheath yarn made of a dyed polyamide yarn wound around said single covered yarn to form a double covered yarn; wherein the first sheath yarn and the second sheath yarn are wound in the same direction. The invention further provides processes for manufacturing a sparkling dyed double covered yarn and fabrics comprising the same. | 3 |
CROSS-REFERENCES TO RELATED APPLICATIONS
Not applicable
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT
Not applicable.
BACKGROUND OF THE INVENTION
(1) Field of the Invention
The inventive concept disclosed is, in a very general sense, related to different embodiments of cooking apparatuses that are used for supporting a single pot or cooking utensil directly atop a heat source. For instance, typical gas or electric cooktop grates have been designed to support small and large pots that span the entire area above a burner on the cooktop. However, in a completely different application of such mechanisms, the inventive concept described herein is concerned with a mechanism for the support of pots, and other containers of foodstuffs directly above an outdoor cooking grill or smoker.
(2) Description of the Related Art, Including Information Disclosed Under 37 CFR 1.97 and 1.98
The following materials present inventive concepts that feature devices designed to perform cooking functions related to the general area of the disclosure herein.
US Published Patent Application #2011/0290231 (Dec. 1, 2011) A gas burner includes a burner body and a simmer plate assembly. The burner body includes a central cavity in which at least one flame is provided. The simmer plate assembly includes a plate portion and a base portion configured to support the plate portion. The assembly is configured to be at least partially and removably inserted into the central cavity. The plate portion is configured to act as a barrier between the at least one flame and a heated object placed above the gas burner.
U.S. Pat. No. 7,650,882 (Jan. 26, 2010) A pot support for a ceramic glass cooktop having integrally formed grates. The pot support is formed of a material able to withstand gas cooking temperatures without substantial alteration of its shape or composition. The pot support is configured to rest in a stable position over a gas burner head to support a relatively small diameter utensil centered over the burner head and to cooperate with the integrally formed grate to support large or small diameter utensils that are supported over the burner off-center relative to the grate.
U.S. Pat. No. 7,661,421 (Feb. 16, 2010) A wok support ring supports the weight of a wok and food items to be cooked in the wok and imparts a rocking motion to the wok as it is moved in a back and forth motion by the worker. A wok rocking device includes the use of a wok support base which moves in a rocking motion via cam tracks with roller followers. When the worker pulls the wok in a back and forth motion, the rollers follow the cam track to cause the wok to rise rapidly and then rock forward near the end of the stroke. A wok rocking device also can utilize movable linkages attached to a wok support base in order to create the rocking motion needed to mix and fold the food items within the wok.
U.S. Pat. No. 6,470,879 (Oct. 29, 2002) The cooking apparatus includes a glass-ceramic panel (1), which has at least one cooking area; a gas burner (3) providing an open flame (3); a cooking vessel support (5) including feet (5b) and a resting surface for a cooking vessel (6) placed on the cooking vessel support (5); and a device for holding the cooking vessel support (5) mechanically fixed and centered over the gas burner (3) including a foot holding device for holding the cooking vessel support (5). The foot holding device includes foot holders (7) for the respective feet, which are preferably formed by depressed or raised regions in the glass-ceramic panel or foot holder parts attached to it.
U.S. Pat. No. 6,196,212 (Mar. 6, 2001) The cooking apparatus includes a glass or glass-ceramic plate (1) providing a cooking surface with a cooking area and provided with a through-going opening (2) in the cooking area; a gas burner (3, 19, 21) arranged in or under the throughgoing opening (2) in the glass or glass-ceramic plate (1), which has a burner ring (3b) for supporting an open flame (3a, 19a, 21a); a cooking vessel support (5,5a) arranged on the glass or glass-ceramic plate over the through-going opening (2) which has a resting surface for a cooking vessel (6) and a device for supplying a mixture of combustible gas and primary air to the burner ring (3b) to form the open flame, whereby substantially all of the secondary air is drawn from a chamber or space under the glass or glass-ceramic plate (1).
U.S. Pat. No. 4,832,295 (May 23, 1989) A fondue stand having four vertically upstanding partition walls defining upper edge surfaces upon which is supported a fondue pot. The vertical partition walls are angularly spaced apart on a main supporting frame such that, when the fondue pot is supported on the upper edge surfaces, the partition walls lie in vertical planes offset from, or at an angle to, the vertical planes containing the diameters of the circular cross section of the fondue pot. In an alternative embodiment, a security ring for a stove range is provided, with the main body portion being circular and having a central cutout from which extends a hollow central hub insertable into the circular opening of the range of the stove, for supporting pots and pans in a safe manner on the range.
U.S. Pat. No. 4,337,752 (Jul. 6, 1982) A collar-like device for reducing lateral heat dissipation from range top heating elements during cooking operations. An integrally-formed annular collar means of generally frusto-conical configuration is adapted to rest atop a range, in surrounding relation to a heating element disposed on said range top. A generally toroidally-shaped pocket of heated air surrounds an item of cookware adjacent its lower portion when such cookware is slideably received within the opening of the collar-like device surrounding the element. A first alternative embodiment has a hollow collar so that a dead air space interiorly of the collar-like device provides an additional thermal barrier. A second alternative embodiment provides a plurality of successively smaller nesting collars to accommodate cookware of differing sizes.
U.S. Pat. No. 4,305,559 (Dec. 15, 1981) The present invention is a round-bottom flask support which comprises a base of honeycomb or honeycomb-like material flat on its lower surface and having a concave upper surface substantially complementary to the flask it is designed to support. The cross section of the base is preferably cylindrical and a cylindrical annular ring engaging the periphery of the base and upper surface can be provided for added dimension stability. The upper surface of the base preferably has a semi-spherical configuration produced by compression of the upper surface of the base toward the lower surface to create “pleats” in at least some cell walls. This provides an added mechanical lock at the cell nodes which reduces the tendency of the honeycomb to separate at the cell nodes and is of particular advantage where the honeycomb is subjected to high temperatures and the adhesive bond may be weakened. The honeycomb base is usually aligned so that the cells extend transversely to the lower surface of the base and at least some cells usually communicate between the lower surface and the upper surface of the base.
U.S. Pat. No. 4,126,120 (Nov. 21, 1978; Bourboulis) Apparatus for distributing heat from a heat source relatively evenly over the bottom of a vessel to be heated is disclosed. A first annular element is provided which includes an upwardly concave dish-shaped annulus circumscribing a hollow center. A releasable connecting element of a first type is located on the underside of the first annular element. A second annular element includes an upwardly concave dish-shaped annulus which is larger than the annulus of the first annular element. A releasable connecting element of a second type complementary to the first type is located on the inner periphery of the annulus of the second annular element so that the elements can be locked together for use and disassembled for cleaning.
BRIEF SUMMARY OF THE INVENTION
The device disclosed is essentially a support means for a pot or other cooking vessel, the device being removably affixed to the upper portion of an outdoor cooking grill or smoker. The support device is formed form preferably aluminum or other material having similar physical characteristics. The support device is configured by joining three identically-shaped rectangular bands at a common junction corresponding to the midpoint of each of the three bands. A series of symmetrical bends are placed at specific intervals along the length of each band such that the cumulative shape of the adjoined bands forms a virtually spherical grid. An arrangement of spring tension coils joins diametrically-opposed rectangular bands to each other. The bands, by forming the spherical shape, and the spring tension coils, enable a balanced, stable grip of the support grid atop an outdoor cooking grill or smoker.
The bottom-most segment of the support device comprises six “feet” emanating from each end of the three bands, the feet being of a semi-rigid elasticity such that the support device may be affixed to the top of the outdoor grill. The support device is further able to withstand cooking temperatures commonly encountered in the use of outdoor grills or smokers. The support device is configured to rest in a stable position centered over the top or smokestack of the outdoor grill. The support device can thereby accommodate a relatively small diameter pot or cooking utensil centered over the top of the outdoor grill.
BRIEF DESCRIPTION OF THE VIEWS OF THE DRAWINGS
FIG. 1 is a three-dimensional view of the support grid 1 showing an assemblage of three symmetrically-bent metallic bands.
FIG. 2 is a profile view common to each of the three bands which comprise the support grid, in particular is shown the first band 5 , and further showing the pattern of bends, arcs, rounds, and linear segments
FIG. 3 illustrates a profile view of the second band 5 ( a ), and further showing opposing tension coil springs 15 ( a ), 16 ( a ) as they are attached to the opposite sides of the second band 5 ( a ), in conjunction with a connection to a center junction ring 11 .
FIG. 4 depicts a left or right tab 18 , 22 the tabs utilized for attachment to the inner surface of each of the bands 5 , 5 ( a ), 5 ( b ) thereby facilitating the connection of the tension coil springs to the interior of the support grid.
FIG. 5 illustrates, from top to bottom, a center bolt 7 , a center locking washer 8 , and a center nut 9 , each of these three components used to conjointly attach all three bands 5 , 5 ( a ), 5 ( b ), through their respective center apertures.
DETAILED DESCRIPTION OF THE INVENTION
The objects, features, and advantages of the concept presented in this application are more readily understood when referring to the accompanying drawings. The drawings, totaling five figures, show the basic components and functions of embodiments and/or methods of use. In the several figures, like reference numbers are used in each figure to correspond to the same component as may be depicted in other figures.
The discussion of the present inventive concept will be initiated with FIG. 1 , which illustrates the support grid 1 in the configuration as a finished product which would be used by a consumer.
The disclosed support grid 1 comprises three identical, primarily longitudinal, conjoined metallic bands, being a first band 5 , a second band 5 ( a ), and a third band 5 ( b ). The three bands 5 , 5 ( a ), 5 ( b ) are composed of a semi-rigid material, enabling a flexing of each of the bands 5 , 5 ( a ), 5 ( b ) as may be desired by a user to. A general perspective view of the inventive concept in its intended utilization is depicted in FIG. 1 . In the various drawing figures disclosed, all three bands 5 ( a ), 5 ( b ), 5 ( c ) have identical components, configurations and dimensions. Therefore, these identical items for the second and third bands 5 ( a ), 5 ( b ) will be further distinguished by attachment of the sub-letter (a) or (b), respectively, to the components of the second and third bands 5 ( a ), 5 ( b ).
To form the support grid 1 , all three bands 5 , 5 ( a ), 5 ( b ) are conjoined at their respective center apertures 6 , 6 ( a ). 6 ( b ) (not visible in FIG. 1 ) by any of a variety of fastening means. In the preferred embodiment, a bolt 7 , a corresponding lock washer 8 , and nut 9 (collectively shown in FIG. 5 ) are used to conjointly fasten each of the three bands 5 , 5 ( a ), 5 ( b ) through their respective apertures 6 , 6 ( a ), 6 ( b ) located at the midpoint of each band 5 , 5 ( a ), 5 ( b ). By viewing FIG. 1 , it can be seen that a systematic and symmetrical bending of the three bands 5 , 5 ( a ), 5 ( b ) results in the formation of six relatively vertical legs culminating in six diametrically opposed boots 41 - 42 , 41 ( a )- 42 ( a ), and 41 ( b )- 42 ( b ).
The fastening means is tightened securely, yet still allowing restricted freedom of rotation of the three bands 5 , 5 ( a ), 5 ( b ) about the axis of the bolt 7 . The support grid 1 , in its intended use, is most stable and effective by a user symmetrically spreading the three bands 5 , 5 ( a ), and 5 ( b ) radially with respect to the axis of the bolt 7 . In this manner, each of the bands 5 , 5 ( a ), 5 ( b ) is oriented, from one to the other, by a separation angle of approximately sixty (60) degrees. This enables the six relatively horizontally opposed boots 41 - 42 , 41 ( a )- 42 ( a ), and 41 ( b )- 42 ( b ) of each of the three bands 5 , 5 ( a ), and 5 ( b ) to be placed atop a cooking grill or smoker in a stable and laterally balanced manner.
For better clarification of the profile and configuration of each of the three bands 5 , 5 ( a ), 5 ( b ), a profile view of the first band 5 is shown in FIG. 2 . The profile of the first band 5 is identical to the profiles of the second and third bands 5 ( a ), 5 ( b ). In FIG. 2 there is shown a sequence of varying bends, arcs, and rounds ( 50 - 59 ) made orthogonally transverse to the first band 5 , which all emanate from, or transform into, linear sections ( 30 - 40 ) of the first band 5 . As can be seen, the first band 5 is symmetrical with respect to the left side in comparison to right side of the first band 5 .
In the preferred embodiment, the general dimensions of each band 5 , 5 ( a ), and 5 ( b ) prior to the symmetrical transverse bending along the length of the bands 5 , 5 ( a ), 5 ( b ), comprise 25.0 inches in length, 1.0 inch in width, and 0.125 inch thick. The boots 41 - 42 , 41 ( a )- 42 ( a ), and 41 ( b )- 42 ( b ) are approximately 1.00 to 1.25 inch in length. These dimensions may be varied in accordance with the type and size of outdoor grill or smoker upon which the support grid 1 will be affixed. When each band 5 , 5 ( a ), 5 ( b ) has undergone the symmetrical bending, the resulting support grid 1 has general dimensions of 9.25 inches from left to right and 6.25 inches from top to bottom. The symmetrical bending of the bands 5 , 5 ( a ), 5 ( b ) thereby forms an inner surface 27 of each band composing the support grid 1 .
Again referring to FIG. 2 , a description of the first band 5 will be conducted in a clockwise manner, initiated at the bottom left section of the first band 5 . A horizontally-oriented segment, termed the “left foot” 30 is the starting point. Continuing to the left of the left foot 30 , an arcuate, ninety-degree bend forms a “left heel” 50 of the band 5 , which then transcends upwardly to form a relatively straight segment comprising a “left leg” 31 of the band 5 . From this point, proceeding upward, a slight bend, termed a “left mid-bend” 51 of approximately ten degrees occurs, which then transforms into a linear segment termed a “left incline” 32 .
Next, in FIG. 2 , there appears an arcuate bend of approximately eighty degrees, entitled a “left inward arc” 52 which transforms into a horizontal “left flat” 33 section, measuring approximately 1.0 inch in the preferred embodiment. Immediately after the left flat 33 occurs a “left outer round” 53 , comprising a ninety degree bend, and forming a vertical segment, termed a “left brace” 34 . Following the left brace 34 is a “left inner round” 54 of ninety degrees resulting in a horizontal segment referred to as a “top surface” 35 .
The top surface 35 features a center aperture 6 (integral to all three bands 5 , 5 ( a ), 5 ( b )), through which a type of fastener may be inserted to join all three bands at a common point. The preferred means of fastening comprises a bolt 7 , fastened by a corresponding lock washer 7 and nut 9 (all shown in FIG. 5 ). The top surface 35 extends rightward and the bends and linear segments previously described occur in the reverse order on the right side of the center aperture 6 . From the center aperture 6 , the sequential description of the first band 5 continues clockwise, with a right inner round 55 , a right brace 36 , a right outer round 56 , a right flat 37 , a right inward arc 57 , a right incline 38 , a right mid-bend 58 , a right leg 39 , a right heel 59 , and a right foot 40 .
It is to be noted that the left foot 30 and the right foot 40 are respectively covered by a boot 41 and 42 , respectively. During the manufacturing process, the boots 41 , 42 are constructed of elastomeric material. This elastomeric material is formed from a process comprising a coating of a plastic dip-type substance which securely adheres to each foot 30 , 40 for a length of approximately 1.0 inch of each foot 30 , 40 .
Further details essential in the description of the first band 5 , include a left side aperture 25 , drilled through the left incline 32 , and a right side aperture 26 drilled through the right incline 38 . Each of these apertures 25 , 26 on opposite sides of the band 5 serve to facilitate the fastening of a rigid left tab 18 and a rigid right tab 22 (shown in FIG. 3 and FIG. 4 ) to the respective inner surfaces 27 of the left and right inclines 32 , 38 . In viewing FIG. 4 , there is illustrated a depiction of a tab 18 , 22 (typical of either a left or right tab 18 , 22 ). The tab 18 , 22 is attached to the inner surface 27 of the directly opposed left and right inclines 32 , 38 , respectively, of each of the bands 5 , 5 ( a ), 5 ( b ).
Both the left and/or right tab 18 , 22 are identical to each other and comprise essentially an oblong, rigid structure bent at an angle of approximately forty-five degrees. Each tab 18 , 22 is further shown having a circular opening 17 , 21 in the upper section of each tab 18 , 22 and an oval opening 19 , 23 in the lower section of the tab 18 , 22 . A threaded fastener may be used to securely attach each tab 18 , 22 to the respective left and right inclines 32 , 38 of the first band 5 . This is done by insertion of the fastener through the left side aperture 25 and into the left circular hole 17 of the left tab 18 . Likewise, the fastener is inserted through the right side aperture 26 and right circular hole 21 of the right tab 22 . In the preferred embodiment, the fastener comprises a rivet 24 ( a ) integral to the left/right incline 32 , 38 and co-axial with the respective left- and right-side apertures 25 , 26 .
Reference is made to FIG. 3 , which depicts the second band 5 ( a ) in its final stage of manufacture/assembly. Two tabs 18 ( a ), 22 ( a ) are secured in place onto their respective left and/or right incline 32 ( a ), 38 ( a ). Shown are a first tension coil spring 15 ( a ), a center closed junction ring 11 , and a second tension coil spring 16 ( a ) are linearly joined to provide a linear, tensioned connection of the left tab 18 ( a ) to the right tab 22 ( a ).
Further details of FIG. 3 show that the first tension coil spring 15 ( a ) culminates with a coil inner hook 14 on one end and a coil outer hook 13 on the opposite end. Also shown is an identical second tension coil spring 16 ( a ) with its coil inner hook 14 and a coil outer hook 13 . The center closed junction ring 11 , which is essentially a closed circular ring, serves as a common connecting point for the inner hook 14 of the first tension coil spring 15 ( a ) and the inner hook 14 of the second tension coil spring 16 ( a ). The outer hook 13 of the first tension coil spring 15 ( a ) and the outer hook 13 of the second tension coil spring 16 ( a ) are connected to the respective left tab 18 ( a ) and right tab 22 ( a ), thereby providing a spring-loaded connection of the left incline 32 ( a ) of the second band 5 ( a ) to its right incline 38 ( a ). In an identical manner, the left side and right side of the first band 5 and the third band 5 ( b ) are provided with the exact spring-loaded connection arrangement.
The accumulative effect of the aligned pairs of tension coil springs 15 - 16 , 15 ( a )- 16 ( a ), and 15 ( b )- 16 ( b ) provide a leveraged, inward-directed force downward to the boots 41 - 42 , 41 ( a )- 42 ( a ), and 41 ( b )- 42 ( b ) of the support grid 1 . Therefore, there is a stabilized, friction-enhanced gripping force for the support grid 1 against the generally rounded exterior of an outdoor grill or smoker.
In the preferred embodiment, each band 5 , 5 ( a ), 5 ( b ), prior to the bending process, comprises dimensions of approximately 25.0 inches in length, 1.0 inches in width, and 0.125 inch in thickness. The dimensions of the bands 5 , 5 ( a ), 5 ( b ) may vary in accordance with the physical characteristics of the particular material used to fabricate the bands 5 , 5 ( a ), 5 ( b ). The support grid 1 itself is formed by the permanent fastening of the first band 5 , the second band 5 ( a ), and the third band 5 b ) to each other at overlapping positions corresponding to the center aperture 6 in the top side 35 , 35 ( a ), 35 ( b ) of each respective band 5 , 5 ( a ), 5 ( b ).
While preferred embodiments of the present inventive concept have been shown and disclosed herein, it will be obvious to those persons skilled in the art that such embodiments are presented by way of example only, and not as a limitation to the scope of the inventive concept. Numerous variations, changes, and substitutions may occur or be suggested to those skilled in the art without departing from the intent, scope, and totality of this inventive concept. Such variations, changes, and substitutions may involve other features which are already known per se and which may be used instead of, in combination with, or in addition to features already disclosed herein. Accordingly, it is intended that this inventive concept be inclusive of such variations, changes, and substitutions, and by no means limited by the scope of the claims presented herein. | Disclosed is a grid-like device for the support of the bottom exterior surface of a cooking vessel, the grid being removably placed atop the upper exterior surface of an outdoor cooking grill or smoker. Three identically-shaped and symmetrically bent metal rectangular bands are conjoined at their midpoints to form essentially a spherical grid shape. A series of symmetrical bends, arcs, and rounds are formed at specific intervals transverse to the length of each band such that the cumulative shape of the adjoined bands forms the grid. The bottom-most segment of the support grid comprises legs and feet of a semi-rigid elasticity such that the support device may be flexibly placed about the top of the grill or smoker. Spring tension coils connect the inner surfaces of the bands to stabilize the grid shape and to impart leveraged gripping force upon the feet of the grid. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to a system for setting markings on a fabric, such as a skirt, on an apparel manufacturing process. More particularly, the present invention relates to method and apparatus for setting markings on a fabric under steam heat pressure, which markings are used to make pleats and darts in an apparel. The markings are automatically set without the use of a hand-operated marker, such as chalk and pencil, and a pattern paper, and therefore the system of the present invention is adapted for use in an automatic mass-producing line.
2. Description of the Prior Art
In an apparel manufacturing markings become unavoidably necessary. It is the common practise to draw lines, dots or any other forms of markings with the use of chalk, a pencil or other hand-operated markers, wherein the markings are drawn with the help of a pattern paper. However, this practise is not applicable to a mass-producing process because of its labor-and time-consuming operation. For example, in a skirt manufacturing, pleating is important, but it is notoriously a time-consuming work. This is a main reason for the high price of pleated skirts.
The present invention aims at overcoming the difficulties and disadvantages pointed out with respect to the conventional practice, and has for its object to provide an improved method and apparatus for setting markings at desired places on a fabric without the use of any pattern paper or a hand-operated marker, such as chalk or a pencil.
Other objects and advantages of the present invention will become apparent from the following description and the accompanying drawings.
SUMMARY OF THE INVENTION
According to the present invention, a system for setting markings on a fabric includes a working table which allows heat steam to pass therethrough, and a pressing means which is moved up and down, the working table and the pressing means each including protruded portions adapted to come into direct contact with a material placed on the working table, the protruded portions being made of heat conducing material so as to become heated at a heated atmosphere.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic front view of a mark setting apparatus according to the present invention;
FIG. 2 is a schematic side view of the apparatus in FIG. 1;
FIG. 3 is a plan view of a working table included in the apparatus;
FIG. 4 is a vertical cross-section through the working table in FIG. 3;
FIG. 4a is a cross-section on specially enlarged scale of the portion circled in FIG. 4;
FIG. 5 is a plan view of a pressing frame included in the apparatus;
FIG. 6 is a vertical cross-section through the pressing frame in FIG. 5;
FIG. 7 is an explanatory view of the pressing frame and the working table when they are in operation;
FIG. 8 is a perspective view of a skirt made of a material processed by the apparatus;
FIG. 9 is a perspective view of a different kind of skirt;
FIG. 10 is a plan view of a modified version of the pressing frame; and
FIG. 11 is a perspective bottom view of a further modified version of the pressing frame.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIGS. 1 and 2 the reference numeral 1 designates a working table horizontally supported about 1000 mm above the floor. Above this working table 1 there is provided a pressing frame 2 which is carried on four pillars 3 through rollers 4. Thus the pressing frame 2 is enabled to vertically move to and from the working table 1, during which a material (a) on the working table is pressed by the pressing frame 2.
As shown in FIGS. 3 and 4, the working table 1 is provided with a porous plate 6 in which a number of pores 5 are produced, a metal net 7 and a mat 8. On the mat 8 an appropriate number of metal bars 9 are crosswisely provided at equal intervals. The working table is covered with a cushioning 10 (hereinafter referred to as the lower cushioning when contrasted with another cushioning on the pressing frame), wherein the cushioning is divided into small parts so as to allow the metal bars 9 to be located therebetween. The working table 1 is provided with a steam reservoir 11 at its bottom. When a heat steam is introduced into the reservoir 11, the steam rises up through the porous plate 6, the metal net 7, the mat 8, and the lower cushioning 10, thereby producing a heated atmosphere on the working table 1.
For the metal bar 9 a thin aluminium bar is preferably employed because of its good thermal conductivity, workability and anti-rust property, but an iron bar can be effectively employed. The metal bar is L-shaped in its cross-section, and is provided with apertures 12 in its erected wall so as to allow a screw bar 13 to pass through as shown in FIG. 4. The screw bar 13 is made of stainless steel, and each metal bar 9 is locked to the screw bar 13 by means of nuts 14. The interval between the adjacent metal bars is determined with the design or type of an apparel to be made.
The cushioning 10 is preferably covered with a white cloth 15 on which, when required, patterns can be drawn as guides. In addition, it is preferred that each upper edge of the metal bars 9 is flush with the cushioning 10 or slightly protrudes.
Referring to FIGS. 5 and 6 the pressing frame 2 includes an outer frame 16 in which several pipes 17 are transversely supported at intervals. Each pipe 17 is adapted to allow a heat steam to pass through, and as shown in FIG. 6, each pipe 17 rests on a metal net 18 under which an upper cushioning 19 is provided. The outer frame 16 are bound by several metal strings 20, wherein each string includes a tightener 21. It is preferred that each string 20 is flush with the undersurface of the upper cushioning 19, or slightly protrudes from it.
In operation, a material (a) is placed on the working table 1 with the pressing frame 2 being kept above the working table. The pressing frame 2 is gradually lowered, and presses the material (a) against the working table 1 by gravity. As shown in FIG. 7, the material (a) is compressed between the upper and lower cushionings 10 and 19, wherein the upper edges of the metal bars 9 and the protruded portions of the metal strings 20 are alternately placed into contact with the material (a). In this way the material (a) is provided with markings in the form of grooves.
At this stage a heat steam is introduced into the tank 11, which steam passes through the metal net 7, the mat 8, the lower cushioning 10, and reaches the material (a) placed between the working table and the pressing frame. The metal bars 9 and the metal strings 20 are heated by the steam, and the material (a) becomes moist. When the material (a) is made of knitted fabrics, the steam at about 135° C. can be effectively supplied for about 3 seconds.
Subsequently, a hot air at about 125° C. is introduced into the tank 11 for about 3 seconds, and a heat steam is also supplied into the pipes 17 so as to dry the material (a) as it is placed between the working table and the pressing frame. When it is found that the material (a) has dried up, the supply of the heat steam into the pipes 17 is stopped, and the hot air remaining between the working table and the pressing frame is sucked at a vacuum so as to allow the material (a) to cool down. Finally, the pressing frame 2 is raised, and the material (a) is made ready to be taken out.
The material (a) is used to make a skirt (A), and the markings in the material (a) make skirt pleats 24 as shown in FIG. 8.
In the illustrated example it has been shown how to produce pleats in a skirt, but the present invention is not limited to the production of pleats. For example, as shown in FIG. 9 darts 22 can be made in addition to the pleats 24. In this case the working table 1 is provided with long metal bars 9b and short metal bars 9a wherein the long bars work to make the pleats 24 while the short bars work to make the darts 22.
When folds are to be made in a skirt, marking blades 23 are provided on the undersurface of the pressing frame 2 as shown in FIG. 11, wherein the position of the marking blades are appropriately determined. The marking blades are likewise made of a thermal conductive material. The shapes and sizes of the metal bars and the marking blades are determined as desired. | A system for setting markings in a fabric, in which a material is pressed at a heat steam and hot air atmosphere under upward and downward loads, the loads being applied thereto by means of protruded pressing means of heat conducing material. | 3 |
CROSS-REFERENCE
[0001] This application claims priority to and is a continuation of U.S. patent application Ser. No. 14/949,675, filed Nov. 23, 2015, which is a continuation of U.S. patent application Ser. No. 14/742,663, filed Jun. 17, 2015, which is a continuation of U.S. patent application Ser. No. 14/184,047, filed Feb. 19, 2014, which is a continuation of U.S. patent application Ser. No. 13/588,966, filed Aug. 17, 2012, which is a continuation of U.S. patent application Ser. No. 11/328,970, filed Jan. 9, 2006, which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 60/643,056, filed Jan. 10, 2005, the full disclosures of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to ophthalmic surgical procedures and systems.
BACKGROUND OF THE INVENTION
[0003] Cataract extraction is one of the most commonly performed surgical procedures in the world with estimates of 2.5 million cases being performed annually in the United States and 9.1 million cases worldwide. This is expected to increase to approximately 13.3 million cases by 2006 globally. This market is composed of various segments including intraocular lenses for implantation, viscoelastic polymers to facilitate surgical maneuvers, disposable instrumentation including ultrasonic phacoemulsification tips, tubing, and various knives and forceps. Modern cataract surgery is typically performed using a technique termed phacoemulsification in which an ultrasonic tip with an associated water stream for cooling purposes is used to sculpt the relatively hard nucleus of the lens after performance of an opening in the anterior lens capsule termed anterior capsulotomy or more recently capsulorhexis. Following these steps as well as removal of residual softer lens cortex by aspiration methods without fragmentation, a synthetic foldable intraocular lens (IOL's) inserted into the eye through a small incision. This technique is associated with a very high rate of anatomic and visual success exceeding 95% in most cases and with rapid visual rehabilitation.
[0004] One of the earliest and most critical steps in the procedure is the performance of capsulorhexis. This step evolved from an earlier technique termed can-opener capsulotomy in which a sharp needle was used to perforate the anterior lens capsule in a circular fashion followed by the removal of a circular fragment of lens capsule typically in the range of 5-8 mm in diameter. This facilitated the next step of nuclear sculpting by phacoemulsification. Due to a variety of complications associated with the initial can-opener technique, attempts were made by leading experts in the field to develop a better technique for removal of the anterior lens capsule preceding the emulsification step. These were pioneered by Neuhann, and Gimbel and highlighted in a publication in 1991 (Gimbel, Neuhann, Development Advantages and Methods of the Continuous Curvilinear Capsulorhexis. Journal of Cataract and Refractive Surgery 1991; 17:110-111, incorporated herein by reference). The concept of the capsulorhexis is to provide a smooth continuous circular opening through which not only the phacoemulsification of the nucleus can be performed safely and easily, but also for easy insertion of the intraocular lens. It provides both a clear central access for insertion, a permanent aperture for transmission of the image to the retina by the patient, and also a support of the IOL inside the remaining capsule that would limit the potential for dislocation.
[0005] Using the older technique of can-opener capsulotomy, or even with the continuous capsulorhexis, problems may develop related to inability of the surgeon to adequately visualize the capsule due to lack of red reflex, to grasp it with sufficient security, to tear a smooth circular opening of the appropriate size without radial rips and extensions or technical difficulties related to maintenance of the anterior chamber depth after initial opening, small size of the pupil, or the absence of a red reflex due to the lens opacity. Some of the problems with visualization have been minimized through the use of dyes such as methylene blue or indocyanine green. Additional complications arise in patients with weak zonules (typically older patients) and very young children that have very soft and elastic capsules, which are very difficult to mechanically rupture.
[0006] Finally, during the intraoperative surgical procedure, and subsequent to the step of anterior continuous curvilinear capsulorhexis, which typically ranges from 5-7 mm in diameter, and prior to IOL insertion the steps of hydrodis section, hydrodilineation and phaco emulsification occur. These are intended to identify and soften the nucleus for the purposes of removal from the eye. These are the longest and thought to be the most dangerous step in the procedure due to the use of pulses of ultrasound that may lead to inadvertent ruptures of the posterior lens capsule, posterior dislocation of lens fragments, and potential damage anteriorly to the corneal endothelium and/or iris and other delicate intraocular structures. The central nucleus of the lens, which undergoes the most opacification and thereby the most visual impairment, is structurally the hardest and requires special techniques. A variety of surgical maneuvers employing ultrasonic fragmentation and also requiring considerable technical dexterity on the part of the surgeon have evolved, including sculpting of the lens, the so-called “divide and conquer technique” and a whole host of similarly creatively named techniques, such as phaco chop, etc. These are all subject to the usual complications associated with delicate intraocular maneuvers (Gimbel. Chapter 15: Principles of Nuclear PhacoEmulsification. In Cataract Surgery Techniques Complications and Management. 2 nd ed. Edited by Steinert et al. 2004: 153-181, incorporated herein by reference.).
[0007] Following cataract surgery one of the principal sources of visual morbidity is the slow development of opacities in the posterior lens capsule, which is generally left intact during cataract surgery as a method of support for the lens, to provide good centration of the IOL, and also as a means of preventing subluxation posteriorly into the vitreous cavity. It has been estimated that the complication of posterior lens capsule opacification occurs in approximately 28-50% of patients (Steinert and Richter. Chapter 44 . In Cataract Surgery Techniques Complications and Management. 2 nd ed. Edited by Steinert et al. 2004: pg. 531-544 and incorporated herein by reference). As a result of this problem, which is thought to occur as a result of epithelial and fibrous metaplasia along the posterior lens capsule centrally from small islands of residual epithelial cells left in place near the equator of the lens, techniques have been developed initially using surgical dissection, and more recently the neodymium YAG laser to make openings centrally in a non-invasive fashion. However, most of these techniques can still be considered relatively primitive requiring a high degree of manual dexterity on the part of the surgeon and the creation of a series of high energy pulses in the range of 1 to 10 mJ manually marked out on the posterior lens capsule, taking great pains to avoid damage to the intraocular lens. The course nature of the resulting opening is illustrated clearly in FIG. 44-10 , pg. 537 of Steinert and Richter, Chapter 44 of In Cataract Surgery Techniques Complications and Management. 2 nd ed (see complete cite above).
[0008] What is needed are ophthalmic methods, techniques and apparatus to advance the standard of care of cataract and other ophthalmic pathologies.
SUMMARY OF THE INVENTION
[0009] The techniques and system disclosed herein provide many advantages. Specifically, rapid and precise openings in the lens capsule and fragmentation of the lens nucleus and cortex is enabled using 3-dimensional patterned laser cutting. The duration of the procedure and the risk associated with opening the capsule and fragmentation of the hard nucleus are reduce, while increasing precision of the procedure. The removal of a lens dissected into small segments is performed using a patterned laser scanning and just a thin aspiration needle. The removal of a lens dissected into small segments is performed using patterned laser scanning and using a ultrasonic emulsifier with a conventional phacoemulsification technique or a technique modified to recognize that a segmented lens will likely be more easily removed (i.e., requiring less surgical precision or dexterity) and/or at least with marked reduction in ultrasonic emulsification power, precision and/or duration. There are surgical approaches that enable the formation of very small and geometrically precise opening(s) in precise locations on the lens capsule, where the openings in the lens capsule would be very difficult if not impossible to form using conventional, purely manual techniques. The openings enable greater precision or modifications to conventional ophthalmic procedures as well as enable new procedures. For example, the techniques described herein may be used to facilitate anterior and/or posterior lens removal, implantation of injectable or small foldable IOLs as well as injection of compounds or structures suited to the formation of accommodating IOLs.
[0010] Another procedure enabled by the techniques described herein provides for the controlled formation of a hemi-circular or curvilinear flap in the anterior lens surface. Contrast to conventional procedures which require a complete circle or nearly complete circular cut. Openings formed using conventional, manual capsulorhexis techniques rely primarily on the mechanical shearing properties of lens capsule tissue and uncontrollable tears of the lens capsule to form openings. These conventional techniques are confined to the central lens portion or to areas accessible using mechanical cutting instruments and to varying limited degrees utilize precise anatomical measurements during the formation of the tears. In contrast, the controllable, patterned laser techniques described herein may be used to create a semi-circular capsular flap in virtually any position on the anterior lens surface and in virtually any shape. They may be able to seal spontaneously or with an autologous or synthetic tissue glue or other method. Moreover, the controllable, patterned laser techniques described herein also have available and/or utilize precise lens capsule size, measurement and other dimensional information that allows the flap or opening formation while minimizing impact on surrounding tissue. The flap is not limited only to semi-circular but may be any shape that is conducive to follow on procedures such as, for example, injection or formation of complex or advanced IOL devices or so called injectable polymeric or fixed accommodating IOLs.
[0011] The techniques disclosed herein may be used during cataract surgery to remove all or a part of the anterior capsule, and may be used in situations where the posterior capsule may need to be removed intraoperatively, for example, in special circumstances such as in children, or when there is a dense posterior capsular opacity which can not be removed by suction after the nucleus has been removed. In the first, second and third years after cataract surgery, secondary opacification of the posterior lens capsule is common and is benefited by a posterior capsulotomy which may be performed or improved utilizing aspects of the techniques disclosed herein.
[0012] Because of the precision and atraumatic nature of incisions formed using the techniques herein, it is believed that new meaning is brought to minimally invasive ophthalmic surgery and lens incisions that may be self healing.
[0013] In one aspect, a method of making an incision in eye tissue includes generating a beam of light, focusing the beam at a first focal point located at a first depth in the eye tissue, scanning the beam in a pattern on the eye while focused at the first depth, focusing the beam at a second focal point located at a second depth in the eye tissue different than the first depth, and scanning the beam in the pattern on the eye while focused at the second depth.
[0014] In another aspect, a method of making an incision in eye tissue includes generating a beam of light, and passing the beam through a multi-focal length optical element so that a first portion of the beam is focused at a first focal point located at a first depth in the eye tissue and a second portion of the beam is focused at a second focal point located at a second depth in the eye tissue different than first depth.
[0015] In yet another aspect, a method of making an incision in eye tissue includes generating a beam of light having at least a first pulse of light and a second pulse of light, and focusing the first and second pulses of light consecutively into the eye tissue, wherein the first pulse creates a plasma at a first depth within the eye tissue, and wherein the second pulse arrives before the plasma disappears and is absorbed by the plasma to extend the plasma in the eye tissue along the beam.
[0016] In yet one more aspect, a method of making an incision in eye tissue includes generating a beam of light, and focusing the light into the eye tissue to create an elongated column of focused light within the eye tissue, wherein the focusing includes subjecting the light to at least one of a non-spherical lens, a highly focused lens with spherical aberrations, a curved mirror, a cylindrical lens, an adaptive optical element, a prism, and a diffractive optical element.
[0017] In another aspect, a method of removing a lens and debris from an eye includes generating a beam of light, focusing the light into the eye to fragment the lens into pieces, removing the pieces of lens, and then focusing the light into the eye to ablate debris in the eye.
[0018] In one more aspect, a method of removing a lens from a lens capsule in an eye includes generating a beam of light, focusing the light into the eye to form incisions in the lens capsule, inserting an ultrasonic probe through the incision and into the lens capsule to break the lens into pieces, removing the lens pieces from the lens capsule, rinsing the lens capsule to remove endothermial cells therefrom, and inserting at least one of a synthetic. foldable intraocular lens or an optically transparent gel into the lens capsule.
[0019] In another aspect, an ophthalmic surgical system for treating eye tissue includes a light source for generating a beam of light, a delivery system for focusing the beam onto the eye tissue, a controller for controlling the light source and the delivery system such that the light beam is focused at multiple focal points in the eye tissue at multiple depths within the eye tissue.
[0020] In yet another aspect, an ophthalmic surgical system for treating eye tissue includes a light source for generating a beam of light having at least a first pulse of light and a second pulse of light, a delivery system for focusing the beam onto the eye tissue, a controller for controlling the light source and the delivery system such that the first and second pulses of light are consecutively focused onto the eye tissue, wherein the first pulse creates a plasma at a first depth within the eye tissue, and wherein the second pulse is arrives before the plasma disappears and absorbed by the plasma to extend the plasma in the eye tissue along the beam.
[0021] In one more aspect, an ophthalmic surgical system for treating eye tissue includes a light source for generating a beam of light, a delivery system for focusing the beam onto the eye tissue, the delivery system including at least one of a non-spherical lens, a highly focused lens with spherical aberrations, a curved mirror, a cylindrical lens, an adaptive optical element, a prism, and a diffractive optical element, and a controller for controlling the light source and the delivery system such that an elongated column of focused light within the eye tissue is created.
[0022] Other objects and features of the present invention will become apparent by a review of the specification, claims and appended figures.
INCORPORATION BY REFERENCE
[0023] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
[0025] FIG. 1 is a plan diagram of a system that projects or scans an optical beam into a patient's eye.
[0026] FIG. 2 is a diagram of the anterior chamber of the eye and the laser beam producing plasma at the focal point on the lens capsule.
[0027] FIG. 3 is a planar view of the iris and lens with a circular pattern for the anterior capsulotomy (capsulorexis).
[0028] FIG. 4 is a diagram of the line pattern applied across the lens for OCT measurement of the axial profile of the anterior chamber.
[0029] FIG. 5 is a diagram of the anterior chamber of the eye and the 3-dimensional laser pattern applied across the lens capsule.
[0030] FIG. 6 is an axially-elongated plasma column produced in the focal zone by sequential application of a burst of pulses ( 1 , 2 , and 3 ) with a delay shorter than the plasma life time.
[0031] FIGS. 7A-7B are multi-segmented lenses for focusing the laser beam into 3 points along the same axis.
[0032] FIGS. 7C-7D are multi-segmented lenses with co-axial and off-axial segments having focal points along the same axis but different focal distances F 1 , F 2 , F 3 .
[0033] FIG. 8 is an axial array of fibers ( 1 , 2 , 3 ) focused with a set of lenses into multiple points ( 1 , 2 , 3 ) and thus producing plasma at different depths inside the tissue ( 1 , 2 , 3 ).
[0034] FIG. 9A and FIG. 9B are diagrams illustrating examples of the patterns that can be applied for nucleus segmentation.
[0035] FIG. 10A-C is a planar view of some of the combined patterns for segmented capsulotomy and phaco-fragmentation.
[0036] FIG. 11 is a plan diagram of one system embodiment that projects or scans an optical beam into a patient's eye.
[0037] FIG. 12 is a plan diagram of another system embodiment that projects or scans an optical beam into a patient's eye.
[0038] FIG. 13 is a plan diagram of yet another system embodiment that projects or scans an optical beam into a patient's eye.
[0039] FIG. 14 is a flow diagram showing the steps utilized in a “track and treat” approach to material removal.
[0040] FIG. 15 is a flow diagram showing the steps utilized in a “track and treat” approach to material removal that employs user input.
[0041] FIG. 16 is a perspective view of a transverse focal zone created by an anamorphic optical scheme.
[0042] FIGS. 17A-17C are perspective views of an anamorphic telescope configuration for constructing an inverted Keplerian telescope.
[0043] FIG. 18 is a side view of prisms used to extend the beam along a single meridian.
[0044] FIG. 19 is a top view illustrating the position and motion of a transverse focal volume on the eye lens.
[0045] FIG. 20 illustrates fragmentation patterns of an ocular lens produced by one embodiment of the present invention.
[0046] FIG. 21 illustrates circular incisions of an ocular lens produced by one embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0047] The present invention can be implemented by a system that projects or scans an optical beam into a patient's eye 1 , such as the system shown in FIG. 1 . The system includes a light source 10 (e.g. laser, laser diode, etc.), which may be controlled by control electronics 12 , via an input and output device 14 , to create optical beam 11 (either cw or pulsed). Control electronics 12 may be a computer, microcontroller, etc. Scanning may be achieved by using one or more moveable optical elements (e.g. lenses, gratings, or as shown in FIG. 1 a mirror(s) 16 ) which also may be controlled by control electronics 12 , via input and output device 14 . Mirror 16 may be tilted to deviate the optical beam 11 as shown in FIG. 1 , and direct beam 11 towards the patient's eye 1 . An optional ophthalmic lens 18 can be used to focus the optical beam 11 into the patient's eye 1 . The positioning and character of optical beam 11 and/or the scan pattern it forms on the eye may be further controlled by use of an input device 20 such as a joystick, or any other appropriate user input device.
[0048] Techniques herein include utilizing a light source 10 such as a surgical laser configured to provide one or more of the following parameters:
[0049] 1) pulse energy up to 1 p repetition rate up to 1 MHz, pulse duration <1 ps
[0050] 2) pulse energy up to 10 p rep. rate up to 100 kHz, pulse duration <1 ps.
[0051] 3) Pulse energy up to 1000 p, rep rate up to 1 kHz, pulse duration <3 ps.
[0052] Additionally, the laser may use wavelengths in a variety of ranges including in the near-infrared range: 800-1100 nm. In one aspect, near-infrared wavelengths are selected because tissue absorption and scattering is reduced. Additionally, a laser can be configured to provide low energy ultrashort pulses of near-infrared radiation with pulse durations below 10 ps or below 1 ps, alone or in combination with pulse energy not exceeding 100 p, at high repetition rate including rates above 1 kHz, and above 10 kHz.
[0053] Short pulsed laser light focused into eye tissue 2 will produce dielectric breakdown at the focal point, rupturing the tissue 2 in the vicinity of the photo-induced plasma (see FIG. 2 ). The diameter d of the focal point is given by d=λF/D b , where F is the focal length of the last focusing element, D b is the beam diameter on the last lens, and λ is the wavelength. For a focal length F=160 mm, beam diameter on the last lens D b =10 mm, and wavelength λ=1.04 um, the focal spot diameter will be d≈λ/(2·NA)≈λF/D b =15 μm, where the numerical aperture of the focusing optics, NA≈D b /(2F).
[0054] To provide for continuous cutting, the laser spots should not be separated by more than a width of the crater produced by the laser pulse in tissue. Assuming the rupture zone being R=15 μm (at low energies ionization might occur in the center of the laser spot and not expand to the full spot size), and assuming the maximal diameter of the capsulotomy circle being D c =8 mm, the number of required pulses will be: N=πD c /R=1675 to provide a circular cut line 22 around the circumference of the eye lens 3 as illustrated in FIG. 3 . For smaller diameters ranging from 5-7 mm, the required number of pulses would be less. If the rupture zone were larger (e.g. 50 μm), the number of pulses would drop to N=503.
[0055] To produce an accurate circular cut, these pulses should be delivered to tissue over a short eye fixation time. Assuming the fixation time t=0.2 s, laser repetition rate should be: r=N/t=8.4 kHz. If the fixation time were longer, e.g. 0.5 s, the required rep. rate could be reduced to 3.4 kHz. With a rupture zone of 50 μm the rep. rate could further drop to 1 kHz.
[0056] Threshold radiant exposure of the dielectric breakdown with 4 ns pulses is about Φ=100 J/cm 2 . With a focal spot diameter being d=15 μm, the threshold pulse energy will be E th =Φ*πd 2 /4=176 μJ. For stable and reproducible operation, pulse energy should exceed the threshold by at least a factor of 2, so pulse energy of the target should be E b =352 μJ. The creation of a cavitation bubble might take up to 10% of the pulse energy, i.e. E b =35 μJ. This corresponds to a bubble diameter
[0000]
d
b
=
6
E
b
π
P
a
3
=
48
µm
.
[0057] The energy level can be adjusted to avoid damage to the corneal endothelium. As such, the threshold energy of the dielectric breakdown could be minimized by reducing the pulse duration, for example, in the range of approximately 0.1-1 ps. Threshold radiant exposure, Φ, for dielectric breakdown for 100 fs is about Φ=2 J/cm 2 ; for 1 ps it is Φ=2.5 J/cm 2 . Using the above pulse durations, and a focal spot diameter d=15 μm, the threshold pulse energies will be E th =Φ*πd 2 /4=3.5 and 4.4 μJ for 100 fs and 1 ps pulses, respectively. The pulse energy could instead be selected to be a multiple of the threshold energy, for example, at least a factor of 2. If a factor of 2 is used, the pulse energies on the target would be E th =7 and 9 μJ, respectively. These are only two examples. Other pulse energy duration times, focal spot sizes and threshold energy levels are possible and are within the scope of the present invention.
[0058] A high repetition rate and low pulse energy can be utilized for tighter focusing of the laser beam. In one specific example, a focal distance of F=50 mm is used while the beam diameter remains D b =10 mm, to provide focusing into a spot of about 4 μm in diameter. Aspherical optics can also be utilized. An 8 mm diameter opening can be completed in a time of 0.2 s using a repetition rate of about 32 kHz.
[0059] The laser 10 and controller 12 can be set to locate the surface of the capsule and ensure that the beam will be focused on the lens capsule at all points of the desired opening. Imaging modalities and techniques described herein, such as for example, Optical Coherence Tomography (OCT) or ultrasound, may be used to determine the location and measure the thickness of the lens and lens capsule to provide greater precision to the laser focusing methods, including 2D and 3D patterning. Laser focusing may also be accomplished using one or more methods including direct observation of an aiming beam, Optical Coherence Tomography (OCT), ultrasound, or other known ophthalmic or medical imaging modalities and combinations thereof.
[0060] As shown in FIG. 4 , OCT imaging of the anterior chamber can be performed along a simple linear scan 24 across the lens using the same laser and/or the same scanner used to produce the patterns for cutting. This scan will provide information about the axial location of the anterior and posterior lens capsule, the boundaries of the cataract nucleus, as well as the depth of the anterior chamber. This information may then be loaded into the laser 3-D scanning system, and used to program and control the subsequent laser assisted surgical procedure. The information may be used to determine a wide variety of parameters related to the procedure such as, for example, the upper and lower axial limits of the focal planes for cutting the lens capsule and segmentation of the lens cortex and nucleus, the thickness of the lens capsule among others. The imaging data may be averaged across a 3-line pattern as shown in FIG. 9 .
[0061] An example of the results of such a system on an actual human crystalline lens is shown in FIG. 20 . A beam of 10 μJ, 1 ps pulses delivered at a pulse repetition rate of 50 kHz from a laser operating at a wavelength of 1045 nm was focused at NA=0.05 and scanned from the bottom up in a pattern of 4 circles in 8 axial steps. This produced the fragmentation pattern in the ocular lens shown in FIG. 20 . FIG. 21 shows in detail the resultant circular incisions, which measured ˜10 μm in diameter, and ˜100 μm in length.
[0062] FIG. 2 illustrates an exemplary illustration of the delineation available using the techniques described herein to anatomically define the lens. As can be seen in FIG. 2 , the capsule boundaries and thickness, the cortex, epinucleus and nucleus are determinable. It is believed that OCT imaging may be used to define the boundaries of the nucleus, cortex and other structures in the lens including, for example, the thickness of the lens capsule including all or a portion of the anterior or posterior capsule. In the most general sense, one aspect of the present invention is the use of ocular imaging data obtained as described herein as an input into a laser scanning and/or pattern treatment algorithm or technique that is used to as a guide in the application of laser energy in novel laser assisted ophthalmic procedures. In fact, the imaging and treatment can be performed using the same laser and the same scanner. While described for use with lasers, other energy modalities may also be utilized.
[0063] It is to be appreciated that plasma formation occurs at the waist of the beam. The axial extent of the cutting zone is determined by the half-length L of the laser beam waist, which can be expressed as: L˜λ/(4·NA 2 )=dF/D b . Thus the lower the NA of the focusing optics, the longer waist of the focused beam, and thus a longer fragmentation zone can be produced. For F=160 mm, beam diameter on the last lens D b =10 mm, and focal spot diameter d=15 μm, the laser beam waist half-length L would be 240 μm.
[0064] With reference to FIG. 5 , a three dimensional application of laser energy 26 can be applied across the capsule along the pattern produced by the laser-induced dielectric breakdown in a number of ways such as, for example:
[0065] 1) Producing several circular or other pattern scans consecutively at different depths with a step equal to the axial length of the rupture zone. Thus, the depth of the focal point (waist) in the tissue is stepped up or down with each consecutive scan. The laser pulses are sequentially applied to the same lateral pattern at different depths of tissue using, for example, axial scanning of the focusing elements or adjusting the optical power of the focusing element while, optionally, simultaneously or sequentially scanning the lateral pattern. The adverse result of laser beam scattering on bubbles, cracks and/or tissue fragments prior to reaching the focal point can be avoided by first producing the pattern/focusing on the maximal required depth in tissue and then, in later passes, focusing on more shallow tissue spaces. Not only does this “bottom up” treatment technique reduce unwanted beam attenuation in tissue above the target tissue layer, but it also helps protect tissue underneath the target tissue layer. By scattering the laser radiation transmitted beyond the focal point on gas bubbles, cracks and/or tissue fragments which were produced by the previous scans, these defects help protect the underlying retina. Similarly, when segmenting a lens, the laser can be focused on the most posterior portion of the lens and then moved more anteriorly as the procedure continues.
[0066] 2) Producing axially-elongated rupture zones at fixed points by:
[0067] a) Using a sequence of 2-3 pulses in each spot separated by a few ps. Each pulse will be absorbed by the plasma 28 produced by the previous pulse and thus will extend the plasma 28 upwards along the beam as illustrated in FIG. 6A . In this approach, the laser energy should be 2 or 3 times higher, i.e. 20-30 μJ. Delay between the consecutive pulses should be longer than the plasma formation time (on the order of 0.1 ps) but not exceed the plasma recombination time (on the order of nanoseconds)
[0068] b) Producing an axial sequence of pulses with slightly different focusing points using multiple co-axial beams with different pre-focusing or multifocal optical elements. This can be achieved by using multi-focal optical elements (lenses, mirrors, diffractive optics, etc.). For example, a multi-segmented lens 30 can be used to focus the beam into multiple points (e.g. three separate points) along the same axis, using for example co-axial (see FIGS. 7A-7C ) or off-coaxial (see FIG. 7D ) segments to produce varying focal lengths (e.g. F 1 , F 2 , F 3 ). The multi-focal element 30 can be co-axial, or off-axis-segmented, or diffractive. Co-axial elements may have more axially-symmetric focal points, but will have different sizes due to the differences in beam diameters in each segment. Off-axial elements might have less symmetric focal points but all the elements can produce the foci of the same sizes.
[0069] c) Producing an elongated focusing column (as opposed to just a discrete number of focal points) using: (1) non-spherical (aspherical) optics, or (2) utilizing spherical aberrations in a lens with a high F number, or (3) diffractive optical element (hologram).
[0070] d) Producing an elongated zone of ionization using multiple optical fibers. For example, an array of optical fibers 32 of different lengths can be imaged with a set of lenses 34 into multiple focal points at different depths inside the tissue as shown in FIG. 8 .
[0071] Patterns of Scanning:
[0072] For anterior and posterior capsulotomy, the scanning patterns can be circular and spiral, with a vertical step similar to the length of the rupture zone. For segmentation of the eye lens 3 , the patterns can be linear, planar, radial, radial segments, circular, spiral, curvilinear and combinations thereof including patterning in two and/or three dimensions. Scans can be continuous straight or curved lines, or one or more overlapping or spaced apart spots and/or line segments. Several scan patterns 36 are illustrated in FIGS. 9A and 9B , and combinations of scan patterns 38 are illustrated in FIGS. 10A-10C . Beam scanning with the multifocal focusing and/or patterning systems is particularly advantageous to successful lens segmentation since the lens thickness is much larger than the length of the beam waist axial. In addition, these and other 2D and 3D patterns may be used in combination with OCT to obtain additional imaging, anatomical structure or make-up (i.e., tissue density) or other dimensional information about the eye including but not limited to the lens, the cornea, the retina and as well as other portions of the eye.
[0073] The exemplary patterns allow for dissection of the lens cortex and nucleus into fragments of such dimensions that they can be removed simply with an aspiration needle, and can be used alone to perform capsulotomy. Alternatively, the laser patterning may be used to pre-fragment or segment the nucleus for later conventional ultrasonic phacoemulsification. In this case however, the conventional phacoemulsification would be less than a typical phacoemulsification performed in the absence of the inventive segmenting techniques because the lens has been segmented. As such, the phacoemulsification procedure would likely require less ultrasonic energy to be applied to the eye, allowing for a shortened procedure or requiring less surgical dexterity.
[0074] Complications due to the eye movements during surgery can be reduced or eliminated by performing the patterned laser cutting very rapidly (e.g. within a time period that is less than the natural eye fixation time). Depending on the laser power and repetition rate, the patterned cutting can be completed between 5 and 0.5 seconds (or even less), using a laser repetition rate exceeding 1 kHz.
[0075] The techniques described herein may be used to perform new ophthalmic procedures or improve existing procedures, including anterior and posterior capsulotomy, lens fragmentation and softening, dissection of tissue in the posterior pole (floaters, membranes, retina), as well as incisions in other areas of the eye such as, but not limited to, the sclera and iris.
[0076] Damage to an IOL during posterior capsulotomy can be reduced or minimized by advantageously utilizing a laser pattern initially focused beyond the posterior pole and then gradually moved anteriorly under visual control by the surgeon alone or in combination with imaging data acquired using the techniques described herein.
[0077] For proper alignment of the treatment beam pattern, an alignment beam and/or pattern can be first projected onto the target tissue with visible light (indicating where the treatment pattern will be projected. This allows the surgeon to adjust the size, location and shape of the treatment pattern. Thereafter, the treatment pattern can be rapidly applied to the target tissue using an automated 3 dimensional pattern generator (in the control electronics 12 ) by a short pulsed cutting laser having high repetition rate.
[0078] In addition, and in particular for capsulotomy and nuclear fragmentation, an automated method employing an imaging modality can be used, such as for example, electro-optical, OCT, acoustic, ultrasound or other measurement, to first ascertain the maximum and minimum depths of cutting as well as the size and optical density of the cataract nucleus. Such techniques allow the surgeon account for individual differences in lens thickness and hardness, and help determine the optimal cutting contours in patients. The system for measuring dimensions of the anterior chamber using OCT along a line, and/or pattern (2D or 3D or others as described herein) can be integrally the same as the scanning system used to control the laser during the procedure. As such, the data including, for example, the upper and lower boundaries of cutting, as well as the size and location of the nucleus, can be loaded into the scanning system to automatically determine the parameters of the cutting (i.e., segmenting or fracturing) pattern. Additionally, automatic measurement (using an optical, electro-optical, acoustic, or OCT device, or some combination of the above) of the absolute and relative positions and/or dimensions of a structure in the eye (e.g. the anterior and posterior lens capsules, intervening nucleus and lens cortex) for precise cutting, segmenting or fracturing only the desired tissues (e.g. lens nucleus, tissue containing cataracts, etc.) while minimizing or avoiding damage to the surrounding tissue can be made for current and/or future surgical procedures. Additionally, the same ultrashort pulsed laser can be used for imaging at a low pulse energy, and then for surgery at a high pulse energy.
[0079] The use of an imaging device to guide the treatment beam may be achieved many ways, such as those mentioned above as well as additional examples explained next (which all function to characterize tissue, and continue processing it until a target is removed). For example, in FIG. 11 , a laser source LS and (optional) aiming beam source AIM have outputs that are combined using mirror DM 1 (e.g. dichroic mirror). In this configuration, laser source LS may be used for both therapeutics and diagnostics. This is accomplished by means of mirror M 1 which serves to provide both reference input R and sample input S to an OCT Interferometer by splitting the light beam B (centerlines shown) from laser source LS. Because of the inherent sensitivity of OCT Interferometers, mirror M 1 may be made to reflect only a small portion of the delivered light. Alternatively, a scheme employing polarization sensitive pickoff mirrors may be used in conjunction with a quarter wave plate (not shown) to increase the overall optical efficiency of the system. Lens L 1 may be a single element or a group of elements used to adjust the ultimate size or location along the z-axis of the beam B disposed to the target at point P. When used in conjunction with scanning in the X & Y axes, this configuration enables 3-dimensional scanning and/or variable spot diameters (i.e. by moving the focal point of the light along the z-axis).
[0080] In this example, transverse (XY) scanning is achieved by using a pair of orthogonal galvanometric mirrors G 1 & G 2 which may provide 2-dimensional random access scanning of the target. It should be noted that scanning may be achieved in a variety of ways, such as moving mirror M 2 , spinning polygons, translating lenses or curved mirrors, spinning wedges, etc. and that the use of galvanometric scanners does not limit the scope of the overall design. After leaving the scanner, light encounters lens L 2 which serves to focus the light onto the target at point P inside the patient's eye EYE. An optional ophthalmic lens OL may be used to help focus the light. Ophthalmic lens OL may be a contact lens and further serve to dampen any motion of eye EYE, allowing for more stable treatment. Lens L 2 may be made to move along the z-axis in coordination with the rest of the optical system to provide for 3-dimensional scanning, both for therapy and diagnosis. In the configuration shown, lens L 2 ideally is moved along with the scanner G 1 & G 2 to maintain telecentricity. With that in mind, one may move the entire optical assembly to adjust the depth along the z-axis. If used with ophthalmic lens OL, the working distance may be precisely held. A device such as the Thorlabs EAS504 precision stepper motor can be used to provide both the length of travel as well as the requisite accuracy and precision to reliably image and treat at clinically meaningful resolutions. As shown it creates a telecentric scan, but need not be limited to such a design.
[0081] Mirror M 2 serves to direct the light onto the target, and may be used in a variety of ways. Mirror M 2 could be a dichroic element that the user looks through in order to visualize the target directly or using a camera, or may be made as small as possible to provide an opportunity for the user to view around it, perhaps with a binocular microscope. If a dichroic element is used, it may be made to be photopically neutral to avoid hindering the user's view. An apparatus for visualizing the target tissue is shown schematically as element V, and is preferably a camera with an optional light source for creating an image of the target tissue. The optional aiming beam AIM may then provide the user with a view of the disposition of the treatment beam, or the location of the identified targets. To display the target only, AIM may be pulsed on when the scanner has positioned it over an area deemed to be a target. The output of visualization apparatus V may be brought back to the system via the input/output device 10 and displayed on a screen, such as a graphical user interface GUI. In this example, the entire system is controlled by the controller CPU, and data moved through input/output device 10 . Graphical user interface GUI may be used to process user input, and display the images gathered by both visualization apparatus V and the OCT interferometer. There are many possibilities for the configuration of the OCT interferometer, including time and frequency domain approaches, single and dual beam methods, etc, as described in U.S. Pat. Nos. 5,748,898; 5,748,352; 5,459,570; 6,111,645; and 6,053,613 (which are incorporated herein by reference.
[0082] Information about the lateral and axial extent of the cataract and localization of the boundaries of the lens capsule will then be used for determination of the optimal scanning pattern, focusing scheme, and laser parameters for the fragmentation procedure. Much if not all of this information can be obtained from visualization of the target tissue. For example, the axial extent of the fragmentation zone of a single pulse should not exceed the distance between (a) the cataract and the posterior capsule, and (b) the anterior capsule and the corneal endothelium. In the cases of a shallow anterior chamber and/or a large cataract, a shorter fragmentation zone should be selected, and thus more scanning planes will be required. Conversely, for a deep anterior chamber and/or a larger separation between the cataract and the posterior capsule a longer fragmentation zone can be used, and thus less planes of scanning will be required. For this purpose an appropriate focusing element will be selected from an available set. Selection of the optical element will determine the width of the fragmentation zone, which in turn will determine the spacing between the consecutive pulses. This, in turn, will determine the ratio between the scanning rate and repetition rate of the laser pulses. In addition, the shape of the cataract will determine the boundaries of the fragmentation zone and thus the optimal pattern of the scanner including the axial and lateral extent of the fragmentation zone, the ultimate shape of the scan, number of planes of scanning, etc.
[0083] FIG. 12 shows an alternate embodiment in which the imaging and treatment sources are different. A dichroic mirror DM 2 has been added to the configuration of FIG. 11 to combine the imaging and treatment light, and mirror M 1 has been replaced by beam splitter BS which is highly transmissive at the treatment wavelength, but efficiently separates the light from the imaging source SLD for use in the OCT Interferometer. Imaging source SLD may be a superluminescent diode having a spectral output that is nominally 50 nm wide, and centered on or around 835 nm, such as the SuperLum SLD-37. Such a light source is well matched to the clinical application, and sufficiently spectrally distinct from the treatment source, thus allowing for elements DM and BS to be reliably fabricated without the necessarily complicated and expensive optical coatings that would be required if the imaging and treatment sources were closer in wavelength.
[0084] FIG. 13 shows an alternate embodiment incorporating a confocal microscope CM for use as an imaging system. In this configuration, mirror M 1 reflects a portion of the backscattered light from beam B into lens L 3 . Lens L 3 serves to focus this light through aperture A (serving as a spatial filter) and ultimately onto detector D. As such, aperture A and point P are optically conjugate, and the signal received by detector D is quite specific when aperture A is made small enough to reject substantially the entire background signal. This signal may thus be used for imaging, as is known in the art. Furthermore, a fluorophore may be introduced into the target to allow for specific marking of either target or healthy tissue. In this approach, the ultrafast laser may be used to pump the absorption band of the fluorophore via a multiphoton process or an alternate source (not shown) could be used in a manner similar to that of FIG. 12 .
[0085] FIG. 14 is a flowchart outlining the steps utilized in a “track and treat” approach to material removal. First an image is created by scanning from point to point, and potential targets identified. When the treatment beam is disposed over a target, the system can transmit the treatment beam, and begin therapy. The system may move constantly treating as it goes, or dwell in a specific location until the target is fully treated before moving to the next point.
[0086] The system operation of FIG. 14 could be modified to incorporate user input. As shown in FIG. 15 , a complete image is displayed to the user, allowing them to identify the target(s). Once identified, the system can register subsequent images, thus tracking the user defined target(s). Such a registration scheme may be implemented in many different ways, such as by use of the well known and computationally efficient Sobel or Canny edge detection schemes. Alternatively, one or more readily discernable marks may be made in the target tissue using the treatment laser to create a fiduciary reference without patient risk (since the target tissue is destined for removal).
[0087] In contrast to conventional laser techniques, the above techniques provide (a) application of laser energy in a pattern, (b) a high repetition rate so as to complete the pattern within the natural eye fixation time, (c) application of sub-ps pulses to reduce the threshold energy, and (d) the ability to integrate imaging and treatment for an automated procedure.
[0088] Laser Delivery System
[0089] The laser delivery system in FIG. 1 can be varied in several ways. For example, the laser source could be provided onto a surgical microscope, and the microscope's optics used by the surgeon to apply the laser light, perhaps through the use of a provided console. Alternately, the laser and delivery system would be separate from the surgical microscope and would have an optical system for aligning the aiming beam for cutting. Such a system could swing into position using an articulating arm attached to a console containing the laser at the beginning of the surgery, and then swing away allowing the surgical microscope to swing into position.
[0090] The pattern to be applied can be selected from a collection of patterns in the control electronics 12 , produced by the visible aiming beam, then aligned by the surgeon onto the target tissue, and the pattern parameters (including for example, size, number of planar or axial elements, etc.) adjusted as necessary for the size of the surgical field of the particular patient (level of pupil dilation, size of the eye, etc.). Thereafter, the system calculates the number of pulses that should be applied based on the size of the pattern. When the pattern calculations are complete, the laser treatment may be initiated by the user (i.e., press a pedal) for a rapid application of the pattern with a surgical laser.
[0091] The laser system can automatically calculate the number of pulses required for producing a certain pattern based on the actual lateral size of the pattern selected by surgeon. This can be performed with the understanding that the rupture zone by the single pulse is fixed (determined by the pulse energy and configuration of the focusing optics), so the number of pulses required for cutting a certain segment is determined as the length of that segment divided by the width of the rupture zone by each pulse. The scanning rate can be linked to the repetition rate of the laser to provide a pulse spacing on tissue determined by the desired distance. The axial step of the scanning pattern will be determined by the length of the rupture zone, which is set by the pulse energy and the configuration of the focusing optics.
[0092] Fixation Considerations
[0093] The methods and systems described herein can be used alone or in combination with an aplanatic lens (as described in, for example, the U.S. Pat. No. 6,254,595 patent, incorporated herein by reference) or other device to configure the shape of the cornea to assist in the laser methods described herein. A ring, forceps or other securing means may be used to fixate the eye when the procedure exceeds the normal fixation time of the eye. Regardless whether an eye fixation device is used, patterning and segmenting methods described herein may be further subdivided into periods of a duration that may be performed within the natural eye fixation time.
[0094] Another potential complication associated with a dense cutting pattern of the lens cortex is the duration of treatment: If a volume of 6×6×4 mm=144 mm 3 of lens is segmented, it will require N=722,000 pulses. If delivered at 50 kHz, it will take 15 seconds, and if delivered at 10 kHz it will take 72 seconds. This is much longer than the natural eye fixation time, and it might require some fixation means for the eye. Thus, only the hardened nucleus may be chosen to be segmented to ease its removal. Determination of its boundaries with the OCT diagnostics will help to minimize the size of the segmented zone and thus the number of pulses, the level of cumulative heating, and the treatment time. If the segmentation component of the procedure duration exceeds the natural fixation time, then the eye may be stabilized using a conventional eye fixation device.
[0095] Thermal Considerations
[0096] In cases where very dense patterns of cutting are needed or desired, excess accumulation of heat in the lens may damage the surrounding tissue. To estimate the maximal heating, assume that the bulk of the lens is cut into cubic pieces of 1 mm in size. If tissue is dissected with E 1 =10 uJ pulses fragmenting a volume of 15 um in diameter and 200 um in length per pulse, then pulses will be applied each 15 um. Thus a 1×1 mm plane will require 66×66=4356 pulses. The 2 side walls will require 2×66×5=660 pulses, thus total N=5016 pulses will be required per cubic mm of tissue. Since all the laser energy deposited during cutting will eventually be transformed into heat, the temperature elevation will be DT=(E 1 *N)/pcV=50.16 mJ/(4.19 mJ/K)=12 K. This will lead to maximal temperature T=37+12° C.=49° C. This heat will dissipate in about one minute due to heat diffusion. Since peripheral areas of the lens will not be segmented (to avoid damage to the lens capsule) the average temperature at the boundaries of the lens will actually be lower. For example, if only half of the lens volume is fragmented, the average temperature elevation at the boundaries of the lens will not exceed 6° C. (T=43° C.) and on the retina will not exceed 0.1 C. Such temperature elevation can be well tolerated by the cells and tissues. However, much higher temperatures might be dangerous and should be avoided.
[0097] To reduce heating, a pattern of the same width but larger axial length can be formed, so these pieces can still be removed by suction through a needle. For example, if the lens is cut into pieces of 1×1×4 mm in size, a total of N=6996 pulses will be required per 4 cubic mm of tissue. The temperature elevation will be DT=(E 1 *N)/pcV=69.96 mJ/(4.19 mJ/K)/4=1.04 K. Such temperature elevation can be well tolerated by the cells and tissues.
[0098] An alternative solution to thermal limitations can be the reduction of the total energy required for segmentation by tighter focusing of the laser beam. In this regime a higher repetition rate and low pulse energy may be used. For example, a focal distance of F=50 mm and a beam diameter of D b =10 mm would allow for focusing into a spot of about 4 μm in diameter. In this specific example, repetition rate of about 32 kHz provides an 8 mm diameter circle in about 0.2 s.
[0099] To avoid retinal damage due to explosive vaporization of melanosomes following absorption of the short laser pulse the laser radiant exposure on the RPE should not exceed 100 mJ/cm 2 . Thus NA of the focusing optics should be adjusted such that laser radiant exposure on the retina will not exceed this safety limit. With a pulse energy of 10 μJ, the spot size on retina should be larger than 0.1 mm in diameter, and with a 1 mJ pulse it should not be smaller than 1 mm. Assuming a distance of 20 mm between lens and retina, these values correspond to minimum numerical apertures of 0.0025 and 0.025, respectively.
[0100] To avoid thermal damage to the retina due to heat accumulation during the lens fragmentation the laser irradiance on the retina should not exceed the thermal safety limit for near-IR radiation—on the order of 0.6 W/cm 2 . With a retinal zone of about 10 mm in diameter (8 mm pattern size on a lens+1 mm on the edges due to divergence) it corresponds to total power of 0.5 W on the retina.
[0101] Transverse Focal Volume
[0102] It is also possible to create a transverse focal volume 50 instead of an axial focal volume described above. An anamorphic optical scheme may used to produce a focal zone 39 that is a “line” rather than a single point, as is typical with spherically symmetric elements (see FIG. 16 ). As is standard in the field of optical design, the term “anamorphic” is meant herein to describe any system which has different equivalent focal lengths in each meridian. It should be noted that any focal point has a discrete depth of field. However, for tightly focused beams, such as those required to achieve the electric field strength sufficient to disrupt biological material with ultrashort pulses (defined as t pulse <10 ps), the depth of focus is proportionally short.
[0103] Such a 1-dimensional focus may be created using cylindrical lenses, and/or mirrors. An adaptive optic may also be used, such as a MEMS mirror or a phased array. When using a phased array, however, careful attention should be paid to the chromatic effects of such a diffractive device. FIGS. 17A-17C illustrate an anamorphic telescope configuration, where cylindrical optics 40 a/b and spherical lens 42 are used to construct an inverted Keplerian telescope along a single meridian (see FIG. 17A ) thus providing an elongated focal volume transverse to the optical axis (see FIG. 17C ). Compound lenses may be used to allow the beam's final dimensions to be adjustable.
[0104] FIG. 18 shows the use of a pair of prisms 46 a/b to extend the beam along a single meridian, shown as CA. In this example, CA is reduced rather than enlarged to create a linear focal volume.
[0105] The focus may also be scanned to ultimately produce patterns. To effect axial changes, the final lens may be made to move along the system's z-axis to translate the focus into the tissue. Likewise, the final lens may be compound, and made to be adjustable. The 1-dimensional focus may also be rotated, thus allowing it to be aligned to produce a variety of patterns, such as those shown in FIGS. 9 and 10 . Rotation may be achieved by rotating the cylindrical element itself. Of course, more than a single element may be used. The focus may also be rotated by using an additional element, such as a Dove prism (not shown). If an adaptive optic is used, rotation may be achieved by rewriting the device, thus streamlining the system design by eliminating a moving part.
[0106] The use of a transverse line focus allows one to dissect a cataractous lens by ablating from the posterior to the anterior portion of the lens, thus planing it. Furthermore, the linear focus may also be used to quickly open the lens capsule, readying it for extraction. It may also be used for any other ocular incision, such as the conjunctiva, etc. (see FIG. 19 ).
[0107] Cataract Removal Using a Track and Treat Approach
[0108] A “track and treat” approach is one that integrates the imaging and treatment aspect of optical eye surgery, for providing an automated approach to removal of debris such as cataractous and cellular material prior to the insertion of an IOL. An ultrafast laser is used to fragment the lens into pieces small enough to be removed using an irrigating/aspirating probe of minimal size without necessarily rupturing the lens capsule. An approach such as this that uses tiny, self-sealing incisions may be used to provide a capsule for filling with a gel or elastomeric IOL. Unlike traditional hard IOLS that require large incisions, a gel or liquid may be used to fill the entire capsule, thus making better use of the body's own accommodative processes. As such, this approach not only addresses cataract, but presbyopia as well.
[0109] Alternately, the lens capsule can remain intact, where bilateral incisions are made for aspirating tips, irrigating tips, and ultrasound tips for removing the bulk of the lens. Thereafter, the complete contents of the bag/capsule can be successfully rinsed/washed, which will expel the debris that can lead to secondary cataracts. Then, with the lens capsule intact, a minimal incision is made for either a foldable IOL or optically transparent gel injected through incision to fill the bag/capsule. The gel would act like the natural lens with a larger accommodating range.
[0110] It is to be understood that the present invention is not limited to the embodiment(s) described above and illustrated herein, but encompasses any and all variations falling within the scope of the appended claims. For example, materials, processes and numerical examples described above are exemplary only, and should not be deemed to limit the claims. Multi-segmented lens 30 can be used to focus the beam simultaneously at multiple points not axially overlapping (i.e. focusing the beam at multiple foci located at different lateral locations on the target tissue). Further, as is apparent from the claims and specification, not all method steps need be performed in the exact order illustrated or claimed, but rather in any order that accomplishes the goals of the surgical procedure.
DETAILED DESCRIPTION OF THE INVENTION
[0111] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. | A system for ophthalmic surgery on an eye includes: a pulsed laser which produces a treatment beam; an OCT imaging assembly capable of creating a continuous depth profile of the eye; an optical scanning system configured to position a focal zone of the treatment beam to a targeted location in three dimensions in one or more floaters in the posterior pole. The system also includes one or more controllers programmed to automatically scan tissues of the patient's eye with the imaging assembly; identify one or more boundaries of the one or more floaters based at least in part on the image data; iii. identify one or more treatment regions based upon the boundaries; and operate the optical scanning system with the pulsed laser to produce a treatment beam directed in a pattern based on the one or more treatment regions. | 0 |
TECHNICAL FIELD OF THE INVENTION
This invention relates to polyurethane systems comprising a mixture of low viscosity polyurethane prepolymers with polyisocyanate crosslinkers and to the coatings prepared therefrom.
BACKGROUND OF THE INVENTION
Two part solvent-based polyurethane coatings systems utilizing aliphatic isocyanates and polyester or acrylic polyols have become the industry standard for weatherable topcoats. These coatings systems combine exceptional resistance to chemical and physical damage with high gloss levels and long term retention of gloss, color and mechanical properties. Traditionally, these coatings systems have been formulated with low viscosity, high functionality liquid polyisocyanate crosslinkers as one component and a high molecular weight, high functionality polyol and associated pigments and additives as the second component.
A major driving force in the reformulation of coatings the world over is the need to reduce solvent emissions. One disadvantage of these traditional polyurethane formulations toward reformulation is the high solvent demand of the polyol component. This factor has limited the volatile organic content (VOC) reduction available with traditional polyol systems. One route to lowering VOC has been to employ lower molecular weight polyols. As formulators have incorporated more and more lower molecular weight (lower viscosity) polyols or reactive diluents, such as low molecular weight hydroxy acrylics or blocked systems such as oxazolidines, into their systems, there has been an inevitable trade-off in physical properties of the resulting low VOC coatings and/or in the handling of the reactive mixture. For example, many of the low VOC polyurethane coatings suffer from poor solvent resistance, poor flexibility, and an extreme sensitivity to catalyst level and its effect on cure profile.
As polyurethane coating formulators have reduced the volatile organic content (VOC) of their formulations, they have found it increasingly difficult to maintain good handling characteristics and mixing ratios. Traditionally, low VOC coatings tend to exhibit very short pot lives (1 h or less), a high sensitivity to the level of added catalyst, and the formulations often require mix ratios of pigmented polyol to isocyanate of from 3.5 to 6:1. Formulators are looking for ways to control the reactivity of their systems more efficiently and attain more attractive mixing ratios, preferably 1:1, while continuing to lower VOC toward zero.
Concurrent with the drive toward lower and lower VOC for conventionally applied coatings, formulators and applicators have also increased the use of plural component application equipment. This type of equipment has been used for many years to apply 100% reactive, fast reacting polyurethane coatings for thick film linings and for adhesives and sealants. With this equipment, the reactive components are heated to generate a lower viscosity component, metered into a chamber designed to rapidly mix the components and then pumped to a traditional airless or air-assisted airless gun for application.
Representative patents pertaining to polyurethane coating formulations and their use as coatings are as follows:
U.S. Pat. No. 3,218,348 discloses a process for preparing polyurethane polyisocyanates which have high molecular weight and do not crystallize from a solution on standing. The polyisocyanates are reacted with a trihydric alcohol such as trimethylolpropane in an organic solvent followed by addition of a dihydric alcohol such as 1,3-butyleneglycol.
U.S. Pat. No. 3,384,624 discloses a process for preparing polyurethane prepolymers free of unreacted polyisocyanate. The prepolymers, which can be used for preparing coatings, castings, paints and lacquers, are prepared by reacting toluenediisocyanate with an active hydrogen containing compound, e.g. a long chain diol and then contacting the prepolymer with a phenolic material in an amount sufficient to remove excess unreacted polyisocyanate. Mole ratios of polyisocyanate to diol range from about 1.3 to 2.1. The resulting blocked polyurethane prepolymer then can be unblocked and chain extended with an organic diamine or polyol.
U.S. Pat. No. 3,726,825 discloses polyurethane coatings having moisture vapor barrier properties as well as high gloss, abrasion resistance, etc. required of such coatings. The linear thermoplastic polyurethane resins are prepared by reacting a non-halogenated organic diisocyanate with an organic dihydroxy compound and from about 0.1 to 0.9 moles of neopentylglycol. The resulting polyurethane prepolymer then is cured under anhydrous conditions.
U.S. Pat. No. 5,208,334 discloses a process for the production of a low viscosity isocyanurate system containing isocyanurate and allophanate groups by catalytically trimerizing a portion of the isocyanate groups, adding a monoalcohol to the organic diisocyanate prior to or during the trimerization reaction and terminating the trimerization by adding a catalyst poison. The unique isocyanurates overcome two problems associated with isocyanates containing isocyanurate groups, one relating to viscosity thereby permitting reduced solvent in the coating formulation and the other relating to incompatibility with the polyol.
U.S. Pat. No. 5,115,071 discloses high performance coating compositions which are based upon the reaction of a prepolymer having a low oligomer content and a polyol. More specifically, the prepolymer is an end capped prepolymer which is formed by the reaction of a diisocyanate and a multifunctional polyol, the prepolymer having at least about 85 preferably 90 percent by weight of a 2:1 adduct of isocyanate to polyol (NCO/OH) and less than about 1 and preferably less than about 0.5% by weight of residual diisocyanate monomer therein.
SUMMARY OF THE INVENTION
This invention relates to improved two part, low VOC polyurethane coatings comprising a low viscosity polyisocyanate crosslinker component having an isocyanate functionality greater than two and a polyol component having a functionality equal to or greater than two. The improvement resides in the utilization of a unique isocyanate component in the two part polyurethane coating formulation. The isocyanate component comprises said low viscosity polyisocyanate crosslinker and an isocyanate terminated or end capped prepolymer formed by the reaction of a diisocyanate and a multifunctional polyol, the prepolymer having at least about 85 preferably 90 percent by weight of a 2:1 adduct of isocyanate to polyol (NCO/OH) and less than about 1 and preferably less than about 0.5% by weight of residual diisocyanate monomer therein.
There are several advantages associated with the utilization of the unique isocyanate component for the low VOC coating composition and these include:
an ability to employ spray application technology which allows the use of elevated temperatures to reduce formulation viscosity without concerns over the working life of the formulation and yet achieve desirable dry times;
an ability to reduce or eliminate the need for solvent and thus produce low or near zero VOC polyurethane topcoats for high performance applications and to produce low VOC polyurethane primer coats;
an ability to decrease worker exposure potential due to lower volatility and reduced isocyanate toxicity systems through the use an isocyanate component comprising in part a prepolymer having a very narrow molecular weight distribution with very low residual diisocyanate monomer;
an ability to formulate and apply the coating formulation at or near to a 1:1 volume ratio; and
an ability to produce polyurethane coatings having excellent physical properties such as tensile strength, scratch and solvent resistance.
DRAWINGS
FIG. 1 is a plot showing a view of viscosity profile verses temperature for a 100% solids isocyanate component.
FIG. 2 is a plot showing a view of viscosity profile verses temperature for a low VOC pigmented/polyol grind.
DETAILED DESCRIPTION OF THE INVENTION
The standard procedure for preparing low VOC 2-part polyurethane coatings involves the use of a low viscosity polyisocyanate crosslinker and a high functionality, high molecular weight polyol component. Traditional low viscosity polyisocyanate crosslinker components having a functionality greater than two include isocyanurates, biurets, uretdiones and allophanates. Isocyanurates are formed by the trimerization of aliphatic or aromatic diisocyanates. Trimerization is effected by reacting 3 moles of the diisocyanate with itself or another polyisocyanate to produce a single isocyanurate ring. Phosphines, Mannich bases and tertiary amines, such as 1,4-diazabicyclo 2.2.2!octane dialkyl piperazines, etc. can be used as trimerization catalysts. The biurets are formed via the addition of a small amount of water to two moles isocyanate and reacting at slightly elevated temperature in the presence of a catalyst. The uretdione is formed by the dimerization of the isocyanate. Allophanates are prepared by the reaction of the diisocyanate with a urethane bond. Another class of isocyanates which may be used are isocyanate adducts of low molecular weight polyols. These adducts are formed by the reaction of a low molecular weight polyol, e.g., a triol such as trimethylolpropane and polyether triols such as ethylene oxide and propylene oxide triols with the diisocyanate.
Representative diisocyanates useful in the synthesis of isocyanurate, biurets, uretdiones and adducts of diisocyanates described above, which are then utilized as one of the constituents in the 2 part polyurethane coating formulation, include conventional aliphatic and aromatic diisocyanates. These diisocyanates which may be used alone or mixed include 1,4-tetramethylene diisocyanate, 1, 6-hexamethylene diisocyanate (HDI), 2,2,4-trimethyl-1,6-hexamethylene diisocyanate, 1,12-dodecamethylene diisocyanate, 1-isocyanato-3-isocyanatomethyl-3,5,5-trimethyl-cyclohexane (isophorone diisocyanate or IPDI), tetramethylxylyl diisocyanate (TMXDI), bis(4-isocyanatocyclohexyl)methane (H 12 MDl), and bis(4-isocyanato*3-methyl-cyclohexyl)methane. Aromatic diisocyanates may also be used in formulating the isocyanate component. They may be mixed with the aliphatic diisocyanate or used by themselves in generating the isocyanate component. The aromatic diisocyanates suffer from UV sensitivity and thus are not preferred for the formulation of weatherable topcoats. On the other hand the aromatic diisocyanates may be blended with the aliphatic diisocyanate component or used alone to enhance chemical resistance, the rate of reaction, etc. Examples of aromatic diisocyanates include toluenediisocyanate (TDI), bis(4-isocyanatophenyl)methane (MDI) and the like.
The second part of the unique isocyanate component for preparing the low VOC polyurethane coatings is a diisocyanate prepolymer having an equivalent weight between 250 and 2000 (preferably between 350 and 1000) grams per equivalent. The prepolymers are formed generally by reacting an aliphatic or aromatic diisocyanate with a polyol or mixture of polyols having an average functionality greater than 2 (generally in the range of from 2.2 to 4) and average equivalent weight generally in the range of 200 to 1000 g/eq. An excess of diisocyanate is reacted with the polyol component at an equivalent ratio of greater than 4:1 equivalents NCO per equivalent OH in the polyol to produce a reaction product having at least 85 preferably 90% by weight of a 2:1 NCO/OH adduct of isocyanate to polyol. The unreacted diisocyanate monomer is removed from the prepolymer by distillation or other treatment to a concentration of less than 1% and preferably less than 0.5% of unreacted diisocyanate. Representative diisocyanates that can be used for producing the prepolymers include the above aliphatic and aromatic diisocyanates.
Conventional long chain polyols are used to produce the isocyanate terminated prepolymers. These include di- or multi-functional alkylene ether polyols such as poly (tetramethyleneglycol, PTMG) polyols; poly(propylene oxide) polyols; and poly(ethylene oxide) polyols. Polyether polyols may also comprise ethylene oxide or propylene oxide adducts of polyols such as the ethylene and propylene oxide adducts of ethylene or butylene glycol. Although not a polyol per se, polycaprolactone acts similarly to a polyether polyol and may be utilized. Polyester polyols such as those formed by the reaction of aliphatic or aromatic dicarboxylic acids with glycols can also be used as the polyol component for preparing the polyurethane prepolymers. Specific examples of acids for forming polyester polyols include isophthalic, terephthalic, and adipic acids. Specific glycols include ethylene glycol, diethylene glycol, butanediol, propylene glycol neopentyl glycol and hexane diol and so forth. Acrylic polyols may also be used as a polyol component. In addition to the conventional polyols recited above, polyols having a functionality greater than 2 can be blended with a long chain diol to produce a polyol component for reaction with the polyisocyanate in an amount such that the average functionality is greater than 2 and preferably between 2.2 and 4 and the average equivalent weight is between 100 and 2000. Representative short chain multifunctional polyols having functionality greater than 2 include trimethylolpropane (TMP), glycerol, pentaerythritol, dipentaerythritol, trihydroxybutane, sucrose, and alkoxylated or esterified adducts of the above.
The low oligomer isocyanate terminated prepolymers utilized in forming the isocyanate component can be prepared by reacting the multi-functional polyol composition with a large (greater than 4 to 1 and typically from 6-10:1 ) equivalent excess of the diisocyanate to polyol. The prepolymers essentially comprise two equivalents diisocyanate per equivalent of polyol because of the high ratio of diisocyanate to polyol in the original reaction mixture. Excess diisocyanate is removed to levels less than 1% preferably less than 0.5% by weight in the prepolymer. Temperatures for effecting reaction between the diisocyanate and polyol are conventional, e.g., 0°-120° C. Care should be exercised during removal of the excess diisocyanate so that allophanates, oligomers and other byproducts are not formed. Further description and/or examples are described in U.S. Pat. No. 5,115,071 and the subject matter of that patent is incorporated by reference.
The isocyanate component of the low VOC coatings is prepared by blending the isocyanate-terminated prepolymer with the low viscosity polyisocyanate crosslinker(s), such as the isocyanurate of hexamethylene diisocyanate (HDI trimer) and/or HDI uretdione, as well as other isocyanurates, uretdiones, biurets,, allophanates, or low molecular weight polyol adducts of HDI, IPDI, H 12 MDI, TMXDI, TDI and MDI in a weight ratio ranging from 10:90 to 90:10 prepolymer to low viscosity polyisocyanate(s). Preferably the blend weight ratio is from about 40:60 to 60:40 based on a total weight of 100 weight parts allowing easy formulating of 1:1 mix ratio. In contrast, conventional systems based on a mixture of pigment and acrylic polyol and cured with a polyisocyanate crosslinker, for example, typically exhibit mix ratios pigmented/polyol to the isocyanate component of 2.5 to 6:1
The higher level of partially reacted prepolymer helps to moderate the high reactivity of the low viscosity, high functionality polyisocyanate allowing greater control over reactivity and it is less sensitive to catalyst level variations, particularly at higher (>23° C.) application temperatures. With better control over the cure speed of the film, one can achieve better film appearance. These systems may be formulated such that the reacting components are at similar viscosities thereby enhancing the ease of mixing particularly for meter-mix-dispense type applicators. A conventionally prepared prepolymer, if used in this blend, would require large amounts of solvent to attain sufficient application viscosity. High molecular weight oligomers in these conventional prepolymers not only increase the solvent demand of the formulation, but also lead to shorter pot lives because of rapid molecular weight build.
A retrospective look at compositional analysis helps to illustrate the above points. First, by using a "pre"-polymer of the type utilized herein, diisocyanate monomer content is reduced and the reactivity of this partially reacted system is simpler to control. Second, casual inspection of traditional prepolymer compositions which have from 55 to 60% of a 2:1 adduct, 35-45% oligomer content having isocyanate to polyol ratios of 3:2, 4:3 and 5:4 and a residual isocyanate monomer content of 2-4% by weight now helps to explain why conventional prepolymers have seen limited use in higher solids coatings formulations. In contrast, an examination of the composition of the prepolymers employed here, having from 85 to about 95% of a 2:1 adduct, a low oligomer content of from 5 to 15% and <1% and preferably <0.5% by weight residual isocyanate monomer content shows why the combination of this prepolymer with the low viscosity polyisocyanate offers some of the observed improvements.
Solvents can be added to the formulation to achieve desired viscosity. Obviously, one would prefer to use as little solvent as possible in producing these low VOC coatings. Typical solvents which can be used include but are not limited to xylene, toluene, methylethylketone, methylamylketone, ethylacetate, tetrahydrofuran, and n-butylacetate.
Conventional catalysts used to accelerate the reaction between the isocyanate component and the polyol component may be incorporated into the formulation. Example of catalysts include metal based compositions, such as dibutyl tin dilaurate and zinc carboxylate.
The following examples are intended to represent various embodiments and are not intended to restrict the scope thereof.
EXAMPLES 1 and 1A Prior Art Isocyanurate of Hexamethylene Diisocyanate/Acrylic Polyol Polyurethane coating Formulation
A conventional polyisocyanate/acrylic polyol coating composition was prepared in a conventional manner. First, the pigmented polyol mix was prepared and then blended with the isocyanate component. The formulation is shown in Table 1 and 2.
A second sample, 1 A, was prepared using the same formulation as Example 1 except that the Dabco and Mooney catalysts were omitted from the formulation. One of the problems associated with the Example 1 formulation was that the pot life was so short there was barely enough time to handle the polyisocyanate/acrylic polyol coating composition after formulation. Thus, Example 1 was repeated as Example 1A except the catalyst was eliminated in order to extend pot life.
TABLE I__________________________________________________________________________ Supplied. SolventRaw Material Component Eq. Wt. % Solids lb./gal lb./gal__________________________________________________________________________Chempol 17-3855 acrylic polyol 637.50 80 8.70 7.26Zoldine RD-4 oxazolidine 89.30 100 7.57 0.00Ti-Pure R-960 TiO.sub.2 pigment 0.00 100 33.20 0.00Nuosperse 657 pigment 0.00 70 7.90 6.55 dispersantTEGO 980 air release agent 0.00 100 7.95 0.00TINUVIN 384 UV adsorber 0.00 95 8.81 7.26Tinuvin 292 hindered amine 0.00 100 8.34 0.00 light stabilizerDABCO 120 tin (IV) catalyst 0.00 100 8.33 0.00MOONEY 18% Zn zinc carboxylate 0.00 84 8.77 7.26 catalystDISLON NS-30 pigment anti- 0.00 15 7.36 7.26 settling agentMethyl amyl ketone 0.00 0 6.80 6.80Desmodur N-3300 HDI isocyanurate 195.00 100 9.70 0.00__________________________________________________________________________
TABLE 2______________________________________Pigmented Polyol Volume Weight Volume SolidsComponent Weight lb. Gallons Solids lb. Gallons______________________________________Chempol 17-3855 339.28 39.00 271.43 29.65Zoldine RD-4 67.86 8.96 67.86 8.96Ti-Pure R-960 400.68 12.07 400.68 12.07Nuosperse 657 4.40 0.56 3.08 0.36TEGO 980 4.32 0.54 4.32 0.54TINUVIN 384 9.73 1.10 9.25 1.04Tinuvin 292 9.25 1.11 9.25 1.11DABCO 120 0.31 0.04 0.31 0.04MOONEY 18% Zn 3.67 0.42 3.08 0.34DISLON NS-30 1.64 0.22 0.25 0.03Methyl amyl ketone 50.35 7.40 0.00 0.00Total 891.49 71.42 769.51 54.14Isocyanate 277.15 28.57 277.15 28.71Component II:Desmodur N-3300Total 1168.64 100.00 1046.64 82.71______________________________________ Weight Solids, % = 89.56 Volume Solids, % = 82.71 P/B Ratio (pigment/binder) = 0.65 PVC, % pigment/volume content = 115.23 Weight/gallon = 11.69 NCO:OH Ratio = 1.10 Mix Ratio = 2.50 VOC, lbs/gal = 1.22
EXAMPLES 2 Prior Art 2:1 Prepolymer/Polyol Weatherable Coating Formulation and Coating Performance
A high solids formulation for weatherable applications based on acrylic polyols is shown. The formulation is detailed in Table 3. The isocyanate prepolymer of this formulation is a commercial prepolymer sold under the trademark Airthane® ASN-540M, based on isophorone diisocyanate (IPDI) and a mixture of neopentyl glycol adipates. The prepolymer had been prepared to have a reacted 2:1 NCO/OH ratio and a residual diisocyanate monomer content of less than 0.5% by weight. More specifically, the prepolymer had a nominal equivalent weight of 540 g/eq (on solids) and an average functionality of about 2.5. It is used in this formulation as an 85% solids solution in methyl amyl ketone (MAK). The oligomer content is less than 15% by weight of the prepolymer. This formulation is delivered at a 1:1 volume mix ratio of prepolymer to polyol in conventional plural component application equipment.
TABLE 3__________________________________________________________________________Typical formulation for high solids weatherable polyurethane topcoatMaterial Weight (%) Volume (%) Supplier Comments__________________________________________________________________________PolyolComponent MixChempol 17-3855 21.02 27.84 CCP acrylic polyolZoldine RD4 1.87 2.84 Angus oxazolidine reactive diluentTi-Pure R960 33.36 11.58 DuPont TiO.sub.2 pigmentDisperbyk 110 1.58 2.14 Byk-Chemie pigment dispersantDislon NS-30 0.14 0.21 King Industries pigment anti- settling agentTinuvin 292 0.77 1.06 Ciba-Geigy hindered amine light stabilizerTinuvin 400 0.91 1.26 Ciba-Geigy UV adsorberTego 980 0.36 0.52 Tego Chemie air release agentDABCO 120 0.05 0.07 Air Products tin (IV)catalyst18% Zn-Oct 0.31 0.40 OMG zinc carboxylate catalystMAK 1.21 2.05 methyl amyl ketoneSubtotal 61.58 49.97IsocyanateComponentAirthane 38.42 50.03 Air-Products isocyanateASN-540M prepolymerTotal 100.00 100.00__________________________________________________________________________ Weight solids = 87.76%; Volume solids = 79.94%; PVC = 15.27%; VOC = 169 g/L (1.41 lb./gal); Mix Ratio: 1:1
EXAMPLE 3 2:1 Prepolymer and Isocyanurate Blend Weatherable Coating Formulation and Coating Performance
A high solids formulation for weatherable applications based on acrylic polyols and similar to Example 2 is shown. The formulation is detailed in Table 4. The isocyanate component consisted of an isocyanurate of hexamethylene diisocyanate blended with a prepolymer. The prepolymer is a commercial prepolymer sold under the trademark Airthane® ASN-540M based on isophorone diisocyanate (1PDI) and a mixture of neopentyl glycol adipates. The weight ratio of isocyanurate to prepolymer was 20/80. This formulation is delivered at a 1:1 volume mix ratio of prepolymer/isocyanurate blend to polyol in conventional plural component application equipment.
TABLE 4______________________________________Raw Material VolumeComponent 1: Weight Volume Weight Solids Solids______________________________________Chempol 17-3855 234.36 26.94 187.49 20.48Zoldine RD-4 46.87 6.19 46.87 6.19Ti-Pure R-960 408.75 12.31 408.75 12.31Nuosperse 657 6.29 0.80 4.40 0.51TEGO 980 4.40 0.55 4.40 0.55TINUVIN 384 9.93 1.13 9.43 1.06Tinuvin 292 9.43 1.13 9.43 1.13DABCO 120 0.31 0.04 0.31 0.04MOONEY 18% Zn 3.74 0.43 3.14 0.34DISLON NS-30 1.68 0.23 0.25 0.03Total 725.76 49.75 674.47 42.64Isocyanate 371.28 41.95 315.59 33.76Component II:AIRTHANE ASN-540MDesmodur N-3300 78.90 8.31 78.90 8.31Total 1175.95 100.00 1068.98 84.72______________________________________ Weight Solids, % = 90.90 Volume Solids, % = 84.72 Weight/gallon = 11.76 NCO:OH Ratio = 1.10 P/B Ratio = 0.65 Mix Ratio = 0.99 PVC, % = 15.19 VOC, lb./gal = 1.07
EXAMPLE 4 Physical and Mechanical Test
Physical and mechanical tests were performed on samples prepared from Examples 1, 1A, 2 and 3. The results are set forth in Table 5.
TABLE 5______________________________________PROCESSING, PHYSICAL AND MECHANICAL PROPERTIES Example 1ATest Example 1 No Cat Example 2 Example 3______________________________________Dry Times (hr.)STT 0.5 1 3 0.5TF 0.5 12 10 2TC 0.5 13.5 16 3.5DFT (mils) 2.5 2.6 2.5 2.3Gloss20 87.9 86.7 84.7 8560 95 93.9 92.6 93.285 97.2 96.6 97.6 96.4HardnessPersoz (s) 110 112 56 98Pencil (gouge) HB HB HB HBAdhesionx-hatch dry 4B 4B 4B 4Bx-cut dry 4A 4A 5A 4Ax-cut, 24 hr wet 4A 4A 3-4A 4AScratch (g) 1800 2000 1500Impact D/R (in- 160/140 160/120 160/160 160/160LB)Chem 24 SpotNaOH 10% 4 4 3 4HCl 10% S2 4 0 4HNO3 35% S2 4 1 1xylene 2 2 1,2 2MEK 2 2 0 0IPA 2 2 2 2MEK rubs 100+ 100+ 100+ 100+comments sl soft sl soft soft, burnish soft, burnish______________________________________ STT = set to touch, TF = tack free, and TC = through cure; Chem spot0 = delaminated, 1 = blistered, 2 = softened, 3 = discolored, and 4no detectable discoloration, sl = slightly.
Although not reported the pot life of Examples 2 and 3 was estimated to be about 1 to 1.5 hours. Surprisingly, although the pot lives were essentially the same, the rate of cure of the 80/20 prepolymer/isocyanurate ratio was much greater. The TF and TC values for the Example 3 formulation were much lower than the Example 2 formulation and lower than the non catalyzed Example 1A formulation. The effect of the isocyanurate addition to the prepolymer blend is also noted in the Persoz hardness. A small amount of isocyanurate increased the Persoz hardness from 56 to 98; the 100% isocyanurate level utilized in Example 1 and 1 A was only slightly higher. Chemical resistance was also enhanced by the utilization of the prepolymer/isocyanurate blend in that total delamination in 10% HCI occurred for the Example 2 formulation while excellent results were obtained with the blend used in Example 3. Resistance to alkali and aromatic solvents was also better.
EXAMPLE 5 Prepolymer/Isocyanurate Blend with Polyester Polyol
A formulation similar to Example 3 was prepared with the exception that the isocyanate component consisting of the Airthane prepolymer, an isocyanurate of hexamethylene diisocyanate, and the uretdione of hexamethylene diisocyanate, contained no solvent, the blend weight ratio of the mixture of prepolymer and the mixture of isocyanurate and uretdione was 50/50 and the polyol component was based on a polyester/polycaprolactone polyol mixture as opposed to the acrylic polyol. It was formulated at less than 24 g/L (0.20 lb./gal). A typical formulation is detailed in Table 6. Viscosity profiles versus temperature for the isocyanate and polyol components are shown in FIGS. 1 and 2, respectively.
TABLE 6______________________________________Typical Formulation for Low VOC Topcoat Weight VolumeMaterial (% (% Supplier Comments______________________________________Polyol/PigmentComponent IChempol 18- 15.00 20.11 CCP polyester polyol2244Tone 0301 6.43 9.10 Union Carbide solvent-free caprolactone- based polyolTi-Pure R960 37.77 14.57 DuPont pigmentDisperbyk 110 1.68 2.52 Byk-Chemie dispersantDislon NS-30 0.16 0.27 King lndustries thixotropeTinuvin 292 0.58 0.89 Ciba-Geigy HALSTinuvin 400 0.68 1.06 Ciba-Geigy UV stabilizerTego 980 0.29 0.47 Tego Chemie air releaseByk 320 0.33 0.61 Byk-Chemie flow aidDABCO 120 0.03 0.04 Air Products catalyst18% Zn-Oct 0.35 0.51 OMG zinc catalystSubtotal 63.30 50.15IsocyanateComponent IIAirthane 18.36 25.38 Air Products isocyanateASN-540 prepolymerDesmodur 9.17 12.12 Miles/Bayer HDI isocyanurateN3300Luxate HD-100 9.17 12.35 Olin HDI uretdioneSubtotal 36.70 49.85Totals 100.00 100.00______________________________________ Weight solids = 98.74%; Volume solids = 97.94%; PVC = 15.57%; VOC = 19 g/ (0.16 lb./gal); Mix Ratio: 1:1
Note the low VOC level in the formulation. It is about one-tenth that of Example 3 which is about 50% lower than a standard isocyanurate based polyurethane coating system.
The use of the low oligomer prepolymer is critical to the success of this mixture. A conventional prepolymer would have too high a viscosity and most likely impart poor sprayability to the formulation. Note, again, that the materials have very similar viscosities at an application temperature of 60° C. The fact that these components have similar viscosity profiles means, in part that the isocyanate and polyol can be easily mixed at the 1:1 ratio. What is also surprising about the viscosity profiles is that the formulations were essentially at zero VOC, yet the two components have very similar viscosities. Usually, with conventional systems, as solvent is reduced to very low levels, viscosity differences increase dramatically, an undesirable result which is avoided through the isocyanate component described herein.
EXAMPLE 6 Physical And Mechanical Property Comparisons Of Formulations 1 And 2
Physical and mechanical property comparisons of the formulations in Examples 1A, 3 and 5 were made. The results are shown in Table 7.
TABLE 7__________________________________________________________________________Representative Film Property Comparison Example 3 Prepolymer Example 5 Prepolymer Example 1 A Polyisocyanate Polyisocyanate Isocyanurate/ Crosslinker Acrylic Crosslinker PolyesterProperty Acrylic Polyol Polyol Polyol__________________________________________________________________________Set time (hours) 1 0.5 2Dry hard (hours) 13.5 3.5 3Pencil Hardness HB HB HBDry Adhesion 4A 4A 4A(ASTM D3359)Wet Adhesion 4A 4A 4A(24 h, D3359)Impact (D/R in-lb.) 160/160 160/160 160/160MEK rubs 100+ 100+ 100+60° Gloss 94.7 92.6 95.3Gloss Retention 88% 92% 97%(1000 h, UV-B313)__________________________________________________________________________
It is important to note that the handling of the isocyanurate/acrylic polyol conventional or control formulation was much more difficult than was the prepolymer/isocyanurate crosslinker based formulation of Examples 3 and 5. Furthermore, the conventional or control formulation had to be formulated at 2.5:1 volume parts isocyanurate to polyol, i.e., a non-integer mix ratio, and the control demonstrated an extreme sensitivity to catalyst level.
EXAMPLE 7 Catalyst Sensitivity Studies
Catalyst sensitivity studies were conducted on Examples 1,2 and 5. The results are shown in Table 8.
TABLE 8______________________________________CATALYST LEVEL SENSITIVITY STUDY(ACRYLIC FORMULATIONS)Catalyst Level set time hr tack time dry hard pot life hr gel time______________________________________Example 1none 5 16 20 0.75 59421/2 x 0.75 1.25 6 0.25 182x 0.17 0.5 3 0.17 83Example 2none 6.5 24 48 3 77631/2 x 3 13 24 1.17 4715x 3 8 22 0.67 23042 x 1.5 3 9 0.33 871Example 5none 16 34 48 3 83471/2 x 1 2 6 0.5 1139x 0.5 1 4 0.5 632______________________________________
The above results show that the Example 5 formulation, even though a polyester polyol was used, with no catalyst the pot life and dry times resembled the prior art prepolymer formulations (Example 2). On the other hand, with added catalyst the Example 5 sample showed very fast dry times with reasonable pot lives. | This invention relates to improved two part, low VOC polyurethane coatings comprising a low viscosity polyisocyanate component having an isocyanate functionality greater than two and a polyol component having a functionality equal to or greater than two. The improvement resides in the utilization of a unique isocyanate component in the two part polyurethane coating formulation. The isocyanate component comprises said low viscosity polyisocyanate component and an isocyanate terminated or end capped prepolymer formed by the reaction of a diisocyanate and a multifunctional polyol, the prepolymer having at least about 85 preferably 90 percent by weight of a 2:1 adduct of isocyanate to polyol (NCO/OH) and less than about 1 and preferably less than about 0.5% by weight of residual diisocyanate monomer therein. | 2 |
FIELD OF THE INVENTION
This invention relates generally to a handle grip for wire handle containers and the like. It relates particularly to a handle grip for shopping basket handles.
BACKGROUND OF THE INVENTION
Hand carried shopping baskets are popular with customers in grocery stores, for example, where smaller quantities of goods are involved, i.e., where wheeled shopping carts are unnecessary. Conventional baskets have two wire handles, each in an inverted U-shaped configuration, pivotally connected to a basket rim in spaced relationship. The basket might be fabricated of wire, itself, although molded plastic baskets are now widely used.
To carry the basket, the two basket handles are brought together and gripped by the shopper in a well-known manner. The basket can be carried easily and little, if any, discomfort is caused by the wire in the shopper's hand when the basket is empty or only lightly loaded. When the basket is loaded, however, its weight causes the wire handles to painfully press into the shopper's hands because forces are concentrated.
Of course, there have been numerous force dispersion handle grips designed for wire handles in the same or similar environments. An example is illustrated in the Sweeny U.S. Pat. No. 4,932,702. None affords a high degree of shopper comfort while still being simple, inexpensive and highly reliable, however. The present invention is directed toward overcoming the shortcomings of the prior art.
SUMMARY OF THE INVENTION
A primary object of the present invention is to provide a new and improved handle grip for shopping basket handles or the like.
Another object is to provide a one-piece, molded plastic handle grip which closes and locks securely on each wire handle of a shopping basket.
Yet another object is to provide a handle grip which is mounted so that the force exerted on the grip during use serves to further prevent opening of the handle.
Still another object is to provide a handle grip which is simple and inexpensive in construction.
A further object is to provide an improved handle grip assembly for two handles on a shopping basket.
The foregoing and other objects are realized in accord with the present invention by providing a clam-shaped, one-piece, molded plastic handle grip which closes and locks securely on each wire handle or bail of a shopping basket. The grips associated with the two handles abut each other when they are grasped in the shopper's hand to carry the basket. This force exerted on the grips causes each grip to remain securely closed and, in fact, as the load in the basket increases the force holding the grip closed increases. The size and shape of each grip, and the assembly of grips, obviates shopper discomfort normally associated with carrying a loaded basket.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention, including its construction and operation, is illustrated more or less diagrammatically in the drawings, in which:
FIG. 1 is a perspective view of a shopping basket whose two wire handles are fitted with handle grips embodying features of the present invention;
FIG. 2 is an enlarged perspective view of the handle grip assembly formed when the handles and grips shown in FIG. 1 are grasped and held by a shopper;
FIG. 3 is a further enlarged front elevational view of a single handle grip embodying features of the invention, in its closed and locked position on a portion of wire handle;
FIG. 4 is a side view of the grip in its open position;
FIG. 5 is a top view of the grip in its open position;
FIG. 6 is a bottom view of the grip in its open position;
FIG. 7 is an end view of the grip in its open position;
FIG. 8 is an enlarged sectional view through a mounted handle grip taken along line 8--8 of FIG. 3; and
FIG. 9 is a sectional view similar to FIG. 8 showing the grip in the process of being closed on a wire handle of a basket.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to the drawings, and particularly to FIGS. 1 and 2, a conventional shopping basket is seen generally at 10. The basket 10 is fabricated of molded plastic, and is adapted to be carried by a shopper through the medium of two U-shaped (inverted) wire handles 11 and 12. As will be seen, each handle 11 and 12 includes a pair of legs 20 pivotally connected to the basket 10, and a base 21 connecting the legs.
Each handle 11 and 12 is fabricated in a conventional manner from either 8 or 9 gauge steel wire. The wire base 21 of each handle 11 and 12 has an offset section 24 at its mid-point, and a handle grip 30 embodying features of the invention is mounted on it. The handle grips 30 for both handles come together in flush, mating relationship when they are gripped by a shopper, as seen in FIG. 2.
Referring now to FIGS. 4-7, a handle grip 30 is shown in its open configuration, i.e., as it appears after fabrication and before mounting on a basket handle 11 or 12. The grip 30 is molded in one piece of plastic using conventional techniques. In the preferred embodiment, the plastic used is a polypropylene.
The handle grip 30 comprises an elongated body component 31 and a correspondingly elongated cover component 32 joined by a somewhat shorter, but still elongated, hinge component 33. The body component 31 is 4 inches long, 0.750 inches deep and 0.598 inches wide in the embodiment illustrated. The cover component 32 is slightly shorter and slightly narrower, for reasons which will hereinafter become apparent.
The body component 31 comprises a combined outer side wall and bottom wall 41 which is scalloped along its length to create four indentations 42 for receipt of the four fingers of a shopper's hand. The wall 41 is arcuate in cross-section along its length. The radius of the arc varies, however, depending upon the position on the wall 41 in relation to the four indentations 42.
The body component 31 also comprises a top wall 44 which joins the combined outer and bottom wall 41. The top wall 44 includes an elongated central wall section 46 and bracketing outer wall sections 47. The central wall section 46 and bracketing outer wall sections are each flat. However, the outer wall sections are inclined downwardly relative to the central wall section 46, as best seen in FIG. 4.
The body component 31 also comprises two end walls 51, and three internal compartment walls 52 which lie parallel to the end walls. The compartment walls 52 provide structural rigidity to the body component 31.
The end walls 51 and the compartment walls 52 each have a roughly semi-circular depression 55 formed therein, as best seen in FIG. 7. These depressions 55 collectively define a receptacle for the offset section 24 of each wire handle, the insertion of which will hereinafter be discussed in detail.
Piercing the arcuate outside and bottom wall 41, in a horizontal path at each of the four scalloped indentations 42, are four locking ports 61. Each of the four locking ports 61 includes a vertically oriented locking lip 62 (see FIG. 9). The operation of the ports 61 and corresponding locking lips 62 will hereinafter be discussed in the context of the assembly of the handle grip 30.
Turning now to the cover component 32 of the grip 30, it will be seen to have a configuration corresponding to that of the inner, exposed side of the body component 31. As such, it comprises a flat wall 71 which has scalloped outer indentations 72. Extending perpendicular to the wall 71, at the base of each indentation 72, is a locking tab 73. Each locking tab 73 has a locking shoulder 74 formed on its lower surface, the purpose of which (as hereinafter discussed) is to mate with a corresponding locking lip 62 in the arcuate outside and bottom wall 41.
The components 31 and 32 are formed unitarily with, and joined by, the hinge component 33, as has been pointed out. The hinge component 33 is approximately one-half the thickness of the walls 41 and 44 making up the components 31 and 32, as will be seen. In this regard, the walls 41 and 44 are approximately 1/8 inch thick and the hinge component 33 is approximately 1/16 inch thick in the handle grip 30 illustrated. The cover component 32 pivots on the hinge component 33 to mate with the body component 31 and form a flat inner side wall for the handle grip 30.
Referring now to FIGS. 3, 8 and 9, in addition to FIGS. 1-7, a grip 30 is shown as it is being closed and locked onto a wire handle section 24 (FIG. 9) and as it appears when locked on (FIGS. 3 and 8). The wire section 24 is first seated in the depressions 55 formed in end walls 51 and compartment walls 52 of the body component 31. The cover component 32 is then closed over the body component 31.
As the cover component 32 closes, the hinge component 33 bends, acting as a hinge. The locking tabs 73 enter corresponding locking ports 61. The locking shoulders 74 pass by, and snap behind, corresponding locking lips 62. As best seen in FIG. 8, the cover component 32 is then permanently locked closed over the body component 31. The tabs 73, in entering the locking ports 61, bend outwardly in elastic deformation until their shoulders 74 pass the lips 62, when they return to their undeformed shape, creating the locking effect described.
The external dimensions of the cover component 32 are such that it nests inside the body component 31, as best seen in FIGS. 4 and 8. As such the cover component 32 nests between portions of the two end walls 51 of the body component 31.
The handle grips 30 for each handle 11 and 12 are identical. However, as will best be seen in FIG. 2, they are oriented 180° from each other when mounted on corresponding handle sections 24. As such, the cover components 32 of two grips 30 engage each other when the basket 10 is lifted. As the basket 10 is loaded, the grips 30 are pressed tightly together. The effect is that the only forces acting on the grips 30 serve to maintain their closed relationship with the handles 11 and 12, rather than disturb it.
While preferred embodiments of the invention have been described, it should be understood that the invention is not so limited and modifications may be made without departing from the invention. The scope of the invention is defined by the appended claims, and all devices that come within the meaning of the claims, either literally or by equivalence, are intended to be embraced therein. | A handle grip and handle grip assembly for shopping baskets. A pair of identical handle grips are fabricated of molded plastic, each comprising a unitary body component and cover component connected by a hinge component. A handle element is seated in each body component and the corresponding cover component closes over the handle element and is locked to the body component. The cover components of the grips engage each other when the basket is carried and the weight of the basket increases the engagement force. | 1 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to entertainment and architectural lighting, and more specifically is a device utilizing a conical lens array to control the divergence and/or shape of a beam of light, and the hue, saturation, and brightness of color of the beam of light emanating from a lighting module.
2. Description of the Prior Art
Lighting modules are often used in the theater, television, touring productions, and architectural applications. The divergence and shape of a light beam, as well as the hue, saturation, and intensity of the color of the light emitted, may be varied according to the wishes of the user to obtain a particular artistic effect. The artistic requirements might be that the emitted light beam remain static, or that it change over time. Cost, speed of changing effects, the quantity of effects produced, the smoothness of transition, compact size and weight, and the efficiency of transmitting light are all factors in the practical usage of a lighting module system.
The prior art most relevant to the present invention is disclosed in Applicant's prior U.S. Pat. No. 6,048,081, issued Apr. 11, 2000, U.S. Pat. No. 6,142,652, issued Nov. 7, 2000. The above referenced patents are incorporated by reference herein in their entirety. The '081 patent discloses a device that diffuses a light beam to control the divergence and/or shape of a beam of light emanating from a lighting module. The '081 device, see FIGS. 1 and 2, includes a light source 10 and a reflector 12 to direct the light along an optic path. A primary lens element 16 reduces the cross section of an effected light region as the light enters a diffusion assembly area 30 in the optic path. Diffusion elements 1801 in the diffusion assembly 18 are deployed in varying combinations and to varying degrees to produce the shape and size of light beam desired by the user. The action of the lens segments 161 allows the diffusion elements to be physically positioned in the optic path but to have no effect on the light until the diffusion elements are rotated so that diffusion element segments align with lens segments, and the diffusion element then changes the light being projected from the lighting module.
Similarly, the '652 patent discloses a device to control the hue, saturation, and brightness of color emanating from a lighting module. The '652 device, see FIGS. 3 and 4, also includes a light source 10 and a reflector 12 to direct the light along an optic path. A primary lens element 16 reduces the cross section of effected light regions as the light enters a filter assembly area 30 in the optic path. Filters 181 ′ in the filter assembly 18 ′ are deployed in varying combinations and to varying degrees to produce the color, hue, and intensity of light desired by the user. As with the '081 device, the refracting action of the '652 lens segments allows the filters to be physically positioned in the optic path but to have no effect on the light until the filters are rotated so that filter element segments align with lens segments, and the filters then change the light being projected from the lighting module.
In working with and developing the prior art systems disclosed above, the inventor has discovered some shortcomings in the prior art. In particular, it has been determined that it is inefficient to treat the light from the light source as though all the light rays are parallel to the center line of the source. Moreover, it has been discovered that placement of the light modifying elements midway between the primary optical element and the secondary optical element also generates some inefficiency in the system.
Accordingly, it is an object of the present invention to provide a light projection module that utilizes light from a source projected at an angle not parallel to a center line of the light path.
It is a further object of the present invention to modify the placement of the light modifying element or elements between the primary optical element and the secondary optical element.
SUMMARY OF THE INVENTION
The present invention is a lighting module that modifies a light beam to affect the size and shape and color characteristics of the projected beam. The device includes a light source and a reflector to direct the light along an optic path. The reflector is formed so that light is directed along a light path that is not parallel to a center line of the reflector. A primary lens element reduces the cross section of an effected light region as the light enters a modifying element area in the optic path. Light modifying elements are deployed in varying combinations and to varying degrees to produce the shape, size, and color of light beam desired by the user. The construction of the light modifying elements allows the elements to be physically positioned in the optic path but to have no effect on the light until the elements are rotated so that light modifying element segments align with lens segments of the primary optical element, and the light modifying element or elements change the light being projected from the lighting module.
An advantage of the present invention is that it provides a single, compact unit that allows the user to project various sizes and shapes of light beams. This eliminates the need for multiple pieces of equipment.
Another advantage of the present invention is that it is simple and inexpensive to manufacture and is therefore reliable and easy to maintain.
Still another advantage of the present invention is that the lens segments allow the diffusion elements to be installed in the optic path, the diffusion elements having no effect when in a non-deployed position.
A further advantage of the present invention is that the use of an angled light reflector increases the efficiency of the system.
These and other objects and advantages of the present invention will become apparent to those skilled in the art in view of the description of the best presently known mode of carrying out the invention as described herein and as illustrated in the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a prior art light beam shaping system.
FIG. 2 shows the effect of the prior art system of FIG. 1 on the transmitted light.
FIG. 3 shows a prior art color filter system.
FIG. 4 shows the effect of the prior art system of FIG. 3 on the transmitted light.
FIG. 5 is a perspective view of a lighting module with a conical lens array according to the present invention.
FIG. 6 is a top view of a lighting module with a conical lens array according to the present invention.
FIG. 6A is a top view of a lighting module with a conical lens array according to the present invention and with a plurality of light modifying elements.
FIG. 7 is a top sectional view of a lighting module with a conical lens array according to the present invention.
FIG. 8 is a front view of a conical lens array according to the present invention.
FIG. 9 shows a segment of the optical ray trace of the system with the light modifying element not introduced into the optical path.
FIG. 10 shows a segment of the optical ray trace of the system with the light modifying element partially deployed in the optical path.
FIG. 11 shows a segment of the optical ray trace of the system with the light modifying element moved off center to compensate for non-parallel light rays.
FIG. 12 is a detail view of a light modifying element as viewed along the optical path.
FIG. 13 is a detail view of an alternate light modifying element viewed along the optical path.
FIG. 14 is a detail view of a light modifying element adapted to control the size of the projected beam.
FIG. 15 is a sectional view of a light modifying element that would be used to produce a wide projected beam.
FIG. 16 is a sectional view of a light modifying element that would be used to produce a narrow projected beam.
FIG. 17 illustrates a typical lighting module device constructed according to the present invention.
FIG. 18 illustrates another typical lighting module device constructed according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is a light beam module that uses a conical lens array to control the divergence, shape, and color—including hue, saturation, and brightness of color—of light emanating from a lighting module. The basic conformation of the light controlling module used in conjunction with a light source is illustrated in FIGS. 5-7.
Referring first to FIG. 5, a light source 10 is shown for reference in describing the operation of the system. The light source 10 may be nearly any type or size light source —arc or incandescent or a light source with a condenser lens. These light sources are well known to those skilled in the art.
The light source 10 is typically located within an optical element that redirects light from the light, a reflector 12 . The reflector 12 , as is the case with the light source 10 , may be of any common type or size. A modified parabolic reflector is depicted in the drawings. However, one of the key differences of the present invention as compared to the prior art is that the reflector 12 is set up so that the light paths of inbound light rays 14 leaving the reflector 12 are not parallel to a center line of the reflector, but rather are deflected inward (see FIGS. 6, 6 A, and 7 ). In the module of the present invention, the optical path also includes a primary optical element 16 , at least one light modifying element 18 , and a secondary optical element 20 . The light rays exit the secondary optical element 20 as outbound light rays 22 .
The inbound light rays 14 emanate from the reflector 12 in substantially parallel paths. However, in the present invention the light rays are not directed along paths parallel to the center of the reflector 12 , but rather are angled inward at an angle α. In the preferred embodiment, αis an angle of 5°. The angling of the light paths causes a larger percentage of the light from the light source 10 to pass through the primary optical element 16 . Optical elements 16 and 20 bend light as a result of their conical shape, therefore light exiting the module becomes again generally parallel, and is directed along a path parallel to the centerline of the device.
As can best be seen in FIGS. 6, 6 A, and 7 , the optical elements 16 and 20 are conical lens arrays. That is, sections of the optical elements 16 and 20 are not cylinders, but rather the arrays are conical in profile, angling upward from a center point of the optical elements 16 and 20 at an angle β. In the preferred embodiment, the angle βis approximately 12°.
The angling of the optical elements 16 and 20 ensures that the maximum refractive angle of light emanating from elements 16 and 20 is constant across the radius of the element. With the cylindrical optical elements of the prior art, the maximum refractive angle varies from an outer radius to an inner radius. Light contacting the conical lens array of the optical elements 16 and 20 of the present invention at an outer radius is subject to the same maximum refractive angle as light contacting the optical element at a middle or an inner radius. This refractive angle, y, is approximately 30° and can be seen clearly in FIG. 9 .
FIG. 8 is a front view of the secondary optical element 20 as viewed in its position along the optical path longitudinal axis. In the preferred embodiment of the present invention, the secondary optical element 20 is comprised of twenty-five identical lens segments 201 . The lens segments 201 are wedge shaped, and are positioned adjacent to one another radially around a center point 202 of the secondary optical element 20 . A focal line 203 of each lens segment 201 optimally originates at the center 202 of the optical element 20 , and emanates outward along a longitudinal center of the lens 201 . The secondary optical element 20 is preferably a unitary element formed from a solid piece of material, typically by a molding process.
While the number of elements 201 , and indeed the shape of the segments 201 , is not critical to the operation of the device, it is preferable to have an odd number of lens segments 201 . It has been found in practice that an odd number of segments produce a more even field of projected light rays 22 . This is more apparent when the projected light falls onto a surface such as a wall or a stage. This is the result of light from region 204 of the optical element 20 diverging slightly in inward and outward directions. With a size element engaged the divergence can be significant. Half of this light diverges in the outward direction and the remaining light diverges in the inward direction. The inward light, as it travels away from the optical element 20 , eventually crosses the center and becomes outward projecting on the opposite side. If, as shown, there are an odd number of segments, this light fills the area not filled by the projected light from 205 and 206 . This filling is accomplished with all segments and in all directions, and results in a more even field of projected light.
FIGS. 9 and 10 are ray traces that show a side view of a pair of typical lens segments 161 . FIG. 9 shows the module with the light modifying element 18 not to introduced into the optical path, and FIG. 10 shows the situation with the light modifying element 18 introduced into the optical path. Inbound light rays 14 enter from the left and strike the lens 161 . Refracted light rays 24 exit each lens 161 and converge at a focal point 26 . All the focal points 26 lie on the corresponding focal lines 163 of the lens segments 161 . The light rays then become divergent light rays 28 as they exit the focal point 26 and strike a lens segment 201 of the secondary optical element 20 . Outbound light rays 22 are then again generally parallel. FIG. 9 is drawn with the assumption that all the inbound light rays 14 are parallel.
However, as FIG. 11 depicts, the inbound light rays 14 are not all parallel. Therefore, to achieve the optimal effect, the focal point must be positioned off center between the primary optical element 16 and the secondary optical element 20 . To capture the maximum percentage of refracted light rays 26 on the light modifying element 18 , length A must be greater than length B.
The secondary optical element 20 has a slightly different focal length as compared to the primary optical element 16 . The difference in focal lengths is determined by the specific application of the light module. If a user did not require generally parallel light, he could eliminate the secondary optical element altogether, which would result in a more diffuse light beam.
The outbound light rays 22 emanate from the secondary lens segments 201 , again with paths essentially parallel to their original direction. The type of optical elements shown herein are of the simple non-symmetric biconvex type, but many other types may be employed to obtain the desired results. A person knowledgeable in the art of optics could devise an endless number of optical elements to obtain the desired result of a reduction of the cross section and/or redirection of the light rays.
A first example of a light modifying element 18 is shown in FIG. 12 . The light modifying element 18 comprises a plurality of active regions 181 and a plurality of passive regions 182 . In the element shown in FIG. 12, the passive regions 182 are open spaces. The active regions are independent segments that are affixed to a peripheral frame 183 . The light modifying element 18 can be constructed to affect either the size or shape of the projected beam, or the color characteristics—including hue, saturation, and brightness—of the projected beam.
It has been found in practice of the invention that machining the light modifying element 18 with open spaces as shown in FIG. 12 is problematic. Accordingly, an alternate construction for a light modifying element 18 ′ is shown in FIG. 13 . The light modifying element 18 ″ is a single piece of material mounted in a frame 183 . The active regions 181 ′ are equivalent to those of the element 18 , and affect the light in a way chosen by the user during construction of the element 18 ′. The passive regions 182 ′ are formed by coating the material in those areas in an element that is not coated, or by removing coating in those areas of a coated element.
FIG. 14 illustrate the structure of a size controlling light modifying element 18 ″. This element is a single piece of glass, and features a radial scalloping pattern as shown in FIGS. 15 and 16. The height of the scallops determines the degree to which the projected light is spread. Many relatively tall scallops lead to a wide projected beam (the situation depicted in FIG. 15 ), while a flat profile (FIG. 16) yields a small projected beam. The tallest portion of the scallop is where the spreading of the light is greatest, and the lowest portion of the scallop is where the spreading of the light is the least.
All the optical components of the present invention are depicted in the drawings as radial arrays, but could just as easily be constructed as linear or matrix arrays. If the arrays are linear or matrix, deployment of the light modifying elements is by linear motion, as opposed to the rotational motion used by the radial arrays.
Referring again to FIGS. 5-11, the light modifying elements are centered around the optic path. It should be noted that any number of light modifying elements can be used in combination. The light modifying elements are oriented perpendicular to the longitudinal axis of the optic path. When in the non-deployed position, the light modifying elements are not in the path of the refracted light rays as the refracted light rays exit the primary optical element 16 and are reduced to focal points by the lens segments 161 .
The centers of the light modifying elements used and all the optical elements employed are coaxial. The line containing those centers defines the center line of the optic path in the device. The frames of the light modifying elements are constrained to rotate about the center line of the optic path. Any number of methods can be chosen to constrain the light modifying elements to this type of motion. Rotational movement of any of the light modifying elements about the optical axis results in the active segments of the light modifying elements being introduced into the light path, and therefore affecting the characteristics of the projected light.
The light modifying elements can be fabricated by any one of many means known to those skilled in the art to obtain equivalent results in the device. The light modifying element may for some applications be of constant effect over its entire surface.
When the light modifying elements 18 , 18 ′, and 18 ″ are in a non-deployed position, the center lines of the light modifying element segments 181 , 181 ′, and 181 ″ are aligned between the focal lines of the primary optical element 16 . When the light modifying elements 18 , 18 ′, and 18 ″ are to be deployed, the elements are rotated so that the light modifying element segments 181 , 181 ′, and 181 ″ begin to intersect the refracted or reflected light rays from the lens segments of the primary optical element 16 .
In FIG. 10, the light modifying element 18 has been rotated about the system centerline so that a segment of the element begins to impinge on the light region. In all the embodiments of the present invention, the light modifying element 18 is placed in the optic path in an area where the primary optical element 16 has reduced the cross sections of the light regions. Thus the rotation of one of the light modifying elements 18 causes the light modifying element to affect the light. If more effect from the light modifying element is desired, the light modifying element is rotated further so that the light modifying element segments 181 are completely in the light path. All the light modifying elements 181 in the light modifying element assembly 18 are deployed in this manner. Again, the lens or reflective segments of the primary optical elements breaking the light into multiple regions of reduced cross section is what allows this unique deployment of the light modifying elements 181 . The light modifying elements 181 are invisible to the light until the light modifying elements 181 are rotated within the light path. The degree of modification of the light is therefore related to the degree of movement of the light modifying element.
The movement of the light modifying elements 18 into and out of the reduced area of the light path can be done manually, or it can be controlled by a motor or solenoid utilizing remote or computer control. An individual knowledgeable in the art of motor or solenoid control could devise numerous ways to control deployment of the light modifying elements 18 .
Preferred embodiments of the present invention result in compact, singular units. Two such embodiments are illustrated in FIGS. 17 and 18.
The above disclosure is not intended as limiting. Those skilled in the art will readily observe that numerous modifications and alterations of the device may be made while retaining the teachings of the invention. Accordingly, the above disclosure should be construed as limited only by the restrictions of the appended claims.
The above disclosure is not intended as limiting. Those skilled in the art will readily observe that numerous modifications and alterations of the device may be made while retaining the teachings of the invention. Accordingly, the above disclosure should be construed as limited only by the restrictions of the appended claims. | A lighting module that modifies a light beam to affect the size and shape and color characteristics of the projected beam includes a light source and a reflector to direct the light along an optic path. The reflector is formed so that light is directed along a light path that is not parallel to a center line of the reflector. A primary lens element reduces the cross section of an effected light region as the light enters a modifying element area in the optic path. Light modifying elements are deployed in varying combinations and to varying degrees to produce the shape, size, and color of light beam desired by the user. The construction of the light modifying elements allows the elements to be physically positioned in the optic path but to have no effect on the light until the elements are rotated so that light modifying element segments align with lens segments of the primary optical element, and the light modifying element or elements change the light being projected from the lighting module. | 5 |
FIELD OF THE INVENTION
[0001] The present invention generally relates to an implant insertion device, and particularly, to a breast implant insertion device and method of using thereof.
BACKGROUND OF THE INVENTION
[0002] Breast implants may be positioned within the chest, for example, in one of three positions: (1) implant over the pectoralis major muscle and under the breast tissue (subglandular); (2) implant partially under the muscle (partial submuscular or “dual plane”); and (3) implant completely under the muscle (submuscular). The subglandular placement puts the implant directly behind the breast tissue and mammary gland and in front of the pectoralis major muscle. This placement requires the least amount of dissection and yields the quickest recovery in comparative studies.
[0003] Partial submuscular placement involves placing the implant under the pectoralis major muscle. Because of the structure of this muscle, the implant is only partially covered. Completely submuscular placement puts the implant firmly behind the muscle. The implant is placed behind the pectoralis major muscle and behind all of the supporting fascia (connective tissue) and non-pectoral muscle groups.
[0004] Regardless of location of the implant, in the case of breast augmentation the surgery is carried out through an incision placed to minimize visibility of the resultant scar. The incision is made in, but is not limited to, one of three areas: (1) peri-areolar incision; (2) inframammary fold incision; and (3) transaxillary incision. The peri-areolar incision enables the surgeon to place the implant in the subglandular, partial submuscular or completely submuscular position, with the implant being inserted, or removed, through the incision. Like the peri-areolar incision, the inframammary fold incision provides for all three placement types and both insertion and removal of the implant through the incision. The incision is made in the crease under the breast, allowing for discreet scarring. Once the incision is made, the implant is inserted and worked vertically into place after creation of an appropriate sized pocket.
[0005] The transaxillary incision is made in the armpit. The incision is made in the fold of the armpit and a channel is dissected to gain access to the desired plane. The implant is inserted into the channel and worked into place. Like the peri-areolar and crease incisions, the armpit incision can be used for implant placement in all the previously described planes. Once the incision is created, the surgeon dissects a path through the tissue to the final destination of the implant. Once that path has been created, the tissue and/or muscle (depending on placement) is separated to create a pocket for the implant.
[0006] Since breast implants are usually placed into the body through incisions considerably smaller than the implant, it is a challenge to introduce them. With friction at the interface between the surface of the implants and the wound margins (body tissue), it is difficult to introduce the implants. Increased manipulation of both implants and patient tissue often results in trauma to both implants and patient tissue, thereby increasing the risk associated with the procedure both in terms of immediate consequences as well as delayed structural failure and the implications deriving therefrom.
[0007] Postoperative infection has also been a consequence of the need to manipulate the implant into place. If this occurs, the removal of the implant may be warranted and permanent disfigurement may result. In addition, bacterial seeding of the wound is postulated to lead to complications such as capsular contracture. The implant may, for example, become seeded with bacteria if it contacts the skin of the patient. Measures are taken in the operating room to avoid such risks. For example, antibiotic solution(s) may be used in the wound, the surgeon's gloves may be changed, and efforts may be made to reduce contact of the implant with the skin. However, such measures suffer from a variety of deficiencies and still provide opportunities for infection or bacterial seeding to occur.
[0008] Accordingly, it would be desirable to provide an implant insertion device capable of overcoming these and other complications alone or in combination.
[0009] Additional features and advantages of the invention will be set forth in the description that follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
SUMMARY OF THE INVENTION
[0010] In an embodiment, an implant insertion device is provided comprising a body defining an interior cavity capable of receiving an implant therein, a neck having an end extending from the body and insertable in an incision of a patient, and an aperture on the neck and in communication with the cavity, where the aperture is positionable substantially coaxially with the incision and the implant is transferable from the cavity to exit out the aperture into the patient. The neck, body, and combination thereof may be foldable or stretchable. The end may be insertable through the incision without contacting the skin of the patient. The body may be flexible, substantially transparent, and combinations thereof. The body may further comprise a second aperture in communication with the cavity for insertion of the implant therein. The second aperture may be larger than the implant. The second aperture may be selectively closeable. The device may further comprise a port in the body that is extendable through at least a portion of the cavity and the first aperture. The port may be glove shaped. The device may further comprise a removable cover over the first aperture. The device may further comprise an implant positioned in the cavity. The implant may be a breast implant. The device may further comprise a compartment capable of being placed in fluid communication with the body. The compartment may contain a fluid including, but limited to a lubricant, disinfectant, sterilizer, antibiotic, antimicrobial, and combinations thereof. The compartment may be positioned in the cavity. The compartment may be selectively openable to release the fluid in the cavity.
[0011] In an embodiment, an implant insertion device comprises a body defining an interior cavity capable of receiving an implant therein, an aperture in communication with the cavity and positionable substantially coaxially with an incision in a patient, where the implant is transferable from the cavity to exit out the aperture into the patient, and a member extending from the body for selectively engaging the patient. The member may engage the patient to maintain alignment of the aperture with the incision, to prevent withdrawal of the device from the patient during insertion of the implant, to prevent over insertion of the device in the patient, and combinations thereof. The member may engage the external surface of the patient's skin. The member may engage a surface inside the patient. The member may be a flexible ring. The member may be a tab. The member may engage the internal surface opposite the external surface of the skin. The device may further comprise a second member extending from the body for engaging the external surface of the patient's skin. The second member may engage the external surface of the patient's skin to maintain alignment of the aperture with the incision, to prevent withdrawal of the device from the patient during insertion of the implant, to prevent over insertion of the device in the patient, and combinations thereof. The second member may be selectively positionable from a first non-engagement position to a second engagement position. The first member and the second member may compress or sandwich the skin therebetween when the second member is positioned in the second engagement position. The second member may be a flexible ring. The second member may have a diameter greater than the diameter of the first member, substantially equal to the diameter of the first member, or smaller than the diameter of the first member.
[0012] In an embodiment, an implant insertion device comprises a body defining an interior cavity capable of receiving an implant therein, an aperture in communication with the cavity and positionable substantially coaxially with an incision in a patient, where the implant is transferable from the cavity to exit out the aperture into the patient, and a neck extending from the body for selectively engaging the incision to maintain the incision in an open position. The aperture may be positioned on the neck. The neck may be moveable from a first non-engagment position to a second engagement position. The neck is insertable in said incision without substantially contacting the skin while in said first non-engagment position. The neck may comprise a first leg for engaging a first side of the incision, and a second leg for engaging a second side of the incision. The first leg and the second leg may be moveable from a first non-engagement position to a second engagement position. The device may further comprise a biasing member for selectively maintaining the first leg and the second leg in the second engagement position. The neck may maintain alignment of the aperture with the incision. The diameter of the neck in the first position is smaller than the diameter of the neck in the second position.
[0013] In one embodiment the invention relates to an implant insertion device comprising: a) a body defining an interior cavity capable of receiving an implant therein, b) an aperture in communication with the cavity, c) positionable substantially coaxially with an incision in a patient, where said implant is transferable from the cavity to exit out the aperture into the patient, and d) a member extending from the body for selectively engaging the patient. In one embodiment the invention relates to the method of using the device of described above to deliver an implant to a patient. In one embodiment the member may engage the patient to maintain alignment of the aperture with the incision, to prevent withdrawal of the device from the patient during insertion of the implant, to prevent over insertion of the device in the patient, and combinations thereof. In one embodiment the member may engage the external surface of the patient's skin. In one embodiment the member may engage a surface inside the patient. In one embodiment the member may be a flexible ring. In one embodiment the member may be a tab. In one embodiment member may engage the internal surface opposite the external surface of the skin. In one embodiment the device may further comprise a second member extending from the body for engaging the external surface of the patient's skin. In one embodiment the second member may engage the external surface of the patient's skin to maintain alignment of the aperture with the incision, to prevent withdrawal of the device from the patient during insertion of the implant, to prevent over insertion of the device in the patient, and combinations thereof. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient. In one embodiment the second member may be selectively positionable from a first non-engagement position to a second engagement position. In one embodiment the first member and the second member may compress or sandwich the skin therebetween when the second member is positioned in the second engagement position. In one embodiment the second member may be a flexible ring. In one embodiment the second member may have a diameter greater than the diameter of the first member, substantially equal to the diameter of the first member, or smaller than the diameter of the first member. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient.
[0014] In one embodiment the invention relates toan implant insertion device comprising: a) a body defining an interior cavity capable of receiving an implant therein, b) a neck having an end extending from the body and insertable in an incision of a patient, c) an aperture on the neck and in communication with the cavity, where said aperture is positionable substantially coaxially with the incision, and d) said implant is transferable from the cavity to exit out the aperture into the patient. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient. In one embodiment the neck, body, and combination thereof may be foldable or stretchable. In one embodiment the end may be insertable through the incision without contacting the skin of the patient. In one embodiment the body may be flexible, substantially transparent, and combinations thereof. In one embodiment the body may further comprise a second aperture in communication with the cavity for insertion of the implant therein. In one embodiment the second aperture may be larger than the implant. In one embodiment the second aperture may be selectively closeable. In one embodiment the device may further comprise a port in the body that is extendable through at least a portion of the cavity and the first aperture. In one embodiment the port may be glove shaped. In one embodiment the device may further comprise a removable cover over the first aperture. In one embodiment the device may further comprise an implant positioned in the cavity. In one embodiment the implant may be a breast implant. In one embodiment the device may further comprise a compartment capable of being placed in fluid communication with the body. In one embodiment the compartment may contain a fluid including, but limited to a lubricant, disinfectant, sterilizer, antibiotic, antimicrobial, and combinations thereof. In one embodiment the compartment may be positioned in the cavity. In one embodiment the compartment may be selectively openable to release the fluid in the cavity. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient.
[0015] In one embodiment the invention relates toan implant insertion device comprising: a) a body defining an interior cavity capable of receiving an implant therein, b) an aperture in communication with the cavity and positionable substantially coaxially with an incision in a patient, where the implant is transferable from the cavity to exit out the aperture into the patient, and c) a neck extending from the body for selectively engaging the incision to maintain the incision in an open position. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient. In one embodiment said aperture may be positioned on the neck. In one embodiment said neck may be moveable from a first non-engagment position to a second engagement position. In one embodiment said neck is insertable in said incision without substantially contacting the skin while in said first non-engagment position. In one embodiment said neck may comprise a first leg for engaging a first side of the incision, and a second leg for engaging a second side of the incision. In one embodiment said first leg and said second leg may be moveable from a first non-engagement position to a second engagement position. In one embodiment said device further comprises a biasing member for selectively maintaining the first leg and the second leg in the second engagement position. In one embodiment said neck may maintain alignment of the aperture with the incision. In one embodiment the diameter of the neck in the first position is smaller than the diameter of the neck in the second position. In one embodiment the invention relates to method of using the device described above to deliver an implant to a patient.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0016] Objects and advantages, together with the operation of the invention, may be better understood by reference to the following detailed description taken in connection with the following illustrations, wherein:
[0017] FIG. 1 is a side view of an implant insertion device and a cross-sectional view of an incision in the tissue of a patient.
[0018] FIG. 2A , FIG. 2B , FIG. 2C , and FIG. 2D are side views of the body of the implant insertion device.
[0019] FIG. 3A and FIG. 3B are side views of the implant insertion device with a removable cover.
[0020] FIG. 4 is a side view of the implant insertion device with a fluid in the cavity.
[0021] FIG. 5 is a side view of the implant insertion device provided with a compartment containing the fluid.
[0022] FIG. 6 is a side view of the implant insertion device with a second aperture.
[0023] FIG. 7A is a side view of the implant insertion device with a selectively closeable second aperture in an open position.
[0024] FIG. 8B is a side view of the implant insertion device with a selectively closeable second aperture in a closed position.
[0025] FIG. 8 is a side view of the implant insertion device with a neck.
[0026] FIG. 8A is a side view of the implant insertion device with a neck in a first non-engagement position.
[0027] FIG. 8B is a side view of the implant insertion device of FIG. 8A with the neck in a second engagement position to maintain the incision in an open position.
[0028] FIG. 8C is a side view of the implant insertion device of FIG. 8A with the neck in the engagement position to expand the incision.
[0029] FIG. 9 is a side view of the implant insertion device with a neck comprising legs.
[0030] FIG. 9A is a side view of the implant insertion device provided with the neck in a first non-engagement position.
[0031] FIG. 9B is a side view of the implant insertion device of FIG. 9A with the neck in a second engagement position.
[0032] FIG. 9C is a side view of the implant insertion device of FIG. 9A with the neck in the engagement position.
[0033] FIG. 10A is a side view of the implant insertion device provided in FIG. 9A with a first member extending from the neck.
[0034] FIG. 10B is a side view of the implant insertion device provided in FIG. 9B with the first member extending from the neck.
[0035] FIG. 10C is a side view of the implant insertion device of FIG. 9C with the first member extending from the neck.
[0036] FIG. 11A is a side view of the implant insertion device provided with the first member in a non-engagment position.
[0037] FIG. 11B is a side view of the implant insertion device provided with the first member in an engagement position.
[0038] FIG. 12 is a side view of the implant insertion device with the first member secured to the body.
[0039] FIG. 13A is a side view of the implant insertion device of FIG. 12 with a leg extending from the first member.
[0040] FIG. 13B is a side view of the implant insertion device of FIG. 13 with the first member in a non-engagement position.
[0041] FIG. 13C is a side view of the implant insertion device of FIG. 13 with a portion of the body and the first member in a non-engagement position.
[0042] FIG. 13D is a side view of the implant insertion device with the neck and the first member in a non-engagement position.
[0043] FIG. 14 is a side view of the implant insertion device provided with a biasing member.
[0044] FIG. 15A is a side view of the implant insertion device with the implant positioned partially therein.
[0045] FIG. 15B is a side view of the implant insertion device of FIG. 15A with the implant extruding outward from the cavity.
[0046] FIG. 16A is a side view of the implant insertion device with the implant positioned in the cavity.
[0047] FIG. 16B is a side view of the implant insertion device of FIG. 16A with the implant exiting therefrom.
[0048] FIG. 17A and FIG. 17B are side views of the implant insertion device provided with a second member.
[0049] FIG. 18A and FIG. 18B are side views of the implant insertion devices of FIGS. 17A and 17B with the second member engaging the external surface of the patient's skin.
[0050] FIG. 19A and FIG. 19B are side views of the implant insertion device provided with the first member and the second member.
[0051] FIG. 20A and FIG. 20B are side views of the implant insertion devices of FIG. 19A and FIG. 19B with the first and second members engaging the tissue of the patient.
[0052] FIG. 21A , FIG. 21B , and FIG. 21C are side views of the neck of the implant insertion device with selectively positionable first and second members.
[0053] FIG. 22A is a side view of the implant insertion device with the second member positioned in a non-engagement position.
[0054] FIG. 22B is a side view of the implant insertion device of FIG. 22A with the second member positioned in an engagement position.
[0055] FIG. 23A is a side view of the implant insertion device with the first and second members positioned in an extended position.
[0056] FIG. 23B is a side view of the implant insertion device of FIG. 23A with the first and second members positioned in a retracted position.
[0057] FIG. 24A is a side view of the implant insertion device with the first and second members positioned in an extended (non-engagement) position.
[0058] FIG. 24B is a side view of the implant insertion device of FIG. 24A with the first and second members positioned in a retracted (engagement) position.
[0059] FIG. 25 is a side view of the implant insertion device with an invertible body.
[0060] FIG. 26 is a side view of the implant insertion device with an access port.
[0061] FIG. 27 is a side view of the implant insertion device with a glove shaped access port.
[0062] FIG. 28 is a side view of the implant insertion device comprising an access port insertable through the incision.
[0063] FIG. 29A is a side view of the implant insertion device with an implant positioned therein.
[0064] FIG. 29B is a side view of the implant insertion device of FIG. 29A with the implant being inserted in the incision.
[0065] FIG. 29C is a side view of the device of FIG. 29A with the implant partially inserted through the incision.
[0066] FIG. 29D is a side view of the device of FIG. 29A with the implant partially inserted through the incision.
[0067] FIG. 29E is a side view of the device of FIG. 29A with the implant inserted through the incision.
[0068] FIG. 30 shows a smaller sized embodiment of the current invention both in open and closed positions.
[0069] FIG. 31 shows a medium sized embodiment of the current invention both in open and closed positions.
[0070] FIG. 32 shows a large sized embodiment of the current invention both in open and closed positions.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0071] While the present invention is described with reference to embodiments described herein, it should be clear that the present invention is not limited to such embodiments. Therefore, the description of the embodiments herein is merely illustrative of the present invention and will not limit the scope of the invention as claimed.
[0072] As shown in FIG. 1 , an implant insertion device 10 (hereinafter referred to as the “device 10 ”) is provided comprising a body 15 defining a cavity 20 therein that is accessible via an aperture 25 . An implant 30 is positionable in the cavity 20 and the aperture 25 is substantially coaxially alignable with an incision 35 in the tissue 37 of a human or animal (hereinafter referred to as the “patient”) for insertion of the implant 30 therein.
[0073] The device 10 may be used for the insertion of a breast implant into a surgical pocket formed in the patient. The breast implant may be any type, including, but not limited to, saline and silicone breast implants. In a non-limiting example, saline breast implants are generally inserted through the incision 35 ranging from about two centimeters to about three centimeters. For silicone breast implants, the incision 35 ranges from about five centimeters and above. It is to be understood, however, that the device 10 may be used with incisions 35 having larger and smaller sizes. In addition, although the implant 30 is described herein as a breast implant, it is to be understood that the device 10 is not limited to breast implants, and may be used to insert any type of implant 30 in the patient.
[0074] The body 15 may be provided in a variety of shapes and materials. In the non-limiting examples as shown in FIG. 2A-D , the body 15 may be substantially cylindrical, spherical, funnel shaped, or bag-like. The body 15 may be comprised of metal, polymers or plastics, composites, and combinations thereof, and may be covered with a friction reducing coating to minimize trauma to the implant 30 and the tissue 37 . The body 15 may be coated with a lubricant including, but not limited to, silicone. In a non-limiting example, the body 15 may be of metal, plastic, polymer, fabrics, composites, and combinations thereof. In a non-limiting example, the body 15 may include, but is not limited to, Mylar®, plastics made from Tygon® brands of plastics, vinyls, polyvinyl chloride, ethylene and alpha-olefin copolymers, silicone, and the like. It is to be understood that the body 15 may be impregnated with an antimicrobial.
[0075] The cavity 20 may extend a portion of or the entire length of the body 15 . In an embodiment, at least a portion of the body 15 is flexible and capable of allowing a user 200 , such as a physician, to manipulate or otherwise apply pressure to the implant 30 via the body 15 when positioned in the cavity 20 by hand or with an instrument to transfer the implant 30 from the cavity 20 and into the patient via the incision 35 . Accordingly, the implant 30 may be inserted in the patient without exposing the implant 30 or the patient and the surgical pocket to contamination from a variety of sources, including but not limited to, the physician's gloves, hands, retractors, and the patient's skin, thereby reducing the chance of infection and bacterial seeding of the implant 30 .
[0076] It is to be understood that the implant 30 is insertable in the cavity 20 via the aperture 25 . The aperture 25 may be smaller (or have a smaller diameter) than the implant 30 , substantially same as the implant 30 , or larger than the implant 30 . In a non-limiting example as best shown in FIG. 15A and FIG. 15B , the aperture 25 may be smaller than the implant 30 and the body 15 may be resistant to stretching, thereby causing the implant 30 to extrude through the aperture 25 . In a non-limiting example as best shown in FIG. 16A and FIG. 16B , a portion of the body 15 adjacent to or surrounding the aperture 25 may be stretchable or expandable to increase the size or diameter of the aperture 25 for insertion or removal of the implant 30 therethrough without substantially compressing or extruding the implant 30 , thereby reducing trauma to the implant 30 .
[0077] As best shown in FIG. 3A , the device 10 may be provided with an implant 30 positioned in the cavity 20 . A cover 45 may be provided for the aperture 25 , for example, to maintain the sterility of at least a portion of the body 15 , the cavity 20 , the implant 30 , and combinations thereof. As shown in FIG. 3B , the cover 45 may be removed before inserting the implant 30 through the incision 35 .
[0078] As shown in FIG. 4 , a fluid 47 may be provided in the cavity 20 , for example, to sterilize the implant 30 . The fluid 47 may include, but is not limited to, lubricant, disinfectant, sterilizer, antibiotic, antimicrobial, and combinations thereof. The disinfectant 47 may be provided in contact with the implant 30 as shown in FIG. 4 , or in a compartment 50 capable of being opened to place the compartment 50 in fluid communication with the cavity 20 as shown in FIG. 5 . The compartment 50 may be opened prior to insertion of the implant 30 through the incision 35 to release the fluid 47 into the cavity 20 . In a non-limiting example, the compartment 50 may be opened by applying pressure to the body 15 , for example, by pinching between the user's 200 fingers.
[0079] A switch 55 may be provided outside of the cavity 20 as shown in FIG. 5 that may be activated to open the compartment 50 . In a non-limiting example, the switch 55 may be a string that can be pulled to open the compartment 50 . It is to be understood, however, that a variety of configurations may be used to open the compartment 50 .
[0080] As shown in FIG. 6 , the body 15 may be provided with a second aperture 60 capable of receiving the implant 30 for placement in the cavity 20 . In a non-limiting example as best shown in FIG. 7A and FIG. 7B , the second aperture 60 may be provided with a closure 65 that may be selectively opened ( FIG. 7A ) and closed ( FIG. 7B ) for access to the cavity 20 . The closure 65 may include, but is not limited to, a Zip-loc closure, a suture, zipper, button, adhesive, strings for tying for tying the second aperture 60 closed, and combinations thereof. The second aperture 60 may have a diameter less than, substantially equal to, or greater than the diameter of the implant 30 .
[0081] In an embodiment as shown in FIG. 8 , the device 10 may be provided with a neck 70 extending from the body 15 and capable of engaging the incision 35 to facilitate insertion of the implant 30 through the incision 35 . As shown in FIG. 9A , FIG. 9B , and FIG. 9C the neck 70 may comprise two or more legs 75 that are positionable in a first non-engagement position for insertion in the incision 35 and a second engagement position to maintain the incision 35 in an open position (having a size or diameter d 1 ). As shown in FIG. 9B and FIG. 9C , the neck 70 may stretch or expand the size or diameter d 1 of the incision 35 while in the engagement position to a larger diameter d 2 . As shown in FIG. 9A , the legs 75 (or neck 70 ) may be inserted in or through the incision 35 without contacting an external surface 90 of the skin (or substantially) any portion of the incision 35 walls), thereby minimizing the introduction of bacteria or other foreign matter to the implant 30 or in the patient's body (including the surgical pocket).
[0082] Although shown as being substantially rod shaped, it is to be understood that the legs 75 (or the neck 70 ) may be any shape capable of insertion in or through the incision 35 . Although shown as extending substantially perpendicularly outward from the body 15 , the legs 75 (or neck 70 ) may extend outward from the body 15 at any angle. Although shown as extending outward from the body 15 substantially parallel to each other, the legs 75 may extend outward from the body 15 at any angle with respect to each other.
[0083] The legs 75 (or neck 70 ) may be biased such that the legs 75 may be compressed to the first non-engagement position for insertion in the incision 35 . When released, the legs 75 extend outward from each other to engage the tissue 37 surrounding the incision 35 to maintain the incision 35 in an open position or increase the size of the incision 35 . In a non-limiting example, the legs 75 may comprise a shape memory material to provide the biasing force to the legs 75 . In a non-limiting example as shown in FIG. 14 , a biasing member 105 may be provided to provide the biasing force to the legs 75 . In a non-limiting example, the biasing member 105 may be a spring. Although the biasing member 105 is shown as being positioned between the legs 75 , it is to be understood that the biasing member 105 may be positioned anywhere on the device 10 to provide the biasing force. In addition, it is to be understood that a variety of materials and configurations may be used to provide the biasing force to the legs 75 .
[0084] A locking mechanism (not shown) may be provided to lock the legs 75 in the first non-engagement position, the second engagement position, or any position therebetween. In a non-limiting example, the locking mechanism may be used to prevent the legs 75 from being compressed inwardly from the second engagement position to prevent accidental withdrawal from the incision 35 .
[0085] As shown in FIG. 10A , FIG. 10B , and FIG. 10C , the neck 70 may be provided with one or more engagement members 80 (hereinafter referred to as “the first member 80 ”). The first member 80 is capable of engaging the patient to prevent removal of the device 10 from the patient during insertion of the implant 30 , to maintain alignment of the aperture 25 with the incision 35 , to prevent over insertion of the device 10 in the patient, and combinations thereof. The first member 80 may extend outward from the body 15 or the neck 70 to engage an internal part of the patient's body. In a non-limiting example, the first member 80 may engage an internal surface 85 opposite the external surface 90 or a portion of a surgical pocket (not shown) in the patient formed for the placement of the implant 30 therein.
[0086] As shown in FIG. 10A , FIG. 10B and FIG. 10C , the first member 80 may extend substantially perpendicularly outward from the legs 75 (or neck 70 ). It is to be understood, however, that the first member 80 may extend at any angle outward from the legs 75 (or neck 70 ) and may be curved or otherwise shaped to conform to the shape of the tissue to which it will engage.
[0087] As shown in FIG. 11A and FIG. 11B , the first member 80 may be selectively moveable between a non-engagement position ( FIG. 11A ) and an engagement position ( FIG. 11B ). The first member 80 may be moved by using one or more actuators 95 , such as a button, tab, or the like. The first member 80 may be positioned in the non-engagement position ( FIG. 11A ) for insertion through the incision 35 and extended to the engagement position ( FIG. 11B ) to engage the internal surface 85 for insertion of the implant 30 through the incision 35 .
[0088] In a non-limiting example, the first member 80 may be secured to the body 15 . The first member 80 may be comprised of metal, polymer, plastic, fabrics, composites, and combinations thereof. It is to be understood that the first member 80 may be rigid, compressible, foldable, expandable, or stretchable. As shown in FIG. 12 , the first member 80 may be substantially ring shaped and may extend outward from a flexible, bag-like body 15 . In a non-limiting example, the first member 80 may be comprised of a flexible material, including but not limited to a polymer, capable of being compressed or folded for insertion through the incision 35 .
[0089] As best shown in FIG. 13A , one or more arms 100 may be provided extending from the first member 80 . As best shown in FIG. 13B , the arms 100 may be manipulated, for example by squeezing together, to compress or fold the first member 80 , the neck 70 , the portion of the body 15 surrounding the aperture 25 , or any combination thereof, to the non-engagement position for insertion through the incision 35 . As shown in FIG. 13C and FIG. 13D , the first member 80 , the neck 70 , the portion the body 15 surrounding the aperture 25 , or any combination thereof, may be folded to the non-engagement position for insertion through the incision 35 . Although not shown in FIG. 13C and FIG. 13D , it is to be understood that one or more arms 100 may be provided.
[0090] Accordingly, the first member 80 , the neck 70 , the portion the body 15 surrounding the aperture 25 , or any combination thereof may be inserted in or through the incision 35 to reduce exposure of the patient and the implant 30 to contamination from the physician's gloves, hands, retractors and the like, thereby reducing the risk of infection or bacteria seeding. The arms 100 (if provided), the neck 70 , the first member 80 , the body 15 , or any combination thereof, may be released to allow the first member 80 , the neck 70 , the portion of the body 15 surrounding the aperture 25 , or any combination thereof, to return to the engagement position as shown in FIG. 13A .
[0091] In an embodiment, an engagement member 120 (hereinafter referred to as “the second member 120 ”) may be provided for engaging the external surface 90 of the patient's skin. As shown in FIG. 17A and FIG. 17B , the first member 120 may be secured to the body 15 or the neck 70 . As shown in FIG. 18A and FIG. 18B , the second member 120 may engage the external surface 90 to secure the device 10 to the patient, to maintain alignment of the aperture 25 with the incision 35 , to prevent over insertion of the any portion of the device 10 in the incision 35 (for example, during insertion of the implant 30 ), and combinations thereof. Over insertion of the device 10 in the patient may introduce bacteria or foreign matter in the patient, or cause trauma to the patient.
[0092] In a non-limiting example, the second member 120 may be capable of providing a vacuum when engaged with the external surface 90 to secure the device 10 thereto. It is to be understood, however, that other configurations of the second member 120 may be used to secure the device 10 to the external surface 90 , including, but not limited to clamps, ribbons, and the like. Although shown as substantially ring shaped, the second member 120 may be any shape capable of engaging the external surface 90 . The second member 120 may be comprised of metal, polymer, plastic, fabrics, composites, and combinations thereof. It is to be understood that the second member 120 may be rigid, compressible, expandable or stretchable.
[0093] It is to be understood that the second member 120 may be integral with the body 15 or the neck 70 and may be removeably secured to the body 15 or the neck 70 . As best shown in FIG. 19A and FIG. 19B , the second member 120 may be provided in combination with the first member 80 . As shown in FIG. 20A and FIG. 20B , the second member 120 may engage the external surface 90 and the first member 80 may engage the internal surface 85 . In a non-limiting example, the second member 120 and the first member 80 may be selectively positionable or biased toward each other to sandwich or compress the tissue 37 therebetween.
[0094] The second member 120 , the first member 80 , or both the second member 120 and the first member 80 may be selectively positionable along the neck 70 or body 15 . In a non-limiting example as shown in FIG. 21A , FIG. 21B , and FIG. 21C , the neck 70 may be provided with a series of apertures 130 . The second member 120 , the first member 80 , or both the second member 120 and the first member 80 may be provided with an actuator 140 , such as a pin, to selectively engage the apertures 130 to lock the second member 120 or the first member 80 at a desired position on the neck 70 .
[0095] In another illustrative example, as shown in FIG. 23A and FIG. 23B , either or both of the members 120 and 80 may be rotated to wrap the body 15 (and/or neck 70 ) thereabout to decrease the distance d m1 and d m2 therebetween (where d m1 >d m2 ). As shown in FIGS. FIG. 24A and FIG. 24B , the second member 120 may be rotated after insertion of the first member 80 through the incision 35 to selectively engage the tissue 37 therebetween. It is to be understood, however, that the foregoing illustrative examples are not limiting and that a variety of configurations may be provided for selectively positioning the members 120 and 80 along the body 15 or neck 70 .
[0096] As shown in FIG. 22A and FIG. 22B , the first member 80 may be inserted through the incision 35 to engage the internal surface 85 . As shown in FIG. 22B , the second member 120 may be selectively positioned to engage the external surface 90 to sandwich or compress the tissue 37 therebetween to, for example, secure the device 10 to the tissue 37 , to maintain alignment of the aperture 25 with the incision 35 , prevent over insertion of the device 10 through the incision 35 , and combinations thereof.
[0097] As shown in FIG. 25 , the body 15 may be capable of being inverted to allow the user 200 to insert their hand 205 (or a portion thereof) through the incision 35 to manipulate or otherwise position the implant 30 in the surgical pocket without directly contacting the skin, the implant 30 , or the surgical pocket. Accordingly, the user 200 may minimize the risk of introducing foreign matter (including but not exclusive to lint from surgical towels or powder from surgical gloves) or bacteria on the implant 30 and in the patient and the surgical pocket.
[0098] In an embodiment as shown in FIG. 26 , a port 150 is provided for insertion of a hand or tool in the cavity 20 . As best shown in FIG. 27 , the port 150 may be shaped like a glove to facilitate insertion of the user's hand 205 therein. The port 150 provides access to the cavity 20 to allow the user 200 to manipulate the implant 30 therein, and allows the user 200 to transfer the implant 30 through the aperture 25 and the incision 35 . As best shown in FIG. 28 , the port 150 may allow the user 200 to insert at least a portion of their hand 205 through the incision 35 , for example, to manipulate the implant 30 in the surgical pocket to facilitate proper positioning. It is to be understood that the port 150 may be comprised of the same material as the body 15 . In a non-limiting example, the body 15 , the neck 70 , and combinations thereof may be comprised of a rigid material and the port 150 may be comprised of a flexible material.
[0099] Turning to the device 10 , an illustrative example of how to use the device 10 as illustrated in FIG. 1-FIG . 29 D is set forth below. As best shown in FIG. 8A , FIG. 9A , FIG. 10A , FIG. 13B , FIG. 13C , and FIG. 13D the neck 70 (or a portion of the body 15 ) may be provided in a non-engagement position for insertion in the incision 35 without contacting (or substantially contacting) the external surface 90 to, for example, minimize the introduction of foreign material in the patient and the surgical pocket. As best shown in FIG. 8B , FIG. 8C , FIG. 9B , FIG. 9C , FIG. 10B , and FIG. 10C , the neck 70 (or a portion of the body 15 ) may be moveable from the non-engagement position to the engagement position to selectively engage the incision 35 walls to maintain the incision 35 in an open position with the aperture 25 substantially coaxially aligned with the incision 35 .
[0100] As shown in FIG. 22A , the first member 80 may be provided to engage the internal surface 85 to, for example, prevent withdrawal of the device 10 from the incision 35 during insertion of the implant. The second member 120 may be provided to engage the external surface 90 to, for example, secure the device 10 to the external surface 90 to maintain alignment of the aperture 25 with the incision 35 , to prevent over insertion of the device 10 in the patient, and combinations thereof. As shown in FIG. 22A and FIG. 22B , the second member 120 may be selectively positionable from a first non-engagement position ( FIG. 22A ) to a second engagement position ( FIG. 22B ).
[0101] As best shown in FIG. 29A and FIG. 29B , the implant 30 may be aligned with the incision 35 for insertion therethrough. It is to be understood that the body 15 (or a portion thereof) may be flexible and allow the user 200 to manipulate or transfer the implant 30 through the incision 35 , as shown in FIG. 29C , FIG. 29D , and FIG. 29E , without directly contacting the implant 30 , to minimize the introduction of foreign matter and bacteria to the implant 30 and in the patient and the surgical pocket. As best shown in FIG. 29B , FIG. 29C , FIG. 29D , and FIG. 29E , the aperture 25 may be larger than the implant 30 and the body 15 may be flexible and shaped so as not to constrict or otherwise compress the implant 30 during insertion through the incision 35 . Accordingly, the device 10 may limit compression or trauma exerted on the implant 30 to that imposed thereon by the tissue 37 surrounding the incision 35 , the fingers, or tools of the user 200 used to transfer the implant 30 therethrough.
[0102] The invention has been described above and, obviously, modifications and alternations will occur to others upon a reading and understanding of this specification. It is to be understood that all features in the various embodiments can be combined with other embodiments. The claims as follows are intended to include all modifications and alterations insofar as they come within the scope of the claims or the equivalent thereof. | The present invention generally relates to an implant insertion device, and particularly, to a breast implant insertion device and method of using thereof. The present invention is related to surgical delivery of an implant. In particular, the invention describes a device for the delivery of a breast implant that avoids contact with the skin reducing potential sources of incidental infection. | 0 |
BACKGROUND OF THE INVENTION
The present invention relates to a DNA Pol-II polymerase to certain deletants and mutants of this enzyme, to genes and vectors encoding them and their use in DNA sequencing.
The following is a discussion of the relevant art, none of which is admitted to be prior art to the appended claims.
DNA polymerases are a family of enzymes involved in DNA repair and replication and have been classified into families sharing homologies to E. coli Pol-I, Pol-II, etc. (see Braithwaite and Ito Nuc. Acid. Res. 787, 1993). DNA polymerases have been isolated from E. coli (e.g. E. coli DNA polymerase I and E. coli polymerase II and more recently thermostable DNA polymerases have been isolated (e.g. from T. aquaticus, U.S. Pat. No. 4,889,818, and from T. litoralis).
European Patent Application 0655 506A relates to modifying DNA polymerases so that they incorporate dideoxynucleotides more efficiently. In particular, it is mentioned that the presence of a polar, hydroxy containing amino acid at a position nearing the binding site for the dNTP substrate is important for the polymerase being able to efficiently incorporate a dideoxynucleotide. Examples of Pol I type polymerases that contain such an amino acid given in the specification are T7 DNA polymerase (position 526) and E. coli DNA polymerase I and Taq DNA polymerase where the phenylalanines at position 762 and 667 respectively have been replaced by tyrosine. No examples are included of Pol II type polymerases containing such a modification although it is mentioned that such polymerases may be modified. Thermococcus litoralis, Pyrococcus furiosus and Sulfolobus solfataricus are thermostable DNA Pol-II polymerases that are mentioned as being preferred for such modification.
SUMMARY OF THE INVENTION
The present invention is based on the discovery that replacing an alanine at position 491 of Pyrococcus furiosus with tyrosine gives an enzyme that has improved incorporation of dideoxynucleotides and improved band uniformity.
Accordingly, the present invention provides a Pol-II type DNA polymerase in which A in the amino acid sequence KN 1 N 2 ANN 3 N 4 YG corresponding to positions 488 to 496 of Pyrococcus furiosus has been replaced by a hydroxy containing amino acid and wherein N 1 is L, V, or I, N 2 is L, F, or Y, N 3 is A or S and N 4 is Y, F, T, S, or H.
Suitably N 1 is L
Suitably N 2 is L
Suitably N 3 is S
Suitably N 4 is F
Preferably the amino acid sequence is KLLYNSFYG.
Suitably the Pol-II type polymerase is an archaeabacterial DNA polymerase for example Pyrococcus furiosus, Thermococcus litoralis or Sulfolobus solfataricus. Preferably it is Pyrococcus furiosus.
The naturally occurring or "wild" type Pol-II DNA polymerases possess exonuclease activity, that is the ability to excise any newly synthesised bases which are incorrectly base paired to the template during chain extension. This property is disadvantageous in DNA sequencing reactions. Accordingly, in a second aspect, the present invention provides a Pol-II DNA polymerase having an amino acid sequence KN 1 N 2 ANN 3 N 4 YG corresponding to positions 488 to 496 of Pyrococcus furiosus as hereinbefore defined in which the exonuclease activity is less than 50% and preferably less than 1% of the wild polymerase. This may be achieved by deleting the region responsible for exonuclease activity or by mutation of appropriate amino acid(s). It has been found that replacement of aspartate by alanine at position 215 of Pyrococcus furiosus reduces the exonuclease activity more than 1000 fold.
In addition, as it is often convenient to express the gene encoding the polymerase in E. coli, then it is preferred to incorporate codons that are highly utilised by E. coli. In the case of Pyrococcus furiosus, this can be accomplished by changing the first 58 codons in the gene to synonymous codons favoured by E. coli. In particular, it is preferred that an alanine codon be inserted at amino acid position 2.
Preferably, the Pol-II type DNA polymerase of the present invention is a purified Pol-II type DNA polymerase or fragment thereof having the DNA polymerase activity of the "wild" type enzyme. In the case of Pyrococcus furiosus this will have, preferably, at least 80% amino acid homology, preferably 90% homology, to at least a contiguous 40 amino and sequence shown in FIG. 1 (amino acid sequence of wild type Pyrococcus furiosus DNA polymerase).
In a further aspect, the present invention provides a gene encoding a Pol-II type DNA polymerase of the present invention.
When used herein, the term "a Pol-II type DNA polymerase or fragment thereof having the DNA polymerase activity of the wild type enzyme" means a DNA polymerase or fragment thereof (as hereinafter defined) which has the ability to replicate DNA with substantially the same efficiency as the wild type enzyme. By "substantially the same efficiency" is meant at least 80% and preferably at least 90% of the efficiency of the enzyme shown in FIG. 1 to incorporate deoxynucleotides.
When used herein, the term "amino acid homology" means the amino acid identity of the parent enzyme or conservative amino acid changes thereto.
By "fragment" is meant an amino-terminal deletant of the enzyme which still retains DNA polymerase activity.
The invention also encompasses a thermostable enzyme composition which comprises a purified thermostable Pol-II type DNA polymerase of the present invention.
The purified enzyme of the present invention has a molecular weight of approximately 90,000 daltons when measured on SDS-PAGE. The temperature optimum of DNA synthesis is near 75° C. under assay conditions.
The term "thermostable polymerase" means an enzyme which is stable to heat (and heat resistant) and is suitable for use in sequencing at an elevated temperature, for example 70° C. The thermostable polymerase herein must satisfy a single criterion to be effective for the sequencing reaction, i.e., the enzyme must not become irreversibly denatured (inactivated) when subjected to the elevated temperatures for the time necessary to effect the reaction. Preferably, the enzyme will not become irreversibly denatured at about 70° C. but may become denatured at higher temperatures. Preferably, the optimum temperature ranges from about 37° C. to 75° C. more preferably 65° C. to 70° C.
In addition to the deletions and amino acid changes to remove the exonuclease activity, the enzyme may have conservative amino acid changes compared with the native enzyme which do not significantly influence thermostability or enzyme activity. Such changes include substitution of like charged amino acids for one another, or amino acids with small side chains, e.g. ala for val. More drastic changes may be introduced at non-critical regions where little or no effect on polymerase activity is observed by such a change.
In yet a further aspect, the present invention provides a host cell comprising a vector containing the gene encoding the DNA sequence corresponding to a Pol-II type DNA polymerase of the present invention.
The DNA polymerases of the present invention are preferably in a purified form. By purified is meant that the DNA polymerase is isolated from a majority of host cell proteins normally associated with it; preferably the polymerase is at least 10% (w/w), e.g., at least 50% (w/w), of the protein of a preparation, even more preferably it is provided as a homogeneous preparation, e.g. homogeneous solution. Preferably the DNA polymerase is a single polypeptide on an SDS polyacrylamide gel.
Silent codon changes such as the following increase protein production in E coli:
substitution of the codon GAG for GAA;
substitution of the codon AGG, AGA, CGG or CGA for CGT or CGC;
substitution of the codon CTT, CTC, CTA, TTG or TTA for CTG;
substitution of the codon GGG or GGA for GGT or GGC.
The present invention also provides a method for determining the nucleotide base sequence of a DNA molecule. The method includes providing a DNA molecule; annealing with a primer molecule able to hybridize to the DNA molecule; and incubating the annealed molecules in a vessel containing at least one, and preferably four deoxynucleotide triphosphates, and a DNA polymerase of the present invention preferably one containing the alanine to tyrosine mutation. Also provided is at least one DNA synthesis terminating agent which terminates DNA synthesis at a specific nucleotide base. The method further includes separating the DNA products of the incubating reaction according to size, whereby at least a part of the nucleotide base sequence of the DNA molecule can be determined.
In preferred embodiments, the sequencing is performed at a temperature between 37° C. and 75° C., and preferably between 65° C. and 70° C.
In other preferred embodiments the Pol-II type DNA polymerase of the invention has less than 1000, 250, 100, 50, 10 or even 2 units of exonuclease activity per mg of polymerase (measured by standard procedure, see below) and is able to utilize primers having only 4, 6 or 10 bases; and the concentration of all four deoxynucleoside triphosphates at the start of the incubating step is sufficient to allow DNA synthesis to continue until terminated by the agent, e.g. a ddNTP.
Preferably, not more than a 50 fold excess of a ddNTP is provided to the corresponding dNTP.
In a related aspect, the invention features a kit or solution for DNA sequencing including a Pol-II type DNA polymerase of the present invention and a reagent necessary for the sequencing such as dITP, deaza dGTP, a chain terminating agent such as a ddNTP, and optionally a pyrophosphatase (if the ddNTP:dNTP ratio is less than 1:1).
The DNA polymerases of the present invention can be constructed using standard techniques. By way of example, in order to prepare a Pyrococcus furiosus polymerase with the alanine to tyrosine mutation mutagenic PCR primers can be designed to incorporate the desired Ala to Tyr codon change in a nucleic acid sequence encoding for a DNA polymerase of Pyrococcus furiosus. The nucleic acid sequence encoding for the wild type DNA polymerase of Pyrococcus furiosus is shown in FIG. 2 (SEQ. ID. NO. 38).
In another related aspect the invention features a method of sequencing a strand of DNA essentially as described above with one or more (preferably 2, 3 or 4) deoxyribonucleoside triphosphates, a Pol-II type DNA polymerase of the present invention, and a first chain terminating agent. The DNA polymerase causes the primer to be elongated to form a first series of first DNA products differing in the length of the elongated primer, each first DNA product having a chain terminating agent at its elongated end, and the number of molecules of each first DNA products being approximately the same for substantially all DNA products differing in length by no more than 20 bases. The method also features providing a second chain terminating agent in the hybridized mixture at a concentration different from the first chain terminating agent, wherein the DNA polymerase causes production of a second series of second DNA products differing in length of the elongated primer, with each second DNA product having the second chain terminating agent at its elongated end. The number of molecules of each second DNA products is approximately the same for substantially all second DNA products differing in length from each other by from 1 to 20 bases, and is distinctly different from the number of molecules of all the first DNA products having a length differing by no more than 20 bases from that of said second DNA products.
In preferred embodiments, three or four such chain terminating agents can be used to make different products and the sequence reaction is provided with a magnesium ion, (e.g. at a concentration between 0.05 and 100mM, preferably between 1 and 10 mM); and the DNA products are separated according to molecular weight in four or less lanes of a gel.
In another related aspect, the invention features a method for sequencing a nucleic acid by combining an oligonucleotide primer, a nucleic acid to be sequenced, between one and four deoxyribonucleoside triphosphates, a Pol-II type DNA polymerase of the present invention, and at least two chain terminating agents in different amounts, under conditions favouring extension of the oligonucleotide primer to form nucleic acid fragments complementary to the nucleic acid to be sequenced. The agents are differentiated from each other by intensity of a label in the primer extension products.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The drawings will first be briefly described.
Drawings
FIG. 1 shows the amino acid sequence of wild type DNA polymerase of Pyrococcus furiosis (SEQ. ID. NO. 37).
FIG. 2 shows the nucleic acid sequence of wild type DNA polymerase of Pyrococcus furiosis (SEQ. ID. NO. 38).
FIG. 3 is a representation of a sequencing gel from reactions using wild type or A491Y Pfu polymerase.
EXAMPLES
The following examples serve to illustrate the DNA polymerases of the present invention and their use in sequencing.
Assay of DNA Polymerase Activity
DNA polymerase activity was assayed by measuring the amount of incorporation of a radiolabeled deoxynucleotide into acid precipitable material using activated salmon sperm DNA as a template (Richardson, C. C. (1966) DNA polymerase from Escherichia coli, pp. 263-276 In G. L. Cantoni and D. R. Davies (ed.), Procedures in nucleic acid research. Harper and Row, New York). A unit of DNA polymerase is the amount of enzyme that catalyzes incorporation of 10 nmoles of deoxynucleotide triphosphate into acid-precipitable material in 30 minutes at 70° C. An assay consists of 2-10 μl of protein solution containing DNA polymerase being incubated with 50 μl of assay mix (20 mM Tris HCl pH 8.5 @ room temperature, 10 mM KCl, 10 mM (NH 4 ) 2 SO 4 , 0.1% (v/v) Triton X-100, 100 μg/ml BSA, 2 mM MgSO 4 , 200 μM each deoxynucleotide triphosphate, 0.2 mg/ml activated salmon sperm DNA, 1 μCi 3000 Ci/mmole α- 33 P! dATP) at 70° C. for 10 minutes. The reaction is stopped by adding the contents of the assay to a tube containing 1 ml each of carrier 50 μg/ml fish sperm DNA, 2 mM EDTA) and precipitant (20% (w/v) trichloroacetic acid, 2% (w/v) sodium pyrophosphate). After incubation on ice for at least 5 minutes, the solution is filtered through a glass fiber filter (e.g. GF/B, Whatman), washed with several mililiters ice-cold wash solution (1N hydrochloric acid, 100 mM sodium pyrophosphate), placed in a counting vial with aqueous liquid scintillation cocktail (e.g. Biosafe II, Research Products International Corp.) and counted in a liquid scintillation counter. DNA polymerase activity of the test solution is calculated from the measured specific activity of the assay mix. The assay has been shown to be linear between 0.01 to 0.2 units per assay reaction and only values between these were accepted as significant.
Measurement of Protein Concentration
Solution protein concentrations are measured spectrophotometrically by determining the absorbance of the test solution at a wavelength of 205 nm (A 205 ) (Scopes, R. K. (1994) pp. 46-48 Protein Purification. Springer-Verlag, New York). The extinction coefficient of polypeptides is taken as E 205 (1 mg·ml -1 )=31.
Assay of Exonuclease Activity
Exonuclease activity was measured as described (Kong, H., Kucera, R. B. and Jack, W., E. (1993) J. Biol. Chem. 268, 1965-1975) using, as substrate a 500 bp PCR product generated from pBR322 labeled with 3 H by incorporation of tritiated TTP. Exonuclease assays were performed in the same buffer (20 mM Tris HCl pH 8.5 @ room temperature, 10 mM KCl, 10 mM (NH 4 ) 2 SO 4 , 0.1% (v/v) Triton X-100, 100 μg/ml BSA, 2 mM MgSO 4 ) and at the same temperature (70° C.) as polymerase assays.
Example 1
Construction of expression vectors pRD and pRD2
It has been shown that overproduction by cloning of tRNA arg can significantly increase the expression of exogenous proteins in E. coli (Brinkmann et al., (1989) Gene 85, 109-114; Schenk et al. (1995) BioTechniques 19, 196-200). Novel expression vectors were created by cloning the gene for tRNA arg onto a vector with tightly-regulated inducible expression for exogenous proteins such as DNA polymerases. To construct these novel vectors, two PCR primers GGAATTCAGATCTAAAAGCCATTGACTCAGCAAG (SEQ. ID. NO. 1) and GGAATTCACATGTGACAGAGCATGCGAGGAAAAT (SEQ. ID. NO. 2) were designed to amplify the gene, promotor and terminator sequences of tRNA arg (argU gene) from E. coli genomic DNA. The sequence of this gene and its regulatory regions has been previously published (Garcia et al. (1986) Cell 45, 453 -459). E. coli genomic DNA was prepared from strain HMS 174 (ATCC #47001). The PCR product was cloned using the vector provided as part of the pMOS Blue T-Vector kit (Amersham Life Science), and two clones were confirmed to have the correct sequence. The argU gene was excised from this vector by means of restriction digestion with the enzyme EcoR I. This fragment was ligated to vector pRE2 (Reddy et al. (1989) Nucleic Acids Res. 17, 10473-10488) which was digested with EcoR I and dephosphorylated. Resulting plasmids were screened for the presence of the argU gene, and inserts of both orientations were obtained. The new plasmid carrying the argU gene transcribed in the same direction as the vector gene for beta-lactamase is designated pRD (SEQ. ID NO. 3); the plasmid with argU transcribed in the opposite direction is designated pRD2 (SEQ. ID. NO. 4).
Example 2
Cloning of Pyrococcus furiosus DNA polymerase
Growth of Pyrococcus furiosus
A culture of Pyrococcus furiosus was a gift of Dr. Frank T. Robb. The culture was grown at 90° C. essentially as described (Archaea: A Laboratory Manual (1995) Robb, F. T. (ed.), Cold Spring Habor Laboratory Press, Plainview, N.Y.). The medium contained: per liter, 5 g Tryptone, 1 g yeast extract, 24 g NaCl, 4 g Na 2 SO 4 , 0.7 g KCl, 0.2 g NaHCO 3 , 0.1 g KBr, 30 mg H 3 BO 3 , 10.8 g MgCl 2 .6H 2 O, 1.5 g CaCl 2 , 25 mg SrCl 2 , 0.4 mg resazurin.
Preparation of Genomic DNA
Frozen cell paste of Pyrococcus furiosus (approximately 350 mg) was resuspended in 700 μl of lysis buffer (50 mM Tris.HCl pH 8.0, 50 mM EDTA, 3% SDS (w/v), 1% 2-mercaptoethanol (v/v)) and incubated for 1 hour at 65° C. This solution was extracted three times with 25:24:1 phenol:chloroform:isoamyl alcohol, twice with chloroform and precipitated with two volumes of 100% ethanol. The pellet was dried briefly in vacuo and dissolved in 700 μl TE (10 mM Tris.HCl pH 8.0, 1 mM EDTA). The concentration of genomic DNA was determined spectrophotometrically by measuring the absorbance at 260 nm (1A 260 =50 μg/ml) and by comparison of UV fluorescence of bands on an ethidium bromide stained agarose gel relative to standard concentration markers.
PCR Amplification of DNA polymerase Gene and Cloning
PCR primers to amplify the DNA polymerase gene from the genome of Pyrococcus furiosus were designed from the published gene sequence (Uemori, T., Ishino, Y., Toh, H., Asada, F. and Kato, I. (1993) Nucleic Acids Res. 21, 259-265) (SEQ. ID. NO. 38). The 5' primer, PFUPOLF (GGGGTACCATATGATTTTAGATGTGGATTACATAAC)(SEQ. ID. NO. 5) hybridizes to nucleotides 1-26 of the DNA polymerase coding sequence and introduces a unique Nde I (CATATG) site on the amplified product. The 3' primer, PFUPOLR2 (TCCCCCGGGCTAGGATTTTTTAATGTTAAGCCA)(SEQ. ID. NO. 6) hybridizes to nucleotides 2305-2328 of the DNA polymerase coding sequence and introduces a unique Sma I site (CCCGGG) on the amplified product.
To minimize errors introduced by Taq DNA polymerase during PCR, a modified "long PCR" was carried out. The PCR reaction contained: 20 mM Tricine (pH 8.8), 85 mM KOAc, 200 μM each dNTP, 5% DMSO, 0.5 mM each primer, 1.5 mM MgOAc (added last as hot-start), 2.5 units Hot Tub DNA polymerase per 100 μl reaction (Amersham), 0.025 U Deep Vent DNA polymerase per 100 μl reaction (New England Biolabs) and 20-100 ng Pyrococcus furiosus genomic DNA per 100 μl reaction. The cycling parameters consisted of: 94° C. 30 seconds, then 68° C. 10 minutes 40 seconds×8 cycles; 94° C. 30 seconds, then 68° C. 12 minutes×8 cycles; 94° C. 30 seconds, then 68° C. 13 minutes 20 seconds×8 cycles; 94° C. 30 s, then 68° C. 14 minutes 40 seconds×8 cycles.
The resulting PCR product was digested with Nde I and Sma I and cloned into similarly digested pRE2 (Reddy, P., Peterkofsky, A. and McKenney, K. (1989) Nucleic Acids Res. 17, 10473-10488) to produce pRE2PFUWT. Constructs made with pRE based vectors were propagated in E. coli strain DH-1 λ+(λcl+). The cloned gene was verified by DNA sequencing.
Example 3
Modification of the Polymerase Gene
Construction of D215A (exonuclease deficient) polymerase gene
Based on alignments of DNA polymerases (Delarue, M., Poch, O., Tordo, N., Moras, D. and Argos, P. (1990) Protein Engineering 3, 461-467; Braithwaite, D. K. and Ito, J. (1993) Nucleic Acids Res. 21, 787-202), the aspartic acid at amino acid position 215 was identified as being homologous to Asp66 of .o slashed.29 DNA polymerase. An acidic residue is highly conserved at this position among DNA polymerases possessing 3'-5' exonuclease activity. Mutation of Asp66 in .o slashed.29 DNA polymerase to alanine (D66A) resulted in a polymerase which had exonuclease activity reduced about 1000-fold relative to the wild type enzyme without affecting DNA polymerase activity (Bernard, A., Blanco, L., Lβzaro, J., Martin, G. and Salas, M. (1989) Cell 59, 219-228). To accomplish the analogous mutation in the Pyrococcus furiosus DNA polymerase gene, two primers were made. Primer D214ABAM (AAGGATCCTGACATTATAGTTACTTATAATGGAGACTCATTCGCCTTCCC) (SEQ. ID. NO. 7) covers the BamH I site at nt 603 of the coding sequence and is mutagenic for the Asp215 codon at nt 644 (GAC->GCC). Primer D214AECO (GGAATTCTTTCCCGAGTTCATAAG) (SEQ. ID. NO. 8) covers the EcoR I site at nt 973. These primers were used in PCR to simultaneously amplify the region between them and introduce the mutation. The resulting PCR product was digested with EcoR I and BamH I and subcloned into pRE2PFUWT to produce pTM100.
Modification of 5' end of DNA polymerase gene
In order to favor high-level expression of the DNA polymerase gene in E. coli, the 5' end of the gene was modified in two ways. Firstly, since the codon utilization of Pyrococcus furiosus differs significantly from that of E. coli, the first 58 codons of the gene were changed to synonymous codons favored by E. coli for highly expressed genes. Secondly, to further mimic a highly expressed E. coli coding sequence, an alanine codon (GCT) was inserted after the initiating methionine. Two long oligonucleotides, MOD95F (GCTATCCTGGACGTTGACTACATCACCGAAGAAGGTAAGCCGGTTATCCGTCTGT TCAAAAAAGAAAACGGTAAATTCAAAATCGAACACGACCG)(SEQ. ID. NO. 9) and MOD95R (ACCGGTGATTTTTTTAACTTCTTCGATTTTAGAGTCGTCACGCAGCAGAGCGTAG ATGTACGGACGGAAGGTACGGTCGTGTTCGATTTTGAATT)(SEQ. ID. NO. 10) which are antiparallel at their 3' ends were used together with primers MOD37F (GGGGTACCATATGGCTATCCTGGACGTTGACTACATC)(SEQ. ID. NO. 11) and MOD32R (GGGGTACCACCGGTGATTTTTTTAACTTCTTC)(SEQ. ID. NO. 12) in a PCR reaction containing 17.5 nM each MOD95F and MOD95R and 500 nM each MOD37F and MOD32R. The resulting 189 bp product contained an Nde I site corresponding to the start of the coding sequence, the changed codons discussed above and a silent Age I site. The product was cloned into pMOSBlue PCR product cloning vector (Amersham) to produce plasmid pTM101 and verified by sequencing. To introduce an Age I site into the gene, PCR was carried out using the unmodified clone (pTM100) as template with primers AGEIMUT (AAATAACCGGTGAACGTCATGGAAAGATTGTG)(SEQ. ID. NO. 13) which introduces a silent mutation for the Age I site and R467 (CCTTTGCTTCATTTTCATCTG)(SEQ. ID. NO. 14). The resulting 350 bp PCR product was cloned into pMOSBlue to produce plasmid pTM102. The modified gene was constructed by ligating the 165 bp fragment of pTM101 digested with Nde I and Age I, the 165 bp fragment of pTM102 digested with Age I and BstB I and the >5 kb fragment of pRE2PFUWT (for exo+) or pTM100 (for exo-) digested with Nde I and BstB I. The resulting exo+ construct is designated pTM103, the exo- construct pTM104. Constructs were verified by restriction digestion with each enzyme used in cloning.
Introduction of Xho I and BssH II cloning sites
Twelve cassette oligonucleotides, six for the sense strand and six for the antisense, which match the sequence of the region between the EcoN I (nt 1309 of the modified coding sequence) and Sac I (nt 1585) restriction sites except for silent mutations which introduce Xho I and BssH II sites at nts 1372 and 1507, respectively, were constructed. The cassette oligos are:
CASST1(AGTAGGCCACAAGTTCTGCAAGGACATCCCTGGTTTTATACCAAGTCTCT)(SEQ. ID. NO. 15),
CASST2(TGGGACATTTGCTCGAGGAAAGACAAAAGATTAAGACAAAAATGAAGGAA)(SEQ. ID. NO. 16),
CASST3(ACTCAAGATCCTATAGAAAAAATACTCCTTGACTATAGACAAAAAGCGAT)(SEQ. ID. NO. 17),
CASST4(AAAACTCTTAGCAAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC)(SEQ. ID. NO. 18),
CASST5(GCTGGTACTGTAAGGAGTGTGCTGAGAGCGTTACTGCCTGGGGAAGAAAG)(SEQ. ID. NO. 19),
CASST6(TACATCGAGTTAGTATGGAAGGAGCT)(SEQ. ID. NO. 20),
CASSB1(CCTTCCATACTAACTCGATGTACTTTCTTCCCCAGGCAGTAACGCTCTCA)(SEQ. ID. NO. 21),
CASSB2(GCACACTCCTTACAGTACCAGCGCGCTTTTGCATAGCCATAATATCCGTA)(SEQ. ID. NO. 22),
CASSB3(GAAAGAATTTGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA)(SEQ. ID. NO. 23),
CASSB4(TTTTTTCTATAGGATCTTGAGTTTCCTTCATTTTTGTCTTAATCTTTTGT)(SEQ. ID. NO. 24),
CASSB5(CTTTCCTCTAACAAATGTCCCAAGAGACTTGGTATAAAACCAGGGATGTC)(SEQ. ID. NO. 25) and
CASSB6 (CTTGCAGAACTTGTGGCCTAC)(SEQ. ID. NO. 26).
Oligonucleotides were purchased 5' phosphorylated using Phosphalink amidite (ABI). Each oligonucleotide was made 20 μM in TE (10 mM Tris.HCl pH 8.0, 0.1 mM EDTA). In one reaction, 2 μl of each oligonucleotide were combined with 3 μl 10× Taq ligase buffer and 1 μl (40 units) Taq DNA ligase (New England Biolabs) and incubated 30 minutes at 45° C. PCR was carried out using 1 μl of this ligated material as substrate and primers CASPCRF2 (TCGCTCCTCAAGTAGGCCACAAGTTCTGCAAGGACATCCC)(SEQ. ID. NO. 27) and CASPCRR2 (TCTTCGAGCTCCTTCCATACTAACTCGATGTACTTTCTTC)(SEQ. ID. NO. 28). The resulting product was digested with Sac I and EcoNI and cloned into similarly digested parent vector pTM103 to produce pTM119 or the same construct in pRD to produce pTM118.
Example 4
Expression and Purification of Pfu DNA polymerase
Expression
E. coli strain M5248 (cI857 Iysogen) harboring the expression plasmid was cultured in LB medium (per liter: 10 g tryptone, 5 g yeast extract, 10 g NaCl) supplemented with 50 μg/ml ampicillin. The culture was grown at 30-32° C. until the OD 600 reached approximately 1.0 at which time the culture temperature was raised to 40°-42° C. Growth continued at this temperature for 2 hours. The cells were harvested and frozen at -20° C. until needed.
Preparation of Extract
Frozen cell paste was resuspended in buffer A (50 mM Tris.HCl pH 8.0, 1 mM EDTA, 0.1% (v/v) each, NP40 and Tween-20) containing 100 mM NaCl, 1 mM PMSF, lysozyme (0.2 mg·ml -1 ) and DNase I (10 μg·ml -1 ) at 0.1 ml buffer per ml original culture volume. After 15 minutes incubation at room temperature, the lysate was subjected to brief sonication, and cleared by centrifugation. The cleared lysate was heated to 70° C. for 10-15 minutes, incubated on ice for 10 minutes and centrifuged again. This heat treatment inactivates detectable DNA polymerase activity resulting from the E. coli host polymerases. The cleared, heat-treated lysate is designated fraction I.
Liquid Chromatography Purification
Fraction I was passed through a column of DEAE cellulose (DE-52, Whatman) equilibrated in buffer A containing 100 mM NaCl and washed with the same buffer. The flow-through fractions containing DNA polymerase activity were collected and loaded onto a column of Heparin Sepharose (Heparin Sepharose CL-6B, Pharmacia) equilibrated in the same buffer. The column was washed and the DNA polymerase activity was eluted with a linear salt gradient of 100-700 mM NaCl in buffer A with the peak of activity eluting at about 300 mM NaCl. The active fractions were pooled, concentrated via ultrafiltration (Centricon-50, Amicon) and dialyzed against storage buffer (50 mM Tris HCl pH 8.2 @ room temperature, 0.1 mM EDTA, 0.1% (v/v) Triton X-100, 0.1% (v/v) NP40 and 50% (v/v) glycerol).
Example 5
Mutagenesis of Pfu DNA polymerase Gene
Mutations were introduced into the coding sequence of the Pyrococcus furiosus DNA polymerase gene in a manner analogous to the cassette mutagenesis used to introduce the BssHII and Xho I restriction sites. For example, mutant A491Y was constructed as follows:
Oligonucleotides CASST1, CASST2, CASST3, CASST5, CASST6, CASSB1, CASSB2, CASSB4, CASSB5, CASSB6 described above were combined with two mutagenic oligonucleotides, A491YT (AAAACTCTTATACAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC) SEQ. ID. NO. 29) and A491YB (GAAAGAATTGTATAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA) (SEQ. ID. NO. 30), both 5' phosphorylated as above to a final concentration of 1.7 μM each oligonucleotide in TE (10 mM Tris.HCl pH 8.0, 0.1 mM EDTA). These two primers are identical to CASST4 and CASSB3, respectively, except the codon for alanine 491 (GCA) has been changed to tyrosine (TAC). To 48 μl of the oligonucleotide mix was add 8.5 μl of annealing buffer (50 mM MgCl 2 , 100 mM Tris.HCl pH 7.5 and 300 mM NaCl). The mixture was heated to 100° C. and slow cooled to 50° C. at which time 8 μl was withdrawn and added to 1 μl Taq DNA ligase buffer and 1 μl (40 units) Taq DNA ligase (New England Biolabs). Incubation continued for 30 minutes at 50° C. PCR was carried out with Ultma DNA polymerase (Perkin-Elmer) using 1 μl of this ligated material as template and oligonucleotides CASST1 and CASSB1 as PCR primers. The resulting 275 bp product was extracted with CHCl 3 , digested with Xho I and BssH II, and cloned into similarly digested pTM118 to produce pTM113.
In a similar fashion, three other mutants were constructed. Using oligonucleotides N492YT (AAAACTCTTAGCATACTCTTTCTACGGATATTATGGCTATGCAAAAGCGC) SEQ. ID. NO. 31) and N492YB (GAAAGAGTATGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA) SEQ. ID. NO. 32), a construct was made which has tyrosine substituted for asparagine 492 (N492Y). Using oligonucleotides 0491YT (AAAACTCTTAGCATACAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC) SEQ. ID. NO. 33) and 0491YB (GAAAGAATTGTATGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA) SEQ. ID. NO. 34), a construct was made which has tyrosine inserted between alanine 491 and asparagine 492 (ω491Y). Using oligonucleotides OTAQ7T (AAAAACCATCAACTACGGTGTTCTCTACGGATATTATGGCTATGCAAAAGCGC) SEQ. ID. NO. 35) and OTAQ7B (GAGAACACCGTAGTTGATGGTTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA) SEQ. ID. NO. 36), a construct was made which has the sequence of seven amino acids TINYGVL replacing the sequence of six amino acids LLANSF at position #490-495 of the Pyrococcus furiosus DNA polymerase coding sequence (ωTAQ7).
Example 6
Characterization of Pfu DNA polymerases
Mutant DNA polymerases were characterized by performing sequencing reactions. The reaction contained annealed primer:template (0.5 pmole universal cycle primer (Amersham) labeled on the 5' end by the action of T4 polynucleotide kinase and γ- 33 p! ATP annealed to 1 μg M13mp18) in reaction buffer (20 mM Tris HCl pH 8.5 @ room temperature, 10 mM KCl, 10 mM (NH 4 ) 2 SO 4 , 0.1% (v/v) Triton X-100, 100 μg/ml BSA, 2 mM MgSO 4 ) and 4-8 units of polymerase. This mixture was divided into four and added to tubes containing 4 μl termination mix. All termination mixes consisted of 50 μM each dNTP in reaction buffer and various amounts of ddNTP. A complement of termination mixes at 100:1 ddNTP:dNTP, for example, contained 5 mM ddG, ddA, ddT or ddC in addition to the dNTPs and buffer. Upon addition of the enzyme primer:template to the termination mixes, the reactions were incubated at 70° C. for 15-30 minutes, stopped by addition of 4 μl stop solution (95% formamide, 10 mM EDTA, 0.1% each bromophenol blue and xylene cyanol), heated to ca. 75° C. for 5 minutes and loaded onto a denaturing polyacrylamide gel and electrophoresed under standard conditions. An autoradiogram of the electrophoresed gel was subjected to densitometry with an optical scanner (SciScan, USB) to determine band intensity.
Wild type Pyrococcus furiosus DNA polymerase requires termination mixes that are 100:1 ddNTP:dNTP to bring about chain termination events distributed evenly in the region 1-400 nt downstream of the primer. The root mean square ("RMS value") of the measured band intensities in the region about 50-200 nt downstream of the primer is approximately 0.65. In other words, the standard deviation of the measured band intensities is 65% of the mean value.
The mutant enzyme A491Y DNA polymerase required termination mixes adjusted to 25:1, 50:1, 25:1 and 25:1 ddNTP:dNTP for G, A, T and C, respectively, to bring about chain termination events distributed evenly in the region 1-400 nt downstream of the primer. Using the same ratios as wild type (100:1 ddNTP:dNTP) resulted in very short extension products i.e. less than 40 from the primer. Therefore, the A491Y mutant is able to utilize ddNTPs more efficiently than the wild type enzyme. More significantly, the band intensities on the autoradiogram of an optimized reaction are much more uniform for the A491Y mutant DNA polymerase than for the wild type DNA polymerase having and RMS value of 0.3. This RMS value reflects a great improvement in band uniformity. FIG. 3 shows sequencing data produced by wild type and A491Y DNA polymerases.
The mutant enzymes ω491Y (tyrosine inserted between A491 and N492), ωTAQ7 (amino acids 489-494 replaced with 7 corresponding amino acids from Taq polymerase including an F->Y substitution) and N492Y were purified and all had significantly reduced specific activities (greater than 100-fold of wild type).
Other embodiments are within the following claims.
__________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 38(2) INFORMATION FOR SEQ ID NO: 1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1:GGAATTCAGATCTAAAAGCCATTGACTCAGCAAG34(2) INFORMATION FOR SEQ ID NO: 2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 34 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2:GGAATTCACATGTGACAGAGCATGCGAGGAAAAT34(2) INFORMATION FOR SEQ ID NO: 3:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 5249 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3:TTCACATGTGACAGAGCATGCGAGGAAAATAGACGACATTTTTGGTGATAATGTCCCAAA60TATGTCCCACTCTGAAATTATGGAGGATATAAAGAAGGCGTAACTGATTGAATTGTAATG120GCGCGCCCTGCAGGATTCGAACCTGCGGCCCACGACTTAGAAGGTCGTTGCTCTATCCAA180CTGAGCTAAGGGCGCGTTGATACCGCAATGCGGTGTAATCGCGTGAATTATACGGTCAAC240CCTTGCTGAGTCAATGGCTTTTAGATCTGAATTCTCATGTTTGACAGCTTATCATCGATA300AGCTTTAATGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGGCACCGTGTATGA360AATCTAACAATGCGCTCATCGTCATCCTCGGCACCGTCACCCTGGATGCTGTAGGCATAG420GCTTGGTTATGCCGGTACTGCCGGGCCTCTTGCGGGATATCGTCCATTCCGACAGCATCG480CCAGTCACTATGGCGTGCTGCTAGTCCAGTAATGACCTCAGAACTCCATCTGGATTTGTT540CAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCGCAGCAACTTGTCGCG600CCAATCGAGCCATGTCGTCGTCAACGACCCCCCATTCAAGAACAGCAAGCAGCATTGAGA660ACTTTGGAATCCAGTCCCTCTTCCACCTGCTGACTAGCGCTATATGCGTTGATGCAATTT720CTATGCGCACCCGTTCTCGGAGCACTGTCCGACCGCTTTGGCCGCCGCCCAGTCCTGCTC780GCTTCGCTACTTGGAGCCACTATCGACTACGCGATCATGGCGACCACACCCGTCCTGTGG840ATCTCTCACCTACCAAACAATGCCCCCCTGCAAAAAATAAATTCATATAAAAAACATACA900GATAACCATCTGCGGTGATAAATTATCTCTGGCGGTGTTGACATAAATACCACTGGCGGT960GATACTGAGCACATCAGCAGGACGCACTGACCACCATGAAGGTGACGCTCTTAAAAATTA1020AGCCCTGAAGAAGGGCAGCATTCAAAGCAGAAGGCTTTGGGGTGTGTGATACGAAACGAA1080GCATTGGCCGTAAGTGCGATTCCGGATTAGCTGCCAATGTGCCAATCGCGGGGGGTTTTC1140GTTCAGGACTACAACTGCCACACACCACCAAAGCTAACTGACAGGAGAATCCAGATGGAT1200GCACAAACACGCCGCCGCGAACGTCGCGCAGAGAAACAGGCTCAATGGAAAGCAGCAAAT1260CCCCTGTTGGTTGGGGTAAGCGCAAAACCAGTTCCGAAAGATTTTTTTAACTATAAACGC1320TGATGGAAGCGTTTATGCGGAAGAGGTAAAGCCCTTCCCGAGTAACAAAAAAACAACAGC1380ATAAATAACCCCGCTCTTACACATTCCAGCCCTGAAAAAGGGCATCAAATTAAACCACAC1440CTATGGTGTATGCATTTATTTGCATACATTCAATCAATTGTTATCTAAGGAAATACTTAC1500ATATGATATCTAGAGGATCCCGGGTACCGAGCTCGTCGACCGATGCCCTTGAGAGCCTTC1560AACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTCGCCGCACTTATGACT1620GTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTGGGTCATTTTCGGC1680GAGGACCGCTTTCGCTGGAGCGCGACGATGATCGGCCTGTCGCTTGCGGTATTCGGAATC1740TTGCACGCCCTCGCTCAAGCCTTCGTCACTGGTCCCGCCACCAAACGTTTCGGCGAGAAG1800CAGGCCATTATCGCCGGCATGGCGGCCGACGCGCTGGGCTACGTCTTGCTGGCGTTCGCG1860ACGCGAGGCTGGATGGCCTTCCCCATTATGATTCTTCTCGCTTCCGGCGGCATCGGGATG1920CCCGCGTTGCAGGCCATGCTGTCCAGGCAGGTAGATGACGACCATCAGGGACAGCTTCAA1980GGATCGCTCGCGGCTCTTACCAGCCTAACTTCGATCACTGGACCGCTGATCGTCACGGCG2040ATTTATGCCGCCTCGGCGAGCACATGGAACGGGTTGGCATGGATTGTAGGCGCCGCCCTA2100TACCTTGTCTGCCTCCCCGCGTTGCGTCGCGGTGCATGGAGCCGGGCCACCTCGACCTGA2160ATGGAAGCCGGCGGCACCTCGCTAACGGATTCACCACTCCAAGAATTGGAGCCAATCAAT2220TCTTGCGGAGAACTGTGAATGCGCAAACCAACCCTTGGCAGAACATATCCATCGCGTCCG2280CCATCTCCAGCAGCCGCACGCGGCGCATCTCGGGCAGCGTTGGGTCCTGGCCACGGGTGC2340GCATGATCGTGCTCCTGTCGTTGAGGACCCGGCTAGGCTGGCGGGGTTGCCTTACTGGTT2400AGCAGAATGAATCACCGATACGCGAGCGAACGTGAAGCGACTGCTGCTGCAAAACGTCTG2460CGACCTGAGCAACAACATGAATGGTCTTCGGTTTCCGTGTTTCGTAAAGTCTGGAAACGC2520GGAAGTCAGCGCCCTGCACCATTATGTTCCGGATCTGCATCGCAGGATGCTGCTGGCTAC2580CCTGTGGAACACCTACATCTGTATTAACGAAGCGCTGGCATTGACCCTGAGTGATTTTTC2640TCTGGTCCCGCCGCATCCATACCGCCAGTTGTTTACCCTCACAACGTTCCAGTAACCGGG2700CATGTTCATCATCAGTAACCCGTATCGTGAGCATCCTCTCTCGTTTCATCGGTATCATTA2760CCCCCATGAACAGAAATTCCCCCTTACACGGAGGCATCAAGTGACCAAACAGGAAAAAAC2820CGCCCTTAACATGGCCCGCTTTATCAGAAGCCAGACATTAACGCTTCTGGAGAAACTCAA2880CGAGCTGGACGCGGATGAACAGGCAGACATCTGTGAATCGCTTCACGACCACGCTGATGA2940GCTTTACCGCAGCTGCCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCA3000GCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCA3060GGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCGCAGCCATGACCCAGTCACGTAGCGA3120TAGCGGAGTGTATACTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCAC3180CATATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCT3240CTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTAT3300CAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGA3360ACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGT3420TTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGT3480GGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGC3540GCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAA3600GCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCT3660CCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTA3720ACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTG3780GTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGC3840CTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTA3900CCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTG3960GTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTT4020TGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGG4080TCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTA4140AATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTG4200AGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCG4260TGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGC4320GAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCG4380AGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGG4440AAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTGCAG4500GCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGAT4560CAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTC4620CGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGC4680ATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAA4740CCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAACAC4800GGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTT4860CGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTC4920GTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAA4980CAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCA5040TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGAT5100ACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAA5160AAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGC5220GTATCACGAGGCCCTTTCGTCTTCAAGAA5249(2) INFORMATION FOR SEQ ID NO: 4:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 5249 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4:TTCAGATCTAAAAGCCATTGACTCAGCAAGGGTTGACCGTATAATTCACGCGATTACACC60GCATTGCGGTATCAACGCGCCCTTAGCTCAGTTGGATAGAGCAACGACCTTCTAAGTCGT120GGGCCGCAGGTTCGAATCCTGCAGGGCGCGCCATTACAATTCAATCAGTTACGCCTTCTT180TATATCCTCCATAATTTCAGAGTGGGACATATTTGGGACATTATCACCAAAAATGTCGTC240TATTTTCCTCGCATGCTCTGTCACATGTGAATTCTCATGTTTGACAGCTTATCATCGATA300AGCTTTAATGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGGCACCGTGTATGA360AATCTAACAATGCGCTCATCGTCATCCTCGGCACCGTCACCCTGGATGCTGTAGGCATAG420GCTTGGTTATGCCGGTACTGCCGGGCCTCTTGCGGGATATCGTCCATTCCGACAGCATCG480CCAGTCACTATGGCGTGCTGCTAGTCCAGTAATGACCTCAGAACTCCATCTGGATTTGTT540CAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCGCAGCAACTTGTCGCG600CCAATCGAGCCATGTCGTCGTCAACGACCCCCCATTCAAGAACAGCAAGCAGCATTGAGA660ACTTTGGAATCCAGTCCCTCTTCCACCTGCTGACTAGCGCTATATGCGTTGATGCAATTT720CTATGCGCACCCGTTCTCGGAGCACTGTCCGACCGCTTTGGCCGCCGCCCAGTCCTGCTC780GCTTCGCTACTTGGAGCCACTATCGACTACGCGATCATGGCGACCACACCCGTCCTGTGG840ATCTCTCACCTACCAAACAATGCCCCCCTGCAAAAAATAAATTCATATAAAAAACATACA900GATAACCATCTGCGGTGATAAATTATCTCTGGCGGTGTTGACATAAATACCACTGGCGGT960GATACTGAGCACATCAGCAGGACGCACTGACCACCATGAAGGTGACGCTCTTAAAAATTA1020AGCCCTGAAGAAGGGCAGCATTCAAAGCAGAAGGCTTTGGGGTGTGTGATACGAAACGAA1080GCATTGGCCGTAAGTGCGATTCCGGATTAGCTGCCAATGTGCCAATCGCGGGGGGTTTTC1140GTTCAGGACTACAACTGCCACACACCACCAAAGCTAACTGACAGGAGAATCCAGATGGAT1200GCACAAACACGCCGCCGCGAACGTCGCGCAGAGAAACAGGCTCAATGGAAAGCAGCAAAT1260CCCCTGTTGGTTGGGGTAAGCGCAAAACCAGTTCCGAAAGATTTTTTTAACTATAAACGC1320TGATGGAAGCGTTTATGCGGAAGAGGTAAAGCCCTTCCCGAGTAACAAAAAAACAACAGC1380ATAAATAACCCCGCTCTTACACATTCCAGCCCTGAAAAAGGGCATCAAATTAAACCACAC1440CTATGGTGTATGCATTTATTTGCATACATTCAATCAATTGTTATCTAAGGAAATACTTAC1500ATATGATATCTAGAGGATCCCGGGTACCGAGCTCGTCGACCGATGCCCTTGAGAGCCTTC1560AACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTCGCCGCACTTATGACT1620GTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTGGGTCATTTTCGGC1680GAGGACCGCTTTCGCTGGAGCGCGACGATGATCGGCCTGTCGCTTGCGGTATTCGGAATC1740TTGCACGCCCTCGCTCAAGCCTTCGTCACTGGTCCCGCCACCAAACGTTTCGGCGAGAAG1800CAGGCCATTATCGCCGGCATGGCGGCCGACGCGCTGGGCTACGTCTTGCTGGCGTTCGCG1860ACGCGAGGCTGGATGGCCTTCCCCATTATGATTCTTCTCGCTTCCGGCGGCATCGGGATG1920CCCGCGTTGCAGGCCATGCTGTCCAGGCAGGTAGATGACGACCATCAGGGACAGCTTCAA1980GGATCGCTCGCGGCTCTTACCAGCCTAACTTCGATCACTGGACCGCTGATCGTCACGGCG2040ATTTATGCCGCCTCGGCGAGCACATGGAACGGGTTGGCATGGATTGTAGGCGCCGCCCTA2100TACCTTGTCTGCCTCCCCGCGTTGCGTCGCGGTGCATGGAGCCGGGCCACCTCGACCTGA2160ATGGAAGCCGGCGGCACCTCGCTAACGGATTCACCACTCCAAGAATTGGAGCCAATCAAT2220TCTTGCGGAGAACTGTGAATGCGCAAACCAACCCTTGGCAGAACATATCCATCGCGTCCG2280CCATCTCCAGCAGCCGCACGCGGCGCATCTCGGGCAGCGTTGGGTCCTGGCCACGGGTGC2340GCATGATCGTGCTCCTGTCGTTGAGGACCCGGCTAGGCTGGCGGGGTTGCCTTACTGGTT2400AGCAGAATGAATCACCGATACGCGAGCGAACGTGAAGCGACTGCTGCTGCAAAACGTCTG2460CGACCTGAGCAACAACATGAATGGTCTTCGGTTTCCGTGTTTCGTAAAGTCTGGAAACGC2520GGAAGTCAGCGCCCTGCACCATTATGTTCCGGATCTGCATCGCAGGATGCTGCTGGCTAC2580CCTGTGGAACACCTACATCTGTATTAACGAAGCGCTGGCATTGACCCTGAGTGATTTTTC2640TCTGGTCCCGCCGCATCCATACCGCCAGTTGTTTACCCTCACAACGTTCCAGTAACCGGG2700CATGTTCATCATCAGTAACCCGTATCGTGAGCATCCTCTCTCGTTTCATCGGTATCATTA2760CCCCCATGAACAGAAATTCCCCCTTACACGGAGGCATCAAGTGACCAAACAGGAAAAAAC2820CGCCCTTAACATGGCCCGCTTTATCAGAAGCCAGACATTAACGCTTCTGGAGAAACTCAA2880CGAGCTGGACGCGGATGAACAGGCAGACATCTGTGAATCGCTTCACGACCACGCTGATGA2940GCTTTACCGCAGCTGCCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCA3000GCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCA3060GGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCGCAGCCATGACCCAGTCACGTAGCGA3120TAGCGGAGTGTATACTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCAC3180CATATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCT3240CTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTAT3300CAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGA3360ACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGT3420TTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGT3480GGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGC3540GCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAA3600GCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCT3660CCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTA3720ACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTG3780GTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGC3840CTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTA3900CCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTG3960GTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTT4020TGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGG4080TCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTA4140AATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTG4200AGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCG4260TGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGC4320GAGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCG4380AGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGG4440AAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTGCAG4500GCATCGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGAT4560CAAGGCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTC4620CGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGC4680ATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAA4740CCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAACAC4800GGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTT4860CGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTC4920GTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAA4980CAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCA5040TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGAT5100ACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAA5160AAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGC5220GTATCACGAGGCCCTTTCGTCTTCAAGAA5249(2) INFORMATION FOR SEQ ID NO: 5:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 36 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5:GGGGTACCATATGATTTTAGATGTGGATTACATAAC36(2) INFORMATION FOR SEQ ID NO: 6:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6:TCCCCCGGGCTAGGATTTTTTAATGTTAAGCCA33(2) INFORMATION FOR SEQ ID NO: 7:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7:AAGGATCCTGACATTATAGTTACTTATAATGGAGACTCATTCGCCTTCCC50(2) INFORMATION FOR SEQ ID NO: 8:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 24 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8:GGAATTCTTTCCCGAGTTCATAAG24(2) INFORMATION FOR SEQ ID NO: 9:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 95 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:GCTATCCTGGACGTTGACTACATCACCGAAGAAGGTAAGCCGGTTATCCG50TCTGTTCAAAAAAGAAAACGGTAAATTCAAAATCGAACACGACCG95(2) INFORMATION FOR SEQ ID NO: 10:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 95 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:ACCGGTGATTTTTTTAACTTCTTCGATTTTAGAGTCGTCACGCAGCAGAG50CGTAGATGTACGGACGGAAGGTACGGTCGTGTTCGATTTTGAATT95(2) INFORMATION FOR SEQ ID NO: 11:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 37 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11:GGGGTACCATATGGCTATCCTGGACGTTGACTACATC37(2) INFORMATION FOR SEQ ID NO: 12:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:GGGGTACCACCGGTGATTTTTTTAACTTCTTC32(2) INFORMATION FOR SEQ ID NO: 13:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:AAATAACCGGTGAACGTCATGGAAAGATTGTG32(2) INFORMATION FOR SEQ ID NO: 14:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 21 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:CCTTTGCTTCATTTTCATCTG21(2) INFORMATION FOR SEQ ID NO: 15:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:AGTAGGCCACAAGTTCTGCAAGGACATCCCTGGTTTTATACCAAGTCTCT50(2) INFORMATION FOR SEQ ID NO: 16:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16:TGGGACATTTGCTCGAGGAAAGACAAAAGATTAAGACAAAAATGAAGGAA50(2) INFORMATION FOR SEQ ID NO: 17:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:ACTCAAGATCCTATAGAAAAAATACTCCTTGACTATAGACAAAAAGCGAT50(2) INFORMATION FOR SEQ ID NO: 18:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18:AAAACTCTTAGCAAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC50(2) INFORMATION FOR SEQ ID NO: 19:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19:GCTGGTACTGTAAGGAGTGTGCTGAGAGCGTTACTGCCTGGGGAAGAAAG50(2) INFORMATION FOR SEQ ID NO: 20:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 26 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20:TACATCGAGTTAGTATGGAAGGAGCT26(2) INFORMATION FOR SEQ ID NO: 21:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21:CCTTCCATACTAACTCGATGTACTTTCTTCCCCAGGCAGTAACGCTCTCA50(2) INFORMATION FOR SEQ ID NO: 22:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22:GCACACTCCTTACAGTACCAGCGCGCTTTTGCATAGCCATAATATCCGTA50(2) INFORMATION FOR SEQ ID NO: 23:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:GAAAGAATTTGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA50(2) INFORMATION FOR SEQ ID NO: 24:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:TTTTTTCTATAGGATCTTGAGTTTCCTTCATTTTTGTCTTAATCTTTTGT50(2) INFORMATION FOR SEQ ID NO: 25:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25:CTTTCCTCTAACAAATGTCCCAAGAGACTTGGTATAAAACCAGGGATGTC50(2) INFORMATION FOR SEQ ID NO: 26:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 21 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26:CTTGCAGAACTTGTGGCCTAC21(2) INFORMATION FOR SEQ ID NO: 27:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27:TCGCTCCTCAAGTAGGCCACAAGTTCTGCAAGGACATCCC40(2) INFORMATION FOR SEQ ID NO: 28:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 40 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28:TCTTCGAGCTCCTTCCATACTAACTCGATGTACTTTCTTC40(2) INFORMATION FOR SEQ ID NO: 29:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29:AAAACTCTTATACAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC50(2) INFORMATION FOR SEQ ID NO: 30:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30:GAAAGAATTGTATAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA50(2) INFORMATION FOR SEQ ID NO: 31:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31:AAAACTCTTAGCATACTCTTTCTACGGATATTATGGCTATGCAAAAGCGC50(2) INFORMATION FOR SEQ ID NO: 32:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 50 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32:GAAAGAGTATGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA50(2) INFORMATION FOR SEQ ID NO: 33:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 53 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33:AAAACTCTTAGCATACAATTCTTTCTACGGATATTATGGCTATGCAAAAGCGC53(2) INFORMATION FOR SEQ ID NO: 34:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 53 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:GAAAGAATTGTATGCTAAGAGTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA53(2) INFORMATION FOR SEQ ID NO: 35:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 53 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35:AAAAACCATCAACTACGGTGTTCTCTACGGATATTATGGCTATGCAAAAGCGC53(2) INFORMATION FOR SEQ ID NO: 36:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 53 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36:GAGAACACCGTAGTTGATGGTTTTTATCGCTTTTTGTCTATAGTCAAGGAGTA53(2) INFORMATION FOR SEQ ID NO: 37:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 776 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: peptide(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37:MetIleLeuAspValAspTyrIleThrGluGluGlyLysProValIle151015ArgLeuPheLysLysGluAsnGlyLysPheLysIleGluHisAspArg202530ThrPheArgProTyrIleTyrAlaLeuLeuArgAspAspSerLysIle354045GluGluValLysLysIleThrGlyGluArgHisGlyLysIleValArg505560IleValAspValGluLysValGluLysLysPheLeuGlyLysProIle65707580ThrValTrpLysLeuTyrLeuGluHisProGlnAspValProThrIle859095ArgGluLysValArgGluHisProAlaValValAspIlePheGluTyr100105110AspIleProPheAlaLysArgTyrLeuIleAspLysGlyLeuIlePro115120125MetGluGlyGluGluGluLeuLysIleLeuAlaPheAspIleGluThr130135140LeuTyrHisGluGlyGluGluPheGlyLysGlyProIleIleMetIle145150155160SerTyrAlaAspGluAsnGluAlaLysValIleThrTrpLysAsnIle165170175AspLeuProTyrValGluValValSerSerGluArgGluMetIleLys180185190ArgPheLeuArgIleIleArgGluLysAspProAspIleIleValThr195200205TyrAsnGlyAspSerPheAspPheProTyrLeuAlaLysArgAlaGlu210215220LysLeuGlyIleLysLeuThrIleGlyArgAspGlySerGluProLys225230235240MetGlnArgIleGlyAspMetThrAlaValGluValLysGlyArgIle245250255HisPheAspLeuTyrHisValIleThrArgThrIleAsnLeuProThr260265270TyrThrLeuGluAlaValTyrGluAlaIlePheGlyLysProLysGlu275280285LysValTyrAlaAspGluIleAlaLysAlaTrpGluSerGlyGluAsn290295300LeuGluArgValAlaLysTyrSerMetGluAspAlaLysAlaThrTyr305310315320GluLeuGlyLysGluPheLeuProMetGluIleGlnLeuSerArgLeu325330335ValGlyGlnProLeuTrpAspValSerArgSerSerThrGlyAsnLeu340345350ValGluTrpPheLeuLeuArgLysAlaTyrGluArgAsnGluValAla355360365ProAsnLysProSerGluGluGluTyrGlnArgArgLeuArgGluSer370375380TyrThrGlyGlyPheValLysGluProGluLysGlyLeuTrpGluAsn385390395400IleValTyrLeuAspPheArgAlaLeuTyrProSerIleIleIleThr405410415HisAsnValSerProAspThrLeuAsnLeuGluGlyCysLysAsnTyr420425430AspIleAlaProGlnValGlyHisLysPheCysLysAspIleProGly435440445PheIleProSerLeuLeuGlyHisLeuLeuGluGluArgGlnLysIle450455460LysThrLysMetLysGluThrGlnAspProIleGluLysIleLeuLeu465470475480AspTyrArgGlnLysAlaIleLysLeuLeuAlaAsnSerPheTyrGly485490495TyrTyrGlyTyrAlaLysAlaArgTrpTyrCysLysGluCysAlaGlu500505510SerValThrAlaTrpGlyArgLysTyrIleGluLeuValTrpLysGlu515520525LeuGluGluLysPheGlyPheLysValLeuTyrIleAspThrAspGly530535540LeuTyrAlaThrIleProGlyGlyGluSerGluGluIleLysLysLys545550555560AlaLeuGluPheValLysTyrIleAsnSerLysLeuProGlyLeuLeu565570575GluLeuGluTyrGluGlyPheTyrLysArgGlyPhePheValThrLys580585590LysArgTyrAlaValIleAspGluGluGlyLysValIleThrArgGly595600605LeuGluIleValArgArgAspTrpSerGluIleAlaLysGluThrGln610615620AlaArgValLeuGluThrIleLeuLysHisGlyAspValGluGluAla625630635640ValArgIleValLysGluValIleGlnLysLeuAlaAsnTyrGluIle645650655ProProGluLysLeuAlaIleTyrGluGlnIleThrArgProLeuHis660665670GluTyrLysAlaIleGlyProHisValAlaValAlaLysLysLeuAla675680685AlaLysGlyValLysIleLysProGlyMetValIleGlyTyrIleVal690695700LeuArgGlyAspGlyProIleSerAsnArgAlaIleLeuAlaGluGlu705710715720TyrAspProLysLysHisLysTyrAspAlaGluTyrTyrIleGluAsn725730735GlnValLeuProAlaValLeuArgIleLeuGluGlyPheGlyTyrArg740745750LysGluAspLeuArgTyrGlnLysThrArgGlnValGlyLeuThrSer755760765TrpLeuAsnIleLysLysSerGlx770775(2) INFORMATION FOR SEQ ID NO: 38:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 2328 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38:ATGATTTTAGATGTGGATTACATAACTGAAGAAGGAAAACCTGTTATTAGGCTATTCAAA60AAAGAGAACGGAAAATTTAAGATAGAGCATGATAGAACTTTTAGACCATACATTTACGCT120CTTCTCAGGGATGATTCAAAGATTGAAGAAGTTAAGAAAATAACGGGGGAAAGGCATGGA180AAGATTGTGAGAATTGTTGATGTAGAGAAGGTTGAGAAAAAGTTTCTCGGCAAGCCTATT240ACCGTGTGGAAACTTTATTTGGAACATCCCCAAGATGTTCCCACTATTAGAGAAAAAGTT300AGAGAACATCCAGCAGTTGTGGACATCTTCGAATACGATATTCCATTTGCAAAGAGATAC360CTCATCGACAAAGGCCTAATACCAATGGAGGGGGAAGAAGAGCTAAAGATTCTTGCCTTC420GATATAGAAACCCTCTATCACGAAGGAGAAGAGTTTGGAAAAGGCCCAATTATAATGATT480AGTTATGCAGATGAAAATGAAGCAAAGGTGATTACTTGGAAAAACATAGATCTTCCATAC540GTTGAGGTTGTATCAAGCGAGAGAGAGATGATAAAGAGATTTCTCAGGATTATCAGGGAG600AAGGATCCTGACATTATAGTTACTTATAATGGAGACTCATTCGACTTCCCATATTTAGCG660AAAAGGGCAGAAAAACTTGGGATTAAATTAACCATTGGAAGAGATGGAAGCGAGCCCAAG720ATGCAGAGAATAGGCGATATGACGGCTGTAGAAGTCAAGGGAAGAATACATTTCGACTTG780TATCATGTAATAACAAGGACAATAAATCTCCCAACATACACACTAGAGGCTGTATATGAA840GCAATTTTTGGAAAGCCAAAGGAGAAGGTATACGCCGACGAGATAGCAAAAGCCTGGGAA900AGTGGAGAGAACCTTGAGAGAGTTGCCAAATACTCGATGGAAGATGCAAAGGCAACTTAT960GAACTCGGGAAAGAATTCCTTCCAATGGAAATTCAGCTTTCAAGATTAGTTGGACAACCT1020TTATGGGATGTTTCAAGGTCAAGCACAGGGAACCTTGTAGAGTGGTTCTTACTTAGGAAA1080GCCTACGAAAGAAACGAAGTAGCTCCAAACAAGCCAAGTGAAGAGGAGTATCAAAGAAGG1140CTCAGGGAGAGCTACACAGGTGGATTCGTTAAAGAGCCAGAAAAGGGGTTGTGGGAAAAC1200ATAGTATACCTAGATTTTAGAGCCCTATATCCCTCGATTATAATTACCCACAATGTTTCT1260CCCGATACTCTAAATCTTGAGGGATGCAAGAACTATGATATCGCTCCTCAAGTAGGCCAC1320AAGTTCTGCAAGGACATCCCTGGTTTTATACCAAGTCTCTTGGGACATTTGTTAGAGGAA1380AGACAAAAGATTAAGACAAAAATGAAGGAAACTCAAGATCCTATAGAAAAAATACTCCTT1440GACTATAGACAAAAAGCGATAAAACTCTTAGCAAATTCTTTCTACGGATATTATGGCTAT1500GCAAAAGCAAGATGGTACTGTAAGGAGTGTGCTGAGAGCGTTACTGCCTGGGGAAGAAAG1560TACATCGAGTTAGTATGGAAGGAGCTCGAAGAAAAGTTTGGATTTAAAGTCCTCTACATT1620GACACTGATGGTCTCTATGCAACTATCCCAGGAGGAGAAAGTGAGGAAATAAAGAAAAAG1680GCTCTAGAATTTGTAAAATACATAAATTCAAAGCTCCCTGGACTGCTAGAGCTTGAATAT1740GAAGGGTTTTATAAGAGGGGATTCTTCGTTACGAAGAAGAGGTATGCAGTAATAGATGAA1800GAAGGAAAAGTCATTACTCGTGGTTTAGAGATAGTTAGGAGAGATTGGAGTGAAATTGCA1860AAAGAAACTCAAGCTAGAGTTTTGGAGACAATACTAAAACACGGAGATGTTGAAGAAGCT1920GTGAGAATAGTAAAAGAAGTAATACAAAAGCTTGCCAATTATGAAATTCCACCAGAGAAG1980CTCGCAATATATGAGCAGATAACAAGACCATTACATGAGTATAAGGCGATAGGTCCTCAC2040GTAGCTGTTGCAAAGAAACTAGCTGCTAAAGGAGTTAAAATAAAGCCAGGAATGGTAATT2100GGATACATAGTACTTAGAGGCGATGGTCCAATTAGCAATAGGGCAATTCTAGCTGAGGAA2160TACGATCCCAAAAAGCACAAGTATGACGCAGAATATTACATTGAGAACCAGGTTCTTCCA2220GCGGTACTTAGGATATTGGAGGGATTTGGATACAGAAAGGAAGACCTCAGATACCAAAAG2280ACAAGACAAGTCGGCCTAACTTCCTGGCTTAACATTAAAAAATCCTAG2328__________________________________________________________________________ | A Pol-II type DNA polymerase wherein an alanine located at the nucleotide binding site is replaced with a hydroxy containing amino acid. | 2 |
RELATED APPLICATION
[0001] This continuation-in-part application of U.S. patent application Ser. No. 10/691,189, filed Oct. 23, 2003, which claims benefit of U.S. Patent application Ser. No. 60/420,822, filed Oct. 24, 2002, both of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates generally to a multi-purpose goggle that can be utilized as a safety goggle suitable for a wide range of activities including: industrial and sporting use as well as a goggle to minimize or eliminate computer vision syndrome resulting from the prolonged use of a computer display terminal, as a platform for a virtual reality visor and for a limited viewing goggle for pilots undergoing instrument flight rating (“IFR”) qualifications. The goggles are configured such that they can be easily manufactured and utilized.
DESCRIPTION OF THE RELATED ART
[0003] Virtually all industrial and sports injuries to the eye are avoidable if suitable eye protection such as goggles are provided. Eye trauma is the leading cause of blindness worldwide. It is estimated that each day two thousand individuals in the United States suffer eye injuries on the job or while playing sports. These injuries incur more than $924 million annually in worker's compensation, and nearly $4 billion in wage and productivity losses according to the U.S. Bureau of Labor Statistics. Nearly 90 percent of all workplace and sports related injuries are preventable with the proper eyewear and safety measures according to statistics from the organization Prevent Blindness America.
[0004] It is evident from the eye injury statistics that large numbers of individuals are not wearing eye protection while in the vicinity of activities that present dangers to the eye. Also, injuries are still occurring despite the use of protective eyewear. Those individuals being injured often wear inappropriate or ill-fitting eyewear for the task being undertaken or do not wear protective eyewear at all times while undertaking the task. The literature suggests that the main reasons individuals do not wear protective eyewear relate to issues of comfort, style, restricted vision, and safety equipment not provided by employers.
[0005] OSHA standards require that employers provide, and workers wear, suitable eye protection. To be effective, the eyewear must be the appropriate type and properly fitted. For example, the Bureau of Labor Statistics survey revealed that 94 percent of injuries to workers wearing eye protection resulted from objects or caustics going around or under the protector. But less than six percent of the injuries happened to workers wearing goggles, which generally offer a tighter fit around the eyes.
[0006] Wearing protective eyewear can prevent 90% of sports-related injuries. Eyeglasses and contact lenses do not provide protection and can even place an athlete at an increased risk for such injuries. The American Academy of Ophthalmology has instituted a campaign for mandatory eyewear for children participating in school-related or community-sponsored athletic events. The Academy recommends that young athletes wear shatterproof goggles, constructed of 3 mm polycarbonate, that are fitted by an eye care professional.
[0007] In general, those individuals that are injured often wear inappropriate safety or ill-fitting eyewear for the task being undertaken, or do not wear protective eyewear at all times while undertaking the task. The finding that safety glasses may not provide adequate protection against small, off-center particles needs to be addressed, and the use of goggles promoted. According to OSHA, eye protection must, protect against the specific hazard(s) encountered in the workplace, be reasonably comfortable to wear, not restrict vision or movement, be durable and easy to clean and disinfect and not interfere with the function of other required personal protection equipment.
[0008] The reasons people give for not wearing safety goggles include, the safety goggles cause headaches, the eye protection is too hot to wear, the goggles are constantly dirty, the eye protection fogs over, the safety glasses never fit correctly, the goggles do not fit over prescription eyeglasses, the goggles lack style or comfort, and cause distortion and limit the field of vision.
[0009] Information relevant to attempts to address these problems can be found in U.S. Pat. Nos. 5,966,746, 5,519,896, 6,357,053, 5,771,499 and 6,178,561. However, each of these references suffers from one or more of the following disadvantages: inability to use existing prescription glasses while wearing the goggles, excessive goggle weight, limitations on range of vision such as obstruction of peripheral vision, uncomfortable to wear because of pressure applied to the head by bands and straps and internal fogging of the lenses brought about by perspiration, and at times respiration, of the wearer.
[0010] In addition to the ability of the multi-purpose goggles to protect against injury to the eye in sporting as well as industrial settings, the present invention is also well adapted to protect the eyes against computer vision syndrome. This condition most commonly occurs when the viewing demand of the task exceeds the visual abilities of the display terminal user. The symptoms of computer vision syndrome can be diminished, or eliminated, if proper equipment is employed. The American Optometric Association defines computer vision syndrome as that complex of eye and vision problems related to near work which are experienced during or related to computer use. The symptoms can vary, but they include eyestrain, headaches, blurred vision (distance, near, or both), dry and irritated eyes, slowed refocusing, neck ache, backache, sensitivity to light, and double vision.
[0011] Discomfort from glare is caused primarily by great disparities in brightness in the field of view. It is much more desirable to eliminate bright sources of light from the field of view and to strive to obtain a relatively even distribution of luminaries. A person is at great risk of experiencing discomfort from glare when the source of light is brighter and closer to the point of attention. For example, seventy five percent of the people who suffer from computer vision syndrome are those who wear eyeglasses. One of the primary reasons that discomfort glare is a problem for computer users is that light often leaves the overhead fluorescent fixture in a wide angle, resulting in light directly entering the worker's eyes. This is particularly a problem for computer workers because they are generally looking horizontally into the screen. A secondary cause of discomfort glare is the reflection of light by the lenses of the eyeglasses in proximity to the eye of the wearer.
[0012] The opaque embodiment of the present invention attempts to utilize the compact geometry of the goggle and its various surfaces such as the upper surface and the lower panels to protect the eyes of the wearer and to minimize the transmission of light rays that ultimately reach the eyes other then through the centrally disposed viewing area.
[0013] In addition to the above objectives, the multi-purpose goggle is well suited for use as a virtual reality visor. A virtual reality system generally comprises a display/sensor apparatus that is worn by a viewer and connected to a computer system capable of manipulating the position and perspective of the image viewed in the display to correspond with the position from which it is being viewed. The present invention will eliminate glare from around the screen of the virtual reality visor while providing the wearer with a comfortable goggle.
[0014] It is a problem in complex computer controlled systems that deal with real world phenomena to present a representation of the phenomena in a manner that is both informative to the user and in a simple presentation format. Computer generated graphics are ubiquitous and are typically used to present an accurate representation of an object in a multidimensional space and the interactions therebetween. Computer generated graphics are also used extensively in simulation systems to present an image of a real world situation or a hypothetical situation to a user for training, analysis or other purposes. Computer generated graphics have become extremely sophisticated and can represent extremely complex and fanciful situations in a manner that is virtually lifelike.
[0015] One area in which computer graphics is making a significant impact is the area of real time display of complex real world phenomena. Goggle mounted display devices (GMD's) are increasingly being utilized for virtual reality and “Telepresence” applications. Such devices generally consist of one or more compact image displaying devices mounted on a goggle type frame that the viewer wears on their head. The said image displaying devices project images into the viewer's eyes via a series of lenses or mirrors so that the viewer perceives the image or images to originate from a source outside of the goggle. In the case of stereoscopic GMD's a separate image is presented to each of the viewer's eyes so that a three dimensional (3D) image can be formed. This 3D image has the additional reality of 3D depth cues such as stereo parallax (the differential shifting of objects within the image due to varying distance from the camera or other imaging source).
[0016] Lastly, the multi-purpose goggle can be used in training by instructors to teach student and experienced pilots to recover from unusual situations. The goggles mimic instrument conditions—generally those in which visibility is less than three miles—by placing over the student's head a goggle that acts like a blinder, allowing for a view of the cockpit instruments but not of the scene that fills the window.
[0017] Therefore, it is an object of the present invention to provide an improvement in the structure of multi-purpose goggles which can obviate or substantially lessen the potential for physical objects impacting the eyes, protecting the eyes from glare that can induce computer vision syndrome, serving as a virtual reality goggle or a partial blinder in a training session for a pilot pursuing her instrument flight rating qualifications or seeking to refresh them.
SUMMARY OF THE INVENTION
[0018] The present invention is directed to multi-purpose goggles that satisfy the demand for maximizing wearing comfort through ergonomic construction, maximizing field of view, minimizing distortion, minimizing fogging, reduces or eliminates computer vision syndrome, provides an ideal platform for a virtual reality display system and functions superbly in the training of pilots seeking their instrument flight rating wherein it can serve to allow viewing of the cockpit instruments but not of the scene that fills the window.
[0019] A goggle having features of the present invention comprises a downwardly extending upper surface with a first end and a second end, a centrally disposed viewing area, a centrally disposed nose bridge and a first and second lower panel disposed opposite one another from the nose bridge. The first and second lower panel join the upper surface proximate the upper surface first end and second ends while the posterior edge of the upper surface is contoured to conform to the topography of the wearer's face.
[0020] Vents are optionally disposed in the goggle and means for supporting the goggle on the head of the wearer are also incorporated. When needed for eye protection in industrial and sporting situations the centrally disposed viewing area is operatively configured for receiving a translucent insert that protects against objects impacting the eyes of a wearer. The translucent insert is preferably constructed of a shatterproof polycarbonate; however, other materials possessing similar characteristics may also be utilized.
[0021] The goggle is preferably constructed in one of several embodiments of either a translucent material or an opaque material. Specifically, with an opaque goggle, the centrally disposed viewing area can be configured to remain open as in the case of a goggle to protect against computer vision syndrome. Another embodiment would utilize a translucent goggle and receive a translucent shatter resistant insert that fills the entire open frontal area as in the case of a goggle that is used in an industrial or sports setting. Another embodiment would utilize an opaque goggle and an opaque insert that partially fills the centrally disposed viewing area and can be utilized, for example, for protecting against the onset of computer vision syndrome or in the training of pilots seeking instrument flight rating qualifications. The opaque insert would fill only a portion of the centrally disposed viewing area allowing the pilot-in-training a view of the cockpit instruments but not of the scene that fills the window of the airplane.
[0022] Another embodiment of the present invention would utilize a virtual reality viewing system to be received into the centrally disposed viewing area of an opaque goggle thereby allowing the eyes of the wearer to be positioned in close proximity to the display system. The lightweight ergonomic goggle coupled with a compact virtual reality viewing system would create an ideal combination that minimizes wearer fatigue and maximizes viewing comfort. Moreover, the goggle eliminates glare from around the screen area. Also, the rearward extension of the upper surface and lower panels will conceal the wires leading to the virtual reality display device from the central processing unit and can provide space for additional componentry as required.
[0023] As mentioned above, translucent goggles are utilized in industrial and sports related settings where maximum observability in all directions is critical to the wearer. The ability to view objects overhead, peripherally and beneath the wearer are critical in certain settings and vision cannot be obstructed without threatening the safety of the wearer.
[0024] The present invention is preferably constructed with the centrally disposed viewing area substantially open; however, an alternative embodiment would have the centrally disposed viewing area of the translucent goggle filled with the same translucent material as the remainder of the goggle. This embodiment would negate the need for an insert as the shielding effect of the closed frontal area would thereby be accomplished.
[0025] The upper surface conforms to the head of the wearer and is configured to accommodate the glasses of a wearer and also preserve the ability of the wearer to see superiorly, laterally and inferiorly to increase the field of vision or view when translucent materials are utilized.
[0026] Because of the ergonomic design, the goggle is capable of accommodating a large range of facial topographies and can also accommodate a substantial variety of glasses without the goggle being excessively heavy or producing the sensation that the goggle is attempting to fall from the face of the wearer. The goggle of the present invention is scalable and can be produced in a variety of sizes. The radius of the upper surface can be adjusted during the manufacturing process to produce goggles for children and adults alike by varying the radius dimension associated with the upper surface and other critical dimensions.
[0027] The preferred embodiment has an upper surface, a centrally disposed viewing area through which the wearer is able to see through or into which can be placed a virtual reality viewing display device, a centrally disposed nose bridge and two lower panels disposed opposite the nose bridge from each other and joining the upper surface at the opposite ends of the upper surface. The posterior edges of the upper surface and lower panels are contoured to conform to the topography of the individual's face and can utilize vents that are optimally located to facilitate movement of air that prevents fogging of the interior surfaces particularly of the inserts that may be received within the viewing area to protect the eyes of the wearer. The goggle upper surface and lower panels extend rearwardly from the face of and toward the ears of the wearer. The goggle preferably employs a head band apparatus that encircles the head of the wearer and supports the goggle on the head of the wearer.
[0028] This multi-purpose goggle has a unique ergonomic design, fashionable, sleek and futuristic looking and is contoured to conform to the topography of the individual's face therefore requiring a minimum amount of tension with a head band to hold it in position on the head of the wearer. The sleek ergonomic design is light in weight and evenly distributes a force across the posterior edges of the upper surface and lower panels thereby maximizing user comfort.
[0029] Usually, goggles pinch the eyeglasses at the nose bridge area or at the temple arms. Goggles are typically made to accommodate eyeglasses by making them oversized. Over sizing adds to the weight and interferes with their cosmetic appearance and comfort, thus resulting in non-use and subsequent eye injuries. The multi-purpose goggle of the present invention is uniquely designed to accommodate eyeglass frames and temple arms. The goggle's design provides a large open frontal area that facilitates viewing. Also, the securing apparatus exhibits a wedge shaped space to accommodate the temple arms of the eyeglasses and the goggle design accommodates a wide range of eyeglass frames.
[0030] Because this goggle conforms to the face of the wearer and has support means that consist of rearward extension of the upper surface and the lower panels, the head-encompassing member maintains the position of the goggle against the face of the wearer with the least amount of pressure. The head-encompassing member and the padding facilitate the formation of a seal between the posterior edges of the upper surface and lower panels and the face of the user that limits the entry of debris, chemicals or light to the eye.
[0031] These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description, appended claims and accompanying drawings.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0032] FIG. 1 is a perspective view of a multi-purpose goggle constructed of translucent material in accordance with a first embodiment of the present invention and positioned on the face of a wearer;
[0033] FIG. 2 is a perspective view of a multi-purpose goggle constructed of opaque material in accordance with a second embodiment of the present invention and positioned on the face of a wearer;
[0034] FIG. 3 is a perspective view of a multi-purpose goggle constructed in accordance with a third embodiment of the present invention, positioned on the face of a wearer and configured for pilot instrument flight rating training or for use in preventing or minimizing computer vision syndrome;
[0035] FIG. 4 is a perspective view of a multi-purpose goggle constructed in accordance with a fourth embodiment of the present invention, positioned on the face of a wearer and configured for receiving a virtual reality display;
[0036] FIG. 5 is an elevation view of the front of a multi-purpose goggle of the present invention;
[0037] FIG. 6 is an elevation view of the interior of a multi-purpose goggle of the present invention with eye glasses disposed therein;
[0038] FIG. 7 is a top plan view of a multi-purpose goggle of the present invention with an eyeglasses frame and lenses disposed therein;
[0039] FIG. 8 is an side elevation view of a multi-purpose goggle of the present invention positioned on the face of a wearer;
[0040] FIG. 9 is a perspective view of the open frontal area of a multi-purpose goggle of the present invention showing a translucent insert being received into the centrally disposed viewing area; and
[0041] FIG. 10 is a perspective view of a multi-purpose goggle of the present invention with the centrally disposed viewing area enclosed.
DETAILED DESCRIPTION OF THE INVENTION
[0042] The preferred embodiment and best mode of the present invention is shown in FIG. 1 . At FIG. 1 , a multi-purpose goggle 10 constructed in accordance with the teachings of the present invention is shown generally at 10 . A first translucent embodiment of the present invention is principally directed to use by individuals engaged in sporting events or at industrial work settings that may potentially be harmful to the eyes if the wearer lacks protection. Examples of sporting events for which these goggles would be appropriate are racquetball, skiing, basketball and baseball among many others activities. All of which incorporate a ball moving at a high rate of speed or the potential for eye injury through impact with other individuals or inanimate objects.
[0043] In industrial settings, for example, flying debris or splashing chemicals present a persistent threat to the safety of the eye and must be guarded against. In these settings a goggle of translucent material such as clear polycarbonate is required to enable the wearer to clearly and fully observe her surroundings.
[0044] In situations where the wearer is engaged in viewing a computer monitor, a second embodiment of the present invention comprises an opaque goggle. FIG. 2 reveals a goggle embodiment similar to that in FIG. 1 except utilizing an opaque upper surface 14 and lower panels 28 , 30 that prevent the transmission of undesirable light to the eyes of the wearer from sources other than the computer monitor 99 through the centrally disposed viewing area 24 thereby reducing or even potentially eliminating computer vision syndrome in some users.
[0045] As seen in FIG. 3 a third embodiment with an opaque upper surface 14 and lower panels 28 , 30 can also be utilized in settings where a student pilot or an experienced pilot undergoing a refresher course of instrument flight rating training has their field of vision restricted to just the cockpit instruments. The use of a detachable insert 110 or a goggle embodiment containing a centrally disposed viewing area 24 that has been reduced in size to facilitate this type of training will be discussed more fully below.
[0046] FIG. 4 depicts a fourth embodiment of the multi-purpose goggle 10 that serves as a platform for a virtual reality display. The virtual reality display device 130 is preferably detachably secured to the goggle. The lightweight, ergonomic design and construction of the multi-purpose goggle 10 creates a superb platform for mounting of the virtual reality display device 130 in the centrally disposed viewing area 24 .
[0047] When viewed from the front of the goggle 10 , as seen in FIG. 5 , the upper surface 14 can be clearly seen merging with the first and second lower panels 28 , 30 . The viewing area 24 is preferably centrally disposed and comprised of a single viewing area; however, alternative embodiments may employ more than one viewing area 24 that is divided, for example, equally in half at the center of the nose bridge 26 .
[0048] As shown in FIGS. 1 through 4 , the protective goggle 10 includes an upper surface 14 that extends downwardly from the face 46 of the wearer. The upper surface 14 , as measured from the center point 15 of the upper surface adjacent the posterior edge 20 , extends downwardly from the face 46 of the wearer in the range of 10 to 40 degrees, and preferably between 20 and 30 degrees, from the horizontal. Additionally, as seen in FIGS. 1 and 5 the upper surface 14 traverses from one side of the face 46 of the wearer to the other side commencing in a first end 16 and terminating at a second end 18 . The upper surface 14 further comprises a posterior edge 20 and an anterior edge 22 .
[0049] The goggle 10 further includes a centrally disposed viewing area 24 , a centrally disposed nose bridge 26 and a first and second lower panel 28 , 30 disposed opposite one another from the nose bridge 26 . The upper edges 184 , 186 of the first and second lower panels 28 , 30 join the upper surface 14 at the first end 16 and second end 18 . The upper edges 184 , 186 are not constrained to be linear but may be curvilinear in configuration. As seen in FIG. 6 , the lower panels 28 , 30 also include edges 42 , 44 contoured to conform to the topography of the face 46 of the wearer. The upper surface 14 is contoured to conform to the topography of the wearer's face 46 along a posterior edge 20 and preferably incorporates foam padding 47 to improve wearing comfort.
[0050] A preferred embodiment incorporates the placement of vents 48 , 50 adjacent the nose bridge 26 to allow the discharge of moisture laden air out of the goggle minimizing fogging when an insert 110 , as seen in FIG. 9 , is positioned within the centrally disposed viewing area 24 . If a full insert 110 were received into the viewing area 24 and vents 48 , 50 were not utilized, perspiration from the face of the wearer 46 could potentially cause fogging of the insert 110 and obstruct the vision of the wearer.
[0051] Embodiments one through four can incorporate a translucent full insert 110 that is configured for insertion into and removal from the centrally disposed viewing area 24 depending upon the needs of the user. The full insert 110 can be placed into the centrally disposed viewing area 24 and held in position by a series of clips 32 attached to the upper surface 14 and the lower panels 28 , 30 . It will be appreciated by those skilled in the art that there are a variety of means for attachment of the clips 32 . It will also be appreciated by those skilled in the art that the clips 32 must be appropriately positioned on the goggle 10 to securely maintain the full insert 110 in position. The full insert 110 is preferably comprised of a translucent shatterproof polycarbonate; however, other materials with similar translucent and shatterproof characteristics may be substituted for polycarbonate.
[0052] As seen in FIG. 9 , the goggle 10 is capable of receiving inserts of varying sizes depending upon the particular needs of the goggle wearer. For example, a full transparent insert 110 is used principally in industrial and sports settings to protect the eyes of the wearer from contact with high speed objects, high temperature materials or caustic chemicals. In another situation, an opaque partial insert 114 is typically utilized with an opaque goggle 10 when a student is training for their instrument flight rating qualification and must have their field of vision limited to the controls within the cockpit. Alternatively, as seen in FIG. 4 , a virtual reality display device 130 can be received into the centrally disposed viewing area 24 of an opaque goggle 10 .
[0053] As seen in FIG. 10 , a fifth embodiment of the goggle 10 can be injection molded with the viewing area 24 enclosed by translucent material to provide maximum protection to the eyes of the wearer against, for example, intrusion by foreign objects or caustic chemicals. In this fifth embodiment, the first and second lower panels 28 , 30 would, in effect, extend across the centrally disposed viewing area 24 thereby negating the need for an insert to protect the wearer against eye injury.
[0054] The upper surface 14 extends into support arms 52 , 54 that traverse rearwardly towards the user's ears approximately 3 to 5 inches from the centrally disposed viewing area 24 . As seen in FIG. 7 , the support arms 52 , 54 are sufficiently robust in their wedge shaped dimensions in order to accommodate the passage of the arms 56 , 58 of a pair of glasses 60 back to the ears of the wearer. At the same time, the support arm 52 , 54 dimensions are preferably minimized to reduce weight and to increase wearing comfort. The goggles 10 , as best seen in FIGS. 1, 8 and 9 also utilize a strap 62 or other appropriate securing device to support the goggle 10 on the head 64 of the wearer.
[0055] As shown in FIG. 8 , the preferred embodiment of the goggle 10 is sufficiently offset from the face 46 of the wearer to accommodate a wide range of eye glasses 60 . As shown in FIG. 7 , a preferred embodiment of the goggle 10 is sufficiently spacious to accommodate a pair of glasses 60 without interference between the lenses 70 and frame 72 with the interior 74 of the goggle.
[0056] The goggle 10 upper surface 14 and lower panels 28 , 30 are preferably formed of a shatter resistant material 1-5 mm in thickness; however, other dimensions may be employed based upon the need of the individual wearer. Examples of the shatter resistant materials include, but are not limited to polycarbonates. In the preferred embodiment of the invention, the upper surface 14 and lower panels 28 , 30 are preferably formed as a single unified component and can be produced using standard injection molding techniques. Additionally, in a preferred translucent embodiment, the joining of the first and second ends 16 , 18 of the upper surface 14 to the first and second lower panels 28 , 30 is performed in such a fashion to avoid the formation of a joint or seam that could detract from the ability of the wearer to see out through the ends 16 , 18 .
[0057] The multi-purpose goggles are manufactured in a fashion that produces a downwardly extending upper surface 14 with a first end 16 and a second end 18 , a centrally disposed open frontal area 24 , a centrally disposed nose bridge 26 , a first and second lower panel 48 , 50 disposed opposite the nose bridge, the first and second lower panels 48 , 50 connecting with the upper surface first and second ends 16 , 18 . The multi-purpose goggle is further provided with a securing apparatus comprising support arms 52 , 54 and a headband 62 for securing the goggle 10 onto the head of the wearer 64 .
[0058] While this invention is susceptible of embodiments in many different forms, this specification and the accompanying drawings disclose only preferred embodiments of the invention. The invention is not intended to be limited to the embodiments so described, and the scope of the invention will be pointed out in the appended claims. | A multi-purpose goggle for protecting the eyes of the wearer in industrial and sporting environments and against glare when the wearer is viewing a computer screen for extended periods of time, for housing a virtual reality display and for use by pilots engaged in training for their instrument flight rating. The goggle housing is comprised of a downwardly extending upper surface with a first end and a second end, a viewing area operatively configured in some embodiments for receiving an insert, a centrally disposed nose bridge and a first and second lower panel disposed opposite the nose bridge and a securing means comprised of rearward extensions of the upper surface and lower panels. | 0 |
BACKGROUND OF THE DISCLOSURE
[0001] The present disclosure relates generally to the field of drilling welts and more particularly to steerable drilling tools.
[0002] In deviated and horizontal drilling applications it is advantageous to use rotary steerable systems to prevent pipe sticking in the deviated and horizontal sections. It is advantageous to have the drill string rotating to prevent differential sticking and to reduce friction with the borehole wall. The rotary steerable system may have a housing that is substantially non-rotating. The present disclosure describes a downhole adjustable bent housing for rotary steerable drilling.
[0003] Directional drilling involves varying or controlling the direction of a wellbore as it is being drilled. Usually the goal of directional drilling is to reach or maintain a position within a target subterranean destination or formation with the drilling string. For instance, the drilling direction may be controlled to direct the wellbore towards a desired target destination, to control the wellbore horizontally to maintain it within a desired payzone or to correct for unwanted or undesired deviations from a desired or predetermined path.
[0004] Thus, directional drilling may be defined as deflection of a wellbore along a predetermined or desired path in order to reach or intersect with, or to maintain a position within, a specific subterranean formation or target. The predetermined path typically includes a depth where initial deflection occurs and a schedule of desired deviation angles and directions over the remainder of the wellbore. Thus, deflection is a change in the direction of the wellbore from the current wellbore path.
[0005] It is often necessary to adjust the direction of the wellbore frequently while directional drilling, either to accommodate a planned change in direction or to compensate for unintended or unwanted deflection of the wellbore. Unwanted deflection may result from a variety of factors, including the characteristics of the formation being drilled, the makeup of the bottomhole drilling assembly and the manner in which the wellbore is being drilled.
[0006] Deflection is measured as an amount of deviation of the wellbore from the current wellbore path and is expressed as a deviation angle or hole angle. Commonly, the initial wellbore path is in a vertical direction. Thus, initial deflection often signifies a point at which the wellbore has deflected off vertical. As a result, deviation is commonly expressed as an angle in degrees from the vertical.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 shows a schematic diagram of a drilling system;
[0008] FIG. 2A shows a steerable drilling assembly;
[0009] FIG. 2B shows the steerable drilling, assembly of FIG. 2 with a deviated steering shaft for altering the drilling direction;
[0010] FIG. 3A shows a section of the steerable assembly with the steering shaft aligned with the housing;
[0011] FIG. 3B shows an end view of the assembly of FIG. 3A ;
[0012] FIG. 4A shows the section of the steerable assembly of FIG. 3A with the rotation of the orienting assemblies and the orienting sleeve to create a deviation angle between the steering shaft and the housing;
[0013] FIG. 4B is an end view of the assembly of FIG. 4A ; and
[0014] FIG. 5 is a block diagram of one embodiment of a steerable drilling apparatus.
[0015] While the disclosed embodiments are susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that the drawings and detailed description herein are not intended to limit the disclosed subject matter to the particular form(s) disclosed, but on the contrary, the intention is to cover all modifications, equivalents and alternatives falling within the scope of the present disclosure as defined by the appended claims.
DETAILED DESCRIPTION
[0016] The illustrative embodiments described below are meant as examples and not as limitations on the claims that follow.
[0017] FIG. 1 shows a schematic diagram of a drilling system 110 having a downhole assembly according to one embodiment of the present disclosure. As shown, the system 110 includes a conventional derrick 111 erected on a derrick floor 112 , which supports a rotary table 114 that is rotated by a prime mover (not shown) at a desired rotational speech. A drill string 120 that includes a drill pipe section 122 extends downward from rotary table 114 into a directional borehole 126 , also called a wellbore. Borehole 126 may travel in a three-dimensional path. The three-dimensional direction of the bottom 151 of borehole 126 is indicated by a pointing vector 152 . A drill bit 150 is attached to the downhole end of dull string 120 and disintegrates the geological formation 123 when drill bit 150 is rotated. The drill string 120 is coupled to a drawworks 130 via a kelly joint 121 , swivel 128 , and line 129 through a system of pulleys (not shown). During the drilling operations, drawworks 130 may be operated to control the weight on bit 150 and the rate of penetration of drill string 120 into borehole 126 . The operation of drawworks 130 is well known in the art and is thus not described in detail herein.
[0018] During drilling operations a suitable drilling fluid (commonly referred to in the art as “mud”) 131 from a mud pit 132 is circulated under pressure through drill string 120 by a mud pump 134 . Drilling fluid 131 passes from mud pump 134 into drill string 120 via fluid line 138 and kelly joint 121 . Drilling fluid 131 is discharged at the borehole bottom 151 through an opening in drill bit 150 . Drilling fluid 131 circulates uphole through the annular space 127 between drill string 120 and borehole 126 and is discharged into mud pit 132 via a return line 135 . A variety of sensors (not shown) may be appropriately deployed on the surface according to known methods in the art to provide information about various drilling-related parameters, such as fluid flow rate, weight on bit, hook load, etc.
[0019] A surface control unit 140 may receive communications, via a telemetry link, from downhole sensors and devices. The communications may be detected by a sensor 143 placed in fluid line 138 and processed according to programmed instructions provided to surface control unit 140 . Surface control unit 140 may display desired drilling parameters and other information on a display/monitor 142 which may be used by an operator to control the drilling operations. Surface control unit 140 may contain a computer, memory for storing data and instructions, a data recorder and other peripherals. Surface control unit 140 may also include well plan and evaluation models and may process data according to programmed instructions, and respond to user commands entered through a suitable input device., such as a keyboard (not shown).
[0020] In one example, a steerable drilling bottom hole assembly (BHA) 159 may comprise dill collars and/or drill pipe, a measurement while drilling system 158 , and a steerable assembly 160 . MWD system 158 comprises various sensors to provide information about the formation 123 and downhole drilling parameters. MWD sensors 164 in BHA 159 may include, but are not limited to, a device for measuring the formation resistivity near the drill bit a gamma ray device for measuring the formation gamma ray intensity, devices for determining the inclination and azimuth of the drill string, and pressure sensors for measuring, drilling, fluid pressure downhole. The above-noted devices may transmit data to a downhole transmitter 133 , which in turn transmits the data uphole to the surface control unit 140 , via sensor 143 . In one embodiment, a mud pulse telemetry technique may be used to communicate data from downhole sensors and devices during drilling operations. A pressure transducer 143 placed in the mud supply line 138 detects mud pulses representative of the data transmitted by the downhole transmitter 133 . Transducer 143 generates electrical signals in response to the mud pressure variations and transmits such signals to surface control unit 140 . Alternatively, other telemetry techniques such as electromagnetic and/or acoustic techniques or any other suitable technique known in the art may be utilized. In one embodiment, hard-wired drill pipe may be used to communicate between the surface and downhole devices. In one example, combinations of the techniques described may be used. In one embodiment, a surface transmitter 180 transmits data and/or commands to the downhole tools using an of the transmission techniques described, for example a mud pulse telemetry technique. This may enable two-way communication between surface control unit 140 and a downhole controller 601 described below.
[0021] BHA 159 may also comprise a steerable assembly 160 for directing a steering shaft 75 attached between the rotating BHA 159 and hit 150 along the desired direction to steer the path of the well.
[0022] Referring to FIGS. 2A-2B , a steerable drilling apparatus 160 is positioned near bit 150 in BHA 159 . Steerable drilling assembly 160 comprises rotatable drive shaft 195 coupled to a rotating member 191 of drill string 120 . Rotatable drive shaft 195 is coupled to a rotating steering shaft 75 by a coupling member 80 . Rotating steering shaft 75 is, in turn, coupled to drill bit 150 for drilling the wellbore 126 . As such, rotation of rotating, member 191 causes drill it 150 to rotate. In one example, rotating member 191 may be a drill string component that rotates at the same speed as the drill string. Alternatively, rotating member 191 may be the output shaft of a drilling motor disposed in drill string 120 , such that rotating member 191 rotates at an increased RPM equal to the motor output RPM plus the drill string RPM.
[0023] As shown, orienting sleeve 50 is rotatably supported between a first orienting assembly 220 A and a second orienting assembly 220 B disposed within a substantially tubular housing 46 . Housing 46 is substantially rotationally stationary in the wellbore during drilling. Rotatable steering shaft 75 is rotatably supported in orienting sleeve 50 . Orienting sleeve 50 is also rotatable with respect to each orienting assembly 220 A,B by actuation of orienting, sleeve actuator 226 . Actuation of first orienting assembly 220 A, second orienting assembly 220 B, and orienting sleeve actuator 226 acts to orient steering shaft 75 and bit 150 in a desired three dimensional direction 252 to control the path of borehole 126 .
[0024] First orienting assembly 220 A and second orienting assembly 220 B are disposed within housing 46 for controlling orienting sleeve 50 . Steering shaft 75 rotates within orienting sleeve 50 . Orienting sleeve 50 may be oriented to change the direction of steering shaft 75 . Orienting sleeve 50 may provide contact bearing support to steering shaft 75 to limit the bending and bending stresses imposed on steering shaft 75 , as described below.
[0025] With reference to FIGS. 3A-4B , orienting assembly 220 A comprises a circular outer ring 45 A that is rotatably supported by bearings 59 , on a circular inner peripheral surface 51 of housing 46 . Note in FIGS. 3B and 4B that the bearings 59 are omitted for clarity. Outer ring 45 A has a circular inner peripheral surface 56 A that is eccentric with respect to inner peripheral surface 51 of housing 46 . Circular inner peripheral surface 56 A of outer ring 45 A rotatably supports orienting sleeve 50 through bearings 59 . Similarly, orienting assembly 220 B comprises a circular outer ring 458 that is rotatably supported by bearings 59 , on circular inner peripheral surface 51 of housing 46 . Outer ring 45 B has a circular inner peripheral surface 56 B that is eccentric with respect to inner peripheral surface 51 of housing 46 . Circular inner peripheral surface 56 B of outer ring 45 B rotatably supports orienting sleeve 50 through bearings 59 .
[0026] Orienting sleeve 50 has an inner peripheral surface 65 that defines an angled longitudinal circular bore 65 which has a centerline CL 3 that is angled with respect to a centerline CL 2 defined by the outer peripheral surface 66 of orienting sleeve 50 by a predetermined angle, θ (shown in FIG. 4A ). By rotating outer rings 45 A,B and the orienting sleeve 50 relative to each other, and relative to housing 46 , shaft 75 may be inclined by angle, θ, such that bit 150 drills in a direction 152 ′ with respect to the borehole centerline, CL 1 , of housing 46 . in the embodiment shown, orienting assemblies 220 A,B also comprise a motors 25 A,B driving a spur gears 27 A,B that engages ring gears 26 A,B. Ring gears 26 A,B are attached to outer rings 45 A,B and controllably drive outer rings 45 A,B under the direction of a downhole controller 601 , discussed below.
[0027] Orienting sleeve 50 may be controllably rotated relative to housing 46 and each outer ring 45 A,B by orienting sleeve actuator 226 . Orienting sleeve actuator 226 comprises a motor 30 driving a spur gear 31 that is operatively engaged with a ring gear 32 attached to outer peripheral surface 66 of orienting sleeve 50 . Motor 30 controllably rotates deflection sleeve 50 under the control of controller 601 . Motors 25 A, 25 B, and 30 may be electric motors, hydraulic motors, or combinations thereof Such motors may incorporate rotational sensors, 607 , 608 , and 615 , respectively, for accurate determination of the rotational angular orientation of the outer rings 45 A,B and deflection sleeve 50 relative to housing 46 .
[0028] The rotational orientation of drilling shaft 75 may be referenced as a toolface angle with respect to the gravitational high side of an inclined wellbore. Alternatively, in a substantially vertical wellbore, the reference may be to a north reference, for example magnetic, true, or grid north. As used herein, the toolface angle is the angle between the discussed reference, high side or north, and the plane containing the angled drilling shaft.
[0029] As indicated above, orienting sleeve 50 may provide contact bearing support to steering shall 75 to limit the bending and bending stresses imposed on steering shaft 75 . In one example, the inner peripheral surface 65 of orienting sleeve 50 may be coated with an abrasion resistant coating 95 to act as a wear resistant bearing surface. Such a coating 95 may extend over the entire length of orienting sleeve 50 . Alternatively, the coating 95 may extend over predetermined portions of inner peripheral surface 65 . Abrasion resistant coating 95 may comprise. at least one of, a natural diamond coating, a synthetic diamond coating, a tungsten coating, a tungsten carbide coating, and combinations thereof. Similarly, at least some portions of steering shaft 75 may be coated For example, the peripheral surface of steering shaft 75 may be coated where they are operationally juxtaposed with coated bearing surfaces on the inner peripheral surface of 65 of orienting sleeve 50 .
[0030] Downhole controller 601 , see FIG. 5 , may be located in housing 46 to control the operation of steerable assembly 160 . Controller 601 may comprise a processor 695 in data communications with any of the orienting assemblies 220 A,B and 226 described above. In one embodiment, the deviation angle of drilling shaft 75 may be controlled by rotating the orientation sleeve 50 described above, and the toolface angle of drilling shaft 75 may be controlled with respect to the housing 46 by the proper rotation of outer rings 45 A,B, thus orienting the drill, bit 150 to drill along a desired path.
[0031] In one example well trajectory models 697 may be stored in a memory 696 that is in data communications with a processor 695 in the electronics 601 . Directional sensors 692 may be mounted in housing 46 or elsewhere in the BHA, and may be used to determine the inclination, azimuth, and highside of the steering assembly 160 . Directional sensors may include, but are not limited to: azimuth sensors, inclination sensors, gyroscopic sensors, magnetometers, and three-axis accelerometers. Depth measurements may be made at the surface and/or downhole for calculating the location of steering assembly 160 along the wellbore 26 . If depth measurements are made at the surface, they may be transmitted to the downhole assembly using surface transmitter 180 described above with reference to FIG. 1 . In operation, electronic interface circuits 693 may distribute power from power source 690 to one, or more, of directional sensors 692 , processor 695 , downhole transmitter 133 , first orienting assembly 220 , second orienting assembly 225 , and deflection sleeve actuator assembly 226 . In addition, electronic interface circuits 693 may transmit and/or receive data and command signals from directional sensors 692 , processor 695 . and telemetry system 691 . Angular rotation sensors 607 , 608 and 615 may be used to determine the rotational positions of outer ring 45 A, outer ring 45 B, and orienting sleeve 75 relative to housing 46 . Power source 690 may comprise batteries, a downhole generator/alternator, and combinations thereof. In one embodiment, models 697 may comprise directional position models to control the steering assembly to control the direction of the wellbore along a predetermined trajectory. The predetermined trajectory may be 2-dimensional and/or 3-dimensional. In addition models 697 may comprise instructions that evaluate the readings of the directional sensors to determine when the well path has deviated from the desired trajectory. Models 697 may calculate and control corrections to the toolface and drilling shaft angle to make adjustments to the well path based on the detected deviations. In one example, models 697 may adjust the well path direction to move back to an original planned predetermined trajectory. In another, example, models 697 may calculate a new trajectory from the deviated position to the target, and control the steering assembly to follow the new path. in one example, the measurements, calculations, and corrections are autonomously executed downhole. Alternatively, direction sensor data may be transmitted to the surface, corrections calculated at the surface, and commands from the surface may be transmitted to the downhole tool to alter the settings of the steering assembly.
[0032] Numerous variations and modifications will become apparent to those skilled in the art. It is intended that the following claims be interpreted to embrace all such variations and modifications. | A method for steering a well comprises disposing a first orienting assembly and a second orienting assembly spaced apart along a circular inner peripheral surface of a housing. An orienting sleeve is rotatably supported between the first orienting assembly and the second orienting assembly, The orienting sleeve has an angled bore therethrough, wherein a first longitudinal axis of the angled bore is inclined by a predetermined angle to a second longitudinal axis referenced to a cylindrical outer peripheral surface of the orienting sleeve. A rotatable steering shaft is rotatably supported along the angled bore to control rotatable steering shaft bending. The rotation of the first orienting assembly, the second orienting assembly, and the orienting sleeve is controllably adjusted to control the steering direction of the rotatable steering shaft. | 4 |
FIELD OF THE INVENTION
This invention relates to a multicolor image-forming method and more particularly, the invention relates to a multicolor image-forming method which is mainly used for two color proofing.
BACKGROUND OF THE INVENTION
Hitherto, as a proofing method for color prints, a method of performing proof printing using a print proofreading machine or a main printing machine has been used. However, proof printing by a proofing method is expensive, printing requires a long period of time, and also there is a limit on the reliability thereof.
On the other hand, various color proofing methods by photographic process having been employed as a simple and easy method in place of the aforesaid printing methods.
As the color proofing method by photographic process, there is a color proofing method using a photopolymer (i.e., pre-press proof), an overlay method and a surprint method.
In the overlay method, plural color proofing sheets each having separation images of each color on a transparent support are prepared and color proofing is performed by superposing these sheets (the assembly of the sheets thus obtained is called a "color test sheet").
The overlay method has the advantages that the method is very simple and inexpensive and the method can be used for continuous inspection by superposing 2 single color sheets or 3 single color sheets only each time, but has the disadvantages that the color test sheet obtained becomes dark to some extent by the superposed synthetic resin sheets and also the incident light is reflected by several sheets to give luster, whereby the impression received from the color test sheet is very different from the quality impression of a print printed by an ordinary printing machine.
On the other hand, in the surprint method, plural single-color layers are superposed on a single support and for that purpose, various kinds of toners are applied onto a common opaque film base or plural light-sensitive layers each corresponding to each color are formed, in succession, on an opaque film base. Details of these methods are described, for example, in U.S. Pat. Nos. 3,671,236 and 3,136,637.
The surprint method has the advantage that the color density is not influenced by the synthetic resin base. Also, the surprint method is more similar to the original printing method and further has the advantage that the occurrence of color stain in the case of superposing sheets as in the aforesaid overlay method is inhibited.
Furthermore, a method of imagewise exposing each of the light-sensitive transfer materials each having, in succession, a peelable layer composed of an organic polymer, a coloring material layer, and a light-sensitive layer on a temporary support, developing the light-sensitive transfer material to form color images on the peelable layer, and then transferring the color images onto an optional support (permanent support) each time by using an adhesive is well known as described in Japanese Patent Publication Nos. 15326/71 and 441/74. This method has the advantage of being usable for various operations such as an overlay type and surprint type as color proof, but has the disadvantage that the method is troublesome, since an adhesive must be used at each transfer of color images and also since it is difficult to keep the preciseness of matching the positions of color images when transferring images of each color.
For removing the aforesaid troublesome defects of these methods, a method of transferring images formed by applying heat and pressure onto a permanent support is disclosed in Japanese Pat. Application (OPI) Nos. 41830/72, 9337/73, and 5101/76 (the term "OPI" as used herein refers to a "published unexamined Japanese patent application"). In particular, Japanese Pat. Application (OPI) No. 5101/76 discloses that a heat-fusible polymer layer is formed on a permanent support as adhesive and also Japanese Pat. Application (OPI) No. 41830/72 discloses a method of directly transferring images onto a permanent support such as an art paper or a coated paper.
However, these methods have various disadvantages. That is, these are the problems that the final image transferred onto a permanent support is right and left reversed and also when a heat-fusible polymer is used as an adhesive, an increase in transfer temperature is required, since the melting point thereof is generally high, whereby the dimensional stability of support is reduced by the influence of heat to cause discrepancies in the matching of the transferred position of each color images. On the other hand, when a heat-fusible polymer having low melting point is used as an adhesive, the surface of the images transferred becomes adhesive and thus the surface is liable to be injured.
For overcoming the aforesaid difficulty, a method of once transferring images onto a temporary image-receiving sheet before transferring the images onto a permanent support was previously proposed in Japanese Pat. Application (OPI) No. 97140/84 (corresponding to U.S. Pat. No. 4,482,625) by the same assignee. That is, according to this method, a temporary image-receiving sheet composed of a support having formed thereon an image-receiving layer composed of a photopolymerizable material is prepared, images of each color are once transferred onto the temporary image-receiving sheet before being transferred onto a permanent support, the color images thus formed on the image-receiving sheet are then retransferred onto a permanent support, and the images thus transferred are overall light-exposed to harden the image-receiving layer composed of the photopolymerizable material thus transferred onto the permanent support.
The above-described image transfer method using a temporary image-receiving sheet (hereinafter referred to simply as an image-receiving sheet) is very effective for solving the aforesaid problem. That is, by utilizing the aforesaid method, a correct image for an original can be obtained on a permanent support. Since the photopolymerizable image-receiving layer of the image-receiving sheet contains an ethylenic polyfunctional monomer, the photopolymerizable image-receiving layer itself is soft, image transfer is possible at a low temperature, and after transferring images thereon, the image-receiving layer having transferred images thereon can be easily hardened by overall light exposure. That is, the aforesaid methods have such advantages that adhesion does not occur after transferring images and the resistance to injury of the final images obtained is high.
In the image-receiving sheet used for the method described in Japanese Pat. Application (OPI) No. 97140/84 described above, the adhesive strength between the photopolymerizable image-receiving layer (i.e., photopolymerizable adhesive layer) and the support is very high in the unexposed state. Accordingly, in transferring the photopolymerizable adhesive layer having images received thereon onto a final support, peeling stripes are liable to form on the surface of the transferred image-carrying photopolymerizable adhesive layer if the support of the image-receiving sheet material is peeled off before applying light exposure. For overcoming this problem, Japanese Pat. Application (OPI) No. 97140/84 provides a method wherein after intimately contacting an image-receiving photopolymerizable adhesive layer onto a final support, the photopolymerizable adhesive layer is first hardened by applying thereto overall light exposure whereby the adhesion between the photopolymerizable adhesive layer and the support for the image-receiving sheet is reduced, and then the image-receiving sheet support is removed.
However, these surprint methods have disadvantages in that they are expensive and they cannot satisfy the need for both high quality and low cost in color proofing by these photographic processes.
SUMMARY OF THE INVENTION
An object of this invention is, therefore, to provide a multicolor image-forming method for color proofing without being accompanied by the aforesaid disadvantages in the conventional techniques.
As the result of various investigations for obtaining a multicolor image-forming method for color proof capable of satisfying the need for both high image quality and low cost, the inventors have discovered that the aforesaid object can be attained by a multicolor image-forming method which comprises image-exposing a light-sensitive heat-sensitive recording material having a diazo compound and a coupling component on a support using a positive image followed by developing to form a color image, image-exposing a light-solubilizing color image-forming material having a coloring material on a substantially transparent support using a positive image followed by development to form a color image, and superposing the light-solubilizing color image-forming material having the color image on the light-sensitive heat-sensitive recording material having the color image, or further heat-pressing the light-solubilizing color image-forming material having the color image superposed on the light-sensitive heat-sensitive recording material having the color image.
DETAILED DESCRIPTION OF THE INVENTION
The multicolor color image-forming method of this invention is very effective in a two-color image-forming method for color proofing.
The light-sensitive heat-sensitive recording materials which are used in the present invention are described, for example, in Japanese Pat. Application (OPI) Nos. 123086/82, 44141/82, 142636/82, 192944/82, and 190886/84 and Gazo Denshi Gakkai Shi (Journal of Image Electron Society), 11, 290 (1982).
The light-sensitive heat-sensitive recording material for use in this invention is explained below.
As a paper for the support of the recording material, a heat-extract neutral paper having pH of from 6 to 9 sized by a neutral sizing agent such as alkylketene dimer, etc., as described in Japanese Pat. Application (OPI) No. 14281/80 is advantageous in terms of storage stability.
Also, a paper having an optical surface roughness of less than 8 μm and a thickness of from 40 to 75 μm described in Japanese Pat. Application (OPI) No. 136492/83, a paper having a density of less than 0.9 g/cm 3 and an optical contact ratio of above 15% described in Japanese Pat. Application (OPI) No. 69091/83, a paper made from a pulp subjected to beating treatment and to above 400 cc Canadian standard freeness (JIS P8121 (JIS refers to Japanese Industrial Standard)) or paper treated to prevent the permeation of coating solution described ir Japanese Pat. Application No. 69097/83, a paper made by a Yankee paper machine, the luster surface thereof being used as the coating surface for improving color density and resolving power described in Japanese Pat. Application (OPI) No. 65695/83, and a paper subjected to a corona discharge treatment for improving coating aptitude described in Japanese Pat. Application (OPI) No. 35985/84 can be used in this invention with good results. Other supports which are used in the field of ordinary heat-sensitive recording papers can be used as the support in this invention.
A diazo compound contained in the recording layer of the light-sensitive heat-sensitive recording material which is used in this invention is a diazonium salt represented by the formula
ArN.sub.2.sup.+ X.sup.-
wherein Ar represents an aromatic moiety, N 2 + represents a diazonium group, and X - represents an acid anion, and the diazo compound can be colored by causing a coupling reaction with the coupling component.
The aromatic moiety is preferably represented by the following formula ##STR1## wherein Y represents a hydrogen atom, a substituted amino group, an alkoxy group, an alkylaryloxy group, an arylthio group, an alkylthio group, or an acylamino group and R represents a hydrogen atom, an alkyl group, an alkoxy group, an aryloxy group, an arylamino group, or a halogen atom (e.g., iodine, bromine, chlorine, and fluorine) and R represents the bond to the diazonium group of the diazonium salt.
Preferred substituted amino groups represented by Y include a monoalkylamino group, a dialkylamino group, an arylamino group, a morpholino group, a piperidino group, and a pyrrolidino group.
In the present invention, these diazonium salts may be used singly or as a mixture thereof.
Specific examples of diazonium groups forming the diazonium salt are 4-diazo-1-dimethylaminobenzene, 4-diazo- 1-diethylaminobenzene, 4-diazo-1-dipropylaminobenzene, 4-diazo-1-methylbenzylaminobenzene, 4-diazo-1-dibenzylaminobenzene, 4-diazo-1-ethylhydroxyethylaminobenzene, 4-diazo-1-diethylamino-3-methoxybenzene, 4-diazo-1-dimethylamino-2methylbenzene, 4-diazo-1-benzoylamino-2,5-diethoxybenzene, 4-diazo-1-morpholinobenzene, 4-diazo-1-morpholino-2,5-diethoxybenzene, 4-diazo-1-morpholino-2,5-dibutoxybenzene, 4-diazo-1-anilinobenzene, 4-diazo-1-toluylmercapto-2,5-diethoxybenzene, 4-diazo-1,4-methoxybenzoylamino-2,5-diethoxybenzene, 1-diazo-4-(N,N-dioctylcarbamoyl)benzene, 1-diazo -2octadecyloxybenzene, 1-diazo-4-(4-tert-octylphenoxy) benzene, 1-diazo-4-(2,4-di-tert-amylphenoxy)benzene, 1-diazo-2-(4-tert-octylphenoxy)benzene, 1-diazo-5-chloro-2-(4-tert-octyl-phenoxy) benzene, 1-diaxo-2,5-bis-octadecyloxybenzene, 1-diazo -2,4-bis-octadecyloxybenzene, and 1-diazo-4-(N-octano-ylamino) benzene.
Specific examples of the acid anion represented by X - are C n F 2n+1 COO - (n represents 3 to 9), C m F 2m+1 SO 3 - (m represents 2 to 8), ClF 2l+1 SO 2 ) 2 CH - (l represents 1 to 18), ##STR2##
Specific examples of the diazo compound (diazomium salt) for use in this invention are illustrated below. ##STR3##
The coupling component for use in this invention is a component forming a dye by causing coupling with the aforesaid diazo compound (diazonium salt) and specific examples thereof are resorcinol, fluoroglycin, sodium 2,3-dihydroxynaphthalene-6-sulfonate, 1-hydroxy-2-naphthoic acid morpholinopropylamide, 1,5-dihydroxynaphthalene, 2,3-dihydroxynaphthalene, 2,3-dihydroxy-6-sulfanylnaphthalene, 2-hydroxy-3-naphthoic acid morpholinopropylamide, 2-hydroxy-3-naphthoic acid-2'-methylamide, 2-hydroxy-3-naphthoic acid ethanolamide, 2-hydroxy-3-naphthoic acid octylamide, 2-hydroxy-3-naphthoic acid N-dodecyloxypropylamide, 2-hydroxy-3-naphthoic acid tetradecylamide, acetanilide, acetoacetanilide, benzoylacetanilide, 1-pnenyl-3-methyl-5-pyrazolone, 2,4-bis(benzoylacetamino)toluene, 1,3-bis(pivaloylacetaminomethyl)benzene, 1-(2',4',6'-trichlorophenyl)-3-benzamido -5-pyrazolone, 1-(2',4',6'-trichlorophenyl) -3-anilino-5-pyrazolone, and 1-phenyl-3-phenylacetamido-5-pyrazolone.
Furthermore, by using two or more kinds of these components, a color image of an optional tone can be obtained.
It is preferred that the recording layer of the light-sensitive heat-sensitive recording material for use in this invention contains a basic material for accelerating the coupling reaction by making the system basic.
As the basic material, a basic material which is sparingly soluble in water or water-insoluble and a material forming an alkali by heating may be used.
Basic materials for use in the present invention include inorganic and organic ammonium salts, organic amines, amides, urea, urea derivatives, thiourea, thiourea derivatives, thiazoles, pyrroles, pyrimidines, piperazines, guanidines, indoles, imidazoles, imidazolines, triazoles, morpholines, piperidines, amidines, formazines, pyridines, etc.
Specific examples thereof are ammonium acetate, tricyclohexylamine, tribenzylamine, octadecylbenzylamine, stearylamine, allylurea, thiourea, methylthiourea, allylthiourea, ethylenethiourea, 2-benzylimidazole, 4-phenylimidazole, 2-phenyl-4-methylimidazole, 2-undecylimidazoline, 2,4,5-trifuryl-2-imidazoline, 1,2-diphenyl -4,4-dimethylimidazoline, 2-phenyl-2-imidazoline, 1,2,3-triphenylguanidine, 1,2-ditolylguanidine, 1,2-dicyclohexylguanidine, 1,2,3-tricyclohexylguanidine, guanidine trichloroacetate, N,N'-dibenzylpiperazine, 4,4'-dithiomorpholine, morpholium trichloroacetate, 2-aminobenzothiazole, and 2-benzoylhydrazinobenzothiazole.
These basic materials may be used singly or as a mixture thereof.
In a preferred embodiment of the light-sensitive heat-sensitive recording material for use in the present invention, at least one of the diazo compound and the coupling component is encapsulated in microcapsules.
The microcapsules containing the reactive compound for use in this invention are obtained by, if necessary, dissolving or dispersing the reactive material as core material in a water-insoluble organic solvent followed by emulsification, and forming microcapsule walls around the core materials by polymerization.
An organic solvent having boiling point of at least 180° C. is preferred as the solvent for the aforesaid purpose. These organic solvents include phosphoric acid esters, phthalic acid esters, other carboxylic acid esters, aliphatic acid amides, alkylated biphenyls, alkylated phenols, chlorinated paraffins, alkylated naphthalenes, diarylethanes, etc.
Specific examples thereof are tricresyl phosphate, trioctyl phosphate, octyldiphenyl phosphate, tricyclohexyl phosphate, dibutyl phthalate, dioctyl phthalate, dilauryl phthalate, dicyclohexyl phthalate, butyl oleate, diethylene glycol dibenzoate, dioctyl sebacate, dibutyl sebacate, dioctyl adipate, trioctyl trimellitate, acetyltriethyl citrate, octyl maleate, dibutyl maleate, isopropylbiphenyl, isoamylbiphenyl, chlorinated paraffin, diisopropylnaphthalene, 1,1'-ditolylethane, 2,4-di-tert-aminophenol, N,N-dibutyl -2-butoxy-5-tert-octylaniline, N,N'-diphenylamidine, N,N',N'-triphenylbenzamizin, and N,N'-diphenylbenzamizin.
In these solvents, ester-containing solvents such as butyl phthalate, tricresyl phosphate, diethyl phthalate, and dibutyl maleate are particularly preferred.
Preferred microcapsules in this invention are prepared by emulsifying a core material containing a reactive material and thereafter forming walls of a polymer around the oil drops. In this case, the reactant(s) for forming the polymer are added to the inside of the oil drops and/or the outside of the oil drops. Specific examples of the polymer are polyurethane, polyurea, polyamide, polyester, polycarbonate, urea-formaldehyde resin, melamine resin, polystyrene, a styrene methacrylate copolymer, a styreneacrylate copolymer, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, etc.
The polymers described above may be used singly or as a mixture thereof.
Preferred polymers are polyurethane, polyurea, polyamide, polyester, and polycarbonate and particularly preferred polymers are polyurethane and polyurea.
Specific examples of the microcapsulation technique and compounds for use therefor are described in U.S. Pat. Nos. 3,726,804 and 3,796,669.
It is preferred that at least one of the diazo compound and the coupling component which are used for the heat-sensitive material is used as the core material of microcapsules. When these components are incorporated in core materials of microcapsules, these core materials may exist in the same microcapsules or in different microcapsules. However, the diazo compound and the coupling component are not contained in the same microcapsules at the same time. Other components which are not contained in the core material of microcapsules are used for the heat-sensitive layer outside the microcapsules.
Also, it is preferred to use the coupling material in an amount of from 0.1 to 30 parts by weight and the basic material in an amount of from 0.1 to 30 parts by weight per 1 part by weight of the diazo compound. Also, the diazo compound is preferably coated at from 0.05 to 5.0 g/m 2 .
For preparing the light-sensitive material for use in the present invention, a suitable binder can be used.
As the binder, various kinds of emulsions of polyvinyl alcohol, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, gum arabic, gelatin, polyvinylpyrrolidone, casein, styrene-butadiene latex, acylonitrilebutadiene latex, polyvinyl acetate, polyacrylic acid ester, ethylenevinyl acetate copolymer, etc., can be used. The amount thereof is from 0.5 to 20 g/m 2 , and preferably from 0.5 to 5 g/m 2 as solid components.
In the present invention, for the light-sensitive heat-sensitive materials, an acid stabilizer such as citric acid, tartaric acid, oxalic acid, boric acid, phosphoric acid, pyrophosphoric acid, etc., can be further used.
The light-solubilizing color image-forming material for use in the present invention is explained below.
As the support for the color image-forming material, various kinds of the supports as described, for example, in Japanese Pat. Application (OPI) No. 97140/84 (corresponding to U.S. Pat. No. 4,482,625) can be used. Specific examples of the support are films of polyethylene terephthalate, polypropylene, polyethylene, polyvinyl chloride, polystyrene, polycarbonate, triacetate, etc. In particular, a biaxially stretched polyethylene terephthalate film is excellent in strength, heat resistance, dimensional stability, transparency, etc. There is no particular restriction on the thickness of the support, but the thickness is preferably from about 10 μm to about 150 μm.
A high molecular weight organic polymer layer containing the coloring material for use in this invention is formed on the support.
The organic high molecular weight polymer layer is a layer composed of the coloring material and a binder (organic high molecular weight polymer) containing it. There is no particular restriction on the coloring material being contained in the organic high polymer layer if the coloring material is soluble in organic solvent and the coloring material can preferably be selected from various dyes and pigments. Specific examples thereof are the various pigments and dyes described in U.S. Pat. No. 4,472,494, Japanese Pat. Application (OPI) Nos. 89916/77, 117142/80 and 127552/80, and Colour Index, published by The American Association of Textile Chemists and Colorists, 2nd ed. (1956).
In particular, when the present invention is applied to color proofs for printing, it is preferred to use pigments for matching the color reproducibility with prints.
Also, various polymers as described, for example, in Japanese Pat. No. Application (OPI) No. 97140/82 (corresponding to U.S. Pat. No. 4,482,625) can be used as the organic high molecular weight polymer for containing the coloring material. Since it is preferred that a light-sensitive layer containing a naphthoquinonediazide series photosensitive material as described hereinafter and the coloring material layer can be developed by one bath, it is preferred to use an alkali-soluble organic high molecular weight polymer.
Examples of the alkali-soluble high molecular weight polymer are polymers having a salt-forming group described in U.S. Pat. No. 2,893,368, cellulose polymers having an acid group described in U.S. Pat. No. 2,927,022, copolymers such as methyl methacrylate/methacrylic acid copolymer described in West German Pat. Application (OLS) No. 2,123,702, acid containing polymers such as styrene/mono-n-butyl maleate copolymer and vinyl acetate/crotonic acid copolymer described in West German Pat. Application (OLS) No. 2,205,146, free carboxylic acid-containing vinyl addition polymers such as copolymers of acrylic acid and one or more alkyl acrylates described in West German Pat. Application (OLS) No. 2,320,849, and methacrylic acid-aralkyl methacrylate copolymers described in Japanese Pat. Publication No. 44615/84.
Also, the organic high molecular weight polymers (binders) described in U.S. Pat. No. 4,472,494, Japanese Pat. Application (OPI) Nos. 16124/72, 89916/77, 117142/80, and 127552/80, phenol resins, rosin, polyhydroxystyrene, etc., can be used as the polymers.
In addition, the coloring material layer can further contain, if necessary, additives such as a plasticizer, a pigment dispersion stabilizer, a surface active agent, etc.
In the case of forming the organic high molecular weight polymer layer containing a coloring material (coloring material layer), the aforesaid coloring material and binder are first dissolved in a proper solvent to provide a coating composition for forming the organic high molecular weight polymer latex (coloring material layer).
As the solvent for preparing the aforesaid coating composition, there are, for example, ketones such as acetone, methyl ethyl ketone, cyclohexanone, etc.; acetic acid esters such as methyl acetate, ethyl acetate, etc.; ethers such as methylcellosole, dioxane, tetrahydrofuran, etc.; and methylene chloride and diacetone alcohol. They may be used singly or as a mixture thereof.
The coloring material layer can be formed by coating the aforesaid coating composition on a support by an ordinary coating means such as whirler, etc.
The content of the coloring material to the binder for the organic high molecular weight polymer layer depends upon the kind of desired image-forming material, but is generally from 5 to 50% by weight based on the amount of the binder. When the invention is applied to a non-silver salt system light-sensitive film for making duplicates, a sufficient optical density is required and hence a large amount of the coloring material is used. When the invention is applied for making color proofs, etc., for the aforesaid overlay method, the optical density may be relatively low and hence the amount of the coloring material may be small.
The thickness of the organic high molecular weight polymer layer (coloring material layer) is preferably in the range of from 0.1 μm to 10 μm, and particularly preferably in the range of from 0.1 μm to 3 μm.
The light-sensitive layer of the light-solubilizing color image-forming material for use in this invention is effective in the layer containing a photosensitive naphthoquinonediazide ester compound in a high molecular weight polymer (binder).
Various naphthoquinonediazide ester compounds for the light-solubilizing image-forming material are known. For example, these photosensitive naphthoquinonediazide ester compounds are described in Japanese Pat. Publication Nos. 22062/61, 1953/62, 3627/62, 13109/62, 15665/62, 18015/63, 12083/63, 21093/65, 26126/65, 27345/70, 3801/65, 1844.5/69, 5604/70, and 13013/76.
In addition, as the photosensitive material for the light-sensitive layer, other photosensitive compositions than the photosensitive naphthoquinone diazide ester compound may be used. Typical examples thereof are combinations of a compound generating an acid by the photodecomposition thereof with an acetal or an O,N-acetal compound described in Japanese Pat. Application (OPI) No. 89003/73, with an ortho ester compound or an amidoacetal compound described in Japanese Pat. Application (OPI) No. 120714/76, with a polymer having an acetal group or a ketal group at the main chain described in Japanese Pat. Application (OPI) No. 133429/78, with an enol ether compound described in Japanese Pat. Application (OPI) No. 12995/80, with an N-acyliminocarbonic acid compound described in Japanese Pat. Application (OPI) No. 126236/80, with a polymer having an ortho ester group at the main chain described in Japanese Pat. Application (OPI) NO. 17345/81, and with a disolfone compound described in Japanese Pat. Application (OPI) NO. 166544/86. Specific examples of the compound generating an acid by the photodecomposition thereof are illustrated below, but they are not to be construed as being limited to these compounds. ##STR4##
It is preferred that the high molecular weight polymer having a function as a tender is alkali-soluble and as such a polymer, a novolak resin is frequently used. Specific examples of a novolak resin are described in U.S. Pat. Nos. 3,184,310 and 3,535,157, Japanese Pat. Publication Nos. 7482/75, 8658/75 and 14042/76, and Japanese Pat. Application (OPI) No. 48403/74.
Also, a mixture of the novolak resin and other high molecular weight compounds can be used and examples of such a mixture are described in U.S. Pat. No. 3,535,157, French Pat. 1,542,334, and Japanese Pat. Publication Nos. 16259/66, 24323/69, and 36961/74.
It is preferred that the ratio (weight ratio) of the photosensitive naphthoquinonediazide ester, which is used for the light-sensitive layer of the light-solubilizing color image-forming material in this invention, to the binder is in the range of from 0.10/1 to 0.5/1.
Also, it is preferred that the thickness of the light-sensitive layer is in the range of from 0.1 μm to 10 μm.
In addition, the coloring material layer and the light-sensitive layer of the light-solubilizing color image-forming material may be combined into one layer as a coloring material-containing light-sensitive layer. The construction and materials for such a coloring material-containing light-sensitive layer are known as described in Japanese Pat. Application (OPI) NO. 97140/84 and in the case of forming a coloring material-containing light-sensitive layer in the light-solubilizing color image-forming material for use in the present invention, the coloring material-containing light-sensitive layer can be easily formed by referring to the above-described examples of the constituting components and known techniques as described in Japanese Pat. Application (OPI) No. 97140/84.
In the light-solubilizing color image-forming material for use in this invention, a peelable layer may be formed between the support and the coloring material layer for, if necessary, transferring the images formed.
The constitution and materials therefor of the peelable layer formed on the support are known as described in Japanese Pat. Application (OPI) Nos. 188537/86 and 134482/87. The material for the peelable layer is generally selected from organic polymers which are not tacky at room temperature, but show tackiness and fusibility when heat is applied, and can be released from the support.
The materials for forming the peelable layer are described, for example, in Japanese Pat. Application (OPI) NO. 97140/84 (corresponding to U.S. Pat. No. 4,482,625). Specific examples thereof include polyacrylic acid esters, acrylic acid ester copolymers, polymethacrylic acid esters, methacrylic acid ester copolymers, polyacrylamide, acrylamide copolymers, polyvinyl acetate, vinyl acetate copolymers, polyvinyl chloride, vinyl chloride copolymers, polyvinylidene chloride, vinylidene chloride copolymers, polystyrene, styrene copolymers, ethylene copolymers (e.g., ethylene-vinyl acetate copolyxer, ethylene-acrylic acid ester copolymer, ethylene-vinyl chloride copolymer, and ethylene-acrylic acid copolymer), polyvinyl acetals (e.g., polyvinyl butyral, and polyvinyl formal), polyester resins, polyamide resins (e.g., nylon and copolymerized nylon), various rubbers (e.g., synthetic rubber and chlorinated rubber), and polyolefins (e.g., polyethylene and polypropylene).
The aforesaid polymers or resins may be used singly or as a mixture thereof. Also, the peelable layer may be composed of two or more layers. Furthermore, if desired, the peelable layer may contain various additives, such as a tackifier, a plasticizer, etc.
For forming the peelable layer on the support, a solution of the aforesaid high molecular weight material is coated on the support by an ordinary manner followed by drying, the aforesaid high molecular weight material is melted by heating and coated on the support (hot melt coating), or a film of the aforesaid high molecular weight material is laminated on the support.
The thickness of the peelable layer is preferably in the range of from 0.2 μm to 10 μm.
The image-exposure steps and development steps for the light-sensitive heat-sensitive recording material and the light-solubilizing color image-forming material in the present invention can be performed according to known methods.
That is, after contact exposure from a positive image, for example, a color separation positive image, a wet development (e.g., using a developer) or a dry development (e.g., using heat) may be applied. The image formation of the light-solubilizing color image-forming material can be performed by referring to the description of Japanese Pat. Application (OPI) No. 97140/84.
The following examples serve to illustrate the present invention, but these examples should not be construed as limiting the scope of the invention. Unless otherwise specified, all parts, percents, ratios and the like are by weight.
EXAMPLE 1
(A) Light-Sensitive Heat-Sensitive Recording Material
In a mixture of 24 g of tricresyl phosphate and 5 g of ethyl acetate were dissolved 3.45 g of the diazo compound shown below and 18 g of an adduct of xylylene diisocyanate and trimethylolpropane (3:1). The solution of diazo compound was dispersed by emulsification in an aqueous solution of 5.2 g of polyvinyl alcohol dissolved in 58 g of water at 20° C. to provide an emulsion having a mean particle size of about 2.5 μm. After adding 100 g of water to the emulsion thus obtained, the mixture was heated to 60° C. with stirring, whereby a microcapsule liquid containing the diazo compound as the core material was obtained ater 2 hours.
Diazo Compound ##STR5##
Then, 10 g of 2-hydroxy-3-naphtholic acid anilide, 10 g of triphenyl guanidine, and 40 g of hydroquinone monobenzyl ether were added to 200 g of an aqueous solution of 5% polyvinyl alcohol and they were dispersed for about 10 minutes by Dyno Mill (trade name, made by Willy A. Bachofen A.G.) to provide a dispersion of the coupling component and triphenyl guanidine having a mean particle size of about 2 μm.
Then, 50 g of the microcapsule liquid of the diazo compound thus obtained was mixed with 50 g of the dispersion of the coupling component, triphenyl guanidine, and hydroquinone monobenzyl ether obtained above to provide a coating composition. The coating composition thus obtained was coated on a flat wood-free paper of 50 g/m 2 using a coating bar at a dry thickness coating weight of 10 g/m 2 and dried for one minute at 25° C. to provide a light-sensitive heat-sensitive recording material.
(B) Light-Solubilizing Color Image-Forming Material
First, for forming a coloring material layer, mother liquid A having the following formula for dispersing pigment was prepared.
Mother Liquor A
______________________________________Styrene-Maleic Acid Copolymer Resin 20 g(Oxylack SH-101 represented by thefollowing formula, trade name, madeby Nippon Shokubai Kagaku Kogyo, Co.,Ltd.; mean molecular weight: 9,000;m.p.: about 190° C.) ##STR6##Methyl Ethyl Ketone 80 g______________________________________
Then using mother liquor A, a pigment dispersion having the following composition for forming a coloring material layer was prepared.
Coloring Material Layer Forming Coating Liquid
______________________________________Mother Liquor A 110 gMethyl Ethyl Ketone 40 gMethylcellosolve Acetate 25 gSeika Fast Yellow H-0755 (trade name, 14.6 gmade by Dainichiseika Color & Chemi-cals Mfg. Co., Ltd., C.I. No. 21095)Seika Fast Carmin 1483 (trade name, 9.8 gmade by Dainichiseika Color & Chemi-cals Mfg. Co., Ltd., C.I. No. 15850)______________________________________
The aforesaid dispersion was prepared by dispersing the above components for 3 hours by a dispersing machine for experiment (paint shaker, made by Toyo Seiki K.K.).
Then, a diluent having the following composition for diluting the pigment dispersion was prepared.
______________________________________Methyl Ethyl Ketone 550 gMethylcellosolve Acetate 130 gFluorine Series Surface Active Agent 2 g(Fluorad FC-430, trade name, madeby Sumitomo 3M Co.)______________________________________
After diluting the aforesaid pigment dispersion with the aforesaid diluent, the dispersion thus diluted was stirred for 10 minutes and then subjected to ultrasonic treatment for 10 minutes to provide a coating liquid for the color material layer. After filtering the coating liquid for the coloring material layer with Filter No. 63 (made by Toyo Roshi K.K.). The coating liquid was coated on a support using whirler and dried for 2 minutes at 100° C. to form a coloring material layer shown below.
Coloring Material Layer
______________________________________Pigment Dispersion/Diluent 3.5 g/46.5 gLayer Thickness 1.0 μmOptical Density (blue filter) 0.4______________________________________
Furthermore, a light-sensitive liquid having the following composition was coated on the coloring material layer with whirler after filtering with the aforesaid Filter No. 63 and dried for 2 minutes at 100° C. (dry thickness: 1.0μm) to form a light-sensitive layer.
______________________________________Addition product of Condensate (mean 15 gpolymerization degree: (3) of Acetoneand Pyrogallol and 2-Diazo-1-naphthol-4-sulfonyl ChlorideNovolak Type Phenol Formaldehyde Resin 30 g(PR-50716, trade name, made bySumitomo Duress Co., Ltd.; mean molecularweight: about 650; m.p.: about 80° C.)Tricresyl Phosphate 5 gn-Propyl Acetate 280 gCyclohexanone 120 g______________________________________
Thus, a light-solubilizing color image-forming material having the coloring material and the light-sensitive layer formed, in succession, on the support was prepared.
The light-sensitive heat-sensitive recording material prepared above was image-exposed with a 1 kW super high-pressure mercury lamp P-607W (trade name, made by Dainippon Screen Mfg. Co., Ltd.) using a color-separated positive for blue print for 45 seconds and then heat-developed using a color art transferring machine (laminator) CA600T (trade name, made by Fuji Photo Film Co., Ltd.) under 450 mm/min. at 125° C. to provide a clear blue positive image.
On the other hand, the light-solubilizing color image-forming material prepared above was image exposed with a 1 kW super high-pressure mercury lamp P-607W (trade name, by Dainippon Screen Mfg. Co., Ltd.) using a color-separated positive for red print for 60 seconds in a superposed state of them with the back surface of the original and the light-sensitive layer of the color image-forming material in face-to-face relationship and then developed by a color art developer CA-1 (trade name, made by Fuji Photo Film Co., Ltd.) diluted 5 times using an automatic processor (Color Art Processor CA-600P, trade name, made by Fuji Photo Film Co., Ltd.) for 34 seconds at 31° C. to provide a clear red positive image.
The light solubilizing color image-forming material having the red image was superposed on the light-sensitive heat-sensitive recording material having the blue image thus obtained as described above while matching the positions of both the images and they were laminated using a color art transferring machine (laminator) CA-600T (trade name, made by Fuji Photo Film Co., Ltd.) to form an image of red and blue having excellent color reproducibility.
EXAMPLES 2 AND 3
By following the same procedure as Example 1 except that as the coupling component for the coating liquid of the light-sensitive heat-sensitive recording material, a mixture of 8.7 g of 2-hydroxy-3-naphthoic acid anilide and 1.3 g of 2,4-dibenzoylacetylaminotoluene (Example 2) or a mixture of 4.0 g of 2-hydroxy-3-naphthoic acid benzylamide and 6.0 g of 1,2-ethylenebispivaloylacetamide (Example 3) was used, and further at the image-exposure of the light-sensitive heat-sensitive recording material, a black positive print (Example 2) or a green positive print (Example 3) was used as an original to provide, thus, a red-black image and a red-green image, each having excellent color reproducibility.
EXAMPLE 4
A light-sensitive heat-sensitive recording material was prepared by the same manner as Example 1 and a blue image was formed using the recording material by the same manner as in Example 1.
A light-solubilizing color image-forming material was prepared as follows.
First, a coating liquid having the following composition for forming a peelable layer was prepared.
______________________________________Alcohol-Soluble Polyamide (CM-8000, 7.2 gtrade name, made by Toray Industries,Inc., "η" = 23 cps (in 10 wt % methanolsolution at 20° C.; m.p.: about 128° C.;specific gravity: 1.12)Polyhydroxystyrene (Resin M, trade 1.8 gname, made by Maruzen Oil Co. Ltd.,mean molecular weight: 5,500)Methanol 400 gMethylcellosolve 100 g______________________________________
The coating liquid was uniformly coated on a polyethylene terephthalate film (support) of 75 μm in thickness and dried to form a peelable layer having a dry thickness of 0.5 μm.
Then, for forming a coloring material layer, mother liquor A having the following formula for pigment dispersion was prepared.
Mother Liquor A
______________________________________Styrene-Maleic Acid Copolymer Resin 20 g(Oxylack SH-101, trade name, made byNippon Shokubai Kagaku Kogyo K. K.)Methyl Ethyl Ketone 80 g______________________________________
Then, two kinds of dispersions of pigments each having each different color having following compositions were prepared using mother liquor A prepared above.
Yellow Coloring Material Layer-Forming Coating Liquid
______________________________________Mother Liquor A 110 gMethyl Ethyl Ketone 40 gMethylcellosolve Acetate 25 gSeika Fast Yellow H-0755 (trade name, 24.4 gmade by Dainichiseika Color & ChemicalsMfg. Co., Ltd.)______________________________________
Magenta Coloring Material Layer-Forming Coating Liquid
______________________________________Mother Liquor A 110 gMethyl Ethyl Ketone 40 gMethylcellosolve Acetate 25 gSeika Fast Carmin 1483 (trade name, 12.2 gmade by Dainichiseika Color & ChemicalsMfg. Co., Ltd.)______________________________________
Each dispersion was prepared by dispersing the above components for 3 hours using a dispersing machine for experiment (paint shaker, made by Toyo Seiki K.K.).
Then a diluent having the following formula for diluting the pigment dispersions was prepared.
______________________________________Methyl Ethyl Ketone 550 gMethylcellosolve Acetate 130 gFluorine Series Surface Active Agent 2 g(Fluorad FC-430, trade name, made bySumitomo 3M Co.)______________________________________
After diluting each of the pigment dispersions with the aforesaid diluent at a rate shown below, the dispersion thus diluted was stirred for 10 minutes and then subjected to a ultrasonic treatment for 10 minutes to provide each coating liquid for a coloring material layer.
After filtering each coating liquid for the coloring material layer with Filter No. 63 (trade name, made by Toyo Roshi K.K.), the coating liquid of each color was coated on each support having the peelable layer described above using whirler and dried for 2 minutes at 100° C. to form each coloring material layer of each color.
Yellow Layer
______________________________________Pigment Dispersion/Diluent 3.5 g/46.5 gLayer Thickness 1.0 μmOptical Density (blue filter) 0.5______________________________________
Magenta Layer
______________________________________Pigment Dispersion/Diluent 4 g/46 gLayer Thickness 0.7 μmOptical Density (green filter) 0.75______________________________________
Furthermore, a light-sensitive liquid having the following composition was coated on each coloring material layer of each color thus formed by whirler after filtering with aforesaid Filter No. 63 and dried for 2 minutes at 100° C. to form a light-sensitive layer (dry thickness of 1.0 μm).
______________________________________Addition Product of Condensate of 15 gAcetone and Pyrogallol (mean polymeri-zation degree: (3) and 2-Diazo-1-naphthol-4-sulfonyl ChlorideNovolak Type Phenol-Formaldehyde 30 gResin (PR-50716, trade name, made bySumitomo Duress Co.)Tricresyl Phosphate 5 gn-Propyl Acetate 280 gCyclohexanone 120 g______________________________________
As described above, each light-solubilizing color image-forming material of each color having the peelable layer containing the alcohol-soluble polyamide, the coloring material layer, and the light-sensitive layer formed, in succession, on the support was obtained.
Each of the two kinds of light-solubilizing color image-forming materials thus prepared was image-exposed to an original using each corresponding color separation mask with a 1 kW super high-pressure mercury lamp 0-607Fw (trade name, made by Dainippon Screen Mfg. Co., Ltd.) for 60 seconds. The original was superposed on the image-forming material with the back surface of the original and the light-sensitive layer of the color image-forming material in a face-to-face relationship and then developed by an automatic processor (Color Art Processor CA-600P, trade name, made by Fuji Photo Film Co., Ltd.) with a color art developer CA-1 (trade name, made by Fuji Photo Film Co., Ltd.) diluted 5 times for 34 seconds at 31° C. to provide clear yellow and red images, respectively.
Then, the light-sensitive heat-sensitive recording material having the blue image described above was superposed on the light-solubilizing color image-forming material having the red color described above while matching the positions of both the images, they were laminated using a color art transferring machine CA-600T (laminator) (trade name, made by Fuji Photo Film Co., Ltd.), and then the support for the light-solubilizing color image-forming material having the red image was peeled off to provide a two color image wherein the red image was transferred onto the blue image on the light-sensitive heat-sensitive recording material.
Then, the light-solubilizing color image-forming material having the yellow image obtained above was further superposed on the two-color image thus obtained while matching the positions of the images and they were laminated using a color art transferring machine CA-600T (laminator) (trade name, made by Fuji Photo Film Co., Ltd.) to provide an image having three colors and excellent color reproducibility.
As described above, according to the multicolor image-forming method of the present invention wherein color images are formed on a light-sensitive heat-sensitive recording material and a light-solubilizing color image-forming material, respectively, the color images thus obtained are superposed on each other, and they are pressured by heating, multicolor images can be very easily obtained at low cost and the image obtained are very excellent in color reproducibility relative to the originals. These merits satisfy both the need for a high image quality and low cost for producing the color images, which are difficult to achieve with a conventional overlay method and surprint method.
While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof. | A multicolor image-forming method which comprises image-exposing a light-sensitive heat-sensitive recording material having a diazo compound and a coupling component on a support using a positive image followed by developing to form a color image, image-exposing a light-solubilizing color image-forming material having a coloring material on a substantially transparent support using a positive image followed by developing to form a color image, and superposing the light-solubilizing color image-forming material having the color image on the light-sensitive heat-sensitive recording material having the color image or, further, heat-pressing the light-solubilizing color image-forming material having the color image superposed on the light-sensitive heat-sensitive recording material having the color image. | 6 |
TECHNICAL FIELD
[0001] The following generally relates to ultrasound imaging and more particularly to vector flow ultrasound imaging.
BACKGROUND
[0002] Ultrasound imaging provides information about the interior of a subject. For example, ultrasound imaging can be used to generate an image of a blood vessel and estimate blood flow velocity inside the blood vessel.
[0003] With conventional blood flow velocity estimation, a pulse-echo field oscillates in the axial direction along the axis of the ultrasound beam. This is illustrated in FIG. 1 in which a transducer array 100 produces an ultrasound beam 102 that propagates in the axial direction along the z-axis (or depth) 104 . Blood scatterers passing through the field of interest produce a signal with a frequency component proportional to the axial velocity, and the axial velocity component (VZ) 106 can be estimated.
[0004] The transverse oscillation (TO) blood velocity estimation approach has been used to estimate both VZ 106 and the transverse velocity component (VX) 108 , along the transverse axis 110 , of the velocity vector 112 . With the transverse oscillation approach, a transverse oscillation is introduced in the ultrasound field, and this oscillation generates signals that depend on the transverse oscillation. The basic idea is to create a double-oscillating pulse-echo field using a one dimensional (1D) transducer array.
[0005] Color flow mapping (CFM) is one approach to visually show velocity. An example of this is shown in FIG. 2 , in which first flow 202 through a first vessel 204 and second flow 206 through a second vessel 208 towards the transducer is displayed using a first color (red shades), and third flow 210 through the first vessel 204 and fourth flow 212 through the second vessel 208 away from the transducer is displayed using a second different color (blue shades). Intensity is proportional to the velocity of the flow.
[0006] Unfortunately, with color flow mapping, the two colors only show relative flow with respect to the ultrasound transducer. Furthermore, with color flow mapping, blood flow perpendicular to the ultrasound beam cannot be seem Moreover, with color flow mapping, the colors do not indicate the direction and magnitude of the blood flow. In view of at least the above, there is an unresolved need for other approaches for visualizing blood flow.
SUMMARY
[0007] Aspects of the application address the above matters, and others.
[0008] In one aspect, an ultrasound imaging console includes receive circuitry that receives a set of echoes produced in response to an ultrasound signal traversing blood flowing in a portion of a vessel in a field of view, a beamformer that beamforms the echoes, a velocity processor that determines flow direction and magnitude of the flowing blood based on the beamformed echoes, and a rendering engine that displays the determined flow direction and magnitude.
[0009] In another aspect, a method includes receiving a set of echoes produced in response to an ultrasound signal traversing blood flowing in a portion of a vessel in a field of view, beamforming the echoes, estimating flow direction and magnitude of blood the flowing blood based on the beamformed echoes, and displaying the determined flow direction and magnitude.
[0010] A computer readable storage medium is encoded with computer readable instructions, which, when executed by a processer, cause the processor to: receive a set of echoes produced in response to an ultrasound signal traversing blood flowing in a portion of a vessel in a field of view, beamform the echoes, estimate flow direction and magnitude of blood the flowing blood based on the beamformed echoes, generate an image based on the beamformed echoes, and displaying indicia representing flow direction and magnitude superimposed over the image, wherein flow direction is displayed using at least one of color or hue and magnitude is displayed using intensity.
[0011] Those skilled in the art will recognize still other aspects of the present application upon reading and understanding the attached description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The application is illustrated by way of example and not limited by the figures of the accompanying drawings, in which like references indicate similar elements and in which:
[0013] FIG. 1 illustrates a prior art approach to estimating blood flow velocity along the axial and transverse direction of a vessel;
[0014] FIG. 2 illustrates a prior art color flow mapping approach for visualizing flow direction relative to the position on the ultrasound transducer;
[0015] FIG. 3 illustrates an example ultrasound scanner configured to visually present blood flow absolute direction and magnitude;
[0016] FIG. 4 illustrates an example visualization of blood flow absolute direction and magnitude along the axial direction;
[0017] FIG. 5 illustrates an example 2D blood flow direction-magnitude map;
[0018] FIG. 6 illustrates example visualization of blood flow absolute direction and magnitude; and
[0019] FIG. 7 illustrates a method.
DETAILED DESCRIPTION
[0020] Initially referring to FIG. 3 , an example ultrasound imaging console 300 is illustrated.
[0021] A transducer array 302 includes a one dimensional (1D) array of transducer elements, which are configured to transmit ultrasound signals and receive echo signals. Examples of suitable 1D arrays include 128 , 192 , and/or other dimension arrays, including square and/or rectangular arrays. The array can be linear, curved, and/or otherwise shaped. The array can be fully populated or sparse and/or a combination hereof.
[0022] Transmit circuitry 304 generates a set of pulses that are conveyed to the transducer array 302 . The set of pulses actuates a corresponding set of the transducer elements of the transducer array 302 , causing the elements to transmit ultrasound signals into an examination or scan field of view. In the illustrated embodiment, transmit circuitry 304 generates a set of pulses which produce a transmit signal suitable at least for velocity imaging.
[0023] Receive circuitry 306 receives echoes generated in response to the transmitted ultrasound signals from the transducer 302 . The echoes, generally, are a result of the interaction between the emitted ultrasound signals and the structure (e.g., flowing blood cells, organ cells, etc.) in the scan field of view.
[0024] A controller 308 controls one or more of the transmit circuitry 304 or receive circuitry 306 . Such control can be based on available modes of operation (e.g., velocity flow, A-mode, B-mode, etc.) of the system 300 . In addition, such control can be based on one or more signals indicative of input from a user.
[0025] A user interface (UI) 310 produces the one or more signals indicative of the input from a user. The UI 310 may include one or more input devices (e.g., a button, a knob, a slider, a touch pad, etc.) and/or one or more output devices (e.g., a display screen, lights, a speaker, etc.).
[0026] One or more beamformers 312 process the echoes, for example, by applying time delays, weighting on the channels, summing, and/or otherwise beamforming received echoes.
[0027] A velocity processor 314 processes the beamformed data. In one instance, this includes processing the beamformed data using a transverse oscillation (TO) approach and determining from the processed data one or more velocity components such as a depth (VZ) velocity component and a transverse (VX) velocity component, including direction and magnitude of flow. The TO approach is described in greater detail in U.S. Pat. No. 6,148,224 to Jenson, titled “Apparatus and Method for Determining Movement and Velocities of Moving Objects, filed on Dec. 30, 1998, and assigned to B-K Medical A/S, which is incorporated herein by reference in its entirety.
[0028] An image processor 316 also receives the beamformed data. For B-mode, the image processor 316 processes the data and generates a sequence of focused, coherent echo samples along focused scanlines of a scanplane. The image processor 316 may also be configured to process the scanlines to lower speckle and/or improve specular reflector delineation via spatial compounding and/or perform other processing such as FIR filtering, IIR filtering, etc.
[0029] A scan converter 318 scan converts the output of the image processor 316 to generate data for display, for example, by converting the data to the coordinate system of the display. The scan converter 318 can be configured to employ analog and/or digital scan converting techniques.
[0030] A rendering engine 320 visually presents one or more images with blood flow information via a graphical user interface (GUI) in a display monitor 322 . With respect to flow imaging, the image may include a 2D angular independent flow image showing both flow direction and magnitude, where direction is shown in absolute direction, as opposed to conventional Doppler imaging, where flow is shown towards and away from the ultrasound probe.
[0031] In one instance, hue is used for direction and intensity is used for magnitude based on direction indicia 324 and magnitude indicia 326 . Additionally or alternatively, graphics, such as vectors, flowlines, particles, animation, and/or other indicia, from the magnitude indicia 326 is used for direction. It is to be appreciated that acquiring angular independent flow information simplifies user manipulation of probe as sonographers do not have to search for the best scan angle. This also allows for a reduction in examination time.
[0032] Less training is required to interpret the images since the flow information in both direction and magnitude is visualized. Furthermore, the displayed image can show complex flow such as turbulence or flow vortex in a vessel, such as the carotid artery, the jugular vein, and/or other blood vessel. Moreover, the peak measured transverse velocity component can be two times larger than the peak measured axial component for the same depth. This opens doors to areas where there is a desire to measure fast blood flow parallel to the transducer surface, such as the flow in the fistulas of hemodialysis patients.
[0033] It is to be appreciated that the components 312 , 314 and/or 316 can be implemented via one or more processors executing one or more computer readable instructions encoded or embedded on computer readable storage medium such as physical memory. Additionally or alternatively, the one or more processors can execute at least one instruction(s) carried by a carrier wave, a signal, or other non-computer readable storage medium such as a transitory medium.
[0034] FIGS. 4 and 5 illustrate an example in which flow direction is shown using graphical indicia (i.e., vectors) and flow direction and magnitude is shown using a two-dimensional color-intensity mapping.
[0035] In FIG. 4 , vessel portions 402 and 404 along long axes of the vessels are shown.
[0036] Vectors 406 in the vessel 402 show flow direction going right to left, generally horizontally or slightly downward at the far right to acutely upward at the far left. Vectors 408 in the vessel 404 show flow going left to right, acutely downward most of the length of the portion 404 .
[0037] The portion 402 is highlighted using darker colors 403 , which is used to show flow direction from left to right. The portion 404 is highlighted using lighter colors 405 , which is used to show flow direction from right to left. Intensity (or brightness) is used to show velocity magnitude, with a higher intensity representing a larger magnitude.
[0038] With respect to the portion 402 , a region about 410 is higher intensity relative to regions about 412 and 414 , and a region 416 has an intensity between the intensity at 410 and 412 . With respect to the portion 404 , regions about 418 and 420 have higher intensity relative to regions about 422 , 424 , 426 and 428 , which have slightly different intensity.
[0039] The vector flow indicia 406 and 408 , the darker colors 403 and the lighter 405 colors (represented via different patterns), and the intensities 410 and 412 and the intensities 420 and 422 are further shown in magnified views 430 and 432 .
[0040] FIG. 5 shows an example velocity direction-magnitude map 500 . An x-axis 502 represent a first color scheme representing transverse velocity direction, with zero transverse velocity at 504 , and a y-axis 506 represent a second color scheme representing axial velocity direction, with zero axial velocity at 508 .
[0041] Regions 510 , 512 , 514 , 516 , 518 , 520 , 522 to 524 show several example colors of the map 500 . The intensity increases from a center region 526 to the periphery of the map 500 .
[0042] FIG. 6 shows the vessel portions 402 and 404 of FIG. 4 in the transverse plane. Likewise, vectors and colors are used to show flow direction and intensity is used to show magnitude. In this embodiment, the color map 500 is concurrently shown.
[0043] In FIGS. 4 and 6 , quantitative information can be variously obtained. In one instance, hovering a mouse pointer over and/or clicking on a region of the portion 402 and 404 invokes the rendering engine 320 to display a numerical value representing the flow.
[0044] In another instance, a curve showing velocity as a function of time is visually presented, which shows how velocity evolves in real-time.
[0045] In yet another instance, a velocity profile curve showing velocity as a function of points taken along a line and as a function of time is displayed. Such a curve may useful for vessel surgery and/or other applications.
[0046] FIG. 7 illustrates an example method.
[0047] It is to be understood that the following acts are provided for explanatory purposes and are not limiting. As such, one or more of the acts may be omitted, one or more acts may be added, one or more acts may occur in a different order (including simultaneously with another act), etc.
[0048] At 702 , an ultrasound signal is transmitted into a field of view.
[0049] At 704 , echoes, in response to the ultrasound signal, are received by a transducer array.
[0050] At 706 , the echoes are beamformed.
[0051] At 708 , flow direction and magnitude are determined
[0052] At 710 , the flow direction and magnitude visually presented, for example, with hue and/or graphics showing direction and intensity showing magnitude, superimposed over a B-mode or other image.
[0053] The methods described herein may be implemented via one or more processors executing one or more computer readable instructions encoded or embodied on computer readable storage medium such as physical memory which causes the one or more processors to carry out the various acts and/or other functions and/or acts. Additionally or alternatively, the one or more processors can execute instructions carried by transitory medium such as a signal or carrier wave.
[0054] The application has been described with reference to various embodiments. Modifications and alterations will occur to others upon reading the application. It is intended that the invention be construed as including all such modifications and alterations, including insofar as they come within the scope of the appended claims and the equivalents thereof. | An ultrasound imaging console includes receive circuitry that receives a set of echoes produced in response to an ultrasound signal traversing blood flowing in a portion of a vessel in a field of view, a beamformer that beamforms the echoes, a velocity processor that determines flow direction and magnitude of the flowing blood based on the beamformed echoes, and a rendering engine that displays the determined flow direction and magnitude. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is based on U.S. Provisional Application Ser. No. 60/475,727, entitled High Power, Current Amplified, Tunable Post Accelerated Split Cavity Microwave Oscillator, filed on Jun. 4, 2003, the teachings of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention (Technical Field):
[0003] The invention relates to microwave generation and more particularly to a resonant frequency (RF) generator that operates at low impedance, amplifies the current to increase the RF output power, allows tuning the frequency of the apparatus, and a method to allow operation as an amplifier
[0004] 2. Background Art
[0005] The efficient generation of microwaves from modulated electron beams requires electron beam velocity spectrums with low ratios of perpendicular energy to axial energy. Devices which violate this criteria pay a large price in terms of efficiency. For example, the virtual cathode oscillator (D. J. Sullivan, “High Power Microwave Generation using a Relativistic Electron Beam in a Waveguide Tube,” U.S. Pat. No. 4,345,220,17 August 1982) has a very high ratio of E-perpendicular/E-parallel at the nominal axial location of the virtual cathode, potentially exceeding unity. Due to challenges in extracting usable RF power from such beams the practical efficiency of this device, a few percent typically, is poor, and no efficient means of harnessing the high modulated currents, often exceeding a few 10s kA at voltages of order 500 kV, has been developed.
[0006] A highly efficient device for modulating electron beams is known as the Split Cavity Oscillator, as described in U.S. Pat. No. 5,235,248. While this device has a high ratio of E-perpendicular/E-parallel at its exit port, this ratio is substantially reduced with acceleration of the modulated electron beam to voltages of order MV. Post-acceleration of a spatially modulated electron beam, as a means to lock in a spatial modulation while substantially increasing axial kinetic energy and thus reducing E-perpendicular/E-parallel, has been used for many years. As far back as 1940 Haeff and Nergaard described post-acceleration in their Inductive Output Amplifier device, as shown in “A wide-band inductive-output amplifier,” A. V. Haeff and L. S. Nergaard, Proc. of the IRE, vol. 28, pp. 126-130, March 1940. With post-acceleration, the SCO modulated beam kinetic energy can be converted to RF electromagnetic fields quite efficiently, exceeding 50%. However, virtual cathode formation limits the attainable current, due to space charge limitations in the modulating cavity of the device.
[0007] The operation of the prior art transit time oscillator (TTO), split cavity oscillator (SCO), and post accelerated split cavity oscillator (PASCO) are next briefly described in order to enable a distinction between previous techniques and the new methods described in the present invention.
[0008] The geometry of the TTO microwave oscillator is depicted in FIG. 1. Its operation relies on the interaction of a direct current (DC) electron beam 10 and the field of a cavity formed by a cylindrical pill box with perfectly conducting walls. The DC electron beam is often produced by a thermionic or field emission cathode 12 . The geometry of the cavity is such that the time of flight 18 across the cavity 20 and the interaction of the beam 10 with the oscillating axial electric field associated with the cavity's axially symmetric mode 22 produce a spatially modulated electron beam 14 . The spatially modulated electron beam 14 is converted to an electromagnetic wave 16 ; this conversion process is depicted symbolically in FIG. 1 since the details of the extraction/conversion process vary depending on the device and/or application. The operation of the TTO is described in detail in “The Split Cavity Oscillator: a high power e-beam modulator and microwave source,” B. Marder, et al., pg. 312, IEEE Trans. Plasma Sci ., vol. 20, 1992. This device is an extremely inefficient oscillator, a problem that is addressed by the SCO.
[0009] The geometry of the SCO microwave oscillator is depicted in FIG. 2. Its operation also relies on the interaction of a direct current (DC) electron beam 40 and the field of a cavity 41 . In this case the cavity 42 is formed by a cylindrical pill box cavity with an intermediate electrically conducting septum 44 (placed exactly midway across the pill box) that extends part ways across the interior of the cavity 42 , as shown in FIG. 2. Distinct from the operation of the TTO, the SCO operates according to a well known energy instability that exists between the electron beam 40 and the cavity 42 , and an externally applied field is not required, as described in “The Split Cavity Oscillator: a high power e-beam modulator and microwave source,” B. Marder, et al., pg. 312, IEEE Trans. Plasma Sci ., vol. 20, 1992. Again, the DC electron beam 40 is often produced by a highly inefficient thermionic or field emission cathode 46 . As with the TTO, the geometry of the SCO cavity is such that the time of flight across the cavity 48 and the interaction of the beam with the Pi-mode of the cavity's oscillating electric field cavity produce a spatially modulated electron beam 50 . The SCO geometry and resulting electromagnetic field mode structure permits the axial length 48 of the cavity to be much shorter than the axial length of the TTO oscillator 18 . Finally, the spatially modulated electron beam 50 is converted to an electromagnetic wave 52 as depicted symbolically in FIG. 2. Note that cathode 46 must produce the entire charge of electron beam 40 , and consequently, operation at high powers requires that cathode 46 be capable of producing high current densities at high voltages. This often results in short cathode lifetimes, and pulse shortening due to gap closure caused by plasma drift across the anode-cathode gap, as shown in “Results of research on overcoming pulse shortening of GW class HPM sources,” K. Hendricks, et al., pg. 81, Digest of Technical Papers, International Workshop on High Power Microwave Generation and Pulse Shortening, Edinburgh, Scotland, 1997. The main disadvantage of the SCO is the large axial velocity spread, and the substantial unwanted perpendicular velocities of the electrons that exit the cavity, leading to poor beam-to-RF power conversion efficiencies. The SCO is described in U.S. Pat. No. 5,235,248. However, this prior art patent describes an apparatus with a very specific geometry (cylindrical pill box with an electrically conducting septum placed exactly midway along the axial length of the cavity) that operates at a single frequency. No capability to adjust the frequency of operation of the device is disclosed or implied in the prior art patent.
[0010] The geometry of the PASCO microwave oscillator is depicted in FIG. 3. Its operation to produce a spatially modulated electron beam 60 is equivalent to the SCO described above. However, once the spatially modulated electron beam 60 is produced, the PASCO uses an accelerating screen or grid 62 at a high relative potential, typically 100's of kV or more, to accelerate the electron beam to relativistic velocities 64 , i.e., close to the speed of light. This greatly reduces the relative axial velocity spread intrinsic to the SCO and represents a major improvement for potential high power and high efficiency operation. The relativistic spatially modulated electron beam 64 is then converted to an electromagnetic wave 66 as depicted in FIG. 3. This technique results in a more tightly velocity-modulated beam, while maintaining excellent spatial bunching allowing more efficient beam-to-RF extraction. The main disadvantages of the PASCO are: (1) the device has an inherent limitation on total current due to space charge depression in the modulating cavity, which ultimately can lead to virtual cathode formation, but at more modest current levels, reduces modulation efficiency; and (2) the PASCO is a fixed frequency device, in that there is no ability to tune its frequency while maintaining axisymmetry.
[0011] Post-acceleration of an electron beam for high power and high efficiency operation is described in U.S. Pat. No. 5,101,168. However, this patent describes methods that were well known prior to the patent's application date. As an example, post-acceleration of an electron beam was described by Haeff and Nergaard, “A wide-band inductive-output amplifier,” A. V. Haeff and L. S. Nergaard, Proc. of the IRE, vol. 28, pp. 126-130, March 1940. Furthermore, post-acceleration of an electron beam was described by Preist and Shrader, “The Klystrode—an unusual transmitting tube with potential for UHF,” D. H. Preist and M. B. Shrader, Proc. of the IEEE, vol. 70, no. 11, pp. 1318-1325, November 1982.
[0012] The present invention, a Current Amplified, Tunable, Post Accelerated, Modulator (CATPAM) apparatus uses techniques of the well known transit time oscillator (TTO) as described in “Interchange of energy between an electron beam and an oscillating electric field,” J. Marcum, Journal of Applied Physics, vol. 17, January, 1946, a split cavity oscillator (SCO) shown in “The Split Cavity Oscillator: a high power e-beam modulator and microwave source,” B. Marder, et al., pg. 312, IEEE Trans. Plasma Sci., vol. 20, 1992, and the post accelerated split cavity oscillator (PASCO) (the PASCO is also known as the Reltron described in “Super RELTRON theory and experiments,” R. Miller, et al., pg. 332, IEEE Trans. Plasma Sci., vol. 20, 1992, in conjunction with unique techniques to operate at low impedance, amplify the current to increase the RF output power, tune the frequency of the device, and a method to allow operation as an amplifier, as opposed to just an oscillator. The disclosed apparatus spatially modulates a direct current (DC) electron beam using instabilities associated with device geometry and transit time effects; or, it directly generates a spatially modulated electron beam using laser-induced electron emission. It then amplifies the resulting electron beam (current), accelerates the spatially modulated beam to relativistic velocities, and converts the kinetic energy of the spatially modulated relativistic electron beam to electromagnetic fields at microwave frequencies. In addition, methods are disclosed that allow the device to be tuned to a desired operating frequency while maintaining nominal axisymmetry. None of the prior art teaches or implies these novel features.
SUMMARY OF THE INVENTION (DISCLOSURE OF THE INVENTION)
[0013] Disclosed is a CATPAM RF generator device that allows for substantial levels of frequency tunability, without the need to break vacuum, while maintaining axisymmetry, and retains all the advantages of the PASCO devices as discussed in the Background Art section of the specification. Additionally, the use of a transmissive electron multiplier allows substantially higher current operation compared with PASCO, reducing the impedance and output power by the multiplication factor. Finally, the use of a RF-modulated laser to generate a seed current permits the use of the device as an amplifier, and greatly increases the output RF pulse width of the device.
[0014] A primary object of the present invention is to provide the ability to tune the frequency of the output microwave signal of the apparatus when it is operated as an oscillator.
[0015] Another object of the present invention is to provide a technique to amplify, or multiply, the electron beam current of the CATPAM, or other, device which creates a modulated electron beam. This method increases the microwave output power of the device, enhances the low impedance properties and efficiency of the device.
[0016] Another object of the present invention to provide a method for amplifying electron beams from an arbitrary device which has previously created a modulated electron beam current.
[0017] Yet another object of the present invention is the provision of a RF-modulated, laser-induced emission of electrons from a cathode.
[0018] An advantage of the present invention is that it increases the microwave output power of the apparatus, enhances the low impedance properties and efficiency of the apparatus.
[0019] Yet another advantage of the present invention is the allowance of the CATPAM to operate without a field emission cathode and without a RF modulator, and helps the CATPAM achieve greater operational efficiency in less volume and with less weight than otherwise would be the case.
[0020] Another advantage of the present invention is the ability of the CATPAM apparatus to operate as an amplifier.
[0021] Other objects, advantages and novel features, and further scope of applicability of the present invention will be set forth in part in the detailed description to follow, taken in conjunction with the accompanying drawings, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The accompanying drawings, which are incorporated into and form a part of the specification, illustrate several embodiments of the present invention and, together with the description, serve to explain the principles of the invention. The drawings are only for the purpose of illustrating a preferred embodiment of the invention and are not to be construed as limiting the invention. In the drawings:
[0023] [0023]FIG. 1 depicts the geometry of the prior art Transit Time Oscillator.
[0024] [0024]FIG. 2 depicts the geometry of the prior art Split Cavity Oscillator.
[0025] [0025]FIG. 3 shows the geometry of the prior art Post Accelerated Split Cavity Oscillator.
[0026] [0026]FIG. 4 illustrates the geometry of the preferred Current Amplified, Post Accelerated Modulator, with frequency tuning method no. 1.
[0027] [0027]FIG. 5 depicts the geometry of the preferred Current Amplified, Post Accelerated Modulator, with frequency tuning method no. 2.
[0028] [0028]FIG. 6 gives details of the geometry of the preferred Current Amplified, Post Accelerated Modulator, with frequency tuning method no. 3.
[0029] [0029]FIG. 7 depicts the geometry of the preferred Current Amplified, Post Accelerated Modulator, with frequency tuning method no. 4.
[0030] [0030]FIG. 8 illustrates the geometry of the preferred Current Amplified, Post Accelerated Modulator, with frequency tuning method no. 2.
[0031] [0031]FIG. 9 shows the conceptual geometry of the current amplification process of the Current Amplified, Post Accelerated Modulator.
[0032] [0032]FIG. 10 depicts the geometry of the preferred Current Amplified, Tunable, Post-Accelerated Modulator, with laser-induced electron emission from the cathode illustrated. The laser is pulsed at an RF frequency, so the electrons that are emitted from the surface of the cathode constitute a spatially-modulated electron beam, obviating the need for a modulating cavity.
[0033] [0033]FIG. 11 graphically provides details of the laser-induced electron emission from the cathode of the Current Amplified, Tunable, Post-Accelerated Modulator. The laser is pulsed at an RF frequency, so the electrons that are emitted from the surface of the cathode constitute a spatially-modulated electron beam, obviating the need for a modulating cavity.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
BEST MODES FOR CARRYING OUT THE INVENTION
[0034] Disclosed is a Current Amplified, Tunable, Post Accelerated, Modulator (CATPAM) that is frequency tunable, high power capable, highly efficient in operation, and exhibits low impedance operation. The CATPAM can operate either as an oscillator or an amplifier, depending on the particular configuration.
[0035] The geometry of the CATPAM microwave oscillator, without current amplification, and with the first of four frequency tuning schemes, is depicted in FIG. 4 (please note that current amplification is not indicated in this figure). As shown, its operation relies on the interaction of a direct current (DC) electron beam 100 and the field of a closed rectangular pill box cavity 101 that contains an intermediate conducting septum 104 that extends partly across the interior centerline 106 of cavity 102 . Again, DC electron beam 100 is often produced by a highly inefficient thermionic or field emission cathode 108 . As with the TTO, the geometry of the modulating cavity 102 is such that the time of flight across the cavity 110 and the interaction of the beam 100 with the oscillating electric field 101 in cavity 102 produce a spatially modulated electron beam 112 . The modulator geometry and resulting electromagnetic field mode structure promotes an instability that generates an oscillating electromagnetic field 101 at the frequency of the modulator's cavity mode. The interaction of the electron beam 100 with the cavity's electromagnetic field and the time of flight across the cavity 110 generate a spatially bunched electron beam 112 on the output side of the cavity 116 . Spatially modulated electron beam 112 is subsequently accelerated by an accelerating grid 118 to a relativistic velocity producing a relativistic spatially modulated electron beam 120 and converted to an electromagnetic wave 122 ; this process is depicted symbolically in FIG. 4 since the details of the extraction/conversion process vary depending on the device and/or application. It is well known that the spatial modulation frequency of the modulator cavity is governed by the resonant frequency of the cavity. As shown in FIG. 4, included is a tuning annulus 124 for tuning (changing) the resonant frequency of cavity 102 , and consequently tuning the spatial modulation of the electron beam 112 . This, in turn, allows one to tune the output frequency of the electromagnetic signal that is ultimately extracted from the apparatus. The width of the tuning annulus 126 , adjustable from outside of the apparatus (not shown) governs the resonant frequency of cavity 102 and the resulting electromagnetic signal that is ultimately extracted from the apparatus. Tuning annulus 124 is introduced into cavity 102 from the interior wall 128 of rectangular pill box cavity 102 , as indicated in FIG. 4.
[0036] The geometry of the CATPAM microwave oscillator, without current amplification and the second of four frequency tuning schemes is depicted in FIG. 5. Its operation relies on the interaction of a direct current (DC) electron beam 200 and cavity 202 in the same manner as described above, though frequency tuning of the device is accomplished in a different manner. As shown in FIG. 5, a second embodiment for a tuning annulus 204 is shown to tune (change) the resonant frequency of the modulator's cavity 202 , and consequently tune the spatial modulation of the electron beam 206 . Tuning annulus 204 is introduced into cavity 202 from the center septum 208 of rectangular pill box cavity 202 , as indicated in FIG. 5. Again, the width of the tuning annulus 210 , adjustable from outside of the device (not shown in the figure) governs the resonant frequency of the cavity and the resulting electromagnetic signal that is ultimately extracted from the device.
[0037] The geometry of the CATPAM microwave oscillator, without current amplification and the third of four frequency tuning schemes is depicted in FIG. 6. Its operation relies on the interaction of a direct current (DC) electron beam 300 and cavity 302 in the same manner as described above, though frequency tuning of the device is accomplished in a different manner. As shown in FIG. 6, a dielectric material 304 with a relative dielectric constant greater than unity (ε r , >1) is disposed in the internal volume of cavity 302 . In an alternative embodiment, plasma which has a dielectric constant less than unity (ε r <1) can be disposed in portions of cavity 302 (not shown). The presence of dielectric material 304 depresses the resonant frequency of cavity 302 , and in turn, reduces (or with plasma, increases) the frequency of the electromagnetic signal that is ultimately extracted from the apparatus. Also included is a tuning annulus 306 used to tune (change) the resonant frequency of cavity 302 , and consequently tune the spatial modulation of electron beam 312 . Tuning annulus 306 is introduced into cavity 302 from the center septum 308 of the rectangular pill box cavity 302 , as indicated in FIG. 6. Again, the width of the tuning annulus 310 , adjustable from outside of the device (not shown in the figure) governs the resonant frequency of cavity 302 and permits the tuning of the resulting electromagnetic signal 314 that is ultimately extracted from the apparatus.
[0038] The geometry of the CATPAM microwave oscillator, without current amplification and the fourth of four frequency tuning schemes is depicted in FIG. 7. Its operation relies on the interaction of a direct current (DC) electron beam 400 and cavity 402 in the same manner as described above, though frequency tuning of the apparatus is accomplished in a different manner, in yet another alternative embodiment. As shown in FIG. 7, a tuning annulus 404 is provided that extends from the wall 406 of pill box cavity 402 and a second annulus 408 that is introduced into cavity 402 from a center septum 410 of rectangular pill box cavity 402 . In this configuration, tuning (changing) the resonant frequency of the cavity, and consequently tuning the spatial modulation of electron beam 412 is accomplished. The widths 414 , 416 of each tuning annulus 404 , 408 work in concert to govern the resonant frequency of cavity 402 and permit the tuning of the resulting electromagnetic signal 430 that is ultimately extracted from the apparatus.
[0039] The geometry of the CATPAM microwave oscillator, with current amplification and the second of four frequency tuning schemes is depicted in FIG. 8. Note that current amplification is possible with any of the tuning schemes, as described above. The invention utilizes current multiplication of a seed beam 601 , which is achieved by allowing an energetic electron beam to impact a thin foil surface 602 with high electric field on its downstream side. The foil is sufficiently thin and of such materials that the forward directed secondary electron cascade process, initiated by the seed beam, results in more electrons being ejected from the downstream surface than are incident on the front surface, per unit area, as described in “Reflection and transmission secondary emission from silicon,” R. Marti nelli, Applied Physics Letters, pp. 313-314, vol. 17, no. 8, 15 October 1970 and “The application of semiconductors with negative electron affinity surfaces to electron emission devices,” Proc. of IEEE, vol. 62, no. 10, pp. 1339-1360, Oct. 1974. The output secondary electron cascade from the exit surface of the foil can be accelerated subsequently by an accelerating grid 608 for further multiplication in a similar manner with a similar foil 606 , and so forth, yielding multiplication factors limited primarily by space charge and beam propagation effects, with the neglect of foil heating. The transmissive, electron multiplier foils as described are also beneficial in mitigating both space charge and beam propagation effects, due their shorting of the radially directed electric field as described in, “Image-field focusing of intense relativistic electron beams in vacuum,” R. J. Adler, Particle Accelerators, vol. 12, pp. 39-44,1982. Because the foil is sufficiently thin, and exit fields sufficiently intense, the multiplication process can occur on a small fraction of an RF period, even for frequencies as high as many GHz. Thus, any pre-existing modulation of the electron beam is well-preserved during the multiplication process. A large electric field on the final foil, provided by a large accelerating voltage 608 , even to fractional or multi-MV levels, can produce high flowing powers in the electron beam; these can be converted into extracted microwave power 620 using a variety of traditional methods, including tuned cavities driving one or more rectangular waveguides, or transmission lines, for example. Without foil current enhancement, the apparatus is limited to modulated currents of approximately 1 kA, for voltages up to approximately 200 kV. With foil enhanced current multiplication, multiplicatively higher currents will be obtainable with CATPAM. The particular nature of electron multiplication is indicated in FIG. 9 in which it is shown that a single electron 600 strikes the transmissive electron multiplier 602 , and three (for explanatory purposes) electrons are emitted on the other side 604 . This process is repeated onto further transmissive electron multipliers 606 until the desired current level is achieved. The resulting high current, spatially modulated electron beam 607 is subsequently accelerated by the high voltage of the accelerating screen 608 which yields a high current, relativistic, spatially modulated electron beam 610 . This configuration provides a method to operate a high current, high power microwave generator using an initial low value of seed current. This technique, in principle, allows for multiplicatively higher currents and current densities than would be available from PASCO or SCO devices. Both self-excited oscillator and amplifier configurations using the current multiplication method can be envisaged.
[0040] To eliminate the modulating cavity (thereby saving weight and volume) the scheme whereby a spatially modulated electron beam is directly produced is illustrated in FIG. 10. Note the absence of a modulating cavity in FIG. 10. There, an intense, temporally-modulated laser light 700 , temporally modulated at RF frequencies, is depicted. A detail drawing of the laser-cathode interaction is depicted in FIG. 11. FIG. 11 shows a laser 701 , which illuminates the cathode; laser light 702 is oscillating at light frequencies, but is modulated (turned on and off) on an RF time scale 704 . The laser initiates the emission of a small number of electrons 706 , a seed current. The small seed current generated in this fashion is subsequently amplified in the manner described previously. Traditional field emission cathode oscillators are typically limited to high power operation in the microsecond regime due to gap closure caused by unwanted plasma generated in the electron generation process. Since the CATPAM oscillator can operate with a small seed current that is subsequently multiplied as described above, the generation of high power RF pulses can occur over much longer times. Production of modulated electron beams on a time scale of order fractional to several microseconds is foreseen.
[0041] Although the invention has been described in detail with particular reference to these preferred embodiments, other embodiments can achieve the same results. Variations and modifications of the present invention will be obvious to those skilled in the art and it is intended to cover in the appended claims all such modifications and equivalents. The entire disclosures of all references, applications, patents, and publications cited above, are hereby incorporated by reference. | Generating and frequency tuning of modulated high current electron beams and a specific efficient, high current, frequency-tunable device for generating intense radio frequency (RF), microwave electromagnetic fields in a standard rectangular waveguide. The invention utilizes current multiplication of a seed electron beam, comprising an energetic electron beam to impact a thin foil surface with high electric field. The transmissive-electron-multiplier foils also mitigate both space charge expansion and improve beam propagation effects, by shorting of the radially directed electric field at the axial location of the foil(s). Foil thinness and intensity of the exit fields provide for a multiplication process occurring in a fraction of an RF period. Both self-excited oscillator and amplifier configurations are envisaged. Also included is both a self-excited microwave generator and an amplifier, using a temporally modulated laser to generate a seed electron beam that is amplified. Methods to tune the oscillator are described that allow tunability over a full waveguide band. | 7 |
RELATED APPLICATION
This is a continuation-in-part of Ser. No. 273,085, filed June 12, 1981, and now abandoned.
BACKGROUND OF THE INVENTION
The present invention relates to a system and apparatus for coulometrically determining the thicknesses of layers of metallic coatings.
At present, there are known and commercially used instruments for measuring coating thicknesses using the coulometric principles based on Faraday's law. The coating thickness is determined by measuring the total quantity of electricity which is necessary for the anodic dissolution of the coating. To do so, the instruments generally employ a cell containing a supply of suitable electrolyte, a power supply necessary for the electro-chemical dissolution of the coating, an indicator of the start and completion of the dissolution of the coating, a meter for evaluation of the duration of dissolution whereby the thickness is measured, and means for automatically controlling the entire operation. However, the need to guarantee constant electrochemical condition during the course of the measurement, which is a fundamental requisite for desirable repeatability and accuracy of the apparatus leaves much to be desired. In order to obtain repetitive accuracy and reproducibility of the thickness measurement, a cell must be provided which exactly limits the surface area at which the dissolution of the coating takes place, and furthermore insures the supply of the proper electrolyte to the surface. It is this cell which, in the known systems, has numerous disadvantages.
In several of the known devices, the electrolytic cell comprises an open vessel which is filled manually with the electrolyte, using for example, an "eye" dropper, pipette, syringe or the like. During the measuring period, the electrolyte in the vessel is usually agitated in an attempt to insure proper mixture. Cells of this type require a relatively large working area, for example, a diameter equal to 1.5 to 3.5 mm. Such apparatus do not allow measurements on smaller areas, or a dissolution faster than about 20 to 50 μm per minute.
Another known type of cell is equipped with a separate electrolyte reservoir. The electrolyte is fed from the reservoir to the surface area being measured by a pump in an attempt to ensure the exchange of electrolyte at the site being measured. This type of apparatus allows a reduction in the work area being measured to a diameter of 1 mm, but is somewhat complex and difficult to manage, and often results in losses of electrolyte.
Reference can be made to the following showing the relevant prior art:
Kutzelnigg A.: Die Prufung metallischer Uberzuge, (S.71) E. Leuze Verlag, Saulgau, BRD, 1965
Plog H.: Schichtdickenmessung, (S.19), E. Leuze Verlag, Saulgau, BRD, 1967
Biestek T., Sekowski S.: Methoden zur Prufung metallischer Uberzuge (S.100), E. Leuze Verlag, Saulgau, BRD, 1973
Furthermore, experience with the operation of these types of cells confirms that the electrolyte transfer, at the beginning and at the end of the measuring period, causes difficulties when placing the cell on, or removing the cell from the workpiece being measured, because the electrolyte tends to escape from the cell most easily at these times. In addition, an effective electrolyte exchange is not fully assured during operation since a partial blocking of the area being tested might occur through the formation of an air bubble in the cell. As a result, extensive variations in measurement accuracy and reproducibility may be encountered in practice.
It is the object of the present invention to provide a process and apparatus for producing the electrolyte exchange directly in the vicinity of a defined controlled are so as to significantly increase the measuring accuracy, to provide uniform coating dissolution over the area to be measured, reduce the size of the measured area to a value smaller than those presently used, and to increase the measuring speed.
It is an object of the present invention to provide a cell in the form of a probe which can be manually held and which contains the electrolyte, which insures proper exchange of electrolyte, and reliable definition of the situs.
It is the object of the present invention to provide a probe which will eliminate errors caused by ion depletion and improper mix at the surface of measurement. As a result of this, it is possible to reduce the size of the measurement area, decrease the time required for a measurement, and reuse the same electrolyte for successive measurements.
It is another object to provide a probe which is capable of holding the electrolyte, without loss of liquid, while the probe is removed from the test specimen. As a result, the probe now becomes truly portable, which means that the probe with its electrolyte can be moved, without emptying, from one surface area to another, or from one specimen to another.
It is another object to provide a system wherein the probe can be easily filled, emptied, or rinsed, without the use of auxiliary devices, such as eyedroppers or pipettes.
It is another object to provide a system by which measurements of multi-layer coatings requiring different electrolytes can be done without the use of auxiliary devices.
It is another object to provide a probe system composed to two main components; an outer sleeve, and a removable inner electrolyte storage chamber. This inner chamber can be removed and replaced with another chamber holding a different electrolyte, without disturbing the position of the outer sleeve which is in contact with the test specimen.
It is another object of the present invention to provide a probe which can be used on areas which are substantially inclined from the horizontal.
These objects as well as others together with numerous other advantages, will be apparent from the folowing disclosure.
SUMMARY OF THE INVENTION
According to the present invention, the objects enumerated above are provided by an apparatus for measuring by a coulometric process the thicknesses of metallic coatings on any surface, comprising a probe for storing electrolyte solution, a power supply, indicating and controlling circuits, and a device for placing the electrolyte under oscillating pressure pulsation. The probe comprises a cylinder defining a chamber for storage of electrolyte, which is provided at one end with a jet nozzle having a central tube of capillary size, and with a gasket or cuff member adpated to be placed in abutment against the surface to be tested. The opposite end of the cylinder is connected to the source of oscillating pressure which imposes on the electrolyte a corresponding movement against the working surface.
By containing the electrolyte in a substantially closed cylinder connected to a source of oscillating or pulsed pressure, the electrolyte may be, on the one hand, fully contained in the probe even during periods of non-use simply by arresting the source of oscillation in an underpressure mode, and, on other hand, fully exchanged at the site of measurement by continuously placing the electrolyte under pulsating pressure. Thereby, stabilization of the working conditions for dissolution and simultaneous manipulation of the device at the area to be measured is greatly simplifed.
In an advantageous embodiment, the cylinder forming the electrolyte storage chamber comprises an inner body element about which a sleeve-like outer element is secured. The outer sleeve is shaped conformingly similar to the cylinder and is provided with a gasket of cuff-like end extending beyond the end of the jet nozzle. The sleeve has a larger diameter than that of the cylinder and is spaced therefrom to provide an annular chamber. The frontal end of the cuff can serve as the gasket abutting the surface of the workpiece, or a gasket can be placed on it. The diameter of the cuff or the gasket secured to its limits the size of the work area and maintains the orifice of the jet nozzle spaced from the surface of the workpiece.
The annular chamber forms a temporary receiving vessel for the electrolyte or fluid issuing from the jet nozzle and allows electrolyte coming from the face of the workpiece to circulate and mix with fresh electrolyte.
Preferably, the outer sleeve and inner cylindrical body element are removably attached so that inner cylinder bodies can be inter-changed without removal of the sleeve element from the workpiece. In this manner, cylinders storing different electrodes may be successively employed to measure successive different layers of coatings.
It is desirable to insure proper mix of partially depleted electrolyte and fresh electrolyte within the storage chamber itself. To this end, a wall is provided within the cylinder forming the storage chamber, which wall is provided with a small hole. Thus, as the electrolyte moves between the two portions of the storage chamber, it is subject to an increase in velocity, thus assuring proper mixing.
Full details of the present invention are set forth in the accompanying description and in the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWING
In the drawings:
FIG. 1 is a schematic view of an electrolytic system for measuring the thickness of metallic coatings, including a probe therefor embodying the present invention, and
FIG. 2 is a longitudinal sectional view of another probe embodying the present invention.
DESCRIPTION OF THE INVENTION
As seen in FIG. 1, the apparatus of the present invention comprises a probe, generally defined by the numeral 1, which is adapted to be placed in abutting relationship to the surface of the coated metal workpiece P.
The probe 1 is formed of an inner cylindrical body having a radially enlarged rear portion 2 and a radially smaller end portion 3 the forward end 4 of which is conically tapered and terminates in a jet nozzle 5. The jet nozzle 5 is provided with a capillary bore 6 which communicates with the interior of the smaller portion 3. This smaller portion 3 and the larger portion 2 define a storage chamber 7 for electrolyte or other fluid used. The rear end of the cylinder is closed by an end wall 8 in which is formed a nipple 9 to which is removably attached a flexible conduit 10.
The storage chamber 7 is divided by a wall 11 having a central hole therein which on pulsing of the electrolyte increases the velocity of the electrolyte to effect a positive mixture of all the fluid in the storage chamber.
Secured around the forward portion of the cylinder and its terminal nozzle 5 is a correspondingly shaped sleeve 12 which defines with the exterior wall of the cylinder an annular chamber comprising a temporary receiving chamber 13 for electrolyte. The sleeve 12 is secured at its rear end to the enlarged section of the cylinder so as to be removable therefrom. Suitably O-ring seals, snap closures or threaded closures can be used to removably attach the sleeve 12 to the cylinder. The forward end of the sleeve 12 is formed in the shape of a terminal cuff 14, having a length somewhat longer than that of the interior jet nozzle 5 so that its frontal end 15 protrudes sufficiently so that when it abuts the workpiece, a space 16 is left between the workpiece and the orifice of the capillary bore 6.
The space 16 forms a working chamber in which electro chemical reaction with the surface of the workpiece takes place. The cuff 14 may be provided with a rubber gasket or it may be removable and replaced with a rubber gasket or packing.
Operatively, the cylinder defines a storage chamber having two sections, the rear section serving for the accumulation and main storage of electrolyte, the forward or reduced diameter portion defining another chamber in which electrolyte from the rear section and electrolyte at the tip of the probe are intermixed. The hole in wall 11 intensifies mixing of the eletrolyte as it passes between the two sections of the cylinder and in this way, increases chemical uniformity in the electrolyte and utilization of electrolyte. Preferably the section area of the orifice in wall 11 and that of the orifice in terminal nozzle 5 is in a ratio of between 4:1 and 6:1 for a total volume of electrolyte of 1 to 5 ml.
At this ratio of size between the hole in the wall 11 and the orifice 6 of the jet nozzle, liquid i.e. electrolyte passing through the hole, in either direction is caused to increase in velocity thus assuring a thorough agitation of the contents of the storage chamber, and a thorough mixture of the partially depleted electrolyte from the surface of the workpiece with the fresher electrolyte in the storage chamber. Thus, dilution of depleted electrolyte is enhanced and the total electrolyte has a longer useful life. Thus, a single charge of electrolyte therefore need not be discarded only after a few measurements but may be used for a large number of measurements.
The flexible conduit 10 may be connected to an outlet of a manifold distribution assembly, generally indicated by the numeral 17, the inlet of which is connected to a pneumatic pump 18. The manifold 17 can be dispensed with and the conduit connected directly to the pump, if desired.
The pump 18, produces under response of a control and indicating unit 19 a continuous oscillating stream of pneumatic pulses in alternating overpressure and underpressure modes. The control and indicating unit also regulates a power supply 20 which provides current to a cathode conductor such as a platinum wire 21 extending through the cylinder. The cathode wire 21 is attached to the tapered end 4 of the cylinder, which end is preferably clad in or formed of a suitable metal although the remainder of the cylinder need not. A second or ground conductor 22 is provided.
In operation, the apparatus works as follows:
The probe must first be filled with the electrolyte. This is accomplished by dipping front end of the probe into a container having a supply of the proper electrolyte. The pump 18 is then switched on and if the manifold 17 is employed, the valve is located to connect to the desired probe.
The pump 18 induces a reciprocal pneumatic pressure variation within the probe. The operating frequency is preferably maintained between the value of 1 Hz and 3 Hz. During this procedure, successive expulsion of air from the chamber 7 through the capillary bore 6 and sucking in of electrolyte is accomplished.
The storage chamber becomes filled with the electrolyte much in the manner as a fountain pen is filled. After switching off the pump and arresting it in its underpressure or vacuum mode, a small vacuum caused by the removal of the air maintains the electrolyte in the reservoir chamber 7. Thereafter the filled probe is withdrawn and it can then be placed on the area which is to be tested without any loss of electrolyte.
After placement of the probe 1 onto the area to be tested so that the gasket or cuff 14 squarely abuts the surface of the test specimen the pump 18 is switched on again. The induced reciprocal oscillation is transmitted to the storage chamber 7 displacing the electrolyte through the jet nozzle 5 on to the surface of the workpiece P, the area of which is, of course, limited by the gasket or cuff 14. The electrolyte is on one hand intensively exchanged due to the pulsing action; and, on the other hand, applied with pressure by the pulsating action onto the surface of the area to be tested.
Preferably, it will be advantageous to provide that the area of the jet nozzle, in relation to the area of the gasket or cuff element, which limits the area of testing, be within the range of about 1:3 to 1:15. In this case, an oscillating frequency of between 1 Hz and 3 Hz will supply a sufficient amount of working electrolyte to the surface being tested, and cause a sufficient exchange of electrolyte at that area. This arrangement will also eliminate the possibility that the orifice of the probe is blocked by an air bubble.
At an appropriate time, the power supply 20 is activated, providing suitable current and a conventional coulometric transfer by means of the cathodic wire 21 and the cathode 4 is initiated. The detection, sensing and measurement of the quantity of electricity passed then takes place through the indicating and control element 19, in conventional manner.
Specifically, the electrolyte pumped through the nozzle 5 impinges on the surface of the workpiece, and as excess electrolyte is fed, tends to move upwardly into the temporary receiving chamber 13 formed between the sleeve 12 and the lower portion 3 of the inner cylinder. Thus, as the electro-chemical reaction takes place in the working chamber 16, the depleted electrolyte is forced away from this site allowing fresher electrolyte to progress toward the actual site of dissolution. In this manner, a sufficient amount of undepleted electrolyte is always present at the site, and gas bubbles avoided.
An additional advantage of providing the annular temporary receiving chamber lies in the fact that the probe can be employed to measure surfaces which are inclined substantially to the horizontal. Electrolyte circulating from the face of the workpiece accumulates in the receiving chamber to a depth sufficient to maintain contact with both the metallic cathode and the workpiece surface so that no break in the electrolytic circuit occurs, within a wide range of angles.
After the measurement has been completed both the power supply 20 and the pump 18 are automatically switched off. The pump is regulated so that it comes to rest in its underpressure mode. This causes the automatic transfer of the working electrolyte back into the storage chamber 7. The probe can then be removed from the workpiece without any loss of the working electrolyte. The detector probe can then be transferred to another measurement area on the same piece, or a different test specimen without the need for replacement or exchange of the working electrolyte.
Complete retraction of the electrolyte into the storage chamber is assured by a combination of the underpressure on top of the electrolyte, caused by the arresting of the pump in its underpressure mode and the overpressure created in the temporary receiving chamber 13 caused by the compression of the air trapped therein by the circulating fluid. The spring action of the trapped air forces the electrolyte back into the storage chamber where it is held due to the underpressure therein. Consequently, none of the electrolyte is lost when the probe is removed from the workpiece or subsequently placed on a new workpiece. Further, this enables the inner cylinder to be removed from the outer cylinder, also without loss of electrolyte, and its replacement with a different inner cylinder containing a different electrolyte.
In this manner, a sequential measurement of successive layers of different metals can be accomplished without removing the outer sleeve from the site of the workpiece.
In referring to over and underpressure, great pressures in excess of atmospheric pressure or great vacuums are not necessarily required, due to the overall small size of the probe and the small volume of electrolyte employed. Only a small difference in pressure between that at the top of the electrolyte in the storage chamber, and the pressure on the electrolyte at the orifice of the jet nozzle is necessary to effect either pulsation or retraction.
It is preferable that the length of the capillary 6 be between 3 and 12 mm and that the ratio between the area of the capillary 6 and that of area of the orifice of the gasket or cuff 14 be between 1:3 to 1:15. As a result of this ratio, accurate capillary action is obtained with a pulse rate of between 1 Hz and 3 Hz. A further advantage of the present invention lies in the fact that the cathode conductor is placed inside the probe in direct contact with the electrolyte pumping through the probe as a result of the oscillating pressure applied on the electrolyte.
Returning to the drawing, the manifold distribution assembly 17 comprises a distribution valve 23 provided with a rotatable slide member 24, a fixed inlet 25 connectable to the pneumatic pump 18 and a plurality of fixed outlets 26, each of which is adaptable for connection to a flexible conduit 10 associated with an individual cylindrical body. Manipulation of the rotary slide 24 will enable selection of the particular cylindrical body for operation. As a consequence, individual cylindrical bodies may be initially filled with a particular electrolyte, as for example, electrolyte for dissolution of Cu, Cr, Ni respectively. An operator can, thus, easily determine the thickness of successive layers of a multi-layer coating by removing the inner body from the sleeve of the probe being used and replacing it with another inner body having the proper electrolyte, without necessarily removing the outer sleeve from the site on the workpiece. One cylindrical body can be filled with distilled water, and used to rinse the site of the workpiece and/or sleeve before initiating a second electrolytic measurement.
Thus, the invention makes possible repetitive measurements of the thickness of both single-layer or multi-layer coating with maximum utilization of the electrolyte and with greater accuracy. The probe is designed as basic equipment for coulometric measuring system, not only of the type designed in the aforementioned pending application, but with other systems as well.
FIG. 2 shows another embodiment of the probe which is similar to that of FIG. 1. Similar numerals depict similar parts. This embodiment differs in the dimension of the inner cylinder body 1, which in FIG. 2 is substantially smaller in radius and does not include a dividing wall. The nozzle portion is somewhat longer axially and comprises a metallic section 104 which forms the cathode and a plastic tip 105 which forms a jet nozzle. Both the metal cathode and plastic tip have a capillary bore 106 which need not be of the same diameter. The outer sleeve 112 extends substantially the full length of the probe and is provided with an O-ring seal 113 and a ring connector 114. The tip of the probe is provided with a rubber gasket 115 which is removable. Operation is similar as in the previously described embodiment.
The present invention provides conditions for a uniform anodic dissolution of the coating on the surface of the test specimen during the entire time interval during which dissolution takes place and for obtaining reproduceable and accurate measurements. Increased speeds of dissolution at a rate greater than heretofore known has also been obtained.
Optimum setting of the operating pulse frequency for pumping the electrolyte solution, their time behavior and amplitude, and of the ratio of nozzle diameter in the working chamber to the diameter of the area being tested can likewise be obtained by the present invention by simple selection of the oscillator control and the probe dimensions.
In addition, the entire area and volume for the entire interval of measurement is optimized. At static connection of the dissolving current supply, errors in determination, generally caused by variable conditions frequent in conventional apparatus, is avoided.
Although the invention is illustrated and described with reference to preferred embodiments thereof, it is to be expressly understood that it is in no way limited to the disclosure of such embodiments, but it is capable of numerous modifications within the scope of the appended claims. | The thicknesses of metallic coatings on a surface is coulometrically measured employing a probe for storing electrolyte solution provided with a power supply and indicating and controlling circuits. The probe comprises a cylinder defining a chamber for storage of electrolyte and having at one end a nozzle of capillary size surrounded by a gasket or cuff adapted to be placed in abutment against the surface to be tested. The opposite end of the cylinder is connected to a source of oscillating pressure which imposes on the electrolyte a corresponding movement against the working surface. | 6 |
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of application Ser. No. 10/204,869 now abandoned filed Dec. 5, 2002 which is a national stage filing of PCT/DE01/00760 filed Feb. 28, 2001 claiming priority to DE 100 09 510.0 filed Feb. 29, 2000.
TECHNICAL FIELD
The present invention relates to a semiwet feed product, a process for its production, a method for its packaging and the product by the latter method.
BACKGROUND OF THE INVENTION
Semiwet feeds, particularly for domestic animals such as dogs and cats, are conventionally produced by extrusion, followed by the cutting up of the extruded strand or extrudate and then frying the cut off pieces yielding products with a moisture content of approximately 17 to 22%.
The packaging of such products gives rise to problems in that due to excessive compression of the product pieces which have a fatty outside they stick together after a short time to form a block, which makes it difficult to separate the product for portioning on feeding after the opening of the pack and may even make it in part impossible. Thus, the vacuum packaging of such products is impossible. This requires a large amount of space during transportation and storage.
The problem of the present invention is therefore to provide a semiwet feed product, in which the described problems can be avoided and which can in particular be packed in space and cost-saving manner.
BRIEF SUMMARY OF THE INVENTION
According to the invention, this problem is solved by a semiwet feed product, which has a wrapping coating applied by a vacuum coating method.
In a preferred embodiment the wrapping coating is fat-containing and in particular in preferred manner contains further nutrients and/or supplements, particularly a trace element mixture.
The invention also relates to a process for the production of a semiwet feed product, in which the product pieces extruded, cut and optionally dried to the desired moisture content in the conventional manner are provided in a vacuum coating method with a wrapping coating, which is preferably fat-containing and in particularly preferred manner contains further nutrients and/or supplements, particularly a trace element mixture.
The invention also relates to a method for the packaging of the semiwet feed product according to the invention, in which in conventional manner the product is introduced into a plastic bag pack and prior to the final sealing of the packs is compressed and shaped by exerting pressure on the product.
The invention finally relates to a packed feed product manufactured according to the aforementioned method.
DETAILED DESCRIPTION OF THE INVENTION
It has surprisingly been found that a semiwet feed product provided with a wrapping coating applied by a vacuum coating method, unlike conventional fried products, has no block formation tendency (as described hereinbefore) when packed, accompanied by compression, in a conventional plastic bag pack. Even after storage for several weeks or months a problem-free separation and therefore portioning of the pack content is possible on opening the pack. It is possible in this way to pack a semiwet feed product in a compressed, space-saving form. Compression leads to a distinct bulk density increase and permits an almost random shaping of the pack. In addition, such a product is very uniformly covered with the coating and, despite a similar fat content, has a less fatty feel and is therefore more pleasant for handling by the pet owner. The semiwet feed product wrapped by the vacuum coating method has a very flexible, soft texture, which is highly advantageous from the esthetic standpoint.
Such a product is obtained that the product pieces extruded, cut and optionally dried to the desired moisture content in the conventional manner are provided in a vacuum coating method with a preferably fat-containing wrapping coating. Such vacuum coating methods are known per se from the prior art.
For the application of vacuum coating methods on filling feed pieces with additional substances reference is made to U.S. Pat. Nos. 4,371,556; 861,606 and 5,716,655. However, they all relate to applications in connection with dry products and make no reference to the described advantages in connection with semiwet feed products.
In vacuum coating methods, the product pieces are exposed to a vacuum and in this state, i.e. under a reduced pressure, are covered with a flowable coating material. In an exemplified method, an extruded strand leaves the extruder at a temperature of approximately 100° C. . Normally the moisture content at this point is approximately 25%. Either before or after cutting, the extruded product can, if necessary, be dried to the desired final moisture content of between 17 and 22%.
Subsequently, the product pieces are filled into a corresponding mixer. The mixer filling opening is closed and the internal pressure is reduced within a relatively short time of e.g. approximately 15 seconds to e.g. approximately 200 millibar. Subsequently the coating material (e.g. fat with a trace element mixture) is introduced into the mixer and the extruded material is mixed therewith. The pressure in the mixer is then again raised to ambient temperature, which leaves a product provided with a corresponding wrapping, which can be subsequently supplied to a standard packaging station.
In said packaging station the product is filled in per se known manner into a plastic bag pack of corresponding size. By exerting pressure the content is compressed and shaped, before the pack is finally sealed in the conventional manner.
The features of the invention disclosed in the above description, the drawings and claims can be essential to the implementation of the different embodiments of the invention, either singly or in random combination. | Semiwet feed product with a wrapping coating applied by a vacuum coating method, process for the manufacture of such a product, method for packaging the same and product packed using said method. | 0 |
BACKGROUND OF THE INVENTION
This invention relates generally to human limb bracing techniques, and more particularly concerns an athletic knee orthosis having uncommonly favorable characteristics.
The field of sports medicine has evolved in the past few years from a fledgling with basically no following into a growing, viable, integral part of orthopaedic surgery. In the past, little thought went into mechanism of injury, post injury rehabilitation, and return to active sports participation.
Within the last few years, major advances have been made in all of the above, including bracing techniques. For years the standard of post knee injury was an elastic knee cage. This evolved into the so-called Lennox-Hill brace and its modifications. While that brace was effective; because of its bulky nature it has not met the needs of many professional as well as "weekend" athletes. Also the Lennox-Hill type braces could not be worn with the type of garment necessary for this sports activity, and typically were left in the back seat of the car when the participant returned to his racing activity.
SUMMARY OF THE INVENTION
It is a major object of the invention to provide an orthosis that overcomes the disadvantages and difficulties of prior braces, and which affords unusual advantages of its own. Basically, the device comprises:
(a) a first elongated rigid member attachable to the side of the upper leg while extending generally in the direction thereof,
(b) a second elongated rigid member attachable to the side of the lower leg while extending generally in the direction thereof,
(c) means pivotably coupling the members, proximate the knee location, and
(d) intermeshed gear parts respectively carried by the members to relatively rotate as either of the members pivots relative to the other of said members.
These and other objects and advantages of the invention, as well as the details of an illustrative embodiment, will be more fully understood from the following description and drawings, in which:
DRAWING DESCRIPTION
FIG. 1 is a side elevation showing the orthosis device in extended condition;
FIG. 2 is a section taken on lines 2--2 of FIG. 1;
FIG. 3 is a frontal view like FIG. 1, but showing the device applied to the leg of a user;
FIG. 4 is a rear elevation of the device as seen in FIG. 3;
FIG. 5 is an elevation showing gearing interconnecting orthosis device members; and
FIG. 6 is a view taken on lines 6--6 of FIG. 1.
DETAILED DESCRIPTION
The illustrated device 10 includes a first elongated member such as lightweight metal bar or link 11 attachable to the outer side (see FIG. 3) of the upper leg 12 of the user, to extend in the direction of that upper leg (i.e. thigh) above the knee 13. The device 10 also includes a second elongated member such as lightweight metal bar or link 14 attachable to the outer side (see FIG. 3) of the lower leg (i.e. calf) 15 of the user, to extend in the direction of that lower leg, below the knee. Members 11 and 15 may consist of aluminum for example.
Also provided is means pivotally coupling the members, proximate the knee location, together with intermeshed gear parts respectively carried by the members to relatively rotate as either of the members pivots relative to the other of the members, thereby controlling such relative rotation. In the example, such means is shown to include two pivots at 16 and 17 having spaced, parallel axes 20 and 21 (which are horizontal if the members 11 and 14 extend in a vertical plane), the pivots connected by parallel links 18 and 19 as shown in FIG. 6. Thus, were it not for the gearing to be described, the members 11 and 14 could freely and independently pivot about pivot axes 20 and 21. The gearing is shown to include spur gear teeth 22 on the lower end of member 11 meshing with spur gear teeth 23 on the upper end of member 14, teeth 22 centered about axis 20, and teeth 23 centered about axis 21. As a result, member 11 can rotate clockwise about axis 20 only if member 14 rotates counterclockwise about axis 21, and vice versa; alternatively, member 14 can rotate counterclockwise about axis 21, in FIG. 3, only if links 18 and 19 swing counterclockwise about axis 20, with member 11 not rotated about axis 20, and vice versa, and member 11 can rotate counterclockwise about axis 21 only if links 18 and 19 swing counterclockwise about axis 21, with member 14 not rotated about axis 20, and vice versa. Combinations of these movements can also occur. Accordingly, good control, with stability, over leg movement is achieved, when member 11 is connected to upper leg 12, and member 14 is connected to lower leg 15.
Unusually advantageous means to attach the members 11 and 14 to the upper and lower leg elements will now be described. First strap means, as at 25 is carried by first member 11, and second strap means, as at 26, is carried by second member 14. The first means 25 includes a relatively wide first elastic strap 25a having an end 25b anchored as by pad 27 to first member 11, and opposite end 25c, and adapted to be wound tightly about the upper leg. The second strap means as at 26 includes a relatively wide second elastic strap 26a having an end anchored as by pad 28 to second member 14, and an opposite end 26c, and adapted to be wound tightly about the lower leg. Pads 27 and 28 are C-shaped or arcuate (see FIG. 2), so that their concave sides fit the wearer's upper and lower legs, as in FIG. 2. They may consist of leather, for example, and contain corresponding C-shaped metal inserts 29 integral with the members 11 and 14.
VELCRO connections are provided on the straps 25 and 26 to hold them in wound condition on the wearer's legs. Thus, VELCRO connection 30 on a leather end extension 31 of strap 25 is adapted to engage VELCRO connection 32 on pad 27; and VELCRO connection 33 on a leather end connection 34 or strap 26 is adapted to engage VELCRO connection 35 on pad 28. The members 11 and 14 are then tightly held to the user's upper and lower legs (see FIG. 3).
The first strap means may also, with unusual advantage include a relatively narrow non-elastic primary strap 40 having an end 40a anchored at 41 to the upper member 11, and so as to extend at an angle α relative to the first strap 25a (see FIG. 1); and having a free opposite end 40b, the strap adapted to be wound about the rear of the knee for connection to the lower member. See for example in FIGS. 3 and 4 the extension of the strap 40 behind the knee at 40c, and then passage of the strap through metallic loop 42 attached to member 14, the strap free end 40b then turned back for connection to the strap 40 (see FIG. 4), as via VELCRO 40b' on free end 40b, and VELCRO 43 on a pad 44 slidable on and along strap 40.
Similarly, the second strap means may also, with unusual advantage, include a relatively narrow, non-elastic secondary strap 50 having an end 50a anchored at 51 to lower member 14, and so as to extend at an angle β relative to the second strap 26a; and having a free opposite end 50b, the strap adapted to be wound about the rear of the knee (in criss-cross relation to strap 40) for connection to the upper member 11. See for example in FIGS. 3 and 4 the extension of the strap 50 behind the knee at 50c, and then passage to the strap through metallic loop 52 attached to member 11 via connection 41, the strap free end 50b then turned back for connection to the strap 50 as via VELCRO 50b' on free end 50b, and VELCRO 53 on a pad 54 slidable on and along strap 50. When straps 40 and 50 are thus tightened, the upper and lower members 11 and 14 are further interconnecting, for stability, and in a manner that causes the strap attachments to the members 11 and 14 via loops 42 and 52 to move apart, relatively, while the strap connection at 40a and 50a to the members 11 and 14 move relatively toward one another, during leg flexing, for stability.
The user way wear a pantleg such as a polyurethane sleeve over his calf, knee and thigh, and the brace adapts itself readily thereto. Thus, pads 27 and 28 may carry VELCRO 60 at their concave inner sides, to connect to such a sleeve. | A knee orthosis incorporates first and second elongated rigid members attachable to the sides of upper and lower leg extents; together with means pivotally coupling the members proximate the knee location, and inter-meshed gear parts respectively carried by the members to relatively rotate as either of the rigid members pivots. Multiple adjustable attachment straps are also provided, two of the straps extending in criss-cross relations behind the knee. | 0 |
This application is a continuation of application no. PCT/DK02/00859, filed Dec. 16, 2002, and claims priority under 35 U.S.C. §119(e) of provisional application 60/342,653, filed Dec. 20, 2001. Each prior application is hereby incorporated by reference, in its entirety.
The present invention relates to novel compounds which are glycine transporter inhibitors and as such effective in the treatment of disorders in the CNS.
BACKGROUND OF THE INVENTION
Glutamic acid is the major excitatory amino acid in the mammalian central nervous system (CNS), and acts through two classes of receptors, the ionotropic and metabotrobic receptors, respectively. The ionotropic glutamate receptors are divided into three subtypes based on the affinities of agonists for these receptors, namely N-methyl- D -aspartate (NMDA), (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propanoic acid (AMPA) and kainic acid (or kainate) receptors.
The NMDA receptor contains binding sites for modulatory compounds such as glycine and polyamines. Binding of glycine to its receptor enhances the NMDA receptor activation. Such NMDA receptor activation may, be a potential target for the treatment of schizophrenia and other diseases linked to NMDA receptor dysfunction. An activation can be achieved by an inhibitor of the glycine transporter.
Molecular cloning has revealed the existence of two types of glycine transporters, GlyT-1 and GlyT-2, wherein GlyT-1 can be further subdivided into GlyT-1a, GlyT-1b and GlyT-1c.
The NMDA receptor is blocked by compounds such as phencyclidine which induce a psychotic state which resembles schizophrenia. Likewise, the NMDA antagonists, such as ketamine, induce negative and cognitive symptoms similar to schizophrenia. This indicates that NMDA receptor dysfunction is involved in the pathophysiology of schizophrenia.
The NMDA receptor has been associated with a number of diseases, such as pain (Yaksh Pain 1989, 37, 111–123), spasticity, myuoclonus and epilepsy (Truong et. al. Movement Disorders 1988, 3, 77–87), learning and memory (Rison et. al. Neurosci. Biobehav. Rev . 1995, 19, 533–552).
Glycine transporter antagonists or inhibitors are believed to be highly beneficial in the treatment of schizophrenia (Javitt WO 97/20533).
Glycine transport antagonists or inhibitors could be useful for the treatment of both the positive and the negative symptoms of schizophrenia and other psychoses, and in the improvement of cognition in conditions where the cognitive processes are diminished, i.e. Alzheimer's disease, multi-infarct dementia, AIDS dementia, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis or diseases wherein the brain is damaged by inner or outer influence, such as trauma to the head or stroke. Likewise, convulsive disorders such as epilepsy, spasticity or myoclonus may benefit from glycine transporter antagonists.
Clinical trials with glycine have been reported, Javitt et. al. Am. J. Psychiatry 1994, 151, 1234–1236 and Leiderman et. al. Biol. Psychiatry 1996, 39, 213–215. The treatment with high-dose glycine is reported to improve the symptoms of schizophrenia. There is a need for more efficient compounds for the treatment of NMDA associated diseases.
The present invention provides compounds which are potent inhibitors of the glycine transporter and consequently they are useful in treating diseases associated with NMDA dysfunction.
SUMMARY OF THE INVENTION
The present invention provides compounds of the general formula I
Y is N, C or CH;
X represent O or S;
m is 1 or 2;
p is 0, 1, 2, 3 or 4;
q is 0, 1 or 2;
s is 0, 1, 2 or 3;
r is 0, 1 or 2;
Q represents C, P—OR 5 , or S═O, wherein R 5 represents hydrogen or C 1-6 -alkyl;
A is OR 6 wherein R 6 represent hydrogen, C 1-6 -alkyl, aryl or aryl-C 1-6 -alkyl, wherein aryl may be substituted with halogen, CF 3 , OCF 3 , CN, NO 2 or C 1-6 alkyl;
AR represents phenyl or a heteraryl;
Each R 4 individually represents C 1-6 -alkyl, C 3-8 -cycloalkyl or C 3-8 -cycloalkyl-C 1-6 -alkyl;
The dotted line represents an optional bond;
Each R 1 , which may be identical or different, is independently selected from the group consisting of C 1-6 -alkyl, or two R 1 , s attached to the same carbon atom may form a 3–6-membered spiro-attached cyclo-alkyl;
Each R 2 , which may be identical or different, is independently selected from the groups consisting of halogen, cyano, nitro, C 1-6 -alk(en/yn)yl, C 1-6 -alk(en/yn)yloxy, C 1-6 -alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yloxy, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, acyl, C 1-6 -alk(en/yn)yloxycarbonyl, C 1-6 -alk(en/yn)ylsulfonyl or —NR 9 R 10 wherein R 9 and R 10 independently represent hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 alk(en/yn)yl or aryl, or R 9 and R 10 together form a 3–7-membered ring which optionally contains one further heteroatom;
Each R 3 , which is substituted on AR, may be identical or different, is independently selected from a group consisting of halogen, cyano, nitro, C 1-6 -alk(en/yn)yl, C 1-6 -alk(en/yn)yloxy, C 1-6 -alk(en/yn)ylsulfanyl, hydroxy, hydroxy-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yloxy, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, C 1-6 -alk(en/yn)ylsulfonyl, aryl, aryl-C 1-6 -alk(en/yn)yloxy, aryl-C 1-6 -alk(en/yn)yl, C 1-6 -alk(en/yn)yloxycarbonyl, acyl, —NHCO—C 1-6 -alk(en/yn)yl, —CONR 11 R 12 wherein R 11 and R 12 independently represent hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl or aryl, or R 11 and R 12 together with the nitrogen to which they are attached form a 3–7-membered ring which optionally contains one further heteroatom;
or NR 13 R 14 wherein R 13 and R 14 independently represent hydrogen, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl or aryl; or R 13 and R 14 together with the nitrogen to which they are attached form a 3–7-membered ring which optionally contains one further heteroatom;
or two adjacent R 3 substituents together form a ring fused to the AR ring selected from the group consisting of
wherein W is O or S, and R′ and R″ are hydrogen or C 1-6 -alkyl:
or two adjacent R 3 substituents together form a heteroaryl containing one or two heteroatom fused to the AR,
or an acid addition salt thereof.
In case of the integers p, q, r or s being 0, the substituents are hydrogen.
If Y represents C, the dotted line is present. The dotted line is not present if Y represents N or CH.
The invention provides a compound of formula I as above for use as a medicament.
The invention provides a pharmaceutical composition comprising a compound of formula I as above or a pharmaceutically acceptable acid addition salt thereof and at least one pharmaceutically acceptable carrier or diluent.
The invention provides the use of a compound of formula I as above or a pharmaceutically acceptable acid addition salt thereof for the preparation of a medicament for the treatment of diseases selected from the group consisting of schizophrenia, including both the positive and the negative symptoms of schizophrenia and other psychoses, and in the improvement of cognition in conditions where the cognitive processes are diminished, i.e. Alzheimer's disease, multi-infarct dementia, AIDS dementia, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis or diseases wherein the brain is damaged by inner or outer influence, such as trauma to the head or stroke, and convulsive disorders such as epilepsy, spasticity or myoclonus.
The invention provides a method for the treatment of diseases selected from the group consisting of schizophrenia, including both the positive and the negative symptoms of schizophrenia and other psychoses, and in the improvement of cognition in conditions where the cognitive processes are diminished, i.e. Alzheimer's disease, multi-infarct dementia, AIDS dementia, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis or diseases wherein the brain is damaged by inner or outer influence, such as trauma to the head or stroke, and convulsive disorders such as epilepsy, spasticity or myoclonus in a living animal body, including a human, comprising administering a therapeutically effective amount of a compound of formula I as above or a pharmaceutically acceptable acid addition salt thereof.
DETAILED DESCRIPTION OF THE INVENTION
A preferred embodiment of the invention is wherein Y is N;
A preferred embodiment of the invention is wherein X is S;
A preferred embodiment of the invention is wherein Q is C;
A preferred embodiment of the invention is wherein A is OH;
A preferred embodiment of the invention is wherein p is 1 or 2.
A preferred embodiment of the invention is wherein m is 1;
A preferred embodiment of the invention is wherein q is 0.
A preferred embodiment of the invention is wherein r is 0 or 1;
A preferred embodiment of the invention is wherein s is 1 or 2.
A preferred embodiment of the invention is wherein AR is phenyl, thiophene, pyridyl, pyrimidyl, thiazolyl, imidazolyl or benzothizolyl;
A preferred embodiment of the above is wherein R 4 is CH 3 ;
A preferred embodiment of the invention is wherein AR is phenyl, r and q are both 0, p is 1 or 2, s is 1 or 2, r is 0 or 1; m is 1, R 1 is CH 3 , A is OH, Q is C, Y is N and X is S;
An even more preferred embodiment of above is wherein each R 3 is independently selected from halogen, C 1-6 -alkoxy or C 1-6 -alkyl;
An even more preferred embodiment of the above is wherein R 3 is selected from the group consisting of Cl, F, OCH 3 , t-butyl, 2-propyl or methyl;.
Particularly preferred embodiments of the invention are wherein the compound of the invention is any of the following:
(+/−)-{4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-Chloro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-Fluoro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-iso-Propyl-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid (+/−)-2-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethylpiperazin-1-yl}-propionic acid {4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2(R)-methyl-piperazin-1-yl}-acetic acid {4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-2(R),5(S)-dimethyl-piperazin-1-yl}-acetic acid {4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2,2-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[5-Chloro-2-(4-trifluoromethyl-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid {4-[5-Chloro-2-(3-methoxy-phenylsulfanyl)-phenyl]-2(R)-methyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-Phenyl-phenyloxy)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-Methyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(4-iso-Propyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-{4-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid (+/−)-2-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-3-methylpiperazin-1-yl}-propionic acid {4-[2-(4-Isopropyl-phenylsulfanyl)-phenyl]-piperazin-1-yl}-acetic acid (+/−)-2-{4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-3-methyl-piperazin-1-yl}-propionic acid
or a pharmaceutically acceptable acid addition salt thereof.
Definition of Substituents
Halogen means fluoro, chloro, bromo or iodo.
The expression C 1-6 -alk(en/yn)yl means a C 1-6 -alkyl, C 2-6 -alkenyl, or a C 2-6 -alkynyl group. The expression C 3-8 -cycloalk(en)yl means a C 3-8 -cycloalkyl- or cycloalkenyl group.
The term C 1-6 alkyl refers to a branched or unbranched alkyl group having from one to six carbon atoms inclusive, including but not limited to methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methyl-2-propyl and 2-methyl-1-propyl.
Similarly, C 2-6 alkenyl and C 2-6 alkynyl, respectively, designate such groups having from two to six carbon atoms, including one double bond and one triple bond respectively, including but not limited to ethenyl, propenyl, butenyl, ethynyl, propynyl and butynyl.
The term C 3-8 cycloalkyl designates a monocyclic or bicyclic carbocycle having three to eight C-atoms, including but not limited to cyclopropyl, cyclopentyl, cyclohexyl, etc.
The term C 3-8 cycloalkenyl designates a monocyclic or bicyclic carbocycle having three to eight C-atoms and including one double bond.
In the term C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl and C 1-6 -alk(en/yn)yl are as defined above.
The terms C 1-6 -alk(en/yn)yloxy, C 1-6 alk(en/yn)ylsulfanyl, hydroxy-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yl, halo-C 1-6 -alk(en/yn)yloxy, C 1-6 -alk(en/yn)ylsulfonyl etc. designate such groups in which the C 1-6 -alk(en/yn)yl are as defined above.
As used herein, the term C 1-6 -alk(en/yn)yloxycarbonyl refers to groups of the formula C 1-6 -alk(en/yn)yl-O—CO—, wherein C 1-6 -alk(en/yn)yl are as defined above.
As used herein, the term acyl refers to formyl, C 1-6 -alk(en/yn)ylcarbonyl, arylcarbonyl, aryl-C 1-6 -alk(en/yn)ylcarbonyl, C 3-8 -cycloalk(en)ylcarbonyl or a C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl-carbonyl group.
The term 3–7-membered ring optionally containing one further heteroatom as used herein refers to ring systems such as 1-morpholinyl, 1-piperidinyl, 1-azepinyl, 1-piperazinyl, 1-homopiperazinyl, 1-imidazolyl, 1-pyrrolyl, or 1-pyrazolyl, all of which may be further substituted with C 1-6 -alkyl.
The term heteroaryl may represent 5-membered monocyclic rings such as 3H-1,2,3-oxathiazole, 1,3,2-oxathiazole, 1,3,2-dioxazole, 3H-1,2,3-dithiazole, 1,3,2-dithiazole, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1H-1,2,3-triazole, isoxazole, oxazole, isothiazole, thiazole, 1H-imidazole, 1H-pyrazole, 1H-pyrrole, furan or thiophene and 6-membered monocyclic rings such as 1,2,3-oxathiazine, 1,2,4-oxathiazine, 1,2,5-oxathiazine, 1,4,2-oxathiazine, 1,4,3-oxathiazine, 1,2,3-dioxazine, 1,2,4-dioxazine, 4H-1,3,2-dioxazine, 1,4,2-dioxazine, 2H-1,5,2-dioxazine, 1,2,3-dithiazine, 1,2,4-dithiazine, 4H-1,3,2-dithiazine, 1,4,2-dithiazine, 2H-1,5,2-dithiazine, 2H-1,2,3-oxadiazine, 2H-1,2,4-oxadiazine, 2H-1,2,5-oxadiazine, 2H-1,2,6-oxadiazine, 2H-1,3,4-oxadiazine, 2H-1,2,3-thiadiazine, 2H-1,2,4-thiadiazine, 2H-1,2,5-thiadiazine, 2H-1,2,6-thiadiazine, 2H-1,3,4-thiadiazine, 1,2,3-triazine, 1,2,4-triazine, 2H-1,2-oxazine, 2H-1,3-oxazine, 2H-1,4-oxazine, 2H-1,2-thiazine, 2H-1,3-thiazine, 2H-1,4-thiazine, pyrazine, pyridazine, pyrimidine, 4H-1,3-oxathiin, 1,4-oxathiin, 4H-1,3-dioxin, 1,4-dioxin, 4H-1,3-dithiin, 1,4-dithiin, pyridine, 2H-pyran or 2H-thiin.
The term aryl refers to carbocyclic, aromatic systems such as phenyl and naphtyl.
The acid addition salts of the invention are preferably pharmaceutically acceptable salts of the compounds of the invention formed with non-toxic acids. Exemplary of such organic salts are those with maleic, fulmaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic and theophylline acetic acids, as well as the 8-halotheophyllines, for example 8-bromotheophylline. Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids.
Further, the compounds of this invention may exist in unsolvated as well as in solvated forms with pharmaceutically acceptable solvents such as water, ethanol and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of this invention.
Some of the compounds of the present invention contain chiral centres and such compounds exist in the form of isomers (i.e. enantiomers or diastereomers). The invention includes all such isomers and any mixtures thereof including racemic mixtures.
Racemic forms can be resolved into the optical antipodes by known methods, for example, by separation of diastereomeric salts thereof with an optically active acid, and liberating the optically active amine compound by treatment with a base. Another method for resolving racemates into the optical antipodes is based upon chromatography on an optically active matrix. Racemic, compounds of the present invention can also be resolved into their optical antipodes, e.g. by fractional crystallization of d- or 1-(tartrates, mandelates or camphorsulphonate) salts. The compounds of the present invention may also be resolved by the formation of diastereomeric derivatives.
Additional methods for the resolution of optical isomers, known to those skilled in the art, may be used. Such methods include those discussed by J. Jaques, A. Collet and S. Wilen in “Enantiomers, Racemates, and Resolutions”, John Wiley and Sons, New York (1981).
Optically active compounds can also be prepared from optically active starting materials.
Pharmaceutical Compositions
The pharmaceutical formulations of the invention may be prepared by conventional methods in the art. For example: Tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting machine: Examples of adjuvants or diluents comprise: corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings, preservatives etc. may be used provided that they are compatible with the active ingredients.
Solutions for injections may be prepared by dissolving the active ingredient and possible additives in a part of the solvent for injection, preferably sterile water, adjusting the solution to desired volume, sterilising the solution and filling it in suitable ampules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc.
The pharmaceutical compositions of this invention or those which are manufactured in accordance with this invention may be administered by any suitable route, for example orally in the form of tablets, capsules, powders, syrups, etc., or parenterally in the form of solutions for injection. For preparing such compositions, methods well known in the art may be used, and any pharmaceutically acceptable carriers, diluents, excipients or other additives normally used in the art may be used.
Conveniently, the compounds of the invention are administered in unit dosage form containing said compounds in an amount of about 0.01 to 100 mg. The total daily dose is usually in the range of about 0.05–500 mg, and most preferably about 0.1 to 50 mg of the active compound of the invention.
The compounds of the invention are prepared by the following general methods: Alkylation of an amine of formula II with an alkylating agent of formula III
L is a suitable leaving group such as halogen or tosylate. The substituents AR, R 1 -R 4 , Y, Q, X, A, m, p, q, r and s are as defined above. The reaction is typically performed in a suitable solvent such as ethanol, N,N-dimethylformamide or acetonitrile containing an inorganic base such as potassium or cesium carbonate or an organic base such N-ethyl diisopropylamine at an elevated temperature of 40–120° C. Compounds of formula I wherein Q is carbon and A is OR 6 wherein R 6 is hydrogen may be prepared from the corresponding esters COOR 6 wherein R 6 is an insoluble polymer or C 1-6 -alkyl, aryl or aryl-C 1-6 -alkyl. The transformation may be performed under basic conditions, for example, using aqueous sodium hydroxide in an alcoholic solvent or acidic conditions for R 6 being a tertiary-butyl group or an insoluble polymer.
Compounds of Formula II May be Prepared by any of the Following Reactions:
a) Chemical transformation of a compound with formula IV
wherein R 1 , R 2 , m, p, q, X, Y and Z are as described above, to the corresponding diazonium compound, and subsequently react with a compound HX-AR-(R 3 ) s , wherein AR, X, R 3 and s are as defined above.
b) A chemical synthesis as depicted in scheme I
wherein AR, R 1 , R 2 , R 3 , s, m, p, q and X are as described above and the circled S represents the solid support.
c) A chemical synthesis as depicted in scheme II where X is O and Y is N.
d) A chemical transformation of a compound of formula V
wherein R 2 , R 3 , X, s and q are as described above and G is a bromine or iodine atom with a compound of formula VI
wherein R 1 , m and p are as defined above.
e) Dehydrating and optionally simultaneously deprotecting a compound of formula VII
wherein R 1 , R 2 , R 3 , X, m, p, q and s are as described above and R is either a hydrogen atom or a BOC group.
f) Hydrogenation of the double bond in a compound of formula VIII
wherein R 1 , R 2 , R 3 , X, m, p, q and s are as described above.
g) Deoxygenation and deprotection of a compound of formula VII
wherein R 1 , R 2 , R 3 , X, m, p, q and s are as described above and R is either a hydrogen atom or a BOC group.
The diazotation followed by reaction with a compound HS—Ar—(R 3 ) s according to method a) is performed by addition of the diazonium salt of the corresponding aniline to a solution of sodium salt of a thiophenol in water containing a copper suspension. The starting material of formula IV is prepared as outlined in the following. A fluoronitrobenzene derivative is reacted with a piperazine derivative in a solvent such as DMF, NMP or other dipolar aprotic solvent containing an organic base such as triethylamine to afford the orthonitophenylpiperazine derivative. The nitro group is then reduced using standard procedures known to those skilled in the art to give the starting material of formula IV.
For 2,5-dimethylpiperazine derivatives the N-Benzyl-2(R),5(S)-dimethylpiperazine was prepared according to known literature procedures (Aicher et al J. Med. Chem . 2000, 43, 236–249). N-Benzyl-2(S),5(R)-dimethylpiperazine was prepared according to patent application WO 00/71535.
The reaction sequence in method b) is prepared according to the methods described in patent application WO 01/49681. The diamines are either commercially available or synthesised by methods known to chemists skilled in the art. Iron-complexes, like η 6 -1,2-dichlorobenzene-η 5 -cyclopentadienyliron(II) hexafluorophosphate and substituted analogues are synthesised according to literature known procedures (Pearson et al. J. Org. Chem . 1996, 61, 1297–1305) or synthesised by methods known to chemists skilled in the art.
The starting material in method c) is prepared by the coupling of an ortho bromophenol with a suitable aryl-boronic acid or boronate ester in a known literature procedure (Evans et al, Tet. Lett , 1998, 39, 2947–2940). The resulting biarylether bromide is then coupled using palladium catalysis to a protected piperazine where the protective group may be typically but not exclusively a tert-butyloxycarbonyl (BOC) derivative or benzyloxycarbonyl (CBZ) and the protecting group (PG) is then removed by acidic cleavage for example using hydrogen chloride in an alcoholic solvent for removal of the BOC group or catalytic hydrogenolysis in the case of the a CBZ removed to give intermediates of formula II where X is O and Y is N. The general methods for removal of suitable protecting groups are described in the textbook Protective Groups in Organic Synthesis T. W. Greene and P. G. M. Wuts, Wiley Interscience, (1991) ISBN 0471623016.
The reaction of a compound of formula V with a diamine of formula VI in method d) was performed in a similar manner as described in Nishiyama et al. Tetrahedron Lett . 1998, 39, 617–620. The starting material of formula VI was prepared in a similar manner as described in Schopfer et al. Tetrahedron 2001, 57, 3069–3073.
The dehydration reaction and optional simultaneous deprotection of a compound of formula VII in method e) was performed in a similar manner as described in Palmer et al J. Med. Chem . 1997, 40, 1982–1989. The starting material of formula VII was prepared from a compound of formula VII wherein R is a BOC group by deprotection with hydrochloric acid in methanol. Compounds of formula VII may be prepared as described in Palmer et al. J. Med. Chem . 1997, 40, 1982–1989.
The reduction of the double bond according to method f) is generally performed by catalytic hydrogenation at low pressure (<3 atm.) in a Parr apparatus, or by using reducing agents such as diborane or hydroboric derivatives as produced in situ from NaBH 4 in trifluoroacetic acid in inert solvents such as tetrahydrofuran (THF), dioxane, or diethyl ether.
The deoxygenation of tertiary alcohol intermediates of formula VII in method g) wherein R is a BOC group, was performed by a modified Barton reduction in a similar manner as described in Hansen et al. Synthesis 1999, 1925–1930. The intermediate tertiary alcohols were prepared from the corresponding properly substituted 1-bromo-phenylsulfanylbenzenes or their corresponding ethers by metal-halogen exchange followed by addition of an appropriate electrophile of the formula IX in a similar manner as described in Palmer et al. J. Med. Chem. 1997, 40, 1982–1989. The properly substituted 1-bromo-phenylsulfanylbenzenes were prepared in a similar manner as described in the literature by reaction of properly substituted thiophenols with properly substituted aryliodides according to Schopfer and Schlapbach Tetrahedron 2001, 57 3069–3073 Bates et al., Org. Lett. 2002, 4, 2803–2806 and Kwong et al. Org. Lett. 2002, 4, (in press). The corresponding substituted 1-bromo-phenoxybenzenes may be prepared as described by Buck et al. Org. Lett. 2002, 4, 1623–1626. Removal of the BOC group was performed by standard methods known to those skilled in the art
EXAMPLES
General Methods
Analytical LC-MS data were obtained on a PE Sciex API 150EX instrument equipped with IonSpray source and Shimadzu LC-8A/SLC-10A LC system. Column: 30×4.6 mm Waters Symmmetry C18 column with 3.5 μm particle size; Solventsystem: A=water/trifluoroacetic acid (100:0.05) and B=water/acetonitrile/trifluoroacetic acid (5:95:0.03); Method: Linear gradient elution with 90% A to 100% B in 4 min and with a flow rate of 2 mL/min. Purity was determined by integration of the UV (254 nm) and ELSD trace. The retention times (RT) are expressed in minutes.
Preparative LC-MS-purification was performed on the same instrument. Column: 50×20 mm YMC ODS-A with 5 μm particle size; Method: Linear gradient elution with 80% A to 100% B in 7 min and with a flow rate of 22.7 mL/min. Fraction collection was performed by split-flow MS detection.
1 H NMR spectra were recorded at 500.13 MHz on a Bruker Avance DRX500 instrument or at 250.13 MHz on a Bruker, AC 250 instrument. Deuterated methylenehloride (99.8% D), chloroform (99.8% D) or dimethyl sulfoxide (99.8% D) were used as solvents. TMS was used as internal reference standard. Chemical shift values are expressed in ppm-values. The following abbreviations are used for multiplicity of NMR signals: s=singlet, d=doublet, t=triplet, q=quartet, qui=quintet, h=heptet, dd=double doublet, dt=double triplet, dq=double quartet, tt=triplet of triplets, m=multiplet and b=broad singlet.
For ion-exchange chromatography, the following material was used: SCX-columns (1 g) from Varian Mega Bond Elut®, Chrompack cat. No. 220776. Prior to use, the SCX-columns were pre-conditioned with 10% solution of acetic acid in methanol (3 mL). For de-complexation by irradiation, a ultaviolet light source (300 W) from Philipps was used. As starting polymer supports for solid phase synthesis, Wang-resin (1.03 mmol/g, Rapp-Polymere, Tuebingen, Germany) was used.
Preparation of Intermediates of Formula IV
2-(3-Methylpiperazin-1-yl)phenylamine
2-Fluoronitrobenzene (7.1 g, 50 mmol) was dissolved in DMF (100 mL) containing triethylamine (10 g, 100 mmol) and placed under a nitrogen atmosphere. To the reaction was added 2-methylpiperazine (5.0 g, 50 mmol). The reaction was heated to 80° C. for 16 hours. The reaction was allowed to cool to room temperature before the solvent was reduced to half volume in vacuo. Ethyl acetate (200 mL) and ice-water (250 mL) were added to the solution and the product was extracted with diethylether (2×200 mL). The aqueous phase was saturated with sodium chloride and extracted with ethyl acetate (2×200 mL). The organic phases were combined, washed with saturated brine, dried over magnesium sulfate, filtered and the filtrate was concentrated in vacuo. The product (10.5 g) was dissolved in ethanol (250 mL). Palladium on charcoal catalyst (10% w/w, 2.2 g) was added to the solution and the solution was hydrogenated in a Parr apparatus at 3 bar for 3 hours. The solution was filtered and evaporated to give the aniline product. Yield (8.0 g, 83%)
The following intermediates were prepared in an analogous fashion:
2-(3,5-Dimethylpiperazin-1-yl)phenylamine 2-(3,3-Dimethylpiperazin-1-yl)phenylamine 4-Methoxy-2-(3-methylpiperzin-1-yl)phenylamine
2-(2(S),5(R)-Dimethylpiperazin-1-yl)phenylamine
2(R),5(S)-Dimethyl-1-N-benzyl-piperazine (6.0 g, 29 mmol) was dissolved in dimethylformamide (100 mL), and triethylamine (6.4 mL, 44 mmol) and the mixture was placed under nitrogen. To the solution was added 2-fluoro-nitrobenzene (3.5 mL, 31 mmol). The reaction was heated at 100° C. for 72 hours The solution was evaporated in vacuo and redissolved in ethyl acetate (100 mL). The solution was then washed with saturated sodium bicarbonate solution (100 mL) and saturated brine solution (100 mL). The separated organic phase was dried over magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The crude product was then purified by flash chromatography, eluting with ethyl acetate/methanol/triethylamine 85:10:5. The product (8.2 g) was dissolved in ethanol (250 mL). Palladium on charcoal catalyst (10% w/w, 2.2 g) was added to the solution and the solution was hydrogenated in a Parr apparatus at 3 bar for 3 hours. The solution was filtered and evaporated to give the aniline product. Yield (5.2 g, 87%)
The following intermediate were prepared in an analogous fashion
2-(2(S),5(R))-Dimethylpiperazin-1-yl)phenylamine
4-Chloro-2-(3,3-dimethyl-piperazin-1-yl)-phenylamine
2,2-Dimethylpiperazine (9.55 g, 84 mmol) was dissolved in dimethylformamide (140 mL). To the solution was added triethylamine (12.07 mL, 83.6 mmol) and the reaction was placed under a nitrogen atmosphere. The solution was heated to 80° C. and 4-Chloro-2-fluoro-nitrobenzene (13.5 g, 76 mmol) was added as a solution in dimethylformamide (35 mL). The reaction was stirred at 40° C. for 16 hours. The solvent was removed in vacuo and the residue dissolved in ethanol (250 mL). Ammonium chloride (28 g) and zinc powder (17 g) were added. The reaction was boiled under reflux at 80° C. for 1 hour and then allowed to stir at 40° C. for 72 hours. The reaction was then filtered and the filtrate evaporated in vacuo. The solid was then washed with ethyl acetate and then a small amount of methanol-Yield: 16.04 g, 88%
The following intermediates were prepared in an analogous fashion
4-Chloro-2-(3-(R)-methyl-piperazin-1-yl)-phenylamine 4-Chloro-2-(3-(S)-methyl-piperazin-1-yl)-phenylamine
Preparation of Intermediates of Formula II by Method a
1-[2-(4-Chloro-phenylsulfanyl)phenyl]-3-methylpiperazine
2-(3-Methylpiperazin-1-yl)phenylamine (0.96 g, 5 mmol) was dissolved in water (30 mL) containing concentrated sulfuric acid (0.28 mL, 5.2 mmol), the solution was cooled to 0° C. and sodium nitrite (0.36 g, 5.2 mmol) was added. The reaction was stirred for 30 minutes before the pH of the reaction was adjusted to pH 7 with sodium acetate. The diazonium salt solution was then added dropwise to a solution of 4-chlorothiophenol in 2 M NaOH (4 mL) containing a copper suspension (0.3 g, 5 mmol). After addition, the mixture was heated to 60° C. for 30 minutes before being allowed to cool to room temperature and ethyl acetate (10 mL) was added. The mixture was filtered and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic extracts were dried over magnesium sulfate, filtered and evaporated in vacuo. The crude product was purified by flash chromatography using silica gel, eluting with ethyl acetate/methanol/ammonia 96:3:1. The pure product was isolated as a colourless oil. Yield (0.18 g, 11%) 1 H NMR (CDCl 3 , 500 MHz) 1.12 (d, 3H); 2.6–2.72 (br m, 2H); 3.0–3.15 (m, 5H); 6.9 (m, 2H); 7.08 (d, 1H); 7.15 (m, 1H); 7.25–7.35 (m, 4H); MS (MH + ) 319.1.
The following compounds were prepared in an analogous fashion:
1-[2-(4-Chloro-phenlsulfanyl)phenyl]-3,5-dimethylpiperazine (+/−)-{4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (+/−)-{4-[2-(4-Chloro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (+/−)-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (+/−)-(4-[2-(4-Fluoro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (+/−)-4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-2-methyl-piperazine (+/−)-4-[2-(4-iso-Propyl-phenylsulfanyl)-phenyl]-2-methyl-piperazine 4-[5-Chloro-2-(4-methoxy-phenylsulanyl)-phenyl]-2(R)-methyl-piperazine 4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-2(R),5(S)-dimethyl-piperazine.
Preparation of Intermediates II According to Method b where A Represents an Insoluble Polymer
Preparation of Iron Complexes
η 6 -1,2-Dichlorobenzene-η 5 -cyclopentadienyliron(II) hexafluorophosphate
Ferrocene (167 g), anhydrous aluminium trichloride (238 g) and powdered aluminium (24 g) were suspended in 1,2-dichlorobenzene (500 mL) and heated to 90° C. in a nitrogen atmosphere for 5 h with intensive stirring. The mixture was cooled to room temperature and water (1000 mL) was added carefully in small portions while cooling on an ice bath. Diethylether (500 mL) were added, and the mixture was stirred at room temperature for 30 minutes. The mixture was extracted with diethylether (3×300 mL). The aqueous phase was filtered, and aqueous ammonium hexafluorophosphate (60 g in 50 mL water) was added in small portions under stirring. The product was allowed to precipitate at room temperature. After 3 hours the precipitate was filtered off, washed intensively with water and dried in vacuo (50° C.) to give 81 g (21%) of the title compound as a light yellow powder. 1 H NMR (D 6 -DMSO): 5.29 (s, 5H); 6.48 (m, 2H); 7.07 (m, 2H).
Preparation of Polystyrene-bound Amines
4-[(piperazin-1-yl)carbonyloxymethyl]phenoxymethyl polystyrene
4-[(4-Nitrophenoxy)carbonyloxymethyl]phenoxymethyl polystyrene (267 g, 235 mmol) was suspended in dry N,N-dimethylformamide (2 L). N-Methylmorpholine (238.0 g, 2.35 mol) and piperazine (102.0 g, 1.17 mol) were added and the mixture was stirred at room temperature for 16 h. The resin was filtered off and washed with N,N-dimethylformamide (2×1 L), tetrahydrofuran (2×1 L), water (1×500 mL), methanol (2×1 L), tetrahydrofuran (2×1 L) and methanol (1×1 L). Finally, the resin was washed with dichloromethane (3×500 mL) and dried in vacuo (25° C., 36 h) to yield an almost colourless resin (240.0 g).
The following polystyrene bound diamines were prepared analogously:
4-[(2,5-Dimethyl-piperazin-1-yl)carbonyloxymethyl]phenoxymethyl polystyrene 4-[(3-Methyl-piperazin-1-yl)carbonyloxymethyl]phenoxymethyl polystyrene
Preparation of Resin-Bound η 6 -aryl-η 5 -cyclopentadienyliron(II) hexafluorophosphates
4-({4-[η 6 -(2-Chlorophenyl)-η 5 -cyclopentadienyliron(II)]piperazin-1-yl}carbonyloxymethyl)phenoxymethyl polystyrene hexafluorophosphate
4-[(piperazin-1-yl)carbonyloxymethyl]phenoxymethyl polystyrene (115.1 g, 92 mmol) was suspended in dry tetrahydrofuran (1.6 L), and η 6 -1,2-dichlorobenzene-η 5 -cyclopentadienyliron(II) hexafluorophosphate (76.0 g, 184 mmol) was added followed by potassium carbonate (50.9 g, 368 mmol). The reaction mixture was stirred at 60° C. for 16 h. After cooling to room temperature, the resin was filtered off and washed with tetrahydrofuran (2×500 mL), water (2×250 mL), tetrahydrofuran (2×500 mL), water (2×250 mL), methanol (2×250 mL), dichloromethane (2×250 mL) and methanol (2×250 mL). Finally, the resin was washed with dichloromethane (3×500 mL) and dried in vacuo (25° C., 36 h) to yield a dark orange resin (142 g).
The following polystyrene bound iron-complexes were prepared analogously:
4-({4-[η 6 -(2-Chlorophenyl)-η 5 -cyclopentadienyliron(II)]-2,5-dimethylpiperazin-1-yl}carbonyloxymethyl)phenoxymethyl polystyrene hexafluorophosphate 4-({4-[η 6 -(2-Chlorophenyl)-η 5 -cyclopentadienyliron(II)]-3-methylpiperazin-1-yl}carbonyloxymethyl)phenoxymethyl polystyrene hexafluorophosphate
Preparation of ortho-(arylsulfanyl)phenyl piperazines
(+/−)-1-[2-(4-Methylphenylsulfanyl)phenyl]-trans-2,5-dimethylpiperazine:
To a solution of 4-methylthiophenol (1.4 g, 9.8 mmol) in a 1:1 mixture of tetrahydrofuran/dimethylformamide (5 mL), sodium hydride (7.4 mmol, 60% in mineral oil) was carefully added at room temperature (Caution: Generation of hydrogen). The mixture was stirred for an additional 30 min after the generation of hydrogen had ceased. Subsequently, 4-({4-[η 6 -(2-chloro-phenyl)-η 5 -cyclopentadienyliron(II)]-trans-2,5-dimethyl-piperazin-1-yl}carbonyloxymethyl)phenoxymethyl polystyrene hexafluorophosphate (3.5 g, 2.45 mmol) was added and the mixture was stirred at 55° C., for 6 h. After cooling to room temperature, the resin was filtered off and washed with tetrahydrofuran (2×50 mL), tetrahydrofuran/water (1:1) (2×50 mL), N,N-dimethylformamide (2×50 mL), water (2×50 mL), methanol (3×50 mL), tetrahydrofuran (3×50 mL), and subsequently with methanol and tetrahydrofuran (each 50 mL, 5 cycles). Finally, the resin was washed with dichloromethane (3×50 mL) and dried in vacuo (25° C., 12 h) to yield a dark orange resin. The thus obtained resin and a 0.5 M solution of 1,10-phenanthroline in 3:1 mixture of pyridine/water (20 mL) was placed in light-transparent reactor tube. The suspension was agitated by rotation under irradiation with visible light for 12 h. The resin was filtered and washed with methanol (2×25 mL), water (2×25 mL) and tetrahydrofuran (3×25 mL) until the washing solutions were colourless (approx. 5 cycles) and the irradiation procedure was repeated until decomplexation was complete (approx. 5 cycles). After the decomplexation was completed, the resin was washed with dichlormethane (3×25 mL) and dried in vacuo (25° C., 12 h) to obtain a light brown resin. 3.7 g (24 mmol) of the thus obtained resin were suspended in a 1:1 mixture of trifluoroacetic acid and dichlormethane (2 mL) and stirred at room temperature for 2.5 h. The resin was filtered off and washed with dichloromethane (5×0.5 mL). After evaporation of the filtrate from volatile solvents in vacuo, an orange oil was obtained. The crude product was purified by preparative LC-MS and subsequently by ion-exchange chromatography.
LC/MS (m/z) 313.2 (MH + ); RT=2.17; purity (UV, ELSD): 87.1%, 98.7%; yield: 47.8 mg (6%).
The following arylpiperazines were prepared analogously:
(+/−)-1-[2-(4-Isopropylphenylsulfanyl)phenyl]-trans-2,5-dimethylpiperazine (+/−)-1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]-trans-2,5-dimethylpiperazine (+/−)-1-[2-(4-Tertbuytylphenylsulfanyl)phenyl]-trans-2,5-dimethyl-piperazine (+/−)-1-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazine (+/−)-1-[2-(4-Isopropyl-phenylsulfanyl)-phenyl]-piperazine.
Preparation of Intermediates of Formula III where A is an Insoluble Polymer
4-[Chloroacetoxymethyl]phenoxymethyl polystyrene
Wang resin (10 g, 10.3 mmol) was suspended in dichloromethane (100 mL) and cooled to 0° C. Diisopropylethylamine (9 mL, 52 mmol) was added. Chloroacetylchloride was added slowly. The reaction mixture was stirred at 0° C. for 30 min and then allowed to heat to room temperature. The reaction mixture was stirred at room temperature for 16 h. The resin was filtered off and washed with N,N-dimethylformamide (3×100 mL), dichloromethane (2×100 mL), dimethylformamide (3×100 mL) and dichloromethane (2×100 mL) and dried in vacuo (25° C., 16 h).
The following resin was prepared in an analogous fashion:
4-[2-Chloropropionyloxymethyl]phenoxymethyl polystyrene
Preparation of Intermediates II by Method c
4-(2-Bromo-phenoxy)-biphenyl
A mixture of 2-bromophenol (2.08 g, 12 mmol), 4-biphenylboronic acid (4.75 g, 24 mmol), Cu(OAc) 2 (2.20 g, 12 mmol) and triethylamine (6.1 g, 60 mmol) in dioxane (100 mL) was stirred for 48 h. The crude mixture was evaporated onto silica gel and purified by column chromatography eluting with ethyl acetate/heptane 1:9. Yield: 0.73 g (19%). 1 H NMR (CDCl 3 , 500 MHz) 7.65 (m, 1H) 7.55 (m, 4H), 7.43 (m, 2H), 7.25–7.38 (m, 2H), 7.00–7.08 (m, 4H); MS(m/z): 325.1.
(+/−)-1-[2-(Biphenyl-4-yloxy)-phenyl]-3-methyl-piperazine
A mixture of 4-(2-bromo-phenoxy)-biphenyl (0.73 g, 2.25 mmol), rac-2-methylpiperazine (0.285 g, 0.285 mmol), Pd 2 dba 3 (0.022 g, 1 mol %), rac-binap (0.043 g, 3 mol %) and NaOBu t (0.300 g, 3.12 mmol) in dry toluene (15 mL) under argon and stirred at 90° C. overnight. After cooling to room temperature the mixture is filtered and evaporated onto silica gel and and purified by column chromatography eluting with ethyl acetate/heptane 1:2. Yield: 0.264 g (34%). 1 H NMR (CDCl 3 , 500 MHz) 7.55 (m, 2H), 7.49 (m, 2H), 7.38 (m, 2H), 7.27 (m, 1H), 7.10 (m, 1H), 6.90–7.00 (m, 5H), 3.30–3.35 (m, 2H), 2.88 (m, 1H), 2.62–2.80 (m, 3H), 2.30–2.40 (m, 1H) 1.60–2.00 (br, 1H), 0.99 (d, 3H); MS(m/z): 345.1.
Preparation of Compounds of the Invention
Example 1
1a (+/−)-{4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
4-[2-(4-Methoxyphenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (0.5 g, 1.5 mmol) and N-ethyldisopropylamine (0.315 mL, 1.8 mmol) was dissolved in acetonitrile (10 mL) and placed under a nitrogen atmosphere. Ethyl bromoacetate (0.19 mL, 1.7 mmol) was added and the mixture was stirred at ambient temperature for 16 hours. To the mixture was then added a small amount of silica gel and the solvent was evaporated in vacuo. The product, absorbed on to silica gel, was poured on to a silica cartridge and eluted with dichloromethane/heptane/ethyl acetate (60:35:5). The ester was isolated from relevant fractions as a light oil (300 mg, 48%). The ester was then dissolved in ethanol (10 mL) and 2N NaOH was added (5 mL). The reaction was stirred for 16 hours at room temperature. The reaction was evaporated in vacuo and the residue was dissolved in ethyl acetate (50 mL). 2N HCl (15 mL) was added and the phases were separated. The aqueous phase was reextracted with ethyl acetate (2×50 mL). The combined organic fractions were dried (MgSO 4 ), filtered and evaporated. The residue was dissolved in a small amount of dichloromethane, precipitated by the addition of heptane and the solvent was removed in vacuo. Yield (280 mg, 100%). 1 H NMR (CDCl 3 , 500 MHz) 0.87 (d, 3H), 1.35 (d, 3H), 3.04 (m, 1H), 3.12 (m, 2H), 3.6 (m, 3H), 4.11 (d, 1H), 4.31(d, 1H), 3.81 (s, 3H), 6.55 (d, 1H), 7.02 (d, 2H), 7.13 (dd, 1H), 7.2 (m, 1H), 7.42 (d, 2H), LC-MS (m/z) (MH) + 387.4 RT=2.22 (UV, ELSD) 98%, 97%
and the following compounds were prepared in an analogous fashion:
1b (+/−)-{4-[2-(4-Chloro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (CDCl 3 , 500 MHz) 0.80 (d, 3H), 1.28 (d, 3H), 2.92–3.18 (m, 3H), 3.64 (m, 3H), 4.06 (d, 1H), 4.29 (d, 1H), 6.78 (d, 1H), 7.12 (t, 1H), 7.26 (m, 2H), 7.50 (m, 4H), LC-MS (m/z) (MH + ) 391.2 RT=2.43 (UV, ELSD) 99%, 99%. Yield 420 mg.
1c (+/−)-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (CDCl 3 , 500 MHz) 0.76 (d, 3H), 1.01 (d, 3H), 1.30 (s, 9H), 2.4–2.6 (m, 2H), 2.9–3.0 (m, 3H), 3.28 (m, 1H), 3.32 (d, 1H), 3.48 (d, 1H), 6.65 (d, 1H), 7.01 (t, 1H), 7.13 (t, 1H), 7.24 (d, 1H), 7.39 (d, 2H), 7.47 (d, 2H), LC-MS (m/z) (MH + ) 412.9 RT=2.70 (UV, ELSD) 95%, 99%. Yield 550 mg.
1d (+/−)-(4-[2-(4-Fluoro-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (CDCl 3 , 500 MHz) 0.80 (d, 3H), 1.25 (d, 3H), 2.8–3.0 (m, 2H), 3.08 (m, 1H), 3.4–3.6 (m, 3H), 3.87 (d, 1H), 4.06 (d, 1H), 6.64 (d, 1H), 7.07 (m, 1H), 7.20 (m, 1H), 7.26 (m, 1H), 7.32 (dd, 2H), 7.54 (dd, 2H), LC-MS (m/z) (MH + ) RT=2.24 (UV, ELSD) 95%, 99%. Yield 180 mg.
1e (+/−)-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 399.2 (MH + ); RT=2.54; purity (UV, ELSD): 100%, 100%; yield: 10.4 mg.
1f (+/−)-{4-[2-(4-iso-Propyl-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 385.1 (MH + ); RT=2.45; purity (UV, ELSD): 88%, 100%; yield: 11 mg.
1g (+/−)-2-(4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-trans 2,5 dimethylpiperazin-1-yl}-propionic acid, hydrochloride
LC/MS (m/z) 427.0 (MH + ); RT=2.76; purity (UV, ELSD): 86%, 98%; yield: 27 mg.
1h (4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl-2(R)-methyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (DMSO, 500 MHz) 1.40 (d, 3H), 3.16 (m, 1H), 3.25–3.48 (m, 4H), 3.63 (m, 1H), 3.75 (m, 1H), 3.80 (s, 3H), 4.15 (d, 1H), 4.30 (d, 1H) 6.55 (d, 1H), 7.02 (d, 2H), 7.13 (dd, 1H), 7.2 (m, 1H), 7.42 (d, 2H)
LC/MS (m/z) 407.3 (MH + ); RT=2.79; purity (UV, ELSD): 95%, 100%; yield: 225 mg.
1i {4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-2(R), 5(S)-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (DMSO-d6, 500 MHz) 0.85 (d, 3H), 1.30 (d, 3H), 2.95 (t, 1H), 3.05 (m, 2H) 3.53 (d, 1H), 3.60–3.65 (m, 2H), 3.80 (m, 3H), 3.92 (d, 1H), 4.10 (d, 1H), 6.55 (d, 1H), 7.02 (d, 2H), 7.13 (dd, 1H), 7.2 (m, 1H), 7.42 (d, 2H)
LC/MS (m/z) 387.3 (MH + ); RT=2.22; purity (UV, ELSD): 97%, 96.9%; yield: 607 mg.
1j {4-[5-Chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2,2-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (DMSO-d6, 500 MHz) 1.58 (s, 6H), 3.20 (s, 2H), 3.20–3.60 (br m, 4H), 3.80 (s, 3H), 3.92 (d, 1H), 4.10 (d, 1H), 6.55 (d, 1H), 6.90 (dd, 1H), 6.96 (d, 2H), 7.13 (s, 1H), 7.40 (d, 2H)
LC/MS (m/z) 421.1 (MH + ); RT=2.41; purity (UV, ELSD): 96%, 98%; yield: 1.18 g.
1k {4-[5-Chloro-2-(4-trifluoromethyl-phenylsulanyl)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 445.1 (MH + ); RT=2.50; purity (UV, ELSD): 88%, 72%; yield: 20 mg.
1l {4-[5-Chloro-2-(3-methoxy-phenylsulanyl)-phenyl]-2(R)-methyl-piperazin-]-yl}-acetic acid, hydrochloride
1 H NMR (DMSO-d6, 500 MHz) 1.32 (d, 3H), 3.05 (m, 1H) 3.10–3.40 (m, 4H), 3.50–3.60 (m, 2H), 4.10 (d, 1H), 4.24 (d, 1H), 6.82 (d, 1H), 6.95 (m, 3H), 7.11 (dd, 1H), 7.2 (s, 1H), 7.38 (dd, 1H)
LC/MS (m/z) 407.2 (MH + ); RT=2.41; purity (UV, ELSD): 99.6%, 100. %; yield: 1.26 g
1m {4-[2-(Biphenyl-4-yloxy)-phenyl]-2-methyl-piperazin-1-yl}-acetic acid, hydrochloride
1 H NMR (DMSO-d6, 500 MHz) 7.60 (m, 4H); 7.40 (m, 2H), 7.32 (m, 1H), 6.95–7.20 (m, 6H), 5.00–6.50 (br, 1H), 4.00–4.10 (m, 1H), 3.80–3.90 (m, 1H), 3.20–3.50 (m, 6H), 3.05–3.15 (m, 1H), 1.17 (m, 3H);
LC/MS (m/z) 403.0; RT=2.45; purity: (UV/ELSD): 96.7%, 99.4; yield: 0.116 g (43%).
Example 2
2a (+/−)-{4-[2-(4-Methyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
A solution of [2-(4-Methyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazine (10 mg, 0.03 mmol) and diisopropylethylamine (0.02 mL, 0.11 mmol) was added to 4-[Chloroacetoxymethyl]phenoxymethyl polystyrene (100 mg, 0.09 mmol). The reaction mixture was agitated by shaking overnight at 70° C. The resin was filtered off and washed with N,N-dimethylformamide (4 mL), methanol (4 mL) and dichloromethane (4 mL). The resin was suspended in a 1:1 mixture of trifluoroacetic acid and dichlormethane (1.5 mL) and shaken at room temperature for 1 h. The resin was filtered off and washed with dichloromethane (1 mL). The organic extracts were collected and evaporated in vacuo. The crude product was purified by preparative LC-MS.
LC/MS (m/z) 371.1 (MH + ); RT=2.24; purity (UV, ELSD): 100%, 100%; yield: 1.6 mg.
The following compounds were prepared in an analogous fashion:
2b (+/−)-{4-[2-(4-iso-Propyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 399.0 (MH + ); RT=2.48; purity (UV, ELSD): 98.3%, 100%; yield: 2.2 mg.
2c (+/−)-{4-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-trans-2,5-dimethyl-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 385.0 (MH + ); RT=2.37; purity (UV, ELSD): 99.8%, 100%; yield: 4.7 mg.
2d (+/−)-2-{4-[2-(4-tert-Butyl-phenylsulfanyl)-phenyl]-3-methylpiperazin-1-yl}-propionic acid, hydrochloride
LC/MS (m/z) 386.7 (MH + ); RT=2.14; purity (UV, ELSD): 91.9%, 99.2%; yield: 3.2 mg.
2e (+/−)-{4-[2-(4-Isopropyl-phenylsulfanyl)-phenyl]-piperazin-1-yl}-acetic acid, hydrochloride
LC/MS (m/z) 370.8 (MH + ); RT=2.35; purity (UV, ELSD): 89.0. %, 99.9%; yield: 3.2 mg.
2f (+/−)-2-{4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-3-methyl-piperazin-1-yl}-propionic acid, hydrochloride
LC/MS (m/z) 386.7 (MH + ); RT=2.63; purity (UV, ELSD): 91.9%, 99.2%; yield: 3.2 mg.
Pharmacological Testing
The compounds of the invention were tested in a well-recognised and reliable test measuring glycine uptake:
[ 3 H]-Glycine Uptake
Cells transfected with the human GlyT-1b were seeded in 96 well plates. Prior to the experiment the cells were washed twice in HBS (10 mM Hepes-tris (pH 7,4), 2,5 mM KCl, 1 mM CaCl 2 , 2,5 mM MgSO 4 ,) and pre-incubated with test compound for 6 minutes. Afterwards, 10 nM 3 H-glycine was added to each well and the incubation was continued for 15 minutes. The cells were washed twice in HBS. Scintillation fluid was added and the Plates were counted on a Trilux (Wallac) scintillation counter.
The test results showed, that the compounds of the invention all showed inhibition below 2000 nM as IC 50 in the above-mentioned assay. Most of the compounds were between 150 nM and 850 nM.
Microdialysis experiments in rodents showed that administration of selected compounds of the invention resulted in an increased concentration of glycine in the brain. Furthermore, in a rodent model of psychosis, selected compounds of the invention reversed the symptoms of amphetamine induced hyperactivity. | The invention provides compounds of the formula
wherein the substituents are as defined in the application. The compounds are valuable glycine transport inhibitors. | 2 |
TECHNICAL FIELD
The present invention concerns a method and apparatus for producing fibre yarn by first extruding a fibre suspension through a nozzle, removing excess water, and finally, by drying the yarn.
Especially an embodiment of the invention concerns a method and apparatus for dewatering the yarn and for twisting the yarn from extruded suspension to dried yarn.
BACKGROUND
Many different types of yarns made of natural fibers are known in the art. One well known example is paper yarn, which is traditionally manufactured from paper sheets. The first and only industrial method was developed in the late 19th century in Germany. It has been refined over time but the basic principle has remained the same and it is still in use today. Typically, paper manufactured from chemical, mechanical or chemi-mechanical pulp is slit to strips (width typically from 5 to 40 mm), which are twisted to thread. Said thread may be subjected to dyeing and finishing. The product (paper yarn) has limited applications because of deficiencies in its properties, such as limited strength, unsuitable thickness, layered or folded structure, and further, the manufacturing method is inefficient.
Cotton is very widely used as raw material in the manufacture of yarns and ropes. However, the cultivation of cotton requires significant water resources and it is widely carried out in regions where there is shortage of water and food. When available water is used for the irrigation of cotton fields, the situation with regard to food supply becomes worse. Thus the use of cotton does not support sustainable development, and there is a need for alternative sources of fiber, suitable for replacing cotton at least partly.
Cotton farming covers 5% of the world's farming area but it uses 11% of all agrochemicals. Intensive farming of cotton has caused pollution to the waters, wear of the soil and it has changed the animal population. In the future highly pollutant cotton can be replaced by cellulose based materials. There are already alternatives to cotton. Rayon is a material produced from cellulose fibers but it still requires heavy chemical treatments.
Methods for producing fibre yarn and other products from cellulosic materials are described in documents JP 4004501 B, JP 10018123, JP 2004339650, JP 4839973, EP 1493859, CN 102912622, CN 101724931, WO 2009028919 and DE 19544097. The methods described usually include chemical treatment of cellulose before or during manufacture of the product.
SUMMARY OF INVENTION
Production of yarn directly from fibres, such as pulp fibres, without a dissolution process or disintegration of the fibres to nanofibres would increase the efficiency and ecofriendliness of the yarn manufacturing process. It would also decrease the raw material cost significantly. Currently there is no industrial scale fibre yarn manufacturing process available for producing fibre yarn from said fibres. Fibre yarn products are produced of cotton yarn, different viscose process yarns etc. Currently there are many attempts to produce yarn from NFC.
For the above reasons, it would be beneficial to provide a method and apparatus for producing yarn directly from cellulose fibres in a manner that is commercially exploitable in industrial scale.
In a first aspect, the invention relates to a method/apparatus for taking advantage of new material by forming it mechanically into a yarn and enabling of producing environmentally friendly material which can substitute cotton and rayon.
Generally speaking the object of the invention is achieved by a novel method and apparatus as defined by the claims.
One embodiment of the invention provides a device and method that can produce cellulose based yarn continuously.
According to other aspects and embodiments of the present invention, the invention provides a yarn product that is cheaper than comparative product made of cotton.
According to one further aspect of the invention, the invention provides new use of wood and other vegetable fibres.
An embodiment of the invention is based on feeding pulp fibre suspension, such as pulp fibre suspension, from a nozzle on a first wire sieve, transporting the suspension on the first sieve to a nip formed by the first and a second sieve having a machine travel direction different from that of the first sieve for twisting and rotating the yarn to be formed between the wire sieves.
According to one embodiment, the relative machine travel directions of the at least two sieves is adjustable.
According to one embodiment, the gap between the at least two wire sieves narrows in the machine travel direction.
According to one embodiment of the invention, the gap between the at least two wires is adjustable.
According to one embodiment of the invention, at least one vacuum suction box is arranged on opposite side of at least one of the wires in relation of the wire gap.
According to one embodiment of the invention, the apparatus is equipped with at least one heating element for drying and treating the yarn to be manufactured.
The various embodiments of the invention provide essential benefits.
New method described herein for producing cellulose based yarn is cleaner to the environment compared to, for example, use of cotton and it can use harvesting surplus of wood and other cellulosic plant material. Finland's harvesting surplus of cellulosic material alone could replace 20% of the world's cotton demand. This device enables industrial scale fibre yarn production using technologies currently available in pulp and paper industry. The invention provides a possibility to create new field of industry and open totally new uses to northern wood fibres.
By the method and apparatus of the invention a fibre yarn can be made of pulp mass that need not be excessively chemically or mechanically processed. The fibre yarn can be used to replace yarn made of other materials. Further, the yarn can be used in new applications utilizing characteristic properties of the fibre yarn such as twistability. The fibre yarns can be recycled several times just like paper or board. The fibre material of the fibre yarn can be sourced from several sources. Wood fibre is suitable but also fibre materials used for manufacture of paper or board can be used as raw materials. The twisting to the yarn inherent for the inventive method increases the strength and elasticity of the yarn as it increases contacts between the fibres in the yarn, i.e. cross linking.
Other objects and features of the invention will become apparent from the following detailed description considered in conjunction with the accompanying drawings. It is to be understood, however, that the drawings are intended solely for purposes of illustration and not as a definition of the limits of the invention, for which reference should be made to the appended claims.
DESCRIPTION OF DRAWINGS
FIG. 1 is a schematic side view of one embodiment of the invention.
FIG. 2 is a schematic cross section of a nozzle that can be utilized for realizing the invention.
FIG. 3 is a schematic perspective view of one embodiment of the invention.
DESCRIPTION OF EMBODIMENTS
Definitions
Machine travel direction is the direction the sieve wires over their operating zone. Return travel direction is the direction on which the sieve wire loop runs on return side.
Operating zone of the wire sieve is the part of the sieve wire loop on which the yarn to be manufactured travels when it is processed.
Centerline of the wire is the centerline of that part of the wire loop on which the yarn to be manufactured travels when it is processed.
Pulp is considered to be mechanical, chemi-mechanical or chemical pulp mass wherein fibres have not been dissolved or disintegrated to nanofibres.
Starting point for this invention is a new method for the manufacture of fibrous yarn for connecting cellulose fibers to solid material. The method is disclosed in WO 2013/034814, which is included herein as reference. The main application for the material was the producing of the yarn by connecting fibers continuously together.
Main functions of this device are dewatering and forming of the cellulose yarn. Based on experiences from manual laboratory scale manufacturing moisture and excess water should be compressed out of the yarn while the yarn is simultaneously twisted to achieve the final form and to maintain the round cross section of the yarn during pressing.
According to the invention the pulp fibre suspension, such as pulp fibre suspension, is extruded between two angled wire sieves and the compression of wire sieves dewater the yarn and angular force element rotates and twists the yarn and the yarn will achieve its final form. The final result would resemble ordinary cotton yarn.
The proper parameters for producing the yarn such as speed, pressure and rotating angle affect to the quality and properties of the yarn. Other significant parameters include the angle of the nozzle, the speed difference between the respective speeds of the sieve and the fiber suspension 13 , which speed difference results in the stretching of the yarn, as well as speed difference between the respective speeds of formation part and drying part.
The embodiment in FIG. 1 comprises a first, lower sieve wire 1 arranged to run in a loop over guide rolls 2 . On the loop is formed a straight part between first guide roll 3 and second guide roll 4 . A second wire sieve 5 is arranged to run on a loop against the straight part of the first wire sieve 1 so that a gap 6 is formed between the wire sieves 1 , 5 . The gap between the two wire sieves 1 , 5 is arranged to narrow in the machine travel direction by guiding the second wire sieve 5 by third and fourth guide roll. This provides a narrowing pressurized gap for removing water from the pulp fibre suspension. The wire sieves 1 , 5 form a narrowing nip that is positioned to begin, in the machine travel direction, after the first guide roll 3 of the first wire sieve 1 . The first guide roll 7 of the second wire sieve 5 is positioned downstream of the first guide roll 3 of the first wire sieve 1 so that that an open space is formed on the first wire sieve 1 on the distance between the first guide roll 3 of the first wire sieve 1 and the first guide roll 7 of the second wire sieve 5 . The operation zone of the formed between the first and second guide rolls 3 , 4 of the second wire sieve 1 .
A nozzle 9 is positioned at the beginning of the operation zone of the apparatus over the open space of the first wire sieve 1 for feeding a pulp fibre suspension 13 on the first wire sieve 1 . On the opposite end of the operation zone is winder roll 11 or corresponding winding apparatus for collecting the manufactured yarn. The second guide roll 8 of the second wire sieve 5 and the second guide roll 4 of the first wire sieve 1 are spaced apart so that open space is formed on the first wire sieve 1 between these guide rolls 4 , 8 . Over this space optional heaters 12 can be placed. Suitable heaters are infrared heaters, hot air dryers or other known dryers or heaters used for example in paper, pulp and board industry. A suction box 14 for removing water and moisture from the yarn through the wire sieve can be placed on opposite side of each wire sieve 1 , 5 in relation to the yarn to be formed. In this example one suction box 14 is placed under the first wire sieve. The wire sieves 1 , 5 and winder roll are rotated by driven guide rolls, for example by means of electric motors or corresponding actuators.
Yarn is manufactured by the above described apparatus by feeding pulp fibre suspension over the first wire sieve 1 so that the running wire sieve 1 transfers the suspension to the nip of first and second wire sieve 1 , 5 . In the gap the yarn to be formed is twisted and rotated and pressed against the surfaces of the wire sieves 1 , 5 . This action removes water effectively and forms a good quality yarn.
One embodiment of a nozzle suitable for implementing the invention is shown in FIG. 2 , depicting a cross-section picture of a nozzle 9 . In this embodiment a circular nozzle is shown. The fiber suspension 13 is fed through the inner die or orifice 17 and if salt or other chemicals 15 are used for crosslinking, they may be fed through outer die or orifice 16 . Other cross-section geometries besides circular may as well be used, such as elliptical or rectangular. When the fibre suspension is pushed through the nozzle it has a velocity and narrow to a circular thin line 18 of fibre suspension. The diameter of the suspension line is defined by exit speed of the suspension 13 and speed of the first wire sieve 1 on which the suspension is fed.
Moist yarn obtained from the nozzle 9 initially contains water typically from 30 to 99.5% w/w. In the dewatering step the solid content of the yarn may be adjusted to desired level until all free water is removed.
The nozzle 9 forms a jet causing the gel formation. The nozzle is designed so that the flow accelerates and orients the fibres inside the nozzle. The crosslinking fluid merges with the fibre suspension outside the nozzle and the gel is formed. To maintain the round shape of the yarn in the wire section the yarn has to be twisted and rotated during the dewatering. This is done by tilting one of the wire sieves so that there is an angle difference in the wire machine direction alignment. Dewatering speed is adjusted by changing the wire gap 6 in machine direction and by vacuums. Jet to wire speed difference changes the tension and stretches the yarn. Wire tension and wire gap causes also pressing of the preformed yarn to the wires.
FIG. 3 shows one embodiment of the apparatus according to the invention. It must be noted that parts and designs not shown in FIG. 1 but shown in FIG. 3 should be considered to be present in both embodiments when functionally needed as some of the part s are shown only in one figure for clarity. In here, the first wire sieve 1 is guided by three guide rolls. These rolls are mounted on a fixed (lower) frame part 19 . Second wire sieve 5 is mounted through its guide rolls to a movable (upper) frame part 20 that is movably mounted on the fixed frame part. An actuator 21 is used for adjusting the relative position of the movable frame part 20 and the fixed frame part 19 . This allows for adjusting the relative positions of the wire sieves 1 , 5 .
The method and apparatus is most suitable for producing yarns using the teachings of WO 2013/034814 that discloses a method for producing cellulose based yarn. The results from earlier experiments show that material properties of this new type of cellulose yarn are promising and good quality yarn has already been made. Previous experiments are made in laboratory scale and produced yarns have not been long enough for making e.g. fabric out of them. This problem can be solved by means of the invention.
Initial shape of the yarn is achieved through fast suspension crosslinking right after the nozzle 9 before the suspension hits the wire. In the nozzle rheology modifiers prevent clogging and the fibres are oriented with the flow. Different compounds are pumped through the nozzle with synchronized speeds and as they get mixed, the crosslinking prevents further mixing and initial dewatering with gravity.
Wet gel yarn 18 is extruded directly to the first wire sieve 1 , which conveys the material between first and second wire sieves 1 , 5 . When the preformed yarn encounters the second, in here upper, wire sieve 5 , water begins to be pressed out of it. The diameter of yarn decreases when it moves along between the wire sieves 1 , 5 . Wire sieves 1 , 5 are aligned so that the gap 6 between them decreases when approaching the output point and an angle difference in machine travel direction (X-Y) direction between the centerlines of the wire sieves 1 , 5 rotates the yarn while pressing.
All free water is removed by pressing and twisting the yarn between the wire sieves 1 , 5 . At this point the strength of the yarn is sufficient for reeling and the final dewatering takes place there. Also further drying of the yarn may be included to this device as described in narration of FIG. 1 .
Angular adjusting of the wires is implemented by two-pieced frame 19 , 20 . Fixed (lower) frame part 19 is solid and movable (upper) frame part 20 can be rotated as depicted by an arrow in FIG. 3 . Movable frame part 20 rotates along two conductors and it is lockable. Conductors permit slight movements also in horizontal plane. It is clear that a person skilled in the art can design various options for implementing this relative movement.
Frame of the device is designed to be easy to adjust and maintain.
The frame of the device is required to have high stiffness because rolls are attached only from one end and they must stay well aligned to get the yarn to uniform quality. Adding features and modifying the placement of the rolls for possible upcoming needs should be easy. It is clear that construction of the frame is not limited to the example shown.
The speeds of the wire sieves 1 , 5 are preferably accurately adjustable to get the operating speed synchronized with the pump that is feeding the material through the nozzle 9 . The operation of wire sieves can be accomplished individually with two PC controlled AC servo motors. The velocities can be automatically synchronized to each other by giving the amount of deviation in angularity of wires.
A fully functional and highly adjustable device for dewatering and forming cellulose yarn can be designed and manufactured according to the invention.
Main production parameters that effect each parameter on the form of yarn are wire sieve speed, rotating angle (angle between the wire sieves) and space between the upper (second) and the lower (first) wire. By changing the wire sieve angle in X-Y plane the force rotating the yarn at horizontal plane is changed. Gap between the wire sieves affect the compression pressure and it can also change the yarn rotation by changing friction force.
In a fully operating manufacturing facility it would be foreseeable to arrange a plurality of parallel nozzles to produce yarn on several production lines simultaneously. After the production stage described above with reference to FIGS. 1 to 3 the simultaneously produced plurality of yarns may be wound together to form one or several thick yarn(s). Such a thick yarn consisting of said individual yarn may then be wound to a roll with or without a supplementary treatment stage of applying suitable chemicals for a particular desired effect.
Rough adjusting for these parameters can be based on results of visual inspection of the yarn. The main goal of the invention is to produce yarn continuously. The specific properties of yarn (constant diameter, tensile strength) can be adjusted by changing operating parameters. The results of the preliminary tests run on the invention were promising and established solid basis for future research.
The purpose of the invention is to provide a device to continuously produce yarn directly from a fibre suspension, preferably pulp fibre suspension. The way of turning fibre suspension into a yarn is completely new.
The device can be easily adjusted to manufacturing needs. The apparatus according to the invention can produce cellulose yarn continuously at very high speeds. Even higher speeds than 10 m/s are possible but then at least motors and drive pulleys needs to be dimensioned and chosen accordingly.
It can be contemplated that the angle and distance of the wires could be accurately adjustable by a computer while the process is ongoing for producing even longer and better shaped yarn. Further, the speed of the wire sieves may be same or different in relation to each other. Speed differences may be utilized for affecting the surface structure and twisting of the yarn, for example.
The invention utilizes preferably liquid penetrable wires, felts or belts as transfer and pressing elements. However, rubber or plastic bands or similar non-penetrable bands might also be used if water removal from the gap between the transfer and pressing elements is arranged, for example by suction. One alternative is use penetrable/non-penetrable pair of transfer and pressing elements.
With similar treatments as used with cotton yarn, cellulose yarn can reach comparable properties to cotton and can be utilized in fabrics. Raw cellulose material costs less than cotton which makes it also economically interesting. In addition, cellulose yarn is environmentally friendly. Raw material for cellulose can be gathered for example from harvesting surplus.
Thus, while there have been shown and described and pointed out fundamental novel features of the invention as applied to a preferred embodiment thereof, it will be understood that various omissions and substitutions and changes in the form and details of the method and device may be made by those skilled in the art without departing from the spirit of the invention. For example, it is expressly intended that all combinations of those elements and/or method steps which perform substantially the same results are within the scope of the invention. Substitutions of the elements from one described embodiment to another are also fully intended and contemplated. It is also to be understood that the drawings are not necessarily drawn to scale but they are merely conceptual in nature. It is the intention, therefore, to be limited only as indicated by the scope of the claims appended. | A method and apparatus for producing fibre yarn is provided. The novel apparatus includes a first transportation and pressing element ( 1 ) and a second transportation and pressing element ( 5 ) arranged adjacent to the first transportation and pressing element ( 1 ) as well as elements for driving the transportation and pressing elements ( 1, 5 ). The first and second transportation and pressing elements ( 1, 5 ) are arranged to form a nip therebetween. The apparatus also includes a nozzle ( 9 ) for feeding fibre suspension ( 6 ), such as pulp fibre suspension, to the nip between the first and second transportation and pressing elements ( 1, 5 ). | 3 |
FIELD OF THE INVENTION
This invention relates to a capacitor input type rectifier having a circuit for preventing or reducing inrush current, and more particularly to a capacitor input type rectifier having a circuit for preventing or minimizing inrush current by applying power when the input current becomes a minimum by detecting the phase of an AC voltage at the time of applying the AC power.
RELATED ART
A rectifier is a circuit for converting an AC current into a DC current. Rectifier circuits are classified as full-wave rectifiers and half-wave rectifiers according to the rectifying method; and into a capacitor input type, a choke input type, a phi (π) input type, and the like, according to the smoothing function. The DC output which is output from the rectifying circuit has a ripple component and thus a voltage regulation of the DC output is necessary, such that a smoothing circuit following the rectifying circuit is required to remove this unbalance and output a smooth DC with no ripple component or oscillations.
With respect to such smoothing circuits, there is a capacitor input type in which a capacitor is directly connected into an output portion of the rectifying circuit; a choke input type in which the capacitor is connected after the choke is connected into an output portion of the rectifying circuit; and a phi (π) input type in which the above two types are combined.
The capacitor input type has a high voltage at the time of outputting DC and has a small ripple component. However, it has the disadvantage that an inrush current flows when the circuit is started.
However, the choke input type has a low voltage unlike the capacitor input type at the time of outputting the DC signal. But since it has advantages in that the voltage regulation is low and the amount of the inrush current is small, generally it is used for a large current circuit.
FIG. 1 shows a conventional rectifier of the capacitor input type with rectifying block 2 connected to an AC voltage source 1, and a smoothing block 3 is connected to an output terminal of the above-mentioned rectifying block 2. The rectifying block 2 is a bridge rectifying circuit formed by four diodes. The smoothing block 3 is constituted by a thermistor TH1 connected to the output terminal of the rectifying block 2, and an input type capacitor C1 connected to the above-mentioned thermistor TH1.
An operation of the conventional rectifier of the capacitor input type according to the above-mentioned construction is as follows. If the switch SW of the AC voltage source 1 is closed (turned ON), and the voltage of the AC voltage source is applied to a bridge rectifying circuit 2, then the AC voltage is rectified by the bridge rectifying circuit 2. The voltage rectified by the bridge rectifying circuit 2 is a pulsating voltage. If a pulsating voltage is applied to the thermistor TH1 of the smoothing block 3 the small amount of the pulsating voltage is applied to the input type capacitor C1 by a voltage drop through the thermistor TH1 and then is smoothed by the input type capacitor C1. If the resistance value of the thermistor TH1 becomes gradually small, because of a temperature rise in accordance with the power dissipation of the thermistor TH1, the voltage drop across the thermistor TH1 becomes small and a large amount of the pulsating voltage is smoothed by the input type capacitor C1. In the case where the temperature of the thermistor Th1 rises and the resistance value of the thermistor TH1 becomes small, if the switch SW1 is closed (turned off) and immediately is turned ON the resistance of the thermistor TH1 remains small and so a large amount of inrush current due to an initial momentary short flows through the input type capacitor C1. Accordingly, to prevent the inrush current, as just described, and only when the resistance value of the thermistor TH1 restores to an original state, is the switch SW turned ON.
As explained above, in the capacitor input type rectifier of the prior art, a power type thermistor was added to an output portion of the rectifying circuit to prevent the inrush current. A thermistor represents a thermally sensitive resistor such that the resistance value varies in accordance with the temperature variation. There is a negative temperature characteristic thermistor wherein the resistance value drops in accordance with a temperature rise, and to the contrary, a positive temperature characteristic thermistor in which the resistance value rises in accordance with the temperature rise. Generally, the thermistor that is used has a negative temperature characteristic. Accordingly, if such a thermistor is used, the AC voltage is rectified before being input into the smoothing circuit, and an initial voltage drop across the thermistor occurs. Gradually, the temperature of the thermistor rises because of the heat generated by the resistance of the thermistor, and the resistance value of the thermistor falls. As a result of that, the inrush current caused by the initial momentary short of the input type capacitor can be prevented to a certain extent.
However, the above-described conventional capacitor input type rectifier has the following disadvantages. After the capacitor input type rectifier operates normally, if the supply of the AC voltage is suspended and the supply of the AC voltage is immediately begun, the resistance value of the thermistor remains small, because the temperature of the thermistor does not drop quickly. Accordingly, the inrush current caused by the initial momentary short of the input type capacitor can not be prevented. Therefore, there is an inconvenience in that an input type capacitor having a rated capacity is not able to prevent the inrush current.
SUMMARY OF THE INVENTION
A primary object of the invention is to provide a capacitor input type rectifier having a circuit for preventing or minimizing an inrush current generated by initiation of rectification.
It is another object of the present invention to provide a capacitor input type rectifier having a circuit for preventing a inrush current which improves product reliability by preventing the breakdown of parts due to the flow of a sudden inrush current.
To accomplish the above objects, the present invention is constituted by an Ac voltage source; a phase detection circuit is connected to the above the AC voltage source and detects the phase of the AC power supply; a rectifying circuit is connected to the phase detection circuit and rectifies the AC voltage according to the output of the phase detection circuit; and a smoothing circuit connected to the rectifying circuit is and smoothes the output of the rectifying circuit.
BRIEF DESCRIPTION OF THE DRAWINGS
The above objects, advantages and features of the invention are believed to be readily apparent from the following description of a preferred embodiment of the best mode of carrying out the invention when taken in conjunction with the following drawings, wherein:
FIG. 1 is a circuit diagram showing a prior art capacitor input type rectifier.
FIG. 2 is a detailed circuit diagram illustrating a capacitor input type rectifier according to the present invention having a circuit for preventing inrush current; and
FIG. 3 is a waveform chart of the phase detection circuit for detecting the phase of an AC voltage according to an embodiment of the present invention.
Throughout the figures the same reference numerals are applied to identical components.
DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 2 is a detailed circuit diagram showing a capacitor input type rectifier having a circuit for preventing inrush current according to a preferred embodiment of the present invention. As shown in FIG. 2, a capacitor input type rectifier having a circuit for preventing inrush current comprises: an AC voltage source 1; a phase detection circuit 4 for detecting the phase of an AC voltage with the input terminals thereof connected to an output of the AC voltage source 1; a phase control rectifying circuit 5, the input terminals of which are connected to the output terminals of the AC voltage source 1 and the phase detection circuit 5 for detecting the AC voltage; and a smoothing circuit 3 the input terminals of which are connected to an output terminal of the phase control rectifying circuit 5.
The AC voltage source 1 comprises an AC voltage source; a switch SW with one side terminal connected to the AC voltage source; and a fuse Fl with one side terminal connected to the other side of the switch SW.
Also, the phase detection circuit 4 for detecting the AC voltage comprises a transformation rectifying section 41 connected to the AC voltage source 1 and which outputs a rectified voltage after transforming the AC voltage into DC voltage; and a comparing section 42 connected to the transformation rectifying section 41, and which compares the output voltage of the transformation rectifying section 41 with a reference voltage and outputs the result thereof into rectifying block 41.
The transformation rectifying section 41 comprises a transformer TRN1 with a first coil connected to the output terminal of the AC voltage block 1; and a bridge rectifying circuit with an input terminal is connected to the second coil of the transformer TRN1.
And the comparing section 42 comprises; a resistor R3 connected between the output terminals of the transformation rectifying section 41; an operational amplifier OP with a noninverting terminal connected to a reference voltage Vref, and an inverting terminal connected to the output terminal of the transformation rectifying section 41; a diode D1 which an anode connected to the inverting terminal of the operational amplifier OP; a capacitor C2 connected between a cathode of the diode D1 and a ground terminal of the operational amplifier OP.
In the embodiment of the present invention, a bridge rectifying circuit is used as a transformation rectifying section, however, such use is for purposes of description and it is to be understood that the invention is not limited to the specific bridge rectifying circuit described herein.
Additionally, a phase control rectifying circuit 5 comprises: a bridge rectifying circuit consisting of two diodes and two silicon controlled rectifiers (SCRs); resistors R1, R2 respectively connected to gate terminals of the SCR. The above SCR is a rectifying element having a property that once the SCR is turned ON, and if the current flowing in the SCR is kept at more than the cut in current, the SCR is conditioned to be turned ON, regardless of the existence or non-existence of the gate current, and if the SCR is conditioned to be turned OFF, the gate signal is restored to control the SCR
A smoothing circuit 3 consists of; a thermistor TH1 with one side terminal connected to the output of a phase control rectifying circuit 5; and a capacitor C1 connected between the other terminal of the thermistor TH1 and ground.
The operation of a capacitor input type rectifier having a circuit for preventing inrush current according to the embodiment of the present invention embodied as described above is as follows.
If the voltage of an AC voltage source is assumed to have the waveform as shown FIG. 3A is input to the transformer TRN1 of a transformation rectifying section 41, the transformer TRN1 transforms the AC voltage into a low voltage of 15 V, and then outputs the transformed voltage to a bridge rectifying circuit B. FIG. 3B illustrates the voltage transformed by transformer TRN1.
If the voltage having the waveform shown in FIG. 3B and transformed into a +15 V DC output is applied to the bridge rectifying circuit B, the applied voltage is rectified by the bridge rectifying circuit B to produce a pulsating voltage which is then applied to resistor R3 of a comparing section 42. If the pulsating voltage is applied to the resistor R3, the diode D1 is turned ON. And as the capacitor C2 is charged, the power is supplied to the operational amplifier OP, and thus the operational amplifier OP is operated. The voltage applied to the resistor R3 is compared with a reference voltage Vref, and in the situation where the voltage applied to the resistor R3 is lower than the reference voltage Vref, a pulse is output from an operational amplifier OP.
FIG. 3C shows a pulsating voltage applied to a resistor R3, and a reference voltage Vref is input to an operational amplifier OP. In the embodiment of the present invention, a reference voltage Vref is 2.5 V; however, the technical scope of the present invention is not limited to this voltage and the reference voltage Vref can be varied in order to precisely detect the phase of an AC voltage.
Also, FIG. 3D shows the output signal of operational amplifier OP. If the SCR of the phase control rectifying circuit 5 is turned ON by the output signal of the operational amplifier OP having the waveform of FIG. 3D, the voltage signal of the AC voltage of the AC voltage source 1 starts to be rectified. If the voltage signal of the AC voltage decreases so that the SCR o the phase control rectifying circuit 5 is turned OFF, the output signal of the phase detection circuit 4 for detecting the AC voltage turns ON the SCR of the phase control rectifying circuit 5. As a result, the voltage of the AC voltage is rectified continuously.
The output signal of the rectified pulsating voltage of the phase control rectifying circuit 5 is output to the smoothing circuit 3, the pulsating voltage is smoothed by the capacitor C1 of the smoothing circuit 3.
As shown in FIG. 2, the comparing section 42 of the phase detection circuit 4 for detecting the AC voltage outputs the pulsating signal, and so makes the SCR of the phase control rectifying circuit 5 turn ON when the voltage value of a sine wave signal, the AC voltage is the smallest phase, namely, when the phase angles are 0, 180, 360 and 540 degrees. Accordingly, only when the AC voltage of the AC voltage source is the smallest is the phase control rectifying circuit 5 allowed to operate. Thus, the inrush current caused by the initial sudden short of the input type capacitor C1 of the smoothing circuit 3 can be minimized.
As explained herein, the capacitor input type rectifier having an effect of preventing an inrush current caused by the initial sudden shorting of the input type capacitor can be provided by starting to rectification, when the AC voltage is the smallest in the embodiment of the present invention. The effect achieved by the present invention can be applied to all power supply circuits using capacitor input type rectifying and smoothing circuitry.
The above description is presented solely for the purpose of describing the invention and those skilled in the rectifier art will readily recognize modifications, alterations and changes to the structure described herein without departing from the spirit and scope of the invention which is too be determined by the appended claims and the equivalents to which the claimed invention is entitled. | A capacitor input type rectifier having a circuit for preventing an inrush current uses an AC phase detector for detecting the time that an AC voltage input has the smallest phase angle and provides an output signal indicative thereof to a phase control rectifier for initiating rectification of the AC voltage to provide a rectified output to a smoothing circuit for smoothing the rectified output of the phase control rectifier. | 7 |
BACKGROUND OF THE INVENTION
The present invention pertains to the field of slidable fasteners (commonly called "zippers") and the repair thereof. In particular, the present invention is used to remedy nearly any inoperable slidable fastener, especially one that has missing or dysfunctional interlocking elements, without removing the inoperable slidable fastener from its article.
Slidable fasteners have been used for decades in a wide variety of articles including clothing, tents, luggage, bags and wallets. A slidable fastener (hence fastener) is generally comprised of a pair of juxtaposed, matable or interlockable stringers, and, depending on the construction and type of fastener, also includes one or more sliders, stops, boxes, and/or separating pins (pins) attached to one or both of its stringers. A "stringer" is a long, tape-like strand with interlocking element/s attached along one edge. Typical interlocking elements employed in a fastener include spaced apart teeth, a coil, and the tongue and groove, however, other types of interlocking elements, such as that disclosed in Shopalovich-917 discussed below, are known in the art. The interlocking element-present edges of the pair of stringers of a fastener face one another and in most cases are joined/separated by the slider that joins/separates the interlocking elements of the left stringer with/from the interlocking elements of the right stringer when the slider is moved up/down the length of the stringer pair. Fasteners employing the tongue and groove type interlocking elements may be joined/separated simply by manually pressing/pulling the tongue and groove together/apart.
In both separating and non-separating fasteners a stop and a box each function to prevent the slider from becoming completely derailed from the stringer, and may further function to keep the closed portion of a fastener below the slider from separating. Although most stops are in the form of a clamp-like member attached over the interlocking elements of one or both stringers, a stop could be effected by a large variety of other means, including stitching over interlocking elements, folding down then securing the end of a stringer, enclosing the end of a stringer(s) in a seam, fusing interlocking elements, or even securing a safety pin at the end of a stringer(s), all of which function to prevent the slider from derailing and/or keeping the lower interlocked portion from separating. In separating zippers, the pins and box enable the user to easily align the slider and two stringers in preparation for zipping up, or, to easily separate the two stringers from one another after unzipping. A fastener is installed in an article by sewing, tacking, glueing or otherwise securing the tape portion (the side without interlocking elements) of each stringer directly to both sides of the opening in which the fastener is to be positioned.
Whenever a fastener breaks down the utility or desirability of the article containing the fastener is reduced or obliterated necessitating repair or replacement of the fastener to return the article to full utility. Generally, there are three reasons why a fastener ceases to function: problems involving the slider, problems with a stop, box or pin, or problems with the interlocking elements of one or both stringers. A fastener can be directly repaired in limited circumstances, but where there is no way to directly repair an inoperable fastener, the only solution left in the art is to remove the offending fastener from the article's opening and install another fastener in the stead thereof.
Fasteners that cease to work properly due to a damaged or missing slider/stop can be directly repaired by first removing the offending slider/stop (if necessary), then either installing an operational stop/slider in the stead thereof, or, in the case of a problem with a stop, using one of the alternative stop measures disclosed supra such as whip stitching over the interlocking elements with needle and thread to form a lump of threads that act as a stop. However, these solutions require the repairer to accurately diagnose the source of fastener inoperabililty which in the case of an inoperable slider may not be obvious, and also requires the repairer to have another slider/stop of the proper size plus tools such as a screwdriver, needle, thread and/or pliers. Unlike the stop and slider, there is no known solution to replace a missing or damaged pin or box because the art requires pins and boxes to be attached to the stringer by a fastener manufacturer. Articles with separating fasteners with missing or dysfunctional pins or box must have the inoperable fastener removed and another separatable fastener installed in the article's opening.
Conventional fasteners with missing, damaged or otherwise dysfunctional interlocking elements cannot be mended at all, the only way to return the article possessing such a fastener to full utility is to remove the inoperable fastener from its article, then install another fastener in the empty opening. This process is tedious and labor intensive, often requiring the taking apart of the article to remove the offending fastener and to insert another fastener therein followed by reassembling the article. In many articles, like tents and luggage, this type of repair is economically or practically infeasible resulting in the article being discarded rather than replacing the inoperable fastener. Sometimes replacement of an inoperative fastener may be impossible because removing the inoperable fastener and installing another would destroy the article containing it. In still other situations an inoperative fastener needs to be repaired immediately, in the field, where sewing machines, thread, pliers and other implements of repair are unavailable, such as in the case when a fastener belonging to a sleeping bag or tent breaks down on a very cold night.
U.S. Pat. No. 4,130,917 (Shopalovich 1978) teaches a water tight fastener having male-female coupling elements wherein the male element is designed such that it can be easily removed then replaced. However, the Shopalovich attempt to solve the problem of zipper malfunction due to missing or damaged interlocking elements is only applicable to Shopalovich type fasteners, not to conventional zippers utilizing teeth/coil elements that are not readily interchangeable. Further, the Shopalovich type fastener does not appear to teach a replaceable female interlockable component thus, a faulty female component is not directly repairable and necessitates replacing that fastener with a functioning one. It should be apparent then, that for the vast majority of fasteners a solution for missing, damaged or otherwise inoperable interlocking elements is yet to be found in the art.
Accordingly, the art has yet to provide a remedy for conventional inoperable fasteners with missing, damaged or otherwise inoperable interlocking elements that does not involve removing the old, inoperable fastener, then sewing or bonding another, operable fastener in the stead thereof. And furthermore, the art has yet to provide a simple, single solution for the non-expert to remedy any inoperable fastener regardless of the cause of inoperability.
SUMMARY OF THE INVENTION
The present invention involves a device for repairing virtually any article having an inoperable fastener by essentially interposing a functional fastener/stringer between the stringers of the inoperable fastener. The new fastener/stringer is positioned in parallel proximity to the old fastener/stringer with the assistance of a channel member affixed to or otherwise integrated with the new fastener/stringer member. Henceforth, the term "new fastener/stringer" and "old fastener/stringer" is hereinafter used to distinguish the fastener/stringer integrated with or affixed to the channel member of the present invention (the "new fastener/stringer") from the inoperable fastener/stringer belonging to the article that is in need of repair (the "old fastener/stringer"); and, the term "affix" means to attach to or be integral with.
Generally, the present invention involves affixing the tape portion of a stringer member (hence stringer) to a channel member in such a way that the new stringer's interlocking element-present edge is sufficiently free from the channel member and the mode of attachment to the channel member that the new stringer is unimpeded during fastener operation. The stringer tape portion may be affixed to the channel member by any suitable means of attachment including sewing, glueing, bonding, welding, fusing, and tacking.
The channel member of the present invention is an elongate, substantially hollow member having a hollow core area and a longitudinal narrow opening. The narrow opening is bordered by opposing upper and a lower edges and is adapted for receiving and holding fast a stringer by its interlocking element-present edge. The channel member is preferably made of a material, such as plastic, that is flexible or resilient enough to permit the lower and/or upper edges to be pried apart to widen the longitudinal opening sufficiently far to admit the entry of the interlocking element portion of an old stringer into the hollow core, yet not so flexible that the edges are not capable of returning to their original or near original position. In this way, the upper and lower edges hold an old stringer fast by compressing the tape of the old stringer just behind the interlocking elements, and/or, by trapping the interlocking elements and resisting their withdrawal from the hollow core.
The channel member may be further adapted to facilitate the insertion of the old stringer into the channel by including a flange portion coextending from an edge of the opening. The flange portion can be unbroken or can be "fringed." The term "fringed" means to have a plurality of contiguous projections and may or may not include a visible space between the projections. Thus, the projections of a fringed flange may be spaced apart and appear comb-like or may be touching or nearly touching and appear keyboard-like. The upper and/or lower edges of the channel member may be adapted to increase their ability to hold onto the old stringer tape, and/or, to increase their ability to trap the interlocking elements of the old stringer. These adaptations may include curving either or both edges inward, making the edges sharp, changing the positions/shapes of the edges and/or channel member body to increase the pressure the edges exert on or against the old stringer, and/or a combination of these adaptations. The term "sharp" can mean thin edged or having points.
It should be apparent that because use of the device of the present invention effectively interposes a new fastener between the stringers of an old fastener, actually using the old fastener as a substrate, the device of the present invention dispenses completely with the inconvenience of removing the old fastener from and installing a new fastener/stringer in an article's opening. This means, for some articles, there may be no need to take the article with the inoperable fastener to a seamstress, luggage repairman or other specialist. And even further, the present invention does not require the user to accurately diagnose the cause of inoperation or possess tools, the proper parts or skills associated with the direct repair of an inoperable fastener because the present invention can effectively remedy virtually any dysfunctional fastener regardless of type of article, location in the article, type of fastener, or cause of fastener inoperation without such tools, parts, diagnosis or mending skills. Finally, the present invention makes it possible to quickly repair the article having an inoperable fastener in the field where tools and/or expertise are absent such as the situation where a zipper in a tent or sleeping bag becomes inoperable on a cold night, or where the zipper of a suitcase malfunctions while traveling. Never before has remedying an inoperable fastener been so simple to use and quick to implement.
It should be evident that while the description of the device of the present invention disclosed above involves affixing a right and left channel member to a new fastener, the present invention also includes a single new stringer affixed to a single channel member without necessarily including a stop, slider, pin or box on the new stringer. While generally it may be more aesthetically pleasing and simpler to use the present invention to interpose an entire new fastener in place of the inoperable old one, the present invention may be used to operationally interpose only one new stringer in an old fastener where only one stringer is needed or desired. For example, the single stringer and channel member embodiment of the present invention could be used to remedy an inoperable non-separating fastener by connecting a new stringer-channel member, having interlocking elements of a compatible size and type, to just one of the old stringers. A slider then would be positioned on the new stringer and old stringer now opposing the new stringer to slide over their respective interlocking elements. This slider could be the slider that belonged to the old fastener, or another. Although the new-old stringer duo and slider just described can function without more to close the opening of the article which contains the same, it is preferable to add an end stop at the bottom of the new-old stringers and a stop at the top of the new stringer to prevent slider derailment and separation below the slider.
Accordingly, it is a prime objective of the present invention to provide an improved and novel device for remedying an inoperable slidable fastener without the need for removing the fastener from its article.
A further object of the present invention is to provide a novel device for remedying an inoperable slidable fastener that is simple to use regardless of cause of fastener dysfunction.
Still another object of the present invention is to provide a new device with which to remedy a slidable fastener or stringer with missing, damaged or otherwise inoperable interlocking elements.
These and still further objects as shall hereinafter appear are fulfilled by the present invention in a remarkably unexpected manner as will be readily discerned from the following detailed description of exemplary embodiments thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a first embodiment of the device of the present invention having a non-separating fastener affixed to a right and a left slotted channel member with fringed flange.
FIG. 2 is a cross section of said first embodiment in use taken along line 2 in FIG. 3.
FIG. 3 is a perspective view of the top portion of said first embodiment shown here in use in an article.
FIG. 3A is a plan view of the bottom portion of said first embodiment in use in the article of FIG. 3.
FIG. 4 is an isolated view of a channel member of said first embodiment.
FIG. 5 is a perspective view of a representative portion of a second embodiment of the present invention.
FIG. 6 is a cross section of a representative portion of a third embodiment of the present invention.
FIG. 7 is a cross section of a representative portion of a fourth embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to FIGS. 1, 2, 3, 3A, and 4, herein is disclosed a first preferred embodiment 1 of the present invention. Comprising said first embodiment 1 is a new fastener 12 having a left and a right stringer 15, 15' with tape portions 8, 8' firmly affixed with adhesive or other means to the respective tops of a left and a right channel member 2, 2', such that channel members 2, 2' are reciprocally positioned on opposite sides of fastener 12 and slider 19 freely slides along stringers 15, 15', as shown. Tape portions 8, 8' have, respectively, stops 10, 10' and coils 9, 9' as shown. End stop 13 is positioned across the ends of both stringers 8 and 8' as shown. To more completely disclose the construction of channel members 2 and 2', channel member 2 is now disclosed in detail detached from tape portion 8. Referring to FIG. 4, channel member 2 comprises a substantially tubular or round wall defining a hollow core 3 and a narrow longitudinal opening 14 (opening 14 is best viewed in FIG. 1) bordered by a lower ridge shaped edge 6 and an upper inwardly tapered and curved edge 7. Channel member 2 further includes an integral fringed flange 4 extending approximately 0.125 of an inch outward from lower edge 6 as shown with approximately 2 comb-like projections per 0.125 inch of longitudinal flange length. The wall of channel member 2 also includes a plurality of spaced apart slots 5 in the channel wall opposite opening 14 reserving a region 55 of channel member 2 on which to adhere said tape portion 8. Channel member 2 is preferably made of flexible plastic using conventional manufacturing methods but could be made with any other material or combination of materials that lends longitudinal flexibility to channel 2.
Referring now to FIGS. 2, 3 and 3A, herein is described how to use said first preferred embodiment to remedy an inoperable old fastener already installed in an article 11 having a left and a right old stringer 16, 16' respectively having tape portions 17, 17', coils 18, 18', and top stops 20, 20', and, end stop 21 positioned across both old stringers 16 and 16' as shown. First, left and right stringers 16, 16' of said old fastener are separated where they are not already separated and the old fastener slider (not depicted) preferably removed. Left coil 18 is manually forced between channel member edges 6 and 7 and through opening 14 of left channel member 2 until coil 18 and stop 20 occupies hollow core 3 and tape portion 17 is compressed between edges 6 and 7. Right stringer 16' is likewise inserted into channel member 2' until the end of new fastener 12 is located as close to old end stop 21 as possible. It should be evident that the resilience of the flexible channel member wall enables edges 6/7 and 6'/7' to spring back after the insertion of coils 18, 18' and compress tape portions 17, 17' as best shown in FIG. 2 Further, edges 6/7 and 6'/7' may also catch onto coils 18/18' and/or stop 20/20'. Thus, the compression and/or the catch actions of edges 6/7 and 6'/7' effectively hold fast the old stringers 16/16' in parallel proximity respective to the stringers 8/8' of fastener 12. It should be further evident that the size of hollow core 3/3' should be at least large enough to physically accommodate coil 18/18' and may be larger so as to accommodate a larger range of interlocking element sizes. Although the new fastener of the present invention and the old fastener being remedied depicted in FIGS. 1-4 are both non-separating fasteners with coils, it should be evident that either/both the new fastener or/and the old fastener could be a separating fastener or could possess interlocking elements other than coils.
The shape and size of the channel member of the present invention, the mode of attachment of the stringer to the channel member, and the location on the channel member where the new stringer is attached can vary widely. Referring now to FIG. 5, a representative portion of a second preferred embodiment of the present invention is shown. Said second preferred embodiment comprises a new fastener having its left and right stringers affixed to respective channel members comparable to that relating to said first embodiment disclosed above. FIG. 5 shows in detail right channel member 36 and right stringer 37 of said second embodiment. Channel member 36 is a cylindrical, flexible plastic tube having a longitudinal opening 33 bordered by upper edge 34 and lower edge 35. Stringer 37 has tape portion 31 and coil 30, wherein tape portion 31 of stringer 37 is affixed with stitching 32 to the outer surface of tube 36 by spreading apart edges 34 and 35 and sewing through tube 36 and stringer 37, as shown. This second embodiment could be further modified to improve its overall flexibility for use in some applications, such as remedying an old fastener belonging to luggage, by providing slots/spaces in the wall of tube 36 in the wall areas, top and/or bottom, that are unoccupied by stitching 32.
Referring now to FIG. 6, a cross sectional view of a representative portion of a third preferred embodiment is shown. Said third preferred embodiment comprises a fastener having right and left stringers affixed to respective flanged channel members comparable to said first preferred embodiment above. FIG. 6 shows in cross sectional detail a left channel member 39 and left stringer 42 of said third preferred embodiment. Channel member 39 includes a flange 54, an upper edge 40, and a lower edge 43 bordering longitudinal opening 38. Upper edge 40 is in the form of a plurality of inwardly curved teeth like points 44 (only one of which is visible in this cross sectional view) for piercing into the tape portion of an old stringer 41 when in use. Lower edge 43 is in the shape of an inwardly directed ridge that further enables said third embodiment to hold old stringer 41 fast in place in channel member 39 when in use. Flange 54 is fringed and also tapered so as to become thinner as it extends away from said edge 43. Channel member 39 is slotted, comparable to that depicted in FIG. 4. New stringer 42 is affixed with an adhesive to the top portion of channel member 39 as shown.
FIG. 7 shows a in cross sectional view of a representative portion of yet another preferred embodiment comparable to the previous embodiments, comprising a new fastener having its right and left stringers affixed to the underside of respective channel members. FIG. 7 shows in cross sectional detail a left channel member 45 and left stringer 49 of said fourth preferred embodiment. Channel member 45 is a boxy in shape and has an upper edge 47, a flattened wall portion 48, and a flange 52 coextensive with wall portion 48 as shown. A flat lower edge 50 (here actually merged with flange 52 and occupying a linear area of flange 52 and/or wall portion 48 opposite upper edge 47) together with upper edge 47 define a longitudinal opening 51 in which an old stringer 46 can be inserted and held in a similar manner as that described for the embodiments above. New stringer 49 is strongly adhered to the underside of said flattened wall portion 48 of channel member 45 as shown. The channel members of this embodiment can likewise be further modified to include slots in the channel member wall(s) and/or a fringed flange in a manner similar to that heretofore disclosed.
It should be evident that the new stringers in all of the embodiments above are attached to the respective channel members such that the interlocking element portion of the stringer is operationally unencumbered by the channel member. It should be further evident that the fasteners utilized in the present invention may be separating or non-separating.
It should also be apparent that due to the versatility of the fastener and fastener repair art that the present invention includes simple embodiments comprising a stringer affixed to a channel member constructed in a similar manner as the embodiments including a fastener taught and described above. This simple embodiment has several possible uses including as a component used to repair an article with an inoperable old fastener having only one dysfunctional stringer with missing or damaged interlocking elements by attaching said simple embodiment having interlocking elements that are matable to the interlocking elements of the remaining stringer of the old fastener to said dysfunctional stringer, then securing a slider, stop, box, and/or pin, or equivalent measure, as needed, to the new stringer of said simple embodiment to result in an article having an operable fastener made of new and old components. Plainly, two of said simple embodiments, one having interlocking elements that are matable with those of the other, could also be used to similarly remedy an inoperable fastener having two dysfunctional stringers.
Another embodiment, intended to be cut-to-length and used as a component for repairing an article with an inoperable fastener, or, for in field/emergency repairs where tools are limited or unavailable, comprises a pair of interlockable stringers affixed respectively to a pair of channel members, a slider joining said stringers, and an end stop (for non-separating fastener result), or alternatively, pins and box (for a separating fastener result), secured to the bottom ends of said stringers. These cut-to-fit embodiments are especially useful in repairing tents and sleeping bags with broken fasteners. It should be evident that after the instant embodiment is cut to the desired length it may be desirable to effect a stop at the top end of one or both new stringers to prevent slider derailment when zipping up.
Finally, even though the present invention is especially applicable for remedying an inoperable stringer/fastener already installed in any article, including clothing, tents, luggage, bags, and wallets, without removing the inoperable stringer from its article, the present invention could be used as a way to simply substitute a fastener of a desired size/type for a fastener of undesired size/type.
From the foregoing, it is readily apparent that a useful embodiment of the present invention has been herein described and illustrated which fulfills all of the aforestated objectives in a remarkably unexpected fashion. It is of course understood that such modifications, alterations and adaptations as may readily occur to the artisan confronted with this disclosure are intended within the spirit of this disclosure. | A device comprising a slidable fastener or slidable fastener stringer affixed to a hollow channel member, wherein said channel member has an upper and a lower edge defining a longitudinal opening for receiving and holding the interlocking elements and/or a portion of the tape of a stringer belonging to an inoperable slidable fastener. The device of the present invention is used particularly to remedy the problem of an inoperable fastener already installed in the article, without removing the inoperable fastener from its article, by connecting the present invention to the old stringer/fastener thereby interposing a functioning fastener/stringer in said article between the stringers of the existing, inoperable fastener. The channel member of the present invention may have slots in its walls to increase its flexibility, may have a flange coextensive with an edge to facilitate insertion of the old stringer between said edges, or may have upper and lower edges modified to increase the ability of said edges to hold onto the old stringer. | 0 |
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to G.B. provisional application, 0515073.5, filed Jul. 22, 2005, the entire contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a connector for use downhole and to a release and/or retrieval tool for releasing, and/or retrieving the connector from downhole.
BACKGROUND OF THE INVENTION
[0003] The use of connectors to join lengths of tubing in oil wells is well known. One particular use of connectors is to connect lengths of tubing together to form a straddle to seal, for example, a perforated zone that is no longer producing hydrocarbons, or a leak in a section of casing.
[0004] Conventional modular straddle systems where the straddle is made up of connected sections of tubing, can be difficult to remove from a well as multiple sections or modules may return to surface at the same time and be too large to be removed from the lubricator section.
[0005] Accordingly, tube connectors that are releasable and tools that release them and allow them to be retrieved from downhole may be desirable in the art.
BRIEF DESCRIPTION OF THE INVENTION
[0006] Disclosed herein relates to a tubing connection release system. The system comprising, a male connector having a profile at one end thereof and receptive to a tubular at one end thereof, a female connector receptive to a tubular at one end thereof and receptive to the male connector at another end thereof. The system further comprising, a sleeve disposed radially inwardly of the female connector, and a collet having at least one deflectable collet finger disposed radially inwardly of the sleeve. The collet being biased to a position within the female connector where at least one collet finger is supported against radially outward deflection. The collet further being urgable by the push-in connector against the bias to a position where at least one collet finger is radially outwardly unsupported such that the profiled end of the male connector is movable into engagement with at least one collet finger.
[0007] Further disclosed herein is a device that relates to a release and retrieval tool. The tool comprising, a body, a first collet selectively repositionably attached to the body such that repositioning relative to the body occurs at a first selected load related to a disengagement position of a target engagement. The tool further comprising, a second collet selectively repositionably attached to the body such that repositioning relative to the body occurs at a second selected load related to a disengagement position of a target device subsequent to the disengagement.
[0008] Further disclosed herein is a device that relates to a diagnostic shifting tool. The tool comprising, a mandrel having at least one recess therein. The tool further having a collet disposed at the mandrel and positionable on the mandrel to support or unsupport a deflectable finger of the collet with respect to a release arrangement. The release arrangement selectively retaining a portion of the collet relative to the mandrel pending the collet experiencing a load exceeding a load retaining capability of the release arrangement. The load retaining capability being selected to allow release at a load less than a load associated with failure of a target device.
[0009] Further disclosed herein is a method for diagnosing a release and retrieval problem. The method comprising, running a release and retrieval tool having a pair of load limited release mechanisms. The method further comprising, engaging a disengagement mechanism in a target device with the tool, attempting to disengage the disengagement mechanism in the target device with the tool, engaging a retrieval feature of the target device with the tool. Subsequently, pulling the tool uphole, and examining the tool release mechanisms for evidence of overload.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The following descriptions should not be considered limiting in any way. With reference to the accompanying drawings, like elements are numbered alike:
[0011] FIG. 1 is a perspective view of a section of tubing section including a female and a male connector portion according to an embodiment of the present invention;
[0012] FIG. 2 is a cross-sectional side view of the female connector of FIG. 1 ;
[0013] FIG. 3 is a cross-sectional side view of the male connector of FIG. 1 ;
[0014] FIG. 4 is a perspective view of a releasing and retrieval tool for releasing and retrieving the section of tubing string of FIG. 1 ;
[0015] FIG. 5 is a cross-sectional side view of the tool of FIG. 4 ;
[0016] FIG. 6 is a cross-sectional side view of the section of tubing string of FIG. 1 prior to engagement with an adjacent section of tubing string;
[0017] FIG. 7 is a cross-sectional side view of the sections of tubing string of FIG. 6 connected;
[0018] FIG. 8 is a cross-sectional side view of the tool of FIG. 4 prior to entering the connected tubing strings of FIG. 7 ;
[0019] FIG. 9 is a cross-sectional side view of the tool of FIG. 8 partially inserted into the connected sections of tubing string;
[0020] FIG. 10 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the tool releasing collet profile engaged with the female connector latch sleeve no-go;
[0021] FIG. 11 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the tool releasing collet profile passing the female connector latch sleeve no-go;
[0022] FIG. 12 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the tool releasing collet shoulder engaged with the female connector latch sleeve no-go;
[0023] FIG. 13 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the tool releasing collet profile engaged with the female connector latch sleeve no-go;
[0024] FIG. 14 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the tool moving towards surface having moved the latch sleeve such the female connector can be pulled away from the adjacent male connector;
[0025] FIG. 15 is a cross-sectional side view of the tool and the connected sections of tubing string particularly showing the retrieving collet engaging the tubing string male connector internal profile permitting the section of tubing string to be recovered;
[0026] FIG. 16 is an enlarged cut away perspective view of the latch collet passing over the male connector external profile;
[0027] FIG. 17 is an enlarged cut away perspective view of the latch collet secured to the male connector external profile;
[0028] FIG. 18 is a cross-sectional side view of the latch collet secured to the male connector external profile;
[0029] FIG. 19 is an enlarged cut away side view of the retrieving collet prior to engaging the male connector portion inlet section;
[0030] FIG. 20 is an enlarged cut away side view of the retrieving collet passing through the male connector portion inlet section;
[0031] FIG. 21 is an enlarged cut away perspective view of the release collet engaging the latch sleeve no-go;
[0032] FIG. 22 is an enlarged cut away side view of the release collet profile engaging the latch sleeve no-go;
[0033] FIG. 23 is an enlarged cut away perspective view of the latch sleeve shown jammed in the secured position by debris;
[0034] FIG. 24 is an enlarged cut away perspective view of the release collet deflecting to pass the latch sleeve no-go; and
[0035] FIG. 25 is an enlarged cut away perspective view of the release collet released from the latch sleeve no-go.
DETAILED DESCRIPTION OF THE INVENTION
[0036] A detailed description of several embodiments of the disclosed apparatus and method are presented herein by way of exemplification and not limitation with reference to the Figures.
[0037] Referring firstly to FIG. 1 , there is shown a section of tubing string generally indicted by reference numeral 10 including a female connector portion 12 , and a male connector portion 14 , according to a first embodiment of the present invention. The tubing string 10 also includes a length of tubing 16 and is shown located inside a cased bore 18 .
[0038] Referring to FIG. 1 and to FIG. 2 , an enlarged cross-sectional side view of the female connector of FIG. 1 , the female connector portion comprises a housing 20 , a latch 22 , and a latch support 24 .
[0039] The latch 22 is a collet 26 , which includes a plurality of collet fingers 28 , each collet finger 28 defining a radially inwardly extending profile 30 . The profile 30 is adapted to engage a complementary recess defined by an adjacent male connector portion profile (not shown). Also visible are a pair of seals 21 , which engage and seal the tubing section 10 to an adjacent tubing section.
[0040] The latch support 24 is an axially moveable sleeve 32 , having a latch engaging surface 33 and a latch support recess 92 .
[0041] The male connector portion 14 can be seen in FIG. 3 , which is an enlarged cross-sectional side view of the male connector portion 14 . The male connector portion 14 comprises a housing 34 defining a raised external profile 36 adapted to engage the collet finger profile 30 of an adjacent female connector portion (not shown).
[0042] FIG. 4 shows a perspective view of a releasing and retrieving tool 40 , for releasing the tubing string 10 from an adjacent tubing string, and retrieving the tubing string 10 to surface. A cross sectional side view of releasing and retrieving tool 40 is shown in FIG. 5 .
[0043] The tool 40 comprises a releasing means 42 and retrieving means 44 .
[0044] The releasing means 42 is a releasing collet 46 comprising a plurality of collet fingers 48 defining an outwardly extending profile 50 . The releasing collet 46 is mounted circumferentially around a lower tool body 52 .
[0045] The retrieving means 44 is also a collet 54 , having fingers 56 defining a radially extending profile 58 . The retrieving collet 54 is mounted to an upper tool body 60 .
[0046] As can be seen from FIG. 5 , both collets 46 , 54 are axially moveable with respect to their respective tool body 52 , 60 . The releasing collet 46 includes a shear screw 62 , which is moveable within a slot 64 defined by the lower tool body 52 . The releasing collet 46 is biased to the rest position shown in FIG. 5 by means of a spring 66 (shown in broken outline). In this position the releasing collet finger profile 50 is prevented from flexing inwardly by an increased diameter portion 68 of the lower body 52 . When the collet 46 is located such that the shear screw 62 is at the other end of the slot 64 , the collet fingers 48 can deflect radially inwards into a reduced diameter portion 70 of the lower body 52 .
[0047] The retrieving collet 54 operates in a similar way, with the shear screw 72 being adapted to slide in slot 74 and the retrieving collet 54 being biased to the rest position shown in FIG. 5 by means of spring 76 (shown in broken outline). The retrieving collet 54 is prevented from flexing inwardly in this rest position by the increased diameter section 78 of the upper body portion 60 . When the retrieving collet 54 has moved axially, such that the shear screw 72 is at the other end of the slot 74 , the collet fingers 56 can deflect inwardly towards the reduced diameter section 80 of the upper body portion 60 .
[0048] FIGS. 6 to 15 are a series of cutaway side views of showing a section of the tubing string 10 connecting to an adjacent section of tubing string 82 ( FIGS. 6 and 7 ) and the tubing string 10 being released from the adjacent string 82 , retrieved to surface by means of a releasing and retrieving tool 40 (FIGS. 8 to 15 ).
[0049] FIG. 6 shows the tubing string 10 being moved in the direction of arrow A, that is downhole, towards the adjacent tubing string 82 . The female connector portion 12 of the string 10 engages the male connector portion 84 of the adjacent string 82 .
[0050] As can be seen from FIG. 7 , the latch collet finger profile 30 passes over and engages the male connector portion external profile 86 . The interim steps of this engagement can be seen more clearly in FIGS. 16 and 17 , which will now be described.
[0051] FIG. 16 shows a partially cutaway enlarged side view of the female connector portion 12 engaging with the male connector portion 84 . As the male connector portion 84 is introduced into the female connector portion 12 , the male portion leading edge 88 impacts on the latch profile 30 . This impact causes the latch collet 26 to move towards the latch spring 90 , depressing the spring 90 .
[0052] As the latch collet 26 moves, the latch engaging surface 33 on the latch support 26 no longer prevents the profiled end of the collet finger 28 deflecting outwardly. As the force in the spring 90 approaches the force applied by the male connector portion 14 , the latch collet 26 will deflect into the recess 92 defined by the latch support sleeve 32 . This deflection permits the collet 26 to open up sufficiently to permit the male connector profile 86 to pass the collet finger profile 30 .
[0053] Turning now to FIG. 17 , once the male connector profile 86 has passed the collet finger profile 30 , the spring 90 forces the collet 26 back to the position in which the latch support sleeve 32 prevents deflection of the fingers 28 . This is shown in FIG. 18 , an enlarged cross-sectional side view of tubing string 10 connected to an adjacent tubing string 82 . In this position, the collet finger profile 30 is secured in position by the latch support sleeve 32 , particularly by the latch engaging surface 33 , preventing the tubing strings 10 , 82 from being pulled apart.
[0054] Referring now to FIG. 8 , this is the first figure in a series showing the release of the tubing string 10 from the tubing string 82 and its retrieval to surface. For this purpose, a releasing and retrieving tool 40 is introduced.
[0055] As the tool 40 is introduced ( FIG. 9 ), the releasing collet profile 58 passes through the male connector portion 14 unhindered as the internal diameter of the male connector portion 14 is wider than the external diameter described by the releasing collet profile 50 .
[0056] The retrieving collet profile 58 , however, describes a greater diameter than the diameter described by the inlet portion 94 of the male connector portion 14 . FIGS. 19 and 20 are partially cutaway enlarged views showing the retrieving collet 54 entering the male connector portion 14 . As the tool 40 passes through the male connector 14 , the retrieving collet profile 58 impacts on the male connector inlet portion 94 . When this happens, the retrieving collet 54 is forced axially against the spring 76 permitting the retrieving collet fingers 56 to deflect into the reduced diameter region 80 of the upper housing body 60 . The axial movement of the retrieving collet 54 is guided by the shear screws 72 sliding in the slot 74 . The deflection of the collet fingers 56 causes a reduction in the diameter described by the collet finger profile 58 , permitting the retrieving collet to pass through the male connector inlet portion 94 .
[0057] The tool 40 then passes through the tubing string 10 to the position shown in FIG. 10 . In this position the releasing collet profile 50 engages a no-go 96 attached to the support sleeve 32 . This engagement forces the collet latch 46 against the spring 66 permitting the collet fingers 48 and the profile 50 to deflect into the lower body reduced diameter portion 70 , permitting the releasing collet to pass by the no-go 96 .
[0058] FIG. 11 shows the collet fingers 48 at their maximum deflection, which occurs as the releasing collet 46 passes the no-go 96 . Once the releasing collet profile 50 has passed the no-go 96 , the spring 66 recovers the releasing collet 46 to its rest position.
[0059] The tool 40 continues into the female connector portion until the collet shoulder 98 impacts on the no-go 96 , as shown in FIG. 12 . This can be seen more clearly in FIG. 21 , a partially cutaway perspective view of the collet shoulder 98 engaging the latch sleeve no-go 96 .
[0060] This impact informs an operator at surface that the tool 40 has reached the extent of its travel. As the tool 40 can travel no further through the tubing string 10 only one section of string can be retrieved. This is particularly important if the lubricator section (not shown) at surface can only permit the removal of one section of tubing string 10 at a time.
[0061] The direction of the tool 40 can now be reversed, that is the tool 40 is now retrieved towards surface.
[0062] Turning now to FIG. 13 , as the tool 40 is retrieved towards surface, the releasing collet profile 50 engages the no-go 96 . As the releasing collet is in its rest position, the shear screws 62 are already at the extreme end of their travel along slot 64 . The force applied through the tool will act on the no-go 96 and in turn on the sleeve 32 . This force pulls the sleeve 32 to the position shown in FIG. 22 , a partially cutaway side view of the releasing collet 46 acting on the no-go 96 to move the latch support sleeve 32 .
[0063] As the movement of the latch support sleeve 32 continues, the no-go 96 moves towards a housing recess 100 . Once the housing recess 100 is reached, the force on the no-go 96 causes the no-go 96 to slide into this recess 100 permitting the retrieval tool 40 to move away from the female connector portion 12 . In this position, shown in FIG. 14 , the latch support sleeve 32 no longer maintains the collet latch fingers 28 , and in particular, the latch profile 30 in contact with the male connector portion 84 . Once the retrieving collet 54 starts to pull on the tubing section 10 , the latch collet fingers 28 can deflect outwards and pass over the male connector profile 86 .
[0064] Referring back to FIGS. 14 and 15 , in FIG. 14 the female connector portion 12 has been successfully released from the adjacent male connector portion 84 , and the tool 40 is moving through the tubing string 10 to a position where the retrieving collet profile 58 can engage an internal profile 38 defined by the male connector portion 14 . As the retrieving collet shear screw 72 is at the maximum extent of its travel within slot 74 , the force applied from surface to the retrieving tool 40 will cause the tubing string 10 to lift to surface (as shown in FIG. 15 ).
[0065] If, for whatever reason, the latch support sleeve 32 will not move, the tool 40 is adapted to release from the female connector portion 12 without causing damage to the connector portion 12 . This is now described with reference to FIGS. 23 to 25 , partially cut away perspective views of the releasing collet 46 passing the latch sleeve no-go 96 .
[0066] Referring firstly to FIG. 23 , debris 102 has built up behind the support sleeve 32 . This debris 102 is preventing the sleeve 32 from moving to a position in which the no-go 96 can enter the recess 100 , and permit the tool 40 to vacate the female connector portion 12 . In this situation, the pulling (or pushing) force applied to the tool 40 is insufficient to move the sleeve 32 . The force increases to a point where the shear screws 62 shear.
[0067] When this happens the lower body portion 52 moves up the tubing string 10 (see FIG. 24 ). Once the lower body 52 moves with respect to the collet fingers 48 , the releasing collet fingers 48 can deflect radially inwards and pass by the no-go 96 ( FIG. 25 ). When the tool 40 is finally recovered to surface, an operator would note that the releasing collet shear screws 62 have been sheared, indicating that the problem with retrieving the tubing string 10 lies in the releasing of the female connector portion 12 from the adjacent male connector portion 84 .
[0068] If the tubing string 10 is stuck, for example, because the female connector 12 portion has not been released from the male connector portion 84 , or if the tubing string 10 is jammed in the case for some other reason, the shear screw 72 will shear, and the upper tool body 60 will move with respect to the retrieving collet 54 towards surface. The retrieving collet fingers 56 can then deflect towards a reduced tool body diameter 70 permitting the retrieving collet 54 to pass the internal profile 38 , and allow the retrieving tool 40 to be recovered to surface.
[0069] In this situation an operator can inspect the tool 40 , and diagnose why the tubing string 10 has not been recovered to surface. If the releasing collet 46 is intact, and the retrieving collet 54 is sheared, then the tubing string 10 has been released from the adjacent string 82 , but it has become stuck or jammed in the casing. If both collets 46 , 54 are sheared, then the releasing collet 46 has failed to release the female connector portion 12 from the male connector portion 84 of the adjacent string 82 .
[0070] Various modifications may be made to the described embodiment without departing from the scope of the invention. For example, it will be understood that the releasing and retrieving tool could engage a profile on the female connector to recover the section of tubing string to surface.
[0071] Those of skill in the art will recognize that the above-described embodiment of the invention provides a connector that can be separated by an internal release mechanism.
[0072] While the invention has been described with reference to an exemplary embodiment or embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the claims. | Disclosed is a tubing connection release system. The system comprising, a male connector having a profile at one end thereof and receptive to a tubular at one end thereof, a female connector receptive to a tubular at one end thereof and receptive to the male connector at another end thereof. The system further comprising, a sleeve disposed radially inwardly of the female connector, and a collet having at least one deflectable collet finger disposed radially inwardly of the sleeve. The collet being biased to a position within the female connector whereat the at least one collet finger is supported against radially outward deflection. The collet further being urgable by the push-in connector against the bias to a position where the at least one collet finger is radially outwardly unsupported such that the profiled end of the male connector is movable into engagement with the at least one collet finger. | 4 |
TECHNICAL FIELD
[0001] The present invention relates to clinical diagnostic instruments which utilise a light source to illuminate the structure under scrutiny.
BACKGROUND
[0002] Instruments that are used for various diagnostic purposes such as the examination of eyes, ears, noses, and throats and other tissue structures often have a light source contained within the instrument enabling it to emit a light beam so as to illuminate the structure under observation. This is both convenient and practical. An image detection means (whether the human eye or otherwise) is used to register and interpret any resultant returning light.
[0003] Such an instrument may be functionally broken down into a number of smaller modules which each perform a discrete technical operation. Most instruments contain at least four modules in their construction, however extra modules may be added to enable additional functions to supplement those of the core modules.
[0004] The first module is an electrical power supply, which may be powered entirely by the mains with or without a transformer low voltage conversion, or a battery (either standard cells, rechargable cells or a combination of both). The latter battery type is preferred, especially the rechargable type especially when trickle charged because it enables the instrument to be portable and ready for use.
[0005] The second module is a means of controlling the electrical power which should be capable of handling the often high currents generated by the power supply whilst also being capable of varying the electrical power according to requirements. Conventional instruments utilise a heavy-duty ganged rheostat, which acts as an on/off switch and a current limiter thereby varying the electrical power which flows through the light source. The rheostat is typically of a low value (e.g. max resistance of ˜8 ohm when first on, down to ˜0 ohms in an approximately linear manner).
[0006] The third module is a means for generating light which typically is a light source element or elements. Conventional instruments typically use incandescent filament based bulbs that draw a large current (e.g. ˜0.2 A to ˜0.8 A) to enable an acceptable amount of visible light to be produced. Such bulbs are often of the halogen gas filled type which are usually of small size and are of a specialised nature.
[0007] The fourth module is a means for transforming the light, which may comprise lenses, filters, collimating means and other means to transform the light. This module is usually specialized for examining the structure under observation (e.g. eyes, ears etc).
[0008] An extra module that is commonly employed is a means of transforming any returning light from structure under scrutiny. This is often a rack of interchangeable lenses enabling fine focus of the light onto the image detection means.
[0009] The modules are typically combined together so as to produce a convenient, often handheld, combined instrument that is flexible and easy to use, whilst also enabling the instrument to be disassembled to enable replacement of modules (for example replacing expired bulbs). Although it is possible to change the fourth module to form a different instrument, in practice instruments are not usually used in this way and dedicated instruments are used for specific tasks.
[0010] To illustrate this, two widely used diagnostic instruments, namely an opthalmoscope (OS) and retinoscope (RS), will now be described. Both the OS and RS project a beam of light, which is used for examining the eye. Currently available handheld OS and RS have a dial (which is part of the rheostat control module) on the handle of the instrument, which enables light output to be smoothly and precisely varied. Such variability of the light beam is preferable for diagnostic purposes. An OS images a bright, small filament via lenses, mirrors and filters to produce a beam of light which is suitable for illumination of the eye. An RS images a bright, small, thin elongated filament in a similar way. The image detection means (usually the human eye) then receives any returned light, possibly via any fine focus lenses. In a typical clinical environment such an instrument may be in intermittent but repetitive use all day.
[0011] Although diagnostic instruments as described above based on filament bulb technology are widely used they suffer from numerous problems:
[0012] Filament bulbs have a limited life and eventually fail. In a typical clinical environment, depending on usage, this may occur as often as every six months. As a consequence such instruments are typically designed to allow the insertion of replaceable bulbs at periodic intervals by allowing separation of the instrument followed by reassembly.
[0013] Filament bulbs get hot during use due to dissipation of large amounts of infrared radiation which in turn is due to their inherent luminous inefficiency. Therefore such instruments are typically designed with a metal, or other heat conducting material, casing to act as a heat sink. A filament bulb will also usually have a container of similar construction, thus also acting as a heat sink.
[0014] Large amounts of infrared radiation is emitted in addition to useful visible light. As examination can often take a prolonged period of time this can often prove uncomfortable to the subject and/or have a possible deteriorating effect on the tissues under scrutiny. Thus, an infra red safety filter is typically incorporated within the fourth module to provide a ‘cool’ beam.
[0015] Due to the low luminous efficiency of filament bulbs they consume a high quantity of electrical power. Thus, for the instrument to be useful in a portable mode of operation, large batteries are needed. Additionally, a control apparatus capable of handling high power (e.g. a heavy rheostat) is needed.
[0016] The spectral light distribution of a filament bulb has a low colour-temperature (i.e. yellowy light). Some instruments incorporate a colour-correction filter to alter the light distribution. This is required to provide an improved colour-rendering-index factor, which is beneficial for analysis of biological tissues or other detailed tasks.
[0017] An incandescent filament emits its light flux effectively in all directions. This light usually has a high degree of coherence due to the small filament size. An optical condenser lens system is typically used to image this light source. To be efficient the condenser lens system should be close to the light source (to reduce light wastage) which necessitates it to be powerful in order to direct a portion of the light ‘forwards’. This ‘forwards’ light is then usually projected by a field lens to a semi-silvered or sight-hole based, or other mirror. Much of the emitted light flux is thus not utilized and is absorbed within the instrument. There is usually no space in such instruments to have a reflector arrangement as an alternative to this.
[0018] Additionally, as bulbs for use in such instruments are required to have a small filament size (for efficient optical imaging purposes), they must be very accurately centered due to the requirements of the complex lens system.
[0019] The filament is surrounded by a fragile glass envelope. The operator must be very careful to avoid touching the glass, as grease from the fingers can cause cracks to develop on the glass envelope contributing to degradation and ultimately reducing the life of the bulb.
[0020] It is the aim of the present invention to overcome at least some of the above problems.
STATEMENT OF INVENTION
[0021] The present inventor has surprisingly found that clinical diagnostic instruments may be improved in a number of aspects if the light source is based on electroluminescent and/or phospholuminescent technology.
[0022] Thus the first aspect of the invention provides a clinical diagnostic instrument which comprises:
[0023] a means for supplying electrical power (a);
[0024] a means for controlling the electrical power (b);
[0025] a means for generating light (c);
[0026] a means for transforming the light prior to illumination of structure under scrutiny (d);
[0027] is characterised in that (c) is based on electroluminescent and/or phospholuminescent technology.
[0028] Another aspect of the invention provides for an instrument as defined above, characterised in that at least one of modules (a), (b) and (d) are designed for incandescent filament technology.
[0029] Another aspect of the invention provides for a use of the clinical diagnostic instrument for analysis of a structure under scrutiny.
[0030] Another aspect of the invention provides for a process of replacing the incandescent filament bulb of a clinical diagnostic instrument with (c), (b)(i) a module that allows an appropriate amount of electrical energy from (a) via (b) to be converted to light energy by (c), (b)(ii) a supplementary module that allows a discrete step and/or a variation (at any rate of change) between 0 and 100 % of the available electrical power to be converted to light energy by (c), and (d)(i) a module that allows transformation of light prior to transformation by (d).
[0031] Another aspect of the invention provides for a process of replacing the incandescent filament bulb, the means for supplying electrical power and the means for controlling the electrical power of a clinical diagnostic instrument with (c), (a) and (b) both designed for (c), and (d)(i) a module that allows transformation of light prior to transformation by (d).
DETAILED DESCRIPTION OF THE INVENTION
[0032] LED Technology
[0033] The preferred embodiment light source is Light Emitting Diode technology (LEDs). Other non-incandescent filament bulb sources of light are conceivable such as light-emitting polymers or LASERs. Each will have different optoelectrical properties as will different generations of a single technology over time.
[0034] The advantages of LEDs as incorporated within a new design are numerous.
[0035] The lifetime of LEDs, when run at manufacturers recommended rating, can be as long as 100,000 hours. Even when run beyond their recommended rating, their lifetime can still be very long compared to analogous incandescent filament type bulbs. Since the lifetime of the LED is approximately the same as the useable life of the instrument as a whole, there would be no need to ever replace a bulb. As a result a new design of instrument may be constructed in one piece thus providing simpler manufacture.
[0036] Most commercially available LEDs give a light flux output that is directional from a narrow solid angle to wide (typically in a solid angle of from 8°-180°). Thus, wasteful light may be reduced or even eliminated entirely. Since LEDs emit light ‘forwards’ and also produce only low levels of infrared radiation, a reduced heat-sinking requirement of the casing is needed.
[0037] Since LEDs produce a ‘cool’ beam the need for a safety or infrared filter is negated. Thus this again allows for simpler manufacture.
[0038] LEDs also consume a much reduced quantity of electrical power which could enable smaller capacity batteries to be fitted. Alternatively, the batteries designed for incandescent filament bulbs may still be employed but enjoying a longer charge life. The heavy, large power rated rheostat could also be replaced with a lighter means of control.
[0039] Spectral light distribution of a white LED gives an almost ideal colour-rendering-index factor (ideally a colour temperature of around 6500K). As a result no colour correction filter is needed thus simplifying overall design.
[0040] Commercially available LEDs are supplied encapsulated in a plastic surround (micro-lensed). The shape of-the surround alters the light flux directionality. Alternatively, the same result may be achieved by external optical means or a combination of both approaches. The light source point area (unencapsulated ˜0.75 mm 2 ) can thus be varied from an approximation to a point source with a high degree of coherence (<1 mm 2 ) through to an extended line source to a larger area (˜5 mm 2 ). As a result, the light emitted from an encapsulated LED is much easier to directly adapt and change than that from filament bulb types.
[0041] Individual LEDs may be combined in an array configuration to form the module e.g. red, green or blue types or two white types etc.
[0042] The light source is protected by an encapsulating surround, which is impervious to most chemical attack and is impact resistant.
[0043] The improved light source allows for a number of preferred embodiments of the invention.
[0044] The New Instrument
[0045] In the first preferred embodiment of the invention, an entirely new design of all four modules is provided which incorporates the above advantages into a new instrument.
[0046] The means for supplying electrical power (a) may supply any quantity of power suitable for diagnostic instruments, typically this is at most 100 watts, preferably at most 20 watts, more preferably at most 5 watts, and most preferably at most 2 watts. The power may be provided from the mains or from a portable battery, but preferably it is from a battery to enable maximum flexibility in use. Such a battery, if present, will preferably have a capacity of no more than 50 Ahr, preferably no more than 20 Ahr, more preferably no more than 5 Ahr and most preferably no more than 2 Ahr. These batteries will typically be physically smaller than those required for incandescent filament bulb technology.
[0047] The means for controlling the electrical power (b) has the primary function of allowing a fraction of the available power to flow to the light source. Such a means may allow a discrete step and/or a variation (at any rate of change) between 0 and 100% of the available electrical power to be converted to light energy by (c).
[0048] This function is preferably provided by a ganged rheostat or a ganged potentiometer circuit or a pulse code modulation circuit or some other electronic means.
[0049] If a rheostat is present its resistance value will be quite different to that used in conventional incandescent filament instruments, typically up to the resistance of the new light source (e.g. LED). The ideal resistance range variation would be one perfectly tailored to the optoelectrical characteristics of the new light source. An approximately linear design however is sufficient for most purposes. The voltage is controlled giving corresponding light output variance as a result. For example a typical white LED run at full light intensity requires a voltage of ˜3.9V and ˜2.9V for low light intensity. A voltage change of ˜1.0V is thus produced as required.
[0050] The means for generating light (c) preferably provides a pre-transformed light with a luminous intensity of at most 2000 lumens, preferably at most 400 lumens, more preferably at most 100 lumens, most preferably at most 40 lumens. Such a light source is based on electroluminescent and/or phospholuminescent technology such as LEDs, light-emitting polymers or LASERs, although LEDs are preferred technology. The light emitted is preferably white light, preferably at a colour temperature of from 3500 to 15,000 Kelvin, more preferably from 4500 to 9000 Kelvin, most preferably from 6000 to 7000 Kelvin.
[0051] Since the new light source may direct the light ‘forwards’ the means for transforming the light prior to illumination of structure under scrutiny (d) may be of much simpler construction than that used for incandescent filament bulb technology. Preferably (d) has no more than six condenser or field lenses, more preferably no more than three, most preferably one. Preferably (d) is devoid of a colour-temperature correction and/or a heat absorbing filter.
[0052] Once the light has illuminated the structure under scrutiny, it may optionally be transformed prior to reception by the detection means (whether the human eye or otherwise). Hence the instrument may also comprise (e) a means for transforming the light returning from the structure under scrutiny. As with incandescent types this is often a rack of interchangeable lenses enabling fine focus on image detection means.
[0053] The modules comprising the instrument are typically contained within a suitable exterior casing to enable ease of use and to provide protection. Instruments based on incandescent filament technology usually need to have separable casings to enable expired bulbs to be replaced. The new instrument may conveniently be manufactured in one piece, using less metal or other such heat conducting material for heat sinking. Hence dense materials of construction are not essential to the overall design and preferably have an average bulk density of no more than 4000 kg/m 3 , preferably no more than 2000 kg/m 3 , more preferably no more than 1000 kg/m 3 .
[0054] The Part-Adapted Instrument
[0055] Since the vast majority of clinical diagnostic instruments in use are based on incandescent filament technology, the present invention allows for replacement modules which are compatible with parts of diagnostic instruments based on incandescent filament technology. Accordingly the present invention provides for a series of clinical diagnostic instruments, that are characterised in that (c) is based on electroluminescent and/or phospholuminescent technology and at least one of modules (a), (b) and (d) are designed for incandescent filament technology. Accordingly these embodiments of the invention provide at least some of the above detailed advantages relating to the new light source. This would be a very cost effective way of deriving benefits of new light source.
[0056] Since electroluminescent and/or phospholuminescent light sources have very different electrical characteristics compared to conventional incandescent filament bulbs, they cannot simply be used as direct replacements and be expected to derive an acceptable light generation and thus optical performance in such instruments There are three main problems which must be overcome before they may be used as such.
[0057] The first problem is that the voltage produced by the power supply in conventional instruments is either much greater or much less than the new light source requires. Thus the new light source would draw too large a current and be damaged and possibly destroyed or draw too little current to be effective in the role intended. If (b) is designed for incandescent filament technology then a supplementary module must be added that can ‘modify’ control function of conventional (b).
[0058] If (b) is designed for incandescent filament technology, the problem of the power supply being too high may be overcome by providing a current limiter (b)(i) into the circuit. There are many ways of embodying this, each with their own advantages and disadvantages, one way to do this is via a low value resistor which causes a small but necessary voltage drop. If the power supply is too low (b)(i) may be a voltage boost circuit that draws its own power from the supply. Thus (b) (i) may be a switched mode circuit either using an inductor or of flying capacitor design, these designs can be used whether the power supply is too high or too low. Alternatively an oscillator/transformer type can be employed. Thus if (a) is designed for incandescent filament technology optoelectrical requirements, then the instrument also comprises a module (b)(i) that allows an appropriate amount of electrical energy from (a) via (b) to be converted to light energy by (c).
[0059] Alternatively this first problem may be overcome by providing a (b) which is specially designed for the new light source (e.g. rheostat value cut off point not dropping to zero ohms). Thus if (a) is designed for incandescent filament technology optoelectrical requirements, module (b) allows an appropriate amount of electrical energy from (a) via (b) to be converted to light energy by (c). Hence (b) would comprise a voltage reduction circuit (e.g. a resistor), or a voltage boost circuit such as a switched mode or oscillator/transformer and a device which allows a discrete step and/or a variation (at any rate of change) between 0 and 100% of the available electrical power to be converted to light energy by (c).
[0060] The second problem is that the means for controlling the electrical power in conventional instruments provides little or no variability of light output of (c) due to a lack of a significant voltage drop across (c) through range of resistance. This is caused by the low resistance (yet high power rating) value of the control rheostat which is designed specifically to cater for the optoelectrical characteristics of incandescent filament light sources (namely low hot resistance/high current). There are many ways of solving this problem, each with their own advantages and disadvantages, for example via a resistor connected in parallel across the voltage supply. Other ways include a negative resistance circuit or an amplifier which is variable in proportion to a sense current which is in turn proportional to the current flowing through a load. Another solution may use pulse code modulation or other electronic control means. Thus if the means for controlling the electrical power (b) is designed for incandescent filament bulb technology (e.g. a low value rheostat) it must also comprise an I/V converter module (b)(ii), that allows a discrete step and/or a variation (at any rate of change) between 0 and 100% of the available electrical power to be converted to light energy by (c). If present (b)(ii) is a resistor or a sense current/amplifier based circuit or other electrical circuit means.
[0061] The third problem is that it is also conceivable that the replacement light source module may need to be used with a means for transforming the light (d) designed for incandescent filament bulb technology. If so, then module (d)(i) is essential which allows transformation of light prior to further transformation by (d). If present (d)(i) comprises a lens, a micro-lens, a holographic optical element or diffraction grating. In a preferred embodiment (c) is based on LED technology and (d)(i) is rigidly attached to (c). If present (d)(i) may comprise a lens with a dioptric modulus power of at least 100 D, preferably at least 1000 D, more preferably at least 3000 D. Additionally (d)(i) may comprise a lens with a dioptric power of (d)(i) is at most 100 D, preferably at most 30 D, more preferably at most 10 D, most preferably substantially zero D.
[0062] In a second preferred embodiment (EMB 2 ) the present invention provides for a clinical diagnostic instrument wherein (c) is based on electroluminescent and/or phospholuminescent technology, and (a), (b) and (d) are designed for incandescent filament technology and (b)(i), (b)(ii) and (d)(i) are present. It is preferred that (c) and at least one of (b)(i), (b)(ii) and (d)(i) are surrounded by a single casing so that (c) may be fitted to an existing instrument designed for incandescent filament technology. Accordingly this embodiment provides for a new replacement bulb.
[0063] In a third preferred embodiment (EMB 3 ) the present invention provides for a clinical diagnostic instrument wherein (c) is based on electroluminescent and/or phospholuminescent technology for which both (a) and (b) are specifically designed but (d) is designed for incandescent filament technology. Accordingly (d)(i) is present, but both (b)(i) and (b)(ii) are not present. It is preferred that (c), (a), (b) and (d)(i) are surrounded by a single casing so that the resultant device may be fitted to an existing module (d) designed for incandescent filament technology. Accordingly this embodiment provides for a new combined light source/controller/power supply device that attaches to a conventional (d).
[0064] In a fourth preferred embodiment (EMB 4 ) the present invention provides for a clinical diagnostic instrument wherein (c) is based on electroluminescent and/or phospholuminescent technology for which (a) is specifically designed but both (b) and (d) are designed for incandescent filament technology. Accordingly (b)(ii) and (d)(i) are present but (b)(i) is not present. Accordingly this embodiment provides for a new light source/power supply device to be fitted between conventional (b) and (d).
[0065] In a fifth preferred embodiment (EMB 5 ) the present invention provides for a clinical diagnostic instrument wherein (c) is based on electroluminescent and/or phospholuminescent technology for which (b) is specifically designed but both (a) and (d) are designed for incandescent filament technology. Accordingly (d)(i) is present but neither (b)(i) nor (b)(ii) are present. Accordingly this embodiment provides for a new light source/controller device fitted to conventional (a) and (d)
[0066] There are many other embodiments that utilise some conventional and new modules.
[0067] The invention will be now illustrated, but in no way limited by, the following examples.
[0068] (Note: for following Figs shaded regions indicate new parts.)
[0069] [0069]FIG. 1 Prior art block diagram.
[0070] [0070]FIG. 2 Circuit diagram of prior art.
[0071] [0071]FIG. 3 Block diagram of the new instrument EMB 1 .
[0072] [0072]FIG. 4 Circuit diagram of the new instrument EMB 1 .
[0073] [0073]FIG. 5 Block diagram of EMB 2 .
[0074] [0074]FIG. 6 Circuit diagram of EMB 2 .
[0075] [0075]FIG. 7 Block diagram of EMB 3 .
[0076] [0076]FIG. 8 Circuit diagram of EMB 3 .
[0077] [0077]FIG. 9 Block diagram of EMB 4 .
[0078] [0078]FIG. 10 Circuit diagram of EMB 4 .
[0079] [0079]FIG. 11 Block diagram of EMB 5 .
[0080] [0080]FIG. 12 Circuit diagram of EMB 5 .
[0081] [0081]FIG. 13 Side view of an encapsulated LED (with micro-lens).
[0082] [0082]FIG. 14 Side view of an encapsulated LED (as a slit).
[0083] [0083]FIG. 15 Side view of physical embodiment of EMB 2 .
[0084] [0084]FIG. 16 Graph of I/V of an incandescent bulb.
[0085] [0085]FIG. 17 Graph of I/V of an LED.
[0086] [0086]FIG. 1 shows prior art block diagram of instrument, showing the modules. The prior art FIG. 1 shows the electrical power supply (a), the control module (b), the light source (c), and the transformation module (d) as separate units in their usual arrangements. These units are combined together so as to produce the final instrument. FIG. 2 shows circuit diagram of prior art instrument. FIG. 2, shown alongside FIG. 11, shows the internal circuitry required to operate the instrument.
[0087] [0087]FIG. 3 shows block diagram of the new instrument, showing combined modules. FIG. 3 shows the preferred embodiment of the first aspect of the invention, the new instrument, showing how the transformation, light source, power and control modules are combined to provide new instrument with new casing design. FIG. 4 shows circuit diagram of the new instrument. FIG. 4, shown alongside FIG. 3, shows how the internal circuitry is similar in layout to that of a conventional filament bulb instrument (see FIG. 2) but differs in the light source, control and power functions.
[0088] [0088]FIG. 5 shows block diagram of preferred embodiment two. FIG. 5 shows the new light source module, incorporating the (b)(i), (b)(ii) and (d)(i). FIG. 6 shows circuit diagram of new preferred embodiment two. FIG. 6, shown alongside FIG. 5 shows how (b)(i) and (b)(ii) are arranged schematically. (d)(i) is also shown in relative position.
[0089] [0089]FIG. 7 shows block diagram of preferred embodiment three. This variation retains original (d) but has new (a), (b) and (c) together with (d)(i). FIG. 8 shows circuit diagram of preferred embodiment three shown alongside FIG. 7 together with relative position of (d)(i).
[0090] [0090]FIG. 9 shows block diagram of preferred embodiment four. This variation retains original (d) and (b) but has new (a) and (c) together with (b)(ii) and (d)(i). FIG. 10 shows circuit diagram of preferred embodiment four shown alongside FIG. 9 which shows how (b)(ii) is arranged schematically. (d)(i) is also shown in relative position.
[0091] [0091]FIG. 11 shows block diagram of preferred embodiment five. This variation retains original (d) and (a) but has new (b) and (c) and (d)(i). FIG. 12 shows circuit diagram of preferred embodiment five shown alongside FIG. 11 which shows how (d)(i) is also shown in relative position.
[0092] [0092]FIG. 13 shows side view of an LED with encapsulation ( 1 ) with a substantially zero dioptric power (i.e. flat top) which has a micro-lens ( 2 ) mounted over light emitting area (not shown) thus enabling forward imaging of light whilst from a physically small area. FIG. 14 shows side view of an LED with encapsulation ( 1 ) formed so that a long thin source of light results. FIG. 15 shows side view of physical embodiment of second preferred embodiment (new replacement bulb), incorporating means to alter function of other modules. (b)(i) (either current limiter or voltage boost configuration) is shown. An I/V converter (as second problem) is shown as (b)(ii). A connector/case is shown in ( 1 ), these are used to connect the light source module to the power supply. This is typically made of an electrically conductive material. The case has the multiple functions of holding the contents secure, acting as a heat sink and also possibly as a connector to the power supply. A holder ( 2 ) performs the function of supporting the light source; it may also act as a heat sink. The light source itself ( 3 ) is housed so that the light is directed in one direction. Any additional optics or method of altering encapsulating optics of (LED) itself may be needed to alter the light as so required; here a lens is shown ( 4 ).
[0093] [0093]FIG. 16 shows graph of typical filament bulb I/V electrical characteristics. Line ( 1 ) shows change, typically described as an ‘S’ shape. FIG. 17 shows graph of I/V electrical characteristics of typical LED. The line ( 1 ) extends from a high current value to a low value: i.e. big difference. The line is roughly in line with actual I/V change needed to produce acceptable light output variance. In contrast line ( 2 ) is only analogous over a very small range: i.e. poor light variance. | A new light source (e.g. LEDs) enables new designs in all or some key elements within diagnostic instruments. New light sources allow improvements in life of light source, infra red emitted, power consumption, colour temperature, light flux directionality, simplification of opitcs design, adaptation of light flux directionality, and overall constructional simplification. The new light source allows for the replacement of some or all of the components designed for incandescent filament bulbs. The improved light source may allow for either an entirely new design of all or some core modules of the instrument, or by alteration of pre-existing modules. | 0 |
TECHNICAL FIELD OF THE INVENTION
The present invention relates generally to memory devices and in particular the present invention relates to non-volatile memory devices.
BACKGROUND OF THE INVENTION
Memory devices are typically provided as internal, semiconductor, integrated circuits in computers or other electronic devices. There are many different types of memory including random-access memory (RAM), read only memory (ROM), dynamic random access memory (DRAM), synchronous dynamic random access memory (SDRAM), and flash memory.
Flash memory devices have developed into a popular source of non-volatile memory for a wide range of electronic applications. Flash memory devices typically use a one-transistor memory cell that allows for high memory densities, high reliability, and low power consumption. Common uses for flash memory include personal computers, personal digital assistants (PDAs), digital cameras, and cellular telephones. Program code and system data such as a basic input/output system (BIOS) are typically stored in flash memory devices for use in personal computer systems.
A charge pump circuit is used in a non-volatile memory device to generate the voltages required for chip operation. A charge pump is an electronic circuit that uses capacitors as energy storage elements to convert DC voltages into other DC voltages.
A typical charge pump uses transistors to control the operation of the pump and connection of voltages to the capacitors. For instance, a typical prior art charge pump can generate a higher voltage through multiple stages. A first stage involves a capacitor being connected across a voltage and charged up. In a second stage, the capacitor is disconnected from the original charging voltage and reconnected with its negative terminal to the original positive charging voltage. Because the capacitor mostly retains the voltage across it, except for leakage, the positive terminal voltage is added to the original, effectively doubling the voltage. The pulsing nature of the higher voltage output is typically smoothed by the use of another capacitor at the output.
FIG. 1 illustrates a typical prior art charge pump circuit. It comprises a charge pump 100 that outputs regulated voltage V out — reg to a parasitic load 101 and a target load 103 . The parasitic load 103 represents line capacitance of the pump output node. The target load 103 is the capacitance of the connected word line to be programmed. Switch SW A 105 is closed during the programming cycles to connect V out — reg to the target load 103 .
FIG. 2 illustrates a timing chart of a typical prior art non-volatile memory device such as the flash memory integrated circuit charge pump circuit of FIG. 1 . The timing chart shows that the I/O lines include the addresses, data, and commands for memory operation.
Referring to FIG. 2 , when the command for a program operation is received (e.g., 10 H), a program enable signal goes high. The program enable signal then causes the charge pump enable signal to go high to initiate the pumping operation in order to precharge bit lines.
One problem with this charge pump operation is that the operation of the pump circuits causes noise on the bit lines. This can cause problems with programming of the cells that are coupled to the bit lines experiencing the noise. Additionally, a fast pump turn-on creates a peak current that causes a downward spike 200 in the supply voltage (V CC ) as illustrated in FIG. 2 . This can result in unstable memory device operation.
For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a need in the art for more efficient use of charge pumps in a non-volatile memory device.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a block diagram of a typical prior art charge pump circuit.
FIG. 2 shows a timing diagram of a typical prior art operation of the charge pump circuit of FIG. 1 .
FIG. 3 shows a portion of one embodiment of a NAND architecture flash memory array.
FIG. 4 shows an operational block diagram of one embodiment of a charge pump circuit of the present invention.
FIG. 5 shows a timing diagram of one embodiment of the operation of the charge pump circuit of FIG. 5 .
FIG. 6 shows a block diagram for one embodiment of a memory system of the present invention.
FIG. 7 shows a block diagram for one embodiment of a memory module of the present invention.
DETAILED DESCRIPTION
In the following detailed description of the invention, reference is made to the accompanying drawings that form a part hereof and in which is shown, by way of illustration, specific embodiments in which the invention may be practiced. In the drawings, like numerals describe substantially similar components throughout the several views. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be utilized and structural, logical, and electrical changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims and equivalents thereof.
FIG. 3 illustrates a simplified diagram of a typical prior art NAND flash memory array. The memory array of FIG. 3 , for purposes of clarity, does not show all of the elements typically required in a memory array. For example, only two bit lines are shown (BL 1 and BL 2 ) when the number of bit lines required actually depends upon the memory density.
The array is comprised of an array of floating gate cells 301 arranged in series strings 304 , 305 . Each of the floating gate cells 301 are coupled drain to source in each series chain 304 , 305 . A word line (WL 0 -WL 31 ) that spans across multiple series strings 304 , 305 is coupled to the control gates of every floating gate cell in a row in order to control their operation. The bit lines BL 1 , BL 2 are eventually coupled to sense amplifiers (not shown) that detect the state of each cell.
In operation, the word lines (WL 0 -WL 31 ) select the individual floating gate memory cells in the series chain 304 , 305 to be written to or read from and operate the remaining floating gate memory cells in each series string 304 , 305 in a pass through mode. Each series string 304 , 305 of floating gate memory cells is coupled to a source line 306 by a source select gate 316 , 317 and to an individual bit line (BL 1 , BL 2 ) by a drain select gate 312 , 313 . The source select gates 316 , 317 are controlled by a source select gate control line SG(S) 318 coupled to their control gates. The drain select gates 312 , 313 are controlled by a drain select gate control line SG(D) 314 .
A selected word line 300 for the flash memory cells 330 - 331 being programmed is typically biased by programming pulses that start at a voltage of around 16V and may incrementally increase to more than 20V. The unselected word lines for the remaining cells are typically biased at V pass . This is typically in an approximate range of 9-10V. The bit lines of the cells to be programmed are typically biased at 0V while the inhibited bit lines are typically biased at V CC .
FIG. 4 illustrates an operational block diagram of one embodiment of the charge pump circuit of the present invention. The circuit is comprised of the charge pump device 400 that generates the V out — reg voltage for programming the memory cells. In one embodiment, this voltage is coupled to the word lines of the subsequently described non-volatile memory array.
The parasitic load 401 represents the total capacitance of the output line of the charge pump device 400 . The target load 403 represents the load capacitance of the word line to which the charge pump device 400 is currently coupled for programming. The intentional load 405 represents the load that is charged up during idle times to provide charge sharing with the target load.
Switches SWA 411 , SWB 413 , and SWC 415 provide the switching between the loads. In one embodiment, these switches 411 , 413 , 415 can be implemented using transistors. SWA 411 couples the target load 403 to the pump 400 . SWB 413 couples the intentional load 405 to the pump. SWC 415 couples the intentional load 405 to the target load 403 .
FIG. 5 illustrates a timing diagram of one embodiment of the circuit of FIG. 4 . This diagram illustrates the I/Ox line that carries the desired operation commands (i.e., read, write, erase), the data to be programmed/read, and the address to which the data is to be written/read.
The PGM_ENABLE line illustrates the state of the program enable signal to memory controller circuit to initiate the program operation. This signal also causes the memory controller to generate the PUMP_ENABLE signal. This signal is responsible for enabling the charge pump device 400 of FIG. 4 to begin the programming operation.
The V out — f signal represents the voltage on the target load as a result of the closing of SWC 415 . V out — reg signal is the voltage that is output from the pump 400 . V out — l is the voltage at the intentional load 405 . The SWA, SWB, and SWC lines represent the opening and closing of the switches 411 , 413 , 415 of FIG. 4 .
In operation, the first program cycle is initiated by a program command or address load command on the I/Ox line. The illustrated command is 80 H but this is for purposes of illustration only as the present invention is not limited to any one received command value or received command that is responsible for initiating the PGM_ENABLE. The received command causes the PGM_ENABLE line to go high to initiate the program operation. The PGM_ENABLE signal causes the PUMP_ENABLE signal to go high and turn on the charge pump 400 . The charge pump remains on during the data loading operation.
V out — reg starts from 0V and rises to a target voltage with SWA closed. The target voltage is dependent on the embodiment and can be any voltage required for programming the memory cell (e.g. 20V). Since V out — reg sees the fixed loading capacitance of the target load 403 +parasitic load 401 , V out — reg rises with an RC time constant. Since SWA is closed, V out — f also tracks V out — reg . V out — l starts from 0V and rises to the target voltage with the closing of SWB 413 .
Once V out — reg reaches the target voltage, the pump 400 is idling (i.e., turned off or slowed down) with just enough output to maintain the V out — reg node at the target voltage. This compensates for junction leakage at the V out — reg node connections.
SWB 413 begins to open and close as shown in FIG. 5 . This charges the intentional load 405 . As can be seen in the timing diagram, SWA 411 and SWB 413 are clocking in an inverse pattern during the remainder of the first program cycle. SWA 411 is closing to compensate for leakage current by the target load 403 . SWB 413 is closing to charge the intentional node and to compensate for leakage current by the intentional load 405 .
During the verify cycle, the PUMP_ENABLE signal remains high, SWA 411 is open, and SWB 413 remains closed. This provides a slow, weak charging to V out — l at the intentional load 405 .
During the second program cycle, PUMP_ENABLE remains high. The stored charge in the intentional load 405 is then used to charge up the target load 403 by charge sharing. This is accomplished by closing SWC 415 as shown in FIG. 5 . Both SWA 411 and SWB 413 are open when SWC 415 momentarily closes. The charge sharing between V out — l and V out — f causes only a minor downward spike in the V out — reg signal that is substantially reduced from the prior art. The peak reduction results in substantially more stable memory device operation.
The V out — f signal begins to rise with the charge sharing initiated by closing SWC 415 . The initial slope of V out — f in the timing diagram of FIG. 5 is the result of the charge sharing. SWC 415 then opens and SWA 411 closes to couple the target load 403 to V out — reg to continue charging up V out — f . For the remainder of the second program cycle, SWA 411 and SWB 413 again clock on and off in an inverse fashion, as shown in the timing diagram, in order to compensate for the leakage current occurring in their respective loads 403 , 405 .
FIG. 6 illustrates a functional block diagram of a memory device 600 that can incorporate the embodiments for programming the non-volatile memory cells of the present invention. The memory device 600 is coupled to a processor 610 . The processor 610 may be a microprocessor or some other type of controlling circuitry. The memory device 600 and the processor 610 form part of an electronic system 620 . The memory device 600 has been simplified to focus on features of the memory that are helpful in understanding the present invention.
The memory device includes an array of flash memory cells 630 or some other type of non-volatile memory cells. The memory array 630 is arranged in banks of rows and columns. The control gates of each row of memory cells is coupled with a word line while the drain and source connections of the memory cells are coupled to bit lines. As is well known in the art, the connection of the cells to the bit lines depends on whether the array is a NAND architecture, a NOR architecture, an AND architecture, or some other array architecture.
An address buffer circuit 640 is provided to latch address signals provided over I/O connections 662 through the I/O circuitry 660 . Address signals are received and decoded by row decoders 644 and column decoders 646 to access the memory array 630 . It will be appreciated by those skilled in the art that, with the benefit of the present description, the number of address input connections and row/column decoders depends on the density and architecture of the memory array 630 . That is, the number of addresses increases with both increased memory cell counts and increased bank and block counts.
The memory integrated circuit 600 reads data in the memory array 630 by sensing voltage or current changes in the memory array columns using sense/buffer circuitry 650 . The sense/buffer circuitry, in one embodiment, is coupled to read and latch a row of data from the memory array 630 . Data input and output buffer circuitry 660 is included for bi-directional data communication over the I/O connections 662 with the processor 610 . Write circuitry 655 is provided to write data to the memory array.
Control circuitry 670 decodes signals provided on control connections 672 from the processor 610 . These signals are used to control the operations on the memory array 630 , including data read, data write, and erase operations. The control circuitry 670 may be a state machine, a sequencer, or some other type of controller. The control circuitry 670 of the present invention, in one embodiment, is responsible for executing the embodiments of the programming method and charge pump control of the present invention.
The flash memory device illustrated in FIG. 6 has been simplified to facilitate a basic understanding of the features of the memory and is for purposes of illustration only. A more detailed understanding of internal circuitry and functions of flash memories are known to those skilled in the art. Alternate embodiments may include the flash memory cell of the present invention in other types of electronic systems.
FIG. 7 is an illustration of a memory module 700 that incorporates the memory cell embodiments as discussed previously. Although the memory module 700 is illustrated as a memory card, the concepts discussed with reference to the memory module 700 are applicable to other types of removable or portable memory, e.g., USB flash drives. In addition, although one example form factor is depicted in FIG. 7 , these concepts are applicable to other form factors as well.
The memory module 700 includes a housing 705 to enclose one or more memory devices 710 of the present invention. The housing 705 includes one or more contacts 715 for communication with a host device. Examples of host devices include digital cameras, digital recording and playback devices, PDAs, personal computers, memory card readers, interface hubs and the like. For some embodiment, the contacts 715 are in the form of a standardized interface. For example, with a USB flash drive, the contacts 715 might be in the form of a USB Type-A male connector. For some embodiments, the contacts 715 are in the form of a semi-proprietary interface, such as might be found on COMPACTFLASH memory cards licensed by SANDISK Corporation, MEMORY STICK memory cards licensed by SONY Corporation, SD SECURE DIGITAL memory cards licensed by TOSHIBA Corporation and the like. In general, however, contacts 715 provide an interface for passing control, address and/or data signals between the memory module 700 and a host having compatible receptors for the contacts 715 .
The memory module 700 may optionally include additional circuitry 720 . For some embodiments, the additional circuitry 720 may include a memory controller for controlling access across multiple memory devices 710 and/or for providing a translation layer between an external host and a memory device 710 . For example, there may not be a one-to-one correspondence between the number of contacts 715 and a number of I/O connections to the one or more memory devices 710 . Thus, a memory controller could selectively couple an I/O connection (not shown in FIG. 7 ) of a memory device 710 to receive the appropriate signal at the appropriate I/O connection at the appropriate time or to provide the appropriate signal at the appropriate contact 715 at the appropriate time. Similarly, the communication protocol between a host and the memory module 700 may be different than what is required for access of a memory device 710 . A memory controller could then translate the command sequences received from a host into the appropriate command sequences to achieve the desired access to the memory device 710 . Such translation may further include changes in signal voltage levels in addition to command sequences.
The additional circuitry 720 may further include functionality unrelated to control of a memory device 710 . The additional circuitry 720 may include circuitry to restrict read or write access to the memory module 700 , such as password protection, biometrics or the like. The additional circuitry 720 may include circuitry to indicate a status of the memory module 700 . For example, the additional circuitry 720 may include functionality to determine whether power is being supplied to the memory module 700 and whether the memory module 700 is currently being accessed, and to display an indication of its status, such as a solid light while powered and a flashing light while being accessed. The additional circuitry 720 may further include passive devices, such as decoupling capacitors to help regulate power requirements within the memory module 700 .
CONCLUSION
In summary, the embodiments of the present invention provide stable memory device operation and reduced program time by enabling the charge pump at some point prior to the data load instead of after the data load, as in the prior art. This minimizes the pump driving current during the program cycle start in order to reduce the supply peak current, thus providing stable device operation. Additionally, an intentional load provides charge sharing to reduce the load on the regulated voltage output from the pump during program cycle start.
Although specific embodiments have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that any arrangement that is calculated to achieve the same purpose may be substituted for the specific embodiments shown. Many adaptations of the invention will be apparent to those of ordinary skill in the art. Accordingly, this application is intended to cover any adaptations or variations of the invention. It is manifestly intended that this invention be limited only by the following claims and equivalents thereof. | A charge pump in a memory device is activated to produce a programming voltage prior to data loading during a programming operation. During an initial programming cycle, first and second load voltages are charged from the charge pump. The first load is removed from the charge pump during a verify operation. The first load voltage is subsequently recharged by charge sharing from the second load voltage so that the charge pump is not initially necessary for recharging the first load voltage. | 6 |
GENERAL TECHNICAL FIELD
[0001] The invention relates to the field of energy management optimization.
[0002] More particularly, the invention relates to a method for regulating the temperature of a built structure equipped with a thermal regulation system.
STATE OF THE ART
[0003] Thermal regulation (via systems called HVAC (Heating, Ventilation and Air-Conditioning)) represents over half the energy used in a building.
[0004] Apart from the improvement in isolation and efficacy/efficiency of HVAC systems, energy savings may be made by controlling and regulating the temperature of the housing more effectively.
[0005] More particularly, optimization of operating ranges and temperature goals (floating instruction, i.e., dynamic) may be undertaken without as such impairing the comfort of the occupants of the housing. Given the local meteorology, thermal modeling:
maximizes energy savings, improves the qualitative sensation of the system by the occupant.
[0008] An additional innovation has been taking into account absences and presences of the occupants of the housing. Evolved thermostats may be configured to lower the instruction over predefined ranges during which the occupants are not supposed to be present in the housing. But if the occupants do not return at the time provided by the thermostat, the housing will be cold or will have heated needlessly (respectively hot or cooled).
[0009] To resolve this difficulty, document WO 2013020970 proposes the geolocation of occupants outside the habitat, which knows whether the occupants are going away from or approaching the habitat, with the aim of regulating the temperature of the habitat.
[0010] Document WO 2014015977 as such especially describes a concept for estimation of the arrival time of the occupant of the housing for regulating the temperatures as a function.
[0011] Document WO 2012068495 proposes lowering the instruction after a given time as soon as the absence of the occupant is detected.
[0012] Finally, document WO 2013058966 presents a method for learning habits of the user as a function of completed cycles so as to anticipate temperatures to be controlled.
[0013] These known technologies exploit geolocation and local learning for more effective thermal regulation and substantial savings, but they may still be improved.
[0014] In particular, these techniques are incapable of considering unforeseen nearby travel (under half an hour, for example), which represent 80% of absences of a user: going out for pizza, visiting parents, going to the doctor, etc.
[0015] Even though such absences may sometimes last for hours, the fact that the user may return at any moment in a few minutes obligates known methods to keep the housing at nominal temperature, resulting in useless power consumption.
[0016] It would be preferable to have a method for regulating the temperature which allows optimal thermal regulation including real energy savings during unforeseen absences, and ensures comfort and simplicity of optimization for the user.
PRESENTATION OF THE INVENTION
[0017] To eliminate the limitations presented previously, the invention proposes a method for regulating the temperature of a built structure equipped with a thermal regulation system configured to regulate temperature of said built structure to a predetermined living temperature, in an operating mode by default, said method comprising, via a data-processing module, performing steps of:
[0018] (a) Detection of an absence of a user in the built structure,
[0019] (b) Emission to the thermal regulation system of an operating limitation instruction of said system by which the thermal regulation system interrupts regulation of the temperature of the built structure to the living temperature
[0020] (c) Estimation as a function of geolocation data of the user of a return travel time of the user,
[0021] (d) Determination of a return temperature as a function of a comfort temperature, different to the living temperature, and of said return travel time, the return temperature being calculated to let the thermal regulation system reach the comfort temperature during the return travel time,
[0022] (e) Emission to the thermal regulation system of a return instruction by which the thermal regulation system regulates the temperature of the built structure to the return temperature.
[0023] Because of this method, it is possible to save on each absence of the user without degrading the comfort when the latter returns. In fact, the fact of applying a floating instruction in place of maintaining the temperature during the absence, in the case of heating, makes for power savings. Also, due to calculating a floating instruction as a function of the length of absence and thermal performance of the built structure, the comfort temperature is assured when the user returns. The length of absence is advantageously defined by the planning and/or the travel time and/or the learning of usual places and/or the question CQ.
[0024] Advantageously, the invention comprises the following characteristics, taken singly or in combination:
the limitation instruction of step (b) consists of stopping the thermal regulation system, said system then operating in a mode known as free from the start of absence of the user, step (e) is performed only if the temperature of the built structure is outside an interval defined by the living and comfort temperatures, step (b) comprises, when the temperature of the built structure reaches a predefined extreme temperature (Te), emission to the thermal regulation system of a temperature maintenance instruction, by which the thermal regulation system regulates the temperature of the built structure to said extreme temperature, the extreme temperature, the comfort temperature and the return temperature are determined by the data-processing module as a function of at least thermal modeling data of the built structure comprising meteorological data recovered from a central server and thermal characteristics of the built structure originating from an experimental design containing the data relative to the built structure during previous uses of the method, steps (c) to (e) are repeated such that the return temperature tends towards the comfort temperature (Tc) at the time when the user is again present in the built structure, calculation of the return temperature takes into account the time interval between two geolocations in addition to estimation of the return travel time, step (c) comprises receipt of the geolocation data in the broad sense from a mobile terminal of the user comprising location means, step (c) comprises emission to the mobile terminal of a question instruction by which the mobile terminal queries the user on his estimation of the return travel time, such that the return temperature is adapted as a function of the response of the user, detection of the absence of the user is carried out by at least one of the following methods: comparison of geolocation data of the mobile terminal of the user and geolocation reference data of the built structure, connection/disconnection from a local network, or detection of absence via presence sensors, step (c) comprises filtering of the geolocation data, said filtering identifying geostatic situations, the comfort temperature has a spread from 0.5 to 5°, preferably from 0.5 to 2°, and preferably from 0.8 to 1.2°, relative to the living temperature, when the presence of a user (U) is detected in the built structure (B), the method comprises a step (f) for emission to the thermal regulation system of a regulation instruction of the temperature by which the thermal regulation system switches back to the operating mode by default, the method comprises a prior step for emission to the thermal regulation system of a pre-limitation instruction before absence of the user, such that when the user leaves, the comfort temperature is already attained, the pre-limitation instruction is triggered by local learning of absences of the user, the method comprises the following steps:
step (a) is performed for each user of the built structure, step (b) is performed if step (a) is verified for each user of the built structure, step (c) is performed for each user of the built structure, step (d) is performed by using the lowest possible estimation of the return travel time,
the thermal regulation system comprises a heating system, and the return temperature is less than the comfort temperature, in turn less than the living temperature, the thermal regulation system comprises an air-conditioning system, and the return temperature is greater than the comfort temperature, in turn greater than the living temperature.
[0046] The invention also proposes a temperature-regulation unit of a built structure, comprising a temperature-regulation system, a data-processing server, comprising a data storage module and a data-processing module, configured to execute:
a module for detection of absence of the user, a module for triggering an operation limitation instruction of said system by which the thermal regulation system interrupts the regulation of the temperature of the built structure at the living temperature, a module for estimation of the return travel time of the user as a function of geolocation data of the user, a module for determination of a return temperature as a function of a comfort temperature different to the living temperature and of said return travel time, the return temperature being calculated for let the thermal regulation system reach the comfort temperature during the return travel time, a module for emission to the thermal regulation system of a return instruction, by which the thermal regulation system regulates the temperature to the return temperature.
[0052] Finally, the invention proposes a built structure comprising a temperature-regulation system, and a thermostat connected to a server according to the preceding claim, or to a server adapted to execute a method as described previously.
PRESENTATION OF THE FIGURES
[0053] Other features, aims and advantages of the invention will emerge from the following description which is purely illustrative and non-limiting and which must be considered with respect to the appended drawings, in which:
[0054] FIG. 1 illustrates architecture for executing the method according to the invention,
[0055] FIG. 2 illustrates a method according to the invention,
[0056] FIGS. 3 to 5 illustrate diagrams of the instruction temperatures and temperatures of the built structure according to embodiments of a method according to the invention,
[0057] FIG. 6 illustrates a method having different embodiments according to the invention,
[0058] FIGS. 7 a , 7 b , 7 c illustrate the adjustment of the return temperatures as a function of estimations of return travel time,
[0059] FIGS. 8 to 11 illustrate different curves of instruction temperature and of temperature of the built structure as a function of some parameters,
[0060] FIG. 12 illustrates geolocation filtering,
[0061] FIG. 13 illustrates anticipation of the absence of the user,
[0062] FIG. 14 illustrates a zone of common travels,
[0063] FIG. 15 illustrates a built structure temperature curve in the case of an air-conditioning system.
[0000] The instruction temperature curves are shown in full lines and the temperature curves of the built structure are shown in dots.
DETAILED DESCRIPTION
[0064] The present thermal regulation method is carried out in an environment of the type of that shown by FIG. 1 .
[0065] The invention relates to a method for thermal regulation of a built structure B, the built structure comprising a thermal regulation system 10 . The built structure B is inhabited by at least one user U and signifies any construction in which a user U may be found. Typically, the built structure B is a house or apartment.
[0066] A temperature probe 11 is connected to a server 20 by a communications network 21 , such as a mobile telephone network or internet. The probe 11 especially measures the temperature T of the built structure B, and sends a signal to the server 20 .
[0067] A mobile terminal 30 of the user U may be connected to the server 20 by the communications network. The mobile terminal 30 may be any equipment capable of connecting to the communications network 21 . It may be for example a smartphone, a touch pad, etc.
[0068] The mobile terminal 30 typically comprises a data-processing module, location means (for example a GPS—“global positioning system”, a base station triangulation “system”, a WIFI connection, etc.), and interface means such as a screen. The mobile terminal 30 may be integrated into a vehicle of the user U. In general, “mobile terminal” means any device having communication means whereof travel coincides with those of the user U.
[0069] The thermal regulation system 10 is adapted to regulate a temperature T of the built structure B. Regulating, means a method, especially by retroaction given the temperature of the built structure, for setting an instruction temperature in the built structure B. Regulating therefore means acting on the temperature (having it evolve up or down) either actively (regulation towards a target temperature) or passive (fully or partially stopping heating) or air-conditioning, for example.
[0070] In default operation, i.e., when the built structure B is inhabited from a sufficiently long time for the permanent or standard regime to be reached (i.e. a significantly long time before a time characteristic of change in temperature of the built structure), the temperature T is at a living temperature Tv, for example 21° C. in winter and 24° C. in summer. The thermal regulation system 10 uses heating and/or air-conditioning, i.e., it comprises a heating and/or air-conditioning system.
[0071] The thermal regulation system 10 may function on electricity, gas, fuel, etc. and comprise emitters such as radiators, “heating” floors, etc.
[0072] Nominal power P n of said thermal regulation system 10 is defined, to which, for a built structure B and given meteorological conditions, a nominal regulation speed V n , may be corresponded, i.e., a nominal variation in temperature T of the built structure B per unit of time t. Coupling these data and the thermal characteristics of the built structure B (type of material, windowed surface, type of thermal regulation system, volume of the built structure, etc.) also stored on the storage module 23 (and for example input by the user U), originating from the post-processing of the data stored in the storage module 23 the built structure B may be modeled thermally, especially via evaluation of the thermal flows. This thermal modeling of the built structure B is done by the processing module 22 of the server 20 .
[0073] Alternatively, the skilled person could model the heat dynamics of the house via empirical data designated as “experimental design”.
[0074] Alternatively, the experimental design may accumulate data relative to the dynamics of evolution of the temperature T in the built structure B in many situations (variety of climatic conditions, conditions of occupation, etc.) and produces instruction reference, temperature values, etc. In light of the non-ideal character of the regulation system and of the built structure (reaction time, variability, etc.), It is evident that the experimental design may be corrected slightly so as to incorporate safety margins.
[0075] As mentioned previously, the server 20 is connected to the communications network 21 . It conventionally comprises a data-processing module 22 (such as a processor) and a data storage module 23 (for example a hard drive). The server 20 may be dedicated equipment (arranged in the built structure B or remote), or may be integrated into a personal computer, an Internet access box, etc. Also, the server 20 may be integrated into the mobile terminal 30 .
[0076] Preferably, the server 20 receives local meteorological data (external temperature, humidity rate, sunshine, wind direction and force, atmospheric pressure, etc.) of the region of placement of the built structure B. These meteorological data preferably come from a nearby weather station and are sent via internet and stored in the storage module 23 of the server 20 .
[0077] The following description takes the example of a heating system. It suffices to symmetrize the values around the living temperature Tv to obtain the method in the case of an air-conditioning system. The skilled person may easily adapt the method ad hoc.
[0078] Also, the method is described for a single user U; the case for several users (family) will be mentioned hereinbelow.
[0000] The aim of the invention is to optimize energy savings and ensure a comfort temperature Tc when the user returns to the built structure B after any absence. The comfort temperature Tc is a temperature different to the living temperature and which is different to it for example by 0.5° to 5°, preferably from 0.5 to 2°, preferably from 0.8° to 1.2°. In the case of the heating system, said comfort temperature Tc is less than the living temperature Tv. In fact, the user U does not immediately feel the real temperature of the built structure B after an absence and he needs some time to regulate to the temperature difference between the exterior and the built structure B. It is therefore not necessary for the built structure B to be directly at the living temperature Tv when the user U returns. During the acclimatization time, the temperature T will evolve from the comfort temperature Tc to the living temperature Tv without the user U suffering from cold. The comfort temperature Tc is therefore a transition temperature which improves energy savings. It should be noted that in some cases the comfort temperature Tc may be variable as a function of external meteorological conditions or seasons for example.
[0079] The comfort temperature Tc may be calculated by the data-processing module 22 of the server 20 by way of the experimental design and/or the thermal modeling of the built structure B to adapt it as a function of periods, and/or determined by the user U. The time necessary for moving from Tc to Tv must be less than the time for adaptation of the body to its environment, so that the latter does not feel the difference in temperature.
[0080] In reference to FIGS. 2 and 3 , in a first step (a) absence of the user U from the built structure B is detected when the user U leaves the built structure B, at the time t 0 .
[0081] The absence t 0 of the user U may be detected by comparison of location data provided by the mobile terminal 30 and location data of the built structure B. The comparison may be made by the mobile terminal 30 or by the server 20 . Alternatively, absence of the user U may be marked by detection of closing of an entry door, or by signaling of the user U, for example by means of an interrupter, by WIFI signal loss, by disconnection of a local network, or by detection via presence sensors.
[0082] In a second step (b) (see FIGS. 2, 3 ), an operating limitation instruction CL is sent to the thermal regulation system 10 . In the case of the heating system, the limitation instruction CL is in this case a decrease instruction by which the thermal regulation system 10 regulates the temperature T of the built structure B down. The invention functions in a mode known as “free”, also called “free intermittence”, i.e., the lowest attainable temperature T is attained during each absence. The limitation instruction CL may integrate an instruction temperature or not.
[0083] The limitation instruction CL may consist of either diminishing the power of the thermal regulation system 10 , or interrupting it completely, enabling a faster drop in temperature T. In all cases it will be evident that the limitation instruction causes a drop in energy consumption of the thermal regulation system 10 , and therefore of the built structure B.
[0084] The invention further provides a hold instruction CM in the event where the temperature T of the built structure B reaches an extreme temperature Te (see FIG. 4 ). The extreme temperature is generally set by public protection agencies. Typically, it may be a minimum temperature of 8° C. in France. At his convenience the user may decide in advance which extreme temperature Te to choose or choose to let the data-processing module 22 determine it. Typically, the limitation instruction CL may include an instruction temperature equal to the extreme temperature Te.
[0085] The operation of the method remains unchanged.
[0086] In a third step (c), geolocation of the user U is performed in a first part c 1 . In a second part c 2 , the return travel time Δtr of the user U is estimated as a function of geolocation data of the user U.
[0087] The geolocation data typically originate from the location means of the mobile terminal 30 of the user U. Estimation of the return travel time Δtr is undertaken by analysis of the position of the user U and known road schemes, of speeds of transport means (car, metro, walking, bike, etc.), of the state of traffic, etc.
[0088] Said analysis is performed by the server 20 after sending of geolocation data by the mobile terminal 30 .
[0089] Alternatively, said analysis may be performed by the mobile terminal 30 which then sends said estimation to the server 20 via the communications network 21 .
[0090] In a fourth step (d), a return temperature Tr is calculated as a function especially of the comfort temperature Tc and of said return time Δtr. “Return temperature” means a temperature of the built structure B from which the thermal regulation system 10 is capable in the return time Δtr of reaching the comfort temperature Tc. In other words, this return temperature Tr is calculated to ensure a temperature spread with the comfort temperature Tc which may be caught up by the thermal regulation system 10 during the return time Δtr. To refine this return temperature as accurately as possible, estimation of the return temperature Tr advantageously involves the experimental design or else the thermodynamic data such as the nominal power P n of the thermal regulation system 10 and its consumption, the thermal modeling of the built structure B (characteristics of the built structure and meteorological data).
[0091] Calculation is performed by the processing module 22 of the server 20 and as explained optionally integrates a safety margin, at the top, to mitigate any return faster than provided (excess speed, unforeseen shortcut) and measuring inaccuracies and/or non-uniformity of heat in the built structure B.
[0092] The return temperature Tr is therefore (in the case of heating) the lowest temperature to which the built structure B may drop for which the comfort temperature Tc may be attained when the user U returns to the built structure B.
[0093] In the case of the heating system, the return temperature Tr is less than or equal to the comfort temperature Tc.
[0094] In a fifth step (e) (see FIGS. 2, 3 ), a return instruction CR is emitted, by which the thermal regulation system 10 regulates the temperature T to the return temperature Tr.
[0095] Typically, the instruction is emitted by the server 20 to the thermostat 11 which controls the thermal regulation system 10 .
[0096] The method advantageously comprises an emission step (f) of a regulation instruction of the temperature T to switch from the comfort temperature Tc to the living temperature Tv when the presence of a user U is detected in the built structure B (see FIG. 5 ). This is a return to the operating mode by default.
[0097] To optimize energy savings to a maximum, steps (c) to (e) are repeated at preferably regular intervals δ tm , (see FIG. 6 ). In fact, since the return of the user U is often unknown, it is necessary for the system to re-evaluate the return instruction CR so as to adjust it to the optimal return temperature Tr, i.e., the lowest possible while letting the heating system reach the comfort temperature Tc when the user U returns. In FIGS. 7 a , 7 b , 7 c , where t′, t″ and t′″ represent the instants at which geolocations are made, the return temperatures Tr are adjusted as a function of estimation of the return travel time Δtr linked to geolocation. The resulting instruction temperature curve is in the form of a level, each end of level corresponding to launching a return instruction CR.
[0098] FIGS. 8 to 11 illustrate different curves of instruction temperature (solid lines) and of temperature of the built structure B (dotted lines) according to the length of the interval δ tm . The less the interval δ tm , the shorter the levels (see FIG. 9 ). When the interval δ tm tends towards 0, i.e. the location and sending of return instruction CT occur quasi-continuously, the instruction temperature curve tends towards a “smoothed” temperature curve (see FIG. 10 ). Alternatively, it will be evident that the invention is not limited to regular repetition of steps (c) to (e). In particular, in the event where it is no longer possible to get geolocation data (for example if the user is in a tunnel, or if his mobile terminal is off), it is possible to define for security reasons the return temperature Tr equal to the comfort temperature Tc: the temperature curve T does not have a level (see FIG. 11 ). Activation of security occurs only when the temperature T is less than the comfort temperature Tc. Alternatively, in the event of loss of geolocation data, the method switches automatically to a programmable regulation mode based on the hours of presence and absence and/or the effective presence of the user or input in the terminal 30 of the preferred temperature T of the built structure B.
[0099] It should be noted that the return temperature Δtr corresponds in fact to the minimum temperature so that the thermal regulation system 10 may connect the comfort temperature Tc to an iteration (δ tm ). In this way, the return temperature Tr may anticipate this iteration. In other words, this return temperature Tr is calculated to ensure a temperature spread with the comfort temperature Tc which may be caught up by the thermal regulation system 10 during the return time Δtr from which the interval δ tm has been subtracted. When the interval δ tm is reduced, the interval becomes small relative to the estimation of the return time Δtr and it becomes possible to assimilate the two values such that convergence of the temperature of the built structure B towards the comfort temperature Tc is ensured: when δ tm tends towards 0, the return temperature Tr tends towards the comfort temperature Tc (see FIG. 10 ). It may be possible to model Δtr as a continuous function of time (updated each time steps (c) to (e) are performed, i.e. every δ tm ).
[0100] Also, because of the safety margin optionally provided in evaluation of the return temperature Tr and measurement and/or non-uniformity inaccuracies of heat in the built structure B, the built structure is effectively at the comfort temperature Tc when the user returns to the built structure B.
[0101] It is important to note that the temperature T curves of the built structure B are separate to the instruction temperature curves.
[0102] Steps (c) to (e) may also be conducted dynamically, i.e. the return temperature Tr is a refined function of the estimation of the return time Δtr. In this embodiment, the temperature T of the built structure B may follow the instruction of the return temperature Tr, such that the temperature of the built structure converges mathematically towards the comfort temperature Tc. Δtr then becomes a continuous function of time.
[0103] According to an embodiment (see FIG. 6 ), the method integrates a test step at the start of step (c) during which the temperature T of the built structure B is measured: if said temperature T is between the living temperature Tv and the comfort temperature Tc then step (c) is not initiated. Such a test ensures that the temperature T drops effectively below the comfort temperature Tc (in the case of the heating system) before performing geolocations and return instructions CR. Alternatively, to make the system reliable and anticipate detection of habit, steps (c) to (e) are initiated in parallel to step (b) from the start of absence. But the result of steps from (c) to (e) is taken into account (i.e. the return instruction CR is sent) only when the test step is verified. In this embodiment the test step is either in the same position as previously, except that the results of steps (c) and (d) are not taken into account, or between the steps (d) and (e).
[0104] According to an embodiment, the method integrates calculation of the derivative of the position of the user U or the derivative of estimation of the return travel time Δtr, to set up a tendency of the built structure B to move away or come closely. Typically, as soon as moving away is detected, the method restarts at step (b) so as to optimize energy savings and as soon as an approach is detected, the method restarts at the second part of step (c). Using tendencies is particularly advantageous in the event where the interval δ tm is considered in addition to estimation of return travel time Δtr for calculation of the return instruction CR, since the tendency detects moving away or approach and integration of the interval δ tm for calculation of the return instruction CR presupposes anticipation of travel by the user U. In such a case, step (c) may be conducted before the test preliminary previously described is true, so as to sketch a tendency before crossing the comfort temperature Tc.
[0105] To limit instructions known as fast-paced, linked to near geolocations (trampling or return travel of a few tens of meters for example) called geostatic, filtering may be applied to step (c). This filtering is typically done by the processing module 22 of the server 20 .
[0106] For example, the filtering may consist of creating a circle of a certain diameter around a geolocation position and, as long as no geolocation identifies the user U outside this circle, no new return temperature Tr is updated and no return instruction CR is emitted. As soon as a geolocation identifies the user U outside this circle, a new circle is created around said geolocation. In FIG. 12 , where t′, t″ and t′″ represent those times when geolocation is carried out, the geolocations at t′ and t″ are considered as geostatic; such filtering is performed during the first part c 1 of step (c). Alternatively, the filtering may consist of creating a return travel time interval around an estimation of return travel time Δtr and verify whether successive said estimations Δtr are inside said interval, in which case no return instruction Tr is emitted; as soon as an estimation is outside the interval, a new interval is created around this value. Such filtering is performed during the second part c 2 of step (c).
[0107] Such filtering events contribute to obtaining a tiered temperature T curve.
[0108] According to an embodiment, the server 20 comprises a local learning method, by accumulation of data originating from the user U in a learning base stored on the processing module 23 .
[0109] This local learning anticipates the absence of the user U and, during a previous step a 0 during which a pre-limitation instruction CPL is emitted at a given time prior to absence of the user U, such that at the time t 0 of the absence of the user U, the built structure B is already at the comfort temperature Tc (see FIG. 13 ). The pre-limitation instruction CPL is thus equivalent to the limitation instruction CL, except that it is emitted before an absence is detected. It will be evident that the limitation instruction CL emitted at step (a) is confirmation of the pre-limitation instruction. In case of error, since the comfort temperature is not felt again by the body it may be raised without inconvenience to the occupant. Step (a) may in this case comprise updating of the learning base.
[0110] This local learning also defines usual places or a travel zone Z (see FIG. 14 ). Originally, this zone Z may be defined as a disc of radius of 100 km for example, then may be refined as per the habits of the user. Such a zone Z covers 95% of daily travel and is particularly adapted for determining travel and refining the value of the return temperature Tr.
[0111] According to an embodiment, step (c) integrates a question instruction CQ which queries the user U, via the mobile terminal 30 , on his estimation of the return travel time Δtr. According to the response of the user, the return instruction CR is adapted. The question instruction CQ is thus given after the geolocation. In particular, this question may be addressed to the user via an application of the mobile terminal or via push notifications (alert message indicating to the user U even when the application is closed) to which a simple contact responds. The response supplied by the user U optimizes energy savings, preventing the return temperature Tr calculated by step (c) from being kept unuseful. In fact, the return temperature Tr is calculated so that the built structure B may be at the comfort temperature Tc when the user U returns, the user U who may begin his return travel any time. However, if it eventuates that the user is not returning, the return temperature Tr may be lower (still in the case of a heating system).
[0112] This embodiment applies particularly advantageously when the user U is outside the usual travel zone Z or, inversely, near home: in fact, a user U a few minutes away from the built structure B will ensure that the return temperature Tr of the built structure B will be kept very close to the comfort temperature Tc while user U may be absent for the entire day.
[0113] It is preferable to limit use of the question instruction CQ so as to limit interventions of the user U in management of the thermal regulation system 10 .
[0114] In particular, the question instruction CQ is advantageously employed only if the filtering defined for step (c) described previously has detected a geostatic position.
[0115] Also, the method applies to several users U. In this case, step (a) is performed for each user U of the built structure B, and step (b) is performed if step (a) is verified for each user U of the built structure B: the limitation instruction CL is emitted if and only if no user U is present in the built structure B. Step (c) is performed for each user U, i.e. geolocation and estimation of the return travel time is performed for each user and step (d) is performed for the lowest possible estimation of return travel time Δtr of all estimations Δtr.
[0116] The method also applies to a plurality of built structures B. In this case, each built structure B is treated independently.
[0117] As has been mentioned, the method also applies both to heating systems and to air-conditioning systems.
[0118] In this second case, the thermal regulation system 10 comprises an air-conditioning system, the return temperature Tr being greater than the comfort temperature Tc, in turn greater than the living temperature Tv (see FIG. 15 ). | The invention relates to a method for adjusting temperatures of a built structure provided with a thermal adjustment system configured to adjust the built structure to a predetermined living temperature. Said method includes implementing, via a data processing module, the steps of: (a) detecting absence of a user, (b) sending, to said system, a limiting instruction whereby said system interrupts adjustment to the living temperature; (c) estimating a return travel time of the user on the basis of geolocation data; (d) determining a return temperature on the basis of a comfort temperature, different from the living temperature, and on the basis of the return travel time, the return temperature allowing said system to reach the comfort temperature during the return travel time; and (e) sending, to said system, a return instruction whereby said system adjusts to the return temperature. | 5 |
BACKGROUND
Hunters, photographers and other wildlife enthusiasts attract animals, especially deer, using processed animal urine. The urine naturally has aromatic characteristics or scent which includes pheromones that attract the animal. The urine is processed to remove impurities found in the urine due to the current methods of urine collection. The processed urine is usually from the species of animal which is desired to be attracted. For example, processed deer urine is used by hunters to attract deer during the hunting season of deer. The example of deer urine will be used throughout this specification as it is the predominant animal lure on the market.
The processed deer urine is sold in a bottled liquid form. A major problem with this type of lure is that it has a short shelf life due to degradation of the urine. Mammal urine degrades quickly because it has a high nitrogen content. The high nitrogen content is present because mammals excrete the unused nitrogen from proteins contained in their food through urea. The urea makes up approximately two to five percent (2-5%) of the urine content. After the urine is excreted by mammals, the easily released nitrogen from the urine combines with hydrogen in the urine to form ammonia. The odor from the ammonia masks the pheromones and other scent qualities of the urine which are used to lure the deer, thereby defeating the purpose of the lure. Once the urine is excreted, the production of ammonia begins and as the urine ages, the strength of the ammonia odor increases. Therefore, as the bottled urine sits on the shelf, the nitrogen is continually combining with hydrogen from the urine to form ammonia.
It is an object of the present invention to provide a method and means to reduce and remove the ammonia produced during the processing of animal urine.
It is an object of the present invention to provide a method and means to halt or at least limit the production of ammonia in stored processed urine until it is used for its intended purpose as an animal lure.
It is also an object of the present invention to remove the smell of ammonia from urine based scents that have not been processed according to the present invention.
SUMMARY OF THE INVENTION
The present invention is a method and means of enhancing urine based lures by using zeolite to absorb nitrogen and ammonia found in the urine. The method includes several steps of mixing zeolite with urine from the collection stage to the packaging of the urine. The method includes the step of passing the urine through zeolite to absorb the nitrogen and the ammonia in the urine. Clinoptilolite was one zeolite found to be quite successful for removing the nitrogen and ammonia. In the method, zeolite is also added to collection channels and collection containers so that the absorption process begins at the collection stage of processing the urine. The urine is filtered through the zeolite prior to packaging of the urine. Finally, the urine is packaged with zeolite. Another method disclosed is mixing urine based lures with zeolite which have not been processed with the zeolite to remove the ammonia smell associated with these lures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional side view of a combination tank according to the present invention.
FIG. 2 is an external view of a bottle to mix the urine and zeolite according to the present invention.
DETAILED DESCRIPTION
The typical manner of collecting deer urine is to keep deer in a pen which has a collection system. The collection system is usually a system of grates with openings as part of the pen floor. Under the openings are collection containers or collection channels which lead to collection containers. When the deer excrete the urine, the urine flows through the grate openings into the collection containers, due to gravity. The urine must be processed because the deer also defecate in the pen and the deer feces, as well as other impurities in the pen, mix with the urine. Processing of the urine entails some form of filtering. Filtering removes the unwanted feces and other impurities from the pen that mix with the urine during the collection process. It is immediately upon excretion, during collection and during filtering of the urine when the natural break down of the urine begins and ammonia is produced from the nitrogen and hydrogen in the urine. The method and means of the present invention counteracts this natural break down of the urine, thereby, providing a stronger lure to attract the deer because the scent is not masked by the ammonia.
The present invention is a method and means of using natural or synthetic zeolite during the processing and storage of the deer urine to prevent the formation of ammonia. The zeolite captures or absorbs the nitrogen of the urine. The zeolite can absorb nitrogen oxides, ammonium ions, sulfur dioxide and heavy metals. The zeolite acts as a molecular sieve, matter absorber and catalyst. Clinoptilolite was one particular zeolite found to be particularly successful in the method of the present invention. Clinoptilolite has the chemical name of Potassium-calcium-sodium-aluminosilicate and one of its empirical formulas is (K 2 ,Ca,Na 2 )O--AL 2 O 3 --10SiO 2 --6H 2 O. Clinoptilolite has a pH stability in the range of 3-10 and can be acquired in the form of various sized stones.
The method begins with placing clinoptilolite stones of various sizes in the collection channels and collection containers. The stones absorb the nitrogen and ammonia in the urine, thereby preventing hydrogen in the urine from combining with the nitrogen. It is believed that hydrogen is an important factor in having a stronger attractant for the deer and should be prevented from combining with the nitrogen. The stone sizes are usually a mixture of fine stones up to approximately one-and-a-half (11/2) inch size stones. The urine is removed from the collection channels and collection containers on a daily basis to make room for additional urine collection. The smaller sized stones are used because the larger the stone, the longer it takes to absorb the nitrogen and ammonia. The clinoptilolite is replaced on a regular basis of about every three to seven (3-7) days. When the urine is removed from the collection channels and collection containers, it is filtered through a two step filtering process. The first step is designed to remove solids such as broken down feces and other impurities from the pen. A coffee filter or its equivalent is used in the first step and the first step is repeated if the filter clogs in order to remove all solid impurities. The second step is filtering the urine through a second filter of clinoptilolite. Approximately one-and-a-half to two (11/2-2) cubic feet of clinoptilolite are used in the second filtering step. The clinoptilolite is replaced in the second filter after approximately fifty (50) gallons of urine has been filtered.
After the two step filtering process, the urine is ready to be packaged. The urine is usually packaged in an amber colored bottle to protect it from sun light. The urine is bottled depending on how much has been collected. It is preferable to have approximately five (5) gallons at a time before bottling. The bottling in the five gallon quantity allows the control of scent quality. If there is not enough urine to be bottled right away, it is frozen until there is enough available to bottle. The urine can be frozen in a five gallon bucket containing approximately one-and-a-half (11/2) cubic feet of clinoptilolite. When the urine is thawed for bottling, it is either placed into a thaw tank with clinoptilolite of variable sizes or thawed in the buckets if it was frozen with the clinoptilolite. The thaw tank has approximately one-and-a-half (11/2) cubic feet of clinoptilolite to thaw five (5) gallons of urine at a time. The thawed urine is then drained from the tank for bottling. In order to preserve the urine in the bottle, one (1) oz. of clinoptilolite is placed into a two (2) oz. bottle and one (1) oz. of urine is then added to the bottle. The size of clinoptilolite in the bottles is preferably smaller than bigger to enable the nitrogen and ammonia to be absorbed at a faster rate. The placing of clinoptilolite in the bottle continues the process of absorbing the nitrogen and ammonia from the urine. This provides a lure which utilizes the full potential of the attractive power in the urine and has a longer shelf life.
FIG. 1 illustrates a combination tank 10 to perform the two step filtering process, thawing process and bottling. The combination tank 10 includes a large tank 12, a smaller removable tank 14 and a drain 16. The removable tank 14 rests within the large tank 12 and has a multitude of holes 18 in its bottom 20. The drain 16 is mounted on the bottom 22 of the large tank 12 and is used to drain the processed urine into the bottles (not shown) for sale. With the removable tank 14 installed, a filter 24 is placed in the bottom 20 of the tank 14 to perform the two step filtering process. The filter 24 is usually a coffee filter or its equivalent. The raw urine is placed in the removable tank 14, where it flows into the large tank 12 by way of the filter 24 and the holes 18. There the urine flows through clinoptilolite 26 at the bottom 22 of the large tank 12 and into the drain 16. When the urine is to be thawed, it can be place in the removable tank 14 or placed directly into the large tank 12 if the removable tank 14 has been removed. In either case of thawing, the large tank 12 would have the clinoptilolite 26 at its bottom 22.
At the retail level, many of the urine based scents sold already smell like ammonia when the consumer buys the product. The following is a method and means of enhancing these urine based scents that have an ammonia smell. Packaged clinoptilolite can be provided to add to the urine based scents which have not been processed with clinoptilolite. One method is to provide clinoptilolite that the user can mix with the urine based scent at a ratio of one-to-one (1 to 1). Another method is to provide one (1) oz. of clinoptilolite 30 in a two (2) oz. bottle 32 that includes a squirt cap 34 as shown in FIG. 2. This allows for the user to add the urine based scent that is normally sold in a one (1) oz. container to the clinoptilolite filled bottle. A smaller size stone of the 8 to 14 stones per linear inch are the preferred size in the bottle, as the smaller stones would have a faster rate of removing ammonia.
While embodiments of the invention have been described in detail herein, it will be appreciated by those skilled in the art that various modifications and alternatives to the embodiment could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements are illustrative only and are not limiting as to the scope of the invention which is to be given the full breadth of the appended claims and any and all equivalents thereof. | The present invention is a method and means of enhancing urine based lures by using zeolite to absorb nitrogen and ammonia found in the urine. The method includes several steps of mixing zeolite with urine from the collection stage to the packaging of the urine. The present invention also includes a method and means for enhancing urine based lures that are already packaged and on the shelf for resale. | 0 |
CROSS-REFERENCE TO RELATED APPLICATIONS
Not applicable.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a method for the manufacture of individual pipe sections of a pipe formed by a product pipe and of at least one channel running along the product pipe, particularly a heat channel in which the product pipe and the channel are fitted with an insulation enclosed with a jacket pipe and a pipe manufactured in that manner.
2. Description of Related Art
Practical applications often require pipes to be heated because the products to be transported within the product pipe exhibit appropriate flowability only at a certain temperature. The heating of the pipes is generally achieved with an accompanying heating system consisting of a heat pipe attached to the product pipe used to transport the product. German Patent No. DE-PS 43 14 761, for example, describes a method for the manufacture of individual pipe sections of a pig pipe. The patent describes a method in which the product pipe is fitted with an additional heating pipe through which the heating of the product to be transported in the product pipe is achieved with steam piped at a high pressure as the heating medium.
Practical applications have shown, however, that the heat transfer between the heating and product pipe is in many cases insufficient due to the linear contact area between the two pipes and due to the fact that steam cannot be used as the heating medium when the product to be transported in the product pipe should not come into contact with water for safety reasons. Furthermore, the known form for the heating channels is disadvantageous for pipes that are not straight, because the fitting of an additional heating pipe to the product pipe is difficult to achieve from a manufacturing point of view, particularly at sharp bends.
OBJECTS OF THE INVENTION
It is an object of the invention to provide a method for the manufacture of individual pipe sections of a pipe such that good heat transfer to the product pipe is achieved and any channel shape can be run along the product pipe in a cost-effective manner.
SUMMARY OF THE INVENTION
The invention is a method for the manufacture of individual pipe sections including a product pipe having a jacket surface and at least one channel running along the jacket surface of the product pipe including the following steps:
a) Arranging a core that exhibits at least the outside contour of the desired channel on the surface of the product pipe such that the channel to be formed upon the removal of the core will be immediately adjacent to the surface of the product pipe and approximately parallel to the product pipe.
b) Inserting the product pipe with the core into a jacket pipe; and
c) Filling the jacket pipe with an insulating mass that exhibits a flowability only during processing.
An advantage of the invention is that any channel type may be manufactured along the product pipe such that it is in direct contact with the surface of the product pipe.
Accordingly, it is a feature of the invention to easily pull an electric heat conductor through the channel arranged in the manner of the invention. It is also possible to run heating gas through the channel. In addition to utilizing the channel as a heating channel, it is also possible to use it for receiving a detector cable or a so-called “sniffing pipe” which can detect leaks in the product pipe.
These and other objects, advantages, and features of this invention will be apparent from the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-section of a preferred embodiment of the invention in a rectangular channel configuration.
FIG. 2 is a cross-section of a preferred embodiment in a configuration with three U-shaped channels.
FIG. 3 is a plan view of a preferred embodiment of the invention consisting of two pipe sections.
DETAILED DESCRIPTION OF THE INVENTION
It was proven particularly advantageous to manufacture the channel by pulling the core out of the jacket pipe after the insulation mass has hardened. In addition to yielding a simple channel manufacture, said method also allows a reuse of the core retrieved in that manner. It also allows the use of a solid core, as opposed to one that merely exhibits the outside contour of the channel, which adds to its durability and reusability. Pulling the core out of the hardened insulation mass produces a channel that runs along the surface of a product pipe and that is in direct contact with the surface of the product pipe, thus ensuring a good heat transfer between heating channel and product pipe.
According to a preferred embodiment of the invention, the material used for the core consists of an elastic material whose cross-section decreases in area with the application of a tensile force. Silicone rubber is such a material, for example. After the insulation mass has hardened, an elastic material is particularly easy to pull out of the pipe section. When applying a tensile force, the outer surface of this elastic core material separates from the hardened insulation mass due to the decreased cross-section and pulling the core out of the channel formed by it requires very little effort.
A further embodiment of the invention proposes that the core material consists of a material that is elastic and expands under pressure. For example, such a core can be formed with a hose that maintains its shape by way of a hydraulic or pneumatic pressure until the insulation mass has hardened. The hose will collapse after lowering the pressure and can be pulled out of the jacket pipe.
A further embodiment of the invention proposes that the core consists of a non-elastic material, to which is applied a separating agent on the outside surface facing the insulation mass and prior to pushing the product pipe and core into the jacket pipe. A core made of a non-elastic material can only be used for generally straight pipe sections, since pulling the core out of the hardened insulation mass would otherwise require much effort. In that respect, the separating agent applied to the outside core surface should reduce the frictional forces between the hardened insulation mass and core. Applying a separating agent has also proven beneficial for a core made of an elastic material.
According to an alternative embodiment of the invention, the channel that is open toward the product line is produced using a hollow profile core of generally “U” shaped cross section that is arranged on the product pipe with its open side facing the product pipe and remains in the jacket pipe after the insulation mass has hardened.
To improve the heat transfer between channel and product pipe and to make the pulling-out of the core from the hardened insulation mass easier, a further embodiment of the invention proposes that a thin coating that preferably promotes the heat transfer be applied to the core surface facing the insulation mass as well as to the portion of the surface of the product pipe touching the core prior to inserting the product pipe with core into the jacket pipe.
According to a preferred embodiment of the invention, this thin coating that preferably promotes the heat transfer is applied to the core surface facing the insulation mass as well as to the entire surface of the product pipe. In this manner, it is possible to achieve a heat transfer from the channel to the entire surface of the product pipe that is not directly heated. In addition to improving the heat transfer, the use of a thin coating that is applied over the surface of the product pipe simplifies a possible recycling of a pipe manufactured in that manner, since the insulation material and the product pipe remain almost completely separated. Metal foils and particularly aluminum foil represent particularly suitable materials. To prevent the thin coating from being pulled out when pulling the core out of the pipe section, a bonding agent can be applied to the thin coating surface facing the insulation material (the outside surface of the thin coating).
A further embodiment provides for the arranging of a spring-elastic element made of an elastic material such as foam on the core surface facing the insulation mass. When using an electric heat conductor to be introduced in the channel, this elastic element functions as a spring element and the heat conductor is pressed against the surface of the product pipe. The elastic element is compressed by the filling and hardening of the insulation mass. The elastic element will expand to achieve its original form after the core has been removed. When using the thin coating that promotes the heat transfer, the spring-elastic element can be arranged on and/or below the thin coating. When using hollow profiles that remain in the jacket pipe, the spring-elastic element can be arranged on the hollow profile's inside surface facing the channel.
The method in accordance with the invention can be developed further by fitting the product pipe and core with a spacer prior to inserting them in the jacket pipe, thus ensuring that they occupy a defined position within the jacket pipe.
Finally, a further embodiment proposes the use of an insulation mass that increases its volume during the hardening process, e.g., polyurethane foam. Polyurethane foam presents the advantage that it exhibits a low heat conductivity and a known compressive strength.
The pipe sections shown in FIGS. 1 and 2 in the form of a cross-section basically consist of product pipe 1 and insulation 3 enclosed by jacket pipe 2 .
To maintain product pipe 1 in a predetermined position in jacket pipe 2 , product pipe 1 is fitted with spacers 4 exhibiting radially arranged webs to ensure a uniform and preferably coaxial position of product pipe 1 within jacket pipe 2 .
Channel 5 that is open toward product pipe 1 is provided on the jacket surface of product pipe 1 to receive, for example, an electrical heat conductor. In the embodiment shown in FIG. 1, rectangular channel 5 is arranged on the bottom of product pipe 1 , while the embodiment shown in FIG. 2 shows three channels 5 arranged at a spacing on the bottom of product pipe 1 .
To increase the heat transfer between the heat conductor and product pipe 1 and to achieve a separation between product pipe 1 and insulation mass 3 for a possible recycling at a later date, thin layer 6 consisting of a material that preferably promotes the heat transfer is applied to the jacket surface of product pipe 1 touching channel 5 and the outside surface of channels 5 . Aluminum foil is a particularly suitable material for thin layer 6 . In the embodiment shown in FIG. 2, thin layer 6 extends across the whole free jacket surface of product pipe 1 .
The first process step in the manufacture of a pipe section exhibiting one or more channels 5 on the jacket surface of product pipe 1 is to dispose core 7 exhibiting the outside contour of channel 5 on the jacket surface of product pipe 1 . To obtain the pipe cross-sections shown in FIGS. 1 and 2, thin layer 6 consisting of an aluminum foil is subsequently placed on the free jacket surface of product pipe 1 as well as on the outside surface of cores 7 .
Spacers 4 are subsequently arranged on product pipe 1 and the unit formed by core 7 and product pipe 1 is inserted in jacket pipe 2 .
In addition to using a thin-walled pipe as jacket pipe 2 , jacket pipe 2 manufactured by way of a spiral-like coiling and folding of a stretched sheet metal band was proven to be very suitable.
After inserting the unit formed by core 7 and product pipe 1 in jacket pipe 2 , the free cross-section of jacket pipe 2 is closed and the free channel cross-section of jacket pipe is subsequently filled with an insulation mass exhibiting a flowability in the processing condition to form insulation 3 . Because polyurethane foam exhibits a low heat conductivity and hardens under pressure, it is considered a particularly suitable insulation mass.
To form channel 5 that is product pipe 1 , core 7 is pulled out of the hardened insulation mass after the insulation mass has hardened. In addition to the simple and cost-effective manufacture of channel 5 that is open toward product pipe 1 , this manufacturing method is characterized by the fact that an almost indefinite number of channel runs are possible along the pipe length and a good heat transfer to product pipe 1 is ensured due to the fact that channel 5 is in direct contact with pipe 1 . In addition to being utilized as a heating channel, channel 5 can also be used to receive a detector cable or as a so-called “sniffing pipe” to discover leaks in product pipe 1 . In the design form shown in FIG. 2 with three channels 5 arranged on the jacket surface of product pipe 1 , each channel 5 can possibly be used for a different purpose.
The connecting of pipe sections produced with this method occurs on site as shown in FIG. 3 in a schematic representation. First, a welded connection is achieved between product pipes 1 which project beyond jacket pipe 2 , insulation 3 , and channel 5 . Next, a channel element 8 is inserted in channels 5 of the piping sections and connected so as to increase the length of channel 5 beyond the connection point. Product pipe 1 and channel 5 are subsequently insulated in a suitable manner and collar 9 is pushed onto the connection, thus connecting jacket pipes.
It may not be necessary to insert channel element 8 at the connection point when channels 5 of the pipe sections are used to receive a heat conductor and when an appropriate insulation is ensured at this connection point.
When channel 5 is used to receive an electric heat conductor, it is advantageous to make the cross-section of the channel several times larger than that of the heat conductor, since this provides the best utilization of the heat convection. Furthermore, this effect is reinforced by rounding the channel corners.
There are of course other alternate embodiments which are obvious from the foregoing descriptions of the invention, which are intended to be included within the scope of the invention, as defined by the following claims. | The invention concerns a method for the manufacture of individual pipe sections of a pipe formed by a product pipe having at least one channel running along the product pipe. Surrounding the product pipe and the channel is a pipe jacket filled with an insulating mass which exhibits a flowability only in the processing condition. The channel running along the product pipe is formed by the outline of a core of material in place during addition of the insulation. | 5 |
TECHNICAL FIELD
[0001] This invention relates generally to network communications and more particularly to the facilitation of home agent allocation and/or selection.
BACKGROUND
[0002] Mobile Internet Protocol version 6 permits a mobile node to roam from link to link without requiring a change of the mobile node's Internet Protocol version 6 address. A mobile node is addressed by its home address which in turn comprises an Internet Protocol version 6 address as assigned by a router in the home domain of the mobile node that acts as a home agent. Movement of the mobile node away from its home link is therefore transparent to transport and higher-layer protocols and applications.
[0003] Most mobile nodes in a third generation (3G) network will not be initially configured with a home agent address, however. Instead, a mobile node dynamically discovers the home agent's global address through a process known as dynamic home agent address discovery. Pursuant to this process, the mobile node transmits an Internet Control Message Protocol version 6 home agent discovery request message using an anycast address. (An anycast address has a property wherein the same address is configured on multiple nodes but a forwarding router will ensure that the packet is received by only one of the nodes that is configured with this address. Therefore only one of the home agents in a network will receive the discovery request and reply to it.) One of the home agent responds with a discovery reply message that comprises addresses for the set of routers that are attached to the mobile node's home link and that are capable of serving as a home agent. (To effect this process, home agents maintain a list of home agents that are present on the link.) The mobile node then selects a home agent from the proffered list. This list is preferably sorted based on the preference level indicated by each home agent.
[0004] Such a process serves relatively well to ensure provision of an active home agent to a mobile node. This approach, however, does not serve all needs. For example, such a home agent list would simply reflect the architectural presence of each home agent. Such a list would not, for example, provide any information regarding more subjective matters such as local loading burdens for a given home agent.
[0005] To meet such needs, the described process has been further embellished with an ability to indicate a so-called preference for each home agent. In particular, the present process allows a system administrator to manually set a preference value in a corresponding home agent preference field that comprises a part of a corresponding router advertisement. It has also been suggested that the home agent might be configured to dynamically set its home agent preference value as a function of, for example, the number of mobile nodes currently being served by that home agent.
[0006] Though such embellishments are helpful, again, not all needs are necessarily suitably met by these prior art practices. As one example, present standards and corresponding comments make no mention of any method by which a home agent might facilitate a more dynamic decision process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] The above needs are at least partially met through provision of the method and apparatus to facilitate use of home agent preference information described in the following detailed description, particularly when studied in conjunction with the drawings, wherein:
[0008] FIG. 1 comprises a flow diagram as configured in accordance with various embodiments of the invention;
[0009] FIG. 2 comprises a schematic view of a message format as configured in accordance with various embodiments of the invention;
[0010] FIG. 3 comprises a schematic view of a message format as configured in accordance with various embodiments of the invention;
[0011] FIG. 4 comprises a schematic view of a message format as configured in accordance with various embodiments of the invention;
[0012] FIG. 5 comprises a schematic view of a message format as configured in accordance with various embodiments of the invention;
[0013] FIG. 6 comprises a flow diagram as configured in accordance with various embodiments of the invention;
[0014] FIG. 7 comprises a block diagram as configured in accordance with various embodiments of the invention;
[0015] FIG. 8 comprises a flow diagram as configured in accordance with various embodiments of the invention; and
[0016] FIG. 9 comprises a signal flow diagram as configured in accordance with various embodiments of the invention.
[0017] Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments of the present invention. It will also be understood that the terms and expressions used herein have the ordinary meaning as is usually accorded to such terms and expressions by those skilled in the corresponding respective areas of inquiry and study except where other specific meanings have otherwise been set forth herein.
DETAILED DESCRIPTION
[0018] Generally speaking, pursuant to these various embodiments, a home agent preference control node receives home agent availability information via, for example, router advertisement messages from home agents in a corresponding network. The home agent preference control node uses this home agent availability information and other information regarding at least one of the home agents to form a corresponding preference value for each of the home agents. The home agent preference control node then transmits home agent list (preferably sorted based on the preference) information to the home agents. This home agent list information identifies the home agents that are available in the network and further sets forth a preference value as corresponds to each of the home agents.
[0019] So configured, the home agents can then thereafter provide such home agent list information to mobile nodes to permit the mobile nodes to select a particular home agent as a function, at least in part, of the home agent list information and in particular the preference value information.
[0020] The other information referred to above can vary with the needs and/or requirements of a given application. Examples include, but are not limited to, information regarding a number of mobile nodes that are currently being served by a given home agent, an average number of mobile nodes that were served by a given home agent over a predetermined period of time, a value indicative of unallocated (or allocated) resources available to a given home agent, and so forth.
[0021] In a preferred approach, the home agent preference control node also receives subsequent updated information from the home agents. This updated information, in turn, permits re-calculation of the preference values. These resultant updated preference values are then provided to the home agents as a substitute for earlier provided information. So configured, pairing of home agents to mobile nodes can be more efficiently and appropriately carried out, both initially and in subsequent times.
[0022] These and other benefits may become more evident upon making a thorough review and study of the following detailed description. Referring now to the drawings, and in particular to FIG. 1 , a home agent preference control node receives 11 router advertisement messages from home agents in the corresponding network (those skilled in the art will recognize and understand that a so-called home agent preference control node can be configured as a stand-alone network element or can be functionally and logically distributed over numerous network elements in accord with well understood prior art practice with respect to such architectural choices and opportunities).
[0023] In accord with present practice, these router advertisement messages comprise, at least in part, home agent availability information (i.e., a corresponding direct or inferred indication that a given home agent is available within the given network). (In the alternative and/or in addition to gleaning such home agent availability information from such router advertisements, the home agent preference control node can access a list of home agents in the network via other means as may be appropriate or available. For example, such a list can be previously provided to the home agent preference control node by, as one illustration, a network administrator or a corresponding information server when such is available.)
[0024] The home agent preference control node also has access to other information regarding the home agents. Pursuant to one optional approach, such other information is received 12 , at least in part, from the home agents themselves. For example, pursuant to one approach, the home agent preference control node can transmit a message to the home agents to request such other information and the home agents can respond accordingly via a synchronous or asynchronous message (as may best comport with available resources and transmission protocols in a given instance). Referring momentarily to FIG. 2 , such a message 20 can utilize the user datagram protocol and can comprise, in addition to an attendant Internet Protocol version 6 header, a user datagram protocol header, and a home agent preference control node (HPCN) address, a type-length-value formatted list of requested parameters 21 that comprise, at least in part, the other information sought by the home agent preference control node. (These type-length-value tuples can have a format as illustrated in FIG. 3 if desired.)
[0025] The other information comprises, in general, information that holds at least some potential as a basis for calculating a preference value for the home agents. The precise nature of such information can and will likely vary from network to network and over time. Some present useful examples comprise:
[0026] a number of mobile nodes currently being served by a given one of the home agents;
[0027] an average number of mobile nodes that were served by a given one of the home agents over a predetermined period of time;
[0028] a value indicative of unallocated resources available to a given one of the home agents to support additional mobile nodes;
a value indicative of the currently allocated resources in a given one of the home agents.
[0030] Referring now momentarily to FIG. 4 , the home agents can respond to such a request with a reply message 40 that again utilizes user datagram protocol formatting. This reply message 40 can comprise, at least in part, the type-length-value formatted list of parameters as was originally requested by the home agent preference control node.
[0031] Referring again to FIG. 1 , the home agent preference control node then uses 13 this gathered information to form a corresponding preference value for at least some, and preferably all, of the home agents. This availability information and corresponding preference values are then transmitted 14 to the home agents in the network. Referring momentarily to FIG. 5 , this transmission can comprise another user datagram protocol formatted message 50 that preferably enumerates the various home agents (and their corresponding address) along with an indication of their calculated and/or otherwise determined preference value. As illustrated, a first home agent has a home agent preference 1 value associated therewith while an Nth home agent has a home agent preference N associated therewith. (As suggested by the “N,” such a message can list any number of home agents as may be available. In the alternative, if desired, multiple messages can be used to convey this information.)
[0032] So configured, and as will be shown below, the home agents can then thereafter provide such home agent list information to mobile nodes to permit the mobile nodes to select a particular home agent as a function, at least in part, of the home agent list information.
[0033] The above-described process permits preference values for a plurality of home agents to be determined in an informed fashion. As noted above, however, conditions influencing such preference calculations likely will change over time in response to a wide variety of factors and conditions. A preferred approach will therefore support dynamic updating of these preference values. For example, and referring now to FIG. 6 , a corresponding process 60 presumes (and/or occasions) periodic receipt 61 of additional or supplemental other information regarding the home agents. This can occur pursuant to a regular schedule or can occur on a more asynchronous or anecdotal fashion. Pursuant to one approach, the home agent preference control node can itself initiate repeated requests for the information of interest. Such repeated requests can be scheduled and/or can be event driven as desired. As one illustrative example, such requests can be repeated at thirty minute intervals during one period of time during the day and at five minute intervals during another time during the day. Pursuant to another approach, the home agent preference control node can specify a periodicity by which each home agent should transmit a message comprising the additional other information. Such a specification could be included, for example, in the original request for information or in one or more of the outbound list messages. Pursuant to yet another approach, one could combine scheduled updates with anecdotal or event-driven requests as may be sourced by the home agent preference control node.
[0034] Upon receiving 61 such additional other information, the home agent preference control node can re-calculate 62 some or all of the preference values as a function, at least in part, of the additional other information. By one approach, this re-calculation can be based entirely upon the new information. By another approach, this re-calculation can account, to some desired degree, for historical information in addition to the newly received information. A resultant updated list of home agents and their corresponding preference values can then be transmitted 63 to the home agents as before.
[0035] The above-described processes can be realized in various ways depending upon the resources and needs of a given application. With reference to FIG. 7 , one illustrative approach comprises a home agent preference control node 70 having a network interface 71 that facilitates operable coupling to a network 72 (such as an intranet or an extranet such as the Internet) and a corresponding plurality of home agents 73 . Home agent availability information and other home agent information as received from the home agents 73 by an optional receiver 74 that operably couples to the network interface 71 (or as is partially or wholly obtained from other sources) is retained in a memory 75 . (Those skilled in the art will recognize that such a memory 75 can comprise a single stand-alone platform as suggested by the illustration, a multiplicity of platforms, or can be integrated with one or more of the other illustrated components. Such architectural and configuration options are well understood in the art and require no further elaboration here.) This stored information can comprise only current information or can include historical data if desired (to facilitate, for example, use of such historical information when re-determining preference values and/or system audits).
[0036] The memory 75 in turn operably couples to a home agent preference calculator 76 . The home agent preference calculator 76 can comprise a stand-alone dedicated-purpose platform but will likely more often be integrated with a multi-function fully or partially programmable element component. This home agent preference calculator serves to determine a preference value for each of the plurality of home agents 73 as a function, at least in part, of the home agent availability information and the other home agent information. In a preferred embodiment the home agent preference calculator 76 effects such a calculation on a substantially frequent basis (using, preferably, updated information) to permit availability of relatively fresh preference value information for use by the system.
[0037] The home agent preference calculator 76 operably couples to a transmitter 77 and serves to provide the above-described list of available home agents and their corresponding calculated preference values. The transmitter 77 is responsive to receipt of such information and/or to other control inputs and transmits, via the network interface 71 , this list to the home agents 73 .
[0038] The home agent preference control node can be configured as a stand-alone platform, but can also be integrated as a part of other network elements if desired. For examples, a home agent platform or a RADIUS server can each be readily configured to comport with these teachings and serve as an effective home agent preference control node.
[0039] Referring now to FIG. 8 , a given home agent can be arranged and configured in various ways to meaningfully participate in such processes as are described above. Pursuant to one approach 80 , the home agent optionally receives 81 a message comprising a request for home agent information from a home agent preference control node. In such a case, the home agent can transmit 82 a corresponding response that contains the expressly or impliedly requested home agent information. In any event, upon receiving 83 a message comprising a list of available home agents in the network, which list includes the home agent and which list provides a preference value for each of the available home agents including this particular home agent, the home agent can use that list by providing 84 it (or at least relevant portions thereof) to mobiles nodes to thereby facilitate selection of a particular home agent by a given mobile node.
[0040] An overall illustration of an application of these teachings appears in FIG. 9 . A home agent preference control node receives, in this illustrative example, router advertisements 90 A and 90 B from the various home agents in the network. Such router advertisements contain home agent availability information as corresponds to each of the home agents. In this illustration, the home agent preference control node transmits a request for other information 91 to the home agents and receives, in response, the other information in corresponding messages 92 A and 92 B. The home agent preference control node then uses this availability information and other information to calculate 93 the preference values described above for the various home agents. The resultant information is then transmitted to the home agents as a home agent list with corresponding preference values 94 . So configured, when a mobile node then transmits a home agent discovery request 95 , a particular one of the home agents can respond with a home agent discovery reply message 96 that includes the list described herein.
[0041] So configured, the existing preference value mechanism for Internet Protocol version 6 can be significantly leveraged to effect a more dynamic and accurate indication of present network home agent resources. This, in turn, can result in an improved average quality of service experience for an increased number of users.
[0042] Those skilled in the art will recognize that a wide variety of modifications, alterations, and combinations can be made with respect to the above described embodiments without departing from the spirit and scope of the invention, and that such modifications, alterations, and combinations are to be viewed as being within the ambit of the inventive concept. For example, upon receiving an updated list as described above, a given home agent may optionally immediately source a router advertisement containing its own new preference value. As another example, when the home agent preference control node fails to receive an update (for X number of opportunities) for a home agent that has previously participated in this process, the home agent preference control node can optionally lower the preference value for that home agent and/or can remove that home agent from the list pending some change in circumstance. | A home agent preference control node gathers information regarding available home agents in a given network. This information includes both information regarding present availability and other information (for example, other information as may pertain the relative availability of one home agent with respect to another). The home agent preference control node utilizes such information to determine a respective preference value for at least some, and preferably all of the network's home agents. Following communication of a resultant list that comprises, at least in part, such preference values, the home agents are then able to respond to home agent discovery inquiries from a mobile node with this information. This, in turn, facilitates selection by the mobile node of a home agent that likely represents at least a relatively efficient distribution of system resources. | 7 |
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is an improvement upon and incorporates by reference in its entirety, as if set forth in full, U.S. patent application Ser. No. 12/462,378, filed on Aug. 3, 2009 (“the '378 Application”).
BACKGROUND
[0002] 1. Field
[0003] Embodiments described herein relate to sense through the wall radar systems and in particular to systems for mitigating interference in sense through the wall radar.
[0004] 2. Description of Related Art
[0005] Radar systems capable of sensing personnel through opaque barriers are of use to the military and to law enforcement. In a typical application, a radar unit may be deployed outside a building, and it may illuminate personnel, or targets, inside the building, with radio-frequency (RF) electromagnetic waves capable of penetrating the wall of the building. Reflections from the targets then return to the radar unit, passing through the wall again on their return, and are detected by the radar unit. The presence of human targets may then be inferred by a processing unit in the radar unit, and their locations may be communicated to the radar operator through an operator interface, which may include a graphical display.
[0006] Reliably identifying targets inside the building may be challenging because of multipath interference. For example, some of the radar radiation may reflect off of the wall, reflect from a target outside the building, and then reflect from the wall again, returning to the radar unit. This reflection from a target outside the building may be mistaken by the radar unit for, and incorrectly displayed to the radar operator as, a target inside the building. The problem of multipath may be exacerbated in sense through the wall applications by the attenuation caused by a wall, as a result of which the signal returning from a desired target inside the building may be weak compared to the signal returning from an undesired target outside the building.
[0007] Some undesired targets, both inside and outside the building, may be eliminated by suppressing stationary targets, using for example signal processing steps described in the '378 Application. Signals reflected from personnel inside the building may survive this suppression method even if the targets are intentionally standing still, because even a person attempting to stand perfectly still will move slightly as a result of heartbeat, breathing, and involuntary postural sway. Because these techniques suppress signals from stationary targets, they may not suppress multipath interference from undesired moving targets, such as personnel and wind-blown foliage outside the building.
[0008] A prior art approach to mitigating multipath interference involves equipping the radar unit with a rear-facing low gain receiving “guard” antenna. This antenna is more sensitive to reflections from undesired targets behind the radar than the main antenna, which is aimed into the building. Reflections detected by the main channel receiver which are also detected in the guard channel are then suppressed by the processing unit, so that they are not displayed to the radar operator. Although this approach helps to reduce the errors caused by multipath, its performance may be inadequate because reflections from inside the building may also reach the guard antenna, through a side lobe of this antenna or after reflection from the operator, resulting in the incorrect rejection by the processing unit of targets inside the building.
[0009] There is a need, then, for a system capable of reliably identifying multipath signals in sense through the wall radar systems.
SUMMARY
[0010] Embodiments of the present invention provide a system and method for sense through the wall radar including mitigation of multipath interference. A main channel of a radar system is operated at a frequency capable of penetrating an opaque barrier such as the wall of a building to sense targets therein. The main channel performance may be impaired by multipath interference, i.e., radar returns resulting from the illumination of targets outside the building by radar radiation reflected from the wall. A guard channel of the radar, operating at a higher frequency which does not penetrate the wall, is used to identify targets outside the building and suppress the multipath interference they produce in the main channel.
[0011] In one embodiment, the system includes a main channel configured to be sensitive to targets both on the near side and the far side of a barrier, a guard channel configured to be sensitive to targets on the near side of the barrier, the guard channel operating at a higher frequency than the main channel, and a processing unit for combining signals from the main channel and signals from the guard channel, the processing unit configured to suppress targets detected by both the main channel and the guard channel.
[0012] In one embodiment, the processing unit includes a main channel beam former for combining the signals from the main channel receiving antenna elements into a multiplicity of main channel receive beams, and a guard channel beam former for combining the signals from the guard channel receiving antenna elements into a multiplicity of corresponding guard channel receive beams, and the processing unit combines the signal from a main channel receive beam with the signal from the corresponding guard channel receive beam to suppress, in the main channel receive beam signal, targets detected by both the main channel and the guard channel.
[0013] In one embodiment, the main channel comprises a main channel transmitting aperture and a main channel receiving aperture, the guard channel comprises a guard channel transmitting aperture and a guard channel receiving aperture, the antenna pattern of the guard channel transmitting aperture is substantially the same as the antenna pattern of the main channel transmitting aperture, and the antenna pattern of the guard channel receiving aperture is substantially the same as the antenna pattern of the main channel receiving aperture.
[0014] In one embodiment, a method for mitigating multipath interference in radar for sensing targets through a wall includes operating a main channel at a first frequency to illuminate, and receive reflections from, targets on both sides of the wall, operating a guard channel at a second frequency higher than the first frequency, to illuminate, and receive reflections from, targets on the near side of the wall, processing the main channel reflections with two fast Fourier transforms to generate a main channel range-Doppler map, truncating the main channel range-Doppler map to form a truncated main channel range-Doppler map, processing the guard channel reflections with two fast Fourier transforms to generate a guard channel range-Doppler map, decimating the guard channel range-Doppler map to form a decimated guard channel range-Doppler map, cross-correlating the truncated main channel range-Doppler map and the decimated guard channel range-Doppler map, and suppressing, in the main channel, targets corresponding to signals in the cross-correlation exceeding a threshold.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Features, aspects, and embodiments are described in conjunction with the attached drawings, in which:
[0016] FIG. 1 is a perspective cutaway view of a setting involving the use of a sense through the wall radar outside a building;
[0017] FIG. 2 is a block diagram of a radar unit according to an embodiment of the present invention;
[0018] FIG. 3 is a data flow diagram showing signal processing steps used in an embodiment of the present invention to suppress undesired targets; and
[0019] FIG. 4 is a flow chart of a method for mitigating multipath interference according to an embodiment of the present invention.
DETAILED DESCRIPTION
[0020] The detailed description set forth below in connection with the appended drawings is intended as a description of the presently preferred embodiments of a high frequency guard channel for interference mitigation in a sense through the wall radar provided in accordance with the present invention and is not intended to represent the only forms in which the present invention may be constructed or utilized. The description sets forth the features of the present invention in connection with the illustrated embodiments. It is to be understood, however, that the same or equivalent functions and structures may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the invention. As denoted elsewhere herein, like element numbers are intended to indicate like elements or features. The terms “radio frequency” and “RF” are used herein, for brevity, to include a frequency range spanning from approximately 500 megahertz (MHz) to 100 gigahertz (GHz). The term “processing unit” is used herein to include any combination of hardware, firmware, and software, employed to process data or digital signals. Processing unit hardware may include, for example, application specific integrated circuits (ASICs), general purpose or special purpose central processing units (CPUs), digital signal processors (DSPs), graphics processing units (GPUs), and programmable logic devices such as field programmable gate arrays (FPGAs).
[0021] Referring to FIG. 1 , in one embodiment a sense through the wall radar unit 12 including an interference mitigation system has two channels, a main channel and a guard channel, operating at a lower and higher frequency respectively. Main channel RF radiation 11 travels along a direct propagation path 14 and illuminates a desired target 16 inside a building 22 , reflects from the target 16 and travels back to the radar unit 12 along the direct path 14 . Radiation from the main channel also travels along one or more indirect propagation paths 18 and illuminates undesired targets 20 outside the building; the radiation reflected from these undesired targets 20 returns to the radar unit 12 along the indirect paths 18 causing multipath interference. The guard channel emits radiation 13 at a higher frequency, with substantially the same radiation pattern as that of the main channel. The guard channel radiation 13 is, because of its higher frequency, substantially incapable of penetrating the wall 24 of the building 22 , so that the guard channel senses only undesired targets 20 outside the building, via indirect paths 18 . A processing unit in the radar unit 12 may then suppress targets sensed by the main channel that correspond to targets also sensed by the guard channel, and display only the desired target 16 to the operator 26 .
[0022] The main channel frequency may preferably be sufficiently low to provide adequate transmission through typical walls, while also having a wavelength short enough to provide acceptable angle accuracy, and to provide acceptable antenna gain without requiring a very large aperture. In an exemplary embodiment, the main channel may operate at an S-band frequency of approximately 3 gigahertz (GHz). The guard channel frequency is then chosen to be higher than the main channel frequency, and sufficiently high that the guard channel is attenuated significantly more than the main channel when passing through an exemplary wall. In one embodiment, an X band frequency of 9 GHz may be used for the guard channel. A wall of concrete 15 centimeters (cm) thick, for example, will attenuate 9 GHz radiation approximately 60 dB more than it attenuates 3 GHz radiation. Reflections from targets on the far side of this wall, which pass through the wall twice, will be 120 dB more attenuated in the guard channel than in the main channel; as a result the guard channel is essentially insensitive to targets on the far side of the wall.
[0023] The main channel and guard channel may have a single aperture each, used for both transmitting and receiving. In this case the antenna pattern of the guard channel, also known as the radiation pattern of the guard channel antenna, is preferably the same as that of the main channel. It is not necessary that they be precisely identical, but if, for example, the guard channel antenna pattern has a null in a direction in which the main channel does not have a null, then multipath interference caused by radiation received from that direction in the main channel may not be suppressed. Further, it is desirable that if the main channel antenna has a lobe in a particular direction, and is particularly sensitive in that direction, the guard channel also have a lobe, and high sensitivity, in that direction. Generally the antenna patterns may be made similar by using similar radiators, with dimensions scaled in proportion to the wavelength of the channel. For example, if the guard channel frequency is three times the main channel frequency, then guard channel radiators that resemble the main channel radiators, scaled down by a factor of three in their linear dimensions, will produce a similar antenna pattern.
[0024] Referring to FIG. 2 , the transmitting and receiving antennas may be separate, for the main channel or the guard channel, or both. For example, the main channel transmitting antenna 52 may be a single low-gain element and the main channel receiving antenna 50 may be an array of elements, suitable for operation as a phased array. In the more general case in which the main channel transmitted pattern differs from the main channel received pattern, it is desirable that the product of the received and transmitted patterns in the guard channel be similar to the corresponding prOduct in the main channel. This may be accomplished by matching the patterns of both the transmitting antennas and the receiving antennas. For example, a scaled-down copy of the main channel transmitting antenna 52 may be used as the guard channel transmitting antenna 62 , and a scaled-down copy of the main channel receiving antenna 50 may be used as the guard channel receiving antenna 60 , where in each case the scaling factor is the ratio of the corresponding wavelengths.
[0025] As described in the '378 Application, the main channel transmitting antenna 52 may be driven by a main channel waveform generator 56 . The guard channel transmitting antenna 62 may be driven by a guard channel waveform generator 66 . The RF analog signals from elements of the main channel receiving antenna 50 may initially be processed by a main channel multi-channel homodyne receiver 54 , constructed for example as described in, and illustrated in FIG. 5 of, the '378 Application, with the exception that in the present invention the guard antenna channel may be omitted from the main channel receiver.
[0026] The output of the main channel multi-channel homodyne receiver 54 may include several digital data streams, each corresponding to one of the receiving antenna elements. In the guard channel, the RF analog signals from the elements of the guard channel receiving antenna 60 may initially be processed by a similar guard channel multichannel homodyne receiver 64 , operating at the guard channel frequency, and generating a digital data stream from each of the guard channel receiving antenna elements. These data streams may be processed by the processing unit 70 and the results communicated to the operator 26 ( FIG. 1 ) through the operator interface 72 .
[0027] Referring to FIG. 3 , in an exemplary embodiment data streams from main channel and the guard channel receivers are initially processed in parallel paths, in steps 1 M through 5 M and 33 , and in steps 1 G through 5 G, 37 , and 39 , before being combined in steps 41 , 43 , and 30 , to mitigate the effects of multichannel interference in the main channel. In the main channel, signal processing for each of the data streams may include an in-phase and quadrature phase (I/Q) detection step 1 M. This may be followed by a channel equalization step illustrated and described in the '378 Application, omitted from FIG. 3 . Next, in a beam former step 2 M, linear combinations of the data streams may be formed, to operate the receive antenna as a phased array receiving simultaneously in multiple beam directions, so that each output stream from the beam former step 2 M is the signal received through a different receive beam of the antenna.
[0028] Next the signal corresponding to each receive beam may be processed with a range compression fast Fourier transform (FFT) 3M, and a Doppler compression FFT 4M to generate a two-dimensional array of complex numbers known as a range-Doppler map. Each cell in this array is identified by a range index and a Doppler index, and the cell value indicates the amplitude of the radar reflections at or near the corresponding range and Doppler frequency values.
[0029] Next, in a low-Doppler clutter removal step 5 M, the central Doppler bin, corresponding to zero Doppler frequency, or the central few Doppler bins, may be excised from the array. The first processing steps 1 G through 5 G in the guard channel may be the same as the corresponding steps 1 M through 5 M in the main channel.
[0030] Because the Doppler frequency is proportional to the carrier frequency, targets with the same range velocity may occur in different Doppler bins of the range-Doppler maps for the main channel and the guard channel which use different radar carrier frequencies. To facilitate the comparison of the range-Doppler maps from the main and guard channels, the guard channel range-Doppler map may be scaled in frequency, and decimated, or under-sampled, in a frequency scaling and decimation step 37 , and the main channel range-Doppler map may be truncated, in a truncation step 33 .
[0031] For example, with 64-point FFTs and a 1.56 Hz Doppler resolution on the main and the guard channel, a target moving with a range velocity of 60 cm per second may fall into Doppler bin 56 in the guard channel, i.e., 24 bins away from bin 32 , which can be defined as the zero-velocity Doppler. If the main channel carrier frequency is one-third the guard channel carrier frequency, then in the main channel the same target will fall into Doppler bin 40 . In this example, with normalized Doppler resolution between the guard and main channels, there will be Doppler bins in the main channel (bins 1 through 21 and bins 43 through 64 in this example) that do not have unambiguous corresponding Doppler bins in the guard channel due to Doppler frequency scaling versus carrier frequency. These extra Doppler bins in the main channel may be discarded for purposes of interference detection processing. To account for the Doppler scaling, the 64 guard channel Doppler bins are decimated by 3 to create a decimated 21 bin guard channel range-Doppler array. Bin 62 of the guard channel range-Doppler map, being 30 bins from the zero-velocity Doppler bin, corresponds in this example to bin 42 of the main channel range-Doppler map, which is 10 bins from the zero-velocity bin. Both the decimated guard channel range-Doppler map and the truncated main channel range-Doppler map are, in this example, 21×64 arrays, having 21 Doppler bins and 64 range bins. The target velocity per bin in the decimated guard channel range Doppler map directly corresponds to the target velocities in the truncated 21 bin main channel range-Doppler array. As can be seen from this example, the processes of decimating and truncating are simpler if the guard channel frequency is an integer multiple of the main channel frequency.
[0032] Next, cells in the decimated guard channel range-Doppler map with amplitudes below a fixed threshold are discarded in a threshold application step 39 . This may be done by setting the corresponding cell values to zero, or by deleting the corresponding index values from a valid-cells list. The threshold may be set to be slightly higher than the amplitude expected due to system noise, i.e., the amplitude expected in the absence of reflections from a target.
[0033] A cross-correlation step 41 may follow the step of applying a threshold 39 . In this step each range bin in the decimated guard channel range-Doppler map is cross-correlated (with zero frequency shift) with the same range bin in the truncated main channel range-Doppler map, to arrive at a correlation coefficient for that range bin. The correlation coefficient r may be calculated for a particular range bin according to the following equation:
[0000]
r
=
∑
i
[
(
x
i
-
x
_
)
(
y
i
-
y
_
)
]
∑
i
(
x
i
-
x
_
)
2
∑
i
(
y
i
-
y
_
)
2
[0034] where the x i are the magnitudes of the cell values of the range bin in the main channel, the y i are the magnitudes of the cell values in the range bin in the guard channel, and x and y are the means of the magnitudes of the cell values in the range bin in the main channel and guard channel respectively. Here, the magnitude of a complex value is the square root of the sum of the squares of the real and imaginary parts of that complex value. The output of the cross-correlation step 41 is a measure of the extent to which reflections from a particular target appear in both the main channel and the guard channel.
[0035] The correlation coefficients generated by the cross-correlation step 41 may then be processed by a threshold application step 43 . The output of this step 43 is the set of correlation coefficients which exceed a predetermined threshold, and which therefore represent targets sensed by both the main channel and guard channel, i.e., targets on the near side of the wall. This list of target-ranges is supplied to the target and interference detection processing step 30 , in which it may be used to suppress targets that otherwise would be displayed to the operator 26 as representing humans inside the building. The target and interference processing step 30 may be implemented in one embodiment in the manner of step 650 in the '378 Application. The suppression of undesired targets may be accomplished, for example, by suppressing detections occurring in the range bins where interference has been identified.
[0036] In an alternate embodiment in which the cross-correlation step 41 is omitted, the output of the threshold application step 39 , which contains target detections in the guard channel, corresponding to targets on the near side of the wall, may be fed directly to the target and interference detection processing step 30 , where it may be used to suppress the corresponding main channel targets. The process of identifying and suppressing undesired targets may be performed independently in each main channel receive beam using the corresponding guard channel receive beam.
[0037] Referring to FIG. 4 , in exemplary embodiment a method for mitigating multipath interference may comprise seven principal steps. With respect to the main channel, in step 80 the main channel is operated to obtain main channel reflection data. In step 82 , fast Fourier transforms are performed on the main channel reflection data to generate a main channel range-Doppler map. In step 84 , the main channel range-Doppler map is truncated to form a truncated main channel range-Doppler map. With respect to the guard channel, in step 90 the guard channel is operated to obtain guard channel reflection data. In step 92 , fast Fourier transforms are performed on the guard channel reflection data to generate a guard channel range-Doppler map. In step 94 , the guard channel range-Doppler map is decimated to form a decimated guard channel range-Doppler map. In step 100 the truncated main channel range-Doppler map is cross-correlated with the decimated guard channel range-Doppler map, and in step 102 , any targets in the main channel for which the corresponding cross-correlation exceeds a predetermined threshold are suppressed.
[0038] Accordingly, it is to be understood that the interference mitigation system constructed according to principles of this invention may be embodied other than as specifically described herein. For example, although the invention has been described in the context of detecting humans inside a building from the outside, it may also be used to detect humans outside a building from the inside, or to detect humans on the other side of a wall or other barrier which is not part of a building. Where in the examples the guard band frequency is triple the main channel frequency it may be a different integer multiple of the main channel frequency, or it may exceed the main channel frequency by a factor that is not an integer. Features disclosed in the '378 Application may be combined with features of the present invention; for example, averaging of the input signals may be used to improve the signal to noise ratio, and motion compensation may be incorporated into the main channel or guard channel or both. The invention is also defined in the following claims. | This invention relates to sense through the wall radar. A main channel of a radar system ( 12 ) is operated at a frequency capable of penetrating opaque barriers such as the wall ( 24 ) of a building ( 22 ) to sense targets ( 16 ) therein. The main channel performance may be impaired by multipath interference, i.e., radar returns resulting from targets ( 20 ) outside the building ( 22 ) illuminated by reflection from the wall ( 24 ). A guard channel of the radar, operating at a higher frequency which does not penetrate the wall ( 24 ), is used to identify targets ( 20 ) outside the building ( 22 ) and suppress the multipath interference they produce in the main channel. | 6 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] Not Applicable
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
BACKGROUND OF THE INVENTION
[0003] This invention relates to pet enclosures and environments, and, in particular, to a pet environment that can serve multiple functions.
[0004] Enclosures and environments for dogs and other animals have long been used. Typical enclosures and environments include beds, cages, boxes, or fences, in which dogs may sleep, socialize with other animals, retreat from family activity, or be contained, for example, overnight, or when the owner is out of the house. However, such enclosures, although adequate for their intended purposes, still have drawbacks.
[0005] For example, a simple corrugated or wooden box may be used to contain a new puppy within the home. However, the box may readily become soiled and begin to emit offensive odors until the puppy becomes fully housebroken and/or the box is disposed of. If the puppy is teething, it will likely chew on, and damage or destroy, the box.
[0006] Furthermore, unless the box allows the puppy to readily see human and animal activity outside of the box, the box will inhibit the socialization process that is important to the development of a good family pet.
[0007] A metal cage somewhat reduces the problems associated with toileting, socialization, and teething, but it inhibits quick and easy access of the puppy for housebreaking and nurturing by both the mother dog and its human owners. It is also generally the most expensive type of pet environment.
[0008] A metal cage, along with corrugated and wooden boxes, is also not very compatible with typical home interior decor.
[0009] Boxes may inhibit a mother dog's view of, and access to, her puppies. If a mother dog should feel that her puppies need her, or she wants to feed (i.e., nurse) them, the mother dog may not have a sufficient view of the puppies to know where they are in the box, and can inadvertently injure them when she steps (or jumps) into the box to be with the puppies.
[0010] When a mother dog nurses her puppies, she most often lays down with her back against the wall of the whelping box. Sometimes, a puppy can be behind the mother, and the mother will lean against the puppy, possibly resulting in the suffocation of that puppy. In a standard wooden whelping box, a small wooden rail is often mounted to the inner surface of the walls. The rail assures that there is a space between the mother's body and the wall of the box. It also discourages the mother from leaning against the wall, since doing so would be uncomfortable. Thus, a clear breathing space for puppies will always be available between the mother's body and the wall of the whelping box to reduce the possibility of a puppy being caught between the mother dog and the wall of the whelping box. However, these rails are permanent and the box is primarily used for the single purpose of whelping.
[0011] Currently, there are many enclosures and environments that are available for pets. However, the respective enclosures are single use enclosures and environments; they serve only as a bed, for containment, a whelping box, or a personal space, for example. We know of no pet enclosures which are capable of serving all these functions at various times. Additionally, many of the currently existing pet enclosures are not easily cleaned; are not easily transportable; and often, do not complement the decor of the room or house in which they are placed.
BRIEF SUMMARY OF THE INVENTION
[0012] Briefly stated, an animal enclosure is provided which can be used for a plurality of purposes. The animal enclosure first of all includes a pen sized to hold the animal (i.e., dog). The pen comprises two side walls, a rear wall, a front wall, and a gate. The gate can be made of a single movable panel, or a plurality of removable panel slats or frames. In the first instance, the single panel is vertically movable in a channel between a raised position in which the gate is closed and a lowered position in which the gate is opened. A fastener is provided to secure the gate panel in a desired location. In the second instance, the gateway includes a channel which receives the panel slats. The slats are added, one on top of the other, until a desired height is reached. The slats can be solid or formed from wire (and opened). Whether the gate is made from a single panel or a plurality of slats, the gate panel can be provided with a top edge guard extending across at least a majority of the top of the panel to provide a smooth, unchewable surface across the top of the gate.
[0013] The enclosure walls are formed by framing (i.e., tubing) and the individual walls are hingedly connected together, such that the frame can be moved between a folded and an opened position. A corner lock is provided to maintain the enclosure in the opened position. The hinges can comprise eye bolts having a head which receives a vertical member of one wall and a shaft which extends through the vertical member of an adjacent wall. Alternatively, the hinges can comprise extruded lengths defining a pair of connected cylinders open along the length of the walls of the cylinders to snappingly receive the tubing of the frame. The corner lock comprises a corner brace which extends between adjacent walls, and is removable from at least one of the walls to which it is attachable to allow for folding of the enclosure.
[0014] A removable, washable pen cover is provided to cover the frame of the pen. The pen cover includes downwardly facing pockets along upper edges thereof which are sized to fit over the frame members. The pen cover has, for example, ties, snaps, or Velcro® fasteners, at the bottom of the cover walls to secure the cover to the frame bottom member.
[0015] An optional top is provided for the pen to give the pen a den-like feeling. The top is removably mountable to the pen. The top is made from a frame having a back edge, a front edge, and side edges. The frame is covered with a removable, washable top cover. The top is hingedly connected to the enclosure at the top back edge using a pair of spaced apart eye bolts as hinges. The eyebolt shafts are received in holes in the pen frame. The eyebolt shafts are not fastened to the pen frame so that the top can be removed very quickly if necessary. Alternatively, the top can be snappingly connected to the frame using the extrusion noted above. A pair of pivotal support arms are spaced rearwardly of the front edge of the top and have free ends which engage the top of the pen to support the front of the top above the pen frame. Preferably, the pen is provided with a plurality of openings into which the top support arms extend to enable the top to be positioned at a desired degree. The top is also provided with side flaps which hang from the top to a point below the top edge of the pen side walls. Because the top is hinged at its back, and elevated at its front, it forms a type of lean-to.
[0016] The enclosure can also be provided with a whelping rail which is removably received in the pen. The whelping rail comprises a frame having a bar member and legs extending diagonally downwardly and outwardly from the bar. The legs support the bar above a bottom of the pen and inwardly from the pen walls.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0017] [0017]FIG. 1 is a perspective view of a dog enclosure of the present invention, showing the pen with its associated removable top and removable whelping rail;
[0018] [0018]FIG. 2 is a front elevational view of the pen with the top;
[0019] [0019]FIG. 3 is a side elevational view of the pen and top, the top being shown in two alternate (lower) positions in phantom;
[0020] [0020]FIG. 4 is a top plan view of the pen and top;
[0021] [0021]FIG. 5 is a perspective view of the pen of the dog enclosure, showing the gate in a partially lowered position to allow a mother dog to enter and exit the pen, yet prevent puppies from exiting the pen, and including a removable whelping rail;
[0022] [0022]FIG. 6 is a view similar to FIG. 5, but showing the gate completely lowered and with the floor of the covering partially cut away to show the operation of the gate;
[0023] [0023]FIG. 7 is a front elevational view of a frame for the pen;
[0024] [0024]FIG. 8 is an enlarged fragmentary view showing the connection of two walls of the frame;
[0025] [0025]FIG. 9 is a perspective view of a cloth cover which covers the frame;
[0026] [0026]FIG. 10 is a fragmentary top plan view of the frame showing the gate assembly for the pen using a flexible single panel for the gate;
[0027] [0027]FIG. 11 is a cross-sectional view of the gate assembly taken along line 11 - 11 of FIG. 10;
[0028] [0028]FIG. 12 is a horizontal fragmentary cross-sectional view of the gate assembly taken along line 12 - 12 of FIG. 11;
[0029] [0029]FIG. 13 is a front elevational view of the gate assembly using slats or frames, rather than a single panel, as the gate;
[0030] [0030]FIG. 14 is a partially exploded end view of an alternative slat for use with the gate of FIG. 13;
[0031] [0031]FIG. 15 is a perspective view of a removable whelping rail accessory for the pen;
[0032] [0032]FIG. 16 is a perspective view of the pen of the enclosure in a folded state; and
[0033] [0033]FIG. 17 is a cross-sectional view of an alternative hinge mechanism for joining together frame members of the pen.
[0034] Corresponding reference numerals will be used throughout the several figures of the drawings.
DETAILED DESCRIPTION OF THE INVENTION
[0035] The following detailed description illustrates the invention by way of example and not by way of limitation. This description will clearly enable one skilled in the art to make and use the invention, and describes what we presently believe is the best mode of carrying out the invention.
[0036] A pet enclosure 1 of the present invention is shown generally in FIG. 1. Although described for use with a dog, the pet enclosure can also be used with cats and other pets. The enclosures 1 includes a pen 3 made from a tubular frame 5 (FIG. 7). A washable soft cover 7 covers the frame 5 and can easily be removed for cleaning. The cover 7 is preferably a cloth cover. The removability of the cover 7 also allows for the cover to be easily changed, for example, between washings or to change the color or pattern of the cover. Hence the cover can be changed to match the decor of the room in which the pen is placed. The pen 3 includes a gate 9 which can be moved between a raised position and a lowered position. In the lowered position, the dog can easily enter and exit the pen 3 . When the gate is raised, dogs (and especially puppies) are prevented from exiting the pen 3 . As will be described below, the gate 9 can be raised or lowered to be at a desired height. That is, the gate can be placed in a fully raised position, a fully lowered position or at a desired position between the fully raised and fully lowered positions. Thus, the gate can be lowered to a desired height which will prevent puppies from exiting the pen, but will allow a mother dog to enter and exit the pen. It is anticipated that the gate will generally be kept in a position, which will allow the mother to freely enter and exit the pen, and yet still contain the puppies in the pen. The adjustability of the gate allows the gate to be raised as the puppies grow to contain the puppies in the pen, yet still allow the mother dog to readily see and gain access to her puppies. The pen 3 is preferably a low-profile pen, having a height approximately equal to the shoulder height of an adult dog of various breeds. To avoid the need to make numerous different sizes of pens, the pen is provided in small, medium, and large sizes. The pet enclosure 1 can optionally be provided with a cover or top 11 and a whelping rail 13 (FIG. 15).
[0037] The features of the soft wall, gated pen with the optional cover and whelping rail allow the pet enclosure to be used throughout the several stages of a pet's life. Thus, by adding (or removing) the top 11 and whelping rail 13 , the pen can be adapted for use not only when the dog is a puppy and full grown dog, but can be used as a birthing place for pregnant females, as well as a place where the mother dog can safely nurse, clean and nurture her puppies.
[0038] When dogs are puppies, the puppies can be placed in the pen to keep them from getting underfoot and possibly injured when there is human activity, and especially when children are around. When the gate is raised, the puppies will not be able to exit the pen. The height of the gate can be varied for the breed of the dog contained in the pen, and can be varied as the puppies grow larger. Thus, the gate can be adjusted to a height that safely contains the puppies, yet permits them to see outside the pen as the puppies grow. Thus, the puppies can enjoy the mental stimulation of seeing human activity going on about them, thereby helping in the socialization process. Additionally, the moderate height of the walls of the pen permit humans to readily interact with puppies while they are in the pen, again, helping with the puppies' socialization process.
[0039] The pen can also serve as a place where the puppies'chewing toys are kept. When the puppies are still young and confined to the pen, the pen will prevent the puppies from chewing on furniture and other household items. However, once the puppies are older and begin to be allowed out of the pen, with the chewing toys readily accessible to the puppies, they have already begun to be conditioned to accept chewing on the toys, rather than on household items, such as rugs and furniture, for example.
[0040] As a contained environment, the pen can be provided with a disposable floor surface or liner during the house breaking process to protect the cover 7 from being soiled. Should a puppy soil the disposable floor surface, it can be quickly and easily removed and thrown away. The disposable floor surface or liner can be as simple as newspapers that are placed on the pen floor. Alternatively, a replaceable liner can be used which has a fluid impervious bottom surface, which is placed against the pen floor, and an absorptive upper surface. Such a liner would protect the pen floor. As another alternative, a removable floor liner can be placed in the bottom of the pen 3 . The use of the disposable and/or replaceable liners will protect the cover 7 so that the cover 7 will not have to be washed as often during the housebreaking process. If the cover 7 itself does becomes soiled, it can be removed and replaced with a clean cover 7 while the soiled cover is being washed.
[0041] Once a puppy has matured, the pen 3 can be fitted with a dog bed, transforming the pen into the dog's own personal environment within the home. The dog bed can be any commercially available dog bed that will fit in the pen 3 . The pen thus becomes a place where the dog can retire to sleep or to retreat from human activity. Additionally, the dog's toys can be kept in the pen, and the dog will know that it can get its toys from the pen when desired. Because the pen is easily folded, and transportable the pen 3 can be moved about the house or taken outdoors. Additionally, the pen can be taken along on family vacations, and set up in a hotel room, vacation home, etc., giving the pet the comfort of a familiar place when taken on vacation.
[0042] For pregnant female dogs, having a known and secure environment is particularly important. As the birthing time approaches, the mother dog may spend more and more time in the pen in anticipation of the birth. Additionally, pregnant dogs tend to prefer darker more confined environments (i.e., den-like environments) when giving birth. To accommodate this, the accessory top cover 11 can be placed on the pen. The top or cover 11 can easily be applied to the pen 3 and set to any one of several desired positions, all of which permit visual access to the pregnant dog by her owners. As discussed below, the cover 11 can be quickly and easily removed from the pen 3 should it be determined that either the birthing mother or one of her puppies is in distress and intervention is needed.
[0043] In anticipation of the birth, the pen 3 can be lined with clean paper, or other disposable linings. The pen can also be fitted with the whelping rail 13 . The rail 13 effectively prevents accidental smothering of a newborn puppy that may become trapped between its mother's body and the wall of the pen. Because the pen is soft-sided, the possibility of this occurring is further reduced.
[0044] Once the puppies are born, the pen provides a safe environment for the puppies. The gate can be positioned to allow for easy entry and exit for the mother, while preventing the puppies from exiting the pen. The gate is preferably lowered to a height that will allow the mother dog to step over the gate without scratching her sensitive underside, and yet sufficiently high to prevent the puppies from exiting the pen. However, the top edge of the gate is smooth, to reduce the possibility of abrading the new mothers sensitive underside as she crosses over the gate. Additionally, the top edge of the gate is made of a hard material that substantially precludes damage to the gate when the puppies chew on it. Further, the walls of the pen 3 are sized such that the mother can look into the pen from outside the pen and see her puppies.
[0045] In a preferred embodiment, the frame 5 (FIGS. 7 and 8) is preferably a tubular frame made from a series of top and bottom horizontal members 21 a,b and vertical side members 23 . The frame members are preferably metal tubes, but could be made from extruded or molded plastic tubes. The members 21 a,b and 23 are assembled together to form four walls: two side walls, a back wall, and a front wall. A gap is formed in the front wall to accept the gate assembly 9 . The horizontal members 21 a,b are preferably straight hollow tubes. The vertical members, on the other hand, have a vertical portion 23 a and top and bottom horizontal portions 23 b . The vertical members are unitary, one-piece tubular members, and are bent to transition between their vertical and horizontal portions. The tubes of the vertical members are swaged (or otherwise reduced in diameter) at the ends of the top and bottom portion to define noses 25 which are frictionally received in the respective ends of the horizontal members. This construction of the frame members lends itself to allow for a small size in shipping and storing of the pens, and more readily accommodates desired changes to the length and width of the pen. To hold the frame members together, bolts 26 extend through the horizontal frame members 21 a and the nose section 25 of the vertical frame members 23 . Nuts 28 are provided to hold the bolts 26 in place. If desired, pins, bolts, ball and detent, or other conventional means can be used to secure the vertical and horizontal members together to form the walls of the frame 7 .
[0046] The connection of the frame walls (i.e., the side walls to the front and back walls) is accomplished using eyebolts 27 and corner braces 44 , as seen in FIGS. 7 and 8. The eyebolts 27 each have a circular head 29 through which the vertical member 23 of one wall extends, and a shaft 31 which extends through an opening in the neighboring vertical member. The end of the shaft 31 is preferably threaded, and a lock nut 33 is applied to the end of the shaft to prevent the shaft from exiting the member through which it extends. Preferably, two eyebolts 27 are used at each corner of the pen, in a vertically spaced apart relationship. As can be appreciated, the eyebolts act as hinges, and allow the walls of the pen 3 to pivot about the corners of the pen. Thus, the pen can be moved between a opened position, as shown in FIGS. 1 - 6 , and a folded position, as seen in FIG. 16. Because the frame 5 is made from lightweight tubing, the frame is light, and when folded, is quite compact. Thus, the folded frame, with its fabric cover, can be easily moved from one location to another. For example, the frame, with its fabric cover, can be moved from one room to another within a house, or, when a family goes on vacation, the frame can be folded and set up easily and quickly in a hotel room or vacation home. A carrier or tube can be provided to contain the folded pen.
[0047] Although eyebolts are shown to connect the frame walls together, the frame elements can be connected with, for example, plastic extrusions 27 ′ (FIG. 17), which snappingly receive the vertical frame members 23 . Such an extrusion would have two identical portions 29 ′ with curved fingers 31 ′ which define cylinders with an elongate slot into which the tubing 23 is snappingly received. The backs of the two portions 29 ′ would then be directly connected together, or connected by a web. The size of the finger would allow for the frame members to pivot in the connector, to allow for folding of the frame.
[0048] Corner braces 44 prevent the pen 3 from inadvertently being folded when in use and in the open position. The corner braces 44 comprise generally U-shaped bolts having two end shafts 43 which are connected by a connecting section 45 . The connecting section 45 extends diagonally underneath the frame 5 and the end shafts extend up through the noses 25 of the frame vertical members 23 . Thus, the corner braces 44 also help in maintaining the frame members together. The ends of the shafts 43 are threaded, and nuts 47 (for example wing nuts) are threaded on to the ends of the shafts 43 to hold the corner brace in place. The corner braces 44 rigidize the frame, and hence, must be removed for the frame to be folded. Although U-bolts are shown for the corner braces, the U-bolts can be replaced with any conventional corner locking device. For example, a pivoting arm can be fixed to the side walls near the front and backs of the side walls. The arm can be provided with a key-hole or bayonet-slot type opening which is received over a headed stud on the front and back walls. The use of a pivoting arm would eliminate the necessity of totally removing the corner brace to fold the pen. Rather, the corner brace would merely need to be unlocked.
[0049] The washable, flexible, removable frame cover 7 is shown in FIG. 9. The cover 7 includes opposed side walls 51 , a front wall 53 , a back wall 55 , and a bottom 57 . The front wall 53 includes a gap or opening 59 for the gate. The walls of the cover 7 extend down the inside of the frame from the top of the frame to the bottom of the frame. Pockets 61 are formed at the tops of the walls and are sized to fit over the frame top members. Holes 63 are formed in the top of the back wall pocket and holes 65 are formed in the top of the side wall pockets. The hole 63 and holes 65 allow for mounting of the top/cover 11 on the frame 3 , as discussed below. Fasteners, such as ties 67 are provided at the corners and at the edge of the gate opening 57 near the bottom of the cover to hold the cover in place on the frame 5 . Because the cover 9 is held in place on the pen frame 3 by the cover pockets 61 and ties 67 , the cover can be easily removed from the pen frame for washing or replacing. Although the fasteners are shown to be ties, bands with snaps, buttons, hook-and-loop fasteners, or other types of commonly available fasteners can be used to removably hold the cover 11 to the frame 3 .
[0050] The gate assembly 9 is shown in FIGS. 7 and 10- 12 . As noted above, because the gate can be lowered or raised a desired amount, to, for example, allow a mother dog to enter and exit the pen, but prevent puppies from exiting the pen, the gate assembly is one of the important features of the pen 3 . The gate assembly 9 includes a gate frame 71 made from a U-shaped tubular member. The frame 71 has a bottom portion 71 a and vertical side portions 71 b,c . As seen in FIG. 7, the frame bottom portion 71 a is raised relative to the bottom members 21 b of the pen frame 5 . The gate frame 71 is secured to the pen frame vertical members 23 by bolts 73 which extend through the gate frame side 71 b and the neighboring pen frame member 23 . Eyebolts 27 are used to hingedly connect the opposite gate frame side 71 c to the neighboring corner vertical member 23 . As can be appreciated, the gate assembly 9 completes the front wall of the frame. The bolts 73 provide for an essentially rigid connection between the gate assembly and the inner end of the front wall; and the eyebolts 27 provide for a hinged connection between the gate and a corner vertical member of the pen frame.
[0051] Braces 75 extend diagonally between the gate frame bottom 71 a and the gate frame sides 71 b,c The braces 75 are sized and positioned so that they will not interfere with the pet's use of the gate. Yet, the size of the braces 75 will strengthen the crush bend that is formed in the tubing which forms the gate frame 71 , and could be dispensed with if the gate was formed in a different manner. For example, separate elbow joints could be used to form the corners of the gate frame 71 .
[0052] A pair of opposed track members 77 are mounted to the sides 71 b,c of the gate frame. The track members 77 include a flange 79 through which bolts extend to secure the members 77 to the gate frame and a pair of spaced apart rails 81 defining a channel 83 . The track 77 extends from a point just below the top of the frame sides to a point below the gate frame bottom portion 71 a and bends inwardly (to be under the bottom of the cover 7 ). A pliable panel 85 is slidably received in the track 77 . The panel 85 is preferably made of flexible plastic, or some other flexible material which can be easily washed. The panel 85 is turned up at its bottom to form a curved portion or end 87 to facilitate movement of the panel across a textured surface (such as carpet, cement, grass, etc.) when the panel 85 is lowered. Hence, the curved end 87 of the panel 85 helps in causing the panel to bend inwardly, to be under the cover bottom 57 as seen in FIG. 6. The curved end 87 of the panel 85 prevents the bottom edge of the panel from catching on the textured surface so that the panel 85 will slide along textured surfaces (such as rug, cement, etc) as easily as it will slide along a smooth surface (such as wood, linoleum, etc.). The curved end 87 of the panel also helps rigidize the end of the panel 85 . As seen in FIG. 11, the curved end 87 generally forms a semi-circle (or an arc of about 180°). Inasmuch as the curved end 87 is provided to facilitate movement of the panel over textured surfaces, the curvature 87 of the curved end could be altered if desired. For example, it could form nearly a complete circle, or only a quarter-circle.
[0053] The curved end 87 of the panel 85 is preferably set inwardly of the edges of the panel so that the curved end 87 will not interfere with removal of the panel 85 from the gate (by pulling the panel 85 up through the track 77 ) so that the panel can be cleaned or replaced, if necessary. The curved end 87 could extend the full width of the panel 85 . In this instance, the curved end would prevent the panel from being pulled up and out of the track 77 . To remove the panel 85 from the track 77 , the panel would be pulled out the bottom of the track.
[0054] The top edge of the panel 85 is capped with a top guard 89 (FIG. 5). The top guard 89 provides a smooth surface to the top edge of the panel 85 to help prevent abrading the teats of a nursing female (and the undersides of pets in general) when crossing through the gate. Additionally, the hard cap 89 prevents puppies (and other chewing pets) from damaging the top of the panel 85 .
[0055] The panel 85 can be held in place frictionally. However, it includes a plurality of holes 91 along one edge thereof. The track 77 includes a hole 93 (FIG. 5) near the bottom thereof. A spring biased pin 95 (FIG. 6) is mounted to the track over the hole 91 . The pin 95 extends through the track hole 93 to engage a selected hole 91 in the panel 85 to keep the panel 85 from sliding, for example, from a dog leaning on the panel 85 .
[0056] In an alternate embodiment, the gate 9 ′ (FIG. 13) has a frame 71 ′ which extends the full height of the pen frame 5 . That is, the gate frame bottom member 71 a ′ is level with the pen frame bottom members 21 b . Rather than using a single panel 85 , the gate 9 ′ is provided with a plurality of slats 85 ′. Slats 85 ′ are simply inserted in (or removed from) the tracks 77 ′ until the gate 9 ′ is raised (or lowered) to a desired position. The slats 85 ′shown in FIG. 13 are formed wire slats. No covering is provided to the slats 85 ′. They are sized so that a puppy can not pass through the slats. The advantage of formed wire slats is that they are light weight and easy to store. For example, a hook or loop can be provided on the side of the cover on which the formed wire slats can be hung. Additionally, the wire form slats form a smooth surface which will not abrade the underside of a dog or the teats of a nursing mother. Further, because they are made of wire, teething puppies will not be able to damage them.
[0057] An alternative slat 81 ″ is shown in FIG. 14. The slat 81 ″ is a solid slat having a tongue 81 a on its top and a groove 81 b on its bottom. The slates 81 ″can be plastic, wood, or metal slats. If plastic, they can be formed as an extrusion and cut to length. Alternatively, they can be injection molded. Because the slats 81 ″are made of plastic, they are inherently softer than the wire slats 81 ′. Thus, a specific one of the slats will be a top slat and be provided with a metal cap to reduce the possibilities of abrasion and prevent teething puppies from damaging the top slat 81 ″. If the slats are made from extruded aluminum, no cap is required.
[0058] As noted above, the whelping rail 13 (FIG. 15) can be inserted in the pen to further reduce the possibility of a puppy becoming lodged between the mother dog and the side of the pen 3 . The whelping rail 13 comprises four tubes—two side tubes 101 , and front and back tubes 103 . Each of the tubes has a horizontal rail portion 105 and leg portions 107 at opposite ends of the rail portion. The tubes are joined together at the leg portions by bolts 109 , for example, which extend through the legs 107 to form the whelping rail 13 . The legs 107 extend from the rail portions 105 at an angle, such that when the whelping rail is formed, the bottom ends of the legs will be received substantially in the corners of the pen and the rails portions 105 will be above the pen bottom and spaced inwardly from the pen walls. The legs 107 are sized and angled such that the rail is about 4 ″ above the pen bottom and about 3 ″from the walls of the pen. If the mother dog leans against the rail, there is a gap between the mother and the wall of the pen. Thus, if a pup is in this area, there will be a space to reduce the possibility of the mother dog suffocating her puppy.
[0059] Because the whelping rail only needs to be used for a short period of time, it is designed to be easily inserted into the pen, simply by dropping it in the pen. Once the puppies are weaned, and are no longer nursing, the whelping rail can be simply lifted out of the pen.
[0060] Turning to FIGS. 1 - 4 , the top 11 includes a tubular frame 111 made from side tubes 113 and front and back tubes 115 which are assembled in substantially the same way as the wall portions of the pen frame 7 . A fabric cover 117 is applied to the top frame 111 . As can be appreciated, the top frame cover 117 is provided with channels along its front edges into which the tubes 113 extend. The rear channel 107 is formed by wrapping or folding the cover about itself, and using hook and loop type fasteners (i.e., Velcro®) to maintain the channels in the cover 117 . Thus, the cover 117 can be easily removed from the top frame 111 for washing. Alternatively, snaps or a zipper, or any other easy-to-use fastener can be used which will allow for easy mounting and dismounting of the cover 117 from the frame 111 .
[0061] The top 11 is hingedly mounted to the pen frame 5 using a pair of hinges 119 . The hinges 119 are eye bolts having a head through which the top frame back tube extends and a shaft which extends into the pen frame top member 21 a . The head 121 is sized so that the top back tube 105 can pivot in the head. The eye-bolt shafts extend through the openings 63 (FIG. 9) in the pen cover 11 and corresponding holes in the pen frame top tube 21 a . Alternatively, sections of the extrusion 27 ′ can be used to hingedly mount the top 11 to the frame 5 . The use of the extrusion 27 ′ would allow for snapping the top 11 onto the frame 5 , while still allowing for pivoting of the top relative to the frame and for quick removability of the top from the frame.
[0062] The top also includes a pair of pivoting arms 131 which support the top 11 in a sloped position, as seen in FIG. 3. The arms 131 each include a top finger 133 which extends through the top frame side tubes at a point slightly rearwardly of the front of the top frame. The end of the fingers 133 are threaded, and accept a nut to secure the arm 131 to the top frame. The forward, free ends, of the arms 131 are received in holes 135 (FIG. 4) in the pen frame top side members. Preferably, there are several holes 135 in the pen frame top members (three holes are shown) so that the slope of the top 11 can be selectively altered. The cover holes 65 are aligned with the frame holes 135 . As can be seen, preferably the pen cover holes 65 are larger than the frame holes 135 . The pen cover holes 63 and 65 are preferably reinforced, to reduce the possibility of the pen cover 117 fraying at the holes. The pen cover holes 63 and 65 can be reinforced, for example with grommets, or by button-hole stitching.
[0063] Preferably, the frame top 11 has a side-to-side width that is slightly smaller than the side-to-side width of the pen 3 , so that the arms 131 can be straight as seen in FIG. 2. Thus, as seen best in FIG. 4, the distance between the outer edges of the top frame side tubes is slightly less than the distance between the inner edges of the pen frame side walls. Additionally, the front-to-back depth of the top 11 is shorter than the front-to-back depth of the pen 3 . The top 11 can also include side flaps 137 (FIG. 3) to enhance the den-like environment formed by the top 11 . The flaps 137 are preferably trapezoidal in shape and are sized to hang from the top frame side top rails to below the pen side rails when the top is in its highest position.
[0064] The top 11 is applied to the pen 3 simply by inserting the eyebolt shafts in the frame back holes, and then inserting the support arms 131 in a desired one of the frame side holes 135 . The top frame 11 is not secured to the pen frame 5 , so that it can be quickly and easily lifted off the pen frame should the master need instant access to the dogs in the enclosure 1 .
[0065] As can be appreciated, the enclosure 1 of the present invention can be used throughout the various stages of a pets life. The use of the easily removable top 11 and whelping rail 13 make adapting the enclosure 1 for birthing and nursing of puppies simple and quick. The unique gate construction allows for the master to control the egress and ingress of pets, and especially of puppies, by raising and lowering the gate a desired amount. The wall height of the pen 5 allows for a mother dog to see into the pen to check on her puppies. Younger puppies can see outside the pen primarily by looking over the lowered gate.
[0066] As various changes could be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense. Although nuts and bolts are used to hold the frame members together, they can be held together in other fashions. For example, a spring mounted finger in the ends 25 of the vertical side members 23 can be received in corresponding holes in the horizontal frame members. The frame members would be pushed together until the spring biased finger is brought into alignment with the corresponding hole, and the finger would pop into the hole, thereby preventing the frame members from inadvertently being separated from each other. The finger could then be pressed down to disassemble the frame 5 . Alternatively, the spring biased finger could be replaced with a screw-down friction lock. The frame cover 9 could be secured to the frame in other fashions. For example, the pockets 53 could be eliminated, and the fabric forming the cover could be extended to be folded around the pen frame members. Fasteners, such as hook and loop fasteners or snaps, for example, could be used to form channels around the frame members to hold the cover 9 to the frame top. Additionally, the ties 53 could be replaced with fabric strips having snaps, Velcro®, etc. at their ends. Although eyebolts are preferred as the hinges, other types of hinge elements, such as plastic extrusions, could also be used to connect the pen frame walls together and to hingedly and removably mount the top to the pen frame. The gate can alternatively comprise an accordioned or folded screen which is secured to the bottom bar of the gate frame and which includes a top bar. The top bar would be provided with snaps, pins, or other equivalent means for securing the gate in a desired position. These examples are merely illustrative. | An animal enclosure is provided which can be used for a plurality of purposes. The animal enclosure first of all includes a pen sized to hold the animal (i.e., dog). The pen is formed from a frame which is covered with a removable, washer cover. The dog enters and exits the pen by way of a gate. The gate includes a panel which is raised to close the gate and lowered to open the gate. The panel can be fixed at a desired position, so that the gate can be partially opened. A washable pen cover is provided to cover the frame of the pen. A top is provided which can be easily mounted to, and removed from, the pen frame. The top is hingedly connected to the frame and includes with a pair of pivotal support arms so that the front of the top can be elevated above the pen to the desired amount. A whelping rail is also provided and which is removably received in the pen. The whelpig rail comprises a frame having a bar member and legs extending disgonally downwardly and outwardly from the bar. The legs support the bar above a bottom of the pen and inwardly from the pen walls. | 0 |
CROSS-REFERENCES TO RELATED APPLICATIONS
This application is a divisional of U.S. Ser. No. 08/451,711 filed May 26, 1995 now abandoned. The entire contents of this prior application are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to molecularly imprinted polymer supports and a method of making these supports. More specifically the present invention involves arranging polymerizable functional monomers around a print molecule using suspension polymerization techniques which is accomplished with a stabilizing copolymer having the following formula: ##STR1## wherein: X is C n F 2n+1 , C n F 2n+1 (CH 2 ) r O--, C n F 2n+1 O-- or C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --O;
Y is (Z) t CH 3 O(CH 2 CH 2 O) m C 2 H 4 --O or (Z) t CH 3 O(CH 2 CH 2 O) m ;
Z is a print molecule;
n is between 1 and 20;
m can be zero to about 500;
p is at least 1;
q can be zero or any positive number;
r is 1-20, preferably 1 or 2;
s is zero or 1; and
t is zero or 1.
The polymer support of the present invention is preferably in bead form and is capable of separating or resolving amino acids, amino-acid derivatives, pharmaceutical compounds and poly-saccharides.
BACKGROUND OF THE INVENTION
Molecular imprinting, also referred to as templating, has been used for chiral separations and involves arranging polymerizable functional monomers around a print molecule. This is achieved either by utilizing non-covalent interactions such as hydrogen bonds, ion-pair interactions, etc. (non-covalent imprinting), or by reversible covalent inter-actions (covalent imprinting) between the print molecule and the functional monomers. The resulting complexes are then incorporated by polymerization into a highly cross-linked macroporous polymer matrix. Extraction of the print molecule leaves sites in the polymer with specific shape and functional groups complementary to the original print molecule. Mosbach, K., Trends in Biochemical Sciences, Vol. 7, pp. 92-96, 1994; Wulff, G., Trends in Biotechnology, Vol. 11, pp. 85-87, 1993; and Andersson, et al., Molecular Interactions in Bioseparations (Ngo. T. T. ed.), pp. 383-394.
Different racemic compounds have been resolved via molecular imprinting, i.e., "amino acid derivatives", see Andersson, et al., Molecular Interactions in Bioseparations (Ngo T. T. ed.), Plenum Press, pp. 383-394, 1993; "drugs", Fischer, et al., J. Am. Chem. Soc., 113, pp. 9358-9360, 1991; Kempe, et al., J. Chromatogr., Vol. 664, pp. 276-279, 1994; and "sugars", Wulff, et al., J. Org. Chem., Vol. 56, pp. 395-400, 1991; Mayes, et al., Anal. Biochem., Vol. 222, pp. 483-488, 1994. Baseline resolution has been achieved in many cases.
An advantage of molecularly imprinted polymers, in contrast to other chiral stationary phases, is the predictable order of elution of enantiomers. Imprintable supports have been prepared from bulk polymerization techniques, using a porogenic solvent to create a block of macroporous polymer. However, bulk polymerization supports must be crushed, ground and sieved to produce appropriate particle sizes for use in separatory columns and analytical protocols. For example, in chromatographic evaluations, polymer particles smaller than 25 μm are generally used. However, from the bulk polymerization process the grinding process used to provide these smaller particles from the bulk polymerization process is unsatisfactory. Grinding produces irregularly shaped particles and an excessive and undesirable quantities of "fines." Typically less than 50 percent (50%) of the ground polymer is recovered as useable particles. Irregular particles generally give less efficient column packing for chromatography and often prove troublesome in process scale-up. Hence, uniformly shaped particles, e.g. beaded polymers, would be preferable in most cases. The grinding process also requires an additional treating step to remove the fines, i.e., sedimentation. This is costly and time consuming. The bulk polymerization and necessary grinding process makes this prior art technique labor intensive, wasteful and unacceptable.
Attempts have been made to use suspension and dis-persion polymerization techniques for producing beads from acrylic monomers which can contain imprinted molecules. In principle these suspension and dispersion polymerization techniques should offer an alternative to bulk polymerization. However, existing suspension and dispersion techniques are not satisfactory because water or a highly polar organic solvent (e.g. an alcohol) is used as the continuous phase for the relatively hydrophobic monomers. These solvents are incompatible with most covalent and non-covalent imprinting mixtures due to the competition between solvent and functional monomers for specific interaction with the print molecule. Since suspension polymerization techniques use the solvent in large molar excess, the solvents saturate the monomer phase and drastically reduce the number and strength of the inter-actions between functional monomers and print molecules. In addition, because of the high solubility of acidic monomers in water, random copolymerization of monomers and cross-linker is probably not achieved. Water soluble print molecules are also lost due to partitioning into the aqueous phase. Not unexpectedly, attempts to make molecularly imprinted polymer beads by suspension polymerization in water have led to only very poor recogni-tion. Damen, et al., J. Am. Chem. Soc., Vol. 102, pp. 3265-3267, 1980; Braun, et al., Chemiker-Zeitung, Vol. 108, pp. 255-257, 1984; Bystrom, et al., J. Am. Chem. Soc., Vol. 115, pp. 2081-2083, 1993. With stable covalent or metal chelate bonds between functional monomers and print molecules prior to polymerization, it may be possible to use aqueous conditions.
Attempts have also been made to produce composite beaded particles by imprinting in the pore network of performed beaded silica, Norrlow, et al., J. Chromatogr., Vol. 299, pp. 29-41, 1984; Wulff, et al., Reactive Polymers, Vol. 3, pp. 261-2757, 1985 or TRIM. However, the preparation requires careful handling and the volume of imprinted polymer per unit column is inevitably reduced by the beads themselves.
Sellergren, B., J. Chromatogr., Vol. 673, pp. 133-141, 1994 and Sellergren, B., Anal. Chem., Vol. 66, pp. 1578-1582, 1994, report the use of dispersion polymerization in a polar solvent mixture for molecular imprinting. The process produces random precipitates rather than regular beads. Acceptable results were only achieved for highly charged print molecules, presumably due to the presence of competing solvent effects.
Thus, a need exists for a method that produces beaded polymers containing molecular imprints that is simple and reproducible, does not compromise the quality of the imprints obtained and eliminates the need for grinding and sieving equipment. A need also exists for a molecular imprinted polymer bead that is uniform.
SUMMARY OF THE INVENTION
The present invention relates to molecular imprinted polymer supports and their preparation via suspension polymerization. The suspension techniques according to the present invention provide for molecular imprinting by using a perfluorocarbon liquid containing polyoxyethylene ester groups as the dispersing phase. The perfluoro-carbon-polyoxyethylene ester containing group compound does not interfere with the interactions between functional monomers and print molecules that are required for the recognition process during molecular imprinting. Controllable "support" particle sizes from about 2 μm to about 100 μm are obtained by varying the amount of stabilizing polymer, or agitating technique.
Accordingly, it is an object of the present invention to provide a method that enables imprinted polymers to be easily produced, in beaded form with an almost quantitative yield of useable material.
It is another object of the present invention to provide a fluorocarbon copolymer that stabilizes the emulsion in suspension polymerization processing without interfering with the interactions between functional monomers and print molecules.
It is a still further object to stabilize an emulsion of functional monomers, cross-linkers, print molecules, initiators and porogenic solvents.
Another object of the present invention is to provide molecularly imprinted polymer bead having a size of about 2 to about 100 μm, in high yield.
A still further object of the present invention is to provide small, about 2-5 μm, beaded packings that provide low back pressure, rapid diffusion, and good separation at high flow rates.
These and other objects and advantages will become more apparent in view of the following description and attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a graph of bead diameter versus PFPS quantity added for a "standard polymerization" containing 1.84 g EDMA, 0.16 g MAA, 4.2 g chloroform and 20 mg AIBN emulsified in 20 ml PMC.
FIGS. 2a-2e show scanning electronmicrographs of beads produced from suspension polymerization in PMC in accordance with the present invention where the beads were placed on aluminum pegs and sputter coated with 15 mm gold using a polaron E5150 coater. The images were obtained using an ISI 100A SEM at 25 kV. The magnification is 500×. 2(a) PF2; 2(b) PF10; 2(c) PF13; 2(d) PF14; and 2(e) PF15.
FIGS. 3a-3e show HPLC traces showing separation of Boc-D, L-Phe by a 25 cm column of Example PF15 (5 μm TRIM beads). Conditions: the column was equilibrated with chloroform+0.25% acetic acid; 1 mg Boc-D,L-Phe in 20 μl mobile phase was injected and eluted with the same solvent at flow rates of 3(a) 0.5 mlmin -1 ; 3(b) 1 mlmin -1 ; 3(c) 2 mlmin -1 ; 3(d) 3 mlmin -1 ; and 3(e) 5 ml-min -1 . At 0.5 ml-min -1 , f/g=0.89, Rs=1.36 and α=1.52 f/g values were 0.89, 0.89, 0.85, 0.76 and 0.61 at 0.5, 1, 2, 3 and 5 mlmin -1 respectively.
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, a suspension polymerization technique based on emulsion of noncovalent imprinting mixtures formed in liquid perfluorocarbons that contain polyoxyethylene ester groups, is provided. Most prior art suspension and dispersion techniques use water or a highly polar organic solvent (e.g. an alcohol) as the continuous phase for the relatively hydrophobic monomers, which is not fully satisfactory. Accordingly, a different approach is required. The present invention provides the "different approach." In addition, the drawbacks of prior art processes, e.g., solvents that are incompatible with most covalent and non-covalent imprinting mixtures due to the competition between solvent and functional monomers for specific interaction with the print molecule are avoided. The present invention avoids the use of dispersants which interfere with the interactions that are required for recognition between print molecules and functional monomers. In order to create reasonably stable emulsion droplets containing monomers, cross-linkers, print molecules, porogenic solvents, and fluorinated surfactants, the invention uses a perfluorocarbon polymer that also contains polyoxyethylene ester groups, with or without a print molecule for providing surface imprinting.
The stabilizing/dispersing agent of the present invention is generally defined by the following formula: ##STR2## wherein: X is C n F 2n+1 , C n F 2n+1 (CH 2 ) r O--, C n F 2n+1 O-- or C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --O;
Y is (Z) t CH 3 O(CH 2 CH 2 O) m C 2 H 4 --O or (Z) t CH 3 O(CH 2 CH 2 O) m ;
Z is a print molecule;
n is between 1 and 20;
m can be zero to about 500;
p is at least 1;
q can be zero or any positive number;
r is 1-20, preferably 1 or 2;
s is zero or 1; and
t is zero or 1.
Block, triblock and multiblock copolymers formed from the acrylated monomers of C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --OH and (Z) t CH 3 O(CH 2 CH 2 O) m C 2 H 4 --OH are also within the scope of the present invention. A preferred stabilizing/dispersing agent according to the present invention is a copolymer containing monomer A defined by the formula: C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 O--CO--CH═CH 2 ; and comonomer B defined by the formula: CH 3 O(CH 2 CH 2 O) m C 2 H 4 O--CO--CH═CH 2 ; where n is between 1 and 20 and m is between 0 and 500. Preferably, n is about 7.5 and m is about 43. Most preferably, the stabilizing/dispersing agent is defined by the following formula, ##STR3## wherein: X is C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --O;
Y is (Z) t CH 3 O(CH 2 CH 2 O) m C 2 H 4 --O
Z is a print molecule;
n is between 1 and 20;
m can be zero to about 500;
p is at least 1;
q can be zero or any positive number;
s is zero or 1;
t is zero or 1, and
enables the production of spherical beads in high yields via a suspension polymerization process.
Preferably, m=about 7.5, n=about 43, p=about 19 and q=about 1. The values m, n, p, and q need not be whole numbers.
As a result of using the stabilizer of the present invention, the physical characterization of beads is achieved either by utilizing non-covalent interactions such as hydrogen bonds, ion-pair interactions, etc. (non-covalent imprinting), or by reversible covalent inter-actions (covalent imprinting) between the print molecule and the functional monomers. The complexes formed are then incorporated by polymerization into a highly cross-linked macroporous polymer matrix formed from the copolymerization of different acrylic monomers. Extraction of the print molecule leaves sites in the polymer with specific shape and functional groups complementary to the original print molecule.
The print molecules that can be used in the present invention include, but are not limited to:
1. D- and L-Boc tryptophans
2. D- and L-Boc phenylanalines
3. D- and L-phenylanalines
4. D- and L-Boc-proline-N-hydroxsuccinimide esters
5. D- and L-Cbz tryptophans
6. D- and L-Cbz-aspartic acids
7. D- and L-Cbz-glutamic acids
8. D- and L-Cbz-tryptophan methyl esters
9. nitrophenyl α and β, D-, L-galactosides
10. (S)-(-) timolol
11. D-fructose
12. D-galactose
13. phenyl α-D-mannopyranoside
14. acryl α and β glucosides
15. (R)-phenylsuccinic acid
16. Ac-L-Trp-OEz
17. L-PheβNA
18. L-LeuAn
19. L-PheAn
20. L-PheGlyAn
21. L-MenPheAn
22. L-PyMePheAn
23. L-PLPheAn
24. N-Ac-L-Phe-L-Trp-OMe
25. diazepham
26. propranolol
27. ephidrine
However the Boc- D- and L-Phe, and L-Phe have been used in the following non-limiting examples.
Reagent Preparation
Monomers
Ethylene glycol dimethacrylate (EDMA) and methacrylic acid (MAA) (Merck, Darmstadt, Germany) were distilled under reduced pressure prior to use. Trimethylolpropane trimethacrylate (TRIM) (Aldrich Chemie, Steinheim, Germany), styrene (Aldrich), methyl methacrylate (MMA) (Aldrich) and benzyl methacrylate (BMA) (Polysciences, Warrington, Mass.) were used as received. 2,2'-azobis (2-methylpropionitrile (AIBN) came from Janssen Chimica, Goel, Belgium.
2-(N-ethylperfluoroalkylsulphonamido)ethanol (PFA-1) (Fluorochem, Old Glossop, UK), PEG2000 monomethylether (MME) (Fluka Chemic A. G., Buchs, Switzerland) and PEG350MME (Sigma, St. Louis, Mo.) were converted to their acrylates by reaction with acryloyl chloride and tri-ethylamine in dichloromethane, were also available commercially (from Fluorochem and Polysciences respectively). Perfluoro(methylcyclohexane) (PMC) and Fluorad FC430 were also obtained from Fluorochem.
Imprint Molecules
Boc-D-Phe, Boc-L-Phe and Boc-D, L-Phe were obtained from Bachem A. G., Bubendorf, Switzerland). (Boc=tert-butoxy carbonyl; Phe=phenylanaline).
Porogenic Solvents
Chloroform (CHCl 3 ) (HPLC grade) was passed down a basic alumina column to remove ethanol and stored over molecular sieves for use as porogenic solvent during imprinting. For HPLC it was used as received. Toluene was dried with sodium and acetonic with molecular sieves prior to use. Other solvents were of analytical grade or better and were used as received.
Preparation of Stabilizers
The most emulsion stabilizing/dispersing polymers (PFPS) according to the present invention are defined by the formula ##STR4## wherein: X is C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --O;
Y is (Z) t CH 3 O(CH 2 CH 2 O) m C 2 H 4 --O;
Z is a print molecule;
n is between 1 and 20;
m can be zero to about 500;
p is at least 1;
q can be zero or any positive number; and
t is zero or 1; and
in particular where n is about 7.5, m is about 43, p is about 19 and q is about 1.
EXAMPLE 1
4 g acryloyl PFA-1 (7.2 mmole) C n F 2n+1 SO 2 N(C 2 H 5 )C 2 H 4 --O--CO--CH═CH 2 and 0.76 g acryloyl PEG2000MME (0.36 mmole) defined by the following formula: CH 3 O(CH 2 CH 2 O) m C 2 H 4 --O--CO--CH═CH 2 , were dissolved in 10 ml of chloroform, where n is about 7.5 and m is about 43. 24 mg (76 μmole) of AIBN was added and dissolved oxygen removed by nitrogen sparring for 5 minutes. The tube was then sealed and the contents poly-merized at 60° C. for 48 hours in a shaking water bath. The resulting solution was slightly turbid and became much more turbid on cooling. Most of the solvent was removed by slow evaporation at 30° C. under reduced pressure (to avoid foaming) and the remainder under reduced pressure at 60° C. The resulting polymer was a sticky pale yellow paste which was used without further treatment.
Other polymer stabilizers were synthesized in a similar fashion using the appropriate ratio of monomers and 1 mole % of AIBN. All formed cream to amber polymers varying from glassy to very soft pastes depending on the composition.
Suspension Polymerizations
The amount of porogenic solvent required to just saturate 20 ml PMC was determined. The required amount of PFPS was dissolved in this volume of porogenic solvent in a 50 ml borosilicate glass tube and 20 ml PMC added and shaken to give a uniform white to opalescent emulsion. 5 ml of "imprinting mixture", (Table 1) was added and emulsified by stirring at 2000 rpm for 5 minutes.
TABLE 1______________________________________ MAA EDM Solvent PFPSEx.* Print Molecule (mg) (g) A (g) (g) (mg)______________________________________PF1 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 10PF2 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 25PF3 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 50PF4 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 75PF5 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 100PF6 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 200PF7 Boc-L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 500PF8 Boc-L-Phe (120) 0.32 1.84 CHCl.sub.3 (4.2) 25PF9 Boc-L-Phe (120) 0.48 1.84 CHCl.sub.3 (4.2) 25PF10 Boc-L-Phe (120) 0.64 1.84 CHCl.sub.3 (4.2) 25PF11 Boc-L-Phe (68) 0.265 1.84 CHCl.sub.3 (4.2) 25PF12 Boc-D,L-Phe (120) 0.16 1.84 CHCl.sub.3 (4.2) 25PF13 None 0.16 1.84 toluene (2.45) 25PF14 None 0.16 1.84 acetone (2.25) 25PF15 Boc-L-Phe (308) 0.4 1.57 CHCl.sub.3 (4.6) 100 TRIMPF16 Boc-L-Phe (308) 0.4 1.57 CHCl.sub.3 (4.6) 25 TRIM______________________________________ · *The beads prepared according to the present invention, as wel as the comparative examples, are designed with the PF code numbers in column 1 of the table.
The polymerization apparatus used for all polymerizations in the present invention comprised a 50 ml boro-silicate glass tube with screw lid, the center of which was drilled to allow the shaft of a stainless steel flat blade stirrer to pass there through. The stirrer blade was about one-half the length of the tube. A rubber seal was used to reduce evaporation through this hole. An additional small hole in the lid allowed a nitrogen stream to be fed into the tube via a syringe needle. The tube was held vertically in a retort stand and stirred with an overhead stirrer. A UV lamp was placed about 5 cm away from the tube and the lamp and tube surrounded with aluminum foil to maximize reflected light.
Emulsions designated PF1-PF16 in Table 1 above were prepared and placed in the reactor which was purged with nitrogen for 5 minutes and then the emulsions polymerized by UV irradiation at 366 nm at room temperature under a gentle nitrogen stream stirring at 500 rpm. Polymerization was continued for 3 hours. The resulting polymer particles (beads) were filtered on a sintered glass funnel and the PMC recovered. The beads were washed extensively with acetone, sonicating to break up loose aggregates of beads (large aggregates were broken up by gentle crushing with a spatula), before drying and storing.
Varying the amount of PFPS used during the polymerization controls bead size, the relationship being shown in FIG. 1. FIG. 1 is a graph of the mean and standard deviation for beads made in accordance with the present invention using different amounts of PFPS. A standard was prepared with 2 g of monomers in a 5 ml total volume (see Table 1). 10 mg PFPS is at the lower limit of the range where stable emulsions can be formed and quite a lot of aggregate was also present in this sample. Using 150 mg or more of PFPS gave only very small irregular particles of 1-2 μm. No beads were apparent in these samples.
Comparative Examples
Two commercial fluorinated surfactants (polyfluoro-alcohol (PFA-1) and fluorad FC430), a homopolymer of acryloyl PFA-1, a range of random copolymers of acryloyl PFA-1 with styrene, methyl methacrylate or benzyl meth-arcylate, and graft copolymers containing perfluoroester groups and PEG groups attached to the main acrylate chain, were also evaluated as stabilizers. Most of these, however, proved to be ineffective. The process was hindered by the high density of the dispersant which caused rapid "creaming" of the emulsion, thus favoring coalescence of dispersed droplets.
Polyacryloyl PFA-1, alone, was evaluated and gave sufficiently stable emulsions for suspension polymerization and gave good quality beads. Unfortunately, due to its poor solubility, this surfactant proved to be extremely difficult to remove from the surface of the beads after polymerization, resulting in extremely hydrophobic surfaces.
The most effective emulsion was achieved using a copolymer of acryloyl-PFA-1 and acryloyl-PEG2000MME (mole ratio 20:1-termed PFPS).
Molecularly Imprinted Bead Properties
Size
The type of emulsification impacts the polymerization process and the resulting molecularly imprinted beads. The preferred method involved stirring at about 2000 rpms for about 5 minutes and gave good uniformity and reproducibility for a bead having a size of between 2 and 25 μm. Five separate polymerizations performed on different days using 25 mg PFPS as the emulsifier gave a mean bead size of 19.7 μm and a standard error of 0.6 μm.
Emulsification in an ultrasonic bath for 5 minutes gave a much broader size distribution with an excessive quantity of small particles. Conventional shaking in a tube 3 or 4 times gave good results if larger beads were desired, i.e., 40 μm to about 100 μm.
The polymerization temperatures also affected the polymerization process and resulting beads. Attempts to use thermal initiation at 45° C. using ABDV as initiator gave only small irregular fragments. UV initiation of polymerization at 4° C. led to a large amount of aggregation. Most polymerizations were performed at ambient temperature (about 20° C.), i.e. at least about 18° C., although some temperature increase occurred during polymerization due to the proximity of the UV lamp. Polymerizations carried out during very warm weather, when ambient temperature reached 30° C., gave slightly smaller beads, indicating that polymerization temperature can also impact bead size while still providing reproducible results.
Polymerizations were also carried out in a range of solvents commonly used in molecular imprinting, e.g., chloroform, toluene, acetonitrile and acetone. The polymerization method can use all of these solvents and hence should be appropriate for most imprinting situations. However, the preferred solvents are chloroform toluene and acetone. The size and surface structure of the beads produced also depends on the porogenic solvent used. Both toluene (26 μm±12 μm-mean±SD) and acetone (52 μm±15 μm) gave larger beads than chloroform (18 pm±8 pm) for 25 mg of PFPS in a "standard" polymerization.
Bead Size Distributions
Suspensions of beads in acetone were dried onto microscope slides and about 150 beads measured at random using a calibrated graticule in an optical microscope. Either 100× or 400× magnification was used depending on the particle size. Some samples were also imaged by SEM. Measurements made from these images compared well with the results from optical determinations.
Scanning Electron Micrographs
Polymer beads were placed on aluminum pegs and sputter coated with 15 nm gold using a Polaron E5150 gold coater. Images were then obtained using an ISI 100A SEM at 25 kV in order to compare the sizes, surfaces and pore structures of beads produced under different conditions.
Scanning electron micrographs of some of the beaded polymer preparations are shown in FIGS. 2a-2e. The method according to the present invention produces substantially spherical beads, both for EDMA(2a-2d) and TRIM(2e) based polymers, and using a variety of porogenic solvents. The incidence of defects, such as surface indentations or small holes, is somewhat higher than is usually observed for water-based suspension polymerizations in water. The morphology of the beads is typical of beads made by suspension polymerization with a slightly denser and smoother surface layer covering a more porous structure in the interior.
The beads made using acetone as porogenic solvent (FIG. 2d) differed from the others. They were larger, had much rougher surface morphology and more "debris" on their surfaces than those prepared using chloroform or toluene. The beads made with toluene as porogenic solvent had a less dense surface shell and somewhat more porous interior structure than those made with chloroform. FIG. 2b shows beads of polymer PF9 which has a lower proportion of cross-linker than that in FIG. 2a (polymer PF2). The beads in FIG. 2b are much more irregular and distorted, suggesting that these particles might remain softer and deformable for longer during polymerization and hence are more prone to distortion due to shear or collision. The internal morphology of these beads also appeared to be more open and porous than that of polymer PF2. This might contribute to the better HPLC performance of the latter. The beads of FIG. 2(c) show PF13 beads and FIG. 2(e) PF15 beads.
High Pressure Liquid Chromatography
To confirm that the polymer beads made according to the present invention are molecularly imprinted, and that the quality of the recognition sites is at least as good as that obtained by traditional bulk polymerization methods, a range of polymers imprinted using Boc-Phe were evaluated by HPLC. This system was chosen since a great deal of information is available on the performance of traditional crushed bulk polymers imprinted with Boc-Phe.
Beads were suspended in a chloroform-acetone (17:3) mixture by sonication and slurry packed into 10 cm by 0.46 cm or 25 cm by 0.46 cm stainless steel columns at 300 bar using an air driven fluid pump and acetone as solvent. The columns were washed with 250 ml methanol:acetic acid (9:1) and then equilibrated with chloroform containing 0.1% or 0.25% acetic acid. 10 μg Boc D- or L- Phe or 20 μg racemate in 20 μl solvent was injected and chromatograms recorded at 254 nm at a flow rate of 0.5 ml/min. Some separations were also run at higher flow rates and with larger amounts of compound loaded. Chromatographic parameters were calculated using standard theory.
The results for HPLC evaluation of six of the polymers are summarized in Table 2.
TABLE 2______________________________________ID.sup.† Ratio.sup.‡ % x-link K'D K'L Alpha Rs f/g______________________________________ CHCl.sub.3 + 0.1% Acetic AcidPF2 1:4 80 0.69 1.44 2.09 0.59 0.51PF8 1:8 71 0.77 1.42 1.88 0.43 0.37PF9 1:12 62.5 1.12 1.88 1.68 0.83 0.73PF10 1:16 56 1.44 2.81 1.81 0.49 0.5PF11 1:12 75 0.71 1.27 1.8 0.87 0.63PF11* 1:12 75 0.79 1.43 1.82 1.23 0.84PF12 1:4 80 0.7 0.7 0 0 0 CHCl.sub.3 + 0.25% Acetic AcidPF2 1:4 80 0.43 0.78 1.81 0.26 0.23PF8 1:8 71 0.54 0.97 1.79 0.31 0.28PF9 1:12 62.5 0.76 1 1.7 0.69 0.66PF10 1:16 56 0.5 1.89 1.89 0.48 0.44PF11 1:12 75 0.63 0.71 1.78 0.48 0.39PF11* 1:12 75 0.84 1.11 1.91 1.08 0.88PF12 1:4 80 0 0.54 0 0 0______________________________________ .sup.† The identification scheme (ID) for the polymers is consistent with the notation developed previously at Table 1. .sup.‡ The ratio shown is that of the print molecule to the methacrylic acid (MAA) monomer.
As the ratio of MAA to print molecule increased the retention times and hence the capacity factors increased due to greater non-specific interaction. The α-values, however, stayed almost constant at about 1.8. This is very similar to values obtained under similar conditions for ground and sieved bulk Boc-Phe polymers (range 1.77 to 2.17). The optimum resolution was found at an MAA:Boc-Phe ratio of 12:1, the value of 0.83 being good for a 10 cm column. Using a longer column (25 cm) of polymer PF11 resulted in near baseline resolution of the enantiomers as has previously been reported for bulk polymers (chromatogram not shown). Polymer PF9, which was only 62.5% cross-linked, performed better than polymer PF11, which had the same print molecule:MAA ratio but was 75% cross-linked. It has previously been shown that separations improve as the degree of cross-linking increases within this range, but this was not observed in these experiments. Polymer PF11 was made using less print molecule (see Table 1) since it is not possible too vary these parameters independently, and it is thus not clear whether the improved resolution was due to the larger number of binding sites or to changes in polymer morphology as a result of the lower cross-linking. Such observations indicate that significant improvements in separation can be achieved by careful optimization of the many compositional and operational variables. The simplicity and speed of the bead polymerization method makes extensive optimization possible.
It has previously been suggested that polymers based on the trifunctional cross-linker TRIM had much better resolution and load capacity than EDMA-based polymers for a range of di and tripeptides. In order to further evaluate the suspension polymerization method according to the present invention, imprints of Boc-L-Phe were made in a TRIM-based polymer. Beads produced using 100 mg of PFPS (PF15) had an average diameter of 5.7 μm, and those using 25 mg PFPS (PF16) a diameter of 18.8 μm, very similar to what would have been expected for EDMA-based polymers with the same amount of stabilizing polymer. Thus, in terms of bead-size prediction, TRIM and EDMA seem to behave very similarly. An SEM picture of beads of PF15 is shown in FIG. 2e. These beads were tested by HPLC and gave excellent resolution and high load capacities, as was noted for the ground and sieved block polymers. The packed column had very low back pressure, and high resolution could be achieved, even at quite high flow rates. FIGS. 3a-3e shows a series of chromatograms for flow rates between 0.5 and 5 mlmin -1 , i.e., 0.5 ml/min, 1 ml/min, 2 ml/min, 3 ml/min and 5 ml/min. Little difference was observed between 0.5 and 2 mlmin -1 , suggesting that diffusion rates are rapid for these small beads. The back pressure was very low and resolution excellent (f/g=0.89, 0.89 and 0.85 at 0.5, 1 and 2 mlmin-1 respectively). Reasonable resolu-tion (f/g=0.61) was still achieved at 5 mlmin-1 (back pressure 1300 psi). Ground and sieved random <25 μm particles do not usually perform well at flow rates above 1 mlmin-1. Working with crushed bulk polymers in the 5 μm size range is difficult. Extensive defining is required to avoid high back pressures in HPLC columns, and sieves below 10 μm are unobtainable, making it necessary to use alternative size fractionation techniques. This result indicates that the beaded imprinted polymers should have significant advantages over "traditional" ground and sieved block polymers, both in the case of preparation and in the performance of the resulting columns.
It is also contemplated that because the stabilizer of the present invention is essentially chemically inert, it may be used as a dispersant for making beaded polymers containing water-sensitive monomer units, e.g., acid chlorides or anhydrides.
Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious to those skilled in the art that certain changes and modifications may be practiced without departing from the spirit and scope thereof as described in the specification and as defined in the appended claims. | The claimed invention is directed to a molecularly imprinted support formed from at least two distinct acylic monomers and at least one imprinted molecule. The support comprises beads having a uniform surface for reproducible presentation thereon. | 1 |
TECHNICAL FIELD
[0001] The present invention relates to a respiratory tract widening tool for respiratory tract management and a respiratory tract widening unit provided therewith.
BACKGROUND
[0002] Sleep apnea that repeats respiratory arrest lasting ten or more seconds a plurality of times during sleep is becoming problematic in recent years. When an apnea condition occurs, a thoracic cavity internal pressure becomes a strong negative pressure, blood accumulates in the thoracic cavity causing a high blood pressure, cardiac disease or the like or sleep is interrupted at deep third and fourth stages, and therefore people feel drowsiness during the daytime and might cause a traffic accident or the like. Sleep apnea is caused by a blockage of the upper respiratory tract, which is a passage of air, and attributable to fat deposition around the neck, tonsillar hypertrophy, micrognathia, falling of the root of tongue into the respiratory tractor the like.
[0003] Conventionally, respiratory tract management auxiliary apparatuses are known which are intended to prevent falling of the root of tongue. This respiratory tract management auxiliary apparatuses provided with a support section that stably supports the load of the lower jaw, a retractable leg that adjusts the distance from the support section to the position of the jaw to be supported, a jaw rest that is attached to the distal end of the leg and contacts and supports the human mandibular angle and an angle adjustment mechanism provided between the leg and the jaw rest.
SUMMARY
Technical Problem
[0004] When one keeps a supine posture for a long time during sleep, one's back is oppressed, the blood circulation of the back is impaired, and one-directional force is applied to the backbone or shoulder for a long time, causing shoulder stiffness or backache. To prevent this, people unconsciously toss and turn in bed, from a supine posture to a lateral position or from a lateral position to a supine posture a plurality of times during sleep.
[0005] However, when the above-described conventional respiratory tract management auxiliary apparatus is applied to sleep apnea prevention, this respiratory tract management auxiliary apparatus fixes the lower jaw with a jaw rest while keeping the support section stable, which results in a problem that people need to keep the supine posture and cannot change the direction of the body such as tossing and turning. That is, the conventional respiratory tract management auxiliary apparatus can secure the respiratory tract only when people are in a supine posture and keep a condition in which the lower jaw is completely fixed, and if, for example, people return to the supine posture again after tossing and turning during sleep, it is not possible to automatically manage the respiratory tract. Therefore, people need to stop sleeping once and fix the apparatus again every time people change the posture, which results in a problem of interrupting comfortable sleeping such as a reduction of sleeping time. Furthermore, when people are unaware that the apparatus comes off while sleeping, the respiratory tract is not managed in the supine posture and sleep apnea cannot be prevented.
[0006] The present invention has been implemented in view of the above-described problems and it is an object of the present invention to provide respiratory tract widening tool and a respiratory tract widening unit provided therewith capable of reliably managing the respiratory tract in a supine posture and easily changing the posture.
[0007] A respiratory tract widening tool of the present invention is a respiratory tract widening tool used attached to an outer periphery of the human neck, including: a main body that comes into contact with a posterior side of the neck when the tool is worn and receives an upward external force in a supine posture; and a pair of jaw retainers that extend forward from the main body spaced apart by a distance equivalent to the diameter of the neck and come into contact with both sides of the lower jaw when the tool is worn, and a protruding section that is provided in the main body and applies stress in a direction of pushing up the lower jaw in a supine posture to the main body, wherein: the main body and the pair of jaw retainers are formed of a restorable member, the main body and jaw retainers deform, when the posture is changed from the supine posture, in conformity with the posture, and when the posture is changed to the supine posture, the external force received by the main body is made to act on the jaw retainers to retain the lower jaw at a height at which the respiratory tract can be managed, and the main body includes a receiving face that is directly downward in a supine posture to press a tool underlay surface facing the neck and also receives a counterforce from the underlay surface.
[0008] According to this configuration, the main body receives an upward external force during the supine posture, the pair of jaw retainers that extend from the main body push up the lower jaw and retain the lower jaw at a height at which the respiratory tract can be managed, and it is thereby possible to prevent the root of tongue from falling into the throat side. That is, in the supine posture, the upward external force received by the main body is made to act on the pair of jaw retainers to keep the height of the lower jaw so that the height of the sub maxilla is not lowered due to relaxation of the neck muscle during sleep (during sound sleep). This prevents the root of tongue attached to the sub maxilla from falling into the throat side, and can thereby manage the respiratory tract. Furthermore, the main body and jaw retainers can be made of restorable members and the respiratory tract widening tool has a structure separated from a pillow or the like, and therefore when the posture is changed from a supine posture to a lateral position or a prone posture, the main body and jaw retainers deform according to the changed posture, and the user can thereby freely change the posture from the supine posture by tossing and turning. Furthermore, when the posture is returned to the supine posture, the main body receives an upward external force and the main body keeps the lower jaw at a height at which the respiratory tract can be managed, and can thereby automatically manage the respiratory tract again without interrupting comfortable sleeping.
[0009] According to this configuration, since the protruding section applies stress in the direction of pushing up the lower jaw to the main body, it is possible to enhance the effect that the upward bent respiratory tract is extended into a substantially rectilinear shape and sufficiently widen the respiratory tract.
[0010] According to this configuration, since the receiving face receives the counterforce from the underlay surface, the main body allows the counterforce to appropriately and uniformly apply to the pair of jaw retainers. Therefore, both lower jaws have a substantially identical height, that is, both sides of the lower jaw are kept at a height at which the respiratory tract can be managed in a stable condition without any one of the sides of the lower jaw being inclined. This allows the respiratory tract to be managed reliably.
[0011] A respitory tract widening tool of the present invention is a respitory tract widening tool used attached to an outer periphery of the human neck, including: a main body that comes into contact with a posterior side of the neck when the tool is worn and received an upward external force in a supine posture; and a pair of jaw retainers that extend forward from the main body spaced apart by a distance equivalent to the diameter of the neck and come into contact with both sides of the lower jaw when the tool is worn, wherein: the main body and the pair of jaw retainers are formed of a restorable member, the main body and jaw retainers deform, when the posture is changed from the supine posture, in conformity with the posture, and when the posture is changed to the supine posture, an external force received by the main body is made to act on the jaw retainers to retain the lower jaw at a height at which the respitory tract can be managed, the main body preferably includes a first main body that is connected to one of the jaw retainers and a second main body that is configured as a body independent of the first main body and connected to the other jaw retainer, and the pair of jaw retainers include adjusting means for adjusting an attaching position of the jaw retainers connected to the first and second main bodies with respect tooth sides of the lower jaw.
[0012] In this case, the main bodies connected to the respective jaw retainers are configured as independent bodies, and the user can thereby easily change the posture such as tossing and turning. Furthermore, since the attaching positions of the respective jaw retainers with respect to the lower jaw are adjusted according to the shape or the like of the lower jaw, even when, for example, the user returns to the supine posture after tossing and turning, it is possible to suppress deviations of the positions of contact of the jaw retainers with the lower jaw and retain the lower jaw at a height at which the respiratory tract can be managed appropriately.
[0013] A respiratory tract widening unit according tithe present invention is a respiratory tract widening unit including the above-described respiratory tract widening tool and a respiratory tract widening tool mat, wherein a head contacting section of the respiratory tract widening tool mat with which the head comes into contact in a supine posture is lower than a tool contacting section with which the main body of the respiratory tract widening tool comes into contact in the supine posture and the repertory tract widening tool mat is made up of a plurality of columnar bodies that are formed of a restorable elastic material and the columnar bodies vertically arranged in the head contacting section are lower than the columnar bodies vertically arranged in the tool contacting section.
[0014] According to this configuration, the head contacting section with which the head comes into contact in the supine posture is lower than the tool contacting section with which the main body comes into contact in the supine posture, and therefore the head is lower than the undersurface of the respiratory tract widening tool and the respiratory tract widening tool is relatively pushed up. That is, in the supine posture, in response to the sinking of the head downward, the respiratory tract widening tool relatively pushes up the lower jaw, and can thereby reliably suppress falling of the root of tongue and more reliably manage the respiratory tract.
[0015] Further according to this configuration, since the plurality of columnar bodies are made of a restorable elastic material, the region of the head contacting section is reliably distinguished from the region of the tool contacting section, it is possible to prevent the respiratory tract widening tool from sinking as the head sinks in the supine posture. Moreover, since the columnar body vertically arranged in the head contacting section is lower than the columnar body vertically arranged in the tool contacting section, the supine posture is set with the head and the respiratory tract widening tool aligned with the head contacting section and the tool contacting section respectively, the head naturally descends and the respiratory tract widening tool pushes up the lower jaw, and the respiratory tract can thereby be managed. Furthermore, when the posture is changed from the supine posture, the plurality of columnar bodies deform as the posture changes, and the user can thereby easily change the body position such as tossing and turning.
[0016] In the respiratory tract widening unit of the present invention, the elastic material may also be made of urethane resin.
[0017] Furthermore, in the respiratory tract widening unit, the respiratory tract widening tool mat is made up of a bag-shaped body filled with a gas, liquid or gel substance.
[0018] According to this configuration, when the head and respiratory tract widening tool come into contact with the respiratory tract widening tool mat, the head sinks more deeply than the respiratory tract widening tool due to the difference in weight, but the volume of the bag-shaped body itself does not change and the sinking of the respiratory tract widening tool is suppressed to an extent that the head sinks deeply. Therefore, the head naturally sinks in a supine posture and the respiratory tract widening tool pushes up the lower jaw, and therefore the respiratory tract can be managed.
[0019] According tithe present invention, it is possible to manage the respiratory tract in a supine posture and allow the user to easily change his/her posture during sleep.
BRIEF DESCRIPTION OF DRAWINGS
[0020] FIG. 1 is an outside perspective view schematically illustrating respiratory tract widening tool according to a first embodiment of the present invention, (a) is an outside perspective view seen from the front and (b) is an outside perspective view seen from thereof;
[0021] FIG. 2 is a schematic view illustrating a respiratory tract widening tool mat according to the present embodiment, (a) is a top view thereof, (b) is a side view seen from the long side and (c) is a side view seen from the short side;
[0022] FIG. 3 is a schematic view illustrating a user wearing the respiratory tract widening tool according to the present embodiment lying in a supine posture on a respiratory tract widening tool mat;
[0023] FIG. 4 is a schematic view illustrating a condition of the respiratory tract widening unit according to the present embodiment in a supine posture, (a) is a diagram illustrating the condition before the supine posture and (b) is a diagram illustrating the condition in the supine posture;
[0024] FIG. 5 is a schematic view illustrating respiratory tract widening tool according to a modification example; and
[0025] FIG. 6 is an outside perspective view schematically illustrating respiratory tract widening tool according to a second embodiment of the present invention, (a) is an outside perspective view seen from the front and (b) is an outside perspective view seen from thereof.
DETAILED DESCRIPTION
[0026] Hereinafter, a respiratory tract widening tool and a respiratory tract widening unit according to embodiments of the present invention will be described in detail with reference tithe accompanying drawings. The respiratory tract widening unit according to the present embodiment is intended to manage the respiratory tract of people in a supine posture and is comprised of respiratory tract widening tool and a respiratory tract widening tool mat placed beneath the respiratory tract widening tool.
First Embodiment
[0027] First, the respiratory tract widening tool will be described.
[0028] FIGS. 1( a ) and ( b ) are outside perspective views of the respiratory tract widening tool according to a first embodiment of the present invention. The respiratory tract widening tool 1 is used attached to an outer periphery of the neck so as to cover the neck from behind the neck, and is provided with a main body 2 that comes into contact with the posterior side of the neck (left side shown in FIG. 1( a )) when the tool is worn and a pair of jaw retainers 3 a and 3 b that extend from both ends of the main body 2 in the same direction (right side shown in FIG. 1( a )).
[0029] The pair of jaw retainers 3 a and 3 b are formed spaced apart by a distance equivalent tithe diameter of the neck and formed into a bent shape so as to come into close contact with the outer periphery of the neck along contours of the lower jaw when the tool is worn. The jaw retainers 3 a and 3 b are comprised of a restorable member that is deformable to an extent that it does not pose an impediment when the user tosses and turns. A pair of jaw contact portions 4 a and 4 b are formed into a shape complementary to the bent shape of the lower jaw in the respective jaw retainers 3 a and 3 b, and the respective jaw contact portions 4 a and 4 b come into contact with both sides of the lower jaw when the tool is worn. That is, regions of the jaw retainers 3 a and 3 b at their roots in the main body 2 are thick and regions corresponding to the jaw contact portions 4 a and 4 b contacting the lower jaw are made to be one step lower so as to have a shape that follows the bent shapes of the lower jaw. The one-step lower regions of the jaw contact portions 4 a and 4 b are preferably formed with roundness to allow the user to change the orientation of the body such as tossing and turning without imposing a burden on the lower jaw even when the posture is changed from a supine posture (face-up position) to a lateral position. As will be described later, in the supine posture, the jaw contact portions 4 a and 4 b come into contact with the lower jaw, thereby cause forces received from the main body 2 to directly and reliably act on the lower jaw so as to retain the lower jaw at a height (angle) at which the respiratory tract can be managed.
[0030] As shown in FIG. 1( a ), the jaw retainers 3 a and 3 b have built-in support members 5 a and 5 b that support the lower jaws as to push up the lower jaw from below in some areas that come into contact with the lower jaw when the tool is worn. The upper sides of the support members 5 a and 5 b constitute the jaw contact portions 4 a and 4 b. A material having predetermined strength that will not be deformed considerably by the lower jaw is selected for the support members 5 a and 5 b (e.g., polyethylene (PE), high density polyethylene (HDPE), medium density polyethylene (MDPE), low density polyethylene (LDPE), polypropylene (PP), polyvinyl chloride (PVC), polyvinylidene chloride, polystyrene (PS), polyvinyl acetate (PVAc), ABSresin, ASresin, acrylic resin (PMM)). On the other hand, a material having excellent air-permeability, a pleasant texture and certain flexibility is preferably selected for the jaw retainers 3 a and 3 b in view that the surface thereof comes into contact with the human body (e.g., polyethylene (PE), high density polyethylene (HDPE), medium density polyethylene (MDPE), low density polyethylene (LDPE), polypropylene (PP), polyvinyl chloride (PVC), polyvinylidene chloride, polystyrene(PS), polyvinyl acetate (PVAc), ABSresin, ASresin, acrylic resin (PMM)). In the present embodiment, the main body 2 and jaw retainers 3 a and 3 b are formed as a single-piece structure, but these components may also be configured as separate pieces.
[0031] A receiving face 2 a which is a flat surface substantially perpendicular to the extending directions of the jaw retainers 3 a and 3 b is formed on the rear of the main body 2 (outer surface opposite to the contact surface that contacts the posterior side of the neck). A tabular body 6 protruding from the rear of the main body 2 on both sides is formed as a single piece and the receiving face 2 a is formed on the outer surface of the tabular body 6 . The main body 2 including the tabular body 6 needs to be rigid enough to receive stress from the underlay surface side such as a resting face or respiratory tract widening tool mat and at the same time resilient (flexible) enough to deform to an extent that it does not pose an impediment when the user tosses and turns, and is preferably formed of an elastic material such as urethane resin, polyethylene (PE), high-density polyethylene (HDPE), medium density polyethylene (MDPE), low density polyethylene (LDPE), polypropylene (PP), polyvinyl chloride (PVC), polyvinylidene chloride, polystyrene (PS), polyvinyl acetate (PVAc), ABSresin, ASresin, acrylic resin (PMM). This receiving face 2 a is placed face down during a supine posture and acts as a surface that receives an upward counterforce from the underlay surface side. That is, in the supine posture, the receiving face 2 a presses, for example, the top surface of the respiratory tract widening tool mat which becomes the underlay surface, and thereby receives a counterforce from the top surface side. To efficiently receive the counterforce from the underlay surface side, it is preferable that the area of the receiving face 2 a be sufficiently large and stress act on the pair of jaw retainers 3 a and 3 b uniformly. Therefore, by adopting the flat receiving face 2 a to secure a sufficient area, both sides of the lower jaw have substantially the same height without one of the lower jaw being inclined in the supine posture and the lower jaw is retained at a height (angle) at which the respiratory tract is managed. On the other hand, when the posture is changed from the supine posture to a lateral position or prone posture, the main body 2 deforms in response to the change in posture to accept a free posture change. Furthermore, when the posture is returned to the supine posture, the main body 2 receives an upward external force as described above, applies this external force to the respective jaw retainers 3 a and 3 b, retains the lower jaw at a height at which the respiratory tract can be managed and can thereby automatically manage the respiratory tract.
[0032] Furthermore, as shown in FIG. 1( b ), a protruding section 7 is provided at a bottom end of the receiving face 2 a on the rear of the main body 2 . The protruding section 7 extends in a direction opposite to the extending direction of the jaw retainers 3 a and 3 b and in the downward direction in the supine posture. The protruding section 7 is formed in a substantially semi-circular shape. A thickness T of the protruding section 7 is set to be greater than a width W of a groove formed in the respiratory tract widening tool mat which will be described later. This protruding section 7 comes into contact with the respiratory tract widening tool matin the supine posture and applies stress in the direction in which the lower jaws pushed up to the main body 2 . That is, the protruding section 7 that comes into contact with the respiratory tract widening tool mat acts, as a fulcrum, so as to incline the direction in which the lower jaw is pushed up from the directly upward direction to the parietal region side (vertex of the head seen from the distal end of the jaw) and stretch the bent portion of the respiratory tract in a substantially rectilinear shape.
[0033] Next, the respiratory tract widening tool mat will be described.
[0034] FIGS. 2( a ) to ( c ) are a top view, side view and side view of the respiratory tract widening tool mat respectively. A respiratory tract widening tool mat 10 is used underlaid beneath the head (including the vicinity of the neck wearing the respiratory tract widening tool 1 ) in a supine posture.
[0035] As shown in FIG. 2( a ),the respiratory tract widening tool mat 10 is configured such that a plurality of columnar bodies 12 are vertically arranged in a grid-like array on the top surface of a rectangular substrate 11 . The plurality of columnar bodies 12 are made of an elastic material having resilience whereby each columnar body 12 is deformed (depressed) when an external force is applied, whereas each columnar body 12 is returned to the original shape when the external force is removed. A low-resilience sponge material such as urethane resin is suitable as the resilient elastic material. This allows the columnar bodies 12 in a region with which the head comes into contact in the supine posture (hereinafter referred to as “head contacting section”) 13 and the columnar bodies 12 in a region with which the receiving face 2 a of the respiratory tract widening tool 1 comes into contact in the supine posture (hereinafter referred to as “tool contacting section”) 14 to separate from each other and support the head and receiving face 2 a independently of each other. Therefore, in the supine posture, when the head and the receiving face 2 a of the respiratory tract widening tool 1 come into contact with the respiratory tract widening tool mat 10 , the columnar bodies 12 with which the head comes into contact by the weight of the head itself sink deeper than the columnar bodies 12 with which the receiving face 2 a comes into contact. This causes the region of the head contacting section 13 to be reliably distinguished from the region of the tool contacting section 14 , and the sinking of the respiratory tract widening tool 1 accompanying the sinking of the head in the supine posture is thereby suppressed and the respiratory tract widening tool 1 is supported in a stable state. Therefore, it is possible to reliably transmit an upward counterforce from the top surface of the respiratory tract widening tool mat 10 to the receiving face 2 a and retain the lower jaw at a height that allows the jaw retainers 3 a and 3 b to manage the respiratory tract. On the other hand, when the posture is changed from the supine posture to, for example, a lateral position, the columnar bodies 12 with which the main body 2 and jaw retainers 3 a and 3 b of the respiratory tract widening tool 1 come into contact deform (depressed) according tithe change in posture, and the user can thereby freely and easily change the body position such as tossing and turning without the change in posture being obstructed. Furthermore, the width W of the grid-like arrayed columnar bodies 12 is formed to be smaller than the thickness T of the protruding section 7 so that the protruding section 7 neither comes into contact with the columnar bodies 12 in the supine posture nor enters the groove.
[0036] In the present embodiment, the respiratory tract widening tool mat 10 is formed of the columnar bodies 12 , but the present invention is not limited to this, and the respiratory tract widening tool mat 10 may also be formed of, for example, uni-directionally consecutive convex bodies or flat elastic bodies in which no grooves are formed. Furthermore, the respiratory tract widening tool mat 10 may also be constructed of a bag-shaped body filled with a gas, liquid or gel substance. In this case, when the head and respiratory tract widening tool 1 (receiving face 2 a ) come into contact with the respiratory tract widening tool mat 10 , the head sinks deeper than the respiratory tract widening tool 1 due to the difference between respective weights, but the volume of the bag-shaped body itself does not change, and therefore the sinking of the respiratory tract widening tool 1 (receiving face 2 a ) is suppressed to an extent that the head sinks deeper. Therefore, in the supine posture, the head naturally descends and the respiratory tract widening tool 1 pushes up the lower jaw that receives an upward counterforce from the bag-shaped body and it is thereby possible to manage the respiratory tract.
[0037] As shown in FIG. 2( b ), in the respiratory tract widening tool mat 10 , the head contacting section 13 is formed in a concave shape in which the surface of contact with the head is caved downward. That is, the head contacting section 13 is formed into a shape substantially complementary to the occipital region. On the other hand, the tool contacting section 14 has no caves like the head contacting section 13 and is kept at a fixed height. Thus, the respiratory tract widening tool mat 10 is configured such that the head contacting section 13 is lower than the tool contacting section 14 in the supine posture. To be more specific, the height of the columnar bodies 12 vertically arranged in the head contacting section 13 are set to be lower than the columnar bodies vertically arranged in the tool contacting section 14 . Since the columnar bodies 12 of the head contacting section 13 and those of the tool contacting section 14 are independent of each other, when the user lies in a supine posture over the head contacting section 13 and the tool contacting section 14 , the respiratory tract widening tool 1 which has been pushed relatively upward pushes up the lower jaw as the head naturally descends, and it is thereby possible to suppress the sinking of the root of tongue and manage the respiratory tract.
[0038] Next, operations and effects when the user wearing the respiratory tract widening tool 1 lies in the supine posture on the respiratory tract widening tool mat 10 will be described using FIG. 3 and FIGS. 4( a ) and ( b ). FIG. 3 is a schematic view when the user wearing the respiratory tract widening tool 1 lies in a supine posture on the respiratory tract widening tool mat 10 , seen from the direction opposite to the parietal region. Furthermore, FIG. 4( a ) shows a condition before the user lies in the supine posture and FIG. 4( b ) shows a condition in which the user is lying in the supine posture.
[0039] First, as shown in FIG. 3 and FIG. 4( a ), the open ends of the jaw retainers 3 a and 3 b of the respiratory tract widening tool 1 are widened to attach the respiratory tract widening tool 1 from the posterior side of the neck, and the jaw contact portions 4 a and 4 b are aligned with the positions at which they come into contact with the lower jaw. Then, the user lies in the supine posture so that the occipital region rests on the head contacting section 13 of the respiratory tract widening tool mat 10 placed on a resting surface or a mattress or the like. At this time, the receiving face 2 a of the main body 2 of the respiratory tract widening tool 1 comes into contact with the tool contacting section 14 of the respiratory tract widening tool mat 10 which becomes the underlay surface. As shown in FIG. 4( b ), when the user sleeps on the respiratory tract widening tool mat 10 in a condition in which the receiving face 2 a is aligned with the tool contacting section 14 , the occipital region naturally descends (direction indicated by an arrow A), while the receiving face 2 a receives a counterforce from the surface of contact with the tool contacting section 14 . The greater the area of the receiving face 2 a, the greater is the upward counterforce received from the respiratory tract widening tool mat 10 , and the sinking of the main body 2 of the respiratory tract widening tool 1 is suppressed.
[0040] Furthermore, the thicker the main body 2 , the greater is the upward force that the main body 2 of the respiratory tract widening tool 1 received from the respiratory tract widening tool mat 10 . Thus, the main body 2 of the respiratory tract widening tool 1 is prevented from sinking, the main body 2 corresponding tithe posterior side of the neck is pushed up (direction shown by a narrow B) by the force received from the tool contacting section 14 of the respiratory tract widening tool mat 10 with the jaw contact portions 4 a and 4 b being in contact with the lower jaw, the support members 5 a and 5 b push up the lower jaw from below retaining the lower jaw at a height at which the respiratory tract can be managed. At this time, the protruding section 7 of the respiratory tract widening tool 1 comes into contact with the columnar bodies 12 of the respiratory tract widening tool unit 10 so as to press the columnar bodies 12 , and the jaw retainers 3 a and 3 b (support members 5 a and 5 b ) are thereby retained while pushing up the lower jaw in the direction toward the parietal regionside (direction shown by an arrow C) via the main body 2 . Thus, it is possible to more reliably prevent the sinking of the root of tongue and manage the respiratory tract.
[0041] On the other hand, when the posture is changed from the supine posture shown in FIG. 4( b ) to a lateral position or the like, the main body 2 and jaw retainers 3 a and 3 b deform in response to the change in posture. This allows the user to freely change the posture from the face-up position such as tossing and turning. When the posture is changed from the face-up position to lateral position, the root of tongue does not sink into the throat, and therefore the respiratory tract is managed without being closed, thus eliminating the necessity for retaining the lower jaw at a height at which the respiratory tract can be managed. When the face-up position is restored from the lateral position, the main body 2 and jaw retainers 3 a and 3 b deform in response to the change in posture and the jaw retainers 3 a and 3 b (support members 5 a and 5 b ) receive stress in the directions shown by the arrows B and C from the respiratory tract widening tool mat 10 via the main body 2 again. This causes the jaw contact portions 4 a and 4 b to support the lower jaw from below to a height at which the respiratory tract can be managed, thus enabling the respiratory tract to be automatically managed.
[0042] By the way, sleep can be classified into REM sleep which is such a shallow sleep state as to have a dream and non-REM sleep which is such a deep sleep state as to have no dream. During sleep of a healthy person, REM sleep and non-REM sleep alternate in cycles of approximately 90 minutes. Sleep apnea or snoring is likely to occur in the case of non-REM sleep and is caused by the front wall of the respiratory tract of the throat or the root of tongue sinking and thereby narrowing or closing the respiratory tract. When sleep apnea or the like occurs, the sleep state is changed from non-REM sleep to REM sleep, and one can no longer obtain deep sleep no matter how much one sleeps, unable to obtain deep sleep or rest one's brain. Furthermore, during non-REM sleep, daily required human growth hormone is secreted from the anterior pituitary in the brain. This human growth hormone is important forth growth and maintenance of muscles and bones or to induce the repair of the stomach and intestines or skin, and in the case where non-REM sleep lasts shorter than a predetermined period, the hormone is not sufficiently secreted and muscle or the like cannot recover from fatigue either.
[0043] According tithe present embodiment, the main body 2 of the respiratory tract widening tool 1 receives an upward force in the supine posture, the pair of jaw retainers 3 a and 3 b extending from the main body 2 come into contact with the opposite sides of the lower jaw and retain the lower jaw at a height at which the respiratory tract can be managed to thereby prevent the root of tongue contacting the lower jaw (bone) from falling into the throat side. That is, in the supine posture, the upward force received by the main body 2 is made to act on the jaw retainers 3 a and 3 b (support members 5 a and 5 b ) to retain the height of the lower jaw so that the height of the sub maxilla is not lowered due to relaxation or the like of the neck muscle during sleep (deep sleep). On the other hand, the main body 2 and the jaw retainers 3 a and 3 b are made of a restorable member and the respiratory tract widening tool 1 has a structure independent of a pillow or the like, and therefore when the posture is changed from the supine posture to a lateral position or prone posture, the main body 2 and the jaw retainers 3 a and 3 b freely deform in conformity with the changed posture. This prevents the root of tongue contacting the sub maxilla from falling into the throat side, and can thereby manage the respiratory tract and allows the user to freely change the posture from the supine posture such as tossing and turning. Furthermore, when the supine posture is restored, the main body 2 receives the upward force and the jaw retainers 3 a and 3 b (support members 5 a and 5 b ) retain the lower jaw at a height at which the respiratory tract can be managed, and it is thereby possible to automatically manage the respiratory tract without disturbing comfortable sleeping. Particularly, the respiratory tract widening unit according tithe present embodiment doubtfully has a great effect in enabling smooth breathing of sleep apnea patients and keeps the aforementioned regular sleep pattern, and thereby has a noticeable effect from the standpoint of health maintenance as well.
[0044] The above embodiment makes the main body 2 extend on both sides to secure a sufficient area of the receiving face 2 a, but the shape of the main body 2 is not limited to this. For example, as shown in FIG. 5 , protruding sections 21 a and 21 b that protrude from the rear of the main body 2 toward both sides may have a small size and have an accurately bent shape instead of a completely flat shape. Furthermore, the protruding section formed at the bottom of the receiving face 2 a may also be a falcate protruding section 22 along the rear of the accurately bent main body 2 as shown in FIG. 5 . Thus, even when the rear of the main body 2 is not completely flat, the main body 2 can receive sufficiently strong stress from the underlay surface side in the supine position, and push up the lower jaw to a height that allows the jaw retainers 3 a and 3 b to manage the respiratory tract.
[0045] As shown in FIG. 5 , when the falcate protruding section 22 is provided along the rear of the accurately bent main body 2 , even if the respiratory tract widening tool mat 10 is not used, the protruding section 22 that directly comes into contact with the resting surface in the supine posture applies the force received from the resting surface to the jaw retainers 3 a and 3 b, and can thereby push up and retain the lower jaw.
[0046] Furthermore, adjusting means such as a hook, magic tape (registered trademark) may be provided on the open end side of the pair of jaw retainers 3 a and 3 b. This makes it possible to adjust the mounting state of the respiratory tract widening tool 1 so as to reliably manage the respiratory tract in the supine posture according to the size and shape of the human face and lower jaw.
[0047] Furthermore, the above embodiment forms the head contacting section 13 of the respiratory tract widening tool mat 10 so as to be lower than the tool contacting section 14 , but the present invention is not limited to this, and the head contacting section 13 and the tool contacting section 14 may be configured to have the same height. That is, the present invention is applicable even when the height of the columnar bodies 12 vertically arranged in the head contacting section 13 is equal to the height of the columnar bodies 12 vertically arranged in the tool contacting section 14 . In this case, as opposed to the case where the occipital region sinks into the head contacting section 13 by the self-weight in the supine posture, the receiving face 2 a of the main body 2 comes into contact with the contact surface of the tool contacting section 14 to prevent the respiratory tract widening tool 1 from sinking together along with the sinking of the head and causes the counterforce received from the contact surface to act on the main body 2 .
Second Embodiment
[0048] Next, a second embodiment of the present invention will be described. A respiratory tract widening tool according to the second embodiment of the present inventions different from the respiratory tract widening tool 1 according to the aforementioned first embodiment only in the configuration of the main body and jaw retainers. Therefore, the present embodiment will only describe differences in particular, and identical components will be assigned the same reference numerals and overlapping explanations will be omitted.
[0049] FIGS. 6( a ) and ( b ) are outside perspective views of the respiratory tract widening tool according to the present embodiment. The respiratory tract widening tool 31 shown in FIG. 6 is provided withal first main body 32 a and a second main body 32 b configured as separate bodies, and jaw retainers 33 a and 33 b configured as separate bodies and connected to the main bodies 32 a and 32 b respectively.
[0050] The first main body 32 a is integrally formed as a single piece with a tabular body 36 a that protrudes on both sides and one jaw retainer 33 a extends from the front of the main body 32 a. Similarly, the second main body 32 b is integrally formed as a single piece with a tabular body 36 b that protrudes on both sides and the other jaw retainer 33 b extends from the front of the main body 32 b. Receiving faces 37 a and 37 b which form flat surfaces substantially perpendicular to the extending direction of the jaw retainers 33 a and 33 b are formed on the rear of the main bodies 32 a and 32 b respectively and protruding sections 38 a and 38 b are provided at the bottom end of the receiving faces 37 a and 37 b respectively. It is preferable to provide the protruding sections 38 a and 38 b since the protruding sections 38 a and 38 b act to cause the protruding direction of the lower jaw to incline from the directly upward direction toward the parietal region side so as to stretch the bent portion of the respiratory tract substantially rectilinearly. However, even in a configuration without the protruding sections 38 a and 38 b, it is also possible to cause external forces received by the receiving faces 37 a and 37 b in the supine posture to act on the respective jaw retainers 33 a and 33 b to retain the lower jaw at a height at which the respiratory tract can be managed.
[0051] Furthermore, adjusting means 39 for adjusting wearing positions of both sides of the lower jaw of the jaw retainers 33 a and 33 b is provided between the pair of jaw retainers 33 a and 33 b. The adjusting means 39 is made up of a hinge (or hook) 40 provided so as to couple distal end sides of the jaw retainers 33 a and 33 b, and an adjusting belt 41 provided so as to bridge between the opposed rear ends of the jaw retainers 33 a and 33 b. When the respiratory tract widening tool 31 is worn, the jaw retainers 33 a and 33 b are coupled together by the hinge 40 , the respiratory tract widening tool 31 is positioned with the lower jaw contact portions 4 a and 4 b of the respective jaw retainers 33 a and 33 b placed in close contact with the outer periphery of the neck along the contours of both sides of the lower jaw in such a way that the receiving faces 37 a and 37 b substantially uniformly receive an external force in the supine posture, and fixed on the occipital region side using the adjusting belt 41 . Thus, even when the posture is changed from the supine posture and restored to the supine posture again, it is possible to cause the upward force received by the receiving faces 37 a and 37 b of the main bodies 32 a and 32 b to act on the jaw retainers 33 a and 33 b appropriately and retain the lower jaw at a height at which the respiratory tract can be managed.
[0052] Thus, according to the present embodiment, since the main bodies 37 a and 37 b connected to the jaw retainers 33 a and 33 b are configured as separate bodies, in addition to the effects of the above-described first embodiment, the present embodiment allows the user to change the posture such as tossing and turning more easily. Furthermore, the wearing positions of the jaw retainers 33 a and 33 b with respect to the lower jaw are adjusted according to the shape or the like of the lower jaw, and therefore even when the posture is restored to the supine posture after tossing and turning, for example, it is possible to suppress deviation of the contact position of the jaw retainers 33 a and 33 b with respect to the lower jaw and appropriately retain the lower jaw at a height at which the respiratory tract can be managed.
[0053] The present invention is not limited to the above-described embodiments, but can be implemented modified in various ways. The size and shape or the like of the above-described embodiments are not limited to those illustrated in the attached drawings, but can be modified as appropriate within a range in which the effects of the present invention can be exerted. Other aspects can be implemented modified as appropriate without departing from the scope of objects of the present invention.
[0054] The present invention is useful for treatment of sleep apnea in the medical field and health maintenance in daily life. | A respiratory tract widening tool capable of reliably managing a respiratory tract in a supine posture and freely changing the posture, and a respiratory tract widening unit provided therewith are provided. | 0 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to vehicle differentials and, in particular, to the location and support of pinion bearings within a differential.
2. Disclosure of Related Art
Differentials are used in vehicles to allow wheels mounted on either side of a vehicle axle to rotate at different speeds. A conventional differential includes a series of gears disposed within a differential housing that transmit torque from a power input shaft to axle half shafts supporting the wheels. One of these gears is a pinion gear. The differential housing defines an opening through which a pinion shaft extends to support the pinion gear. Bearings are disposed within the opening to allow the pinion shaft to rotate relative to the housing. An input yoke is coupled to the pinion shaft and to the power input shaft to transmit torque from the power input shaft to the pinion shaft.
Conventional differentials have several problems. First, the pinion shaft and input yoke extend outwardly from the differential housing for a relatively large distance (“pinion standout”). As a result, the differential requires additional space and the mounting of vehicle suspension components and other vehicle components is made for difficult. Second, installation and proper placement of the pinion bearings often require the use of spacers or shims during assembly thereby increasing assembly time.
There is thus a need for a differential for a vehicle that will minimize or eliminate one or more of the above-mentioned deficiencies.
SUMMARY OF THE INVENTION
The present invention provides a differential for a vehicle.
A differential in accordance with the present invention includes a differential housing that defines a first opening. The differential also includes a pinion shaft disposed within the first opening and configured for rotation about an axis extending through the first opening. The differential further includes an input yoke disposed about a least a portion of the pinion shaft. Finally, the differential includes a first bearing set disposed about the input yoke. The differential may also include a second bearing set axially spaced from the first bearing set and also disposed about the input yoke.
A differential in accordance with the present invention has several advantages as compared to conventional vehicle differentials. The location of the bearing set(s) on the input yoke shortens the overall length of the pinion shaft while still allowing sufficient engagement between the pinion shaft and input yoke. As a result, pinion standout is reduced. The location of the bearing sets further allows the use of a preassembled bearing pack comprised of the bearing sets and a carrier for the bearing sets for proper positioning of the bearing sets within the differential housing opening. As a result, spacers and/or shims are not required and differential assembly time may be significantly reduced.
These and other features and objects of this invention will become apparent to one skilled in the art from the following detailed description and the accompanying drawings illustrating features of this invention by way of example.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a sectional view of a differential in accordance with the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings wherein like reference numerals are used to identify identical components in the various views, FIG. 1 illustrates a differential 10 in accordance with the present invention. Differential 10 is provided to allow wheels (not shown) disposed on either side of the vehicle, and supported on axle half shafts (not shown) extending from differential 10 , to rotate at different speeds. Differential 10 is particularly adapted for use in a heavy truck. It should be understood, however, that the present invention is not limited to use in heavy trucks and may be used in a wide variety of vehicles. Differential 10 may include a housing 12 , a differential gear assembly 14 , a pinion shaft 16 , an input yoke 18 , a carrier 20 , and bearing sets 22 , 24 .
Housing 12 provides structural support for the other components of differential 10 . Housing 12 also protects the other components of differential 10 from foreign objects and elements. Housing 12 may be made from conventional metals and metal alloys such as steel and may include multiple members 26 , 28 , 30 that are sized relative to components of differential 10 and coupled together using conventional fasteners (not shown). Member 26 of housing may define an opening 34 at a forward end. Opening 34 may be centered about an axis 36 extending through pinion shaft 16 .
Differential gear assembly 14 is provided to allow the wheels supported on either side of the vehicle to rotate at different speeds. Assembly 14 may include a pinion gear 38 , a ring gear 40 , and a conventional bevel gear set (not shown) disposed within a differential carrier (not shown).
Pinion gear 38 is provided to transfer torque from pinion shaft 16 to ring gear 40 . Pinion gear 38 may be made from conventional metals and metal alloys and may comprise a hypoid gear. Gear 38 rotates about axis 36 . Gear 38 is disposed about shaft 165 and may be integral therewith or mounted thereto using a conventional spline connection or in other ways customary in the art. Gear 38 may also include a pilot portion 42 extending rearwardly that is supported for rotation by bearings 44 disposed in a pilot web 46 of housing member 26 .
Ring gear 40 is provided to transfer torque from pinion gear 38 to the bevel gear set and is conventional in the art. Ring gear 40 may also be made from conventional metals and metal alloys and may also comprise a hypoid gear. Gear 40 is affixed to the carrier or may be integral therewith.
The bevel gear set (not shown) is provided to transfer torque from ring gear 40 to the axle half shafts supporting the vehicle wheels. The bevel gear set is conventional in the art.
Pinion shaft 16 is provided to transmit power from a power input shaft (not shown) to pinion gear 38 and is conventional in the art. Pinion shaft 16 may include a first portion 48 having a first diameter, a second portion 50 having a second diameter greater than the first diameter and a tapered portion 52 joining portions 48 , 50 . Pinion shaft 16 may include a plurality of splines 54 extending axially along portion 48 from a forward end of shaft 16 to tapered portion 52 . Pinion shaft 16 may also include a threaded shank 56 extending from a forward end of shaft 16 and integral therewith.
Input yoke 18 is provided to transmit power from a power input shaft (not shown) to pinion shaft 16 . Yoke 18 may be coupled to the power input shaft through a conventional universal joint (not shown) and is configured for rotation about axis 36 . Yoke 18 includes a generally cylindrical body 58 with a circular flange 60 radiating outwardly from body 58 at a forward end of body 58 . Body 58 defines a bore 62 sized to receive pinion shaft 16 and extends axially along shaft 16 to the rearward end of shaft 16 such that one axial end of yoke 18 is proximate pinion gear 38 . Yoke 18 may include a plurality of splines 64 configured for engagement with splines 54 of pinion shaft 16 . In accordance with the present invention, splines 64 may be disposed radially inwardly of bearing set 22 . Yoke 18 may be retained on shaft 16 by a nut 66 and a washer (not shown) disposed about stud 56 of shaft 16 .
Carrier 20 is provided to position and support bearing sets 22 , 24 within opening 34 of housing 12 and may be made from conventional metals or metal alloys. Carrier 20 is generally cylindrical in shape and is sized to be received within opening 34 of housing 12 . Carrier 20 includes a radially outwardly extending flange 68 at a forward end that abuts a shoulder 70 formed in housing 12 upon installation of carrier 20 within opening 34 . Carrier 20 may be held within opening 34 by a cap 72 that is fastened to member 26 of housing 12 using conventional fasteners (not shown). Carrier 20 is disposed about axis 36 and defines a bore 74 configured to receive bearing sets 22 , 24 . A radially inwardly extending flange 76 within bore 74 defines a pair of shoulders 78 , 80 and helps enable proper positioning of bearing sets 22 , 24 without the need for spacers or shims.
Bearings sets 22 , 24 are provided to allow rotation of input yoke 18 and pinion shaft 16 relative to carrier 20 and housing 12 . Bearing sets 22 , 24 are conventional in the art and may comprise tapered roller bearings. Each bearing set 22 , 24 includes a cone 82 , 84 , respectively, defining an inner bearing race and a cup 86 , 88 , respectively, defining an outer bearing race. Cone 82 of bearing set 22 is in engagement with a shoulder 90 defined in input yoke 18 and cup 86 of bearing set 22 is in engagement with shoulder 78 of carrier 20 . Cone 84 of bearing set 24 is in engagement with pinion gear 38 while cup 88 of bearing set 24 is in engagement with shoulder 80 of carrier 20 . In accordance with the present invention, bearing sets 22 , 24 are disposed about input yoke 18 between yoke 18 and carrier 20 . In particular, cones 82 , 84 are supported on body 58 of yoke 18 . The relative location of bearing sets 22 , 24 and input yoke 18 result in a significant improvement as compared to conventional differentials. In particular, yoke 18 is moved forward in differential 10 thereby enabling a reduction in pinion standout, but still allowing yoke 18 to maintain proper engagement with pinion shaft 16 because the lengths of splines 54 , 64 are not reduced. Further, bearing capacity remains the same in the inventive differential.
While the invention has been particularly shown and described with reference to the preferred embodiments thereof, it is well understood by those skilled in the art that various changes and modifications can be made in the invention without departing from the spirit and scope of the invention. | A differential having pinion bearings supported on the input yoke is provided. The differential includes a housing having an opening through which a pinion shaft extends. The input yoke is disposed about a portion of the pinion shaft and one or both pinion bearing sets are then disposed about the input yoke. This configuration reduces pinion standout and allows for installation of a pre-assembled bearing pack (i.e., without spacers or shims), but does not reduce the length of the splines on the input yoke or bearing capacity. | 5 |
FIELD OF THE INVENTION
The present invention relates to improvements in window opening control devices, and more particularly to a device that is capable of limiting the travel of a casement window.
BACKGROUND OF THE INVENTION
One safety concern for children, with respect to the windows that may be installed into residential homes and other buildings, are its features that may serve to prevent accidental egress and serious injury from a fall. One preventative feature is the height that the windows are installed above the floor, which prevents toddlers from accidentally falling out, and inhibits small children from creatively seeking to observe the outside view from the sill of the window, which could result in an accidental fall therefrom.
Opening control devices for windows (WOCDs), which serve to releasably limit the travel that a window may undergo to a relatively small amount, which may be roughly four inches, are another feature that has been employed on sliding sash windows for that reason. They have also been utilized thereon to prevent unauthorized entry into the dwelling from the outside by an intruder. However, preventative measures in the form of WOCDs have not been pursued as vigorously for casement windows, which typically are hingedly connected in some fashion to the master window frame.
As building codes have sought to regulate the construction industry to improve child safety through the use of such devices (see e.g., ASTM F2090-10: “Standard Specification for Window Fall Prevention Devices with Emergency Escape (Egress) Release Mechanisms”), tradeoffs have been proposed to reduce the height restrictions for window installations where such devices are utilized. But such lessening of these window height requirements only serves to place greater importance on the integrity of the WOCDs, particularly their ability to automatically reset themselves, after having been manually released to open the casement window beyond its restricted range of movement.
The window opening control device of the present invention is uniquely adapted to not only limit the range of travel of the casement window to prevent accidental falls therefrom, and to automatically reset itself, but to also avoid the necessity of having to remove the screen from the window in order for the device to function properly.
OBJECTS OF THE INVENTION
It is an object of the invention to provide a window opening control device that may releasably limit the travel of a casement window to an amount preventing accidental egress therefrom.
It is another object of the invention to provide a window opening control device for a casement window that is easily released to permit full travel of the casement window when desired.
It is a further object of the invention to provide a safety switch for a window opening control device for a casement window that prevents tampering by young children who may seek to impermissibly operate the safety device.
It is another object of the invention to provide a window opening control device for a casement window that automatically resets the device, after the window has been moved back to the closed position.
Further objects and advantages of the invention will become apparent from the following description and claims, and from the accompanying drawings.
SUMMARY OF THE INVENTION
A device may limit opening of a sash window that is hingedly coupled to a master window frame, and may include: a bracket attached to the sash; a first arm having a first end pivotally coupled to the bracket; a second arm having a first end pivotally coupled to the second end of the first arm; a means for biasing the second arm into a retracted position; and a release assembly. The release assembly may be secured within the master window frame and may include a hook member that is pivotable between a first position and a second position.
With the hook member occupying the first position, the hook portion thereon may be releasably received in an opening in the second end of the second arm, when the first and second arms are in the retracted position, and the sash is closed and received by the master window frame.
The first arm may normally occupy its retracted position, with respect to the bracket that is fixedly secured to the sash, by rotating downward into a vertically oriented position, and may be limited to that position through the prevention of any over-travel by a stop protruding from the bracket. The second arm may be configured to normally occupy its retracted position, with respect to the vertically oriented first arm and the bracket, by being biased against gravity to rotate upwardly to be positioned, and travel limited by a stop on the first arm, to occupy a somewhat vertical position, being at a small acute angle with respect to the first arm.
Once the hook portion of the hook member has been releasably received within the opening in the second end of the second arm, as described above, the sash may be opened, and the amount that it may be opened will be travel-limited according to the length of the first and second arms. The sash of the casement window being travel limited in this manner will prevent a small child from accidentally falling through the gap between the sash and the master window frame. When the user desires to open the window even further, the second arm may be disengaged from the hook of the release assembly, by rotating the hook to be in the second position.
The hook may be configured to extend from a graspable switch member, in order for a user's hand to more easily cause its pivotal movement between the first and second positions. The hook and switch member may be installed directly into a master window frame that is particularly configured to receive its envelope and permit pivotal movement therein, or it may instead be received within a base member that itself is adapted to be received within a simple opening in the master window frame and secured thereat.
The combination of the switch member and base member may serve to enable additional functionality. The switch member may be configured to receive a spring biased safety button therein, which may be slidable between a protruding position and a depressed position. The safety button may be configured to inhibit pivoting of the switch member and hook combination from its first position, when the button occupies its spring biased outwardly disposed position. When the button is depressed, pivoting of the switch member is no longer inhibited, and it may be pivoted into the second position to release the second arm from the hook member. The helical spring may also have its ends adapted to provide torsional biasing of the switch member relative to the base member, so that when the user releases their grasp of the switch member, it may be biased so that the combination switch member and hook member occupy the first position, and may readily accommodate engagement with the catch assembly.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a perspective view of the window opening control device of the present invention, installed upon a casement window master frame and its sash window, and with the device being used to releasably secure the window sash to prevent further travel of the opened window beyond the safe limit.
FIG. 2 illustrates the window opening control device and casement window of FIG. 1 , but with the device having been released to permit further travel of the opened window sash.
FIG. 2A is an enlarged detail view of the release assembly on the window frame and the catch assembly on the sash, as seen in perspective view of FIG. 1 .
FIG. 2B is an enlarged detail view of the bracket of the catch assembly of FIG. 1 , showing the possible use of backing plates to accommodate installation on a sash with a different profile.
FIG. 2C is a side view of the release assembly and a portion of the catch assembly, as installed on the casement window of FIG. 1 .
FIG. 2D is a front view of the release assembly protruding through the master frame of the casement window of FIG. 2C .
FIG. 2E is a top view of the release assembly of FIG. 2D , shown by itself.
FIG. 2F is a perspective view of the release assembly of FIG. 2E , but shown with the switch member cut away.
FIG. 2G is a bottom perspective view of the switch member.
FIG. 2H is a perspective view of the assembled hook member, the turning switch, and the safety button of the present invention.
FIG. 3 illustrates the catch assembly and the release assembly of the window opening control device of FIG. 2 , with the casement window omitted from the view, and with the catch assembly releasably secured to the release assembly, the arms of the catch assembly being in the retracted position, and with the sash having been closed with respect to the master frame.
FIG. 4 illustrates the catch assembly and the release assembly of the window opening control device of FIG. 3 , but with the arms of the catch assembly shown extended, for when the sash is opened with respect to the master frame, and thereby travel limited.
FIG. 4A illustrates a reverse perspective view of the release assembly of FIG. 4 , where the safety button has not been depressed.
FIG. 4B is an enlarged detail view of the release assembly retaining the second arm of the catch assembly, as seen in FIG. 4 .
FIG. 5 illustrates the catch assembly and the release assembly of the window opening control device of FIG. 4 , but with the safety button having been depressed, and the switch member pivoted to release the hook of the release assembly from the opening of the second arm of the catch assembly.
FIG. 5A illustrates a reverse perspective view of the release assembly of FIG. 5 , where the safety button has been depressed, and the switch member pivoted.
FIG. 5B is an enlarged detail view of the release assembly shown in FIG. 5 .
FIG. 6 illustrates the catch assembly and the release assembly of the window opening control device of FIG. 5 , but with arms of the catch assembly moving into the retracted position as a result of spring biasing.
FIG. 7 is an exploded view of the parts used for assembly and installation of the opening control device of the present invention.
FIG. 8 is a perspective view of the bracket of the catch assembly of the opening control device of the present invention.
FIG. 8A is a front view of the bracket of the catch assembly of FIG. 8 .
FIG. 8B is a side view of the bracket of the catch assembly of FIG. 8 .
FIG. 8C is an end view of the bracket of the catch assembly of FIG. 8 .
FIG. 9 is a perspective view of the first arm of the catch assembly of the opening control device of the present invention.
FIG. 9A is a front view of the first arm of the catch assembly of FIG. 9 .
FIG. 9B is a side view of the first arm of the catch assembly of FIG. 9 .
FIG. 9C is an end view of the first arm of the catch assembly of FIG. 9 .
FIG. 10 is a perspective view of the second arm of the catch assembly of the opening control device of the present invention.
FIG. 10A is a front view of the second arm of the catch assembly of FIG. 10 .
FIG. 10B is a side view of the second arm of the catch assembly of FIG. 10 .
FIG. 10C is an and view of the second arm of the catch assembly of FIG. 10 .
FIG. 11 is a perspective view of the torsion spring of the catch assembly of the opening control device of the present invention.
FIG. 11A is a front view of the torsion spring of the catch assembly of FIG. 11 .
FIG. 11B is a side view of the torsion spring of the catch assembly of FIG. 11 .
FIG. 11C is an end view of the torsion spring of the catch assembly of FIG. 11 .
FIG. 12 is a perspective view of the rivet of the catch assembly of the opening control device of the present invention.
FIG. 12A is a front view of the rivet of the catch assembly of FIG. 12 .
FIG. 12B is a side view of the rivet of the catch assembly of FIG. 12 .
FIG. 12C is an end view of the rivet of the catch assembly of FIG. 12 .
FIG. 13 is a perspective view of the base member of the release assembly of the opening control device of the present invention.
FIG. 13A is a front view of the base member of the release assembly of FIG. 13 .
FIG. 13B is a side view of the base member of the release assembly of FIG. 13 .
FIG. 13C is an end view of the base member of the release assembly of FIG. 13 .
FIG. 14 is a perspective view of the switch member of the release assembly of the opening control device of the present invention.
FIG. 14A is a front view of the switch member of the release assembly of FIG. 14 .
FIG. 14B is a side view of the switch member of the release assembly of FIG. 14 .
FIG. 14C is an end view of the switch member of the release assembly of FIG. 14 .
FIG. 15 is a perspective view of the hook member of the release assembly of the opening control device of the present invention.
FIG. 15A is a front view of the hook member of the release assembly of FIG. 15 .
FIG. 15B is a side view of the hook member of the release assembly of FIG. 15 .
FIG. 15C is an end view of the hook member of the release assembly of FIG. 15 .
FIG. 16 is a perspective view of the safety button of the release assembly of the opening control device of the present invention.
FIG. 16A is a front view of the safety button of the release assembly of FIG. 16 .
FIG. 16B is a side view of the safety button of the release assembly of FIG. 16 .
FIG. 16C is an end view of the safety button of the release assembly of FIG. 16 .
FIG. 17 is a perspective view of the spring of the release assembly of the opening control device of the present invention.
FIG. 17A is a front view of the spring of the release assembly of FIG. 17 .
FIG. 17B is a side view of the spring of the release assembly of FIG. 17 .
FIG. 17C is an end view of the spring of the release assembly of FIG. 17 .
FIG. 18A shows the decal of the exploded view of FIG. 7 that may be used to position holes on the sash for proper positioning thereon of the catch assembly of the opening control device of the present invention.
FIG. 18B shows the decal of FIG. 18B being further used to coordinate the hole positions on the sash with proper positioning of the holes on the master window frame, for proper mounting thereon of the release assembly.
FIG. 19 is an exploded view of the parts forming a second embodiment of the opening control device of the present invention, including a V-shaped torsion spring.
FIG. 20 illustrates the catch assembly and the release assembly of the second embodiment of the window opening control device of the present invention, with the casement window omitted from the view, and with the catch assembly releasably secured to the release assembly, the arms of the catch assembly being in the retracted position, and with the sash having been closed with respect to the master frame.
FIG. 21 illustrates the catch assembly and the release assembly of the window opening control device of FIG. 20 , but with the arms of the catch assembly shown extended, for when the sash is opened with respect to the master frame, and thereby travel limited.
FIG. 22 is a first perspective view of the base member of the release assembly of the second embodiment of the opening control device of the present invention.
FIG. 22A is a second perspective view of the base member of FIG. 22 .
FIG. 22B is a third perspective view of the base member of FIG. 22 .
FIG. 22C is a fourth perspective view of the base member of FIG. 22 .
FIG. 22D is a fifth perspective view of the base member of FIG. 22 .
FIG. 22E is a sixth perspective view of the base member of FIG. 22 .
FIG. 23 is a front view of the base member of FIG. 22 .
FIG. 23A is a rear view of the base member of FIG. 22 .
FIG. 24 is a first side view of the base member of FIG. 22 .
FIG. 24A is a second side view of the base member of FIG. 22 .
FIG. 25 is an end view of the base member of FIG. 22 .
FIG. 26 is a first perspective view of the switch member of the release assembly of the second embodiment of the opening control device of the present invention.
FIG. 26A is a second perspective view of the switch member of FIG. 26 .
FIG. 26B is a third perspective view of the switch member of FIG. 26 .
FIG. 26C is a fourth perspective view of the switch member of FIG. 26 .
FIG. 26D is a fifth perspective view of the switch member of FIG. 26 .
FIG. 26E is a sixth perspective view of the switch member of FIG. 26 .
FIG. 27 is a front view of the switch member of FIG. 26 .
FIG. 27A is a rear view of the switch member of FIG. 26 .
FIG. 28 is a first side view of the switch member of FIG. 26 .
FIG. 28A is a second side view of the switch member of FIG. 26 .
FIG. 29 is a first end view of the switch member of FIG. 26 .
FIG. 29A is a second end view of the switch member of FIG. 26 .
FIG. 30 is a perspective view of the hook member of the release assembly of the second embodiment of the opening control device of the present invention.
FIG. 31 is a front view of the hook member of FIG. 30 .
FIG. 32 is a side view of the hook member of FIG. 30 .
FIG. 33 is an end view of the hook member of FIG. 30 .
FIG. 34 is a perspective view of the torsion spring of the catch assembly of the release assembly of the second embodiment of the opening control device of the present invention.
FIG. 35 is a front view of the torsion spring of FIG. 34 .
FIG. 36 is a side view of the torsion spring of FIG. 34 .
FIG. 37 is an end view of the torsion spring of FIG. 34 .
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates a perspective view of the catch assembly of the window opening control device of the present invention having been installed upon a master frame and sash of a casement window. The device is being used thereon to releasably secure the sash to the master frame to prevent further travel of the opened window sash beyond the safe limit. Depressing of a safety button and pivoting of a switch member causes release of the device to permit further travel of the opened window sash, as seen in FIG. 2 .
The two main assemblies of the opening control device of the present invention are seen in the enlarged detail view of FIG. 2A , and consist of the catch assembly 100 , and the release assembly 200 . The catch assembly 100 and release assembly 200 may be secured to the sash window 11 and the master window frame 21 , respectively, and are discussed further hereinafter.
The catch assembly 100 may consist of a bracket 110 , a first arm 120 , a second arm 130 , and a torsion spring 140 . The bracket 110 is shown in detail within FIGS. 8-8C . Bracket 110 may be a generally flat plate that may be pocketed to reduce weight in-between certain features that are necessary to enable use of the bracket. Bracket 110 may include a pair of mounting holes 111 A and 111 B, which may be formed with a countersink to accommodate flush head mounting screws therein, in order to suitably mount the bracket to the side of the sash 11 . A hole 112 in the bracket 110 may be used for pivotal mounting thereto of the first arm 120 , which may be pivotally mounted using a rivet 159 , or other suitable pivotal fastening means. The bracket 110 may include a protruding stop member thereon, which may be used to limit travel of the pivotally mounted first arm 120 with respect to the bracket, when the arm is in the retracted position. The mounting holes 111 A and 111 B may be symmetrically positioned in the bracket, and may be symmetrically positioned with respect to the hole 112 that is used for pivotal mounting of the first arm 120 , which may be centered therein. With the hole 112 being centrally positioned, the pivotal stop may be located towards one end of the bracket 110 , to reduce loading of those features of the bracket. In order to be able to use the bracket for mounting to either a left-hand or a right-hand sash of the casement window, there may be a first pivotal stop 113 A located at one end of the bracket 110 , and a second pivotal stop 113 B located at the other end of the bracket. Each of the stops 113 A and 113 B of bracket 110 of the catch assembly 100 may have a “V” shaped cavity formed by a slanted surface 113 S ( FIG. 8 ) of the stop, which works for guiding automatic alignment of the first arm 120 when the catch assembly 100 is biased back towards the sash 11 , and thereafter the stop 113 completely inhibits further rotation of the first arm 120 at the fully retracted position with respect to bracket 110 .
The first arm 120 is shown in detail in FIGS. 9-9C , and may be an elongated thin plate member, which may be formed of plastic, metal, or any other suitable material. Proximate to the first end 121 of the arm 120 may be a hole 123 usable for pivotal mounting of the arm to the hole 112 of bracket 110 . Hole 123 may be an eccentric or slotted hole, through which the first arm 120 is riveted with the bracket 110 of catch assembly 100 via the rivet 159 . It provides free movements of the first arm 120 in all directions when the first arm 120 retracts to the sash 11 when the catch assembly 100 is unlocked from the release member 200 . Proximate to the second end 122 of the first arm 120 may be a hole 124 for the pivotal mounting thereto of the second arm 130 . Also proximate to the second end 122 may be a recess 126 in the side of the plate, which may be generally flat at a central portion. The first arm 120 may have a stop 125 positioned thereon to be in proximity to hole 124 . The stop could simply be a mechanical fastener that is fastened to the plate, such as a rivet or a nut and bolt. Alternatively, the stop could be a protrusion that is integral with the plate or bonded thereto, or the stop could be a portion of the plate being stamped and raised to protrude beyond the flat plane of one side of the arm. The latter option is shown in FIG. 9A , which may be seen to produce a straight edge for the stop that may generally be aligned with the position of the edge of the second arm 130 where it is to be restrained in the retracted position.
The second arm 130 is seen in detail within FIGS. 10-10C , and may, in general, be constructed similar to first arm 120 . Second arm 130 may be an elongated thin flat plate member, with a hole 133 proximate to its first end 131 , to be usable for pivotal mounting of the second arm to hole 124 of the first arm 120 . At the first end 131 of the second arm 130 , a small protrusion 134 may protrude orthogonally from the side of the arm, and may be formed by any of the means cited above for producing stop 125 . The protrusion 134 shown within FIG. 10 is shown as a small tab at the first end 131 that is bent at roughly a 90 degree angle. The protrusion 134 works as a stop to limit the over rotation of the second arm 130 with respect to the first arm 120 , and is received in the recess 126 of the first arm 120 when the sash is to maximum limit opening position, which his discussed further hereinafter. The second end 132 of the second arm 130 may have a shaped opening 135 therein, which may be generally rectangular, and which may further have a notch 135 N therein, both of which are discussed later as to the operation of the opening control device.
The pivotal mounting of the second arm 130 to the first arm 120 may utilize a simple rivet or other mechanical fastener, and one of many different varieties of springs, which may be a tension spring or a torsion spring. Merely to be exemplary, use of torsion spring 140 and rivet 150 is utilized herein. An exemplary torsion spring 140 is illustrated within FIGS. 11-11C , and may include a small number of helical windings 140 W or even just a portion of one winding that may terminate in a first end 141 via a radial portion 141 R, and in a second end 142 . The first and second ends 141 and 142 may be used to bias the second arm 130 with respect to the first arm 120 . (An alternative V-shaped torsion spring 340 is disclosed hereinafter discussed alternate embodiment).
In this exemplary arrangement, a rivet 150 , which is shown in detail within FIGS. 12-12C , may have a first post 151 extending from the head 153 , and a second post 152 telescoping therefrom. Pivotal mounting of the first and second arms 120 and 130 may be achieved by first receiving the helical windings 140 W of the torsion spring 140 upon the first post 151 of rivet 150 , such that its radial portion 141 R of the first end 141 is received through opening 153 P in the head 153 of the rivet 150 (see FIG. 7 and FIG. 3 ). Next, the second arm 130 may be mounted upon the rivet 150 such that hole 133 of the second arm is received upon, and sized to be pivotal with respect to, the first post 151 of the rivet. The first arm 120 may then be mounted upon the rivet 150 such that hole 124 of the arm is received upon its second post 152 . The side of the arm may abut the shoulder ISIS formed by the side of the post 151 and the post 152 . The second end 142 of torsion spring 140 may loop about the side of the elongated flat plate of the first arm, as seen for example in FIG. 4 . The post 152 may then be bucked to fixedly secure the first arm 120 to the shoulder ISIS, so that there will be no relative motion therebetween. Instead of relying upon the bucked post 152 to fixedly secure the first arm 120 to the rivet 150 , the post 152 may have a flat side 152 D, as seen in FIG. 12A , to form a D-shaped profile, which may be mated to a correspondingly keyed opening 124 D ( FIG. 9A ) that may be used instead of the plain round hole.
Therefore, as seen in FIG. 2A , when the bracket 110 of catch assembly 100 is properly mounted to the sash (i.e., with the bracket generally oriented in the vertical direction and using backing plate(s) 110 A/ 110 B that are shown in FIG. 2B to accommodate different sash/frame profiles), the first arm 120 may normally pivot downwardly (clockwise in the view) about the bracket due to gravity, until reaching the stop 113 A of the bracket. At the same time, torsional biasing provided by torsion spring 140 may cause the second arm 130 to pivot upwardly (counterclockwise in the view), in opposition of the force of gravity, until the side of the second arm contacts the stop 125 on the first arm 120 . Without any forces acting upon the catch assembly 100 , it may normally occupy this retracted position that is illustrated within FIG. 2A .
An exemplary release assembly 200 is shown separately in FIG. 4A , but in its simplest form it may instead consist of a hook element configured to be pivotally received in the master window frame, where a hook portion of the element may be configured to engage the shaped opening 135 in the second end of the second arm 130 , and be disengaged therefrom through its pivotal motion within the master window frame. This pivotal movement of this hook element that enables engagement within the opening and disengagement therefrom of its hook portion, especially using the notch 135 N in the second arm 130 , may be seen in viewing FIGS. 4B and 5B . This simple version of the hook element may be a slightly modified version of the combination of the hook member 210 and base member 230 that are discussed hereinafter.
For ease of manufacturing and/or other reasons, this simplified hook element may be replaced by the combination of the separate hook member 210 that is shown within FIGS. 15-15C and the separate graspable switch member 220 that is shown within FIGS. 14-14C .
The hook member may take many different shapes, however, the exemplary hook member 210 shown in FIG. 15 may be a narrow, thin-shaped material that is formed to have a hook portion 212 extending from one end of its shank 211 . The other end of the shank 211 may have an eye formed thereat, or it may instead be formed with a return flange 214 that extends from a cross-member 213 to create a clasp portion 210 C. The clasp portion 210 C may be fixedly secured to a corresponding retaining member 222 formed within a recess 220 R of the switch member 220 , so that the angled hook portion 210 C of hook 210 protrudes outwardly therefrom (see FIG. 2H ). The length of the shank 211 and its shape may be particularly formed so as to permit the hook portion 212 to be somewhat flexible with respect to the clasp portion 210 C, after it has been secured to the retaining member 222 of the switch member 220 . The clasp portion 210 C of hook member 210 may be fixedly secured within the corresponding recess 220 R of the switch member 220 using a friction fit, or using adhesive, or mechanical fasteners, or any suitable fastening means or combination thereof.
The shaft 221 of the switch member 220 may be formed to be pivotally received within a corresponding opening in the window master frame, and such an opening may be added to a window that is already installed and in service in a dwelling. However, to more easily accommodate installation of the release assembly 200 within the master frame of a newly manufactured window, and to further accommodate additional features of the opening control device of the present invention, the switch member 220 may instead be formed to be pivotally received within a base member 230 , which is illustrated within FIGS. 13-13C .
The base member 230 may have a correspondingly shaped shaft 231 that extends from a flange 232 . The flange 232 may have a pair of holes 233 A and 233 B formed therein to receive fasteners for mounting of the base member to the master window frame 21 , as seen in FIG. 2C . FIG. 2D shows the shaft 231 of the base member 230 installed within, and protruding from, the opening in the master window frame.
The shaft 221 of the switch member 220 may have a stop 223 protruding therefrom ( FIG. 14 ), which may serve to limit pivotal travel of the switch member to 90 degrees of travel within the shaft 231 of the base member 230 ( FIGS. 4A and 5A ). The travel of the switch member 220 may be so limited by a pair of corresponding stops formed within the hollow of the shaft 231 of the base member 230 .
As an additional safety precaution, to better prevent a mischievous child from rotating the switch member 220 to disengage the opening control device to open the window fully, the device of the current invention may furthermore include a safety button 240 , which is illustrated within FIGS. 16-16C , and which may be biased by the helical spring 250 that is shown within FIGS. 17-17C . The safety button 240 may have a cylindrical head portion 240 H, from which may extend two pairs of legs—a first pair of legs, 241 A and 241 B, and a second pair of legs, 242 A and 242 B. The safety button 240 may also have a post 243 protruding away from the bottom of the head portion 240 H, upon which may be received the first end 251 of the helical spring 250 .
This combination of helical spring 250 and safety button 240 may be received within the opening 224 in the shaft of the switch member 220 , such that the pairs of legs are slidably received within corresponding elongated recesses therein, which may serve to prevent rotation of the safety button with respect to the switch member. The second pairs of legs, 242 A and 242 B, as seen in FIG. 16 , which may be longer than the first pair of legs, may have respective outwardly extending flanges 242 A F and 242 B F .
Although it may be understood by one skilled in the art that other features may be used to similarly accomplish functional mating of the safety button 240 , the switch member 220 , and the base member 230 , the second pair of legs 242 A and 242 B of the safety button may herein be received through correspondingly shaped openings 225 A and 225 B in the switch member ( FIGS. 7 and 14A ), to secure the safety button to the switch member. The second pair of legs will need to be elastically deflected inwardly in order for the outwardly extending flanges 242 A F and 242 B F of the legs to be received through the opening 224 in the shaft 221 of the switch member 220 . Once having passed therethrough, the legs would naturally deflect back to their undeformed position, as seen in FIG. 16A , and may thereby secure the safety button 240 with respect to the switch member 220 , as a portion of the outwardly extending flanges 242 A F and 242 B F of the legs would now overhang beyond the diametrical periphery of the shaft 221 (see FIGS. 14C and 16B ). The helical spring 250 retained between the safety button 240 and the base member 230 may serve to normally bias the button to have a portion protrude outwardly beyond the graspable handle portion 226 of the switch member 220 ( FIG. 4A ).
This subassembly—the switch member 220 , the safety button 240 , and the spring 250 —may be coupled with the base member 230 , with the shaft 221 of the switch member being received within the opening 234 of the shaft 231 of the base member 230 . The second pair of legs 242 A and 242 B may again need to be elastically deflected inwardly in order for the outwardly extending flanges 242 A F and 242 B F thereon that protrude beyond the diametrical periphery of the shaft 221 , to be received through the opening 234 in the shaft 231 of the base member 230 . The outwardly extending flanges 242 A F and 242 B F may also be aligned to be received through the correspondingly shaped openings 235 A and 235 B in the base member (see FIG. 7 , and FIGS. 13A, 14A, and 16B ). Once having passed therethrough, the second pair of legs would again naturally deflect outwardly back to their undeformed position and would extend slightly beyond the periphery of the opening 234 ( FIG. 13A ), to thereby secure the subassembly of the switch member 220 , spring 250 , and safety button 240 with respect to the base member 230 . In addition, with the formation of the shaped openings 235 A and 235 B in the base member, the lateral extent of which may protrude in the axial direction to be slightly beyond the point where the outwardly extending flanges 242 A F and 242 B F overhang the periphery of the opening 234 of the shaft 231 , pivoting of the switch member relative to the base member may thereby be inhibited. This functions as a safety—a means of preventing inadvertent actuation of the release member of opening control device, by some person not familiar with the device (i.e., a child-proof safety). However, by depressing the safety button 240 to overcome the biasing by spring 250 , the portion of the outwardly extending flanges 242 A F and 242 B F of the second pair of legs that were still nested within the lateral extent of the openings 235 A and 235 B in the base member, may now protrude beyond its extent, and thus the switch member is then free to pivot until such pivoting is limited by the aforementioned stops, being after roughly 90 degrees of rotation (see FIGS. 2F, 2G, and 2H ).
Another additional feature that may be incorporated into release assembly 200 may be the further provision that the helical compression spring 250 that is used to normally bias the safety button 240 outwardly from the opening 224 in the switch member 220 , may also be formed to have its first and second ends 251 and 252 be usable for providing torsional biasing of the switch member 220 relative to the base member 230 . The radial over-center portion 253 of spring 250 at its first end 251 ( FIG. 17C ) may be received in the groove 243 G in the post 243 of the head 240 H of the safety button 240 ( FIG. 16 ). Also, the outwardly extending hook portion 254 at the second end 252 of the spring 250 may similarly be restrained within a portion of the base member 230 . Therefore, when the safety button 240 of the release assembly 200 is depressed and the switch member 220 is manually pivoted 90 degrees to thereby also pivot hook portion 212 ( FIG. 5A ), after the user releases his/her grip from the switch member, the dual-biasing spring 250 may then serve to bias the switch member to counter-rotate the 90 degrees, and as well as serve to bias the safety button to translate outwardly to once again be positioned as seen in FIG. 4A .
Operation of the opening control device of the present invention may thus be understood by initially viewing FIG. 2 . With the catch assembly 100 shown in its normally retracted position on window sash 11 , as described hereinabove, the opened window sash may then be dosed, which may serve to bring the catch assembly on the sash into proximity with the release assembly 200 on the master window frame, and cause engagement between the hook portion 212 of the hook member 210 and the shaped opening 135 of the second arm 130 . This is illustrated within FIG. 3 , in which the sash and the master window frame are not shown, to better illustrate the engagement therebetween, which occurs automatically through the mere closing of the window. The flexibility of the shank 211 of the hook 210 may serve to aid in the engagement therebetween, as the approaching side of the second arm 130 may cause the angled hook portion 212 to deflect out of its way, and then it may deflect back, as the opening 135 in the arm reaches the hook portion 212 . The generally rectangular shape of the opening 135 in the second arm 130 may also serve to better accommodate capture of the hook portion 212 of the shank 211 of hook member 210 , which will be protruding substantially orthogonally from the master window frame 21 .
When the user opens the window, the bracket 110 on the sash moves away from the release assembly 200 on the master window frame. The engagement between the hook portion 212 of the hook member 210 and the shaped opening 135 of the second arm 130 serves to overcome the torsional biasing of the spring 140 , so that increasing distance between the sash 11 and master frame 21 ( FIG. 1 ) results in the extension of the first and second arms 120 and 130 , as seen in FIG. 4 . (Note, recess 126 on first arm 120 and small tab 134 on second arm 130 may prevent over-travel therebetween). The length of the first and second arms 120 and 130 may be sized so that this limited travel of the sash 11 is small enough to prevent a child from accidentally falling through the opening and may be roughly four inches.
As seen in FIGS. 1 and 2 , the opening control device may be positioned on an upper part of the sash and master window frame to make it more difficult for a small child to reach the release assembly. When an adult desires to open the window beyond the travel limited position of FIG. 1 , the safety button 240 of the release assembly 200 , as seen in FIG. 4A , may be depressed and the switch member 220 may be rotated, so that it appears as shown in FIG. 5A . This results in the hook portion 212 of hook member 210 moving from its initial engaged position, as seen in FIG. 4B , to the disengage position, as seen in Figure SB. Note that the notch 135 N in the opening 135 of the second arm 130 may be shaped as shown in FIG. 14A , so that with the second arm extended as seen in FIG. 4 , rotation of the book member 210 would not tend to cause its hook portion 212 to jam against the side of second arm, and may freely exit from the opening 135 through the notch, as shown in Figure SB. The hook member may thus be freely rotated from its first hooked position, wherein the hook 212 of the release assembly is connected with the second arm of the catch assembly, to its second unhooked or position. Once the hook 210 is disengaged, retraction of the arms may occur, where the force of gravity may cause the first and second arms 120 and 130 to drop vertically, and the second arm may also pivot with respect to the first arm, due to biasing by spring 140 , and both may move away from the release assembly 200 , as seen in FIG. 6 , until reaching the retracted position seen in FIG. 2 . The sash may now be fully opened.
An alternate embodiment of the catch assembly 100 and release assembly 200 may be catch assembly 101 and release assembly 201 that is formed using component parts being generally the same as those in FIG. 7 , but with some minor adjustments have been made thereto, and with the modified parts being shown within the exploded view of FIG. 19 .
The torsion spring 140 of FIG. 7 and FIGS. 11-11C may be replaced by torsion spring 340 , which is shown in detail within FIGS. 34-37 . Torsion spring 340 may include a small number of helical windings 340 W that may terminate in a first leg 341 and a second leg 342 . At the end of the first leg 341 being distal from the windings may be formed a hook portion 341 H, and at the end of the second leg 342 may be formed a hook portion 342 H. The first and second legs 341 and 342 may be used to bias the second arm 130 with respect to the first arm 120 . However, with this arrangement, the bias that is applied by torsion spring 340 is applied directly to arms 120 and 130 , whereas, for spring 140 , the bias is applied through the rivet 150 and its connection to the first arm 120 . As seen in FIG. 20 , for catch assembly 101 and release assembly 201 , the hook portion 341 H of the first leg 341 of torsion spring 340 may wrap around the first arm 120 , in proximity to its stop 125 , while the hook portion 342 H of the second leg 342 may wrap around the second arm 130 . When the first arm 120 and second arm 130 are extended by opening of the sash, the torsion spring is elastically deformed, and as seen in FIG. 21 , the first and second legs 341 and 342 of the spring 340 being so deformed apply a biasing force to the arms 120 and 130 . Here again, once the release assembly 201 no longer has its hook secured within the opening 135 of the second arm, the spring 340 will bias the two arms to rotate toward each other until the side of the second arm contacts stop 125 , as seen in FIG. 20 .
For release assembly 201 , the hook member used therein may take a slightly different shape, and a hook member 410 , which is shown in detail within FIGS. 30-33 , may be used instead of hook 210 . Hook 410 may be formed similar to hook 210 , but may have a hook portion 410 C that is more rectangular in shape, and its return flange 414 may have a bent end flange 415 thereon, which may serve to more positively retain the hook in engagement with the switch member. The release assembly 201 may also use a base member 430 and a switch member 420 , with the features of each being shown in detail within FIGS. 22-25 , and FIGS. 26-29 , respectively.
The examples and descriptions provided merely illustrate a preferred embodiment of the present invention. Those skilled in the art and having the benefit of the present disclosure will appreciate that further embodiments may be implemented with various changes within the scope of the present invention. Other modifications, substitutions, omissions and changes may be made in the design, size, materials used or proportions, operating conditions, assembly sequence, or arrangement or positioning of elements and members of the preferred embodiment without departing from the spirit of this invention. | A device may limit opening of a sash hingedly coupled to a master frame, and includes: a bracket attached to the sash; a first arm having a first end pivotally coupled to the bracket; a second arm having a first end pivotally coupled to the first arm's second end; means for biasing the second arm into a retracted position; and a release assembly. The release assembly is secured to the master frame and includes a hook pivotable between a first position and a second position, which, in the first position, may be releasably received in an opening in the second end of the second arm when the second arm is in the retracted position, as the sash is closed and received within the master window frame The second arm is disengaged from the hook, permitting fill opening of the sash, when the hook is pivoted into the second position. | 4 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to preparation of polychlorinated pyridine mixtures by direct liquid phase chlorination of pyridine or pyridine hydrochloride. Typical of the products produced are 2-chloro-, 3-chloro-, 2,6-dichloro-, 3,5-dichloro, 2,3,5-trichloro, 2,3,6-trichloro-, 3,4,5-trichloro, 2,3,4,5-tetrachloro-, 2,3,5,6-tetrachloro- and 2,3,4,5,6-pentachloropyridine. These products have utility, for example, as intermediates for herbicides and insecticides. A further aspect of the present invention relates to the separation of these mixed chloropyridines and then further chlorination to yield valuable higher chlorinated pyridines such as 2,6-dichloro-, 2,3,5-trichloro-, 2,3,6-trichloro-, and 2,3,5,6-tetrachloropyridine.
2. Description of the Prior Art
The utility of 2-chloropyridine as an intermediate to fungicidal and bactericidal compositions is described by Bernstein et al U.S. Pat. No. 2,809,971 and by McClure et al U.S. Pat. No. 3,159,640. In Orvik U.S. Pat. No. 4,275,212 and Fah et al U.S. Pat. No. 4,287,347, the utility of 2,3,5-trichloropyridine is described as an intermediate for herbicidal compositions. Bowden et al U.S. Pat. No. 4,108,856 describe a vapor phase chlorination process for producing 2,3,5-trichloropyridine from 3,5-dichloropyridine. 2,6-dichloropyridine is catalytically chlorinated in the liquid phase at greater than 180° C. to yield the valuable insecticidal intermediate 2,3,5,6-tetrachloropyridine in Smith et al U.S. Pat. No. 3,538,100.
The conversion of 2,3,6-trichloropyridine to 2,3,5,6-tetrachloropyridine by liquid phase ferric chloride catalyzed chlorination is taught by Dietsche et al U.S. Pat. No. 4,256,894.
Weis et al U.S. Pat. No. 4,258,194 describe a process for producing 2,3,5-trichloropyridine from 2,3,4,5-tetrachloropyridine. The valuable insecticidal intermediate 2,3,5,6-tetrachloropyridine is produced from 2,3,4,5,6-pentachloropyridine in a process described by Weis U.S. Pat. No. 4,259,495.
Brewer et al U.S. Pat. No. 3,732,230 describes a liquid phase chlorination of pyridine hydrochloride at temperatures from about 130° C. to about 175° C. with greater than 30 psig hydrogen chloride partial pressure in the reactor. The chief reaction products are 2,3,4,5-tetrachloropyridine, 2,3,5- and 3,4,5-trichloropyridine, small amounts of 3,5-dichloropyridine and a dimer polymer of pyridine.
SUMMARY OF THE INVENTION
It has been discovered that high yields of mixtures rich in chlorinated pyridines may be achieved by noncatalytically chlorinating pyridine or pyridine hydrochloride in a diluent in the liquid phase at temperatures of at least about 150° C. to about 250° C. or 260° C. while maintaining strong agitation and a feed ratio of chlorine to pyridine of at least about 4:1 by weight while feeding the chlorine and pyridine or pyridine hydrochloride to the reaction mass in a primary reactor. The pyridine can be dissolved in carbon tetrachloride or fed full strength into the reactor. It is desirable to have a supply of carbon tetrachloride available for flushing the feed line in the event of a shutdown because stagnant pyridine would otherwise tend to degrade in the feed line. If pyridine hydrochloride is the desired feed form, it is fed directly through a sparger into the bottom of the primary reactor. After the pyridine or pyridine hydrochloride has been partially chlorinated in the primary reactor, the polychloro pyridine is subjected to further chlorination in another reactor for such times and temperatures as appropriate to maximize the yield of the desired end product or products.
The percent of volatiles realized by liquid phase chlorination according to the present invention is dependent upon the diluent composition, the extent of mixing of the reactants and diluent, the pyridine feed rate to reaction mass volume, the weight ratio of chlorine-to-pyridine being fed, and the chlorine partial pressure, which influences chlorine solubility. The composition of the diluent media in which the reaction proceeds is important in practice of this invention, to secure good yields of the desired volatile chlorinated pyridines. Its function in this invention is quite different from the initiator charge described in Taplin U.S. Pat. No. 3,424,754, which deals with alpha-picoline liquid phase chlorination. In U.S. Pat. No. 3,424,754, the initiator charge has the function of evolving HCl when contacted with chlorine at the reaction temperature in order to react with alpha-picoline to form picoline hydrochloride. In the present invention, the diluent's function is to be reactively less competitive for the chlorine dissolved in it and to help remove the heat of reaction evolved by the chlorination of the pyridine.
Examples of some compounds usable as diluents in practice of the present invention, in that they generate one mole or less of HCl per mole of compound when contacted with chlorine under the reaction conditions of the present invention, are: 3-chloro-, 5-chloro-, 6-chloro-, 5,6-dichloro-, 3,5-dichloro-, 3,6-dichloro-, 3,4,5-trichloro- and 3,5,6-trichloro-2-trichloromethyl pyridine, 2-chloro-, 6-chloro-, 2,6-dichloro-3-trichloromethyl pyridine, and 2,3,6-trichloro-, 2,3,5,6-tetrachloro- and 2,3,4,5,6-pentachloro pyridine, and mixtures thereof. This list is not meant to be exhaustive of all possible diluent constituents but is illustrative of compounds useful for the purpose. The diluent may be the chlorinated pyridine/picoline products from a previous reaction which meet the above criteria and is high in volatiles content.
In practice of the present invention, an excess of chlorine is fed relative to that needed for the pyridine and pyridine hydrochloride chlorination, which excess provides additional agitation and hence better mixing, and also a higher chlorine partial pressure which increases the chlorine solubility in the reaction media. A chlorine to pyridine weight ratio of at least about 4:1 is needed. As the temperature increases in excess of 200° C., the weight ratio of chlorine to pyridine fed needs to be higher in order to achieve the high yields of the desired volatile chloro-pyridines. This is necessary because chlorine reacts more rapidly with the pyridine or pyridine hydrochloride as the temperature increases and therefore the chlorine dissolved in the reaction medium must be more rapidly replaced. This is accomplished by increasing the rate of chlorine addition relative to the pyridine flow rate which increases the chlorine partial pressure and hence its mole fraction in the liquid reaction medium. Gas solubilities tend to decrease with rising temperature, but an increase in system pressure also increases the chlorine solubility. The chlorine partial pressure in the vapor space over the reaction mass should be greater than 50% of the total pressure.
The pyridine or pyridine hydrochloride feed is to be controlled relative to the reaction volume so no more than about 10% by volume of light phase accumulates relative to the chlorinated pyridine phase at temperatures in excess of about 150° C. Potential decomposition products can result above this temperature in the absence of cooling and excess chlorine. Since pyridine hydrochloride and the diluent are somewhat immiscible and of different densities, good mixing is necessary in order to achieve dispersion of chlorine and pyridine or pyridine hydrochloride into the diluent.
Controlling these variables results in high yields of volatile polychlorinated pyridines in the liquid phase at temperatures in excess of 150° C.
Care must be taken to ensure metallic impurities such as iron, copper, aluminum and other Lewis Acid type metals are excluded from the reaction mass, as they will cause different reactions in the chlorination that may not be desirable.
BRIEF DESCRIPTION OF THE DRAWING
The FIGURE is a schematic diagram of a reaction system for practicing the process of the present invention on a continuous batch basis.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
EXAMPLE 1
The FIGURE schematically illustrates a continuous batch type reaction system for producing mixtures rich in polychlorinated pyridines according to the present invention. Primary reactor R1, secondary reactor R2, and absorber C2 are suitably glass of cylindrical configuration, electrically heated and each about 1 liter in volume, and with an inside diameter of 4 inches and an inside height of 7 inches. Water cooled scrubber column C1 is suitably of cylindrical design, 11/2 inches in diameter, containing as packing some 18 inches of 1/4 inch glass rings.
Scrubber column C1 includes a holding tank or reservoir T1 and the overhead vapor from column C1 is delivered through vent line 10 to disengaging tank T2 in which the carbon tetrachloride collects, with the chlorine and hydrogen chloride evolving from column C1 being delivered by vent line 12 and sparged into hydrochlorination tank T3. For startup, pyridine hydrochloride, suitably previously prepared conventionally, as by sparging anhydrous HCl into a pool of pyridine maintained between 80° C. and 100° C. until saturated with HCl, is charged to hydrochlorination tank T3 and pyridine hydrochloride is withdrawn from tank T3 and delivered to bottom discharging sparger 14 in reactor R1 through line 16. An alternate startup mode involves feeding pyridine dissolved in carbon tetrachloride through lines 68 and 70 thence into line 14, generating hydrogen chloride which is vented to hydrochlorination tank T-3. For startup, also, primary reactor R1 was charged through charge line 18 with 1200 grams of diluent, consisting of chlorinated pyridines from a previous reaction (suitably comprising about 22.4% 2-trichloromethyl pyridine, 70.0% 6-chloro-, 3.9% 5,6-dichloro-, and 2.2% 3,6-dichloro-2-trichloromethyl pyridine by weight). 600 grams of like diluent material were also charged to secondary reactor R2 through charge line 20. 450 grams of a suitable absorbent were charged through charge line 64 to absorber C2, the composition of the absorbent selected for this example being the same as that charged to R1 and R2.
The absorbent charged to C2 needs to have a melting point of less than 80° C. and substantial solubility with carbon tetrachloride. Its purpose is to absorb higher melting chlorinated pyridines, e.g. those with melting points greater than 80° C., namely, 2,6-dichloro-, 2,3,5,6-tetrachloro- and 2,3,4,5,6-pentachloro pyridine. If these higher melting point chloropyridines were allowed to enter the scrubber column C1 in substantial quantity, they would tend to plug the column packing. The refluxing carbon tetrachloride in scrubber column C1 tends to concentrate the entrained chloropyridines that enter it in the bottom tank T1 thereof, and keep the overhead vapors substantially free of chlorinated pyridines which would otherwise plug the vapor outlet 10. Some typical examples which meet the criteria of suitable absorbent materials are 6-chloro, 5,6-dichloro-, 3,6-dichloro-, 3,5-dichloro-2-trichloromethyl pyridine, and mixtures thereof.
The operational startup sequence is that of introducing the diluent to the primary and secondary reactors, then initiating chlorine flow, then heating the reactors to desired reaction temperature, then initiating the pyridine or pyridine hydrochloride flow. By this procedure the pyridine or pyridine hydrochloride only sees excess chlorine in the reactors and degradation thereof to nonvolatiles is avoided. Once reactors R1 and R2 were charged, external heat was applied and the temperature of primary reactor R1 thereof was maintained at 235° C., with secondary reactor R2 being maintained at 235° C. and absorber C2 maintained at 140° C. Chlorine gas from a suitable pressurized source was delivered to the reactor R1 through feed line 22 and bottom placed sparger 24 at a flow rate of 380 grams per hour. The flow rate of pyridine dissolved in carbon tetrachloride at a volume ratio of 1:1 was sparged into reactor R1 through bottom placed sparger 14, the discharge stream of which is closely adjacent (with about 1/2 inch spacing) to the discharge stream of chlorine sparger 24, and was maintained at a rate equivalent to 21.8 grams pyridine per hour, amounting to a chlorine to pyridine feed ratio of about 17.4:1.
As will be understood, the pyridine fed to primary reactor R1 releases hydrogen chloride from the reaction with the chlorine. This hydrogen chloride along with excess chlorine is vented from reactor R1 through vent line 26 and sparged into the charge in secondary reactor R2 through bottom discharging sparger 28, the overhead vapor including hydrogen chloride and excess chlorine being vented from reactor R2 and delivered through line 30 to absorber C2, thence through line 62 to scrubbing column C1, thence through line 10 and line 12 to hydrochlorinating tank T3, the vapor flow from which passes through line 32 to hydrogen chloride and chlorine gas recovery means known per se, for recycling of the chlorine gas to the process and recovery of the hydrogen chloride, as desired. Once hydrogen chloride gas is being generated and is passing through the system to hydrochlorination tank T3, the pyridine feed into tank T3 through line 15 can be started if that is the desired feed mode.
Secondary reactor R2 is only partially charged with diluent at startup. This is for the reason that, as the volume of the reaction mass in reactor R1 increases in the course of the reactor, a portion of the reaction mass is moved from reactor R1 to reactor R2 (by volatilization and entrainment) through line 26 and through discharge line 34 for further chlorination in reactor R2. The temperature in secondary reactor R2 influences the degree of continued chlorination.
When the liquid volume in secondary reactor R2 increases to the point where the reactor R2 is filled to its operating level, further increase in liquid volume is taken care of by progressively discharging the excess through line 36, 38 to storage surge tank S1 from which it is discharged through discharge line 40 to vacuum distillation column C3. In addition, absorbent and entrained reaction products that have been absorbed in C2 likewise are discharged through line 66 and line 38 to storage surge tank S1. This mixture of components in storage tank S1 is also fed through line 40 to vacuum distillation column C3. The lower boiling chlorinated pyridine products from storage tank S1 are distilled in C3 and are collected and discharged overhead through line 42 for further treatment as intermediate products, final products, or for further chlorination as individual products. The absorbent and diluent materials, which are higher boiling than the chlorinated products manufactured in the reaction system, are concentrated in the bottom of distillation column C3 and are returned to the process through discharge line 44 which is connected to reactor R1 through line 46, to reactor R2 through line 48, and to absorber C2 through line 50.
Liquid discharge from holding tank T2 is delivered to scrubber column C1 through line 56 to return carbon tetrachloride to the column C1, with makeup of carbon tetrachloride from an appropriate supply if necessary, as indicated at 58. The liquid phase fraction collecting in bottom tank T1 of the scrubber column C1 is returned to absorber C2, as indicated at line 60.
Excess chlorine, hydrogen chloride, some volatile corrosive chloro-pyridine hydrochlorides, and entrained chlorinated pyridines, some of which have melting points in excess of 100° C., are transferred to secondary reactor R2 from primary reactor R1 by heated vent line 26 and bottom discharging sparger 28, with the volatile hydrochlorides being absorbed and reacted further in secondary reactor R2. These hydrochlorides are very corrosive and tend to form solids on condenser surfaces that are in the 30° C. to 100° C. temperature range, the operating temperature range of scrubber column C1 and, along with the high melting chloropyridines, would there cause a plugging problem in column C1 if passed directly from primary reactor R1 to the scrubber column C1. Their absorption and further reaction in secondary reactor R2 help eliminate such plugging problems and absorber C2 completely eliminates the high melting chloropyridines in the vent line 62 to column C1. The excess chlorine, hydrogen chloride and entrained products passing to column C1 through absorber C2 vent line 62 are there scrubbed with carbon tetrachloride discharged to column C1 through line 56. The entrained chlorinated pyridine products buildup in tank T1 and the liquid level therein is controlled by recycling the excess liquid back to absorber C2 through discharge line 60. When the level in absorber C2 reaches the operating level, processing of the excess material is begun through line 66 for removal of the high melting chloropyridine reaction products from the absorber material. These chlorinated pyridine products are removed from the absorbent material by vacuum distillation in C3. Process absorbent is then recycled back to C2 through line 44 and line 50.
The residence time in each reactor R1 and R2 varies from about 5 to about 40 hours, and the total cycle time in the reactors is about 10 to 80 hours. From the previously described feed and reaction conditions set forth in Example 1, 40.8 grams per hour of product was obtained that contained about 5.6% 3-chloro-, 31.3% 2-chloro-, 15.1% 3,5-dichloro-, 2.4% 2,3-dichloro-, 23.1% 2,6-dichloro-, 2.6% 3,4,5-trichloro-, 2.8% 2,3,6-trichloro-, 4.7% 2,3,4,5-tetrachloro-, and 10.0% 2,3,4,5,6-pentachloropyridine. The volatiles content of the reaction mass was greater than 99%. These compounds can be separated by vacuum distillation for further chlorination of the pure compounds or further processing to useful products. For example, 2-chloropyridine is easily separated by vacuum distillation and is a valuable commercial product per se without further processing.
In practice of the invention appropriate variation in residence time is determinable on a predictable basis, taking into consideration the product composition desired, and the reactor pressure and reactor temperature. In addition, the quantity of diluent recycled to the reactors may also be varied to vary the residence time. In any event, as earlier indicated, the feed rate of pyridine or pyridine hydrochloride relative to the reaction volume is to be controlled so that no greater than about 10% by volume of lighter phase (undiluted pyridine hydrochloride) exists in the reaction mass.
The gases in vent line 32 from hydrochlorination tank T3 are predominantly excess chlorine and hydrogen chloride, which stream can be separated or purified by a number of conventional techniques such as absorption of the hydrogen chloride in water, or drying the chlorine and compressing the chlorine gas for recycle, or fractional distillation.
The analysis of the reaction products obtained in Example 1 is given in the following TABLE ONE. (All of the numbers in TABLES ONE, TWO, and FOUR are % by weight.)
TABLE ONE______________________________________Compound Example 1______________________________________ ##STR1## 5.6% ##STR2## 31.3 ##STR3## 15.1 ##STR4## 2.4 ##STR5## 23.1 ##STR6## 2.6 ##STR7## 2.8 ##STR8## 4.7 ##STR9## 10.0______________________________________
EXAMPLES 2 THROUGH 6
Examples 2 through 6 serve to illustrate some of the process variables which can occur in practice of the present invention, and for such purpose were conducted as simplified batch processes. A chlorination reactor comprising a 1000 ml spherical glass reactor, heated by an electric heating mantle, was equipped with two sparge tubes and a line which was vented through a 5000 ml glass knockout pot to a caustic scrubber. The spargers were bottom placed and closely spaced (2 centimeters apart) and the respective feed lines to the spargers were fed through rotometers and flow controlled through respective needle valves, one being supplied from the source of chlorine gas, and the other supplied from a source of pyridine (Examples 2, 3, 4) or pyridine hydrochloride (Examples 5, 6). In each run the procedure followed was the same except for the variables investigated, namely diluent composition, temperature, chlorine-to-pyridine feed ratio, residence time, and pyridine flow rate relative to reaction mass volume.
In Example 2, which is illustrative, the reactor was charged with 760 grams of diluent, the composition of which is given in the following TABLE TWO, and chlorine feed was initiated through the chlorine sparger at the rate of 380 grams per hour and the charge heated to a temperature of 170° C. Pyridine dissolved in an equal volume of carbon tetrachloride was then sparged into the reactor at the rate of about 19.8 grams per hour for a period of 4 hours. The weight ratio of chlorine to the pyridine being fed during the reaction was about 19.2:1. The reaction process parameters are tabulated in the following TABLE THREE.
In Example 2, the gross weight of the resulting reaction product was 905 grams, indicating a net production of 145 grams of product. The product was a clear tractable fluid, with a volatiles proportion of greater than 99%, as measured by internal standard gas chromatography. The constituency of the product was as tabulated in TABLE FOUR.
As indicated, additional runs, designated Examples 3, 4, 5 and 6 involved the diluents set forth in TABLE TWO, the parameters set forth in TABLE THREE, and produced reaction products comprising the compounds set forth in TABLE FOUR.
TABLE TWO______________________________________DILUENT COMPOSITIONCompound Examples 2,3,4 Examples 5,6______________________________________ ##STR10## -- 1.2% ##STR11## 72.5% 50.7 ##STR12## 4.4 -- ##STR13## 20.1 11.3 ##STR14## 2.8 -- ##STR15## -- 18.1 ##STR16## -- 18.6______________________________________
TABLE THREE______________________________________Ex 2 Ex 3 Ex 4 Ex 5 Ex 6______________________________________Initial 170° C. 190° C. 220° C. 210° C. 150° C.ReactorTempDiluent 760 gms 770 gms 775 gms 478 gms 465 gmschargeFeed pyridine/ pyridine/ pyridine/ pyridine pyridineForm CCl.sub.4 CCl.sub.4 CCl.sub.4 hydro- hydro- chloride chlorideCl.sub.2 380 380 380 380 380Flow gms/hr gms/hr gms/hr gms/hr gms/hrRatePyridine 19.8 30 14.3 25 18flow rate gms/hr gms/hr gms/hr gms/hr gms/hrCl.sub.2 to 19:1 12.7:1 26.5:1 14.1:1 21:1Pyridineratio(by weight)Reaction 4 hrs 8 hrs 4 hrs 3.5 hrs 6 hrsTimewith bothCl.sub.2 andpyridinefeedsAmt of 145 gms 220 gms 105 gms 151 gms 157 gmsproductproducedVolatility 99% 99% 99% 98% 99%ofproducedproduct______________________________________
TABLE FOUR______________________________________ Exam- Exam- Exam- Exam- Exam-Compound ple 2 ple 3 ple 4 ple 5 ple 6______________________________________ ##STR17## 2.0% -- 1.1% 18.0% 7.9% ##STR18## 18.2 30.2% 52.3 17.2 -- ##STR19## 35.8 27.6 7.9 41.9 60.0 ##STR20## 2.9 9.2 28.7 2.5 -- ##STR21## 4.4 5.2 1.2 -- -- ##STR22## 10.9 11.4 3.5 4.0 4.4 ##STR23## 21.1 13.1 2.4 5.7 22.7 ##STR24## -- -- -- -- 2.7 ##STR25## 4.4 -- 2.8 -- --______________________________________
Examples 7 through 11 are presented to demonstrate the chemistry of additional liquid phase chlorination after separation of various components from the reactor R2 effluent, as by vacuum distillation to yield the essentially pure compounds prior to such additional chlorination.
In Example 7, 2-chloropyridine, which has utility as an intermediate for fungicidal and bactericidal compositions, upon further chlorination in the liquid phase yields as its main reaction product 2,6-dichloropyridine.
EXAMPLE 7
Fifty grams of 2-chloropyridine were chlorinated in a 250 ml spherical chlorinator with 70 grams/hr. of chlorine for 3 hours at 160° C. Of the 33% 2-chloropyridine reacted, 87% went to the 2,6-dichloropyridine. This data is presented in TABLE FIVE.
This illustrates the predominant reaction occurring in Example 7: ##STR26##
TABLE FIVE______________________________________Liquid Phase Chlorination of 2-chloropyridine Initial Molar Molar Concentration afterCompound Concentration 3 hr @ 160° C.______________________________________ 100% 67.1% ##STR27## 0.9 ##STR28## 28.7 ##STR29## 0.9 ##STR30## 1.7 ##STR31## 0.8______________________________________
In Example 8, 2,6-dichloropyridine is converted in high yields to 2,3,5,6-tetrachloropyridine by ferric chloride catalyzed liquid phase chlorination.
EXAMPLE 8
Fifty grams of 2,6-dichloropyridine and 2 grams of anhydrous ferric chloride were chlorinated at 190° C. in the liquid phase with 70 grams per hour of chlorine for 8.25 hours to yield a 97.6% conversion to 2,3,5,6-tetrachloropyridine. TABLE SIX lists these results.
This illustrates the reaction occurring in Example 8: ##STR32##
TABLE SIX______________________________________Liquid Phase Chlorination of 2,6-dichloropyridinewith 4 weight % FeCl.sub.3 Molar Molar Concen- Concentration tration Initial after after Molar 2 hrs @ 8.25 hrsCompound Concentration 190° C. @ 190° C.______________________________________ 100% 51% -- ##STR33## 49 1.7% ##STR34## -- 97.6 ##STR35## -- 0.6______________________________________
EXAMPLE 9
Seventy-five grams of a mixture rich in 3-chloropyridine were chlorinated for 4 hours at 200° C. and 2 hours at 210° C. with 70 grams per hour chlorine to yield mixtures rich in 2,3,5- and 2,3,6-trichloropyridine. TABLE SEVEN lists these results:
This illustrates the reactions occurring in EXAMPLE 9: ##STR36##
TABLE 7______________________________________Liquid Phase Chlorination of 3-chloropyridine Molar Concentration Initial After 4 hrs @ Molar 200° C. + 2 hrsCompound Concentration @ 210° C.______________________________________ 100% -- ##STR37## 11.5% ##STR38## 24.0 ##STR39## 8.3 ##STR40## 20.8 ##STR41## 35.4______________________________________
EXAMPLE 10
Twenty-five grams of 3,5-dichloropyridine were chlorinated with 70 grams/hr of chlorine for 8 hours at 180° C. to yield a mixture rich in 2,3,5-trichloropyridine. TABLE EIGHT lists these results.
This illustrates the predominant reaction occurring in Example 10: ##STR42##
TABLE EIGHT______________________________________Liquid Phase Chlorination of 3,5-dichloropyridine Initial Molar Molar Concentration afterCompound Concentration 8 hrs @ 180° C.______________________________________ 100% 43.5% ##STR43## 55.2 ##STR44## 1.3______________________________________
EXAMPLE 11
Liquid chlorination of a mixture rich in 2,3,6-trichloropyridine catalyzed with four weight percent ferric chloride is illustrated in TABLE NINE and Example 11.
Fifty grams of a mixture rich in 2,3,6-trichloropyridine was chlorinated at 195° C. for 41/4 hours. The concentration of 2,3,6-trichloropyridine decreased from 89.4% to 1.7% while the concentration of 2,3,5,6-tetrachloropyridine increased from 4.5% to 97.6%. TABLE NINE lists the results.
This illustrates the predominant reaction occurring in Example 11: ##STR45##
TABLE NINE______________________________________ Initial Molar Concentration Molar after 4.25 hrs atCompound Concentration 195° C. + 4% FeCl.sub.3______________________________________ 89.4% 1.7% ##STR46## 4.5 97.6 ##STR47## 0.6______________________________________
It has been demonstrated that various liquid phase, uncatalyzed and catalyzed chlorinations of products obtained from vacuum distillation column C3 result in a method of producing mixtures rich in 2,3,5-trichloropyridine and/or 2,3,5,6-tetrachloropyridine, if desired. Useful chlorinated pyridines such as 2-chloropyridine may be separated out by vacuum distillation prior to their chlorination, if desired.
The main criteria for the absorbent charge in absorber C2 is that it is nonreactive at the temperature at which the absorber operates (140° C.), is a compound or mixture of compounds having a melting point less than 80° C., and is mutually soluble in carbon tetrachloride so that it doesn't plug up the scrubbing column C1, either through not melting or freezing or lack of solubilization. The absorber charge, being nonreactive, is basically a one time charge and recycled after removal of the absorbed product components, with only slight makeup from time to time. Functionally, the absorbent acts and is handled in much the same way as the carbon tetrachloride in the scrubbing column C1.
The chlorination process described in Taplin U.S. Pat. No. 3,424,754 relies on chlorine gas sparging into the liquid reaction mass to dissolve the chlorine in the reaction mass and to mix alpha-picoline hydrochloride with the initiator charge. According to Chemical Engineering Handbook, Perry, 3d Edition, page 1215 (1950), agitation produced by the degree of gas sparging involved in the process of U.S. Pat. No. 3,424,754 (estimated to be about 1.5 cubic foot per square foot minute at 200° C.) is usually too mild to move immiscible liquids with appreciable density differences into good contact with each other. In reactions according to the present invention, it is a practical necessity to maintain the reaction mass well mixed so that there is good contact and quick dispersion of the pyridine hydrochloride into the diluent at the desired reaction temperatures of greater than 150° C. because the polychlorinated pyridine diluent and the pyridine hydrochloride are immiscible and have substantially different densities (about 1.6 and about 1.2 grams per cubic centimeter, respectively), and because pyridine hydrochloride is unstable in this temperature range, i.e. the salt tends to break down to its components, namely hydrogen chloride and pyridine. If there is breakdown into the components, the hydrogen chloride is volatile and escapes through the vent system and pyridine builds up in a lighter liquid phase.
Yields of volatile chlorinated pyridines in excess of 99% and other new useful products are obtained when care is taken to ensure a high partial pressure of chlorine and sufficient mixing and quick dispersion of the pyridine or pyridine hydrochloride into a chlorine rich diluent which does not substantially compete for the available chlorine. This is accomplished by sparging chlorine (in excess of that needed for the reaction) and pyridine or pyridine hydrochloride at closely spaced locations near the bottom of the reactor means containing the polychlorinated pyridine diluent charge. The mixing required to ensure adequate contact between the liquids and gas can be achieved by high gas flow rate sparging, mechanical agitation, or a combination of both. High gas flow rates as described by Braulich, A. J.; Ch. E. Journal, Volume 11, No. 1, pp 73-79, can achieve mixing of a magnitude almost equivalent to high power input mechanical mixing. Several disadvantages are inherent in the use of high gas flow rates, however. They are:
(a) high entrainment of the reactor liquids to the scrubber column C1 where they are scrubbed with carbon tetrachloride and must be recycled to the reaction system.
(b) a large volume of chlorine gas which must be purified, dried, and recycled.
Another mode of operation to enhance mixing is to combine mechanical agitation with chlorine gas and pyridine or pyridine hydrochloride sparging to achieve the desired degree of mixing and excess chlorine. High maintenance of mechanical seals and agitators are some of the disadvantages of such a mechanical agitation system.
An increase in reactor back pressure aids in increasing the chlorine concentration in the reaction liquid. The stoichiometric amount of chlorine reacted per pound of pyridine fed is about 2:1 by weight. Chlorine in excess of the stoichiometric requirement is considered essential to ensure that the pyridine or pyridine hydrochloride does not form undesirable tars and polymers. Therefore, weight ratios of at least about 4:1 of chlorine to pyridine being fed are deemed necessary in practice of the present process.
Care must be taken not to exceed the thermal stability of the diluent system. Diluents such as 6-chloro- or 5,6-dichloro-2-trichloromethyl pyridine can decompose vigorously at temperatures greater than 260° C.
The above-described embodiments are intended to be illustrative, not restrictive. The full scope of the invention is defined by the claims, and any and all equivalents are intended to be embraced therein. | Preparation of high yields of mixtures rich in polychlorinated pyridines by maintaining a chlorine to pyridine weight ratio of greater than about 4:1 when reacting chlorine and pyridine or pyridine hydrochloride non-catalytically in the liquid phase at temperatures in excess of about 150° C., the reactants being contained in a well mixed diluent producing 1 mole or less of hydrogen chlorine per mole of diluent by reaction with the chlorine in the indicated temperature range. Reaction in a primary reactor is followed by selective further chlorination to obtain desired final products useful as intermediates in the formation of herbicides and the like. | 2 |
TECHNICAL FIELD
This invention relates to the art of carbonaceous articles and their manufacture. In the preferred embodiments, the invention relates to methods and apparatus for the manufacture of carbon and graphite electrodes from carbonaceous, self-baking electrode paste.
BACKGROUND ART
Self-baking electrodes are known. This type of electrode is made by baking a carbonaceous paste in conjunction with operation of an electric arc furnace, which receives the baked electrode. An early such electrode is shown in U.S. Pat. No. 1,442,031 (Soderberg), which includes a container for holding electrode paste and bakes the paste by heating it. Unbaked electrode paste cannot carry a large electric current, but the baked paste is capable of carrying substantial electrical current and is used for supplying the large amounts of electric current required for operation of electric arc furnaces. Applicant's prior U.S. Pat. No. 4,756,813 teaches a self-baking electrode wherein electric current, both for operating a furnace and baking the paste, is supplied to the paste through a centrally-located mandrel. U.S. Pat. No. 3,524,004 (Van Nostran et al.) also shows supply of electric current to the center of the electrode to bake the paste and supply of a portion of the current required by the furnace to the exterior of the electrode. U.S. Pat. No. 4,527,329 (Bruff) shows a process for manufacture of a furnace electrode in situ where heat for baking the paste is supplied independently of the current operating the furnace.
Further, it is known to extrude a self baking electrode by application of pressure to the electrode paste, as shown in applicant's prior U.S. Pat. No. 4,756,004. While the structure shown in this patent is useful, the baked electrode is susceptible to inadequate baking on the one hand and becoming stuck in the housing on the other.
Known methods for making self-baking electrodes have not been successful, primarily because of the difficulties arising from the interaction between the baking zone and the various parts of the baking apparatus. The Van Nostran apparatus, for example, uses a screw to advance the baked paste, but strong adherence between the screw and the baked paste eventually results in an inability to continue advancing the electrode and consequent failure. Similarly, production of self baking electrodes in accordance with applicant's prior patents has been problematic because of the adhesion between the baked paste and the paste container.
SUMMARY OF THE INVENTION
In accordance with a first aspect of the invention, carbonaceous articles are made by baking and extruding "self-baking" carbonaceous paste independently of a furnace. These articles are preferably electrodes for electric arc furnaces but may be electrodes for electrolytic refining of metals, such as aluminum, or articles for a variety of other purposes. Manufacture of carbonaceous articles independent of a furnace has several advantages including the ability to bake the articles without concern for the immediate operating requirements of the furnace and the ability to locate the manufacturing facility remote from the furnace. (The term "baked paste" is used herein to mean paste that has achieved at least the rigidity required to maintain its shape, but which may be considered only partially baked because volatile components in an amount greater than about one percent remain. The term "unbaked paste" is used to refer to paste that is not capable of maintaining its shape outside the paste container.)
The articles are baked and extruded in basically the desired shape for final use and then machined, if necessary, to the final shape. The finished articles are moved to the desired location and used in the known manner. A baking facility is generally capable of making electrodes at a rate greater than that required by a single electric arc furnaces, which means that the electrodes so made may be used to supply a plurality of furnaces. Similarly, articles designed for use in other processes, such as electrodes for electrolytic refining, are made in proportion to the rate of use that is most economical.
When a carbonaceous article is fully baked in the baking station it can be further processed for use, for example, by detaching the article from the remainder of the extrusion. If the article has not been fully baked in the baking station, it may be baked further by application of heat by known techniques. For example, the baked paste may be supplied with electric current by an electric circuit separate from that which supplies the baking current, whereby the article is further heated by resistance heating (I 2 R heating). Preferably, however, the baked article is further heated inductively by passing it through induction coils. Other heating devices, such as a gas heater may also be useful in some circumstances. When the partially baked article is used as an electrode in an electric arc furnace, the paste may be additionally baked by furnace current supplied through the electrode or by heat from the furnace.
In accordance with another embodiment of the invention, baked paste is converted to graphite by heating the paste to a high temperature (2500° C. or greater) and holding it at the elevated temperature. This is accomplished, preferably, by passing the electrode through an induction coil where it is heated inductively. Paste maintained at this high temperature must be insulated to prevent the loss of heat. The insulating material, which is preferably carbon black, is supported around the electrode by a cylindrical tube made of inductively-transparent materials, such as those described in U.S. Pat. No. 4,921,222 (Mott).
Conversion of the baked paste to graphite is preferably done as the paste exits the container where the initial baking is done to obviate cooling and consequent reheating of the article. Alternatively, however, articles may be converted to graphite at a separate location. The additional heat is preferably provided by induction, and when the conversion is done as the paste exits the baking container, the induction coil and insulating structure are contiguous to the container. If the conversion is done in a remote location, the coil and insulating structure may receive a single article or be large enough to receive a number of articles simultaneously.
Applicant has discovered that a primary cause of problems in extrusion of baked articles is excessive adhesion between the baked paste and the structure containing the unbaked paste, such as the paste container and the central conductor, or mandrel. This adhesion results from the inability to control the size or location of the baking zone in the paste. Thus, when a central electrode is employed to provide the baking current, the baking zone should be located close to the tip of the central electrode. Movement of the baking zone away from the tip of the electrode, toward the exit end of the paste container, results in insufficient baking and consequent risk of break-out of green paste into the tubular cavity formed in the paste by the electrode. If the baking zone moves in the opposite direction, away from exit end of the paste container, the baked carbon will hang up in the container and prevent further extrusion. Thus, it is an objective of this invention to provide methods and apparatus for controlling the position of the baking zone whereby the paste is properly baked but does not interfere with extrusion of the baked paste.
In accordance with a preferred embodiment of the invention, changes in the longitudinal location of the baking zone are detected by measuring changes in the force required to extrude the article. An increase in the force required to extrude an article indicates that the baking zone is growing, or moving away from the exit of the paste container. Conversely, a decrease in the required extrusion force indicates that the baking zone is shrinking, or moving toward the end of the paste container. Changes in the required extrusion force are detected in the preferred embodiment by detecting a decrease in the extrusion, or "slipping" rate when holding the extrusion force steady. If the baking energy is also steady, a decrease in the slipping rate will result in an excessive baking rate because the baking energy required is a function of the slipping rate. This imbalance can be corrected by decreasing the baking rate or by increasing the slipping rate, or both. In the preferred embodiment, predetermined baking and slipping rates are determined at the outset, and small corrections are made during baking by adjusting the extrusion force to adjust the slipping rate while holding the baking energy steady.
Changes in the force required to extrude the baked paste may be measured by various techniques. In the preferred embodiment, a load cell is held to the baked article by a moving support element, which is preferably a rod or shaft of a hydraulic cylinder, ball screw mechanism, or other device that provides an element capable of programmed motion. In the preferred embodiment, the shaft engages the bottom of the extruded article, and the load cell is held between the two. The load cell may be placed in other locations, however, such as the periphery of the article, if the shaft engages the periphery. The shaft is driven to move at the expected slipping rate, and an increase in the force detected by the load cell indicates that the baked article is moving toward the shaft faster than the shaft is receding. This, in turn indicates that the adhesion forces have decreased and that the baking zone is shrinking. Decreases in the force detected by the load cell indicate the converse. In the embodiment where the article is extruded by application of pressure to the paste, a control circuit is provided to adjust the paste pressure applied by the paste pump until the rate of extrusion again matches the speed of the shaft. If the article is extruded by another technique, such as by the screw shown in the Van Nostran patent, the extrusion mechanism, e.g., the motor driving the screw, is controlled.
If small changes in the paste pressure do not reestablish the desired position of the baking zone, the speed of the shaft, the input baking energy, the extruding forces, or all of these may be adjusted.
The slipping rate may, of course, be measured in other ways, such as optically, electrically, or mechanically.
In accordance with yet another aspect of the invention, the moving shaft applies a significant force to the article in a direction opposing extrusion. Thus, the extrusion forces must overcome the sum of the adhesion forces and the opposing force. The advantage of such a system when extrusion is caused by paste pressure is that the pressure can be higher than that required to overcome the adhesion forces by an amount that depends on the magnitude of the opposing force. Baking the paste under continuously-applied higher pressure has been found to produce an article superior to those previously obtained. Preferably, the pressure in the paste is at least about 70 psi. The resulting carbon article is denser, stronger, and lower in resistivity, because the paste is compacted by the high pressures, and the gasses are cracked in the pores of the article at higher pressure.
Applicant has discovered that carbon paste has a tendency to bake unevenly in the peripheral direction and that this complicates the extrusion process and results in an inferior product. Uneven baking occurs during resistance heating because the resistivity of the paste decreases as the paste bakes. In the embodiment where the baking current flows between a central electrode, or mandrel, and a peripheral electrode, the paste in the paths initially carrying higher current, for any reason, will bake faster, resulting in lower resistivities in those paths and drawing yet more current. Thus, the paste lying in those paths will be preferentially baked, and the remaining parts of the paste will be incompletely baked. This asymmetry is corrected in the preferred embodiment by providing a plurality of spaced, peripheral electrodes and a control circuit for adjusting the current flowing from the central electrode to each respective peripheral electrode. The magnitude of the current flowing in the individual paths can be determined in any of several ways, such as by measuring the temperature of the paste adjacent each of the electrodes, relatively higher temperatures indicating faster baking. In addition, the central electrode itself is preferably divided into segments, e.g., four segments, to provide more precise control of the current and to decrease the time required to alter the baking pattern. In this embodiment, the control circuit adjusts the current flowing among the segments of the central electrode and the individual electrodes on the periphery of the baking zone to control accurately the peripheral location of the baking zone.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a vertical cross section of a prior art self-baking electrode.
FIG. 2 is a side view of an apparatus for producing an electrode in accordance with the invention by using electric resistance means for additional heating of the partially-baked electrode portion and also illustrating use of the electrode so made with a furnace.
FIG. 3 is a side view of an apparatus similar to that shown in FIG. 3 wherein a hydraulic cylinder supports the electrode and a load cell provides data indicating the location of the baking zone.
FIG. 4 is a side view of another embodiment of the invention wherein the partially-baked electrode is heated further by induction.
FIG. 5 is a side view of an embodiment of the invention wherein the electrode paste is converted to graphite by induction heating.
FIG. 6 is a cross section taken along line 6--6 of FIG. 5.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates a portion of a prior art self-baking electrode, such as that shown in U.S. Pat. No. 4,756,004. A pressure container illustrated as a vessel 2 is supplied with self-baking paste 4 through an inlet shown as a supply tube 6. The supply tube and pressure vessel are heated by any known means, illustrated in the drawings as steam tubes 8, to maintain the temperature of the paste whereby it can flow through the tube and into the vessel. Electric current is supplied to the paste in the vessel through a conductor 10, which is connected to a power bus 12 by a cylindrical bus 14. The cylindrical bus is water-cooled and includes an outer casing 16 to provide a water jacket 18. Current flows from the conductor 10 through the paste to form a baking zone 19, and the lower end of the container forms an exit through which a baked portion 20 of the electrode exits the vessel. The lower end of the vessel includes a support band 22, which may be formed in any of several know ways. The support band 22 supports a portion of the weight of the electrode and is adjustable to allow the electrode to advance at the desired rate in response to the weight of the electrode and the force applied by the pressurized paste.
FIG. 2 illustrates an embodiment of the invention for making an electrode for use in an electric arc furnace. A pressure baking vessel 24 similar to that shown in FIG. 1 is supported above a metallurgical electric-arc furnace 26 such that an extruded electrode 40 is directed into the furnace for supplying electric current to create the arc during operation of the furnace. The paste is supplied to the pressure vessel through inlet 6 by a pump 7, and the pressure of the paste extrudes baked paste 28 through the outlet formed by the end of the vessel. The paste is heated by conduction of current between each conducting segment 11 of the centrally-located mandrel electrode 10 and respective ones of the peripherally located electrodes 30. The baking current flowing through the paste between the mandrel 10 and the electrodes 30 is controlled by controller 32. The electrode 40 is supported by any of several known means, this embodiment illustrating the use of slipping shoes 34 to support the electrode. These slipping shoes serve the same general purpose as does the support band 22 in FIG. 1 and include a stationary set of shoes and a moving set as known in the art. The moving shoes move with the electrode as it slips, and the fixed shoes support the electrode while the moving shoes reset positions.
The slipping shoes and the support band can be controlled whereby the vertical motion of the electrode can be monitored by instruments mounted on these elements. Thus, the grip of the band 22 and the rate of motion of the slipping shoes 34 will determine the vertical motion of the baked electrode. As will be described in detail below, the invention includes precise measurement of the vertical motion of the electrode and feedback to the pressure pump 7 to control the location of the baking zone. Further, the invention includes application of a significant force resisting extrusion of the electrode to allow use of larger pressures during baking, and the band 22 or the slipping shoes can be controlled to provide this force.
The main electric power for operation of the furnace is provided by the power supply 36, which, for example, provides 10 megawatts of electric power through contacts 38 for conduction through baked paste 40 and into the furnace. It will be appreciated that because the electric circuit having controller 32 is separate from the electric circuit having the power supply 36, the two systems may be operated separately to provide the desired degree of baking in the upper part of the electrode and the necessary current for operation of the furnace.
The electrode in FIG. 2 is baked by the current provided by controller 32. If the baking is not complete in that too many volatile components remain, heat from the furnace 26 or current provided by the main power supply 36 will provide further baking.
The baking is often not even about the periphery of the electrode. This asymmetry indicates that the individual baking zones corresponding to respective electrodes 30 are not equidistant from the end of the pressure vessel 2. In the embodiment shown, the controller includes a separate controller for each of the eight electrodes 30, which are evenly spaced about the periphery of the electrode portion 28. The individual controllers, for example, halmar controllers, control the current flowing through each of the individual electrodes. Thus, in addition to controlling the overall amount of current passing through the electrode paste, the controller 32 further ensures that the baking current is evenly distributed throughout the paste by adjusting the current flowing to each of the individual electrodes to avoid uneven baking of the electrode. In the preferred embodiment the controller accomplishes this by including a thermocouple as a part of the electrode 30 to monitor the temperature of the baked electrode at each of the individual electrodes 30. The controller then adjusts the current flowing through that electrode to cause the baking to be even throughout the electrode.
For example, if it is desired to provide baking heat generated by at least 2400 amperes flowing through the baking zone, a controller capable of controlling current in the range of zero to 1000 amperes can be used for each of the electrodes 30. This means that the desired 2400 amperes can be provided by 800 amperes from as few as three of the electrodes. Thus, if the baking in one portion of the paste is lagging that in the remainder of the paste, the controller can reduce the current flow in selected electrodes 30 and direct the baking current to the other electrodes to cause the baking to even out.
In the embodiment where the central electrode comprises a plurality of segments spaced about the circumference of the central electrode, the controller is arranged to direct the current intended to flow to electrodes 30 located on one side of the baking zone through segments 11 that are also located on that same side of the baking zone. This arrangement prevents formation of current paths that originate at the central electrode on one side of the baking zone and then reverse direction to flow to an electrode 30 on the opposite side of the baking zone. Forcing the current to flow to the electrodes 30 of choice by this geometry results in faster response to changes in the current flow.
FIG. 3 illustrates an embodiment where the article in the form of a cylindrical electrode is not supplied to a furnace directly. The electrode may, however, be used in an electric arc furnace not physically connected to the baking station. For example, the electrode may be made as described below, processed further chemically or physically, such as by machining and/or combination with other electrodes, and then transported to the furnace for use as an electrode with known equipment. Articles of other shapes and for other uses may be extruded by the same techniques, as well.
As noted above the magnitude of the force arising from adhesion between the baked paste and the sides of the container, which includes the frictional force, is a good indicator of the longitudinal location of the baking zone. The force of adhesion on a sixteen-inch diameter electrode has been determined to be 22 to 85 pounds per square inch of contact area between the baking zone of the electrode and the housing. This provides 21,000 to 82,000 pounds of resistance to movement of the electrode.
The preferred technique, shown in FIG. 3, for controlling the position of the baking zone is to detect very small changes in the slipping rate and adjust the pressure of the paste to achieve the desired slipping rate. Thus, it may be determined that for a given baking power input a slipping rate of seven inches per hour is to be expected. The paste pressure is then set to obtain that nominal slip rate. The actual slipping rate is measured by placing a load cell between the bottom of the extruded article and a shaft that engages the load cell and moves at the expected rate. In the embodiment of FIG. 3, the baked article 40, which in the drawings is in the shape of an electrode, is supported on a shaft 46 of a hydraulic cylinder 48. The hydraulic cylinder is controlled to move at the expected slipping rate, for example, by a solenoid-activated valve. The force applied to the shaft by the article is detected by a load cell 50. An increasing force detected by the load cell as it moves away from the housing 24 at the expected slipping rate indicates that slipping rate is greater than expected, which indicates that the baking zone is shrinking and providing smaller adhesion forces. A decreasing force indicates the opposite. The load cell may be placed at other locations and be other types of devices, depending on the mode of engagement between the shaft and the baked article. In the embodiment of FIG. 2, where slipping shoes are used to support the electrode, the compression load cell 50 my be replaced by a tensional load cell. Further the hydraulic cylinder can as well be a ball-screw, rack-and-pinion, or like mechanism capable of providing a resisting force at a controlled rate of movement.
In the preferred embodiment, the hydraulic cylinder 48 provides a substantial force resisting advancement of the electrode while still permitting advancement of the electrode at a predetermined rate. For example, the resistance force provided by the hydraulic cylinder may be 7,000 pounds, and the slipping rate may be seven inches per hour. If the resisting force on a sixteen-inch diameter electrode is 7,000 pounds, the pressure on the unbaked paste must be 7,000 pounds divided by the cross-sectional area of the electrode to overcome this resisting force. Thus, the pressure in the paste must overcome the adhesion force noted above plus the 7000 pound additional resisting force. This increased pressure produces an article that has been found to have the superior physical and electrical properties discussed above.
Changes in the adhesion forces between the housing and the baked paste are detected very quickly in the FIG. 3 embodiment because the load cell is inelastic. Thus, movement of the load cell away from the article is sensed almost instantaneously, and the control system 51 increases the pressure applied to the paste until the predetermined force is attained, indicating that the desired extrusion rate has been again achieved. Similarly, if the adhesion forces decrease, the extruded article will push harder against the load cell, which will be sensed by the load cell, and the controller 51 will reduce the pressure on the paste.
The above describes a situation where changes in the location of the bake zone are small and can be corrected by relatively small changes in the pressure of the paste. This situation occurs when the baking rate and the extrusion rate essentially match. If these rates do not match, however, the rate of extrusion or the baking rate must be adjusted. The baking rate is changed by altering the energy applied to the bake zone and depends on the method of heating being used. If the method of heating is resistance (I 2 R) heating, the current though the paste is reduced. If the method of heating is inductive, the current in the induction coils is reduced.
In the embodiment of FIG. 3, the baking rate and the slipping rate are varied in stepwise fashion, and the pressure on the paste is continuously varied. It is also possible to vary the slipping and baking rates continuously, however.
______________________________________ Cause of changeForce on in forces on load Short term Long termload cell cell correction correction______________________________________Increases Bake zone is Reduce paste Increase baking shrinking and pressure to power or decrease extrusion rate is maintain set set extrusion rate. increasing extrusion rateDecreases Bake zone is Increase pressure Decrease baking growing and on paste to maintain power or increase extrusion rate is set extrusion rate set extrusion rate. decreasing______________________________________
FIG. 4 illustrates another embodiment of the invention where induction heating is employed to bake the paste in the container and to bake further the extruded article. Thus, the pressure baking system 24 includes a container such as that shown in FIG. 1 that is capable of withstanding pressure and further that is made of inductively transparent materials. A preferred such material is the inductively-transparent, composite disclosed in U.S. Pat. No. 4,921,222. A first induction coil 41 carrying current supplied by source 39 is placed around the container near the exit end to heat the paste inductively by forming a baking zone. The baked article is extruded by the pressure of the paste as described above.
A second induction coil 42 carrying current from source 43 is located adjacent the extruded article after it has emerged from the pressure baking system to further bake the article. Inductive heating as shown in this figure may be used in conjunction with a furnace, similar to that shown in FIG. 2, or independent of a furnace, as shown in FIG. 3. Further, the location of the baking zone is controlled in the manner discussed with respect to FIG. 3 by controlling the slipping rate for a predetermined current through coils 41.
Inductive heating of the electrode is particularly useful when the baked carbon paste is to be converted to graphite, which requires the article to be heated to a temperature above 2500° C. for a predetermined period of time. This high temperature requires an energy source of significant size and high temperature insulation to reduce escape of heat from the hot electrode. FIGS. 5 and 6 illustrate a preferred embodiment for producing a graphite article.
In accordance with the embodiment shown in FIGS. 5 and 6, the electrode from the system 24 is extruded directly into an inductive heating station comprising an insulating, tubular structure 52 and an induction coil 42. The source of heat for baking in this embodiment is illustrated to be resistive, but it may be inductive as in FIG. 4, gas flame, or otherwise. The secondary heating, is preferably inductive, but may be others as well. When inductive heating is used, the tubular structure is made of materials that are transparent to the frequencies produced by the induction coil, whereby a major part of the energy produced by the coil is transmitted to the electrode to raise it to the desired temperature. In the preferred embodiment, the tubular structure 52 is made of a composite material comprising substantially continuous glass fibers and inorganic cement forming a matrix for the fibers as described in U.S. Pat. No. 4,921,222 (Mott).The length of the tubular structure is such that the transit time of the electrode through the structure is at least equal to the time required for achieving the desired temperature and converting the baked electrode paste to graphite. Thus, a cylindrical graphite article for use as an electrode or for other purposes exits the end of the tubular structure 52 opposite the housing 24.
FIG. 6 is a cross section taken along line 6--6 of FIG. 5 and illustrates the placement of insulation 54, such as carbon black, between the outer surface of the baked electrode and the inner surface of the tubular structure. The carbon black provides thermal insulation for the high temperature electrode and does not degrade at the high temperatures. The carbon black is maintained in the tubular structure by a seal placed at the end of the structure remote from the housing 24.
It will be appreciated that a unique system for providing a baked electrode to a furnace or for other purposes has been described. Modifications within the scope of the appended claims will be apparent to those of skill in the art. | A carbonaceous article is made by baking paste under continuously applied high pressure. The paste is extruded as it is baked to form the article, and the article may be further machined after baking. A force opposing extrusion is applied to the article to allow high pressures to be provided to the paste. The location of the baking zone both longitudinally and peripherally is carefully controlled to preclude over or under baking. Longitudinal control of the baking zone is effected by measuring the force required to extrude baked paste, and peripheral control is effected by measuring the extent of the baking at several peripheral locations and controlling the baking current at these locations. The article may be an electrode for supply to an electric arc furnace immediately after baking or to a furnace remote from the baking station. The article may also be converted to graphite by heating the article to a graphitizing temperature, and the additional heat may be provided by electric resistance heating or by induction heating. | 7 |
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a process for preparing stereoisomerically enriched 3-heteroaryl-3-hydroxypropionic acid derivatives by reducing 3-heteroaryl-3-oxopropionic acid derivatives in the presence of ruthenium-containing catalysts.
[0002] Stereoisomerically enriched 3-hydroxypropionic acid derivatives, in particular those which bear a heteroaryl radical in the 3-position, are valuable intermediates, for example, in the preparation of liquid-crystalline compounds, agrochemicals and pharmaceuticals.
[0003] Process for preparation comprising the catalytic reduction of ketones to stereoisomerically enriched secondary alcohols is known in principle. Useful reducing agents are typically molecular hydrogen or, in the case of transfer hydrogenations, organic hydrogen donors, for example formic acid or isopropanol. An advantage of transfer hydrogenations is that the safety precautions which have to be taken when handling highly flammable molecular hydrogen under pressure can be dispensed with. It is also generally possible to work at ambient pressure. A review of transfer hydrogenations as a method for catalytic reduction of ketones is given, for example, by Zassinovich et al. in Chem. Rev. 1992, 92, 1051-1069 and Noyori et al. in Ace. Chem. Res. 1997, 30, 97-102 and Wills et al. in Tetrahedron, Asymmetry, 1999, 2045.
[0004] Noyori et al. (JACS 1996, 118, 2521-2522, Ace. Chem. Res. 1997, 30, 97-102) describe the use of ruthenium complexes as catalysts and triethylamine/formic acid for the enantioselective reduction of simple ketones.
[0005] However, there still existed the need to provide an efficient process which allows the preparation of stereoisomerically enriched 3-heteroaryl-3-hydroxypropionic acid derivatives from 3-heteroaryl-3-oxopropionic acid derivatives.
SUMMARY OF THE INVENTION
[0006] A process has now been found for preparing stereoisomerically enriched 3-hetero-aryl-3-hydroxypropionic acid derivatives, which is characterized in that
[0007] a) compounds of the formula (I)
heteroaryl-CO—CH 2 W (I);
[0008] where
[0009] heteroaryl is a mono-, bi- or tricyclic aromatic radical having a total of from 5 to 18 ring atoms where each cycle may have no, one, two or three ring atoms and there may be one, two, three, four or five ring atoms in the entire aromatic radical selected from the group of oxygen, sulphur and nitrogen, and where the mono-, bi- or tricyclic aromatic radical may optionally be mono- or polysubstituted and
[0010] W is C(O)YR 1 n where Y is oxygen and n=1 or Y is nitrogen and n=2, or
[0011] W is CN, and
[0012] R 1 is in each case independently hydrogen, C 1 -C 20 -alkyl, C 4 -C 14 -aryl or C 5 -C 15 -arylalkyl or, in the case that Y is nitrogen, both R 1 radicals together are C 3 -C 12 -alkylene,
[0013] b) in the presence of a ruthenium-containing catalyst and
[0014] c) in the presence of at least one amine, at least some of which is present in protonated form,
[0015] d) are reacted with formic acid, formates or mixtures thereof
[0016] e) optionally in the presence of organic solvent.
[0017] As would be realized, the scope of the invention also encompasses any desired combinations of the ranges and preferred ranges specified for each feature.
DETAILED DESCRIPTION OF THE INVENTION
[0018] The invention is described more fully herunder with particular reference to specific embodiments thereof. For the purposes of the invention, stereoisomerically enriched (enantiomerically enriched, diastereomerically enriched) 3-heteroaryl-3-hydroxypropionic acid derivatives are stereoisomerically pure (enantiomerically pure or diastereomerically pure) 3-heteroaryl-3-hydroxy-propionic acid derivatives or mixtures of stereoisomeric (enantiomeric or diastereomeric) 3-heteroaryl-3-hydroxypropionic acid derivatives in which one stereoisomer (enantiomer or diastereomer) is present in a larger absolute portion, preferably 70 to 100 mol % and very particularly preferably 85 to 100 mol %, than another diastereomer, or than the other enantiomer.
[0019] For the purposes of the invention, alkyl is, in each case independently, a straight-chain or cyclic, and, independently thereof, branched or unbranched, alkyl radical which may be further substituted by C 1 -C 4 -alkoxy radicals. The same applies for the alkylene moiety of an arylalkyl radical -;
[0020] For the purposes of the invention, alkyl can be C 1 -C 4 -alkyl, for example, methyl, ethyl, 2-ethoxyethyl, n-propyl, isopropyl, n-butyl and tert-butyl; C 1 -C 8 -alkyl, for example, n-pentyl, cyclohexyl, n-hexyl, n-heptyl, n-octyl or isooctyl; C 1 -C 12 -alkyl, for example, norbornyl, n-decyl and n-dodecyl, and C 1 -C 20 , for example, n-hexadecyl and n-octadecyl.
[0021] For the purposes of the invention, aryl is, for example and with preference, carbocyclic aromatic radicals or heteroaromatic radicals which contain no, one, two or three heteroatoms per cycle, but at least one heteroatom in the entire heteroaromatic radical which is selected from the group of nitrogen, sulphur and oxygen.
[0022] The carbocyclic aromatic radicals or heteroaromatic radicals may further be substituted by up to five substituents per cycle, each of which is, for example and with preference, independently selected from the group of hydroxyl, C 1 -C 12 -alkyl, cyano, COOH, COOM where M is an alkali metal ion or half an equivalent of an alkaline earth metal ion, COO—(C 1 -C 12 -alkyl), COO—(C 4 -C 10 -aryl), CO—(C 1 -C 12 -alkyl), CO—(C 4 -C 10 -aryl), O—(C 1 -C 12 -alkyl), O—(C 4 -C-10-aryl), N(C 1 -C 12 -alkyl) 2 , NH—(C 1 -C 12 -alkyl), fluorine, chlorine, bromine, C 1 -C 12 -fluoroalkyl where fluoroalkyl is a singly, multiply or fully fluorine-substituted alkyl radical as defined above, CONH 2 , CONH—(C 1 -C 12 -alkyl), NHCOO—(C 1 -C 12 -alkyl). The same applies to the aryl moiety of an arylalkyl radical.
[0023] In formula (I), heteroaryl is preferably a mono- or bicyclic aromatic radical having a total of 5 to 12 ring atoms where, in each cycle, no, one or two, and in the entire aromatic radical, one, two, three or four, ring atoms selected from the group of oxygen, sulphur and nitrogen may be present, and where the mono- or bicyclic aromatic radical bears no, one, two or three radicals per cycle which are each independently selected from the group of hydroxyl, C 1 -C 12 -alkyl, cyano, COOH, COOM, COO—(C 1 -C 12 -alkyl), COO—(C 4 -C 10 -aryl), CO—(C 1 -C 12 -alkyl), CO—(C 4 -C 10 -aryl), O—(C 1 -C 12 -alkyl), (C 1 -C 12 -alkyl)-O—(C 1 -C 12 alkyl), (C 4 -C 10 aryl)-O—(C 1 -C 12 -alkyl), O—(C 4 -C 10 -aryl), O—CO—(C 4 -C 10 -aryl), O—CO—(C 1 -C 1 2 -alkyl), OCOO—(C 1 -C 12 -alkyl), N—(C 1 -C 12 -alkyl) 2 , NH—(C 1 C 12 -alkyl), N(C 4 -C 10 -aryl) 2 , NH—(C 4 -C 10 -aryl), fluorine, chlorine, bromine, iodine, NO 2 , SO 3 H, SO 3 M, SO 2 (C 1 -C 12 -alkyl), SO(C 1 -C 12 -alkyl), C 1 -C 12 -fluoroalkyl where fluoroalkyl is a singly, multiply or fully fluorine-substituted alkyl radical as defined above, NHCO—(C 1 -C 12 -alkyl), CONH 2 , CONH—(C 1 -C 12 -alkyl), NHCOO—(C 1 -C 12 -alkyl), PO(C 4 -C 10 -aryl) 2 , PO(C 1 -C 12 -alkyl) 2 , PO 3 H 2 , PO 3 M 2 , PO 3 HM, PO(O(C 1 -C 12 -alkyl) 2 , where M is in each case an alkali metal ion or half an equivalent of an alkaline earth metal ion.
[0024] In formula (I), heteroaryl is particularly preferably 2- or 3-thiophenyl, 2- or 3-furanyl, 2- or 3-pyrrolyl, 3- or 4-pyrazolyl 1-, 2-; or 4-thiazolyl, 1-, 2-, or 4oxazolyl, 2-, 4- or 5-imidazolyl, 2-, 3-, or 4-pyridyl, 2- or 3-pyrazinyl, 2-, 4-, or 5-pyrimidyl, 3-, 4-, 5- or 6-pyridazinyl, 2- or 3-indolyl, 3-indazolyl, indazolyl, 2- or 3-benzofuranyl, 2- or 3-benzothiophen-yl, 2-, 3- or 4-quinolinyl, isoquinolinyl 2-, 4-, 6- or 7-pteridinyl or 2-, 3-, 4-, 5-, 6-, 8-, 9- or 10-phenanthrenyl where each of the radicals mentioned bears no, one or two radicals per cycle, each of which is independently selected from the group of C 1 -C 4 -alkyl, cyano, COO—(C 1 -C 4 -alkyl), O—(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , NH—(C 1 -C 4 -alkyl), fluorine, chlorine, bromine or C 1 -C 4 -fluoroalkyl, for example trifluoromethyl, 2,2,2-trifluoroethyl or pentafluoroethyl.
[0025] Heteroaryl in formula (I) is very particularly preferably 2-thiophen-yl.
[0026] W in formula (I) is preferably COOR 1 where R 1 is hydrogen the C 1 -C 8 -alkyl.
[0027] R 1 in formula (I) is preferably C 1 -C 12 -alkyl, phenyl, o-, m- or p-tolyl, p-nitro-phenyl or benzyl.
[0028] R 1 in formula (I) is particularly preferably methyl, ethyl, 2-ethoxyethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, cyclohexyl and n-hexyl, and also trifluoro-methyl, chloromethyl, benzyl and phenyl, and also 1,5-pentylene, 1,4-butylene and 3-propylene.
[0029] Very particularly preferred compounds of the formula (I) are methyl 3-oxo-3-(4-pyridinyl)propanoate, ethyl 3-oxo-3-(4-pyridinyl)propanoate, isopropyl 3-oxo-3-(4-pyridinyl)propanoate, tert-butyl 3-oxo-3-(4-pyridinyl)propanoate, 2-ethyl-hexyl 3-oxo-3-(4-pyridinyl)propanoate, 3-oxo-3-(4-pyridinyl)propanamide, N,N-dimethyl-3-oxo-3-(4-pyridinyl)propanamide, N-methyl-3-oxo-3-(4-pyridinyl) propanamide, N,N-diethyl-3-oxo-3-(4-pyridinyl)propanamide,N-ethyl-3-oxo-3-(4-pyridinyl) propanamide, 3-oxo-3-(N-piperidinyl)-1-(4-pyridinyl)- 1 -propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(4-pyridinyl)-1-propanone, 3-oxo-3-(4-pyridinyl) propanenitrile, methyl 3-oxo-3-(3-pyridinyl)propanoate, ethyl 3-oxo-3-(3-pyridinyl)propanoate, isopropyl 3-oxo-3-(3-pyridinyl)propanoate, tert-butyl 3-oxo-3-(3-pyridinyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-pyridinyl)propanoate, 3-oxo-3-(3-pyridinyl)propanamide, N,N-dimethyl-3-oxo-3-(3-pyridinyl)propanamide, N-methyl-3-oxo-3-(3-pyridinyl)propanamide, N,N-diethyl-3-oxo-3-(3-pyridinyl)propanamide, N-ethyl-3-oxo-3-(3-pyridinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-pyridinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-pyridinyl)-1-propanone, 3-oxo-3-(3-pyridinyl)propanenitrile, methyl 3-oxo-3-(2-pyridinyl)propanoate, ethyl 3-oxo-3-(2-pyridinyl)propanoate, isopropyl 3-oxo-3-(2-pyridinyl)propanoate, tert-butyl 3-oxo-3-(2-pyridinyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-pyridinyl)propanoate, 3-oxo-3-(2-pyridinyl)propanamide, N,N-dimethyl-3-oxo-3-(2-pyridinyl)propanamide, N-methyl-3-oxo-3-(2-pyridinyl)propanamide, N,N-diethyl-3-oxo-3-(2-pyridinyl)propanamide, N-ethyl-3-oxo-3-(2-pyridinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-pyridinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-pyridinyl)-1-propanone, 3-oxo-3-(2-pyridinyl)propanenitrile, methyl 3-oxo-3-(5-pyrimidinyl)propanoate, ethyl 3-oxo-3-(5-pyrimidinyl)propanoate, isopropyl 3-oxo-3-(5-pyrimidinyl)propanoate, tert-butyl 3-oxo-3-(5-pyrimidinyl)propanoate, 2-ethylhexyl 3-oxo-3-(5-pyrimidinyl)propanoate, 3-oxo-3-(5-pyrimidinyl)propanamide, N,N-dimethyl-3-oxo-3-(5-pyrimidinyl)-propanamide, N-methyl-3-oxo-3-(5-pyrimidinyl) propanamide, N,N-diethyl-3-oxo-3-(5-pyrimidinyl)propanamide, N-ethyl-3-oxo-3-(5-pyrimidinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(5-pyrimidinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(5-pyrimidinyl)-1-propanone, 3-oxo-3-(5-pyrimidinyl) propanenitrile, methyl 3-oxo-3-(4-pyrimidinyl)propanoate, ethyl 3-oxo-3-(4-pyrimidinyl)propanoate, isopropyl 3-oxo-3-(4-pyrimidinyl)propanoate, tert-butyl 3-oxo-3-(4-pyrimidinyl)propanoate, 2-ethylhexyl 3-oxo-3-(4-pyrimidinyl)propanoate, 3-oxo-3-(4-pyrimidinyl)propanamide, N,N-dimethyl-3-oxo-3-(4-pyrimidinyl)propanamide, N-methyl-3-oxo-3-(4-pyrimidinyl)propanamide, N,N-diethyl-3-oxo-3-(4-pyrimidinyl)propanamide, N-ethyl-3-oxo-3-(4-pyrimidinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(4-pyrimidinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(4-pyrimidinyl)-1-propanone, 3-oxo-3-(4-pyrimidinyl)propanenitrile, methyl 3-oxo-3-(2-pyrimidinyl)propanoate, ethyl 3-oxo-3-(2-pyrimidinyl)propanoate, isopropyl 3-oxo-3-(2-pyrimidinyl) propanoate, tert-butyl 3-oxo-3-(2-pyrimidinyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-pyrimidinyl)propanoate, 3-oxo-3-(2-pyrimidinyl)propanamide, N,N-dimethyl-3-oxo-3-(2-pyrimidinyl)propanamide, N-methyl-3-oxo-3-(2-pyrimidinyl)-propanamide, N,N-diethyl-3-oxo-3-(2-pyrimidinyl)propanamide, N-ethyl-3-oxo-3-(2-pyrimidinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-pyrimidinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-pyrimidinyl)-1-propanone, 3-oxo-3-(2-pyrimidinyl)propanenitrile, ethyl 3-(6-chloro-3-pyridinyl)-3-oxopropanoate, ethyl 3-(2,6-dichloro-3-pyridinyl)-3-oxopropanoate, ethyl 3-oxo-3-(4,5,6-trichloro-3-pyridinyl)propanoate, ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxo-propanoate, methyl 3-(3-chloro-1-benzothien-2-yl)-3-oxopropanoate, methyl 3-oxo-3-(3-thiophenyl)propanoate, ethyl 3-oxo-3-(3-thiophenyl)propanoate, isopropyl 3-oxo-3-(3-thiophenyl)propanoate, tert-butyl 3-oxo-3-(3-thiophenyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-thiophenyl)propanoate, 3-oxo-3-(3-thiophenyl)propanamide, N,N-dimethyl-3-oxo-3-(3-thiophenyl)propanamide, N-methyl-3-oxo-3-(3-thiophenyl)propanamide, N,N-diethyl-3-oxo-3-(3-thiophenyl)propanamide, N-ethyl-3-oxo-3-(3 thiophenyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-thiophenyl)-1-propanone, 3-3oxo-3-(N-pyrrolidinyl)-1-(3-thiophenyl)-1-propanone, 3-oxo-3-(3-thiophenyl)propanenitrile, methyl 3-oxo-3-(2-thiophenyl)propanoate, ethyl 3-oxo-3-(2-thiophenyl)propanoate, isopropyl 3-oxo-3-(2-thiophenyl)propanoate, tert-butyl 3-oxo-3-(2-thiophenyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-thiophenyl)propanoate, 3-oxo-3-(2-thiophenyl) propanamide, N,N-dimethyl-3-oxo-3-(2-thiophenyl)propanamide, N,N-diethyl-3-oxo-3-(2-thiophenyl)propanamide, N-ethyl-3-oxo-3-(2-thiophenyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-thiophenyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-thiophenyl)-1-propanone, 3-oxo-3-(2-thiophenyl)propanenitrile, methyl 3-oxo-3-(3-pyrrolyl)propanoate, ethyl 3-oxo-3-(3-pyrrolyl)propanoate, isopropyl 3-oxo-3-(3-pyrrolyl)propanoate, tert-butyl 3oxo-3-(3-pyrrolyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-pyrrolyl)propanoate, 3-oxo0-3-(3-pyrrolyl)propanamide, N,N-dimethyl-3-oxo-3-(3-pyrrolyl)propanamide, N-methyl-3-oxo-3-(3-pyrrolyl)propanamide, N,N-diethyl-3-oxo-3-(3-pyrrolyl)propanamide, N-ethyl-3-oxo-3-(3-pyrrolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-pyrrolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-pyrrolyl)-1-propanone, 3-oxo-3-(3-pyrrolyl)propanenitrile, methyl 3-oxo-3-(2-pyrrolyl)propanoate, ethyl 3-oxo-3-(2-pyrrolyl)propanoate, isopropyl 3-oxo-3-(2-pyrrolyl)propanoate, tert-butyl 3-oxo-3-(2-pyrrolyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-pyrrolyl)propanoate, 3-oxo-3-(2-pyrrolyl)propanamide, N,N-dimethyl-3-oxo-3-(2-pyrrolyl)propanamide, N-methyl-3-oxo-3-(2-pyrrolyl)propanamide, N,N-diethyl-3-oxo-3-(2-pyrrolyl)propanamide, N-ethyl-3-oxo-3-(2-pyrrolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-pyrrolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-pyrrolyl)-1-propanone, 3-oxo-3-(2-pyrrolyl)propanenitrile, methyl 3-oxo-3-(1-thiazolyl)propanoate, ethyl 3-oxo-3-(1-thiazolyl)propanoate, isopropyl 3-oxo-3-(1-thiazolyl)propanoate, tert-butyl 3-oxo-3-(1-thiazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(1-thiazolyl)propanoate, 3-oxo-3-(1-thiazolyl)propanamide, N,N-dimethyl-3-oxo-3-(1-thiazolyl)propanamide, N-methyl-3-oxo-3-(1-thiazolyl)propanamide, N,N-diethyl-3-oxo-3-(1-thiazolyl) propanamide, N-ethyl-3-oxo-3-(1-thiazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(1-thiazolyl)propanenitrile, methyl 3-oxo-3-(2-thiazolyl) propanoate, ethyl 3-oxo-3-(1-thiazolyl)propanoate, isopropyl 3-oxo-3-(1-thiazolyl)propanoate, tert-butyl 3-oxo-3-(1-thiazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(1-thiazolyl)propanoate, 3-oxo-3-(1-thiazolyl)propanamide, N,N-dimethyl-3-oxo-3-(1-thiazolyl)propanamide, N-methyl-3-oxo-3-(1-thiazolyl)propanamide, N,N-diethyl-3-oxo-3-(1-thiazolyl)propanamide, N-ethyl-3-oxo-3-(1-thiazolyl) propanamide, 3-oxo-3-(N-piperidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(1-thiazolyl) propanenitrile, methyl 3-oxo-3-(4-thiazolyl)propanoate, ethyl 3-oxo-3-(1-thiazolyl)propanoate, isopropyl 3-oxo-3-(1-thiazolyl)propanoate, tert-butyl 3-oxo-3-(1-thiazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(1-thiazolyl)propanoate, 3-oxo-3-(1-thiazolyl)propanamide, N,N-dimethyl-3-oxo-3-(1-thiazolyl)propanamide, N-methyl-3-oxo-3-(1-thiazolyl)propanamide, N,N-diethyl-3-oxo-3-(1-thiazolyl)-propanamide, N-ethyl-3-oxo-3-( 1-thiazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-( 1-thiazolyl)propanenitrile, methyl 3-oxo-3-( 1-oxazolyl) propanoate, ethyl 3-oxo-3-(1-thiazolyl)propanoate, isopropyl 3-oxo-3-(1-thiazolyl)propanoate, tert-butyl 3-oxo-3-(1-thiazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(1-thiazolyl)propanoate, 3-oxo-3-(1-thiazolyl)propanamide, N,N-dimethyl-3-oxo-3-(1-thiazolyl)propanamide, N-methyl-3-oxo-3-(1-thiazolyl)propanamide, N,N-diethyl-3-oxo-3-(1-thiazolyl)propanamide, N-ethyl-3-oxo-3-(1-thiazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-( 1-thiazolyl)propanenitrile, methyl 3-oxo-3-(2-oxazolyl)propanoate, ethyl 3-oxo-3-(1-thiazolyl)propanoate, isopropyl 3-oxo-3-(1thiazolyl)propanoate, tert-butyl 3-oxo-3-(1-thiazolyl)propanoate, 2-ethylhexyl-3-oxo-3-(1-thiazolyl)propanoate, 3-oxo-3-(1-thiazolyl)propanamide, N,N-dimethyl-3-oxo-3-(1-thiazolyl) propanamide, N-methyl-3-oxo-3-(1-thiazolyl)propanamide, N,N-diethyl-3-oxo-3-(1-thiazolyl)propanamide, N-ethyl-3-oxo-3-(1-thiazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-( -thiazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(1-thiazolyl)-1-propanone, 3-oxo-3-(1-thiazolyl)propanenitrile, methyl 3-oxo-3-(4-oxazolyl)propanoate, ethyl 3-oxo-3-(4-oxazolyl)propanoate, isopropyl 3-oxo-3-(4-oxazolyl)propanoate, tert-butyl 3-oxo-3-(4-oxazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(4-oxazolyl)propanoate, 3-oxo-3-(4-oxazolyl)propanamide, N,N-dimethyl-3-oxo-3-(4-oxazolyl)propanamide, N-methyl-3-oxo-3-(4-oxazolyl)propanamide, N,N-diethyl-3-oxo-3-(4-oxazolyl)propanamide, N-ethyl-3-oxo-3-(4-oxazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(4-oxazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl) 1(4-oxazolyl)-1-propanone, 3-oxo-3-(4-oxazolyl)propanenitrile, methyl 3-oxo-3-(3-pyrazolyl)propanoate, ethyl 3-oxo-3-(3-pyrazolyl)propanoate, isopropyl 3-oxo-3-(3-pyrazolyl)propanoate, tert-butyl 3-oxo-3-(3-pyrazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-pyrazolyl)propanoate, 3-oxo-3-(3-pyrazolyl)propanamide, N,N-dimethyl-3-oxo-3-(3-pyrazolyl)propanamide, N-methyl-3-oxo-3-(3-pyrazolyl)propanamide, N,N-diethyl-3-oxo-3-(3-pyrazolyl)propanamide, N-ethyl-3-oxo-3-(3-pyrazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-pyrazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-pyrazolyl)-1-propanone, 3-oxo-3-(3-pyrazolyl)propanenitrile, methyl 3-oxo-3-(4-pyrazolyl)propanoate, ethyl 3-oxo-3-(4-pyrazolyl)-propanoate, isopropyl 3-oxo-3-(4-pyrazolyl)propanoate, tert-butyl 3-oxo-3-(4-pyrazolyl)propanoate, 2-ethylhexyl 3-oxo-3.-(4-pyrazolyl)propanoate, 3-oxo-3-(4-pyrazolyl)propanamide, N,N-dimethyl-3-oxo-3-(4-pyrazolyl)propanamide, N-methyl-3-oxo-3-(4-pyrazolyl)propanamide, N,N-diethyl-3-oxo-3-(4-pyrazolyl)propanamide, N-ethyl-3-oxo-3-(4-pyrazolyl)propanamide, 3-oxo-3-(1-piperidinyl)-1-(4-pyrazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl) -(4-pyrazolyl)-1-propanone, 3-oxo-3-(4-pyrazolyl)propanenitrile, methyl 3-oxo-3-(2-imidazolyl)propanoate, ethyl 3-oxo-3-(2-imidazolyl)propanoate, isopropyl 3-oxo-3-(2-imidazolyl)propanoate, tert-butyl 3-oxo-3-(2-imidazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-imidazolyl)propanoate, 3-oxo-3-(2-imidazolyl)propanamide, N,N-dimethyl-3-oxo-3-(2-imidazolyl)propanamide, N-methyl-3-oxo-3-(2-imidazolyl)propanamide, N,N-diethyl-3-oxo-3-(2-imidazolyl)-propanamide, N-ethyl-3-oxo-3-(2-imidazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-imidazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-imidazolyl)-1-propanone, 3-oxo-3-(2-imidazolyl)propanenitrile, methyl 3-oxo-3-(4-imidazolyl)propanoate, ethyl 3-oxo-3-(4-imidazolyl)propanoate, isopropyl 3-oxo-3-(4-imidazolyl)propanoate, tert-butyl 3-oxo-3-(4-imidazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(4-imidazolyl)propanoate, 3-oxo-3-(4-imidazolyl)propanamide, N,N-dimethyl-3-oxo-3-(4-imidazolyl)propanamide, N-methyl-3-oxo-3-(4-imidazolyl)propanamide, N,N-diethyl-3-oxo-3-(4-imidazolyl)propanamide, N-ethyl-3-oxo-3-(4-imidazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(4-imidazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(4-imidazolyl)-1-propanone, 3-oxo-3-(4-imidazolyl)propanenitrile, methyl 3-oxo-3-(5-imidazolyl)propanoate, ethyl 3-oxo-3-(5-imidazolyl)propanoate, isopropyl 3-oxo-3-(5-imidazolyl)propanoate, tert-butyl 3-oxo-3-(5-imidazolyl)propanoate, 2-ethylhexyl 3-oxo-3-(5-imidazolyl)propanoate, 3-oxo-3-(5-imidazolyl) propanamide, N,N-dimethyl-3-oxo-3-(5-imidazolyl)propanamide, N-methyl-3-oxo-3-(5-imidazolyl)propanamide, N,N-diethyl-3-oxo-3-(5-imidazolyl) propanamide, N-ethyl-3-oxo-3-(5-imidazolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(5-imidazolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(5-imidazolyl)-1-propanone, 3-oxo-3-(5-imidazolyl)propanenitrile, methyl 3-oxo-3-(3-furanyl)propanoate, ethyl 3-oxo-3-(3-furanyl)propanoate, isopropyl 3-oxo-3-(3-furanyl)propanoate, tert-butyl 3-oxo-3-(3-furanyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-furanyl)propanoate, 3-oxo-3-(3-furanyl)propanamide, N,N-dimethyl-3-oxo-3-(3-furanyl)propanamide, N-methyl-3-oxo-3-(3-furanyl)propanamide, N,N-diethyl-3-oxo-3-(3-furanyl)propanamide, N-ethyl-3-oxo-3-(3-furanyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-furanyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-furanyl)-1-propanone, 3-oxo-3-(3-furanyl)propanenitrile, methyl 3-oxo-3-(2-furanyl)propanoate, ethyl 3-oxo-3-(2-furanyl)propanoate, isopropyl 3-oxo-3-(2-furanyl)propanoate, tert-butyl 3-oxo-3-(2-furanyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-furanyl)propanoate, 3-oxo-3-(2-furanyl)propanamide, N,N-dimethyl-3-oxo-3-(2-furanyl)propanamide, N-methyl-3-oxo-3-(2-furanyl)propanamide, N,N-diethyl-3-oxo-3-(2-furanyl )propanamide, N-ethyl-3-oxo-3-(2-furanyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-furanyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-furanyl)-1-propanone, 3-oxo-3-(2-furanyl)propanenitrile, methyl 3-oxo-3-(3-indolyl)propanoate, ethyl 3-oxo-3-(3-indolyl)propanoate, isopropyl 3-oxo-3-(3-indolyl)propanoate, tert-butyl 3-oxo-3-(3-indolyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-indolyl)propanoate, 3-oxo-3-(3-indolyl)propanamide, N,N-dimethyl-3-oxo-3-(3-indolyl)propanamide, N-methyl-3-oxo-3-(3-indolyl)propanamide, N,N-diethyl-3-oxo-3-(3-indolyl)propanamide, N-ethyl-3-oxo-3-(3-indolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-indolyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-indolyl)-1-propanone, 3-oxo-3-(3-indolyl)propanenitrile, methyl 3-oxo-3-(2-indolyl)-propanoate, ethyl 3-oxo-3-(2-indolyl)propanoate, isopropyl 3-oxo-3-(2-indolyl)propanoate, tert-butyl 3-oxo-3-(2-indolyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-indolyl)propanoate, 3-oxo-3-(2-indolyl)propanamide, N,N-dimethyl-3-oxo-3-(2-indolyl)propanamide, N-methyl-3-oxo-3-(2-indolyl)propanamide, N,N-diethyl-3-oxo-3-(2-indolyl)propanamide, N-ethyl-3-oxo-3-(2-indolyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-indolyl)-1-propanone, 3-6oxo-3-(N-pyrrolidinyl)-1-(2-indolyl)-1-propanone, 3-oxo-3-(2-indolyl)propanenitrile, methyl 3-oxo-3-(3-benzofuranyl)propanoate, ethyl 3-oxo-3-(3-benzofuranyl)propanoate, isopropyl 3-oxo-3-(3-benzofuranyl)propanoate, tert-butyl 3-oxo-3-(3-benzofuranyl) propanoate, 2-ethylhexyl 3-oxo-3-(3-benzofuranyl)propanoate, 3-oxo-3-(3-benzofuranyl)propanamide, N,N-dimethyl-3-oxo-3-(3-benzofuranyl)propanamide, N-methyl-3-oxo-3-(3-benzofuranyl)propanamide, N,N-diethyl-3-oxo-3-(3-benzofuranyl)propanamide, N-ethyl-3-oxo-3-(3-benzofuranyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-benzofuranyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-benzofuranyl)-1-propanone, 3-oxo-3-(3-benzofuranyl)propanenitrile, methyl 3-oxo-3-(2-benzofuranyl)propanoate, ethyl 3-oxo-3-(2-benzofuranyl)propanoate, isopropyl 3-oxo-3-(2-benzofuranyl)propanoate, tert-butyl 3-oxo-3-(2-benzofuranyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-benzofuranyl)propanoate, 3-oxo-3-(2-benzofuranyl)propanamide, N,N-dimethyl-3-oxo-3-(2-benzofuranyl)propanamide, N-methyl-3-oxo-3 (2,benzofuranyl)propanamide, N,N-diethyl-3-oxo-3-(2-benzofuranyl)propanamide, N-ethyl-3-oxo-3-(2-benzofuranyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-benzofuranyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-benzofuranyl)-1-propanone, 3-oxo-3-(2-benzofuranyl)propanenitrile, methyl 3-(2-benzothiophenyl)-3-oxopropanoate, ethyl 3-oxo-3-(2-benzothiophenyl)propanoate, isopropyl 3-oxo-3-(2-benzothiophenyl)propanoate, tert-butyl 3-oxo-3-(2-benzothiophenyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-benzothiophenyl)propanoate, 3-oxo-3-(2-benzothiophenyl)-propanamide, N,N-dimethyl-3-oxo-3-(2-benzothiophenyl)propanamide, N-methyl-3-oxo-3-(2-benzothiophenyl)propanamide, N,N-diethyl-3-oxo-3-(2-benzothiophenyl)propanamide, N-ethyl -oxo-3-(2-benzothiophenyl)-propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-benzothiophenyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-benzothiophenyl)-1-propanone, 3-oxo-3-(2-benzothiophenyl)propanenitrile, methyl 3-(3-benzothiophen-yl)-3-oxopropanoate, ethyl 3-oxo-3-(3-benzothiophenyl)propanoate, isopropyl 3-oxo-3-(3-benzothiophenyl)propanoate, tert-butyl 3-oxo-3-(3-benzothiophen-yl)propanoate, 2-ethylhexyl 3-oxo-3-(3-benzothiophenyl)propanoate, 3-oxo-3-(3-benzothiophenyl)propanamide, N,N-dimethyl-3-oxo-3-(3-benzothiophenyl)-propanamide, N-methyl-3-oxo-3-(3-benzothiophenyl)propanamide, N,N-diethyl-3-oxo-3-(3-benzothiophenyl)propanamide, N-ethyl-3-oxo-3-(3-benzothiophenyl)-propanamide, 3-oxo-3-(N-piperidinyl) 1-(3-benzothiophenyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-benzothiophenyl)-1-propanone, 3-oxo-3-(3-benzothiophenyl)propanenitrile, methyl 3-(2-quinolinyl)-3-oxopropanoate, ethyl 3-oxo-3-(2-quinolinyl)propanoate, isopropyl 3-oxo-3-(2-quinolinyl)propanoate, tert-butyl 3-oxo-3-(2-quinolinyl)propanoate, 2-ethylhexyl 3-oxo-3-(2-quinolinyl)propanoate, 3-oxo-3-(2-quinolinyl)propanamide, N,N-dimethyl-3-oxo-3-(2-quinolinyl)propanamide, N-methyl-3-oxo-3-(2-quinolinyl)propanamide, N,N-diethyl-3-oxo-3-(2-quinolinyl)propanamide, N-ethyl-3-oxo-3-(2-quinolinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(2-quinolinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(2-quinolinyl)-1-propanone, 3-oxo-3-(2-quinolinyl)-propanenitrile, methyl 3-(3-quinolinyl)-3-oxopropanoate, ethyl 3-oxo-3-(3-quinolinyl)propanoate, isopropyl 3-oxo-3-(3-quinolinyl)propanoate, tert-butyl 3-oxo-3-(3-quinolinyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-quinolinyl)propanoate, 3-oxo-3-(3-quinolinyl)propanamide, N,N-dimethyl-3-6oxo-3-(3-quinolinyl)propanamide, N-methyl-3-oxo-3-(3-quinolinyl)propanamide, N,N-diethyl-3-oxo-3-(3-quinolinyl)propanamide, N-ethyl-3-oxo-3-(3-quinolinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-quinolinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-quinolinyl)-1-propanone, 3-oxo-3-(3-quinolinyl)-propanenitrile, methyl 3-(3-isoquinolinyl)-3-oxopropanoate, ethyl 3-oxo-3-(3-isoquinolinyl)propanoate, isopropyl 3 oxo-3-(3-isoquinolinyl)propanoate, tert-butyl 3-oxo-3-(3-isoquinolinyl)propanoate, 2-ethylhexyl 3-oxo-3-(3-isoquinolinyl)propanoate, 3-oxo-3-(3-isoquinolinyl)propanamide, N,N-dimethyl-3-oxo-3-(3-isoquinolinyl)propanamide, N-methyl-3-oxo-3-(3-isoquinolinyl)propanamide, N,N-diethyl-3-oxo 3-(3-isoquinolinyl)propanamide, N-ethyl-3-oxo-3-(3-isoquinolinyl)propanamide, 3-oxo-3-(N-piperidinyl)-1-(3-isoquinolinyl)-1-propanone, 3-oxo-3-(N-pyrrolidinyl)-1-(3-isoquinolinyl)-1-propanone, 3-oxo-3-(3-isoquinolinyl)propanenitrile, and even greater preference is given to methyl 3-oxo-3-(2-thiophen-yl)propanoate and ethyl 3-oxo-3-(2-thiophenyl)propanoate.
[0030] The process according to the invention is carried out in the presence of a ruthenium-containing catalyst.
[0031] For example and with preference, the catalysts used are those which comprise ruthenium complexes. Preferred ruthenium complexes are those which are obtainable by reacting compounds of the formula-(II) with compounds of the formula (III), or complexes of the formula (IV). Particular preference is given to using those ruthenium complexes which are obtainable by reacting compounds of the formula (II) with compounds of the formula (III). In a preferred embodiment, the molar ratio of compounds of the formula (III) to compounds of the formula (II) is 2:1 to 3:1, more preferably 2.01:1 to 2.4:1.
[0032] Advantageously, compounds of the formula (III) and compounds of the formula (II) are mixed and the mixture is taken up in organic solvent. Before being added to the reaction mixture, the resulting mixture may also be admixed with a base, preferably a tertiary amine and stirred, for example and with preference, for 10 to 30 min, the molar amount of tertiary amine being, for example and with preference, 1:1 to 3:1, particularly preferably 1:1to 2:1, based on compounds of the formula (III).
[0033] For organic solvents and tertiary amines, the same statements and preferred ranges apply as will be described in detail below.
[0034] In the compounds of the formula (II)
[RuX 2 (arene)] 2 (II)
[0035] arene is a coordinated aromatic compound having 6 to 12 ring carbon atoms which may further be substituted by up to 6 radicals, each of which is independently selected from the group of C 1 -C 8 -alkyl, benzyl and phenyl and
[0036] X is, for example and with preference, chlorine, bromine or iodine, more preferably chlorine.
[0037] Arene is preferably benzene or naphthalene which may be substituted by up to 6 radicals, each of which is selected independently from the group of methyl, ethyl, n-propyl, isopropyl and tert-butyl.
[0038] Arene is preferably mesitylene, cumene or benzene.
[0039] Particularly preferred compounds of the formula (II) are (benzene)dichlororuthenium dimer, (mesitylene)dichlororuthenium dimer and (cumene)dichlororuthenium dimer, and even greater preference is given to (cumene)dichlororuthenium dimer.
[0040] In the formula (III)
[0041] R 3 and R 4 are each independently, for example, C 1 -C 20 -alkyl, C 4 -C 15 -aryl or C 5 -C 16 -arylalkyl, or R 3 and k4 together are a straight-chain or branched C 3 -C 12 -alkylene radical, and
[0042] R 5 is C 1 -C 20 -alkyl, C 1 -C 20 -fluoroalkyl or C 4 -C 15 -aryl.
[0043] R 3 and R 4 are preferably identical and are each phenyl or are together straight-chain C 3 -C 8 -alkylene, for example 1,3-pentylene or 1,4-butylene, and R 3 and R 4 are particularly preferably identical and are each phenyl.
[0044] R 5 is preferably C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, phenyl or naphthyl which may be substituted by no, one, two;, three,6.four or five radicals which are selected from the group of C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoroalkyl, fluorine and chlorine.
[0045] R 5 is particularly preferably methyl, trifluoromethyl, pentafluoroethyl, nona-fluorobutyl, phenyl, p-tolyl, p-ethylphenyl, p-anisyl, p-ethoxyphenyl, p-chlorophenyl, 2,4,6-trimethylphenyl, 2,4,6-triisopropylphenyl, p-fluorophenyl, pentafluorophenyl and naphthyl.
[0046] R 5 is very particularly preferably p-tolyl, phenyl and naphthyl.
[0047] R 5 is even more very particularly preferably p-tolyl.
[0048] The compounds of the formula (III) preferably had a stereoisomeric purity of 90% or more, particularly preferably of 95% or more and very particularly preferably of 98.5% or more.
[0049] Compounds of the formula (III) include:
[0050] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-p-tolylsulphonamide,
[0051] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-o-tolylsulphonamide,
[0052] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-m-tolylsulphonamide,
[0053] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]phenylsulphonamide,
[0054] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-4-ethylphenylsulphonamide,
[0055] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-3-ethylphenylsulphonamide,
[0056] N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2,4,6-trimethylphenyl-sulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2,4,6-triisopropylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-4-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-3-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-4-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-3-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-4-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-3-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-2-methoxyphenyl-sulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-1-naphthylsulphonamide, N-[(1R,2R) and (1S,2S),-2-amino-1,2-diphenylethyl]-2-naphthylsulphonamide, N-[(1R;2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-pentafluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-methanesulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-1,2-diphenylethyl]-trifluoromethanesulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-p-tolylsulphonamide, N-[( 1R,2R) and (1S,2S)-2-aminocyclohexyl]-o-tolylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-m-tolylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-phenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-4-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-3-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2,4,6-trimethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2,4,6-triisopropylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-4-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-3-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-4-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-3-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-4-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-3-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-1-naphthylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-2-naphthylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-pentafluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-methanesulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclohexyl]-trifluoromethanesulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-p-tolylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-o-tolylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-m-tolylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-phenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-4-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-3-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2-ethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2,4,6-trimethylphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2,4,6-triisopropylphenylsulphonamide, N-[(1-R,2R) and (1S,2S)-2-aminocyclopentyl]-4-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-3-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2-chlorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-4-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-3-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2-fluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-4-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-3-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-2-methoxyphenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]-1-naphthylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-cyclopentyl]-2-naphthylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-cyclopentyl]-pentafluorophenylsulphonamide, N-[(1R,2R) and (1S,2S)-2-amino-cyclopentyl]-methansulphonamide, N-[(1R,2R) and (1S,2S)-2-aminocyclopentyl]trifluoromethanesulphonamide.
[0057] In the formula (IV)
[RuX 2 (arene){(III)}] (IV)
[0058] arene and X each have the definitions and preferred ranges given under formula (II) and (III) in the formula (IV) represents compounds of the formula (III) having the definitions and preferred ranges given there.
[0059] Compounds of the formula (IV) include:
[0060] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-p-tolylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0061] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-o-tolylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0062] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenyl ethyl]-m-tolylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0063] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]phenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0064] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-ethylphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0065] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-ethylphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0066] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-ethylphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0067] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-trimethylphenyl-sulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0068] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-triisopropyl-phenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0069] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-chlorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0070] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-chlorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0071] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1I,2-diphenylethyl]-2-chlorophenylsulphonamidato-κN]chloro [(η 6 )-cumene]ruthenium(II)
[0072] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-fluorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0073] [N-[( 1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-fluorophenylsulphonamidato-κN]chloro[(η 6 ) -cumene]ruthenium(II)
[0074] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-fluorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0075] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0076] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-methoxyphenylsulphonamidato-κN]chloro[(κ 6 )-cumene]ruthenium(II)
[0077] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)ato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0078] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-1-naphthylsulphonamidato-κN]chloro[(-q 6 )-cumene ruthenium(II)
[0079] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0080] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]pentafluorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0081] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]methanesulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0082] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]trifluoromethanesulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0083] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-p-tolylsulphonamidato-κN]chloro [(η 6 ) 1,3,5-trimethylbenzene]ruthenium(II)
[0084] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-o-tolylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0085] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-m-tolylsulphonamidato-κN]chloro [(η 6 ) 1,3,5-trimethylbenzene]ruthenium(II)
[0086] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]phenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0087] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-ethyl-phenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0088] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-ethylphenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0089] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-ethylphenylsulphonamidato-κN]chloro [(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0090] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-trimethylphenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0091] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-triisopropyl-phenylsulphonamidato-κN]chloro [(η6)-1,3,5-trimethylbenzene]ruthenium(II)
[0092] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-chlorophenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0093] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-chlorophenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0094] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-chlorophenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0095] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-fluorophenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0096] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-fluorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0097] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-fluorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0098] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methoxy-phenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0099] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-methoxyphenyl-sulphonamidato-κN]chloro[(η 6 -)-1,3,5-trimethylbenzene]ruthenium(II)
[0100] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-methoxyphenyl-sulphonamidato-κN]chloro [(η 6 )-1,3,5 trimethylbenzene]ruthenium(II)ato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0101] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-1-naphthylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0102] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0103] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]pentafluorophenylsulphonamidato-κN]chloro[(η 6 ) 1,3,5-trimethylbenzene]ruthenium(II)
[0104] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]methanesulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0105] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]trifluoromethanesulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0106] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-p-tolylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0107] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-o-tolylsulphonamidato-κN]chloro[(κ 6 )-benzene]ruthenium(II)
[0108] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-m-tolylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0109] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]phenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0110] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-ethylphenylsulphonamidato-κN]chloro [(η 6 )-benzene]ruthenium(II)
[0111] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-ethylphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0112] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-ethylphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0113] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-trimethylphenyl-sulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0114] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2,4,6-triisopropylphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0115] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-chlorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0116] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-chlorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0117] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-chlorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0118] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-fluorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0119] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-fluorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0120] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-fluorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0121] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-4-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0122] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-3-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0123] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-methoxyphenylsulphonamidato-κN]chloro [(η 6 )-benzene]ruthenium(II)ato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0124] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-1-naphthylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0125] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0126] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]pentafluorophenyl-sulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0127] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]methanesulphonamidato-κN](chloro[(η 6 )-benzene]ruthenium(II)
[0128] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,2-diphenylethyl]trifluoromethanesulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0129] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-p-tolylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0130] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-m-tolylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0131] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]phenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0132] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-ethylphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0133] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-2,4,6-trimethylphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0134] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-chlorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0135] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-chlorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0136] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-fluorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0137] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-fluorophenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0138] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0139] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0140] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-1-naphthylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0141] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0142] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]methanesulphonamidato-κN]chloro[(η 6 )-benzene]ruthenium(II) p 1 [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]trifluoromethanesulphonamidato,-κN]chloro[(η 6 )-benzene]ruthenium(II)
[0143] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-p-tolylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0144] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-m-tolylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0145] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]phenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0146] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl] -4-ethylphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0147] [N-[(1R,2R and 1S,2S)-2-(amino-κN -cyclohexyl]-2,4,6-trimethylphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0148] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-chlorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0149] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-chlorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0150] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-fluorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0151] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-fluorophenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0152] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-methoxyphenylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0153] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-methoxyphenylsulphonamidato-κN]chloro[η 6 )-cumene]ruthenium(II)
[0154] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-1-naphthylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0155] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0156] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]methanesulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II),
[0157] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]trifluoromethanesulphonamidato-κN]chloro[(η 6 )-cumene]ruthenium(II)
[0158] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-p-tolylsulphonamidato-κN]chloro[(η 6 )-1,3 5-trimethylbenzene]ruthenium(II)
[0159] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-m-tolylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0160] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]phenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0161] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-ethylphenylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0162] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl] -2,4,6-trimethylphenyl-sulphonamidato-κN]chloro[(η 6 ) 1,3,5-trimethylbenzene]ruthenium(II)
[0163] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-chlorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0164] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-chlorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0165] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-fluorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0166] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-fluorophenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,51-trimethylbenzene]ruthenium(II)
[0167] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-4-methoxyphenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0168] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-3-methoxyphenyl-sulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0169] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-1-naphthylsulphonamidato-κN]chloro[(η 6 ) 1,3,5-trimethylbenzene]ruthenium(II)
[0170] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]-2-naphthylsulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0171] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-cyclohexyl]methanesulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II) and
[0172] [N-[(1R,2R and 1S,2S)-2-(amino-κN)-1,3,5-cyclohexyl]trifluoromethanesulphonamidato-κN]chloro[(η 6 )-1,3,5-trimethylbenzene]ruthenium(II)
[0173] Particularly preferred catalysts for the purposes of the invention are those which comprise ruthenium complexes which are obtainable by reacting S,S— or R,R—N-p-toluenesulfonyl-1,2-diphenylethylenediamine with (cumene)dichlororuthenium dimer.
[0174] The process according to the invention is carried out in the presence of at least one amine, preferably an amine of which at least some is present in protonated form.
[0175] Also, formic acid, formates or mixtures thereof are used for the process according to the invention.
[0176] Preference is giving to using mixtures of formic, acid with amines. In this way, the corresponding ammonium formates are at least partially formed and can be used in a similar manner.
[0177] Useful amines are in particular those of the formula (V)
NR 6 R 7 R 8 (V)
[0178] where
[0179] R 6 , R 7 and R 8 are each independently hydrogen, C 1 -C 8 -allyl or benzyl.
[0180] Particularly preferred amines are ammonia and those of the formula (V) where R 6 , R 7 and R 8 are each independently C 1 -C 8 -alkyl or benzyl.
[0181] Particularly preferred amines are those of the formula (V) where R 6 , R 7 and R 8 are identical and are each ethyl, n-butyl or n-hexyl, and even greater preference is given to the use of triethylamine.
[0182] The molar ratio of formic acid to tertiary amine may be, for example, 1:1 to 3:1, and preference is given to a ratio of 1.01:1 to 1.5:1.
[0183] The molar ratio of formic acid based on substrate used may be, for example, 1:1 to 3:1, and preference is given to 1:1 to 1.5: 1, particular preference to 1.02:1 to 1.1:1.
[0184] The process according to the invention may be carried out in the presence or absence, preferably in the presence, of organic solvent.
[0185] Examples of suitable organic solvents include:
[0186] amides, for example dimethylformamide, N-methylpyrrolidinone, optionally halogenated aliphatic or araliphatic solvents having up to 16 carbon atoms, for example toluene, o-, m- and p-xylene, chloroform dichloromethane, chlorobenzene, the isomeric dichlorobenzenes, fluorobenzene, nitrites, for example acetonitrile, benzonitrile, dimethyl sulfoxide or mixtures thereof.
[0187] Preferred solvents are acetonitrile, N-methylpyrrolidinone, chloroform, dichloro-methane, chlorobenzene, the isomeric dichlorobenzenes, fluorobenzene or mixtures thereof, and particular preference is given to dichloromethane, acetonitrile, N-methylpyrrolidone or mixtures thereof.
[0188] The reaction temperature maybe, for example, −10to 150° C., and preference is given to 20 to 100° C., particular preference to 20 to 80° C.
[0189] The reaction times are, for example, between 0.5 h and 48 h, preferably between 6 and24 h.
[0190] The molar amount of ruthenium may be, for example, 0.01 to 1.0 mol %, based on the substrate used, and preference is given to 0.02 to 0.2 mol %, very particular preference to 0.02 to 0.1 mol %.
[0191] It is advantageous, although not obligatory, to carry out the reaction in a substantially oxygen-free atmosphere. Substantially oxygen-free means, for example, a content of 0 to 1% by volume, preferably 0 to 0. 1% by volume, of oxygen.
[0192] The reaction may be accelerated by removing carbon dioxide which is released during the reaction. Advantageous, and therefore encompassed by the invention, is intensive stirring of the reaction mixture at an average stirrer speed of, for example, 100 to 3,000 min −1 , preferably 500 to 1,500 min −1 . Alternatively, or in supplementation thereto, the removal of carbon-dioxide may be supported by passing through or passing over an inert gas stream through or over the reaction mixture. Examples of suitable gases include nitrogen, noble gases, for example argon, or mixtures thereof.
[0193] In the manner according to the invention, stereoisomerically enriched 3-heteroaryl-3-hydroxypropionic acid derivatives of the formula (VI)
heteroaryl-CH(OH)—CH 2 W (VI)
[0194] where heteroaryl and W have the same definitions and preferred ranges as were named under the formula (I) are obtained.
[0195] Depending on the choice of the configuration of the ligands, the S- or R-configured products at the 3-position are obtainable.
[0196] The stereoisomerically enriched 3-heteroaryl-3-hydroxypropionic acid derivatives which can be prepared according to the invention are suitable in particular for use in a process for preparing liquid-crystalline compounds, agrochemicals and pharmaceuticals or intermediates thereof.
[0197] A particularly preferred embodiment of the process according to the invention is described hereinbelow, without imposing any limitation.
[0198] In a stirred tank, a 1:1 mixture (molar) of formic acid and triethylamine is prepared by simple mixing and the 3-heteroaryl-3-oxopropionic acid derivative is added to this biphasic mixture in an equimolar amount or a slight deficiency. Depending on the solubility of the substrate, an amount of an organic solvent is added. This mixture is inertized by passing through nitrogen and the mixture is heated to the desired reaction temperature with vigorous stirring.
[0199] The catalyst is added to this mixture as a solution in dichloromethane in molar ratios compared to the substrate of, for example, 1:500 to 1:5000, and the reaction mixture is stirred for the desired time. The conversion is followed by chromatography.
[0200] The reaction mixture may subsequently be worked up by processes known to those skilled in the art. It has proven advantageous to add solvents and dilute aqueous hydrochloric acid or water to the reaction mixture for workup. After phase separation, the product may be isolated in da-manner known per se from the organic phase either distillatively or by a suitable crystallization process.
[0201] The advantage of the present invention is that 3-heteroaryl-3-hydroxypropionic acid derivatives can be obtained in stereoisomerically enriched form in a manner which is efficient and can be performed in a technically simple manner to achieve high yields.
EXAMPLES
[0202] General Procedure for the Transfer Hydrogenation of 3-Heteroaryl-3-Oxopropionic Acid Derivatives
Examples 1-10
[0203] In a Schlenk vessel, the catalyst solution -is prepared by weighing in 2.03 mol equivalents of 1S,2S—N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (S,S-TsDPEN) and 1 mol equivalent of [(cumene)RuCl 2 ] 2 , stirring this mixture in 5 ml of CH 2 Cl 2 and admixing with 2 mol equivalents of Et 3 N for 15 min.
[0204] In a 100 ml multi-necked flask equipped with a sparging stirrer, reflux condenser and thermometer, a formic acid/Et 3 N mixture (molar ratio 1:1, molar ratio 1.05:1 based on the substrate) is prepared by slowly adding HCOOH dropwise to Et 3 N by a dropping funnel within 5 min with stirring and ice-cooling. The appropriate keto compound is then added to this biphasic mixture (500-5000 eq. based on the catalyst), the homogeneous yellow solution is optionally admixed with solvent, and the entire mixture is degassed by passing through argon for 20 min. It is heated to the target temperature and the dark red catalyst solution is added all at once by syringe to the reaction mixture with vigorous stirring. The mixture is stirred under argon for the stated time.
[0205] The mixture is diluted with water and CH 2 Cl 2 and stirred for a further 10 min, and, after phase separation, the H 2 O phase is extracted 2× with CH 2 Cl 2 . The combined organic phases are washed with NaCl solution, dried over MgSO 4 and filtered, and then the solvent is removed on a rotary evaporator. The crude product is either distilled and recrystallized, for example from hexane/petroleum ether or from hexane/dichloromethane, or used as a crude mixture in further reactions. The product is obtained in 90-100% yield.
[0206] The conversion and enantiomer analysis is effected by gas chromatography.
[0207] Methyl 3-hydroxy-3-(4-pyridinyl)propanoate (1)
[0208] [0208] 1 H NMR (d1-chloroform, 400 MHz): δ=8.54, 7.35 (each d, each 2H, Py-H, 2J=6 Hz), 5.12 (dd, 1H, CHOH), 3.69 (s, 3H, OCH3), 2.71 (m, 2H, CHH) ppm.
[0209] Chiral GC: 15.49, 16.07 min.
[0210] Ethyl 3-hydroxy-3-(4-pyridinyl)propanoate (2)
[0211] [0211] 1 H NMR (d1-chloroform, 400 MHz): δ=8.54, 7. 32 (each d, each 2H, Py-H, 2J=6 Hz), 5.13 (dd, 1H, CHOH), 4.19 (q, 2H; OCH2), 2.73 (m, 2H, CHH), 1.27 (t, 3H, CH3) ppm.
[0212] Chiral GC: 18.33, 18.60 min.
[0213] Ethyl 3-hydroxy-3-(3-pyridinyl)propanoate (3)
[0214] [0214] 1 H NMR (d1-chloroform, 400 MHz): δ=8.62, 8.61, 7.77, 7.33 (each m, each 1H, Py-H), 5.19 (dd, 1H, CHOH), 3.75 (s, 3H, OCH3), 3.44 (d, 1 H, OH), 2.77 (m, 2H, CHH) ppm.
[0215] Chiral GC: 16.69, 17.56 min.
[0216] Ethyl (3S) 3-(6-chloro-3-pyridinyl)-3-hydroxypropanoate (4)
[0217] [0217] 1 H NMR (d1-chloroform, 400 MHz): δ=8.32 (d, 2H, Py-H, J =2 Hz), 7.66 (dd, 2H, Py-H, J=2 Hz, J=8 Hz), 7.26 (d, 2H, Py-H, J=8 Hz), 5.12 (dd, 1H, CHOH), 4.12 (q, 2H, OCH2), 2.68 (m, 2H, CHH), 1.22 (t, 3H, CH3) ppm.
[0218] Chiral GC: 14.12, 14.74 min.
[0219] Methyl 3-hydroxy-3-(3-thiophenyl)propanoate (5)
[0220] [0220] 1 H NMR (d1-chloroform, 400 MHz): δ=7.30, 7.23, 7.08 (each m, each 1H, Ar—H), 5.22 (dd, 1H, CHOH), 3.72 (s, 3H, OCH3), 2.79 (m, 2H, CHH) ppm.
[0221] Chiral GC: 15.56, 15.99 min.
[0222] (S)-Methyl 3-hydroxy-3-(2-thiophenyl)propanoate (6)
[0223] [0223] 1 H NMR (d1-chloroform, 400 MHz): δ=7.23 (m, 1H, Ar—H), 6.95 (m, 2H, Ar—H), 5.36 (dd, 1H, CHOH), 3.71 (s, 3H, OCH3), 2.86 (m, 2H, CHH) ppm.
[0224] [0224] 13 C-NMR (d1-chloroform, 100 MHz): δ=185.3 (C═O), 146.8 (C, Ar), 127.1 (CH, Ar), 125.3 (CH, Ar), 124.1 (CH, Ar), 66.9 ( C HOH), 52.4 (CH3), 43.5 (CH2) ppm.
[0225] Chiral GC: 14.05, 14.41 min.
[0226] Methyl 3-(3-chloro-1-benzothien-2-yl)-3-hydroxypropanoate (7)
[0227] [0227] 1 H NMR (d1-chloroform, 400 MHz): δ=7.79 (m, 2H, Ar—H), 7.3-7.5 (m, 2H, Ar—H), 5.69 (dd, 1H, CHOH), 3.77 (s, 3H, OCH3) 2.8-3.0 (m, 3H, CHH and OH) ppm.
[0228] Chiral GC: 22.74, 23.47 min.
[0229] Methyl 3-hydroxy-3-(3-furanyl)propanoate (8)
[0230] [0230] 1 H NMR (d1-chloroform, 400 MHz): δ=7.42, 7.39, 6.40 (each m, each 1H, Ar—H), 5.09 (dd, 1H, CHOH), 4.19 (q, 2H, OCH2), 3.30 (br, 1H, OH), 2.73 (m, 2H, CHH), 1.27 (t, 3H, CH3) ppm.
[0231] Chiral GC: 5.56, 5.84 min.
[0232] Methyl 3-hydroxy-3-(2-furanyl)propanoate (9)
[0233] [0233] 1 H NMR (d1-chloroform, 400 MHz): δ=7.39, 6.34, 6.29 (each m, each 1H, Ar—H), 5.14 (dt, 1H, CHOH), 4.21 (q, 2H, OCH2), 3.24 (d, 1H, OH), 2.90 (dd, 2H, CHH), 2.82 (dd, 2H, CHH), 1.28 (t, 3H, CH3) ppm.
[0234] Chiral GC: 9.02, 9.25 min.
[0235] Ethyl 3-hydroxy-3-(2-pyridinyl)propanoate (10)
[0236] [0236] 1 H NMR (d1-chloroform, 400 MHz): δ=8.53, 7.70, 7.42, 7.20 (each m, each 1H, Ar—H), 5.19 (m, 1H, CHOH), 4.18 (q, 2H, OCH2), 2.90 (dd, 1H, CHH), 2.76 (dd, 1H, CHH), 1.25 (t, 3H, CH3) ppm.
[0237] Chiral GC (TMS ester): 22.92, 23.52 min.
[0238] The results of Examples 1-10 are compiled in Table 1.
TABLE 1 Enantiomeric Example Time [h] S/C Conversion [%] excess (ee) [%] 1 18 500 100 87.4 2 18 500 100 82.8 3 18 500 99.2 81.9 4 18 500 100 62.5 5 18 500 100 37 6 18 500 100 98.2 (S) 7 18 500 100 93.1 8 18 500 98.7 92.3 9 18 500 99.9 96.6 10 18 500 100 88.6
Examples 11-15
[0239] Solvent influence on the converation rates (TOF) and enantioselectivities in the reduction of methyl 3-oxo-3-(2-thiophenyl)propanoate.
[0240] Procedure of the experiment as in Example 1, but with magnetic stirring.
[0241] The results of Examples 11-15 are compiled in Table 2.
TABLE 2 Ex- Average Average Conversion ample S/C Solvent TOF (1 h) TOF (8 h) (16 h) Ee [%] 11 1000 CH 2 Cl 2 185 106 100 97.4 12 1000 none 204 108 100 97.0 13 1000 NMP 159 112 100 97.7 14 1000 CH 3 CN 334 115 100 97.0 15 1000 DMSO 152 90 87, 7 97.1
Examples 16-19
[0242] Influence of the removal of CO 2 on the conversion and reaction rate in the transferhydrogenation of methyl 3-oxo-3-(2-thiophenyl)propanoate [1] .
[0243] The results of Examples 16-19 are compiled in Table 3.
TABLE 3 Example S/C Stirring Sparging t [h] C [%] 16 1500 magnetic closed apparatus 48 33 17 1500 magnetic passing Ar over 48 80 18 1200 KPG stirrer passing Ar over 17 100 19 1200 KPG stirrer passing Ar through 12 99
Examples 20-23
[0244] Examples 20-23 were carried out in a similar manner to Example 1.
[0245] 3-Hydroxy-3-(2-furanyl)propanenitrile (20)
[0246] [0246] 1 H NMR (D1-chloroform, 400 MHz): δ=7.41 (m, 1H, Ar—H), 6.38, (m, 2H, Ar—H), 5.04 (dd, 1H, CHOH), 3.03 (br, 1H, OH), 2.90 (m, 2H, CHH) ppm.
[0247] Chiral GC: 6.47, 7.29 min. ee=94.5%.
[0248] (S)-3-Hydroxy-3-(2-thiophenyl)propanenitrile (21)
[0249] [0249] 1 H NMR (D1-chloroform, 400 MHz): δ=7.32, 7.08, 7.01 (each m, each 1H, Ar—H), 5.28 (dd, 1H, CHOH), 2.86 (m, 3H, CHH and OH) ppm.
[0250] Chiral GC: 13.23, 13.56 min. ee 97.-1%.
[0251] 3-Hydroxy-3-(3-thiophenyl)propanenitrile (22)
[0252] [0252] 1 H NMR (D1-chloroform, 400 MHz): δ=7.37, 7.33, 7.12 (each m, each 1H, Ar—H), 5.12 (dd, 1H, CHOH), 2.80 (m, 2H, CHH) 2.75 (br, 1H, OH) ppm.
[0253] Chiral GC: 13.61, 13.97 min. ee=95.9%.
[0254] 3-Hydroxy-3-(6-chloro-3-pyridinyl)propanenitrile (23)
[0255] [0255] 1 H NMR (D1-chloroform, 400 MHz): δ=8.40 (d, 2H, Py-H, J=2 Hz), 7.80 (dd, 2H, Py-H, J=2 Hz, J=8 Hz), 7.37 (d, 2H, Py-H, J=8Hz), 5.14 (dd, 1H, CHOH), 2.82 (m, 2H, CHH) ppm.
[0256] Chiral GC: 24.78, 25.14 min. ee=73.3%.
[0257] The results of Examples 20-23 are compiled in Table 4.
TABLE 4 Example t [h] S/C C [%] ee [%] 20 20 250 100 94.5 21 20 250 100 97.1 22 20 250 100 95.9 23 20 250 100 73.3
[0258] Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims. | The present invention relates to a process for preparing stereoisomerically enriched 3-heteroaryl-3-hydroxycarboxylic esters by reducing 3-heteroaryl-3-oxocarboxylic esters in the presence of ruthenium-containing catalysts. | 2 |
FIELD OF THE INVENTION
The instant invention relates to the field of dishwashers, and in particular, to a liquid detergent dispenser for automatically inserting a predetermined amount of detergent into a dishwasher.
BACKGROUND OF THE INVENTION
Dishwashers have become indispensable modern day appliances. The appliances eliminate the burden of washing and drying eating utensils by use of a chamber capable of automatically performing such tasks. A further advantage of the dishwasher is that the chamber provides a storage location for soiled eating utensils thereby economizing the washing process to provide the use of water and detergent efficiently.
As with any cleaning process, there exists a need for adding a detergent which acts as the mechanism for loosening embedded food particles. While conventional dishwashers include various mechanisms to dispense detergent at the proper time, a problem with such dishwashers is the inability to monitor and dispense an accurate amount for any particular dishwashing cycle. Some dispensers may employ markings to indicate to the homeowner the preferred amount of detergent before the washing cycle begins. These markings are hard to see, highly inaccurate, and nearly impossible to level off the detergent to the desired level marking. Most users therefore, fill the dispenser to the top and even overfill each time. When liquid detergent is used, it must be added right before the dishwashing cycle begins as liquid detergent has a tendency to leak out of the container causing interference with dispenser operation and lessening the effectiveness of the cleaning cycle. When granular detergent is used it must be added just before the dishwashing cycle begins, or the granular detergent tends to cake in the dispenser and does not thoroughly dissolve until sometime into the rinse cycle. Further, adding of detergent is easily forgotten when numerous members of a household are adding utensils to the dishwasher chamber. The individual who turns on the dishwasher may forget to add the necessary detergent thinking another performed the chore. In this situation the dishwasher goes through a complete cycle without any cleaning what-so-ever, only a rinsing. If the individual whose task it is to unload the dishwasher does not observe that the dishwasher went without detergent, but instead thinks that perhaps just some of the utensils did not come out very clean, the cooking utensils, dishes, etc. will be put away unclean and possibly even put away with harmful bacterial contamination on every item in the dishwasher.
Conventional detergent dispensers also present a problem most evident to those attempting to economically purchase liquid detergent in a bulk quantity. The lifting of a large volume container of fluid can cause injury to the elderly, small children, or the like individual who might be slightly physically impaired. The manual filling of door mounted dispensers requires the individual to balance the container while attempting to determine how much detergent should be placed within the dispenser.
The inefficiency also leads to a waste of detergent sending excess surfactants to discharge which inhibits both municipal and septic containers. In addition, excess detergent can damage glassware and fragile utensils as many liquid detergents have a high pH which is caustic. Liquid detergent may also contain sodium hypochlorite which is dangerous to store even temporarily especially in door-mounted dispensers and can burn infants or those people having tender skin. Thus, the amount of detergent used is critical to health, safety, operation, and the environment.
U.S. Pat. No. 3,370,597 discloses a dishwashing machine with a liquid sanitizer dispenser. The dispenser includes a motor driven pump and spray device incorporating a gravity fed pump with an integrated solenoid and dispensing valve. The main purpose of the device is to inject chlorine into the dishwasher for disinfection of the eating utensils. Cycling of the injection system is independent of the detergent dispensing cycle.
U.S. Pat. No. 3,749,288 discloses a liquid dispenser integrated into a wall of a dishwasher for inserting a wetting agent to assist the washing cycle.
U.S. Pat. No 5,282,901 discloses a removable liquid dispenser for inserting detergent into an industrial warewash machine. A probe is placed into the wash chamber for monitoring the conductivity of the wash water. The warewash chamber maintains a volume of water wherein the conductivity provides a relationship to water quality. The device is complicated and not suited for residential purposes, nor does it have the ability to monitor the amount of liquid detergent left in the supply container, or stop the machine from going through a wash cycle when there is no detergent available.
Thus, what is lacking in the art is a detergent dispenser that can be incorporated into a conventional dishwasher having the ability to automatically dispense liquid detergent from either an independent container or by use of an integrated reservoir, said dispenser including an ability to monitor the amount of detergent dispensed, the ability to monitor the amount of detergent left in the container before running out, and the ability to stop the machine from operating when there is no detergent available to be dispensed.
SUMMARY OF THE INVENTION
The instant invention discloses an apparatus for injecting detergent into a conventional residential dishwasher. In a preferred embodiment, the apparatus consists of an electric pump which operates on a timer used in conjunction with an existing dishwasher wherein the pump transfers liquid detergent from a container through the side wall of a dishwasher. The apparatus is energized/triggered by the same electrical impulse that triggers the currently used door-mounted detergent dispenser, thereby providing detergent at the proper time. The apparatus couples to the dishwasher water inlet solenoid which then allows transfer of fresh water to the dishwasher only when there is adequate detergent available to be dispensed. The apparatus includes a means for deenergizing the water inlet solenoid should the pump's sensing mechanism determine that an inadequate amount of detergent exists in the detergent container. The sensing mechanism and a suction tube is placed into an independent detergent container positioning both tubes along a bottom portion of the container for drawing of the detergent and monitoring its contents. An upper aperture provides venting of the container preventing collapse of the container as fluid is drawn.
The tubes are incorporated into a cap to simplify setting up the system allowing the cap to be easily exchanged for an existing cap. The tubes are placed into a container of liquid detergent by simply removing the packing cap and threading on the modified cap of the instant invention.
The pumping mechanism utilizes a timer allowing an individual to set the amount of detergent to be dispensed. Predetermined settings allow an individual to quickly determine the amount of detergent to be dispensed. A self cleaning dispersion valve placed in the dishwasher prevents back flow of water to prevent diluting of the detergent and is self-cleaned during the wash cycle.
An alternate embodiment of the invention positions a storage container beneath the dishwasher allowing the consumer to internally fill the container. A benefit is the space saving feature and the ability to use low cost detergent packs. In addition, by providing a container with the instant invention, various liquid level monitoring mechanisms can be used.
In all embodiments, a sensor determines whether the liquid level within the container has fallen to a point that requires replenishment and alerts the user to this condition by use of a light and of an alarm mechanism. A solenoid trigger allows three additional wash cycles providing the homeowner with ample opportunity to replenish the detergent before it is completely exhausted. After the third wash cycle, the pumping mechanism's sensor discontinues the supply of electricity to the water inlet solenoid, thereby preventing the start of another wash cycle. When the user replenishes the supply of detergent, the pumping mechanism's sensor reconnects the electrical supply to the water inlet solenoid and normal dishwasher operation can resume. The instant invention allows for the modification of dishwasher design to include a detergent level monitor on the panel, as well as contemplates the operation of the pumping mechanism controls from the front panel of the dishwasher. It can be noted that the system also allows for the insertion of a small amount of detergent at the end of a cycle which acts as an air freshener.
Thus, an objective of the instant invention is to provide an automatic liquid detergent dispenser for use in combination with a new or existing dishwasher providing efficiency in detergent dispersion.
Another objective of the instant invention is to disclose an automatic detergent dispenser capable of utilizing existing liquid detergent storage containers.
Still another objective of the instant invention is to disclose a method of monitoring the level of liquid in a detergent container, including a means for detection of a low level condition providing both visual and audible indication of the level.
Yet still another objective of the instant invention is to provide additional wash cycles once a low liquid level is detected thereby allowing a homeowner sufficient time to replenish the detergent.
Yet still another objective of the instant invention is to incorporate a liquid detergent transfer pump together with a water inlet solenoid so as to provide a shut off of the water should an inadequate amount of detergent be available.
Yet still another objective of the instant invention is to position a detergent storage container in an open space beneath the dishwasher for optimum space use. Refilling of the container is accomplished by use of a side mounted access tube fluidly communicated with the storage container.
Yet another objective of the instant invention is to disclose a self-cleaning detergent fill, injection, and vents capable of maintaining a heightened level of moisture in the system to prevent detergent thickening.
Other objects and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying drawings wherein are set forth, by way of illustration and example, certain embodiments of this invention. The drawings constitute a part of this specification and include exemplary embodiments of the present invention and illustrate various objects and features thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a pictorial view of the preferred embodiment of the instant invention drawing from a conventional liquid detergent container;
FIG. 2 is a pictorial view of an alternative embodiment having an integrated storage container;
FIG. 3 is a pictorial view of an embodiment employing a remote storage container;
FIG. 4 is a pictorial view of a remote storage container being filled from a soft walled liquid dispenser;
FIG. 5 is a pictorial view of an embodiment having a remote storage container with multiple sensors;
FIG. 6 is a pictorial view of a mechanical liquid level indicator used in conjunction with a sensing mechanism in a remote storage container;
FIG. 7 is a perspective view of a side wall fill port;
FIG. 8 is a perspective view of the fill port shown in FIG. 7 in an open position and a fill tube positioned therein;
FIG. 9 is a cross-sectional side view of FIG. 7;
FIG. 10 is a perspective view of the liquid dispenser delivery mechanism;
FIG. 11 is a pictorial view of FIG. 10 illustrating detergent delivery;
FIG. 12 is an exploded view of FIG. 10;
FIG. 13 is a cross-sectional side view of FIG. 12;
FIG. 14 is a perspective view of an alternative embodiment for detergent dispensing;
FIG. 15 is a cross-sectional side view of FIG. 14;
FIG. 16 is a perspective view of the liquid detergent container vent;
FIG. 17 is a cross-sectional side view of FIG. 16 with the vent shown in a closed position;
FIG. 18 is a cross-sectional side view of FIG. 16 with the vent shown in an open position;
FIG. 19 is a front view of dishwasher control panel incorporating pump controls on the facade of the dishwasher panel, and a systems monitor to indicate detergent level.
DETAILED DESCRIPTION OF THE INVENTION
Although the present invention is herein described in terms of a basic embodiment, it will be readily apparent to those skilled in this art that various modifications, rearrangements, and substitutions can be made without departing from the spirit of the invention. The scope of the present invention is thus only limited by the claims appended hereto.
Now referring to FIG. 1, set forth is a pictorial view of a conventional residential kitchen depicting a cabinet 100 supporting a utility sink 102 adjacent to a dishwasher 104. The apparatus of the instant invention consists of a pump 10 that is operated on electricity as illustrated by electrical cord 12 inserted into wall socket 106, wherein the pump 10 is placed within a housing 14 having a timing mechanism such as a potentiometer or the like control switch 16 that permits the pump to run for a predetermined amount of time. A "light" setting 18 allows the pump to run at a minimal amount of time delivering only a small amount of detergent, perhaps 1/2 oz when regular water supply is "soft". A "normal" setting 20 allows the pump to operate a predetermined period of time to allow the pump to transfer an amount of liquid detergent into the dishwasher, perhaps the 11/4 A oz. typically required for an average dishwashing cycle and, an "extra" setting 22 provides pump operation leading to an additional amount of detergent transferred, perhaps 2 oz. for those instances where the dishwasher is expected to clean an oversized load, or when "hard" water conditions are present.
The transfer means is a pump 10 which is fluidly coupled to a liquid detergent storage means, capable of holding at least one pint of liquid, in this instance a container 108 wherein the shipping cap, not shown, is removed and replaced with a modified cap 24 having four apertures allowing detergent removal. A first aperture is coupled to tube 26 which is juxtapositioned a small distance from the bottom wall of the container 108 and allows for liquid detergent transfer through pump 10 outward through delivery tube 28 into injection fitting 30 mounted through the side wall of dishwasher 104. A second tube 32 allows liquid detergent transfer from container 108 through pump 10 and returns the detergent through return tube 34. This operation allows for continuous liquid sensing.
When the level of detergent drops beneath the entry opening 36 of the second tube 32, a sensor determines lack of fluid providing an alarm to indicate that the liquid container 106 is low on detergent. Alarm indication is provided by a light 38 located on the facade of the pump housing and having an audible alarm 40. Vent 42 is provided for aspiration to prevent collapse of the container while liquid detergent is being withdrawn.
The pump 10 is electrically coupled to the existing detergent drawer 112 of the dishwasher to initiate pump operation at a time predetermined by the manufacturer of the dishwasher. Water inlet solenoid 46 is electrically coupled to the liquid level sensing mechanism so that when a low level of liquid detergent is sensed, three additional washing cycles are allowed and then water inlet solenoid 46 is disconnected electrically thereby preventing any additional wash cycles until detergent is replenished.
Referring to FIG. 2, an alternative embodiment of the invention illustrates the pump 10 with the aforementioned control switch 16, coupled to a storage container 50. Pump 10 is operated on 120 VAC as provided by electrical cord 12 inserted into wall socket 106 having a DC step down transformer allowing direct pump control. In this embodiment the storage container 50 accepts a manual refill of detergent with a fill. port aperture 52 allowing insertion of liquid detergent. The fluid level is visually determined by indicator 54 which operates via a well known twist rod float 56 mechanism. It should be noted that the storage container 50 may be made of translucent material thereby eliminating the need for a visual float indicator as the level may be determined by viewing through the side wall of the storage container 50.
Operation of this embodiment remains similar to the previous embodiment by positioning the apparatus within an open cabinet 100 next to a dishwasher 104. The operation of the pump 10 is initiated by detergent drawer 112 electrically coupled by cable 44 to the pump controller mechanism. In addition, inlet solenoid 46 is electrically coupled to the apparatus providing a delayed shut off of water if an insufficient amount of detergent exists within the storage container 50.
In operation, suction tube 58 is juxtapositioned along bottom wall of storage container 50 providing an inlet for the pumping mechanism with outlet tube 28 coupled to injection fitting 30 placed through the side wall of dishwasher 104. A tube opening 60 assists in determining the fluid level within the container by providing an indicator to the pump 10 when the level of liquid detergent falls below the aperture opening. As with the previous embodiment, inadequate fluid level operates light 38 and audible alarm 40 so as to provide an indication to the homeowner of a low level condition. In addition, as previously mentioned, the apparatus provides approximately three additional dishwasher cycles once the liquid has fallen below tube opening 60 before disengaging inlet solenoid 46. It will be obvious to one of ordinary skill in the art that the amount of dishwashing cycles after the fluid falls beneath the low level pick up may be adjusted in accordance with the size and shape of the liquid detergent container and the detergent setting, i.e., LT.--NOR.--EXTRA. Vent 62, described later in the specification, prevents collapse of the storage container 50 as the pump 10 draws detergent from the chamber.
Now referring to FIGS. 3 and 4, set forth is an alternative embodiment of the instant invention having a container 70 remotely located beneath dishwasher chamber 114. An alternative sensing mechanism 72 may consist of an electrode for detecting the level of liquid within the container 70. Suction tube 74 is fluidly coupled to pump 76 which transfers liquid through dispensing tube 78 into dispensing mechanism 80 placed in the side wall of the dishwasher chamber 114. Filling of the container 70 is provided by aperture 82 having connecting pipe 84 fluidly communicating with an upper portion of container 70.
Detergent container 116 may be temporarily placed on the upper rack 120 with a fill tube 118 placed into aperture 82 allowing transfer of its contents into container 70. As will be described later in this specification, aperture cap 86 is of a design to engage aperture 82 for sealing of connecting pipe 84, yet providing a means for a moisture rich environment to be maintained in container 70 to prevent thickening of the detergent. FIG. 4 is identical to FIG. 3 with the exception of pictorial illustration of a flexible dispenser 122. This allows a cost savings to the homeowner by elimination of a heavy detergent container 116 as the flexible dispenser 122 is used only for a quick transfer, not storage, of the detergent into the container 70 before disposal.
Now referring to FIG. 5, set forth is a variation of the integrated storage container having three electrodes indicating either empty 90, 1/2 full 92 and full 94 fluid levels. As with the previous embodiments, transfer tube 74 is coupled to transfer pump 76 which engages dispensing tube 78 for subsequent insertion through the side wall of the dishwasher.
Now referring to FIG. 6, container 200 is illustrated beneath dishwasher 104 having fill port 202 positioned along dishwasher chamber floor 124 wherein the previously described mechanical visual indicator 204 threadingly engages opening 206 of the fill port 202. Visual indicator 204 includes a floating mechanism 208 placed along twist rod 210 providing a rotational movement to an indicator in relation to the amount of rod twist. As with the previous embodiment, liquid detergent is transferred via suction tube 212 coupled to transfer pump 214 for delivering fluid through tube 216 and into the dishwasher chamber 114 via dispensing mechanism 218. Vent 220 is located along the upper portion of container 200 allowing the visual indicator 204 to tightly seal the container to prevent water from entering the fill port during the dishwasher cycle. In this manner, liquid detergent is delivered through fill tube 118 into the opening 206. Low level determination is performed by sensing mechanism 224 which operates along the previously described principles of a sensing electrode.
FIGS. 7 through 9, set forth the aperture cap 86, as previously described, which is used for coupling to aperture 82 having connecting pipe 84 secured to a storage container located beneath the dishwasher chamber. The aperture cap 86 includes a plurality of venting holes 230 positioned on an outer surface 232 of the cap with a raised ridge 234 allowing for ease of twisting the cap for insertion and removal. Flexible gasket 236 prevents misplacement of the cap while opened. The cap has inner coupling tabs 238 which fit within slot 240 with a twist lock section 242 for securing the cap in position. It is noted that the gasket 236 forms around the inner surface of the cap for sealing against wall member 243. As noted in FIG. 9, aperture cap 86 shown in a sealed position wherein gasket 236 provides a seal with excess moisture drained by sloping surface 248 through aforementioned venting holes 230. A venting check valve is formed by flexible member 250 positioned along a rear portion of aperture cap 86 having a plurality of venting holes 252 which allows a small amount of moisture to bleed into connecting pipe 84 to help maintain a high moisture level thereby preventing thickening of the liquid detergent.
Now referring to FIGS. 10 through 13, set forth is the liquid injection dispenser member 275 mounted on a side wall 270 of a dishwasher having an inner lip 272 and an outer lip 274 engaging the dishwasher side wall 270 therebetween. Tube 276 is secured to the liquid injection dispenser member 275 by a coupling mechanism 278. As shown in FIG. 10, the liquid injection dispenser member 275 is in a closed position with cap 280 set in position by placement against cap seat 281 of inner lip 272. In FIG. 11, cap 280 of liquid injection dispenser member 275 is opened, the distance allowing the dispensing of detergent 282 to enter into the dishwasher chamber. Cap 280, as further illustrated by FIG. 12 is removable from chamber 284 allowing ease of cleaning or replacement if required. The cap 280 and spring 290 are housed in insertion fitting 286 and are held in place by a compression fit between a raised groove 289 on insertion fitting 286 and a recessed groove 291 on chamber 284. A plurality of raised ridges 288 along the surface of the insertion fitting 286 eases the removal and replacement thereof. Spring 290 is located within the cap 280 causing the cap to be drawn to a tight seal against cap seat 281 when no fluid is being dispensed through tube 276. It is noted that while dispensing of liquid detergent is taking place, it is performed during a cycle wherein the inlet solenoid is allowing water into the dishwasher chamber, thereby the displacement of the cap 280 allows for continually rinsing of the dispensing mechanism while detergent is being delivered and, after the deliverance, the washing water provides a removal of detergent from surfaces of cap 280 and cap seat 281 so as to eliminate the sticking of cap 280 upon closure.
Referring to FIGS. 14 and 15, set forth is yet another embodiment of a liquid dispenser member having an elbow 300 with a float ball 302 placed within floatable cage 304 which allows detergent to carry through dispensing tube 306 forcing float ball 302 upward until the deliverance of detergent stops float ball 302 is resituated to prevent water from entering elbow 300. It should be noted that a small amount of water entering elbow 300 is deemed beneficial as it provides additional moisture to the storage container which helps to prevent solidification of the detergent. As shown in FIG. 15, the elbow 300 can be easily removed for repair, cleaning, or replacement wherein housing 312 is operatively associated with inlet section 314 having locking tabs 316 which engage locking slots 318 of housing 312.
Now referring to FIGS. 16 through 18, the vent 220 includes a plurality of openings 320 which allow air to be drawn into the housing. Spring 322 is forced into a closed position by suction caused upon the transfer of liquid from the vented container. When sufficient air has displaced liquid within the vented container, openings 320 are disjoined from chamber 324 by the upward movement of chamber 324 providing a check valve type operation to inhibit additional air from entering the container.
As shown in FIG. 19, a pictorial of a dishwasher 350 having the controls integrated directly into the control panel is shown and made possible by the second embodiment of this invention wherein the homeowner may depress a light 352, normal 354, or extra heavy setting 356, as dependent upon the types of eating utensils to be washed, and hardness of water supply. As noted, next to each section is an illustration of the need for a light amount of detergent for china versus an extra heavy amount of detergent which is used for pots and pans. A systems monitor 360 is provided which allows a reading of the amount of detergent within the container providing a graphic illustration of a low, medium, or full amount of detergent.
It is to be understood that while a certain form of the invention is illustrated, it is not to be limited to the specific form or arrangement of parts herein described and shown. It will be apparent to those skilled in the art that various changes may be made without departing from the scope of the invention and the invention is not to be considered limited to what is shown in the drawings and described in the specification. | The instant invention is an automatic detergent dispenser for residential dishwashers allowing transfer of liquid from a store purchased container or an integrated storage receptacle. The invention allows an individual to determine the amount of detergent to be transferred with provisions to operate the detergent transfer only upon demand preventing operation of the dishwasher if an insufficient amount of detergent is available. An alternative embodiment allows positioning of a storage container beneath the dishwasher chamber with provisions to fill the container. | 0 |
CROSS-REFERENCE TO RELATED PATENT APPLICATION
This application claims the benefit of U.S. Provisional Applications 61/268,803 and 61/243,246, which were respectively filed on Jun. 16, 2009, and on Sep. 17, 2009, and which are incorporated herein in their entirety by reference.
GOVERNMENT INTERESTS
This invention was funded, at least in part, with a government grant from the National Institute of Standards and Technology (NIST) pursuant to contract number 70NANB7H6168. This invention was also funded, at least in part, with a government support under Grant No. CCF-0621990 entitled “Nano: Applications, Architectures, and Circuit Design for Nano-scale Magnetic Logic Devices” awarded by the National Science Foundation (NSF). Accordingly, the United States government may therefore have certain rights in this invention.
FIELD OF THE DISCLOSURE
The present disclosure relates to magnetic quantum-dot cellular automata, more particular to non-majority magnetic logic gates and arrays based on misaligned magnetic islands.
BACKGROUND
Nanomagnetic logic (NML), also known as, Magnetic Quantum-Dot Cellular Automata (MQCA) consists of using nanomagnetic islands arranged in such a way that allows logic functions to be performed by using NML circuits. Wires, gates, and inverters have already been demonstrated to function at room temperature. It is estimated that if 10 10 magnets switch at 10 8 times/second, then the magnets would only dissipate about 0.1 W of power. These nanomagnet based devices can remain non-volatile provided that their size/shape remains above the superparamagnetic limit which means that these nanomagnets devices can be used to realize both logic and memory devices. If non-volatility can be sacrificed, research suggests that binary state in nanomagnets with feature sizes below the superparamagnetic limit should also be stable for around 1 millisecond. This retention time is sufficient to perform logic operations. Device switching times could also be reduced.
The fundamental building blocks for NML circuits can (i) be made with standard lithographic techniques and (ii) have all been experimentally demonstrated at room temperature. Wires that exhibit ferromagnetically ordering ( FIG. 1 a - c ) can be formed by orienting rectangular magnets next to each other so that their magnetic poles are within a commonly shared axis as shown in the FIG. 1 a - c . Likewise anti-ferromagnetically coupled bit wires can be formed by orienting rectangular magnets next to each other so that their magnetic poles are parallel to each other and not within a commonly shared axis as shown in FIG. 2 a - c.
Because the energy difference between magnetization (binary) states in an NML device can be hundreds of kT at room temperature, an applied magnetic clock is needed to facilitate the re-evaluation of an NML ensemble subsequent to when input states are changed. The applied magnetic clock provides the necessary energy that modulates the barrier between magnetization states so that fringing fields from individual magnets can quickly bias neighboring magnets into their respective thermodynamically favorable magnetization state that corresponds to the logically correct output states associated with the input(s). This reordering of magnetization states is guided by either antiferromagnetic or ferromagnetic coupling which is dependent upon the relative positions of how the particularly adjacent magnets are geometrically arranged.
For example, reordering of magnetization states in an antiferromagnetic coupled horizontal line would proceed as shown in FIG. 3 - i to FIG. 3 - iii (where just 3 devices are shown for simplicity). After the field of the left most magnet is externally driven by an Input (not shown) to flip its magnetic state, the applied magnetic clock field (H) is then subsequently imposed on all of the magnets (e.g., in an antiferromagnetically ordered line) which drives the internal magnetic fields (sideways arrows) of the center and right most magnets to be biased along their hard (shorter) axes (as shown in the transition from FIG. 3 - i to FIG. 3 - ii ). Note that the internal magnetic field (up arrow) of the left most magnet is unaffected by the applied magnetic clock field (H) because it remains biased along its easy (long) axis driven by the continued imposition of the external magnetic field at the Input (not shown). As a result of imposing the applied magnetic clock field which drives the internal magnetic fields of the center and right most magnets pointed towards their hard axes (i.e., nullify), the energetic barriers of the center and right most magnets needed to reach their new energetically favorable magnetization state are considerably lowered. Flux from neighboring magnets can then efficiently bias these magnets into a new magnetically stable state (FIG. 3 - iii ) when the applied magnetic clock field (H) is removed.
It is known that fringing field-based interactions between single domain magnets with nanometer feature sizes can be used as a driving force to perform Boolean logic operations. With NML, logic functionality results from a complex interplay of shape anisotropy and magnet-to-magnet coupling. Magnet shape anisotropy, i.e., an elongated easy axis, creates a bi-stable system, and binary values (1/0) can be arbitrarily assigned to different magnetization directions. For many magnet shapes, the easy axis states are energetically equivalent for a magnet in isolation. When considering magnet ensembles, in clocked systems, fringing fields from individual devices can set the state of a neighboring device when that device is in a metastable logic state. It is known that these fringing field interactions can be used to implement majority voting gates and, in principle, implement any Boolean function.
To date, all known proposals for Boolean logic designs using NML architecture have either been majority gate based or assumed magnets with a uniform shape. Majority gates can be transformed into AND/OR or NAND/NOR gates and can be used to implement any Boolean function (as for AND/OR gates, inversion is possible with an antiferromagnetically ordered wire with an odd number of devices). One way of transforming a majority gate into either a AND/OR or NAND/NOR gate configuration is to permanently fix one of the inputs to a logic 0 or logic 1. Thus, Boolean logic can be realized using majority voting gates by arbitrarily setting one input of a majority gate to a logic ‘0’ or ‘1’, to transform the gate to a two input AND/OR gate. However, reducing a clocked majority gate to a 2-input AND/OR gate is non-trivial. The fixed/held input must be designed such that it does not impede the switching of the compute magnet (e.g., by providing too strong of a bias). If this does happen, a stuck-at fault will ensue as the two other inputs will not be able to drive the gate to a logically correct state.
Some advantages of NML designs include high scalability with ultra-low active power and essentially zero leakage power. NML are also thought to be inherently radiation resistant. To date, known NML designs have utilized elementary symmetrical shapes, i.e., rectangular and ellipsoid devices, have been used for majority gate logic designs.
As depicted in FIGS. 4-5 , majority logic gates (MLG) have been used as a basis to demonstrate that magnetic quantum-dot cellular automata (MQCA) can be used to successfully implement various Boolean logic functions. Magnetic logic manipulates spin-polarized electrons in the magnetic material where information can be arbitrarily correlated with either “spin up” or “spin down” electrons. However, not all Boolean functions map well to majority voting gates (i.e. XOR). More specifically, an XOR gate constructed from majority gate-based AND/OR logic will likely require a relatively large footprint.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood and aspects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings wherein:
FIGS. 1A-C are a Scanning Electron Micrograph (SEM) Image, Magnetic Force Microscopy (MFM) Image and an arbitary magnetic field vector corresponding to a ferromagnetically coupled bit line;
FIGS. 2A-C are a SEM Image, MFM Image and an arbitary magnetic field vector corresponding to an antiferromagnetically coupled bit line;
FIGS. 3 i - iii is a stylistic portrayal of a magnetic state reordering along an antiferromagnetically coupled bit line;
FIG. 4 depicts one majority gate based AND logic gate layout showing four operational magnetic vector combinations and their respective outcome;
FIG. 5 depicts one majority gate based OR logic gate layout showing four operational magnetic vector combinations and their respective outcome and their respective outcome;
FIG. 6 illustrates some of the geometric and angular misalignment configurations through to be possible for MAMI of the present invention;
FIG. 7 is one non-majority based AND logic gate layout and sweeping scenario showing four operational magnetic vector combinations and their respective outcome of the present invention;
FIG. 8 depicts four possible layouts and sweeping scenarios forming non-majority based AND logic gates of the present invention;
FIG. 9 is one non-majority based OR logic gate layout of the present invention showing all four operational magnetic vector combinations and their respective outcome;
FIG. 10 depicts four layouts and sweeping scenarios forming non-majority based OR logic gates of the present invention;
FIG. 11 depicts four layouts and sweeping scenarios forming non-majority based NAND logic gates of the present invention;
FIG. 12 depicts four layouts and sweeping scenarios forming shaped based NOR logic gates of the present invention;
FIG. 13 is a perspective view of a magnetic logic gate array of the present invention;
FIG. 14 is a perspective view of a non-majority magnetic logic gate device of the present invention;
FIG. 15 a is an XOR logic gate configuration using majority gates;
FIG. 15 b is an XOR logic gate configuration using non-majority logic gate device the present invention;
FIG. 16 is another XOR logic gate configuration using non-majority logic gate device of the present invention;
FIG. 17 is Magnetization (My) as a function of time for slant edged MAMIs where the initial magnetization was originally along the x-axis and at the saturation magnetization;
FIG. 18 is a demagnetizing energy profile as a function of magnetization angle for two MAMI asymmetric magnets (S) and a symmetric rounded rectangular magnet (RR);
FIG. 19 is a magnetization profile along a y-axis (My) of a MAMI magnet as a function of applied magnetic field along the x axis (Hx) that depicts asymmetric behavior;
FIG. 20 is M-H curves for symmetrical and asymmetrical magnets;
FIG. 21 a is a non-majority OR gate of the present invention;
FIG. 21 b is a truth table for the non-majority OR gate of the present invention;
FIG. 21 c is a non-majority AND gate of the present invention;
FIG. 21 d is a truth table for the non-majority AND gate of the present invention;
FIG. 22 is a magnetization profile along a y-axis (My) of a MAMI magnet as a function of applied magnetic field along the x axis (Hx) showing different threshold energetics for three different transitions in a non-majority gate; and
FIG. 23 is a magnetization profile along a y-axis (My) of a MAMI magnet as a function of applied magnetic field along the x axis (Hx) showing different threshold energetics for the same transition a non-majority gate as a function of Hx with or without a helper cell.
The same reference numerals refer to the same parts throughout the various figures.
DETAILED DESCRIPTION
Referring now to the drawings, and in particular FIGS. 1-3 , 6 - 16 , and 21 thereof, one envisioned example of the non-majority magnetic logic gate device 10 , such as those shown in FIGS. 13-14 , comprises a substrate 20 ; a plurality of symmetrically aligned magnetic islands (SAMIs 30 ), a misaligned magnetic island (MAMI 60 ), a plurality of magnetic field inputs (MFIs 70 ) and at least one magnetic field output (MFO 80 ). The SAMIs 30 are disposed on the substrate 20 so that most of the SAMIs 30 are disposed either substantially perpendicular or substantially in parallel relative to a sweeping direction of an applied magnetic clock field 40 and such that the applied magnetic clock field 40 is applied substantially parallel or perpendicular to a plane 50 of the substrate 20 . Most of the SAMIs 30 have lengths longer than their widths which respectively define easy and hard magnetic axes. Most of the SAMIs 30 are electrically isolated from each other. Of those SAMIs 30 that are symmetrically aligned lengthwise side by side next to each other tend towards exhibiting antiferromagnetic coupling with each other. Of those SAMIs 30 that are symmetrically aligned widthwise side by side next to each other tend towards exhibiting ferromagnetic coupling with each other. The MAMI 60 is also disposed on the substrate 20 and the MAMI 60 also has a length longer than a width that respectively define easy and hard magnetic axes. The MAMI 60 is electrically isolated from the SAMIs 30 but the MAMI 60 is magnetically coupled and sandwiched in between two SAMIs 30 . The MAMI 60 is configured to exhibit a magnetization ground state bias which is dependent upon the sweeping direction of the applied magnetic clock field 40 . The MFIs 70 are disposed on the substrate 20 and are magnetically coupled to some of the SAMIs 30 . The MFO 80 is disposed on the substrate 20 and magnetically coupled to the MAMI 60 .
The clocking of the applied magnetic clock field 40 may be at any frequency. Some envisioned clocking frequencies of that the applied magnetic clock field 40 are between 1 Hz to about 1 GHz.
The strength of the applied magnetic clock field 40 is designed to be sufficiently strong to rotate magnetization moments of the SAMIs 30 and the MAMI 60 from the easy axes to the hard axes into a neutral logic state such that fringing fields from the neighbor SAMI/MAMI can set a given device into a logically correct state.
The distances between adjacent SAMIs 30 and the MAMI 60 disposed on the substrate 20 should be designed so that magnetic flux lines are sufficiently strong enough to magnetically influence each other.
Although all of the SAMIs 30 do not necessarily have to be along the plane 50 of the substrate 20 , one envisioned configuration is that all of the SAMIs 30 are disposed along the plane 50 of the substrate 20 .
Although all of the SAMIs 30 do not necessarily have to be disposed perpendicular or parallel to the sweeping direction of the applied magnetic clock field 40 , one envisioned configuration is that all of the SAMIs 30 are disposed either substantially perpendicular or substantially in parallel relative to the sweeping direction of the applied magnetic clock field 40 .
Although all of the SAMIs 30 do not necessarily have lengths longer than their respective widths, some SAMIs 30 may even have circular shapes. One envisioned configuration is that all of the SAMIs 30 have lengths longer than their respective widths. Another envisioned geometric configuration is that some of the SAMIs 30 have elongated rectangular shapes.
The MAMI 60 may be any geometrically and/or angularly misaligned magnetic island (2 or 3 dimensional) configuration in which some of 2 dimensional configurations are depicted in FIG. 6 . One envisioned geometric configuration of the MAMI 60 is that it has a slant edged rectangular shape which is substantially lined up parallel and/or perpendicular to the sweeping direction of the applied magnetic clock field 40 . Another envisioned configuration is that the MAMI 60 has an elongated rectangular shape (i.e., symmetrical in geometry) that is aligned so that it is not parallel and not perpendicular (i.e., angularly misaligned) to the sweeping direction of the applied magnetic clock field 40 .
One mode of the sweeping direction of the applied magnetic clock field 40 is that it is left to right with respect to the substrate 20 . Another sweeping direction of the applied magnetic clock field 40 is right to left with respect to the substrate 20 .
An envisioned orientation of the applied magnetic clock field 40 is that it is applied substantially parallel to the plane 50 of the substrate 20 . Another envisioned orientation of the applied magnetic clock field 40 is that it is applied substantially perpendicular to the plane 50 of the substrate 20 .
An envisioned distributive arrangement of the SAMIs 30 is that some of the SAMIs 30 are aligned to form antiferromagnetic coupled binary wires 130 . Still another envisioned distributive arrangement of the SAMIs 30 is that some of the SAMIs 30 are aligned to form ferromagnetic coupled binary wires 140 .
An envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that it comprises an OR gate as shown in FIGS. 9 , 10 , and 21 a - b . Yet another envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that it comprises an AND gate as shown in FIGS. 7 , 8 and 21 c - d . Still another envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that it comprises a NAND gate as shown in FIG. 11 . Still yet another envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that it comprises a NOR gate as shown in FIG. 12 . Accordingly the device 10 may comprise any number of logic functions which can include AND, OR, NAND, NOR and even comprise a logical memory like a bit of MRAM.
A envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that they are all together substantially aligned perpendicular to the sweeping direction of the applied magnetic clock field 40 . Still another envisioned arrangement of the MAMI 60 sandwiched between two SAMIs 30 is that they are all together aligned substantially in parallel with respect to the sweeping direction of the applied magnetic clock field 40 .
An envisioned example of the device 10 is that the MAMIs 60 are magnetically coupled and sandwiched between pairs of SAMIs 30 to form an XOR gate as shown in FIG. 15 .
The compositional makeup of the SAMIs 30 and MAMIs 60 may be made of any known material so long as they exhibit magnetic properties. For example, it is envisioned that the SAMIs 30 and the MAMI 60 can be composed of magnetic material selected from the group consisting of a rare earth metal, ferrites, hipernom, hipernik, HyMu-80, monimax, Mo-permalloy, nilomag, remalloy, sanbold, supermumetal, ultraperm, vicalloy, 78 Permalloy, permalloy, supermalloy, AlNiCo, AlSiFe (sendust), Co, CoFe, CoFeB, CoFeV (supermendur), CoFeCr (hiperco), CoPt, CoZrTa, CoFe (permendur), CuZn, FeN, FeO, FeAlN, FeTaN, NiFe (permalloy), NiFeMo supermalloy, NiFe supermalloy, NiFeCuCr (mumetal), NiFeCo, MnZn, and combinations thereof.
The non-majority magnetic logic gate device 10 may also further comprise a plurality of MAMIs 60 in which the MAMIs 60 are magnetically coupled and sandwiched between corresponding respective pairs of SAMIs 30 .
The non-majority magnetic logic gate device 10 may also further comprise a plurality of MFOs 80 magnetically coupled to the MAMIs 60 . It is important to note that the MFOs 80 do not necessarily have to be immediately adjacent to the MAMIs 60 . That is either antiferromagnetic or ferromagnetic coupled binary wire 140 s (as shown in FIGS. 1-3 and 13 - 14 can be used to magnetically couple any of the MAMIs 60 to their respectively coupled MFOs 80 .
The non-majority magnetic logic gate device 10 may also further comprise an XOR gate which is composed of three adjacent SAMIs 30 aligned linearly together and one MAMI 60 . The three linearly aligned together adjacent SAMIs 30 are magnetically coupled to each other and the one MAMI 60 is magnetically coupled to a middle one of the three adjacent SAMIs 30 .
The non-majority magnetic logic gate device 10 may also further comprise an applied magnetic clock field 40 circuit 120 configured to produce and to sweep the applied magnetic clock field 40 .
The non-majority magnetic logic gate device 10 may also further comprise a dielectric layer 90 , a cladding layer 100 , a fill layer 110 , and an applied magnetic clock field 40 circuit 120 . It is preferable that the dielectric layer 90 is disposed on the substrate 20 and the cladding layer 100 is on the dielectric layer 90 . It is also preferable that the fill layer 110 on the cladding layer 100 and applied magnetic clock field 40 circuit 120 buried in the fill layer 110 .
Another envisioned example of the present invention is that it comprises a non-majority magnetic logic gate device 10 . The non-majority magnetic logic gate device 10 of this example comprises a substrate 20 , a plurality of SAMIs 30 , a MAMI 60 , a plurality of MFIs 70 and a MFO 80 . The plurality of SAMIs 30 are disposed on the substrate 20 such that most of the SAMIs 30 are disposed either substantially perpendicular or substantially in parallel relative to a sweeping direction of an applied magnetic clock field 40 so that the applied magnetic clock field 40 is applied substantially parallel or perpendicular to a plane 50 of the substrate 20 . Most of the SAMIs 30 have lengths longer than widths that respectively define easy and hard magnetic axes and that most of the SAMIs 30 are electrically isolated from each other. Of those SAMIs 30 that are symmetrically aligned lengthwise side by side next to each other tend towards exhibiting antiferromagnetic coupling with each other. Of those SAMIs 30 that are symmetrically aligned widthwise side by side next to each other tend towards exhibiting ferromagnetic coupling with each other. Three adjacent SAMIs 30 aligned linearly together are magnetically coupled to each other. The MAMI 60 is also disposed on the substrate 20 in which the MAMI 60 is configured to have a length longer than a width that respectively define easy and hard magnetic axes. Accordingly, the MAMI 60 is configured to exhibit a magnetization ground state bias which is dependent upon the sweeping direction of the applied magnetic clock field 40 and that the MAMI 60 is electrically isolated from the SAMIs 30 . The MAMI 60 is also disposed next to the three adjacent SAMIs 30 so that the MAMI 60 is magnetically coupled to only a middle one of the three adjacent SAMIs 30 in which the three adjacent SAMIs 30 and the MAMI 60 comprise an XOR gate. The MFIs 70 are also disposed on the substrate 20 and magnetically coupled to some of the SAMIs 30 . The MFO 80 is also disposed on the substrate 20 and magnetically coupled to the MAMI 60 .
Yet another envisioned example is that present invention can comprise a magnetic logic gate array 150 . The magnetic logic gate array 150 comprises a substrate 20 ; a plurality of non-majority magnetic logic gate devices 10 , MFIs 70 and MFOs 80 . The non-majority magnetic logic gate devices 10 are disposed on the substrate 20 in which the devices 10 comprises SAMIs 30 and MAMIs 60 . The SAMIs 30 are disposed on the substrate 20 in which most of the SAMIs 30 are disposed either substantially perpendicular or substantially in parallel relative to a sweeping direction of an applied magnetic clock field 40 such that the applied magnetic clock field 40 is applied substantially parallel or perpendicular to a plane 50 of the substrate 20 . Most of the SAMIs 30 having lengths longer than widths that respectively define easy and hard magnetic axes and that most of the SAMIs 30 are electrically isolated from each other. Of those SAMIs 30 that are symmetrically aligned lengthwise side by side next to each other tend towards exhibiting antiferromagnetic coupling with each other. Of those SAMIs 30 that are symmetrically aligned widthwise side by side next to each other tend towards exhibiting ferromagnetic coupling with each other. The MAMIs 60 are also disposed on the substrate 20 in which the MAMIs 60 have lengths longer than widths that respectively define easy and hard magnetic axes and that the MAMIs 60 are electrically isolated from the SAMIs 30 . Most MAMIs 60 are magnetically coupled and sandwiched in between corresponding pairs of adjacent SAMIs 30 . The MAMI 60 is configured, i.e., geometrically and/or angularly misaligned, to exhibit a magnetization ground state bias which is dependent upon the sweeping direction of the applied magnetic clock field 40 . The MFIs 70 are disposed on the substrate 20 and magnetically coupled to some of the SAMIs 30 . The MFOs 80 are disposed on the substrate 20 and magnetically coupled to the MAMIs 60 .
The following simulated examples were generated using the Object Oriented Micro-Magnetic Framework (OOMMF) developed by the National Institute of Standards and Technology (NIST). The OOMMF uses a Landau-Lifshitz ODE solver to relax 3D spins on a 2D mesh of square cells. Unless otherwise note, all of the following simulations assume magnets made from supermalloy (79% Ni, 15% Fe, and 5% Mo) which is a soft magnetic material with a uniaxial anisotropy constant of essentially zero. Thus there is no easy/hard axis associated with the magnetic material itself and any easy/hard axis is only defined by the magnet shape. Unless otherwise noted, a saturation magnetization of 8.0×10 5 A/m and an exchange stiffness constant of 1.05×10 −11 J/m are used to model supermalloy. It is also assumed that the damping coefficient is 0.1, instead of 0.5, which corresponds more to experimental results. A stopping criteria, i.e., dm/dt, was chosen instead of a time cutoff. Each OOMMF simulation time step step was only considered to be complete when the maximum change in magnetization per unit time (across all spins associated with a given circuit element) fell below 1 degree/ns. A stopping criteria, i.e., dm/dt, was chosen instead of a time cutoff. Finally, unless otherwise noted, all simulated magnets were set to have a footprint of 50×75×25 nm 3 .
Simulation Example 1
Asymmetry and Magnetization Behavior
Simulations of magnetic properties of magnets having “slanted” or “cut” edges as illustrated in the inserts in FIG. 17 . In the simulations three slanted magnets initially have a strong x-component of magnetization (e.g., they are biased along their hard/short axes). If no field is applied to keep a given device in this metastable state, and the magnetic material is polycrystalline (e.g., permalloy or supermalloy), then the devices should relax into a magnetization state determined by its easy/long axis. In clocked lines of magnets, the fringing fields from a neighboring device will ideally determine the sign of the final magnetization state. In the presence of no applied bias, what state a magnet with a rounded rectangular shape might eventually relax into would essentially be random.
However, as magnetic moments tend to align along a magnet's edge, a slanted edge can give a device a envisioned y-component of magnetization. Both the position of the slant and the initial x-component (direction) of magnetization both dictate what state a device will ultimately relax to. This effect is captured quantitatively in FIG. 17 where we considered three magnets with slanted edges. Slant edge magnets v1 and v2 have a 50×75×25 nm 3 footprints and v3 has a 40×60×20 nm 3 footprint. Each slant edge magnet device was initialized with both a positive and negative x-component of magnetization and was allowed to relax with no external clocking field or Hy bias applied. The placement of the slant and the direction of the initial x-component of the magnetization consistently lead to a envisioned y-component of magnetization of each of the slant edge magnet devices (e.g., ↑ or ↓ states).
Simulation Example 2
Asymmetry and Magnetization Behavior
If a magnet with a slanted edge on its upper left initially has a strong positive y-component of magnetization and an external field is applied from left-to-right along its hard axis and then removed, there is no My state change. If the initial y-component of magnetization is negative and the same field is applied even with no Hy bias, there is an My state change. In FIG. 19 this phenomenon is seen via OOMMF simulation of supermalloy magnets with various sizes and shapes. Slant position and direction of the Hx field/initial Mx state determine the final My state.
The My state transition can be explained by plotting a device's demagnetizing energy, i.e., the internal energy that opposes the direction of magnetization, as a function of angle of magnetization FIG. 18 . Each peak of the asymmetrical (i.e., slant) magnets is not centered at zero degrees as compared to the case for a symmetric rounded rectangular magnet. Rather each peak of the asymmetrical magnets is shown shifted to the left. This explains the My sign change in FIG. 18 . The maximum magnetization energy is at an angle below horizontal. If the applied Hx field causes a device to move past this angle, even if some initial y-component of magnetization is retained, when Hx is removed, the devices relax such that My is positive.
In our second set of simulations, we again considered a magnet in isolation with a slanted edge in isolation (specifically slant edge magnet v1 of FIG. 17 ). As in the first simulation example the slant edge magnet was initially magnetized such that its y-component of magnetization was equal to the saturation magnetization (Ms) of supermalloy (↑). We then applied an external field along the magnet's hard axis (in the positive x-direction) that increased in magnitude from 0 A/m to 120,000 A/m in 800 A/m increments. The field was then removed in a similar fashion. These simulations results are illustrated in FIG. 19 . Note that this device always retains some of its initial y-component of magnetization state (↑). Next, the slant edge magnet was in an initial state such that My was negative (↓). Again, we applied a field along the device's hard axis, from left-to right, then gradually increased in magnitude. Given these initial conditions, when the external field (Hx) reaches 70,000 A/m, the position of the slant and the direction of the applied field include a transition from a down state (↓) to an up state (↑) even with no Hy bias is applied to the device.
Simulation Example 3
Asymmetry and Magnetization Behavior
Magnetic state changes (e.g., from ↑ or ↓) can also be facilitated with combinations of hard axis and fringing fields as well. The clocking fields (Hx) place each magnet in an ensemble into a state such that it can be switched into a new, logically correct state by its neighbor's fringing fields (i.e., Hy).
This effect is depicted quantitatively in FIG. 20 where a rounded rectangular and a slanted edge magnet were considered. Each simulated magnet was set to have a 50×75 nm 2 footprint and a constant 46,000 A/m bias was applied along a mangnet's hard axis in each case. For each shape, a magnet can transition from a ↑ or ↓ state with a significantly lower Hy bias. However, while the M-H curve for the rounded rectangle device is symmetric (the same bias is required to facilitate an ↑ to ↓ and ↓ to ↑ transition), the M-H curve for the magnet with a slanted edge is asymmetric. Given the direction of the applied field (Hx) and the device's initial state, a stronger field is required to make the magnet transition to a state against that suggested by the position of its slant, e.g., 12,334 A/m field is required for a ↑ to ↓ transition while a field of 15,915 A/m is required for a ↑ to ↓ transition. Still, while a 30% larger Hy bias is needed, a state transition “against” the slant and direction is still possible.
Simulation Example 4
Asymmetry and Logic
FIG. 21 a depicts a 3 magnet ensemble which implements a logic OR function. If i 1 and i 2 have the same My state, output magnet ‘o’ will see a net Hy bias that induces ferromagnetic ordering in i 1 , o, and i 2 . If the magnet is sufficiently nulled, fringing fields from the two inputs will also influence the output magnet's My state. The bias needed to facilitate a state transition for ferromagnetic ordering (in the presence of a given Hx field) can be determined via an M-H curve generated via OOMMF simulation (See FIG. 20 ). While the M-H curve for a magnet with a slanted edge is asymmetric, if the two input magnets could provide the higher Hy bias, they can facilitate the state transitions required for the top and bottom input combinations in the truth table of FIG. 21 b . As shown in FIG. 21 c - d , a 2-input AND can be realized if the slanted edge is on the bottom left.
In an actual circuit, the Hy biases will not be externally applied but instead will come from neighboring devices. For example, referring back to FIG. 21 a , the fringing fields from i 1 and i 2 might generate the Hy bias that ultimately sets the state of the slanted output magnet. With this configuration, there are four combinations of magnetization states that and i 2 could represent (See FIG. 21 b ). Based on the simulation results, if the “target” magnet with the slanted edge were initially biased such that Mx=Ms, and the input magnets were in opposite magnetization states, the target magnet would be expected to settle into a ↑ state—as the fringing fields from the two inputs effectively cancel. Similarly, if the target magnet is sufficiently biased along its hard axis, and the combined Hy biasing fields from i 1 and i 2 are sufficiently strong, then they are expected to be able to set the magnetization state My of the slant-edge target. If we equate a state to a binary 0 and a ↑ state to a binary 1, a magnet with a slanted edge could implicitly implement the logic OR function. Note that if the slanted edge were on the bottom left as shown in FIG. 21 c , a logic AND function would result ( FIG. 21 d ).
The average Hy bias produced by a 50×75×25 nm 3 supermalloy magnet even 15 nm away from a potential target is ˜25,000 μm. Thus, even if both input magnets in FIG. 21 a have the same magnetization state, FIG. 20 suggests that the fringing fields from the magnets alone will be insufficient to switch the state of the target (as the MH curves there also include a 46,000 A/m Hx bias). This suggests that we will also need to leverage an external/clock field applied along a target magnet's hard axis in order to facilitate any potential state change given the biases that 2 inputs might actually provide at some reasonable distance away. We are particularly interested in facilitating a state transition with the smallest external field possible as larger currents would be needed to generate larger fields per the mechanism in FIG. 14 —which will only increase system energy demands.
We consider a circuit structure like that illustrated in FIG. 21 a . The target magnet was initialized to a state opposite of that suggested by each of the four possible input combinations. (There are four possible state transitions.) In each instance, a field was applied parallel to the target magnet's hard axis. Our objective was to measure the magnitude of the external field required to facilitate a state transition. Three of the four simulation results are reported in FIG. 22 . (The ↑↓↑ to ↑↑↑ case is the “easiest” and is now shown to improve graph readability.) As one can see, higher external fields are required for the case where inputs are in opposite magnetization states. (This makes sense as there is essentially no Hy helper bias.) However, the simulations where inputs with opposite magnetization states are not symmetric—e.g., a greater external field is required if the top input is ↑ and the bottom input is ↓ than if the bottom input is ↑ and the top input is ↓.
This can be explained quantitatively by considering the structure illustrated in FIG. 21 when the line is in a ferromagnetically ordered state (e.g., all devices are ↓). If we measure the flux density 2 nm away from the top and bottom of the magnet with the slanted edge, the average flux density is approximately 13% higher between o and i 2 than between o and i 1 (See Table 1). In essence, the position of the slant on the top of the target leads to weaker coupling between i 1 and o than between i 2 and o. Thus, when the bottom magnet is in an ↑ state, and the top magnet is in a ↓ state, not only does the bottom magnet exert more control over the target, but it is also pushing the target to a logically correct state. For the opposite input combination, a greater external field is required as we essentially need to overcome the effects of a small “anti-bias” from the bottom magnet in a ↓ state.
TABLE 1
Effect of By on target magnet with different spacings between
input and target with slanted edges
Distance
Avg By
Case
(nm)
(mT)
Target - Bottom
15
−416
Target - Top
15
−336
Target - Top
10
−417
Target - Bottom
15
−413
Simulation Example 5
Asymmetry and Logic
As magnetic field strength is a function of distance, if allowable by a fabrication process, one way to ensure that both inputs have equal control over a slanted target is to change the distance between i 1 and o as depicted in FIG. 21 a . This effect is illustrated quantitatively in FIG. 23 where the ↑↓↓ to ↑↑↓ in case is again considered. Like the simulation results summarized in FIG. 22 , we simulated an applied local field along the target magnet's hard axis. However, in this simulation, the spacing between i 1 and o was 10 nm instead of 15 nm. (The spacing between i 2 and o remained at 15 nm.) As seen in FIG. 23 , the target magnet now changes state with a lower magnitude field (Hx). Similarly, from Table 1, in a ferromagnetically ordered line, the flux density between the top and bottom inputs and the target is essentially equal. Again, if enabled by a given fabrication process, these results suggest that asymmetric placement of the two inputs could allow for lower field and hence lower energy operations as the previous “worst case” is mitigated.
Finally, it is noted that realistically, an external field will not simply be applied to just a slanted target but rather the external field will be applied to all magnets in the ensemble. As such i 1 and i 2 will become weaker drivers as the clocking field will increase each magnet's x-component of magnetization. As also seen in FIG. 23 , the net effect of this is that a higher external field is required to facilitate a state transition in symmetric ↑↓↓ to ↑↑↓ case.
Simulation Example 6
Fringing Field Magnitude
One important design parameter is magnet “drive strength”, e.g., how much of a bias will it produce on the neighboring device that it is supposed to drive. To determine which shape configuration produces a stronger Hy bias, we consider each configuration in both states via simulation and measure the field produced on an equivalently sized footprint 15 nm away (assuming a magnet will drive a neighbor to its right). As seen in Table II the “slant on the left” configuration is an approximately 18% stronger driver.
TABLE II
Hy bias produced by 50 × 75 × 25 nm 3
supermalloy target magnet 15 nm away
Avg. Hy bias
Magnet
State
(A/m)
Slant left
up
−17866
Slant left
down
17866
Slant right
up
−15133
Slant right
down
15133
Simulation Example 7
Clocking
Another important design parameter is the magnitude of the external field required to facilitate a state transition. As such, we also studied which slant placement makes it easier to put a device into a metastable state as suggested by the input combinations that require state transitions. Again, four different configurations are considered: (i) a target that is initially in a state dictated by the slant and the direction of the applied switching field and where the inputs would suggest a state transition against the envisioned direction of the slant, and (ii-iv) a target that is initially in a state against that dictated by the slant and the direction of the applied switching field and where we cycle through all input combinations to put it into a correct state. (Here, the “hard cases” occur when the fringing fields from each input cancel and the slant determines the state transition.)
For each of these configurations we considered a 3 magnet line terminated by the block. The first magnet in the line was slanted. Local fields were applied over the target/slanted magnet to mimic new input drivers and the external field applied to this system was increased from 0 until all of the magnets in the line switched into the logically correct state suggested by the applied local fields. We studied the state of the last magnet in the line as a function of the applied clock—as this captures proper switching behavior of the line. Again, we found that the “slant left” placement allows for each simulation to transition into a logically correct state with the lowest overall external field. (With the “slant right” configuration, there is less coupling between the input magnet (a MAMI) and its right neighbor (a SAMI) which makes it more difficult for the other magnets in the line to transition through a metastable state. It is worth noting that if inputs are asymmetric, larger external fields are required. This maximum external field would then become a system design parameter as it would ensure that all the lines will transition correctly for all input combinations. Given these results, a gate with a slant on the left should require lower fields to transition to a neutral state, and can be a stronger driver.
Simulation Example 8
Shape Gate v Majority Gate
A two input XOR gate is used as a vehicle to discuss how shape-based logic can impact system level performance. The implicit majority voting function associated with magnetic logic will not enable a more efficient two input XOR gate. Majority gates must be reduced to AND/OR gates to implement the Boolean function A′B+B′A. A schematic of what a gate might look like if it were to be constructed with nanomagnets appears in FIG. 15 . (A majority gate design appears in FIG. 15 a and a shape-based design appears in FIG. 15 b .). The shape based design reduces extraneous interconnection which can in turn reduce gate delay by approximately 25% and reduce the gate footprint by almost 60%. As automata-like local interconnect and slower magnet switching times can only degrade performance, a shape based logic approach can only improve system level performance. Additionally, shape based logic gates appear to be controllable with the same fields necessary to control antiferromagnetic order bit lines of similarly sized magnets (good from the standpoint of system-level energy).
As to the manner of usage and operation of the present invention, the same should be apparent from the above description. Accordingly, no further discussion relating to the manner of usage and operation will be provided.
While an envisioned example of the non-majority magnetic logic gate device has been described in detail, it should be apparent that modifications and variations thereto are possible, all of which fall within the true spirit and scope of the invention. With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present disclosure.
Those of ordinary skill in the art will appreciate that the apparatus and methods described herein are susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modification which fall within its spirit and scope.
Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those of ordinary skill in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention. | A non-majority magnetic logic gate device for use in constructing compact and power efficient logical magnetic arrays is presented. The non-majority magnetic logic gate device includes a substrate, symmetrically aligned magnetic islands (SAMIs), at least one misaligned magnetic island (MAMI), magnetic field inputs (MFIs), and at least one magnetic field output (MFO). The SAMIs and MAMI are electrically isolated from each other but are magnetically coupled to one another through their respective magnetic fringe fields. The MAMI is geometrically and/or angularly configured to exhibit a magnetization ground state bias which is dependent upon which direction the applied magnetic clock field is swept. Non-majority logic gates can be made from layouts containing the SAMIs and the MAMI which contain a smaller number of components as comparable majority logic gate layouts. | 6 |
BACKGROUND OF THE INVENTION
The present invention relates to oilfield equipment, and more particularly to an apparatus for separating water and oil that can be use in-situ.
Conventionally, an oil well is encompassed with a water-retaining moat, or ditch designed to rain water washed away from the area surrounding the drilling or production rig. The ditch is formed about the periphery of a zone defined by the governmental regulations for the protection of the environment. When small amounts of oil escape from the well bore or are spilled by trucks, the rain water tends to carry the oil droplets, along with the rain water into the ditch, wherein the oil-water mixture is retained. A levee is constructed on the outer edge of the ditch to prevent the water from the ditch escaping outside of the defined zone.
Despite all efforts, heavy rains and sometimes flood waters fill the ditch to capacity and cause the water mixed with the suspended oil to flow over the levee, thereby contaminating the surrounding area. From time to time, the ditch is inspected to make sure that the level of liquids in the trench has not exceeded the allowable value. A part of the ditch is made intentionally at a lower level to created the so-called sump. Even the best inspections may miss a critical increase in the liquid level within the sump, which may quickly fill to capacity and overflow if not carefully monitored. From time to time, the water with suspended oil particles is pumped out and transported away from the site to a de-contamination facility, where the oil may be recovered. Naturally, such transportation increases the cost of the oilfield operation.
The present invention contemplates provision of an oil-water separator that can be installed in the trench surrounding the oil well to capture oil and prevent it from being carried over the levee by rising water.
SUMMARY OF THE INVENTION
It is, therefore, an object of the present invention to provide an in situ apparatus for separating oil from water that can be installed in an oilfield ditch.
It is another object of the present invention to provide an oil-water separator that has oil-absorbing means for retaining a quantity of oil within the apparatus, thereby preventing escape of the oil and contamination of the surrounding areas.
These and other objects of the present invention are achieved through a provision of an oil-water separator that is adapted for positioning in the ground next to the trench surrounding an oilfield. A portion of the separator housing is buried below the trench bottom, while the inlet conduit is positioned at about the same level as the trench bottom.
A plurality of buoyant oil-absorbing members are positioned in the housing; the trench water with oil particles suspended therein is admitted through the inlet conduit. The oil particles contact the oil-absorbing members and adhere thereto. An outlet conduit is positioned downstream from the oil-absorbing members. The outlet conduit is connectable to a pump to allow removal of the oil-free trench water from the housing. A diverting pipe coupled to the outlet of the pump diverts the water away from the housing and the trench. The water can be diverted over the levee surrounding the trench or to other desired location. As a result the oil is removed from the trench water, and the level of liquid in the trench is controlled.
BRIEF DESCRIPTION OF THE DRAWINGS
Reference will now be made to the drawings, wherein like parts are designated by like numerals and wherein
FIG. 1 is a perspective view of the oil-water separator in accordance with the present invention.
FIG. 2 is a perspective view of the oil-water separator apparatus in accordance with the present invention transported to or from the job site.
FIG. 3 is a schematic view of the separator apparatus in accordance with the present invention positioned in the trench adjacent an oilfield, with the ditch not having any water.
FIG. 4 is a schematic view similar to FIG. 3 , with the ditch half full of water.
FIG. 5 is a schematic view similar to FIGS. 3 and 4 , with the ditch being full of water.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Turning now to the drawings in more detail, numeral 10 designates the oil-water separator apparatus in accordance with the present invention. As can be seen in the drawings, the separator 10 comprises a separator housing 12 having a closed bottom 14 , vertical front wall 16 , back wall 20 , a pair of side walls 18 and 22 , and an open top 24 . The walls 16 , 18 , 20 , and 22 and the bottom 14 define an interior hollow chamber of the housing 12 . The side wall 22 is provided with an inlet conduit 26 extending outwardly in a transverse relationship to the vertical wall 22 . The inlet conduit 26 has an inlet opening 28 for admitting liquid into the separator housing 12 .
An opening 30 is formed in the upper part of the wall 22 , and the conduit 26 is positioned therein. The inlet conduit 26 communicates with an interior chamber of the housing 12 through the opening 30 . A water-permeable mesh screen 32 is positioned in the opening 30 to prevent floating debris, such as sticks, leaves, and other such undesirable objects from entering the interior chamber of the housing 12 .
A vertical dividing plate 40 is positioned inside the housing 12 , dividing the interior chamber of the housing into two distinct portions, an inlet portion 42 and an outlet portion 44 . The dividing plate 40 is secured and extends from a top edge 46 of the front wall 16 and the back wall 20 . The vertical dimensions of the dividing plate 40 are smaller than the height of the vertical walls 16 and 20 , such that a channel 48 is formed below a lower edge 50 of the separating plate 40 . The horizontal dimensions of the plate 40 are slightly smaller or equal to the distance between the front wall 16 and the back wall 20 .
A slot 52 is formed in the plate 40 at a level approximately co-planar with the bottom of the inlet conduit 26 . An inner water permeable mesh screen 54 is inserted through the slot 52 to extend substantially across the width of the housing 12 , from the side wall 18 to the side wall 22 . An outlet conduit 56 is positioned in the outlet portion 44 of the interior chamber to allow removal of liquid from the interior of the housing 12 . The outlet conduit 56 has an outlet opening 58 . The conduit 56 is operationally connected to a pump 60 to facilitate removal of the liquid form the housing 12 . The open top 24 of the housing 12 is protected by a pair of hinged covers 62 and 64 which are secured to extension plates 66 , 68 , which are mounted on the upper edge of the walls 16 and 20 . The securing plates 66 and 68 extend vertically outwardly from the edge 46 , allowing pivotal movement of the covers 62 and 64 . A cutout 70 is formed in the cover 64 to accommodate extension of the outlet conduit 56 from the chamber portion 44 outside of the housing 12 . The bottom, inlet end 72 of the outlet conduit 56 rests on the screen 54 , as can be seen in FIG. 1 .
The present invention provides for the use of a plurality of oil absorbing members 80 , which are positioned in the chamber portion 42 above the screen 54 . The absorbent members 80 are formed from porous material suitable for attracting and retaining as much oil particles as possible. The absorbent members 80 , which can be two or more in number, are buoyant; they float close to the surface of the liquid inside the chamber portion 42 , as will be described in more detail hereinafter.
Turning now to FIGS. 3–5 , the oil-water separator 10 in accordance with the present invention is seen positioned in an oilfield adjacent an oil well 82 . A ditch, or trench, 84 surrounds the oil well 82 . The separator 10 is partially buried in the soil wherein a hole 86 has been formed. Most of the separator housing 12 is below the ground level 83 . The hole 86 is immediately adjacent to the ditch 84 , preferably close to the lowest, sump area of the ditch 84 . The inlet conduit 26 is positioned close to the bottom 88 of the ditch 84 so as to receive water through the opening 28 .
A certain quantity of water is initially deposited into the housing 12 , with the level of preloaded water 90 reaching about the level of the mesh screen 54 . The absorbent members 80 rest on the screen 54 , initially above the water level 90 . The outlet conduit 56 is connected to the pump 60 , and the outlet of the pump 60 is connected to a diverting conduit 92 . An outlet 94 of the diverting conduit 92 extends above a levee 96 formed around the ditch 84 .
Gradually, the rainwater and run-off collect in the ditch 84 . When the level of water reaches the inlet conduit 26 , the water is allowed to freely enter the conduit 26 and flow into the housing. The direction of the water flow is schematically illustrated by arrows 98 . The water, with the oil particles suspended therein enters the inlet portion 42 of the interior chamber. The absorbent members 80 attract the oil particles that tend to float on the water surface. Water, substantially free from the oil particles, floats under the dividing plate 40 , along the channel 48 into the chamber portion 44 . The liquid level substantially equalizes in the portion 42 and the portion 44 of the interior chamber with the level of water in the trench 84 . Any debris that entered the chamber portions 42 and 44 through the screen 32 is additionally screened by the screen 54 on its path upwardly in the chamber portion 44 .
The water, now substantially free from oil and debris, enters the outlet conduit 56 . When the pump 60 is activated, the water is pumped out of the separator housing 12 and into the diverting conduit 92 . From there, the water can be pumped over the levee 96 . When the ditch 84 becomes full with water, as schematically shown in FIG. 5 , the pump 60 may be turned on either manually or automatically, to be activated based on the water level predetermined by the operator. The water is pumped from the ditch 84 through the separator 10 and over the levee 96 , thereby preventing oil accumulated in the ditch 84 from being released into the surrounding areas outside of the levee 96 .
If desired, the level of water in the ditch 84 can be continuously monitored and controlled by the automatic operation of the pump 60 . In the alternative, an operator may inspect the level of liquid in the ditch 84 and start operation of the pump 60 to remove a portion of water from the ditch 84 . From time to time, the operator can inspect the status of the absorbent members 80 by opening the cover 62 and visually inspecting the absorbent members. When the absorbent members 80 become saturated with oil, the can be easily removed from the interior of the housing 12 and new absorbent members can be positioned by dropping them on the screen 54 . Should the screen 54 become clogged with small leaves or other particles, the operator can clean the screen by lifting the covers 62 and 64 and obtaining access to the interior chamber and the screen 54 .
The separator apparatus 10 of the present invention requires little monitoring and can function for a long time without repairs or adjustments. When the job in the oilfield is complete, the apparatus 10 can be removed from the ground and transported to the new job site after the water from the housing 12 has been drained.
Many changes and modifications can be made in the design of the present invention without departing from the spirit thereof. I therefore pray that my rights to the present invention be limited only by the scope of the appended claims. | An oil-water separator for use in a trench, which surrounds an oilfield. The separator is positioned in the ground such that an inlet conduit extends at about the same level as the bottom of the trench. The trench water is admitted into the housing, where it contacts a plurality of buoyant oil-absorbing members, causing the oil particles to adhere to the surface of the oil-absorbing members. An outlet conduit located downstream from the oil-absorbing members is connectable to a pump to cause the oil-free water to be pumped from the housing and diverted away from the trench. | 2 |
FIELD OF THE INVENTION
The present invention relates to an assembly set for a series of geared motors.
BACKGROUND INFORMATION
An inverter motor is described, for example, in German Published Patent Application No. 197 04 226, an inverter for supplying the motor with power being connected at the terminal box of the motor.
Geared motors include motors that are connected directly or indirectly to at least one gear unit.
German Published Patent Application No. 101 16 595 describes a series of geared motors, in which a motor shaft is connectable to a shank pinion or a plug-on pinion. However, an adapter is necessary for the plug-on pinion.
SUMMARY
An example embodiment of the present invention provides a modular system of geared motors.
According to an example embodiment of the present invention, an assembly set may provide that the drive-end motor bearing shield has an interface on the output side, such that
(i) a lateral-force-free gear unit or (ii) a gear unit not free of lateral force is directly connectable,
the rotor shaft being connected non-positively, integrally and/or positively on the output side to a pinion,
the direct connection being implemented such that the pinion is provided as the input gearing part of the gear unit.
In this context, it may be provided that an interface is produced of the kind that direct mounting of a planetary gear unit or a gear unit having an input spur-gear stage is possible. The pinion may be implemented as a shank pinion and/or plug-on pinion, thereby making it possible to increase the range of gear ratios able to be covered by the assembly set considerably.
The pinion and rotor shaft may be in one piece, and therefore, no pinion may be necessary. In this manner, it may be possible to reduce the manufacturing tolerances.
The assembly set for a series of geared motors may include gear units driven by electric motors,
the series including at least one size able to be characterized by at least one physical, mechanical and/or geometrical variable, e.g., such as rated power output, shaft height or torque,
the electric motors each including at least a motor housing, a rotor including rotor shaft, and a drive-end motor bearing shield,
within one size, the motor housing having an interface to the motor bearing shield on the output side, such that at least two different variants of the output-side motor bearing shield are connectable to the motor housing,
the output-side bearing shield including a bearing for the rotor shaft,
(i) in a first variant, the drive-end motor bearing shield having an interface on the output side, such that the drive-end motor bearing shield is connectable to a flange of an adapter,
the adapter including a first adapter part and the adapter flange,
the assembly set including at least two types of the first adapter part connectable to the adapter flange, the interface between the adapter flange and the drive-end motor bearing shield of the first variant including a centering device,
the first adapter part of the first type
being connectable to a gear unit not free of lateral force, such as a gear unit with a helical-gear stage disposed on the input side, with the aid of an interface encompassing a two-dimensional, open fitting, thus, with the aid of an interface allowing shifts in a plane for setting the backlash of the gear unit not free of lateral force,
including an adapter shaft,
including at least two bearings and
having a first device for the compensation of axial expansions, e.g., thermally caused expansions,
the first adapter part of the second type
being connectable by an interface to a lateral-force-free gear unit, such as a planetary gear unit,
including an adapter shaft,
having a second device for the compensation of axial expansions, e.g., thermally caused expansions, and
including one bearing,
(ii) in a second variant, the drive-end motor bearing shield having an interface on the output side, such that a lateral-force-free gear unit, and alternatively, a gear unit not free of lateral force, is directly connectable,
in the second variant, it being possible to provide at least two types of rotor shafts when working with the same housing of the motor,
in the case of the rotor shaft of the first type, a plug-on pinion being provided on the output side and
in the case of the rotor shaft of the second type, a shank pinion being provided on the output side,
the direct connection being implemented such that the shank pinion or plug-on pinion is provided to mesh with at least one gearing part of the gear unit.
In this context, it may be provided that servo gear units, such as planetary gear units and other low-backlash gear units, are connectable to a motor either directly or via an adapter. Therefore, the unit volume, torsional rigidity and mass moment of inertia of the geared motor are also adaptable to the requirements of the specific application, without many parts being necessary, for in spite of the few parts included, the modular system may provide an extremely large variance within each size.
In an example embodiment, all the gear units have an open fitting as interface on the input side. This may provide that the pinion of the adapter shaft or rotor shaft to be introduced is radially displaceable together with the associated components, such that it is able to be brought to the desired position. In the case of the helical-gear stage, this means a possibility for adjusting the backlash, in the case of the planetary-gear stage, a centering of the sun wheel.
A bellows coupling may be provided as a first device for the compensation of axial expansions. Provided as a second device for the compensation of axial expansions may be at least one compensating disk, e.g., at a bearing of the adapter part. This may provide that it is possible to compensate for location and position deviations of the shafts, thus, the adapter shaft and the rotor shaft, and also for thermally caused expansions in a simple, cost-effective manner.
The gear units of the series may be designed to be low-backlash, such that, e.g., after adjusting the backlash with the aid of the displacements, the backlash on the whole may be less than 3 angular minutes per individual gear stage and/or gear unit. An advantage is that the gear units may be usable for servo technology.
The lateral-force-free gear unit connected to the adapter part and having a bearing arrangement on one side may encompass a higher air volume for the pressure equalization than the lateral-force-free gear unit having a bearing arrangement on both sides. Thermally caused air-pressure increases may be reducible, and therefore the danger of the gear unit becoming leaky may be decreased.
The gear unit may have a planetary-gear stage as input stage. This may provide that a servo gear unit free of lateral force on the input side and having a high gear ratio may be provided.
The gear unit not free of lateral force may be a double-stage gear unit whose gear stage situated on the input side is implemented as a spur-gear stage, e.g., having helical-toothed gear wheels. A high gear ratio may thus be attainable in the case of this double-stage gear unit, and the input spur-gear stage may be produced inexpensively.
The second stage of the gear unit not free of lateral force may be a right-angle gear stage. Not only colinear servo gear units, but also right-angle servo gear units may be produced using a small number of parts.
The right-angle gear unit may be arranged to be single-stage, e.g., as a hypoid gear unit. In this manner, a non-colinear gear unit having a high gear ratio may be produced within the series.
The gear units may be servo gear units, e.g., for exact positioning.
Further features and aspects hereof are described below.
LIST OF REFERENCE NUMERALS
1 motor housing
2 rotor with cylindrical shaft end
3 rotor with feather key for plug-on pinion
4 rotor for shank pinion
5 adapter part with two bearings
6 adapter part with one bearing
7 right-angle gear unit
8 planetary gear unit with cylindrical output-shaft end
9 planetary gear unit with flange block output
10 planetary gear preliminary stage
11 adapter flange
12 motor bearing shield with bearing
13 motor bearing shield with bearing
14 motor bearing shield with bearing
21 centering bore
22 rotor shaft
23 motor bearing shield
24 interface
25 bearing
26 shaft seal ring
31 plug-on pinion
32 rotor shaft
33 motor bearing shield
35 bearing
36 shaft seal ring
41 shank pinion
42 rotor shaft
45 bearing
46 shaft seal ring
50 gear-side coupling half
51 centering bore
52 adapter shaft
53 plug-on pinion
54 shaft seal ring
55 bearing
56 housing of the adapter part
57 bearing
58 motor-side coupling half
59 metal bellows
60 fastening screw
61 clamping ring
62 adapter flange
63 slit
64 housing of the adapter part
65 bearing
66 shaft seal ring
67 adapter shaft
68 centering bore
69 shank pinion
70 spur gear
71 bearing
72 pinion
73 crown-toothed wheel
74 open fitting
75 housing part
76 shaft
80 centering bore
81 planet-carrier shaft
82 shaft seal ring
83 bearing
84 bearing
85 needle bearing
86 planet wheel
87 planet spindle
88 spatial volume
89 clamping nut
90 bearing
91 planet spindle
92 planet wheel
93 housing
94 shaft seal ring
95 planet carrier
96 screw plug
97 spatial volume
98 needle bearing
121 asynchronous motor
122 synchronous motor with square flange
123 asynchronous motor as servo motor
124 inverter motor
125 series-connected gear unit
126 adapter
127 helical gear unit
128 parallel-shaft gear unit
129 helical-bevel gear unit
130 worm gear unit
131 spiroplan gear unit
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a series part, the components being illustrated in combination possibilities.
FIG. 10 illustrates a further part of the series, the components being illustrated in combination possibilities.
FIGS. 2 to 4 illustrate motor bearing shields 12 to 14 of the motors as individual parts.
FIGS. 5 and 6 illustrate individual adapter parts 5 , 6 and 11 .
FIGS. 8 and 9 illustrate planetary-gear-unit parts.
FIG. 7 illustrates right-angle gear unit 7 illustrated in FIG. 1 as an individual part.
FIG. 11 illustrates a double-stage right-angle gear unit with an adapter.
FIG. 12 illustrates a planetary gear unit with an adapter.
FIG. 13 illustrates a planetary gear unit with an adapter.
DETAILED DESCRIPTION
FIG. 10 illustrates combination possibility for a series of gear units. In this context, the assembly set for the series of geared motors is arranged such that different motors are connectable to different gear units, directly or with the aid of an adapter. The gear units illustrated in FIG. 10 do not have to be implemented as servo gear units.
FIG. 1 illustrates a part that is compatible with the series of geared motors, thus has corresponding interfaces. This part includes servo geared motors that are able to be assembled in various combinations. The gear units illustrated in this context and connectable to the motors are servo gear units.
This part illustrated in FIG. 1 is discussed first of all in the following:
The motor includes a motor housing 1 with stator. Depending on the requirement, an encoder and/or a brake is/are connectable on the non-drive end. On the drive end, the housing has an interface for connection to a motor bearing shield 12 , 13 , 14 . The interface is formed by the drive-end geometrical formation of the motor housing and the positioning of the bores. The matching counter-interface is implemented in motor bearing shield 12 , 13 , 14 . Thus, motor housing 1 is connectable to all motor bearing shields 12 , 13 , 14 , each of which in turn differs at other points, however. The associated seats of the bearings and/or shaft-seal-ring seats may be implemented differently and/or different rotor shafts may be accommodated. Rotor 2 , 3 , 4 , including in each case the rotor shaft, may be selected differently. A non-drive-end bearing of rotor 2 , 3 , 4 is encompassed by the motor housing. The further drive-end bearing is encompassed by the motor bearing shield.
Rotor 2 is implemented with a drive-end, cylindrical shaft end. This is also illustrated clearly in FIG. 2 . In this context, rotor shaft 22 of rotor 2 also includes a centering bore 21 . Motor bearing shield 23 includes a bearing seat for bearing 25 and a shaft-seal-ring seat for shaft seal ring 26 . Interface 24 is implemented in the manner mentioned above in the case of the motor bearing shield and the motor housing.
As illustrated in FIG. 3 , rotor 3 is implemented with rotor shaft 32 , rotor shaft 32 being supported by bearing 35 in motor bearing shield 33 , which corresponds to motor bearing shield 12 , and being sealed against it by shaft seal ring 36 . Interface 24 of motor bearing shield 33 is implemented to match the same motor housing, as also in the case of FIG. 2 . Rotor shaft 32 of rotor 3 is connected on the drive end by a feather key to a plug-on pinion 31 .
As illustrated in FIG. 4 , rotor 4 is implemented with rotor shaft 42 , rotor shaft 42 being supported by bearing 45 in motor bearing shield 33 , which corresponds to motor bearing shield 12 , and being sealed against it by shaft seal ring 46 . Interface 24 of motor bearing shield 33 is implemented to match the same motor housing, as also in the case of FIG. 2 . Rotor shaft 42 of rotor 4 is connected on the drive end to a shank pinion 41 .
In further exemplary embodiments of the present invention, rotors 2 , 3 , 4 are practicable in different electromechanical variants, e.g., as rotor with short-circuit cage for forming an asynchronous motor, or as rotor with pasted-on magnets for forming a synchronous motor. However, further variants of motors, such as reluctance motors, direct-current motors or other electric motors, etc., are also usable. To that end, the interface and the rotor may be implemented to match accordingly.
Instead of motor bearing shield 12 , motor bearing shield 14 is also usable with rotors 3 or 4 , motor bearing shield 14 having the same interface 24 toward motor housing 1 . The connection of all gear units 127 , 128 , 129 , 130 , which have a corresponding flange and are illustrated in FIG. 10 , is permitted with the aid of this motor bearing shield 14 . Gear units which, like right-angle gear unit 131 , are arranged with a motor bearing shield integrated into the gear-unit housing, are not connectable. Only upon omission of indicated motor bearing shield 14 , is it connectable.
In further exemplary embodiments of the present invention, each motor bearing shield may also be implemented as a square flange. Thus, further combination possibilities may be provided, with only a little more expenditure on components.
In the exemplary embodiment illustrated in FIG. 1 , the motor formed with motor bearing shield 12 is connectable to a planetary gear unit with or without planetary-gear preliminary stage 10 , or to a right-angle gear unit 7 . In this context, the planetary gear unit is implemented as planetary gear unit 8 having a cylindrical output-shaft end, or as planetary gear unit 9 having a flange block output.
In the exemplary embodiment illustrated in FIG. 1 , the motor formed with motor bearing shield 13 is connectable via the adapter, formed of adapter flange 11 and adapter part 6 , to a planetary gear unit with or without planetary gear preliminary stage 10 , or via the adapter formed of adapter flange 11 and adapter part 5 , to right-angle gear unit 7 . In this context, the planetary gear unit is implemented as planetary gear unit 8 having a cylindrical output-shaft end, or as planetary gear unit 9 having a flange block output.
Asynchronous motor 121 may be implemented as a standard motor in accordance with the IEC standard. However, further manufacturer-specific designs are also usable. One manufacturer-specific example embodiment is also illustrated in FIG. 1 . Motor housing 1 is usable for various motors which differ due to motor bearing shield 12 , 13 , 14 and rotors 2 , 3 , 4 . For example, a rotor 4 with shank pinion and a rotor 3 with plug-on pinion may also be provided. An extremely compact, direct mounting of one of gear units 7 , 8 , 9 , 10 may thereby be feasible, and it may thus be possible to dispense with adapters etc. Since shank pinions and plug-on pinions are provided within the series modular system, a wide range of gear ratios is already attainable in the spur-gear stage disposed on the input side, the indicated pinion being the input gearing part of this spur-gear stage.
Synchronous motor 122 is arranged with a square flange, and is therefore connectable to corresponding components which have a matching interface. For example, adapter 126 or series-connected gear unit 125 are practicable on the motor side with such an interface. In the case of direct connection to the gear unit, gear unit 127 , 128 , 129 or 130 is also feasible with such a flange. As illustrated in FIG. 10 , however, gear units 127 , 128 , 129 and 130 , adapter 126 and series-connected gear unit 125 are implemented with a round flange. Not only asynchronous motor 121 , but also asynchronous motor 123 , implemented as a servo motor, or inverter motor 124 are connectable to the indicated round flanges
Series-connected gear unit 125 includes a double-stage or triple-stage helical gear unit, and may be used for applications having a very high gear reduction.
Adapter 126 is connectable on the output side to gear unit 127 , 128 , 129 or 130 . Therefore, the oil chamber of gear unit 127 , 128 , 129 or 130 may remain closed upon exchange of motor 121 , 122 , 123 , 124 arranged at adapter 126 at the drive end.
Series-connected gear unit 125 and adapter 126 may also be provided with a square flange on the input side.
Parallel-shaft gear unit 128 and helical gear unit 127 each include two or three spur-gear stages. Helical-bevel gear unit 129 includes a spur-gear stage arranged on the input side and a bevel-gear stage disposed on the output side. Worm gear unit 130 includes a spur-gear stage arranged on the input side and a worm-gear stage disposed on the output side. Spiroplan gear unit 131 includes a spiroplan gear stage, thus, a right-angle gear stage.
A gear unit free of lateral force on the input side, e.g., planetary gear unit 8 , 9 , 10 , may be connectable to a motor in the same manner as a gear unit not free of lateral force on the input side, e.g., a gear unit having a spur-gear stage disposed on the input side, like gear unit 7 . The gear-side interface of the motor, or of the motor plus adapter, is thus identical for lateral-force-free gear units and gear units not free of lateral force.
The mass moment of inertia may be selectable, and therefore adaptable to the customer application, thus, the driven load. Thus, if a high mass moment of inertia is desired, and even a low torsional rigidity, a geared motor with adapter is selected, e.g., components 1 , 2 , 13 , 11 , 6 , 8 or components 1 , 2 , 13 , 11 , 5 , 7 illustrated in FIG. 1 . A low torsional rigidity also means an, e.g., “smoother” drive; thus, sudden changes in torque of the geared motor are absorbed to a certain extent. If, on the other hand, a low mass moment of inertia and a high torsional rigidity are needed, a geared motor without adapter, thus, with motor connected directly to the gear unit, is selected, e.g., components 1 , 3 , 12 , 7 or components 1 , 3 , 12 , 8 or components 1 , 4 , 12 , 9 illustrated in FIG. 1 .
The gear units, e.g., gear units 7 , 8 , 9 , 10 , are designed with low backlash, e.g., with a backlash of less than 3 angular minutes per gear stage.
The motor-side interface of adapter flange 11 may be implemented with very little tolerance, thus highly precisely. Thus, the motor with its motor bearing shield 13 may be able to be disassembled very precisely. For example, the indicated interface may be implemented with less tolerance, thus, more precisely than the interface of the adapter toward the gear unit.
FIG. 5 is a sectional view of the adapter including adapter part 5 and adapter flange 11 . FIG. 6 is a sectional view of the adapter including adapter part 6 and adapter flange 11 . In common—and therefore reusable within the modular system—is adapter flange 62 , which is connected to the housing of adapter part 5 or 6 by fastening screws 60 .
As illustrated in FIG. 5 , the cylindrical shaft end of rotor shaft 2 is connectable with the aid of clamping ring 61 to motor-side coupling half 58 , which has a slit that may make the clamping effect of clamping ring 61 predictable and definable. Gear-side adapter shaft 52 of the adapter has a centering bore 51 and is connected to a plug-on pinion 53 . Adapter shaft 52 is sealed by shaft seal ring 54 against housing 56 of adapter part 5 , and is supported in it by bearings 55 , 57 , bearing 57 being sealingly implemented, and therefore a certain sealing of the lubricant, e.g., grease or semi-fluid grease, toward the motor being achieved. Toward the gear unit, e.g., toward its interior chamber having a different lubricant such as oil, etc., the sealing may be achieved by shaft seal ring 54 . Between shaft seal ring 54 and bearing 55 , an annular space is partially filled with lubricant, e.g., grease or semi-fluid grease, and thus a storage volume for lubricant may be provided.
Gear-side coupling half 50 is connected, e.g., positively, non-positively and/or integrally, to adapter shaft 52 . The metal bellows is welded at its respective axial end areas to gear-side coupling half 50 and motor-side coupling half 58 . It thus transmits the entire torque. The use of the adapter encompassing this metal bellows 59 thus may make available a geared motor having low torsional rigidity. Because of the large mass of the rotating parts, e.g., of the adapter, as well, this geared motor then also may exhibit a high moment of inertia or mass moment of inertia. The interface of the adapter toward the gear unit is implemented as a so-called open fitting, and therefore may allow small relative, radial displacements. Consequently, upon insertion of plug-on pinion 53 into gear unit 7 , plug-on pinion 53 itself and adapter shaft 52 , as well as housing 56 of adapter part 5 are fixed in that position and alignment predefined essentially by the position of the gearing parts of gear unit 7 . Therefore, the gear unit is already adjustable during manufacturing, and the connection of the adapter may not disturb the adjustments of the gear unit. Compensation is thus made for small deviations caused by manufacturing, by shifting or rotating adapter shaft 52 in the space. The setting of the distance between axes, and thus also the backlash of the input spur-gear stage of gear unit 7 may be adjustable by radial shift of housing 56 toward the housing of gear unit 7 . The indicated shifts are on the order of magnitude of one or several tenths. In this connection, the backlash is adjustable such that it may be less than 3 angular minutes.
On the other hand, adapter flange 62 has an interface toward the motor, such that the motor together with rotor shaft 2 may be exactly positioned upon being screwed onto adapter flange 62 , i.e., the spatial position and alignment of motor bearing shield 13 with motor housing 1 and rotor shaft 2 is established by the screwing-on process. To that end, adapter flange 62 is provided at its interface with a fitting, and motor bearing shield 13 is provided with a corresponding formation. Metal bellows 59 accommodates radial and axial deviations from an ideal position.
The motor has components made of different materials. For example, the stator, e.g., also motor housing 1 , is of aluminum, the rotor, e.g., the rotor shaft, of steel. Therefore, different thermal expansions may result, which also take effect in the direction of the adapter. To compensate for these expansions, motor-side coupling half 58 and gear-side coupling half 50 have an axial distance relative to each other of, for example, one or several millimeters. In response to thermally caused linear expansions of the rotor shaft, compensation is thus made possible by metal bellows 59 .
As illustrated in FIG. 6 , the cylindrical shaft end of rotor shaft 2 is connectable with the aid of clamping ring 61 to adapter shaft 67 , which has a slit 63 that may make the clamping effect of clamping ring 61 predictable and definable. In addition, in the area of motor-side slit 63 , adapter shaft 67 is implemented as a hollow shaft for the insertion of the rotor shaft. Adapter shaft 67 of the adapter is connected to a shank pinion 69 that has a centering bore 68 . Adapter shaft 67 is sealed by shaft seal ring 66 against housing 64 of adapter part 6 and is supported in it by bearing 65 . Bearing 65 is sealingly implemented toward the motor. Between shaft seal ring 66 and bearing 65 , an annular space is partially filled with lubricant, e.g., grease or semi-fluid grease, and thus a storage volume for lubricant is provided.
Thus, the adapter illustrated in FIG. 6 may make available a geared motor having high torsional rigidity. Because of the smaller mass of the rotating parts, e.g., also of the adapter, in comparison to the adapter illustrated in FIG. 5 , this geared motor may exhibit a low moment of inertia or mass moment of inertia. The interface of the adapter toward the gear unit is implemented as a so-called open fitting, and therefore may allow small relative, radial displacements. Therefore, upon insertion of plug-on pinion 69 into gear unit 8 , 9 or 10 , shank pinion 69 itself and adapter shaft 67 , as well as housing 64 of adapter part 6 are fixed in the position and alignment essentially predefined by the position of the gearing parts of gear unit 8 , 9 or 10 , e.g., by the planets of the input planetary-gear stage of gear unit 8 , 9 or 10 . Consequently, the gear unit is already adjustable during manufacturing, and the connection of the adapter may not disturb the adjustments of the gear unit. Compensation is thus made for small deviations caused by manufacturing, by shifting or rotating adapter shaft 67 in the space. Because, for example, of the use of plug-on pinion 69 as sun wheel of the input stage of gear unit 8 , 9 or 10 , the spatial volume for movement of shank pinion 69 upon insertion into gear unit 8 , 9 or 10 may be sharply limited. However, the open fitting may permit the exact final position of the housing of adapter part 6 and of the housing of gear unit 8 , 9 or 10 relative to each other to adapt to the position of the sun wheel predefined by that of the planets.
On the other hand, adapter flange 62 has an interface toward the motor, such that the motor together with rotor shaft 2 may be exactly positioned upon being screwed onto adapter flange 62 , i.e., the spatial position and alignment of motor bearing shield 13 with motor housing 1 and rotor shaft 2 is established by the screwing-on process. To that end, adapter flange 62 is provided at its interface with a fitting, and motor bearing shield 13 is provided with a corresponding formation.
To compensate for thermal expansions, compensating disks are inserted as elastic rings in the region of bearing 65 . Therefore, thermal expansions may be essentially passed on to shank pinion 69 and are compensated in gear unit 8 , 9 or 10 , since the sun wheel and planets may be shiftable relative to each other by small amounts without considerable functional losses. To that end, gear unit 8 , 9 or 10 makes spatial volume available that is provided axially in front of the upper and behind the lower end face of the sun wheel, as illustrated in FIGS. 12 and 13 , as well.
A difference between the adapters illustrated in FIGS. 5 and 6 is that the adapter illustrated in FIG. 5 has two bearings 54 , 57 for adapter shaft 52 , whereas only one bearing 65 is provided for adapter shaft 67 . Bearing 65 is provided as a fixation aid during assembly. Since shank pinion 69 is used as sun wheel, no take-up of lateral force may be necessary. However, the adapter illustrated in FIG. 5 is provided for assembly with the input spur-gear stage of gear unit 7 , lateral forces then acting on plug-on pinion 53 , which are absorbed by bearings 55 , 57 .
FIG. 7 illustrates gear unit 7 , thus, the right-angle gear unit, which, toward the motor, has the same interface with open fitting as the planetary gear unit. Therefore, the motor with its motor bearing shield 12 is thus connectable both to right-angle gear unit 7 and to one of planetary gear units 8 , 9 , 10 . FIG. 7 illustrates the interface with open fitting 74 more precisely. The pinion connected to the adapter shaft is inserted into right-angle gear unit 7 until it engages with spur gear 70 , and the housing of the adapter part or of motor bearing shield 12 abuts axially against the housing of gear unit 7 . Additionally, a relative radial shift of the housing is then carried out such that the desired amount of the backlash of the spur-gear stage of less than 3 angular minutes may be achieved. Finally, the connection is then secured with fastening screws in a manner resistant to fatigue.
Not only the adapter with adapter part 5 , but also a direct mounting of the motor with the aid of motor bearing shield 12 may be made possible, the shank pinion or plug-on pinion then being provided directly at the rotor shaft of rotor 3 or 4 . Therefore, an extremely compact type of construction may be achieved, which at the same time may be compatible with the standard motor, including rotor shaft 2 with cylindrical shaft end, via the adapter. After the connection of the adapter or motor, spur gear 70 engages with the respective pinion, a backlash of, e.g., less than three angular minutes being provided. Spur gear 70 is connected by feather keys to shaft 76 , which also encompasses pinion 72 . Shaft 76 and pinion 72 may be designed in one piece. Shaft 76 is supported by bearing 71 , which is connected to housing part 75 of gear unit 7 . Pinion 72 engages with crown-toothed wheel 73 , that is supported by a bearing in housing part 75 of gear unit 7 .
In FIG. 8 , planetary gear unit 8 is illustrated enlarged as an individual part. The interface toward the motor or adapter is implemented as an open fitting in the manner already mentioned. After the connection, the pinion, thus shank pinion or plug-on pinion, connected to the rotor shaft or adapter shaft acts as the sun wheel of the planetary gear unit. Spatial volume 88 is able to compensate for thermal expansions. The spatial volume may have an axial extension toward the sun wheel, e.g., between 0.2 mm and 2 mm. The sun wheel engages with planet wheels 86 and, upon connection, is essentially codetermined in its position and alignment. Planet wheels 86 are in each case supported via one or even two needle bearings 85 , arranged axially behind each other, on planet spindles 87 , which are provided in bores of planet-carrier shaft 81 , that has a centering bore 80 . Planet-carrier shaft 81 is supported by bearings 83 , 84 in the housing, and sealed against it by shaft seal ring 82 . Clamping nut 89 serves at its outer periphery as a bearing surface for the sealing lip of the shaft seal ring. The housing also features a recess having a screw plug for filling or emptying the lubricant.
Planetary gear unit 9 is illustrated enlarged as an individual part in FIG. 9 , this planetary gear unit having a flange block interface on the output side. This interface may be implemented as an industrial robot interface in accordance with the standard EN ISO 9409-1. The interface toward the motor or adapter is implemented as an open fitting in the manner already mentioned. After the connection, the pinion, thus shank pinion or plug-on pinion, connected to the rotor shaft or adapter shaft acts as the sun wheel of the planetary gear unit. Spatial volume 97 is able to compensate for thermal expansions. The spatial volume may have an axial extension toward the sun wheel, e.g., between 0.2 mm and 2 mm. The sun wheel engages with planet wheels 92 and, upon connection, is essentially codetermined in its position and alignment. Planet wheels 92 are in each case supported via one or even two needle bearings 98 , arranged axially behind each other, on planet spindles 91 , which are provided in bores of planet-carrier shaft 95 , that has a central bore which is tightly closed by a screw plug 96 . The indicated bore may be implemented as a threaded bore, and screw plug 96 has a corresponding thread. As illustrated in FIG. 9 , screw plug 96 is releasable for filling or emptying the lubricant, and is then connectable again. Planet-carrier shaft 95 is supported by bearing 90 in the housing and sealed against it by shaft seal ring 94 , planet carrier 95 being processed in one area at its outer periphery such that the area is usable as a bearing surface for the sealing lip of the shaft seal ring.
FIG. 11 illustrates the assembly of right-angle gear unit 7 with adapter part 5 and adapter flange 11 , interface 74 being implemented as an open fitting for adjusting the backlash between spur gear 70 and plug-on pinion 53 .
FIG. 12 illustrates the assembly of planetary gear unit 8 with adapter part 6 and adapter flange 11 , interface 74 being implemented as an open fitting for the compensation of tolerances. In this context, planet wheels 86 essentially codetermine the position and alignment of shank pinion 69 used as sun wheel, e.g., in the radial alignment.
FIG. 13 illustrates the assembly of planetary gear unit 9 with adapter part 6 and adapter flange 11 , interface 74 being implemented as an open fitting for the compensation of tolerances. In this context, planet wheels 92 essentially codetermine the position and alignment of shank pinion 69 used as sun wheel, e.g., in the radial alignment.
Thus, a connection of IEC standard motors with the aid of an adapter, or manufacturer-specific motors without adapter, may be provided to a gear unit, the manufacturer-specific motors being designed with a rotor shaft encompassing a shank pinion or plug-on pinion. Therefore, an extremely compact, direct connection to a gear unit may be made possible, which, however, may also be usable with standard motors connectable via adapter.
The adapters may compensate for the thermal linear expansion of the rotor shaft, and therefore the gear unit and the motor may be able to be thermally decoupled by the adapters.
Both single-stage or multi-stage gear units with or without lateral force may be produced on the input side, thus gear units with input helical gear stage or planetary gear stage may be connectable. Depending on the type of gear unit, the adapter may be implemented with lateral-force compensation, thus with adapter part 5 , or without lateral-force compensation, thus with adapter part 6 . Consequently, a large number of variation possibilities may be provided.
Moreover, the adapter may have the additional function of permitting centering of the pinion upon insertion into the gear unit.
In the case of the open fitting, it may be provided that prior to tightening the fastening screws, radial shifts are permitted between adapter and gear unit which are greater than corresponding shifts between adapter and motor.
Not only the entire right-angle gear unit may have a backlash of less than 3 angular minutes, but also the planetary gear unit and even the double-stage planetary gear unit, which is formed of planetary-gear preliminary stage 10 and planetary gear unit 9 or 8 .
The motor with rotor 2 may thus be implemented as a direct-mounting motor ( 1 , 2 , 13 ), and with another motor bearing shield 14 , which permits the connection with gear units 127 , 128 , 129 , 130 , 131 illustrated in FIG. 10 , motor bearing shield 14 being connectable to adapter 126 or to series-connected gear unit 125 . As illustrated in FIGS. 1 and 10 , an encircled 1 is used for the graphic illustration of this connection possibility.
The encircled 2 reference numeral represents that a direct connection of motor housing 1 together with rotors 3 or 4 to gear units 127 , 128 , 129 , 130 , 131 may also be made possible. To that end, motor housing 1 is provided with an interface which corresponds to the interface of the indicated gear units.
Therefore, not only standard gear units 127 , 128 , 129 , 130 , 131 are usable for the motor housing, but also servo gear units 7 , 8 , 9 .
The number of parts in the geared motors may be as small as possible, the reuse within the modular system may be as great as possible, and the application variants covered may be as diverse as possible. For example, both servo geared motors and standard geared motors are indicated as variants.
The series may be designed and implemented such that all servo gear units of FIG. 1 have only integral gear ratios.
The same adapter is used in the variants illustrated in FIG. 12 and FIG. 13 . However, the planetary gear unit illustrated in FIG. 13 is supported on both sides, the planetary gear unit illustrated in FIG. 12 on one side, e.g., the output side. Therefore, adapter-side bearing 90 needs overall axial length. This overall length is taken into account by the design and overall axial length of adapter shaft 67 together with shank pinion 69 such that the shank pinion as sun wheel is inserted completely between planet wheels 92 . The same adapter is provided in FIG. 12 . So that shank pinion 69 is completely inserted between planet wheels 92 in this planetary gear unit as well, housing 801 of the planetary gear unit is lengthened such that interface 74 , thus, the open fitting, sits at the corresponding axial position relative to the planet wheels, as also in FIG. 13 . As illustrated in FIG. 12 , an increased air volume is thereby formed between planet-carrier shaft 81 and the open fitting, which contributes to the reduction in air pressure in response to temperature elevation. This reduction in air pressure may be advantageous, e.g., during assembly or in the event of temperature elevations during operation. On the whole, therefore, because of the set goal of the greatest possible number of combinations, an increased overall length is accepted in one variant of the series. An advantage may be the reduction in air pressure in the event of a temperature elevation, viewed relatively with respect to a smaller unit volume of the gear unit. This may be achieved, for example, in the case of servo gear units, since there during a positioning task, high rotational speeds may occur which may lead to corresponding heating. Therefore, in the present series, the indicated increase in overall length is intentionally accepted, to thus attain two advantages, e.g., first, the combination diversity, and secondly, the reduction in air pressure.
In comparison to FIG. 13 , the increased air volume may be seen clearly in FIG. 12 . If, instead of the adapter, a motor having a drive-end bearing shield is directly attached, the air volume is formed in analogous fashion.
Instead of double-stage right-angle gear unit 7 , a single-stage hypoid gear unit may be provided. This may provide that the gear ratio is an integer, even if the efficiency is slightly less.
In the case of the indicated direct mounting, it may be provided that no coupling may be needed, and therefore the number of parts, and thus also the costs may be reduced. In addition, the type of construction may therefore be compact, as well.
As illustrated in FIG. 5 , the deformation of the metal bellows compensates for thermal expansions; as illustrated in FIG. 6 , the compensation is by displaceable bearing 65 .
Right-angle gear unit 7 may be configured such that on the whole, it has an integral gear ratio, e.g., in the range of 3 to 30. To achieve the different gear ratios, the gearing parts are interchanged within one size; in so doing, depending on the desired gear ratio, one set, including a crown-toothed wheel and a hypoid pinion, is exchanged for a second set, including a different crown-toothed wheel and a different hypoid pinion. In addition, the spur gears of the input gear stage are varied such that on the whole, an integral gear ratio may always be present. Given a constant distance between axes, thus within a specific size, the varying of the spur gears includes the helix angle and the profile offset.
For the hypoid stage of right-angle gear unit 7 , the first indicated set may be designed for the gear ratio i=3, the second set for the gear ratio i=7.5.
The gear ratios within one size, which, using as few different gearing parts as possible, may cover a range of gear ratios which may be as broad and densely filled as possible, are i=3, 4, 6, 8, 10, 15, 20, 25, 30, 35 and 40. In this context, the gear ratios of i=3 to 10 may be produced by the hypoid set, where i=3, and the remaining gear ratios with the set where i=7.5.
A series may include 6 sizes, thus 6 different distances between axes, for the spur-gear stage of right-angle gear unit 7 . All industrially customary sizes or output classes may be covered by this number. In addition, an optimal relationship between parts variety and piece number may be attainable at the same time. In the case of even larger sizes, e.g., in the megawatt range or more, the piece numbers may be small, such that the advantage of the multiple use of parts for different variants may become small, but the conceptual disadvantages may increase, for example, the material quantities, and thus the material costs for the housing, as well.
The sizes may be designed such that the maximally transmittable torque of the sizes is graduated in the manner M1*(2^(n−1)), n being the size numbered from 1 to 6 and M1 being the maximally transmittable torque of the smallest size, thus for n=1.
Deviations from the indicated formula M1*(2^(n−1)) may be, if they are less than 18%. This may be a particularly advantageous value.
The value M1=40 Nm may be especially advantageous, since the above-indicated advantageous part of the market for industrial gear units may thus be able to be covered, while retaining the cited advantages.
Values for M1 between 10 Nm and 100 nm may also be advantageous.
The series may include two types of low-backlash gear units, e.g., the indicated gear units with 3 angular minutes, and gear units of the same kind which, however, have 6 angular minutes. Therefore, more cost-effective gear units with 6 angular minutes and corresponding geared motors may also be able to be produced and offered. | A spare part set for a gearmotor series includes transmissions actuated by electric motors. The series has at least one dimension which may be characterized by at least one physical, mechanical and/or geometrical value, e.g., by nominal power, axis height or torque. Each electric motor includes at least one crankcase, a rotor provided with a rotor axis and a side-shield for a motor bearing arranged within a given size. The crankcase includes an interface with the side-shield for a motor bearing, which is selected such that at least two different embodiments thereof are connectable to the said crankcase. | 8 |
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. Ser. No. 12/441,945, filed Feb. 12, 2010, which is a national stage application of International Application No. PCT/US2007/078805, filed Sep. 18, 2007, which claims the benefit of U.S. Provisional Application No. 60/845,600, filed Sep. 19, 2006, the entire contents of which are hereby incorporated by reference herein.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] This invention was made, in part, with Government support under Grant No. U01CA111275-01 from the National Institutes of Health. The U.S. Government may have certain rights in this invention.
FIELD
[0003] The invention generally relates to biomarkers for prostate cancer and methods based on the same biomarkers.
BACKGROUND
[0004] Prostate cancer is the leading cause of male cancer-related deaths and afflicts one out of nine men over the age of 65. The American Cancer Society estimates that over 200,000 American men will be diagnosed with prostate cancer and over 30,000 will die this year. While effective surgical and radiation treatments exist for localized prostate cancer, metastatic prostate cancer remains essentially incurable and most men diagnosed with metastatic disease will succumb over a period of months to years.
[0005] Prostate cancer is detected by either a digital rectal exam (DRE), or by the measurement of levels of prostate specific antigen (PSA), which has an unacceptably high rate of false-positives. The diagnosis of prostate cancer can be confirmed only by a biopsy. Radical prostatectomy, radiation and watchful waiting are generally effective for localized prostate cancer, but it is often difficult to determine which approach to use. Since it is not possible to distinguish between the indolent and more aggressive tumors current therapy takes a very conservative approach.
[0006] While imaging, X-rays, computerized tomography scans and further biopsies can help determine if prostate cancer has metastasized, they are not able to differentiate early stages. Understanding the progression of prostate cancer from a localized, early, indolent state, to an aggressive state, and, ultimately, to a metastatic state would allow the proper clinical management of this disease. Furthermore, early-indolent prostate cancer may be progressive or non-progressive toward aggressive forms.
SUMMARY
[0007] In one aspect, the present invention provides a method of diagnosing whether a subject has prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 and comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to diagnose whether the subject has prostate cancer.
[0008] In another aspect, the present invention also provides a method of determining whether a subject is predisposed to developing prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to determine whether the subject is predisposed to developing prostate cancer.
[0009] In yet another aspect, the invention provides a method of monitoring progression/regression of prostate cancer in a subject comprising analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and the first sample is obtained from the subject at a first time point; analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, where the second sample is obtained from the subject at a second time point; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to monitor the progression/regression of prostate cancer in the subject.
[0010] In another aspect, the present invention provides a method of assessing the efficacy of a composition for treating prostate cancer comprising analyzing, from a subject having prostate cancer and currently or previously being treated with a composition, a biological sample to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers in the sample to (a) levels of the one or more biomarkers in a previously-taken biological sample from the subject, where the previously-taken biological sample was obtained from the subject before being treated with the composition, (b) prostate cancer-positive reference levels of the one or more biomarkers, and/or (c) prostate cancer-negative reference levels of the one or more biomarkers.
[0011] In another aspect, the present invention provides a method for assessing the efficacy of a composition in treating prostate cancer, comprising analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point; administering the composition to the subject; analyzing a second biological sample from the subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point after administration of the composition; comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the efficacy of the composition for treating prostate cancer.
[0012] In yet another aspect, the invention provides a method of assessing the relative efficacy of two or more compositions for treating prostate cancer comprising analyzing, from a first subject having prostate cancer and currently or previously being treated with a first composition, a first biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; analyzing, from a second subject having prostate cancer and currently or previously being treated with a second composition, a second biological sample to determine the level(s) of the one or more biomarkers; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the relative efficacy of the first and second compositions for treating prostate cancer.
[0013] In another aspect, the present invention provides a method for screening a composition for activity in modulating one or more biomarkers of prostate cancer, comprising contacting one or more cells with a composition; analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more biomarkers of prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers with predetermined standard levels for the biomarkers to determine whether the composition modulated the level(s) of the one or more biomarkers.
[0014] In a further aspect, the present invention provides a method for identifying a potential drug target for prostate cancer comprising identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and identifying a protein affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
[0015] In yet another aspect, the invention provides a method for treating a subject having prostate cancer comprising administering to the subject an effective amount of one or more biomarkers selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer.
[0016] In another aspect, the invention also provides a method of distinguishing low grade prostate cancer from high grade prostate cancer in a subject having prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for low grade prostate cancer and/or high grade prostate cancer in the sample, where the one or more biomarkers are selected from Tables 3, 8, 11, 20 and/or 26 and comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or to high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer in order to determine whether the subject has low grade or high grade prostate cancer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 provides an importance plot of one example of metabolites to distinguish Normal (N), Localized cancer tumor (T), and Metastatic tumor (M) tissue types.
[0018] FIG. 2 provides an importance plot of one example of metabolites to distinguish Normal prostate tissue (N) and Localized prostate tumor tissue (T).
[0019] FIG. 3 provides an importance plot of one example of metabolites to distinguish Non-cancer tissue (Control) and lower grade prostate cancer tissue (PCA) using urine samples.
[0020] FIG. 4 provides an importance plot of one example of metabolites to distinguish lower grade prostate cancer tissues and higher grade prostate cancer tissues from urine samples.
[0021] FIG. 5 provides an importance plot of one example of metabolites to distinguish non-cancer tissue (Control) and lower grade prostate cancer tissue (PCA) using plasma samples.
[0022] FIG. 6 provides an importance plot of one example of metabolites to distinguish lower grade prostate cancer tissues and higher grade prostate cancer tissues using plasma samples.
[0023] FIG. 7 provides an importance plot of one example of metabolites to distinguish subjects with lower grade prostate cancer and higher grade prostate cancer.
DETAILED DESCRIPTION
[0024] The present invention relates to biomarkers of prostate cancer, methods for diagnosis of prostate cancer, methods of distinguishing between low grade and high grade prostate cancer, methods of determining predisposition to prostate cancer, methods of monitoring progression/regression of prostate cancer, methods of assessing efficacy of compositions for treating prostate cancer, methods of screening compositions for activity in modulating biomarkers of prostate cancer, methods of treating prostate cancer, as well as other methods based on biomarkers of prostate cancer. Prior to describing this invention in further detail, however, the following terms will first be defined.
DEFINITIONS
[0025] “Biomarker” means a compound, preferably a metabolite, that is differentially present (i.e., increased or decreased) in a biological sample from a subject or a group of subjects having a first phenotype (e.g., having a disease) as compared to a biological sample from a subject or group of subjects having a second phenotype (e.g., not having the disease). A biomarker may be differentially present at any level, but is generally present at a level that is increased by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, by at least 100%, by at least 110%, by at least 120%, by at least 130%, by at least 140%, by at least 150%, or more; or is generally present at a level that is decreased by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent). A biomarker is preferably differentially present at a level that is statistically significant (i.e., a p-value less than 0.05 and/or a q-value of less than 0.10 as determined using either Welch's T-test or Wilcoxon's rank-sum Test).
[0026] The “level” of one or more biomarkers means the absolute or relative amount or concentration of the biomarker in the sample.
[0027] “Sample” or “biological sample” means biological material isolated from a subject. The biological sample may contain any biological material suitable for detecting the desired biomarkers, and may comprise cellular and/or non-cellular material from the subject. The sample can be isolated from any suitable biological tissue or fluid such as, for example, prostate tissue, blood, blood plasma, urine, or cerebral spinal fluid (CSF).
[0028] “Subject” means any animal, but is preferably a mammal, such as, for example, a human, monkey, mouse, or rabbit.
[0029] A “reference level” of a biomarker means a level of the biomarker that is indicative of a particular disease state, phenotype, or lack thereof, as well as combinations of disease states, phenotypes, or lack thereof. A “positive” reference level of a biomarker means a level that is indicative of a particular disease state or phenotype. A “negative” reference level of a biomarker means a level that is indicative of a lack of a particular disease state or phenotype. For example, a “prostate cancer-positive reference level” of a biomarker means a level of a biomarker that is indicative of a positive diagnosis of prostate cancer in a subject, and a “prostate cancer-negative reference level” of a biomarker means a level of a biomarker that is indicative of a negative diagnosis of prostate cancer in a subject. A “reference level” of a biomarker may be an absolute or relative amount or concentration of the biomarker, a presence or absence of the biomarker, a range of amount or concentration of the biomarker, a minimum and/or maximum amount or concentration of the biomarker, a mean amount or concentration of the biomarker, and/or a median amount or concentration of the biomarker; and, in addition, “reference levels” of combinations of biomarkers may also be ratios of absolute or relative amounts or concentrations of two or more biomarkers with respect to each other. Appropriate positive and negative reference levels of biomarkers for a particular disease state, phenotype, or lack thereof may be determined by measuring levels of desired biomarkers in one or more appropriate subjects, and such reference levels may be tailored to specific populations of subjects (e.g., a reference level may be age-matched so that comparisons may be made between biomarker levels in samples from subjects of a certain age and reference levels for a particular disease state, phenotype, or lack thereof in a certain age group). Such reference levels may also be tailored to specific techniques that are used to measure levels of biomarkers in biological samples (e.g., LC-MS, GC-MS, etc.), where the levels of biomarkers may differ based on the specific technique that is used.
[0030] “Non-biomarker compound” means a compound that is not differentially present in a biological sample from a subject or a group of subjects having a first phenotype (e.g., having a first disease) as compared to a biological sample from a subject or group of subjects having a second phenotype (e.g., not having the first disease). Such non-biomarker compounds may, however, be biomarkers in a biological sample from a subject or a group of subjects having a third phenotype (e.g., having a second disease) as compared to the first phenotype (e.g., having the first disease) or the second phenotype (e.g., not having the first disease).
[0031] “Metabolite”, or “small molecule”, means organic and inorganic molecules which are present in a cell. The term does not include large macromolecules, such as large proteins (e.g., proteins with molecular weights over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000), large nucleic acids (e.g., nucleic acids with molecular weights of over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000), or large polysaccharides (e.g., polysaccharides with a molecular weights of over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000). The small molecules of the cell are generally found free in solution in the cytoplasm or in other organelles, such as the mitochondria, where they form a pool of intermediates which can be metabolized further or used to generate large molecules, called macromolecules. The term “small molecules” includes signaling molecules and intermediates in the chemical reactions that transform energy derived from food into usable forms. Examples of small molecules include sugars, fatty acids, amino acids, nucleotides, intermediates formed during cellular processes, and other small molecules found within the cell.
[0032] “Metabolic profile”, or “small molecule profile”, means a complete or partial inventory of small molecules within a targeted cell, tissue, organ, organism, or fraction thereof (e.g., cellular compartment). The inventory may include the quantity and/or type of small molecules present. The “small molecule profile” may be determined using a single technique or multiple different techniques.
[0033] “Metabolome” means all of the small molecules present in a given organism.
[0034] “Prostate cancer” refers to a disease in which cancer develops in the prostate, a gland in the male reproductive system. “Low grade” or “lower grade” prostate cancer refers to non-metastatic prostate cancer, including malignant tumors with low potential for metastisis (i.e. prostate cancer that is considered to be less aggressive). “High grade” or “higher grade” prostate cancer refers to prostate cancer that has metastasized in a subject, including malignant tumors with high potential for metastisis (prostate cancer that is considered to be aggressive).
I. Biomarkers
[0035] The prostate cancer biomarkers described herein were discovered using metabolomic profiling techniques. Such metabolomic profiling techniques are described in more detail in the Examples set forth below as well as in U.S. Pat. No. 7,005,255 and U.S. patent application Ser. Nos. 11/357,732, 10/695,265 (Publication No. 2005/0014132), 11/301,077 (Publication No. 2006/0134676), 11/301,078 (Publication No. 2006/0134677), 11/301,079 (Publication No. 2006/0134678), and 11/405,033, the entire contents of which are hereby incorporated herein by reference.
[0036] Generally, metabolic profiles were determined for biological samples from human subjects diagnosed with prostate cancer as well as from one or more other groups of human subjects (e.g., healthy control subjects not diagnosed with prostate cancer), as well as from human subjects diagnosed with lower grade prostate cancer and human subjects diagnosed with metastatic/high grade prostate cancer. The metabolic profile for biological samples from a subject having prostate cancer was compared to the metabolic profile for biological samples from the one or more other groups of subjects. Those molecules differentially present, including those molecules differentially present at a level that is statistically significant, in the metabolic profile of samples from subjects with prostate cancer as compared to another group (e.g., healthy control subjects not diagnosed with prostate cancer) were identified as biomarkers to distinguish those groups. In addition, those molecules differentially present, including those molecules differentially present at a level that is statistically significant, in the metabolic profile of samples from subjects with low grade prostate cancer as compared to high grade prostate cancer were also identified as biomarkers to distinguish those groups.
[0037] The biomarkers are discussed in more detail herein. The biomarkers that were discovered correspond with the following group(s):
Biomarkers for distinguishing subjects having prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 1, 2, 4, 5, 6, 7, 9, 10, 15, 18, 22, 24); Biomarkers for distinguishing subjects having low grade prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 1, 6, 9, 22); Biomarkers for distinguishing subjects having metastatic/high grade prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 2, 7, 10, 24); Biomarkers for distinguishing subjects having metastatic/high grade prostate cancer vs. subjects having low grade prostate cancer (see Tables 3, 8, 11, 20, 26).
[0042] Although the identities of some of the biomarkers compounds are not known at this time, such identities are not necessary for the identification of the biomarkers in biological samples from subjects, as the “unnamed” compounds have been sufficiently characterized by analytical techniques to allow such identification. The analytical characterization of all such “unnamed” compounds is listed in the Examples. Such “unnamed” biomarkers are designated herein using the nomenclature “Metabolite” followed by a specific metabolite number.
IIA. Diagnosis of Prostate Cancer
[0043] The identification of biomarkers for prostate cancer allows for the diagnosis of (or for aiding in the diagnosis of) prostate cancer in subjects presenting one or more symptoms of prostate cancer. A method of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers of prostate cancer in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to diagnose (or aid in the diagnosis of) whether the subject has prostate cancer. The one or more biomarkers that are used are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 and combinations thereof. When such a method is used to aid in the diagnosis of prostate cancer, the results of the method may be used along with other methods (or the results thereof) useful in the clinical determination of whether a subject has prostate cancer.
[0044] Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include chromatography (e.g., HPLC, gas chromatography, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), enzyme-linked immunosorbent assay (ELISA), antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) that are desired to be measured.
[0045] The levels of one or more of the biomarkers of Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 may be determined in the methods of diagnosing and methods of aiding in diagnosing whether a subject has prostate cancer. For example, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 or any fraction thereof, may be determined and used in such methods. Determining levels of combinations of the biomarkers may allow greater sensitivity and specificity in diagnosing prostate cancer and aiding in the diagnosis of prostate cancer, and may allow better differentiation of prostate cancer from other prostate disorders (e.g. benign prostatic hypertrophy (BPH), prostatitis, etc.) or other cancers that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having prostate cancer). For example, ratios of the levels of certain biomarkers (and non-biomarker compounds) in biological samples may allow greater sensitivity and specificity in diagnosing prostate cancer and aiding in the diagnosis of prostate cancer and may allow better differentiation of prostate cancer from other cancers or other disorders of the prostate that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having prostate cancer).
[0046] One or more biomarkers that are specific for diagnosing prostate cancer (or aiding in diagnosing prostate cancer) in a certain type of sample (e.g., prostate tissue sample, urine sample, or blood plasma sample) may also be used. For example, when the biological sample is prostate tissue, one or more biomarkers listed in Tables 1, 2, 13, and/or 15, may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer. When the biological sample is blood plasma, one or more biomarkers listed in Tables 4, 6, 7, 22, and/or 24 may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer. When the biological sample is urine, one or more biomarkers listed in Tables 5, 9, 10, and/or 18 may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer.
[0047] After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to prostate cancer-positive and/or prostate cancer-negative reference levels to aid in diagnosing or to diagnose whether the subject has prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of a diagnosis of prostate cancer in the subject. Levels of the one or more biomarkers in a sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of a diagnosis of no prostate cancer in the subject. In addition, levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-negative reference levels are indicative of a diagnosis of prostate cancer in the subject. Levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-positive reference levels are indicative of a diagnosis of no prostate cancer in the subject.
[0048] The level(s) of the one or more biomarkers may be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using various techniques, including a simple comparison (e.g., a manual comparison) of the level(s) of the one or more biomarkers in the biological sample to prostate cancer-positive and/or prostate cancer-negative reference levels. The level(s) of the one or more biomarkers in the biological sample may also be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using one or more statistical analyses (e.g., t-test, Welch's T-test, Wilcoxon's rank sum test, random forest).
[0049] In addition, the biological samples may be analyzed to determine the level(s) of one or more non-biomarker compounds. The level(s) of such non-biomarker compounds may also allow differentiation of prostate cancer from other prostate disorders that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having a prostate disorder). For example, a known non-biomarker compound present in biological samples of subjects having prostate cancer and subjects not having prostate cancer could be monitored to verify a diagnosis of prostate cancer as compared to a diagnosis of another prostate disorder when biological samples from subjects having the prostate disorder do not have the non-biomarker compound.
[0050] The methods of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer may also be conducted specifically to diagnose (or aid in diagnosing) whether a subject has low grade prostate cancer and/or high grade prostate cancer. Such methods comprise (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers of low grade prostate cancer (and/or high grade prostate cancer) in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive and/or low grade prostate cancer-negative reference levels (or high grade prostate cancer-positive and/or high grade prostate cancer-negative reference levels) in order to diagnose (or aid in the diagnosis of) whether the subject has low grade prostate cancer (or high grade prostate cancer). Biomarker specific for low grade prostate cancer are listed in Tables 1, 6, 9, 22 and biomarkers specific for high grade prostate cancer are listed in Tables 2, 7, 10, 24.
[0000] IIB. Methods of Distinguishing Low Grade Prostate Cancer from High Grade Prostate Cancer
[0051] The identification of biomarkers for distinguishing low grade prostate cancer versus high grade prostate cancer allows low grade prostate cancer and high grade prostate cancer to be distinguished in patients. A method of distinguishing low grade prostate cancer from high grade prostate cancer in a subject having prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) in the sample of one or more biomarkers of low grade prostate cancer that distinguish over high grade prostate cancer and/or one or more biomarkers of high grade prostate cancer that distinguish over low grade prostate cancer, and (2) comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer of the one or more biomarkers in order to determine whether the subject has low grade or high grade prostate cancer. The one or more biomarkers that are used are selected from Tables 3, 8, 11, 20, and/or 26 and combinations thereof.
[0052] Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include chromatography (e.g., HPLC, gas chromatography, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), enzyme-linked immunosorbent assay (ELISA), antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) that are desired to be measured.
[0053] The levels of one or more of the biomarkers of Tables 3, 8, 11, 20, and/or 26 may be determined in the methods of diagnosing and methods of aiding in diagnosing whether a subject has prostate cancer. For example, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 3, 8, 11, 20, and/or 26 or any fraction thereof, may be determined and used in such methods. Determining levels of combinations of the biomarkers may allow greater sensitivity and specificity in distinguishing between low grade and high grade prostate cancer.
[0054] One or more biomarkers that are specific for distinguishing between low grade and high grade prostate cancer in a certain type of sample (e.g., prostate tissue sample, urine sample, or blood plasma sample) may also be used. For example, when the biological sample is prostate tissue, one or more biomarkers listed in Table 3 may be used. When the biological sample is blood plasma, one or more biomarkers listed in Table 8 or 26 may be used. When the biological sample is urine, one or more biomarkers listed in Table 11 or 20 may be used.
[0055] After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer-negative and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer of the one or more biomarkers in order to determine whether the subject has low grade or high grade prostate cancer. Levels of the one or more biomarkers in a sample matching the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of low-grade prostate cancer in the subject. Levels of the one or more biomarkers in a sample matching the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of high-grade prostate cancer in the subject. If the level(s) of the one or more biomarkers are more similar to the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels), then the results are indicative of low grade prostate cancer in the subject. If the level(s) of the one or more biomarkers are more similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (or less similar to the low grade prostate cancer-positive reference levels), then the results are indicative of high grade prostate cancer in the subject.
[0056] The level(s) of the one or more biomarkers may be compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer using various techniques, including a simple comparison (e.g., a manual comparison) of the level(s) of the one or more biomarkers in the biological sample to low grade prostate cancer-positive and/or high grade prostate cancer-positive reference levels. The level(s) of the one or more biomarkers in the biological sample may also be compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer using one or more statistical analyses (e.g., t-test, Welch's T-test, Wilcoxon's rank sum test, random forest).
[0057] In addition, the biological samples may be analyzed to determine the level(s) of one or more non-biomarker compounds. The level(s) of such non-biomarker compounds may also allow differentiation of low grade prostate cancer from high grade prostate cancer.
III. Methods of Determining Predisposition to Prostate Cancer
[0058] The identification of biomarkers for prostate cancer also allows for the determination of whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer. A method of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers listed in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to determine whether the subject is predisposed to developing prostate cancer. The results of the method may be used along with other methods (or the results thereof) useful in the clinical determination of whether a subject is predisposed to developing prostate cancer.
[0059] As described above in connection with methods of diagnosing (or aiding in the diagnosis of) prostate cancer, any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample.
[0060] As with the methods of diagnosing (or aiding in the diagnosis of) prostate cancer described above, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 or any fraction thereof, may be determined and used in methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer.
[0061] After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to prostate cancer-positive and/or prostate cancer-negative reference levels in order to predict whether the subject is predisposed to developing prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the subject being predisposed to developing prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the subject not being predisposed to developing prostate cancer. In addition, levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-negative reference levels are indicative of the subject being predisposed to developing prostate cancer. Levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-positive reference levels are indicative of the subject not being predisposed to developing prostate cancer.
[0062] Furthermore, it may also be possible to determine reference levels specific to assessing whether or not a subject that does not have prostate cancer is predisposed to developing prostate cancer. For example, it may be possible to determine reference levels of the biomarkers for assessing different degrees of risk (e.g., low, medium, high) in a subject for developing prostate cancer. Such reference levels could be used for comparison to the levels of the one or more biomarkers in a biological sample from a subject.
[0063] As with the methods described above, the level(s) of the one or more biomarkers may be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using various techniques, including a simple comparison, one or more statistical analyses, and combinations thereof.
[0064] As with the methods of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer, the methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer may further comprise analyzing the biological sample to determine the level(s) of one or more non-biomarker compounds.
[0065] The methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer may also be conducted specifically to determine whether a subject having no symptoms of prostate cancer is predisposed to developing low grade prostate cancer and/or high grade prostate cancer. Biomarker specific for low grade prostate cancer are listed in Tables 1, 6, 9, and 22 and biomarkers specific for high grade prostate cancer are listed in Tables 2, 7, 10, and 24.
[0066] In addition, methods of determining whether a subject having low grade prostate cancer is predisposed to developing high grade prostate cancer may be conducted using one or more biomarkers selected from Tables 3, 8, 11, 20, and 26.
IV. Methods of Monitoring Progression/Regression of Prostate Cancer
[0067] The identification of biomarkers for prostate cancer also allows for monitoring progression/regression of prostate cancer in a subject. A method of monitoring the progression/regression of prostate cancer in a subject comprises (1) analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point, (2) analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point, and (3) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to monitor the progression/regression of prostate cancer in the subject. The results of the method are indicative of the course of prostate cancer (i.e., progression or regression, if any change) in the subject.
[0068] The change (if any) in the level(s) of the one or more biomarkers over time may be indicative of progression or regression of prostate cancer in the subject. In order to characterize the course of prostate cancer in the subject, the level(s) of the one or more biomarkers in the first sample, the level(s) of the one or more biomarkers in the second sample, and/or the results of the comparison of the levels of the biomarkers in the first and second samples may be compared to prostate cancer-positive, prostate cancer-negative, low grade prostate cancer-positive, low grade prostate cancer-negative, high-grade prostate cancer-positive, and/or high grade prostate cancer-negative reference levels as well as low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers are increasing or decreasing over time (e.g., in the second sample as compared to the first sample) to become more similar to the prostate cancer-positive reference levels (or less similar to the prostate cancer-negative reference levels), to the high grade prostate cancer reference levels, or, when the subject initially has low grade prostate cancer, to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer, then the results are indicative of prostate cancer progression. If the comparisons indicate that the level(s) of the one or more biomarkers are increasing or decreasing over time to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels), or, when the subject initially has high grade prostate cancer, to low grade prostate cancer reference levels and/or to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, then the results are indicative of prostate cancer regression.
[0069] As with the other methods described herein, the comparisons made in the methods of monitoring progression/regression of prostate cancer in a subject may be carried out using various techniques, including simple comparisons, one or more statistical analyses, and combinations thereof.
[0070] The results of the method may be used along with other methods (or the results thereof) useful in the clinical monitoring of progression/regression of prostate cancer in a subject.
[0071] As described above in connection with methods of diagnosing (or aiding in the diagnosis of) prostate cancer, any suitable method may be used to analyze the biological samples in order to determine the level(s) of the one or more biomarkers in the samples. In addition, the level(s) one or more biomarkers, including a combination of all of the biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 or any fraction thereof, may be determined and used in methods of monitoring progression/regression of prostate cancer in a subject.
[0072] Such methods could be conducted to monitor the course of prostate cancer in subjects having prostate cancer or could be used in subjects not having prostate cancer (e.g., subjects suspected of being predisposed to developing prostate cancer) in order to monitor levels of predisposition to prostate cancer.
V. Methods of Assessing Efficacy of Compositions for Treating Prostate Cancer
[0073] The identification of biomarkers for prostate cancer also allows for assessment of the efficacy of a composition for treating prostate cancer as well as the assessment of the relative efficacy of two or more compositions for treating prostate cancer. Such assessments may be used, for example, in efficacy studies as well as in lead selection of compositions for treating prostate cancer.
[0074] A method of assessing the efficacy of a composition for treating prostate cancer comprises (1) analyzing, from a subject having prostate cancer and currently or previously being treated with a composition, a biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, and (2) comparing the level(s) of the one or more biomarkers in the sample to (a) level(s) of the one or more biomarkers in a previously-taken biological sample from the subject, wherein the previously-taken biological sample was obtained from the subject before being treated with the composition, (b) prostate cancer-positive reference levels (including low grade prostate cancer-positive and/or high grade prostate cancer-positive reference levels) of the one or more biomarkers, (c) prostate cancer-negative reference levels (including low grade prostate cancer-negative and/or high grade prostate cancer-negative reference levels) of the one or more biomarkers, (d) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or (e) high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer. The results of the comparison are indicative of the efficacy of the composition for treating prostate cancer.
[0075] Thus, in order to characterize the efficacy of the composition for treating prostate cancer, the level(s) of the one or more biomarkers in the biological sample are compared to (1) prostate cancer-positive reference levels, (2) prostate cancer-negative reference levels, (3) previous levels of the one or more biomarkers in the subject before treatment with the composition, (4) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or (5) high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer.
[0076] When comparing the level(s) of the one or more biomarkers in the biological sample (from a subject having prostate cancer and currently or previously being treated with a composition) to prostate cancer-positive reference levels and/or prostate cancer-negative reference levels, level(s) in the sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition having efficacy for treating prostate cancer. Levels of the one or more biomarkers in the sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition not having efficacy for treating prostate cancer. The comparisons may also indicate degrees of efficacy for treating prostate cancer based on the level(s) of the one or more biomarkers.
[0077] When comparing the level(s) of the one or more biomarkers in the biological sample (from a subject having high grade prostate cancer and currently or previously being treated with a composition) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer, level(s) in the sample matching the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition having efficacy for treating prostate cancer. Levels of the one or more biomarkers in the sample matching the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition not having efficacy for treating prostate cancer.
[0078] When the level(s) of the one or more biomarkers in the biological sample (from a subject having prostate cancer and currently or previously being treated with a composition) are compared to level(s) of the one or more biomarkers in a previously-taken biological sample from the subject before treatment with the composition, any changes in the level(s) of the one or more biomarkers are indicative of the efficacy of the composition for treating prostate cancer. That is, if the comparisons indicate that the level(s) of the one or more biomarkers have increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition having efficacy for treating prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers have not increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have not increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition not having efficacy for treating prostate cancer. The comparisons may also indicate degrees of efficacy for treating prostate cancer based on the amount of changes observed in the level(s) of the one or more biomarkers after treatment. In order to help characterize such a comparison, the changes in the level(s) of the one or more biomarkers, the level(s) of the one or more biomarkers before treatment, and/or the level(s) of the one or more biomarkers in the subject currently or previously being treated with the composition may be compared to prostate cancer-positive reference levels (including low grade and high grade prostate cancer-positive reference levels), prostate cancer-negative reference levels (including low grade and high grade prostate cancer-negative reference levels), low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer.
[0079] Another method for assessing the efficacy of a composition in treating prostate cancer comprises (1) analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point, (2) administering the composition to the subject, (3) analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point after administration of the composition, and (4) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the efficacy of the composition for treating prostate cancer. As indicated above, if the comparison of the samples indicates that the level(s) of the one or more biomarkers have increased or decreased after administration of the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, if the level(s) have increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition having efficacy for treating prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers have not increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have not increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition not having efficacy for treating prostate cancer. The comparison may also indicate a degree of efficacy for treating prostate cancer based on the amount of changes observed in the level(s) of the one or more biomarkers after administration of the composition as discussed above.
[0080] A method of assessing the relative efficacy of two or more compositions for treating prostate cancer comprises (1) analyzing, from a first subject having prostate cancer and currently or previously being treated with a first composition, a first biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 (2) analyzing, from a second subject having prostate cancer and currently or previously being treated with a second composition, a second biological sample to determine the level(s) of the one or more biomarkers, and (3) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the relative efficacy of the first and second compositions for treating prostate cancer. The results are indicative of the relative efficacy of the two compositions, and the results (or the levels of the one or more biomarkers in the first sample and/or the level(s) of the one or more biomarkers in the second sample) may be compared to prostate cancer-positive reference levels (including low grade and high grade prostate cancer-positive reference levels), prostate cancer-negative reference levels (including low grade and high grade prostate cancer-negative reference levels), low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer to aid in characterizing the relative efficacy.
[0081] Each of the methods of assessing efficacy may be conducted on one or more subjects or one or more groups of subjects (e.g., a first group being treated with a first composition and a second group being treated with a second composition).
[0082] As with the other methods described herein, the comparisons made in the methods of assessing efficacy (or relative efficacy) of compositions for treating prostate cancer may be carried out using various techniques, including simple comparisons, one or more statistical analyses, and combinations thereof. Any suitable method may be used to analyze the biological samples in order to determine the level(s) of the one or more biomarkers in the samples. In addition, the level(s) of one or more biomarkers, including a combination of all of the biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 or any fraction thereof, may be determined and used in methods of assessing efficacy (or relative efficacy) of compositions for treating prostate cancer.
[0083] Finally, the methods of assessing efficacy (or relative efficacy) of one or more compositions for treating prostate cancer may further comprise analyzing the biological sample to determine the level(s) of one or more non-biomarker compounds. The non-biomarker compounds may then be compared to reference levels of non-biomarker compounds for subjects having (or not having) prostate cancer.
[0000] VI. Methods of Screening a Composition for Activity in Modulating Biomarkers Associated with Prostate Cancer
[0084] The identification of biomarkers for prostate cancer also allows for the screening of compositions for activity in modulating biomarkers associated with prostate cancer, which may be useful in treating prostate cancer. Methods of screening compositions useful for treatment of prostate cancer comprise assaying test compositions for activity in modulating the levels of one or more biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26. Such screening assays may be conducted in vitro and/or in vivo, and may be in any form known in the art useful for assaying modulation of such biomarkers in the presence of a test composition such as, for example, cell culture assays, organ culture assays, and in vivo assays (e.g., assays involving animal models).
[0085] In one embodiment, a method for screening a composition for activity in modulating one or more biomarkers of prostate cancer comprises (1) contacting one or more cells with a composition, (2) analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more biomarkers of prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and (3) comparing the level(s) of the one or more biomarkers with predetermined standard levels for the one or more biomarkers to determine whether the composition modulated the level(s) of the one or more biomarkers. As discussed above, the cells may be contacted with the composition in vitro and/or in vivo. The predetermined standard levels for the one or more biomarkers may be the levels of the one or more biomarkers in the one or more cells in the absence of the composition. The predetermined standard levels for the one or more biomarkers may also be the level(s) of the one or more biomarkers in control cells not contacted with the composition.
[0086] In addition, the methods may further comprise analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more non-biomarker compounds of prostate cancer. The levels of the non-biomarker compounds may then be compared to predetermined standard levels of the one or more non-biomarker compounds.
[0087] Any suitable method may be used to analyze at least a portion of the one or more cells or a biological sample associated with the cells in order to determine the level(s) of the one or more biomarkers (or levels of non-biomarker compounds). Suitable methods include chromatography (e.g., HPLC, gas chromatograph, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), ELISA, antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers (or levels of non-biomarker compounds) may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) (or non-biomarker compounds) that are desired to be measured.
VII. Method of Identifying Potential Drug Targets
[0088] The identification of biomarkers for prostate cancer also allows for the identification of potential drug targets for prostate cancer. A method for identifying a potential drug target for prostate cancer comprises (1) identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and (2) identifying a protein (e.g., an enzyme) affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
[0089] Another method for identifying a potential drug target for prostate cancer comprises (1) identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and one or more non-biomarker compounds of prostate cancer and (2) identifying a protein affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
[0090] One or more biochemical pathways (e.g., biosynthetic and/or metabolic (catabolic) pathway) are identified that are associated with one or more biomarkers (or non-biomarker compounds). After the biochemical pathways are identified, one or more proteins affecting at least one of the pathways are identified. Preferably, those proteins affecting more than one of the pathways are identified.
[0091] A build-up of one metabolite (e.g., a pathway intermediate) may indicate the presence of a ‘block’ downstream of the metabolite and the block may result in a low/absent level of a downstream metabolite (e.g. product of a biosynthetic pathway). In a similar manner, the absence of a metabolite could indicate the presence of a ‘block’ in the pathway upstream of the metabolite resulting from inactive or non-functional enzyme(s) or from unavailability of biochemical intermediates that are required substrates to produce the product. Alternatively, an increase in the level of a metabolite could indicate a genetic mutation that produces an aberrant protein which results in the over-production and/or accumulation of a metabolite which then leads to an alteration of other related biochemical pathways and result in dysregulation of the normal flux through the pathway; further, the build-up of the biochemical intermediate metabolite may be toxic or may compromise the production of a necessary intermediate for a related pathway. It is possible that the relationship between pathways is currently unknown and this data could reveal such a relationship.
[0092] For example, the data indicates that metabolites in the biochemical pathways involving nitrogen excretion, amino acid metabolism, energy metabolism, oxidative stress, purine metabolism and bile acid metabolism are enriched in prostate cancer subjects. Further, polyamine levels are higher in cancer subjects, which indicates that the level and/or activity of the enzyme ornithine decarboxylase is increased. It is known that polyamines can act as mitotic agents and have been associated with free radical damage. These observations indicate that the pathways leading to the production of polyamines (or to any of the aberrant biomarkers) would provide a number of potential targets useful for drug discovery.
[0093] The proteins identified as potential drug targets may then be used to identify compositions that may be potential candidates for treating prostate cancer, including compositions for gene therapy.
VIII. Methods of Treating Prostate Cancer
[0094] The identification of biomarkers for prostate cancer also allows for the treatment of prostate cancer. For example, in order to treat a subject having prostate cancer, an effective amount of one or more prostate cancer biomarkers that are lowered in prostate cancer as compared to a healthy subject not having prostate cancer may be administered to the subject. The biomarkers that may be administered may comprise one or more of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer. In some embodiments, the biomarkers that are administered are one or more biomarkers listed in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer and that have a p-value less than 0.10. In other embodiments, the biomarkers that are administered are one or biomarkers listed in Tables 1, 2 and/or 3 that are decreased in prostate cancer by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent).
IX. Methods of Using the Prostate Cancer Biomarkers for Other Types of Prostate Cancer
[0095] It is believed that some of the biomarkers for major prostate cancer described herein may also be biomarkers for other types of cancer, including, for example, lung cancer or kidney cancer. Therefore, it is believed that at least some of the prostate cancer biomarkers may be used in the methods described herein for other types of cancer. That is, the methods described herein with respect to prostate cancer may also be used for diagnosing (or aiding in the diagnosis of) any type of cancer, methods of monitoring progression/regression of any type of cancer, methods of assessing efficacy of compositions for treating any type of cancer, methods of screening a composition for activity in modulating biomarkers associated with any type of cancer, methods of identifying potential drug targets for any type of cancer, and methods of treating any type of cancer. Such methods could be conducted as described herein with respect to prostate cancer.
X. Methods of Using the Prostate Cancer Biomarkers for Other Prostate Disorders
[0096] It is believed that some of the biomarkers for prostate cancer described herein may also be biomarkers for prostate disorders (e.g. prostatitis, benign prostate hypertrophy (BHP)) in general. Therefore, it is believed that at least some of the prostate cancer biomarkers may be used in the methods described herein for prostate disorders in general. That is, the methods described herein with respect to prostate cancer may also be used for diagnosing (or aiding in the diagnosis of) a prostate disorder, methods of monitoring progression/regression of a prostate disorder, methods of assessing efficacy of compositions for treating a prostate disorder, methods of screening a composition for activity in modulating biomarkers associated with a prostate disorder, methods of identifying potential drug targets for prostate disorder, and methods of treating a prostate disorder. Such methods could be conducted as described herein with respect to prostate cancer.
XI. Other Methods
[0097] Other methods of using the biomarkers discussed herein are also contemplated. For example, the methods described in U.S. Pat. No. 7,005,255 and U.S. patent application Ser. No. 10/695,265 may be conducted using a small molecule profile comprising one or more of the biomarkers disclosed herein.
[0098] In any of the methods listed herein, the biomarkers that are used may be selected from those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 having p-values of less than 0.05 and/or those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 having q-values of less than 0.10. The biomarkers that are used in any of the methods described herein may also be selected from those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer (as compared to the control) or that are decreased in remission (as compared to control or prostate cancer) by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent); and/or those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 that are increased in prostate cancer (as compared to the control or remission) or that are increased in remission (as compared to the control or prostate cancer) by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, by at least 100%, by at least 110%, by at least 120%, by at least 130%, by at least 140%, by at least 150%, or more.
EXAMPLES
[0099] The invention will be further explained by the following illustrative examples that are intended to be non-limiting.
I. General Methods
[0100] A. Identification of Metabolic Profiles for Prostate Cancer
[0101] Each sample was analyzed to determine the concentration of several hundred metabolites. Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed, and, after appropriate quality control (QC), the information derived from each analysis was recombined. Every sample was characterized according to several thousand characteristics, which ultimately amount to several hundred chemical species. The techniques used were able to identify novel and chemically unnamed compounds.
[0102] B. Statistical Analysis
[0103] The data was analyzed using T-tests to identify molecules (either known, named metabolites or unnamed metabolites) present at differential levels in a definable population or subpopulation (e.g., biomarkers for prostate cancer biological samples compared to control biological samples or compared to patients in remission from prostate cancer) useful for distinguishing between the definable populations (e.g., prostate cancer and control, low grade prostate cancer and high grade prostate cancer). Other molecules (either known, named metabolites or unnamed metabolites) in the definable population or subpopulation were also identified.
[0104] Data was also analyzed using Random Forest Analysis. Random forests give an estimate of how well individuals in a new data set can be classified into existing groups. Random forest analysis creates a set of classification trees based on continual sampling of the experimental units and compounds. Then each observation is classified based on the majority votes from all the classification trees. In statistics, a classification tree classifies the observations into groups based on combinations of the variables (in this instance variables are metabolites or compounds). There are many variations on the algorithms used to create trees. A tree algorithm searches for the metabolite (compound) that provides the largest split between the two groups. This produces nodes. Then at each node, the metabolite that provides the best split is used and so on. If the node cannot be improved on, then it stops at that node and any observation in that node is classified as the majority group.
[0105] Random forests classify based on a large number (e.g. thousands) of trees. A subset of compounds and a subset of observations are used to create each tree. The observations used to create the tree are called the in-bag samples, and the remaining samples are called the out-of-bag samples. The classification tree is created from the in-bag samples, and the out-of-bag samples are predicted from this tree. To get the final classification for an observation, the “votes” for each group are counted based on the times it was an out-of-bag sample. For example, suppose observation 1 was classified as a “Control” by 2,000 trees, but classified as “Disease” by 3,000 trees. Using “majority wins” as the criterion, this sample is classified as “Disease.”
[0106] The results of the random forest are summarized in a confusion matrix. The rows correspond to the true grouping, and the columns correspond to the classification from the random forest. Thus, the diagonal elements indicate the correct classifications. A 50% error would occur by random chance for 2 groups, 66.67% error for three groups by random chance, etc. The “Out-of-Bag” (OOB) Error rate gives an estimate of how accurately new observations can be predicted using the random forest model (e.g., whether a sample is from a diseased subject or a control subject).
[0107] It is also of interest to see which variables are more “important” in the final classifications. The “importance plot” shows the top compounds ranked in terms of their importance. There are different criteria for ranking the importance, but the general idea is that removing an important variable will cause a greater decrease in accuracy than a variable that is less important.
[0108] C. Biomarker Identification
[0109] Various peaks identified in the analyses (e.g. GC-MS, LC-MS, MS-MS), including those identified as statistically significant, were subjected to a mass spectrometry based chemical identification process.
Example 1
Tissue
[0110] Biomarkers were discovered by (1) analyzing tissue samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0111] The tissue samples used for the analysis were 16 control tissues that were cancer free tissues derived from sections of prostate tissue not containing cancer cells (i.e. from cancerous prostate glands and that were determined to be free of cancerous cells), 12 prostate tissue samples from localized prostate cancer tumors (i.e. lower grade prostate cancer) and 14 prostate tissue samples from distal metastatic prostate cancer tumors (i.e. high grade prostate cancer). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0112] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate Cancer vs. Control, Metastatic/High Grade Prostate Cancer vs. Control, Metastatic/High Grade Prostate Cancer vs. Lower Grade Prostate Cancer).
Biomarkers:
[0113] As listed below in Table 1, biomarkers were discovered that were differentially present between tissue samples from lower grade, localized prostate cancer tumors and Control prostate tissue that was determined to be free of cancerous cells (i.e. sections of prostate tissue not containing cancerous cells from cancerous prostate glands removed from the patient). Table 2 lists biomarkers that were discovered that were differentially present between tissue from prostate tumor samples from subjects with metastatic prostate cancer (i.e. high grade prostate cancer) and Control prostate tissue. Table 3 lists biomarkers that were discovered that were differentially present between tissue samples from prostate tumor samples from subjects with metastatic prostate cancer (i.e. high grade prostate cancer) and tissue samples from lower grade, localized prostate cancer tumors.
[0114] Tables 1-3 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer (PCA) mean level as compared to the control mean level (Table 1), the high grade prostate cancer mean level as compared to the control mean level (Table 2), and the high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 3). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refer to the GC library and the number 61 refers to the LC library.
[0000]
TABLE 1
Prostate Cancer Biomarkers from subjects with Lower Grade Prostate
Cancer compared to Control subjects.
%
Li-
Change
COMPOUND
brary
p-value
q-value
in PCA
Metabolite-3139
61
<0.0001
0.0019
147%
Metabolite-1114
61
<0.0001
0.0053
55%
uridine
61
1.00E-04
0.0064
71%
Metabolite-3778
61
1.00E-04
0.0064
−67%
dethiobiotin
50
1.00E-04
0.0064
62%
Metabolite-3094
50
1.00E-04
0.0075
62%
N-acetyl-D-galactosamine
50
2.00E-04
0.0092
214%
4-hydroxy-2-
61
3.00E-04
0.0092
110%
quinolinecarboxylic acid
Metabolite-4019
50
3.00E-04
0.0092
104%
Metabolite-2688
61
3.00E-04
0.0092
20%
proline
50
3.00E-04
0.0092
59%
Metabolite-1111-possible-
61
3.00E-04
0.0092
92%
methylnitronitroso-
guanidine-or-ethyl-
thiocarbamoylacetate
glutamic acid
50
4.00E-04
0.0095
83%
3-hydroxy-3-
50
5.00E-04
0.0107
82%
methylglutarate
Metabolite-3810
61
6.00E-04
0.0119
−45%
Metabolite-1576
61
6.00E-04
0.0119
116%
Metabolite-4637
50
7.00E-04
0.0134
55%
Metabolite-1595-possible-
61
7.00E-04
0.0134
−58%
glutathione-metabolite
glycine
50
8.00E-04
0.0142
67%
leucine
50
9.00E-04
0.0145
61%
threonine
50
9.00E-04
0.0145
51%
histidine
50
0.001
0.0151
58%
anthranilic acid
50
0.0012
0.0167
53%
asparagine
50
0.0012
0.0167
81%
L-allo-threonine
50
0.0014
0.0177
48%
n-hexadecanoic acid
50
0.0014
0.0177
36%
1-7-dihydro-6h-purin-
61
0.0016
0.0193
43%
6-one
N-acetyl-D-glucosamine
50
0.0016
0.0193
125%
DL-homocysteine
61
0.0019
0.021
118%
sn-Glycerol-3-phosphate
50
0.0019
0.021
98%
Isobar-2-includes-3-
61
0.0021
0.0219
58%
amino-isobutyrate-2-
amino-butyrate-4-
aminobutanoic acid-
dimethylglycine-choline-
3-phospho-l-serine
61
0.0023
0.0228
18%
Isobar-27-includes-L-
61
0.0024
0.0228
90%
kynurenine-alpha-2-
diamino-gamma-
oxobenzenebutanoic acid
Metabolite-4051
50
0.0024
0.0228
108%
alpha-amino-adipate
50
0.0026
0.0228
99%
Metabolite-4117-possible-
61
0.0026
0.0228
163%
propranolol-or-2-heptyl-3-
hydroxy-quinolone
cholesterol
50
0.0027
0.0228
46%
Metabolite-5128
61
0.0027
0.0228
−85%
Isobar-6-includes-valine-
61
0.0029
0.0228
36%
betaine
Metabolite-4616
61
0.0029
0.0228
269%
Metabolite-4015
50
0.0029
0.0228
102%
Metabolite-2973
50
0.0029
0.0228
−25%
valine
50
0.003
0.0233
38%
malic acid
50
0.0032
0.0237
62%
Metabolite-1211
61
0.0033
0.0241
−52%
Isobar-22-includes-
61
0.0037
0.0263
44%
glutamic
acid-O-acetyl-L-serine
tetradecanoic acid
50
0.0038
0.0263
59%
phosphate
50
0.0039
0.0265
68%
possible-ISOBAR-DL-
50
0.004
0.0267
71%
aspartic acid-
Metabolite-2466
61
0.0041
0.0271
99%
Metabolite-2548
61
0.0044
0.0283
−32%
Metabolite-3848
61
0.0045
0.0283
117%
Metabolite-2109
61
0.0046
0.0283
120%
tryptophan
61
0.0046
0.0283
38%
2-acetamido-1-amino-1-2-
50
0.0054
0.0324
134%
dideoxy-beta-D-
glucopyranose
Metabolite-3998
50
0.0057
0.0324
53%
5-oxoproline
50
0.0057
0.0324
48%
riboflavine
61
0.0058
0.0324
67%
phytonadione
50
0.0059
0.0324
45%
Metabolite-2074
61
0.0059
0.0324
−42%
9-12-octadecadienoic
50
0.0061
0.0328
74%
acid-z-z-carnitine
61
0.0063
0.033
47%
Metabolite-3370
61
0.0063
0.033
37%
uracil
50
0.0067
0.0343
129%
noradrenaline
50
0.0068
0.0344
50%
tyrosine
61
0.007
0.0348
41%
cysteine
50
0.0073
0.036
800%
25-hydroxycholesterol
50
0.0075
0.0364
18%
Metabolite-4030-possible-
61
0.0076
0.0366
109%
glutethimide-or-securinine
N-acetylserotonin
50
0.008
0.0376
279%
Metabolite-2108
61
0.0081
0.0376
78%
phenylalanine
61
0.0082
0.0376
36%
Isobar-3-includes-inositol-
61
0.0088
0.0395
63%
1- phosphate-mannose-6-
phosphate-glucose-6-
phosphate-D-mannose-1-
phosphate-alpha-D-
glucose-1-phosphate-alpha-
D-galactose-1-phosphate
Metabolite-1713
61
0.0089
0.0395
82%
Metabolite-1977
61
0.0094
0.0412
218%
octadecanoic acid
50
0.0099
0.0429
25%
3-nitro-L-tyrosine
50
0.0101
0.0434
82%
Metabolite-2064
61
0.0112
0.0472
44%
Metabolite-2389
61
0.0123
0.051
36%
Metabolite-4617
61
0.0124
0.051
53%
orotidine-5-phosphate
61
0.013
0.0528
125%
serine
50
0.0135
0.0542
40%
spermine
50
0.0143
0.0565
−78%
Metabolite-2041
61
0.0145
0.0565
157%
Metabolite-1465
61
0.0146
0.0565
174%
N-5-aminocarbonyl-
50
0.0158
0.0607
136%
L-ornithine
2-deoxy-D-ribose
61
0.0164
0.062
44%
heptadecanoic acid
50
0.0168
0.0622
76%
Metabolite-3165
61
0.0172
0.0622
26%
methionine
61
0.0173
0.0622
43%
S-adenosyl-l-homocysteine
61
0.0173
0.0622
41%
Isobar-24-includes-L-
61
0.0174
0.0622
46%
arabitol-adonitol
glycerol
50
0.0175
0.0622
51%
Metabolite-2690
61
0.019
0.0662
147%
Metabolite-3176-possible-
61
0.0191
0.0662
−22%
creatine
Metabolite-4632
50
0.0197
0.0675
44%
aspartate
61
0.0207
0.0695
54%
Metabolite-3027
50
0.0207
0.0695
108%
mannose-6-phosphate
50
0.022
0.0734
179%
Metabolite-5215
50
0.0225
0.0742
−27%
Metabolite-2055
61
0.0229
0.0744
−35%
uridine-5-monophosphate
61
0.023
0.0744
−38%
Metabolite-4046
50
0.0249
0.0797
305%
Metabolite-4355
50
0.0256
0.0797
36%
Metabolite-4058
50
0.0256
0.0797
104%
Carnosine
61
0.0256
0.0797
−45%
Metabolite-1070
61
0.0263
0.0811
109%
Metabolite-5228
50
0.0279
0.0852
52%
Metabolite-2753
61
0.0286
0.0861
224%
Metabolite-4116
61
0.0289
0.0861
34%
Metabolite-2272
61
0.0292
0.0861
152%
Metabolite-4027
50
0.0294
0.0861
145%
xanthine
61
0.0298
0.0861
172%
Metabolite-2924
50
0.0298
0.0861
51%
N-N-dimethylarginine
61
0.0318
0.0911
224%
Metabolite-4017
50
0.0322
0.0915
52%
glutamine
50
0.0333
0.0924
39%
isoleucine
50
0.0335
0.0924
26%
Metabolite-1498
61
0.0336
0.0924
48%
adenine
50
0.0336
0.0924
65%
Metabolite-2005
61
0.0345
0.0941
45%
sarcosine
50
0.0354
0.0958
150%
Metabolite-3498
61
0.0366
0.098
55%
Metabolite-5210
50
0.0396
0.1052
−23%
arginino-succinate
61
0.043
0.1132
93%
Putrescine
50
0.0432
0.1132
−82%
Metabolite-1104
61
0.0441
0.1144
−35%
taurine
61
0.0455
0.1171
−21%
Metabolite-1597
61
0.0461
0.1178
29%
Metabolite-4043
50
0.0469
0.119
33%
Metabolite-3183-possible-
61
0.0475
0.1195
107%
gamma-L-glutamyl-L-
phenylalanine-or-
aspartame
N-6-trimethyl-l-lysine
61
0.0486
0.1215
35%
Metabolite-2250
61
0.0508
0.1261
71%
creatinine
61
0.0514
0.1261
−25%
melatonin
50
0.0516
0.1261
111%
Metabolite-2105
61
0.0541
0.1311
100%
2-deoxyuridine-5-
61
0.0571
0.1375
−41%
triphosphate
tyramine
50
0.0591
0.1404
32%
inositol-1-phosphate
50
0.0592
0.1404
40%
4-methyl-2-oxopentanoate
61
0.0597
0.1405
162%
Metabolite-5186
61
0.0601
0.1406
600%
fumaric acid
50
0.0638
0.1482
82%
2-deoxyuridine
61
0.0676
0.156
74%
Metabolite-1085-possible-
61
0.0688
0.1576
45%
isolobinine-or-4-
aminoestra-1-3-5-10-
triene-3-17beta-diol
Metabolite-4868-possible-
61
0.0703
0.1598
114%
Bradykinin
Metabolite-2846
61
0.0753
0.1701
141%
arachidonic acid
50
0.0765
0.1705
52%
Metabolite-1831-possible-
61
0.0769
0.1705
30%
Cl-adduct-of-citrulline
Metabolite-3099
50
0.0771
0.1705
43%
trans-4-hydroxyproline
50
0.0776
0.1705
63%
Metabolite-3783
61
0.0782
0.1708
−39%
L-alpha-
61
0.0793
0.172
58%
glycerophosphorylcholine
glycerate
61
0.0798
0.172
42%
cytidine
61
0.0819
0.1741
101%
Isobar-40-includes-
61
0.0825
0.1741
−41%
Maltotetraose-stachyose
Metabolite-1679
61
0.0831
0.1741
347%
Metabolite-4032
50
0.0836
0.1741
108%
Metabolite-3752
61
0.0841
0.1741
756%
Isobar-32-includes-N-
61
0.0847
0.1741
34%
acetyl-D-glucosamine-N-
acetyl-D-mannosamine
pantothenic acid
61
0.0849
0.1741
40%
glyceric acid
50
0.085
0.1741
27%
xylitol
50
0.0907
0.1831
65%
Metabolite-2075
61
0.0915
0.1831
148%
Metabolite-3430
61
0.0916
0.1831
63%
Metabolite-3668
61
0.0917
0.1831
−47%
5-6-dihydrouracil
61
0.0928
0.1831
94%
Metabolite-3138
61
0.0933
0.1831
62%
Metabolite-2056
61
0.0933
0.1831
−20%
Metabolite-4362
50
0.0944
0.1834
−41%
Metabolite-4514
50
0.095
0.1834
−19%
Metabolite-2607
61
0.0959
0.1834
−45%
Isobar-21-includes-gamma-
61
0.096
0.1834
70%
aminobutyryl-L-histidine-L-
anserine
Isobar-5-includes-
61
0.0963
0.1834
57%
asparagine-ornithine
Metabolite-3957
61
0.0968
0.1834
43%
Isobar-30-includes-
61
0.0993
0.1867
−35%
maltotetraose-stachyose
D-sorbitol-6-phosphate
50
0.0996
0.1867
53%
Metabolite-2981
50
0.1017
0.1894
17%
ribulose-5-phosphate
50
0.1041
0.1929
−25%
Metabolite-3123
61
0.1082
0.1987
−42%
Isobar-18-includes-D-
61
0.1085
0.1987
67%
fructose-1-phosphate-beta-
D-fructose-6-phosphate
Metabolite-1593
61
0.111
0.2022
−44%
uric acid
61
0.1119
0.2027
−19%
Metabolite-3178
61
0.1128
0.2027
−30%
Metabolite-1455
61
0.1131
0.2027
−81%
Metabolite-1286
61
0.1145
0.204
−16%
Isobar-1-includes-mannose-
61
0.1166
0.2068
−35%
fructose-glucose-galactose-
alpha-L-sorbopyranose-
Inositol-D-allose
o-phosphoethanolamine
50
0.1196
0.211
44%
Metabolite-1608
61
0.1206
0.2115
−59%
Metabolite-3539
61
0.1217
0.2123
−57%
Metabolite-4593
50
0.1257
0.217
37%
palmitoleic acid
50
0.1257
0.217
78%
Metabolite-3896
61
0.1274
0.2176
65%
1-methyladenosine
61
0.1274
0.2176
100%
Metabolite-1203-possible-
61
0.1333
0.2253
86%
acetylbrowniine-tricornine-
germine-or-veracevine
Metabolite-3771
61
0.1338
0.2253
−18%
pyridoxamine-phosphate
61
0.1341
0.2253
−33%
Metabolite-2212
61
0.135
0.2253
320%
Spermidine
50
0.1367
0.2253
−51%
Metabolite-3992-
61
0.1375
0.2253
14%
Metabolite-3044
61
0.1385
0.2253
30%
3-methyl-L-histidine
61
0.1389
0.2253
21%
Metabolite-2546
61
0.1393
0.2253
−36%
fructose
50
0.1396
0.2253
−47%
Metabolite-3816
61
0.1397
0.2253
−43%
Metabolite-2255
61
0.1406
0.2253
44%
Metabolite-3073
50
0.1407
0.2253
−39%
succinate
50
0.1456
0.2314
−54%
Metabolite-2292
61
0.1459
0.2314
−35%
glutathione-reduced
61
0.1467
0.2314
−43%
alanine
50
0.1494
0.2346
21%
Metabolite-4053
50
0.1527
0.2387
26%
Metabolite-4567
61
0.1555
0.2419
−37%
Metabolite-3832-possible-
61
0.1614
0.2499
−30%
phenol-sulfate
Metabolite-5189
61
0.1668
0.2571
263%
saccharopine
61
0.1679
0.2575
23%
Metabolite-1216
61
0.1699
0.2577
53%
Metabolite-5227
50
0.1704
0.2577
45%
citric acid
50
0.1708
0.2577
−37%
catechol
61
0.1712
0.2577
77%
Metabolite-4615
61
0.1733
0.2594
−13%
Metabolite-3808
61
0.1747
0.2594
−20%
Metabolite-1609
61
0.1753
0.2594
−35%
D-allose
50
0.1754
0.2594
−37%
elaidic acid
50
0.1821
0.2681
84%
Metabolite-2129
61
0.1835
0.269
110%
Metabolite-2185
61
0.1864
0.2706
35%
azelaic acid
61
0.1875
0.2706
63%
Metabolite-1088
61
0.1879
0.2706
81%
Metabolite-5232
50
0.1879
0.2706
109%
Isobar-17-includes-
61
0.1887
0.2706
25%
arginine-N-
alpha-acetyl-ornithine
hypotaurine
50
0.1917
0.2736
36%
Metabolite-4150
50
0.1936
0.2744
−36%
Metabolite-2111
61
0.1939
0.2744
33%
Metabolite-1457
61
0.1957
0.2758
−35%
DL-cystathionine
50
0.1983
0.2783
22%
Metabolite-5147
61
0.2019
0.2822
243%
Metabolite-3476
61
0.2033
0.2828
−23%
benzoic acid
50
0.2043
0.2831
−14%
Metabolite-5109
61
0.2069
0.2843
89%
Metabolite-3102
50
0.2082
0.2843
25%
Metabolite-3974
61
0.2083
0.2843
38%
Metabolite-1351
61
0.2086
0.2843
19%
mannose
50
0.2108
0.2858
−32%
quinolinic acid
61
0.2114
0.2858
42%
gamma-L-glutamyl-
61
0.2161
0.2896
−28%
L-glutamine
Metabolite-1186
61
0.2164
0.2896
−54%
Metabolite-2766
61
0.2183
0.2896
−34%
phosphoenolpyruvate
50
0.2184
0.2896
105%
Metabolite-4080
50
0.2187
0.2896
71%
Metabolite-2139
61
0.221
0.2915
41%
Metabolite-2900-
61
0.222
0.2915
24%
Metabolite-2388
61
0.2232
0.2915
24%
2-deoxy-D-glucose
50
0.2236
0.2915
−30%
5-hydroxyindoleacetate
50
0.2255
0.2928
210%
Metabolite-4869
61
0.2292
0.2964
−38%
Metabolite-2774
61
0.2377
0.306
47%
Metabolite-2232
61
0.2385
0.306
−36%
3-methoxy-L-tyrosine
50
0.2401
0.3069
−29%
inositol
50
0.2414
0.3071
−29%
glucono-gamma-lactone
50
0.2434
0.3071
−31%
Metabolite-4133
50
0.2441
0.3071
34%
Metabolite-4014
50
0.2444
0.3071
−17%
galactose
50
0.2449
0.3071
30%
Metabolite-3813
61
0.248
0.3097
115%
Metabolite-1980
61
0.2537
0.3151
119%
Metabolite-5108
61
0.2542
0.3151
72%
Metabolite-2703
61
0.2562
0.3165
31%
Metabolite-5110
61
0.2632
0.3239
63%
Metabolite-5207
50
0.2649
0.3247
13%
Metabolite-2027
61
0.2671
0.3262
47%
2-keto-L-gulonic acid
50
0.2795
0.34
12%
Metabolite-3064
61
0.2832
0.3434
50%
glucose-6-phosphate
50
0.2849
0.3439
−28%
Metabolite-5166
61
0.2857
0.3439
49%
3-amino-isobutyrate
50
0.2892
0.3457
−27%
dulcitol
50
0.2894
0.3457
−27%
Metabolite-3034
50
0.2933
0.349
22%
Metabolite-4667
61
0.2942
0.349
18%
Metabolite-2806
61
0.2996
0.3541
−12%
Metabolite-5089
61
0.3011
0.3541
−65%
4-hydroxyphenylpyruvate
61
0.3034
0.3541
−17%
Metabolite-4075
50
0.3039
0.3541
36%
Metabolite-4235
61
0.3039
0.3541
−67%
glutarate
61
0.3122
0.358
47%
beta-nicotinamide-adenine-
61
0.3134
0.358
445%
dinucleotide
Metabolite-1327-possible-
61
0.3175
0.358
30%
bilirubin
guanine
50
0.3177
0.358
26%
Metabolite-1323-possible-
61
0.3181
0.358
−31%
4-sulfobenzyl-alcohol
Metabolite-3708
61
0.3196
0.358
−10%
Metabolite-4706
61
0.3202
0.358
42%
Metabolite-3545
61
0.3204
0.358
76%
Metabolite-3132
61
0.3217
0.358
23%
niacinamide
61
0.3243
0.358
12%
Metabolite-3514-retired-
61
0.3248
0.358
−89%
topiramate
Metabolite-5167
61
0.3248
0.358
43%
Metabolite-5170
61
0.3251
0.358
854%
Metabolite-3951
61
0.3267
0.358
13%
Metabolite-2768
61
0.3321
0.358
798%
allantoin
61
0.3332
0.358
−15%
Metabolite-2347
61
0.3332
0.358
−16%
Metabolite-3436
61
0.3332
0.358
−21%
Metabolite-5087
61
0.3338
0.358
−53%
Metabolite-3576
61
0.3374
0.358
23%
Metabolite-3694
61
0.3383
0.358
36%
Metabolite-3522
61
0.3398
0.358
−85%
Metabolite-2406
61
0.3409
0.358
31%
Metabolite-3364
61
0.3409
0.358
12%
Metabolite-3997
61
0.3409
0.358
43%
Metabolite-4018
61
0.3409
0.358
38%
suberic acid
61
0.3409
0.358
15%
Metabolite-3022
50
0.3409
0.358
8%
Metabolite-1329
61
0.3409
0.358
10%
Metabolite-3756
61
0.3409
0.358
25%
Metabolite-5086
61
0.3409
0.358
−41%
Metabolite-1911
61
0.3431
0.3582
64%
gamma-glu-cys
61
0.3432
0.3582
60%
N-acetylneuraminate
61
0.3469
0.3609
−14%
Metabolite-2691
61
0.3544
0.3669
33%
Metabolite-3531
61
0.3572
0.3669
−70%
Metabolite-3180
61
0.3575
0.3669
46%
L-homoserine-lactone
61
0.3583
0.3669
12%
Metabolite-1974
61
0.3584
0.3669
−18%
Metabolite-2141
61
0.3594
0.3669
29%
Metabolite-1333
61
0.3625
0.3684
28%
GABA
50
0.3631
0.3684
−20%
adenosine
61
0.3676
0.3719
−18%
Metabolite-5226
50
0.3709
0.3741
33%
Metabolite-2036
61
0.3733
0.3748
−38%
Metabolite-1616
61
0.3739
0.3748
76%
Metabolite-3833
61
0.3752
0.375
20%
Metabolite-2348
61
0.3836
0.3813
69%
S-5-adenosyl-L-methionine
61
0.3839
0.3813
30%
Metabolite-4331
61
0.3854
0.3817
26%
Metabolite-3475
61
0.3873
0.3824
−19%
n-dodecanoate
50
0.3957
0.3895
15%
Metabolite-3952
61
0.399
0.3914
−14%
Metabolite-3837
61
0.3999
0.3914
−33%
Metabolite-1819
61
0.4015
0.3917
−15%
Metabolite-2853
61
0.4036
0.3926
−20%
Metabolite-3517
61
0.4048
0.3926
−34%
Metabolite-3526
61
0.4155
0.4018
−23%
Metabolite-2711
61
0.4182
0.4029
11%
5-s-methyl-5-
61
0.419
0.4029
33%
thioadenosine
xanthosine
50
0.4265
0.4088
−18%
Metabolite-5107
61
0.4345
0.4153
36%
Metabolite-1248-possible-
61
0.4438
0.421
22%
avermectin-aglycone
ornithine
50
0.4438
0.421
19%
Metabolite-3984
61
0.4443
0.421
58%
Metabolite-3215
61
0.4466
0.4219
−18%
Metabolite-2181
61
0.45
0.423
23%
Metabolite-1392
61
0.4505
0.423
−49%
Metabolite-4512
50
0.4516
0.423
34%
Metabolite-5209
50
0.4539
0.4241
−16%
Metabolite-2198
61
0.4573
0.4251
−19%
Metabolite-4931
61
0.4578
0.4251
11%
Metabolite-3604
61
0.4589
0.4251
30%
maltose
50
0.4614
0.4253
−13%
Metabolite-1330
61
0.4623
0.4253
−50%
Metabolite-1843
61
0.4644
0.4253
35%
Metabolite-5214
50
0.4665
0.4253
−19%
Metabolite-3056
61
0.467
0.4253
−23%
Metabolite-4084
50
0.468
0.4253
−5%
Metabolite-2567
61
0.4682
0.4253
15%
Metabolite-3893
61
0.4774
0.4323
−14%
Metabolite-3543
61
0.4785
0.4323
−47%
Metabolite-4503
50
0.4815
0.4338
21%
Isobar-31-includes-
61
0.4912
0.4406
−14%
maltotriose-melezitose
histamine
61
0.4917
0.4406
−13%
D-ribose
50
0.4931
0.4407
−17%
Metabolite-3390
61
0.4987
0.4445
−4%
6-phosphogluconic acid
61
0.5166
0.4592
−7%
Metabolite-2319
61
0.5186
0.4597
24%
lactate
50
0.523
0.4624
8%
Metabolite-4096-
61
0.5325
0.4695
−7%
gamma-glu-gly-leu-
Metabolite-4518
50
0.5347
0.4701
22%
Metabolite-1129
61
0.536
0.4701
23%
Metabolite-3003
50
0.5401
0.4724
15%
Metabolite-5213
50
0.5456
0.476
−11%
Metabolite-1069-possible-
61
0.549
0.4771
25%
dehydroepiandrosterone-
sulfate-
Metabolite-1575
61
0.5511
0.4771
−16%
3-hydroxybutanoic acid
50
0.5512
0.4771
−22%
Metabolite-4238
61
0.553
0.4773
14%
pyrophosphate
50
0.5551
0.4779
20%
Metabolite-2867
61
0.5592
0.4788
25%
Metabolite-1718
61
0.5602
0.4788
20%
arabinose
50
0.5604
0.4788
−14%
Metabolite-3401
61
0.5676
0.4836
−18%
beta-alanine
50
0.5697
0.4842
−12%
Metabolite-2897
61
0.5738
0.4856
−13%
Metabolite-1394-possible-
61
0.5743
0.4856
23%
Losartan
Metabolite-4428
61
0.5759
0.4857
21%
Metabolite-2099
61
0.5866
0.4924
26%
Metabolite-3220
61
0.5868
0.4924
10%
Metabolite-3317
61
0.5908
0.4932
19%
biliverdin
61
0.5908
0.4932
−12%
Metabolite-3002
50
0.5925
0.4934
6%
Metabolite-3955
61
0.5991
0.4976
−4%
Metabolite-3020
50
0.6009
0.4979
12%
Metabolite-3189
61
0.6061
0.5009
−23%
Metabolite-1970
61
0.6121
0.5046
19%
Metabolite-1963
61
0.6203
0.5078
−9%
Metabolite-1113-possible-
61
0.6216
0.5078
−6%
acetylcarnitine-or-
isopentyl-adenine
Metabolite-3016
50
0.6232
0.5078
−12%
caffeine
61
0.6241
0.5078
22%
ethylmalonic acid
61
0.6247
0.5078
38%
cystine
50
0.6255
0.5078
8%
Metabolite-2558
61
0.6268
0.5078
−21%
uridine-5-
50
0.629
0.5084
8%
diphosphoglucose
3-methyl-2-oxovaleric acid
61
0.634
0.5112
26%
dihydroxyacetone-
61
0.6396
0.5144
11%
phosphate
Metabolite-4497
50
0.6462
0.5184
−12%
Metabolite-2313
61
0.649
0.5184
7%
Metabolite-3085
50
0.6493
0.5184
−5%
Metabolite-3996
50
0.6552
0.521
−9%
L-histidinol
61
0.6557
0.521
−9%
Metabolite-1573
61
0.6598
0.5231
−9%
Metabolite-2407
61
0.6624
0.5238
−18%
Metabolite-5126
61
0.665
0.5246
11%
Metabolite-4448
61
0.6685
0.5261
−8%
alpha-D-ribose-5-
50
0.6795
0.5319
9%
phosphate
cytidine-5-
61
0.6818
0.5319
11%
monophosphate
Metabolite-1979-Cl-
61
0.6823
0.5319
5%
adduct-of-C6H10O5
Metabolite-2-Aminoethyl-
61
0.6831
0.5319
4%
phosphonate
sorbitol
50
0.6839
0.5319
−21%
Metabolite-2368
61
0.6862
0.5324
56%
Metabolite-1961-retired-
61
0.7054
0.5461
45%
glycocholic acid
Metabolite-4523
50
0.7076
0.5464
7%
alpha-4-
50
0.7136
0.5498
20%
dihydroxybenzene-
propanoic acid
Metabolite-1342-possible-
61
0.728
0.5591
−15%
phenylacetylglutamine
Metabolite-4020
50
0.7305
0.5591
9%
Metabolite-3554
61
0.7316
0.5591
14%
Metabolite-2174
61
0.7325
0.5591
9%
Metabolite-4002
50
0.7391
0.5629
8%
DL-pipecolic acid
61
0.7474
0.5674
−8%
Metabolite-2824
61
0.7484
0.5674
14%
Metabolite-3807
61
0.7516
0.5685
−4%
Metabolite-3129
61
0.7585
0.5724
−3%
Metabolite-2194
61
0.7641
0.5735
−9%
ascorbic acid
50
0.7647
0.5735
−10%
biotin
61
0.7657
0.5735
−9%
Metabolite-1975
61
0.7669
0.5735
−8%
Metabolite-1349
61
0.7721
0.576
−6%
Metabolite-2072
61
0.7799
0.5792
−9%
Metabolite-1142-
61
0.7817
0.5793
4%
possible-5-hydroxy-
pentanoate-or-beta-
hydroxyisovaleric acid
Metabolite-4806
50
0.7875
0.581
3%
Metabolite-4796
50
0.7882
0.581
−9%
4-Guanidinobutanoic acid
61
0.7894
0.581
6%
Metabolite-3489
61
0.7984
0.5855
−7%
Metabolite-1116
61
0.799
0.5855
−5%
Metabolite-2827
61
0.8024
0.5867
13%
Metabolite-3772
61
0.814
0.5923
4%
Metabolite-2143
61
0.8147
0.5923
−12%
Metabolite-3960
61
0.8168
0.5923
2%
Metabolite-3040
50
0.8172
0.5923
3%
Metabolite-3994
61
0.8202
0.5931
−8%
Metabolite-2180
61
0.8237
0.5944
−7%
Metabolite-2118
61
0.8311
0.5974
−3%
Metabolite-4787
61
0.8315
0.5974
15%
Metabolite-4516
50
0.8341
0.5979
−6%
Metabolite-4168
61
0.8386
0.598
4%
uridine-5-
50
0.841
0.598
7%
diphosphoglucuronic
acid
Metabolite-4134
50
0.8433
0.598
3%
Metabolite-4271
50
0.8442
0.598
−17%
Metabolite-2121
61
0.8444
0.598
8%
Metabolite-4013
61
0.8451
0.598
5%
urea
50
0.8512
0.6007
−2%
Metabolite-4272
50
0.8534
0.6007
−4%
Metabolite-1653
61
0.855
0.6007
6%
Metabolite-1183
61
0.8561
0.6007
9%
Metabolite-5229
50
0.8587
0.6012
3%
glucarate
50
0.8678
0.6063
14%
Metabolite-1187
61
0.8864
0.6163
5%
beta-D-lactose
50
0.8875
0.6163
3%
Metabolite-2279
61
0.8877
0.6163
−4%
Metabolite-5212
50
0.8914
0.617
3%
alpha-L-sorbopyranose
50
0.8925
0.617
−3%
Metabolite-4354
50
0.9014
0.6219
−2%
Metabolite-3014
50
0.9104
0.6256
1%
Metabolite-3534
61
0.9131
0.6256
−5%
Metabolite-3966
61
0.9137
0.6256
−4%
Metabolite-1497
61
0.9149
0.6256
−2%
Metabolite-3379
61
0.9178
0.6256
−2%
Metabolite-1288
61
0.9188
0.6256
3%
Metabolite-2237
61
0.9222
0.6256
4%
Metabolite-3755
61
0.9248
0.6256
2%
Metabolite-3980
61
0.9253
0.6256
−3%
picolinic acid
61
0.9259
0.6256
3%
Metabolite-2821
61
0.9284
0.6261
−2%
L-kynurenine
50
0.9317
0.627
−3%
inosine
61
0.9399
0.6272
−1%
Metabolite-2724
61
0.9415
0.6272
−1%
Isobar-19-includes-
61
0.9431
0.6272
1%
D-saccharic acid-
2-deoxy-D-galactose-
2-deoxy-D-glucose-L-
fucose-L-rhamnose
Metabolite-4510
50
0.9434
0.6272
−1%
alpha-keto-glutarate
61
0.9448
0.6272
−6%
3-methylglutaric acid
61
0.9453
0.6272
0%
Metabolite-3051
61
0.9454
0.6272
2%
Metabolite-3484
61
0.9472
0.6272
−3%
Metabolite-1303
61
0.9513
0.6276
−2%
Metabolite-3074
50
0.9517
0.6276
3%
guanosine
61
0.9553
0.6288
0%
hippuric acid
61
0.9589
0.6288
2%
Metabolite-5211
50
0.9591
0.6288
3%
Metabolite-5187
61
0.9644
0.6297
1%
Metabolite-1496
61
0.9648
0.6297
0%
Metabolite-4550
61
0.9663
0.6297
−2%
Metabolite-3365
61
0.97
0.6309
1%
Metabolite-4611
50
0.9734
0.6318
0%
Isobar-4-includes-Gluconic
61
0.9753
0.6318
1%
acid-DL-arabinose-D-
ribose-L-xylose-
DL-lyxose-D-xylulose
1-methyladenine
50
0.979
0.633
2%
3-phospho-d-glycerate
61
0.9819
0.633
1%
Metabolite-4365
50
0.9829
0.633
−1%
Metabolite-4866
61
0.9912
0.6371
0%
Metabolite-4003
61
0.9994
0.6412
0%
[0000]
TABLE 2
Prostate Cancer Biomarkers from subjects with Metastatic,
High Grade Prostate Cancer compared to Control subjects.
% Change
COMPOUND
Library
p-value
q-value
in PCA
inosine
61
<0.0001
<0.0001
−269%
Metabolite - 2-Aminoethyl-phosphonate
61
<0.0001
<0.0001
−437%
Metabolite - 1597
61
<0.0001
<0.0001
110%
Metabolite - 1498
61
<0.0001
<0.0001
188%
octadecanoic acid
50
<0.0001
<0.0001
136%
Metabolite - 3390
61
<0.0001
<0.0001
−330%
riboflavine
61
<0.0001
<0.0001
196%
leucine
50
<0.0001
<0.0001
216%
phosphate
50
<0.0001
<0.0001
150%
anthranilic acid
50
<0.0001
<0.0001
140%
glycerol
50
<0.0001
<0.0001
352%
Metabolite - 3808
61
<0.0001
<0.0001
−452%
valine
50
<0.0001
<0.0001
103%
Metabolite - 1595-possible-glutathione-
61
<0.0001
<0.0001
−695%
metabolite
n-hexadecanoic acid
50
<0.0001
<0.0001
365%
heptadecanoic acid
50
<0.0001
<0.0001
201%
Metabolite - 3998
50
<0.0001
<0.0001
101%
Metabolite - 1679
61
<0.0001
<0.0001
597%
phenylalanine
61
<0.0001
<0.0001
93%
Isobar-24-includes-L-arabitol-adonitol
61
<0.0001
<0.0001
313%
Metabolite - 2292
61
<0.0001
<0.0001
−644%
tryptophan
61
<0.0001
<0.0001
112%
Metabolite - 3893
61
<0.0001
<0.0001
−757%
xanthine
61
<0.0001
<0.0001
1072%
glycerate
61
<0.0001
<0.0001
375%
Metabolite - 3178
61
<0.0001
<0.0001
−1223%
ribulose-5-phosphate
50
<0.0001
<0.0001
−272%
noradrenaline
50
<0.0001
<0.0001
88%
Metabolite - 3085
50
<0.0001
<0.0001
−224%
Metabolite - 2272
61
<0.0001
<0.0001
594%
Metabolite - 4013
61
<0.0001
<0.0001
443%
taurine
61
<0.0001
<0.0001
−219%
uracil
50
<0.0001
<0.0001
933%
Metabolite - 3165
61
<0.0001
<0.0001
75%
Metabolite - 2973
50
<0.0001
<0.0001
−214%
histidine
50
<0.0001
<0.0001
120%
adenosine
61
<0.0001
1.00E−04
−276%
9-12-octadecadienoic acid-z-z-
50
<0.0001
1.00E−04
518%
isoleucine
50
<0.0001
1.00E−04
68%
Metabolite - 3772
61
<0.0001
1.00E−04
83%
DL-homocysteine
61
<0.0001
1.00E−04
216%
pantothenic acid
61
<0.0001
1.00E−04
164%
Metabolite - 3778
61
<0.0001
1.00E−04
−327%
Metabolite - 4611
50
<0.0001
1.00E−04
388%
Isobar-6-includes-valine-betaine
61
<0.0001
1.00E−04
78%
tetradecanoic acid
50
<0.0001
1.00E−04
810%
Metabolite - 3810
61
<0.0001
1.00E−04
−261%
proline
50
<0.0001
1.00E−04
209%
Metabolite - 1576
61
1.00E−04
1.00E−04
204%
Metabolite - 5210
50
1.00E−04
1.00E−04
−231%
4-hydroxyphenylpyruvate
61
1.00E−04
1.00E−04
−423%
Metabolite - 3102
50
1.00E−04
1.00E−04
918%
gamma-L-glutamyl-L-glutamine
61
1.00E−04
1.00E−04
−433%
Metabolite - 1977
61
1.00E−04
1.00E−04
382%
palmitoleic acid
50
1.00E−04
1.00E−04
1547%
n-dodecanoate
50
1.00E−04
1.00E−04
418%
Metabolite - 1114
61
1.00E−04
1.00E−04
106%
Metabolite - 4617
61
1.00E−04
1.00E−04
217%
Metabolite - 5107
61
1.00E−04
1.00E−04
268%
L-allo-threonine
50
1.00E−04
2.00E−04
86%
threonine
50
1.00E−04
2.00E−04
88%
Metabolite - 3138
61
1.00E−04
2.00E−04
268%
tyrosine
61
1.00E−04
2.00E−04
68%
Metabolite - 1349
61
1.00E−04
2.00E−04
−885%
arachidonic acid
50
1.00E−04
2.00E−04
164%
Metabolite - 4046
50
1.00E−04
2.00E−04
3090%
Metabolite - 4620
61
1.00E−04
2.00E−04
854%
Metabolite - 4075
50
1.00E−04
2.00E−04
971%
urea
50
2.00E−04
2.00E−04
234%
Metabolite - 2181
61
2.00E−04
2.00E−04
189%
Metabolite - 5209
50
2.00E−04
2.00E−04
−539%
Metabolite - 2108
61
2.00E−04
2.00E−04
155%
Metabolite - 1351
61
2.00E−04
2.00E−04
366%
glycine
50
2.00E−04
2.00E−04
101%
Metabolite - 3003
50
2.00E−04
2.00E−04
122%
Metabolite - 4134
50
2.00E−04
2.00E−04
458%
Metabolite - 1329
61
2.00E−04
2.00E−04
171%
Metabolite - 1394-possible-Losartan
61
2.00E−04
2.00E−04
158%
Metabolite - 3014
50
2.00E−04
2.00E−04
327%
Metabolite - 1116
61
3.00E−04
3.00E−04
446%
Metabolite - 5212
50
3.00E−04
3.00E−04
−488%
Metabolite - 1465
61
3.00E−04
3.00E−04
512%
Metabolite - 5228
50
3.00E−04
3.00E−04
86%
Isobar-2-includes-3-amino-isobutyrate-
61
3.00E−04
3.00E−04
249%
2-amino-butyrate-4-aminobutanoic acid-
dimethylglycine-choline-
glutathione-reduced
61
3.00E−04
3.00E−04
−819%
1-7-dihydro-6h-purin-6-one
61
3.00E−04
3.00E−04
63%
Metabolite - 2924
50
3.00E−04
3.00E−04
332%
methionine
61
3.00E−04
3.00E−04
68%
Metabolite - 4649
61
4.00E−04
3.00E−04
224%
fumaric acid
50
4.00E−04
3.00E−04
196%
Metabolite - 1593
61
4.00E−04
4.00E−04
−409%
inositol-1-phosphate
50
4.00E−04
4.00E−04
163%
Metabolite - 4051
50
4.00E−04
4.00E−04
663%
lactate
50
4.00E−04
4.00E−04
49%
Metabolite - 4117-possible-propranolol-
61
4.00E−04
4.00E−04
267%
or-2-heptyl-3-hydroxy-quinolone
N-N-dimethylarginine
61
4.00E−04
4.00E−04
267%
Metabolite - 3370
61
4.00E−04
4.00E−04
79%
citric acid
50
5.00E−04
4.00E−04
−1943%
glyceric acid
50
5.00E−04
4.00E−04
125%
Metabolite - 3215
61
5.00E−04
4.00E−04
110%
1-methyladenosine
61
6.00E−04
5.00E−04
620%
5-hydroxyindoleacetate
50
6.00E−04
5.00E−04
−319%
S-5-adenosyl-L-methionine
61
6.00E−04
5.00E−04
230%
catechol
61
7.00E−04
5.00E−04
595%
Metabolite - 5110
61
7.00E−04
5.00E−04
278%
Metabolite - 1069-possible-
61
7.00E−04
5.00E−04
−379%
dehydroepiandrosterone-sulfate-
Metabolite - 4593
50
7.00E−04
5.00E−04
113%
elaidic acid
50
7.00E−04
5.00E−04
526%
Metabolite - 3833
61
7.00E−04
6.00E−04
247%
Metabolite - 2711
61
8.00E−04
6.00E−04
84%
carnitine
61
8.00E−04
6.00E−04
155%
D-allose
50
8.00E−04
6.00E−04
−1265%
Metabolite - 3094
50
9.00E−04
6.00E−04
49%
Metabolite - 5108
61
9.00E−04
6.00E−04
237%
Metabolite - 3064
61
9.00E−04
6.00E−04
195%
L-alpha-glycerophosphorylcholine
61
9.00E−04
6.00E−04
361%
Metabolite - 5128
61
9.00E−04
6.00E−04
−2480%
Metabolite - 2567
61
9.00E−04
6.00E−04
132%
uric acid
61
9.00E−04
7.00E−04
142%
quinolinic acid
61
0.001
7.00E−04
173%
Metabolite - 4518
50
0.001
7.00E−04
618%
Metabolite - 4428
61
0.001
7.00E−04
210%
Metabolite - 5214
50
0.0011
7.00E−04
−421%
Metabolite - 3044
61
0.0011
7.00E−04
187%
Metabolite - 3816
61
0.0011
7.00E−04
−2267%
Metabolite - 1831-possible-Cl-adduct-
61
0.0011
7.00E−04
142%
of-citrulline
guanosine
61
0.0012
7.00E−04
−191%
3-methyl-L-histidine
61
0.0012
8.00E−04
83%
Metabolite - 1843
61
0.0012
8.00E−04
524%
cysteine
50
0.0012
8.00E−04
988%
Metabolite - 5187
61
0.0012
8.00E−04
354%
ethylmalonic acid
61
0.0012
8.00E−04
1277%
Metabolite - 2766
61
0.0012
8.00E−04
−2129%
Metabolite - 1104
61
0.0014
8.00E−04
−200%
3-methoxy-L-tyrosine
50
0.0014
9.00E−04
−570%
Metabolite - 3807
61
0.0014
9.00E−04
346%
DL-pipecolic acid
61
0.0015
9.00E−04
296%
Metabolite - 2041
61
0.0015
9.00E−04
198%
malic acid
50
0.0015
9.00E−04
88%
Metabolite - 4331
61
0.0016
9.00E−04
97%
Metabolite - 5166
61
0.0017
0.001
157%
Metabolite - 2111
61
0.0018
0.001
134%
Metabolite - 5167
61
0.0018
0.001
146%
Metabolite - 2867
61
0.0018
0.001
−6300%
3-phospho-d-glycerate
61
0.0018
0.001
−210%
Metabolite - 2109
61
0.0019
0.001
179%
Metabolite - 5232
50
0.0019
0.0011
422%
D-ribose
50
0.002
0.0011
−466%
Metabolite - 3771
61
0.002
0.0011
−163%
alanine
50
0.002
0.0011
86%
Metabolite - 2753
61
0.002
0.0011
227%
xanthosine
50
0.002
0.0011
−391%
arabinose
50
0.002
0.0011
−437%
Metabolite - 1323-possible-4-
61
0.0021
0.0011
311%
sulfobenzyl-alcohol
Metabolite - 3489
61
0.0021
0.0011
−552%
trans-4-hydroxyproline
50
0.0022
0.0011
208%
Metabolite - 3966
61
0.0022
0.0012
159%
Metabolite - 1713
61
0.0025
0.0013
212%
Metabolite - 2237
61
0.0026
0.0013
307%
Metabolite - 2548
61
0.0026
0.0013
97%
Metabolite - 3364
61
0.0026
0.0013
272%
melatonin
50
0.0026
0.0013
227%
Isobar-5-includes-asparagine-ornithine
61
0.0028
0.0014
105%
Metabolite - 1819
61
0.0029
0.0014
69%
inositol
50
0.0029
0.0014
−541%
spermine
50
0.0029
0.0014
−5110%
Metabolite - 1288
61
0.003
0.0014
221%
Metabolite - 5109
61
0.0031
0.0015
385%
thymine
50
0.0031
0.0015
561%
Isobar-19-includes-D-saccharic acid-2-
61
0.0031
0.0015
−213%
deoxy-D-galactose-2-deoxy-D-glucose-
L-fucose-L-rhamnose
Metabolite - 2141
61
0.0032
0.0015
263%
Metabolite - 1327-possible-bilirubin
61
0.0033
0.0015
84%
Metabolite - 2900-
61
0.0034
0.0016
152%
alpha-4-dihydroxybenzenepropanoic
50
0.0034
0.0016
2300%
acid
Metabolite - 3183-possible-gamma-L-
61
0.0035
0.0016
241%
glutamyl-L-phenylalanine-or-aspartame
glutamic acid
50
0.0036
0.0017
114%
5-s-methyl-5-thioadenosine
61
0.0036
0.0017
235%
2-deoxy-D-ribose
61
0.0037
0.0017
68%
4-hydroxy-2-quinolinecarboxylic acid
61
0.0037
0.0017
81%
Metabolite - 4869
61
0.0038
0.0017
184%
Metabolite - 4015
50
0.0038
0.0017
247%
N-acetylserotonin
50
0.0038
0.0017
1007%
allantoin
61
0.0039
0.0018
164%
Metabolite - 2118
61
0.0041
0.0018
−138%
Metabolite - 2323
61
0.0041
0.0018
111%
Isobar-22-includes-glutamic acid-O-
61
0.0041
0.0018
52%
acetyl-L-serine
mercaptopyruvate
61
0.0043
0.0019
130%
3-methylglutaric acid
61
0.0044
0.0019
319%
Metabolite - 2139
61
0.0045
0.0019
165%
Spermidine
50
0.0045
0.0019
−2575%
Metabolite - 3974
61
0.0045
0.0019
114%
azelaic acid
61
0.0045
0.0019
90%
Metabolite - 5186
61
0.0048
0.002
6750%
4-acetamidobutyric acid
61
0.0048
0.002
754%
Metabolite - 5215
50
0.0049
0.002
−151%
dethiobiotin
50
0.0049
0.002
45%
Metabolite - 1496
61
0.0049
0.002
46%
Metabolite - 3955
61
0.0049
0.002
−138%
2-keto-L-gulonic acid
50
0.0054
0.0022
−167%
Metabolite - 5170
61
0.0055
0.0022
−600%
Metabolite - 2466
61
0.006
0.0024
−194%
caffeine
61
0.0064
0.0026
−287%
Isobar-40-includes-Maltotetraose-
61
0.0066
0.0027
−264%
stachyose
Metabolite - 1211
61
0.0069
0.0027
−188%
Metabolite - 4706
61
0.0069
0.0027
304%
Metabolite - 4027
50
0.0069
0.0027
520%
Metabolite - 4150
50
0.007
0.0028
−483%
4-methyl-2-oxopentanoate
61
0.0072
0.0028
194%
Metabolite - 1216
61
0.0073
0.0028
109%
Metabolite - 3837
61
0.0074
0.0029
210%
S-adenosyl-l-homocysteine
61
0.0075
0.0029
72%
Metabolite - 2768
61
0.0077
0.0029
−800%
suberic acid
61
0.008
0.0031
106%
Metabolite - 3554
61
0.0081
0.0031
272%
pyrophosphate
50
0.0081
0.0031
120%
Metabolite - 3996
50
0.0081
0.0031
86%
3-hydroxy-3-methylglutarate
50
0.0084
0.0031
123%
Metabolite - 4615
61
0.0084
0.0031
120%
4-Guanidinobutanoic acid
61
0.0084
0.0031
110%
Metabolite - 2348
61
0.0088
0.0032
151%
Metabolite - 1980
61
0.0088
0.0032
138%
N-5-aminocarbonyl-L-ornithine
50
0.0089
0.0033
177%
Metabolite - 3997
61
0.009
0.0033
1100%
fructose
50
0.0093
0.0034
−336%
Metabolite - 1286
61
0.0093
0.0034
−127%
Metabolite - 1342-possible-
61
0.0094
0.0034
229%
phenylacetylglutamine
Metabolite - 4866
61
0.0099
0.0036
−479%
Metabolite - 3020
50
0.0103
0.0037
97%
Metabolite - 2607
61
0.0103
0.0037
147%
Metabolite - 1609
61
0.0104
0.0037
−227%
Metabolite - 4516
50
0.0115
0.0041
−213%
1-methyladenine
50
0.0116
0.0041
−580%
Metabolite - 2232
61
0.0116
0.0041
−242%
picolinic acid
61
0.0118
0.0041
137%
Metabolite - 2774
61
0.0126
0.0044
96%
Metabolite - 2690
61
0.0127
0.0044
2080%
Metabolite - 3221
61
0.0128
0.0044
107%
Isobar-30-includes-maltotetraose-
61
0.0132
0.0045
−202%
stachyose
Metabolite - 3180
61
0.0134
0.0046
174%
Metabolite - 3220
61
0.0134
0.0046
267%
Metabolite - 3752
61
0.0135
0.0046
1122%
Metabolite - 4787
61
0.0135
0.0046
−540%
Metabolite - 4365
50
0.0146
0.0049
−229%
Metabolite - 3957
61
0.0147
0.0049
59%
DL-cystathionine
50
0.0148
0.0049
271%
2-deoxyuridine
61
0.0149
0.0049
128%
Metabolite - 3379
61
0.0151
0.005
−138%
sarcosine
50
0.0153
0.005
2138%
Metabolite - 4018
61
0.0155
0.0051
813%
cholesterol
50
0.0162
0.0053
33%
5-6-dihydrouracil
61
0.017
0.0055
154%
5-oxoproline
50
0.0174
0.0057
55%
3-amino-isobutyrate
50
0.0177
0.0057
1561%
Metabolite - 1961-retired-glycocholic
61
0.0179
0.0058
691%
acid
Metabolite - 4043
50
0.0185
0.0059
38%
Metabolite - 2981
50
0.0186
0.0059
27%
Metabolite - 3984
61
0.0186
0.0059
800%
tyramine
50
0.0186
0.0059
38%
Metabolite - 3526
61
0.0194
0.0061
127%
Metabolite - 4168
61
0.0198
0.0062
54%
Putrescine
50
0.0199
0.0062
−2967%
Metabolite - 2099
61
0.0204
0.0064
−247%
pyridoxamine-phosphate
61
0.0205
0.0064
−197%
sn-Glycerol-3-phosphate
50
0.0214
0.0066
738%
GABA
50
0.022
0.0068
−192%
Metabolite - 4362
50
0.0223
0.0069
−215%
uridine-5-diphosphoglucose
50
0.0226
0.0069
−142%
saccharopine
61
0.0231
0.007
81%
Metabolite - 3132
61
0.0231
0.007
−195%
Metabolite - 4550
61
0.0234
0.0071
92%
asparagine
50
0.0235
0.0071
81%
Metabolite - 2143
61
0.0238
0.0071
345%
Metabolite - 1970
61
0.0253
0.0076
141%
L-kynurenine
50
0.0258
0.0077
335%
Metabolite - 1129
61
0.0259
0.0077
−183%
Metabolite - 1333
61
0.0263
0.0078
−268%
Metabolite - 2406
61
0.0264
0.0078
238%
Metabolite - 4632
50
0.0266
0.0078
53%
Metabolite - 3123
61
0.0267
0.0078
87%
Metabolite - 1911
61
0.0274
0.008
100%
Metabolite - 2806
61
0.0277
0.0081
−154%
Metabolite - 4014
50
0.0292
0.0085
69%
Metabolite - 1608
61
0.0295
0.0085
−605%
Metabolite - 1974
61
0.0295
0.0085
218%
Metabolite - 3708
61
0.0297
0.0085
46%
Metabolite - 3896
61
0.0297
0.0085
360%
Metabolite - 1303
61
0.0303
0.0086
−256%
Metabolite - 2212
61
0.0308
0.0087
453%
glutarate
61
0.0309
0.0087
155%
Metabolite - 3436
61
0.0316
0.0089
148%
D-sorbitol-6-phosphate
50
0.0319
0.009
−190%
Metabolite - 3430
61
0.0324
0.0091
110%
Metabolite - 3992-
61
0.033
0.0092
−132%
Isobar-1-includes-mannose-fructose-
61
0.034
0.0094
−187%
glucose-galactose-alpha-L-
sorbopyranose-inositol-D-allose
Metabolite - 2390
61
0.0345
0.0096
343%
Metabolite - 3002
50
0.0346
0.0096
33%
Metabolite - 3545
61
0.0354
0.0097
165%
Metabolite - 1186
61
0.0373
0.0102
−1210%
Metabolite - 1111-possible-
61
0.0375
0.0103
50%
methylnitronitrosoguanidine-or-ethyl-
thiocarbamoylacetate
Metabolite - 5207
50
0.0377
0.0103
−136%
Metabolite - 3016
50
0.0379
0.0103
−184%
Metabolite - 1963
61
0.0393
0.0106
−151%
xylitol
50
0.0393
0.0106
123%
Metabolite - 3022
50
0.0396
0.0107
92%
Metabolite - 2897
61
0.0416
0.0112
92%
uridine-5-monophosphate
61
0.0433
0.0116
−161%
Metabolite - 2027
61
0.044
0.0117
490%
2-deoxyuridine-5-triphosphate
61
0.0444
0.0118
−174%
Metabolite - 3034
50
0.0448
0.0119
67%
3-hydroxybutanoic acid
50
0.0476
0.0125
218%
3-methyl-2-oxovaleric acid
61
0.0477
0.0125
241%
Metabolite - 3980
61
0.0484
0.0127
−169%
niacinamide
61
0.052
0.0135
−138%
Isobar-27-includes-L-kynurenine-alpha-
61
0.052
0.0135
645%
2-diamino-gamma-oxobenzenebutanoic
acid
Metabolite - 4133
50
0.0522
0.0135
120%
Metabolite - 2827
61
0.0526
0.0136
−202%
Metabolite - 5189
61
0.0536
0.0138
110%
Metabolite - 2778
61
0.0537
0.0138
269%
Metabolite - 3027
50
0.0537
0.0138
130%
biliverdin
61
0.0539
0.0138
−151%
Metabolite - 3813
61
0.0547
0.0139
146%
uridine-5-diphosphoglucuronic acid
50
0.055
0.014
129%
Metabolite - 3951
61
0.0551
0.014
64%
phytonadione
50
0.0554
0.014
29%
Metabolite - 3139
61
0.0565
0.0142
71%
Metabolite - 3176-possible-creatine
61
0.0567
0.0142
−129%
Metabolite - 1718
61
0.0568
0.0142
−169%
Metabolite - 3783
61
0.0574
0.0143
−174%
Metabolite - 4616
61
0.0585
0.0145
210%
sorbitol
50
0.0592
0.0147
841%
Metabolite - 2064
61
0.0623
0.0154
54%
cytidine
61
0.0628
0.0155
181%
Metabolite - 5126
61
0.0633
0.0156
−145%
beta-alanine
50
0.0642
0.0157
52%
Metabolite - 4567
61
0.066
0.0161
632%
glucarate
50
0.0686
0.0166
−326%
Metabolite - 3539
61
0.0687
0.0166
143%
Metabolite - 3056
61
0.0688
0.0166
1354%
Metabolite - 2072
61
0.0689
0.0166
368%
Metabolite - 4032
50
0.0745
0.0179
162%
Metabolite - 5229
50
0.0758
0.0182
−144%
beta-nicotinamide-adenine-dinucleotide
61
0.0761
0.0182
2363%
Metabolite - 3960
61
0.0763
0.0182
−140%
Metabolite - 2121
61
0.0771
0.0183
98%
Metabolite - 3238
61
0.0778
0.0185
247%
Metabolite - 3129
61
0.0848
0.02
−118%
25-hydroxycholesterol
50
0.0913
0.0215
11%
Metabolite - 5226
50
0.0977
0.023
100%
Metabolite - 1575
61
0.1
0.0234
−188%
3-nitro-L-tyrosine
50
0.1027
0.024
96%
Metabolite - 1142-possible-5-
61
0.104
0.0242
428%
hydroxypentanoate-or-beta-
hydroxyisovaleric acid
Metabolite - 2250
61
0.1053
0.0245
−150%
gamma-glu-cys
61
0.1128
0.0261
−229%
Metabolite - 2853
61
0.1138
0.0263
79%
Metabolite - 3756
61
0.1144
0.0264
593%
Metabolite - 2368
61
0.115
0.0264
−507%
o-phosphoethanolamine
50
0.1171
0.0268
70%
Metabolite - 1497
61
0.1186
0.0271
−135%
Metabolite - 3475
61
0.1222
0.0278
−148%
Metabolite - 2185
61
0.1229
0.0279
61%
alpha-L-sorbopyranose
50
0.1302
0.0295
−139%
Metabolite - 4512
50
0.1307
0.0295
−167%
histamine
61
0.1324
0.0298
−130%
Metabolite - 1085-possible-isolobinine-
61
0.135
0.0303
34%
or-4-aminoestra-1-3-5-10-triene-3-
17beta-diol
Isobar-18-includes-D-fructose-1-
61
0.1383
0.0309
52%
phosphate-beta-D-fructose-6-
phosphate
Metabolite - 2824
61
0.1384
0.0309
125%
Metabolite - 3848
61
0.1384
0.0309
55%
biotin
61
0.1397
0.0311
−169%
L-homoserine-lactone
61
0.1404
0.0311
−118%
cytidine-5-monophosphate
61
0.1411
0.0312
41%
Metabolite - 3952
61
0.1461
0.0322
−144%
Metabolite - 3576
61
0.1462
0.0322
26%
Metabolite - 2821
61
0.1476
0.0324
291%
Metabolite - 2255
61
0.1483
0.0324
−169%
mannose
50
0.1503
0.0328
−147%
alpha-amino-adipate
50
0.1518
0.033
113%
Metabolite - 3696-retired-isobar-
61
0.152
0.033
230%
glycocheBenignoxycholic acid-
glycodeoxycholic acid
glucose-6-phosphate
50
0.153
0.0331
−144%
Metabolite - 2724
61
0.1543
0.0333
51%
Metabolite - 1616
61
0.1552
0.0334
−158%
Metabolite - 2347
61
0.1567
0.0337
42%
Metabolite - 2313
61
0.1604
0.0344
22%
Metabolite - 2389
61
0.1657
0.0354
22%
mannose-6-phosphate
50
0.1678
0.0357
−200%
Metabolite - 4503
50
0.1692
0.036
426%
serine
50
0.1707
0.0362
22%
Metabolite - 2005
61
0.172
0.0364
52%
Metabolite - 4806
50
0.1728
0.0364
22%
Metabolite - 4030-possible-
61
0.1763
0.0371
52%
glutethimide-or-securinine
Metabolite - 3832-possible-phenol-
61
0.1775
0.0372
199%
sulfate
glucono-gamma-lactone
50
0.1776
0.0372
−143%
Metabolite - 1070
61
0.1836
0.0383
23%
Metabolite - 4019
50
0.1844
0.0384
32%
Metabolite - 4355
50
0.1854
0.0385
22%
N-acetyl-D-glucosamine
50
0.186
0.0385
31%
Metabolite - 2198
61
0.1861
0.0385
−144%
Metabolite - 4053
50
0.1928
0.0397
45%
Isobar-3-includes-inositol-1-phosphate-
61
0.1941
0.0399
−127%
mannose-6-phosphate-glucose-6-
phosphate-D-mannose-1-phosphate-
alpha-D-glucose-1-phosphate-alpha-D-
galactose-1-phosphate
maltose
50
0.1978
0.0406
426%
Metabolite - 4868-possible-Bradykinin
61
0.1998
0.0409
−120%
Metabolite - 4497
50
0.2013
0.0411
−132%
Isobar-4-includes-Gluconic acid-DL-
61
0.2053
0.0418
−129%
arabinose-D-ribose-L-xylose-DL-lyxose-
D-xylulose
Metabolite - 1457
61
0.2062
0.0419
41%
Metabolite - 2691
61
0.2102
0.0426
48%
Metabolite - 2075
61
0.2122
0.0428
−161%
dulcitol
50
0.2122
0.0428
−146%
Metabolite - 4931
61
0.2153
0.0433
30%
orotidine-5-phosphate
61
0.2187
0.0439
81%
Metabolite - 3074
50
0.2196
0.0439
86%
hypotaurine
50
0.221
0.044
60%
N-acetyl-D-galactosamine
50
0.2211
0.044
33%
Metabolite - 4116
61
0.2274
0.0452
16%
Metabolite - 3476
61
0.2356
0.0467
−137%
adenine
50
0.2383
0.0471
58%
N-6-trimethyl-l-lysine
61
0.2389
0.0471
−132%
2-deoxy-D-glucose
50
0.2399
0.0472
−142%
Metabolite - 3317
61
0.2414
0.0474
42%
glutamine
50
0.2426
0.0475
55%
Metabolite - 1573
61
0.247
0.0482
42%
Isobar-32-includes-N-acetyl-D-
61
0.2551
0.0497
24%
glucosamine-N-acetyl-D-mannosamine
Metabolite - 1248-possible-avermectin-
61
0.2596
0.0505
−135%
aglycone
Metabolite - 2388
61
0.2679
0.052
19%
Metabolite - 2546
61
0.2715
0.0525
91%
Metabolite - 1113-possible-
61
0.28
0.054
23%
acetylcarnitine-or-isopentyl-adenine
alpha-D-ribose-5-phosphate
50
0.2826
0.0544
−129%
Metabolite - 5227
50
0.2888
0.0555
1117%
Metabolite - 3534
61
0.2998
0.0575
58%
2-acetamido-1-amino-1-2-dideoxy-beta-
50
0.3037
0.0581
25%
D-glucopyranose
Metabolite - 5211
50
0.3045
0.0581
−184%
Metabolite - 1653
61
0.3126
0.0595
−127%
Metabolite - 2036
61
0.3211
0.061
115%
Metabolite - 4003
61
0.3245
0.0615
−124%
Metabolite - 4058
50
0.3276
0.0619
27%
Metabolite - 2055
61
0.3345
0.0631
−122%
3-phospho-l-serine
61
0.3436
0.0646
−109%
Metabolite - 3073
50
0.3654
0.0686
45%
Metabolite - 4272
50
0.3717
0.0696
−119%
Metabolite - 1203-possible-
61
0.3764
0.0703
−140%
acetylbrowniine-tricornine-germine-or-
veracevine
Metabolite - 4448
61
0.4001
0.0746
−116%
Metabolite - 2846
61
0.4122
0.0767
80%
Metabolite - 5213
50
0.4147
0.077
−118%
galactose
50
0.4216
0.0781
17%
hippuric acid
61
0.4252
0.0786
−139%
Metabolite - 3514-retired-topiramate
61
0.4327
0.0798
−341%
Isobar-21-includes-gamma-
61
0.4395
0.0808
37%
aminobutyryl-L-histidine-L-anserine
uridine
61
0.4426
0.0812
−108%
Metabolite - 1330
61
0.4441
0.0813
57%
Metabolite - 3994
61
0.4454
0.0814
−128%
Metabolite - 4017
50
0.4508
0.0822
16%
Metabolite - 5147
61
0.461
0.0838
196%
Metabolite - 4637
50
0.4761
0.0864
12%
Metabolite - 3668
61
0.477
0.0864
23%
Metabolite - 3365
61
0.4807
0.0868
−127%
Metabolite - 1455
61
0.4815
0.0868
−171%
Metabolite - 4096-gamma-glu-gly-leu-
61
0.4858
0.0874
−109%
Metabolite - 1187
61
0.4937
0.0886
−126%
Metabolite - 2194
61
0.5147
0.0922
30%
Metabolite - 3543
61
0.5175
0.0925
44%
possible-ISOBAR-DL-aspartic acid-
50
0.519
0.0925
22%
Metabolite - 3522
61
0.5205
0.0925
−231%
Metabolite - 2105
61
0.521
0.0925
15%
dihydroxyacetone-phosphate
61
0.532
0.0942
−116%
Metabolite - 3051
61
0.5346
0.0945
29%
Metabolite - 3755
61
0.5481
0.0967
12%
Metabolite - 3604
61
0.5512
0.097
−129%
Metabolite - 4238
61
0.5582
0.098
23%
Metabolite - 4523
50
0.5592
0.098
13%
Metabolite - 2407
61
0.5602
0.098
−133%
Metabolite - 4354
50
0.5857
0.1021
−112%
Metabolite - 2129
61
0.5869
0.1021
17%
Metabolite - 4002
50
0.5873
0.1021
13%
Metabolite - 1392
61
0.5947
0.1031
36%
6-phosphogluconic acid
61
0.5976
0.1034
8%
phosphoenolpyruvate
50
0.6017
0.1039
16%
Carnosine
61
0.6048
0.1042
−112%
alpha-keto-glutarate
61
0.6073
0.1044
47%
Metabolite - 3484
61
0.6115
0.1049
27%
Metabolite - 2279
61
0.6193
0.1061
−115%
Metabolite - 2074
61
0.6245
0.1067
−118%
Isobar-31-includes-maltotriose-
61
0.6315
0.1077
−115%
melezitose
N-acetylneuraminate
61
0.639
0.1088
11%
ascorbic acid
50
0.6412
0.1089
18%
Metabolite - 4084
50
0.6527
0.1106
−104%
Metabolite - 1088
61
0.6537
0.1106
16%
Metabolite - 4020
50
0.6567
0.1108
12%
creatinine
61
0.6624
0.1116
6%
Metabolite - 2174
61
0.6687
0.1124
15%
Metabolite - 3498
61
0.6739
0.1129
12%
Metabolite - 3401
61
0.6742
0.1129
16%
succinate
50
0.6845
0.1144
−120%
L-histidinol
61
0.6889
0.1149
−108%
Metabolite - 4667
61
0.6922
0.1152
−109%
Metabolite - 4510
50
0.6961
0.1156
9%
Metabolite - 3099
50
0.6979
0.1157
7%
Metabolite - 2056
61
0.7004
0.1158
−106%
Metabolite - 1183
61
0.7152
0.118
−118%
beta-D-lactose
50
0.7236
0.1192
14%
Metabolite - 4796
50
0.7305
0.1201
14%
Metabolite - 4235
61
0.7549
0.1238
−126%
Metabolite - 4514
50
0.7707
0.1262
−105%
Metabolite - 3531
61
0.7817
0.1277
−126%
Metabolite - 5089
61
0.783
0.1277
−121%
benzoic acid
50
0.797
0.1297
−103%
Isobar-17-includes-arginine-N-alpha-
61
0.808
0.1312
6%
acetyl-ornithine
ornithine
50
0.8172
0.1325
−106%
Metabolite - 2319
61
0.8211
0.1328
−111%
cystine
50
0.8239
0.1329
−104%
Metabolite - 5086
61
0.8247
0.1329
−110%
Metabolite - 3189
61
0.8275
0.1331
7%
guanine
50
0.8461
0.1356
8%
Metabolite - 3517
61
0.8465
0.1356
9%
Metabolite - 3040
50
0.8495
0.1358
−104%
Metabolite - 2558
61
0.8782
0.1401
7%
Metabolite - 2180
61
0.8839
0.1408
−104%
arginino-succinate
61
0.8933
0.1419
−103%
Metabolite - 4080
50
0.8946
0.1419
4%
Metabolite - 2688
61
0.9212
0.1459
−101%
aspartate
61
0.9268
0.1463
2%
Metabolite - 2703
61
0.9278
0.1463
−103%
Metabolite - 5087
61
0.9434
0.1485
−104%
Metabolite - 3694
61
0.9614
0.1509
−102%
Metabolite - 1979-Cl-adduct-of-
61
0.9624
0.1509
−101%
C6H10O5
Metabolite - 1975
61
0.9674
0.1514
1%
Metabolite - 4271
50
0.9952
0.1555
1%
[0000]
TABLE 3
Prostate Cancer Biomarkers from subjects with Metastatic, High Grade Prostate
Cancer compared to subjects with Lower Grade Prostate Cancer.
% Change
in high
COMPOUND
Library
p-value
q-value
grade PCA
inosine
61
<0.0001
<0.0001
−63%
Metabolite - 3390
61
<0.0001
<0.0001
−69%
octadecanoic acid
50
<0.0001
<0.0001
89%
Metabolite - 2-Aminoethyl-phosphonate
61
<0.0001
<0.0001
−78%
glycerol
50
<0.0001
<0.0001
200%
n-hexadecanoic acid
50
<0.0001
<0.0001
241%
leucine
50
<0.0001
1.00E−04
96%
Metabolite - 1498
61
<0.0001
2.00E−04
95%
Metabolite - 4013
61
<0.0001
2.00E−04
418%
Isobar-24-includes-L-arabitol-adonitol
61
<0.0001
2.00E−04
183%
4-hydroxyphenylpyruvate
61
<0.0001
2.00E−04
−71%
Putrescine
50
<0.0001
2.00E−04
−81%
glycerate
61
<0.0001
2.00E−04
235%
xanthine
61
<0.0001
2.00E−04
331%
uridine
61
<0.0001
2.00E−04
−46%
Metabolite - 1597
61
<0.0001
3.00E−04
63%
Metabolite - 4611
50
<0.0001
3.00E−04
388%
uracil
50
1.00E−04
5.00E−04
351%
3-phospho-d-glycerate
61
1.00E−04
6.00E−04
−53%
tetradecanoic acid
50
1.00E−04
6.00E−04
472%
Metabolite - 3102
50
1.00E−04
6.00E−04
716%
inositol
50
1.00E−04
6.00E−04
−74%
riboflavine
61
1.00E−04
6.00E−04
77%
Metabolite - 3772
61
1.00E−04
6.00E−04
76%
Metabolite - 3085
50
1.00E−04
6.00E−04
−53%
9-12-octadecadienoic acid-z-z-
50
1.00E−04
6.00E−04
256%
anthranilic acid
50
1.00E−04
6.00E−04
57%
n-dodecanoate
50
1.00E−04
6.00E−04
351%
Metabolite - 3215
61
1.00E−04
6.00E−04
157%
palmitoleic acid
50
1.00E−04
6.00E−04
825%
urea
50
1.00E−04
6.00E−04
241%
Metabolite - 4620
61
1.00E−04
6.00E−04
854%
valine
50
2.00E−04
7.00E−04
47%
Metabolite - 2466
61
2.00E−04
7.00E−04
−74%
Metabolite - 1349
61
2.00E−04
7.00E−04
−88%
Metabolite - 4075
50
2.00E−04
8.00E−04
689%
Metabolite - 3808
61
2.00E−04
8.00E−04
−72%
Metabolite - 5209
50
2.00E−04
8.00E−04
−78%
Metabolite - 4134
50
2.00E−04
8.00E−04
444%
Metabolite - 1116
61
2.00E−04
8.00E−04
476%
Metabolite - 4150
50
2.00E−04
8.00E−04
−68%
Metabolite - 3014
50
3.00E−04
9.00E−04
322%
Metabolite - 2548
61
3.00E−04
9.00E−04
189%
Metabolite - 3178
61
3.00E−04
0.001
−88%
uric acid
61
3.00E−04
0.001
200%
Metabolite - 1351
61
3.00E−04
0.001
291%
Metabolite - 4046
50
3.00E−04
0.001
688%
Metabolite - 1329
61
4.00E−04
0.001
147%
Metabolite - 4649
61
4.00E−04
0.0011
224%
Metabolite - 3992-
61
4.00E−04
0.0011
−33%
Metabolite - 2272
61
4.00E−04
0.0012
176%
Metabolite - 2181
61
5.00E−04
0.0013
135%
Metabolite - 4869
61
5.00E−04
0.0013
361%
arabinose
50
5.00E−04
0.0013
−73%
D-ribose
50
5.00E−04
0.0013
−74%
xanthosine
50
5.00E−04
0.0013
−69%
Isobar-19-includes-D-saccharic acid-2-
61
6.00E−04
0.0015
−53%
deoxy-D-galactose-2-deoxy-D-glucose-L-
fucose-L-rhamnose
3-methoxy-L-tyrosine
50
6.00E−04
0.0015
−75%
2-keto-L-gulonic acid
50
6.00E−04
0.0015
−47%
Metabolite - 2766
61
7.00E−04
0.0015
−93%
lactate
50
7.00E−04
0.0017
38%
Metabolite - 3893
61
7.00E−04
0.0017
−85%
tryptophan
61
8.00E−04
0.0017
53%
phenylalanine
61
8.00E−04
0.0017
43%
Metabolite - 1819
61
8.00E−04
0.0018
99%
Metabolite - 1323-possible-4-sulfobenzyl-
61
9.00E−04
0.0019
495%
alcohol
Metabolite - 3123
61
0.001
0.0021
223%
guanosine
61
0.001
0.0022
−48%
proline
50
0.0011
0.0022
94%
N-acetyl-D-galactosamine
50
0.0011
0.0022
−58%
Metabolite - 2255
61
0.0011
0.0022
−59%
pantothenic acid
61
0.0011
0.0022
89%
Metabolite - 5212
50
0.0011
0.0022
−80%
DL-pipecolic acid
61
0.0012
0.0023
329%
Metabolite - 5187
61
0.0012
0.0023
348%
Metabolite - 5207
50
0.0012
0.0023
−35%
creatinine
61
0.0013
0.0023
41%
Metabolite - 4518
50
0.0013
0.0024
490%
Metabolite - 3807
61
0.0013
0.0024
363%
Metabolite - 2924
50
0.0014
0.0024
187%
Metabolite - 4617
61
0.0014
0.0024
107%
Metabolite - 3165
61
0.0014
0.0024
39%
Metabolite - 4428
61
0.0014
0.0024
155%
Metabolite - 5107
61
0.0014
0.0024
170%
Metabolite - 3833
61
0.0015
0.0024
188%
Metabolite - 2607
61
0.0015
0.0024
348%
ethylmalonic acid
61
0.0015
0.0024
894%
Metabolite - 3837
61
0.0017
0.0028
363%
Metabolite - 3132
61
0.0017
0.0028
−58%
Metabolite - 4051
50
0.0018
0.0028
266%
Isobar-3-includes-inositol-1-phosphate-
61
0.0018
0.0029
−52%
mannose-6-phosphate-glucose-6-
phosphate-D-mannose-1-phosphate-alpha-
D-glucose-1-phosphate-alpha-D-galactose-
1-phosphate
Metabolite - 3003
50
0.0019
0.0029
94%
allantoin
61
0.002
0.0031
211%
Metabolite - 3138
61
0.0021
0.0032
128%
catechol
61
0.0021
0.0032
292%
heptadecanoic acid
50
0.0022
0.0032
71%
Metabolite - 1843
61
0.0022
0.0033
361%
N-6-trimethyl-l-lysine
61
0.0023
0.0033
−44%
phosphate
50
0.0024
0.0034
49%
Isobar-2-includes-3-amino-isobutyrate-2-
61
0.0025
0.0035
121%
amino-butyrate-4-aminobutanoic acid-
dimethylglycine-choline-
niacinamide
61
0.0025
0.0036
−35%
Metabolite - 2237
61
0.0026
0.0037
291%
Metabolite - 2567
61
0.0028
0.0038
101%
S-5-adenosyl-L-methionine
61
0.0028
0.0038
153%
Metabolite - 3489
61
0.0028
0.0038
−81%
Metabolite - 2867
61
0.0029
0.0039
−99%
1-methyladenosine
61
0.0029
0.0039
260%
thymine
50
0.0031
0.0041
561%
Metabolite - 3543
61
0.0032
0.0041
174%
D-sorbitol-6-phosphate
50
0.0032
0.0041
−66%
Metabolite - 2250
61
0.0033
0.0042
−61%
citric acid
50
0.0034
0.0043
−92%
L-alpha-glycerophosphorylcholine
61
0.0035
0.0043
192%
Metabolite - 1288
61
0.0035
0.0043
212%
elaidic acid
50
0.0035
0.0044
241%
alpha-4-dihydroxybenzenepropanoic acid
50
0.0036
0.0044
1900%
Metabolite - 3996
50
0.0036
0.0044
104%
Metabolite - 2711
61
0.0037
0.0044
65%
mannose-6-phosphate
50
0.0038
0.0045
−82%
Metabolite - 1457
61
0.0038
0.0045
115%
Metabolite - 3364
61
0.0039
0.0046
232%
glyceric acid
50
0.0039
0.0046
78%
Metabolite - 4615
61
0.004
0.0046
154%
uridine-5-diphosphoglucose
50
0.004
0.0046
−35%
Metabolite - 2323
61
0.0041
0.0047
111%
Metabolite - 1333
61
0.0042
0.0047
−71%
Metabolite - 3966
61
0.0042
0.0047
171%
3-methylglutaric acid
61
0.0043
0.0047
319%
mercaptopyruvate
61
0.0043
0.0047
130%
D-allose
50
0.0043
0.0047
−87%
Metabolite - 1342-possible-
61
0.0043
0.0047
286%
phenylacetylglutamine
isoleucine
50
0.0044
0.0047
33%
Metabolite - 3044
61
0.0046
0.0049
120%
4-acetamidobutyric acid
61
0.0048
0.0051
754%
3-phospho-l-serine
61
0.0051
0.0053
−22%
Metabolite - 3531
61
0.0051
0.0053
160%
Metabolite - 3514-retired-topiramate
61
0.0053
0.0055
170%
inositol-1-phosphate
50
0.0054
0.0055
88%
Metabolite - 1392
61
0.0057
0.0059
164%
Metabolite - 2973
50
0.006
0.006
−38%
Metabolite - 5214
50
0.0062
0.0062
−71%
Metabolite - 1394-possible-Losartan
61
0.0063
0.0063
109%
Metabolite - 4550
61
0.0065
0.0064
95%
Metabolite - 3816
61
0.0065
0.0064
−92%
Metabolite - 2141
61
0.0068
0.0066
181%
Metabolite - 3526
61
0.0075
0.0072
196%
Metabolite - 1831-possible-Cl-adduct-of-
61
0.0078
0.0075
86%
citrulline
Metabolite - 1330
61
0.0079
0.0076
216%
spermine
50
0.0085
0.0081
−91%
Metabolite - 5186
61
0.0087
0.0081
879%
Metabolite - 4637
50
0.0087
0.0081
−28%
Metabolite - 3708
61
0.0087
0.0081
61%
Metabolite - 1496
61
0.0087
0.0081
46%
3-methyl-L-histidine
61
0.009
0.0082
51%
Metabolite - 3668
61
0.009
0.0082
132%
taurine
61
0.0091
0.0083
−42%
Metabolite - 5210
50
0.0092
0.0083
−44%
histidine
50
0.0093
0.0083
39%
Metabolite - 3522
61
0.0094
0.0084
182%
Metabolite - 4014
50
0.01
0.0088
104%
quinolinic acid
61
0.0101
0.0088
93%
Metabolite - 1465
61
0.0101
0.0088
124%
Metabolite - 3539
61
0.0102
0.0089
460%
Metabolite - 1186
61
0.0105
0.0091
−82%
arachidonic acid
50
0.0106
0.0091
74%
Metabolite - 3998
50
0.0108
0.0092
32%
carnitine
61
0.0111
0.0094
74%
Metabolite - 2900-
61
0.0111
0.0094
103%
alanine
50
0.0115
0.0096
54%
Isobar-6-includes-valine-betaine
61
0.0115
0.0096
30%
Metabolite - 3997
61
0.0116
0.0096
740%
Metabolite - 3554
61
0.0121
0.0099
226%
Metabolite - 2111
61
0.0121
0.0099
76%
Metabolite - 4019
50
0.0125
0.0102
−35%
Metabolite - 3221
61
0.0128
0.0103
107%
Metabolite - 5110
61
0.0132
0.0107
131%
N-acetyl-D-glucosamine
50
0.0134
0.0107
−42%
4-Guanidinobutanoic acid
61
0.0136
0.0108
98%
5-s-methyl-5-thioadenosine
61
0.0137
0.0108
152%
Metabolite - 5087
61
0.014
0.011
105%
ribulose-5-phosphate
50
0.014
0.011
−51%
Metabolite - 3020
50
0.0146
0.0114
76%
Metabolite - 3436
61
0.0152
0.0118
213%
3-amino-isobutyrate
50
0.0162
0.0125
2172%
Metabolite - 3955
61
0.0171
0.0131
−25%
Metabolite - 2897
61
0.0171
0.0131
121%
Metabolite - 3220
61
0.0175
0.0133
235%
Metabolite - 5089
61
0.0177
0.0134
133%
Metabolite - 2690
61
0.0191
0.0142
784%
suberic acid
61
0.0191
0.0142
79%
Metabolite - 2688
61
0.0191
0.0142
−18%
Metabolite - 4235
61
0.0193
0.0142
140%
Metabolite - 1974
61
0.0194
0.0142
289%
gamma-L-glutamyl-L-glutamine
61
0.0195
0.0142
−68%
Metabolite - 2347
61
0.02
0.0145
69%
Metabolite - 4706
61
0.0201
0.0145
184%
picolinic acid
61
0.0201
0.0145
131%
Metabolite - 2143
61
0.0204
0.0146
408%
Metabolite - 4866
61
0.0209
0.0149
−79%
Metabolite - 4018
61
0.0212
0.015
564%
2-acetamido-1-amino-1-2-dideoxy-beta-D-
50
0.0214
0.0151
−46%
glucopyranose
adenosine
61
0.022
0.0155
−56%
sarcosine
50
0.0225
0.0157
795%
Metabolite - 1069-possible-
61
0.0229
0.0159
−79%
dehydroepiandrosterone-sulfate-
DL-cystathionine
50
0.0233
0.0161
203%
Metabolite - 5086
61
0.0236
0.0163
53%
Metabolite - 3064
61
0.0242
0.0166
96%
L-kynurenine
50
0.0252
0.0172
347%
pyrophosphate
50
0.0256
0.0173
84%
Spermidine
50
0.0257
0.0173
−92%
Metabolite - 1961-retired-glycocholic acid
61
0.0257
0.0173
444%
Metabolite - 1608
61
0.0261
0.0174
−60%
Metabolite - 5109
61
0.0261
0.0174
156%
3-hydroxybutanoic acid
50
0.0263
0.0174
305%
Metabolite - 1114
61
0.0264
0.0174
33%
Metabolite - 5232
50
0.0267
0.0176
150%
N-acetylserotonin
50
0.0272
0.0178
192%
Metabolite - 3984
61
0.0287
0.0187
468%
Metabolite - 1595-possible-glutathione-
61
0.0293
0.019
−66%
metabolite
trans-4-hydroxyproline
50
0.0308
0.0199
89%
Metabolite - 4593
50
0.0311
0.02
56%
Carnosine
61
0.0326
0.0209
63%
Metabolite - 2139
61
0.0342
0.0218
88%
beta-alanine
50
0.0345
0.0218
74%
Metabolite - 2390
61
0.0345
0.0218
343%
Metabolite - 2292
61
0.035
0.022
−76%
Metabolite - 2075
61
0.0355
0.0222
−75%
Metabolite - 4331
61
0.0357
0.0222
56%
Metabolite - 2108
61
0.0374
0.0232
44%
Metabolite - 3370
61
0.0394
0.0242
31%
Metabolite - 4168
61
0.0394
0.0242
49%
Metabolite - 4868-possible-Bradykinin
61
0.0397
0.0243
−61%
DL-homocysteine
61
0.0409
0.0249
45%
sn-Glycerol-3-phosphate
50
0.0414
0.0251
322%
Metabolite - 3139
61
0.0421
0.0254
−31%
Metabolite - 5126
61
0.0422
0.0254
−38%
Metabolite - 1129
61
0.0427
0.0256
−56%
Metabolite - 1203-possible-acetylbrowniine-
61
0.0434
0.0258
−62%
tricornine-germine-or-veracevine
Metabolite - 5108
61
0.0435
0.0258
95%
Metabolite - 4027
50
0.0437
0.0259
153%
Metabolite - 2099
61
0.0442
0.0261
−68%
arginino-succinate
61
0.0455
0.0267
−50%
L-allo-threonine
50
0.0477
0.0279
26%
Metabolite - 2853
61
0.0497
0.029
124%
Metabolite - 1576
61
0.0509
0.0295
41%
Metabolite - 1303
61
0.0513
0.0296
−60%
noradrenaline
50
0.0515
0.0296
26%
Metabolite - 1713
61
0.0518
0.0297
71%
Metabolite - 2778
61
0.0537
0.0305
269%
sorbitol
50
0.0539
0.0305
1085%
Metabolite - 1718
61
0.0539
0.0305
−51%
Metabolite - 4567
61
0.0542
0.0305
1058%
gamma-glu-cys
61
0.0543
0.0305
−73%
caffeine
61
0.0545
0.0305
−71%
Metabolite - 5167
61
0.0553
0.0308
72%
fumaric acid
50
0.0577
0.032
63%
Metabolite - 3379
61
0.0578
0.032
−26%
Metabolite - 1970
61
0.059
0.0324
102%
Metabolite - 2406
61
0.0591
0.0324
159%
threonine
50
0.0604
0.033
24%
Metabolite - 2072
61
0.0621
0.0338
417%
Metabolite - 5229
50
0.0624
0.0339
−32%
Metabolite - 3960
61
0.0638
0.0343
−30%
Metabolite - 3022
50
0.0639
0.0343
79%
Metabolite - 5166
61
0.064
0.0343
72%
Metabolite - 3056
61
0.0644
0.0344
1785%
Metabolite - 2027
61
0.0656
0.0349
301%
Metabolite - 4015
50
0.0678
0.0359
72%
Metabolite - 2118
61
0.0694
0.0366
−26%
Metabolite - 1070
61
0.0695
0.0366
−41%
Metabolite - 4516
50
0.0724
0.038
−50%
Metabolite - 4365
50
0.0728
0.038
−56%
Metabolite - 2806
61
0.0732
0.038
−26%
Metabolite - 3896
61
0.0733
0.038
179%
glutathione-reduced
61
0.0737
0.0381
−78%
Metabolite - 3180
61
0.0751
0.0387
88%
3-methyl-2-oxovaleric acid
61
0.0755
0.0388
170%
Metabolite - 3073
50
0.0767
0.0392
138%
Metabolite - 1327-possible-bilirubin
61
0.0774
0.0395
41%
Metabolite - 3238
61
0.0778
0.0395
247%
L-homoserine-lactone
61
0.0786
0.0398
−24%
uridine-5-diphosphoglucuronic acid
50
0.0813
0.041
114%
Metabolite - 1248-possible-avermectin-
61
0.0825
0.0414
−39%
aglycone
Metabolite - 3974
61
0.0853
0.0427
55%
Isobar-27-includes-L-kynurenine-alpha-2-
61
0.0883
0.0441
293%
diamino-gamma-oxobenzenebutanoic acid
tyrosine
61
0.0893
0.0444
19%
Metabolite - 2105
61
0.0921
0.0456
−42%
Metabolite - 4017
50
0.0939
0.0462
−24%
saccharopine
61
0.094
0.0462
47%
Metabolite - 3002
50
0.0977
0.0479
25%
Metabolite - 4512
50
0.0991
0.0484
−55%
Metabolite - 1977
61
0.1008
0.0491
51%
Metabolite - 3771
61
0.1044
0.0506
−25%
Metabolite - 3498
61
0.1048
0.0506
−28%
aspartate
61
0.1051
0.0506
−34%
Metabolite - 1142-possible-5-
61
0.1082
0.0519
407%
hydroxypentanoate-or-beta-
hydroxyisovaleric acid
Metabolite - 4058
50
0.1102
0.0528
−38%
Metabolite - 3980
61
0.1154
0.0551
−39%
Metabolite - 1111-possible-
61
0.1163
0.0552
−22%
methylnitronitrosoguanidine-or-ethyl-
thiocarbamoylacetate
5-hydroxyindoleacetate
50
0.1165
0.0552
−90%
Metabolite - 2121
61
0.1176
0.0556
84%
Metabolite - 3183-possible-gamma-L-
61
0.1218
0.0574
64%
glutamyl-L-phenylalanine-or-aspartame
Metabolite - 3951
61
0.1225
0.0575
45%
Metabolite - 3832-possible-phenol-sulfate
61
0.1246
0.0583
327%
Metabolite - 2703
61
0.1261
0.0588
−26%
Metabolite - 3756
61
0.1282
0.0596
454%
Metabolite - 2546
61
0.1302
0.0603
197%
Metabolite - 3016
50
0.1372
0.0633
−39%
Metabolite - 3810
61
0.1419
0.0653
−31%
Metabolite - 3534
61
0.1426
0.0654
67%
melatonin
50
0.1438
0.0657
55%
Metabolite - 2821
61
0.1453
0.0662
300%
Metabolite - 1497
61
0.1469
0.0668
−25%
alpha-L-sorbopyranose
50
0.1505
0.0682
−26%
Metabolite - 3696-retired-isobar-
61
0.152
0.0686
230%
glycochenodeoxycholic acid-
glycodeoxycholic acid
Metabolite - 2724
61
0.1527
0.0687
52%
Metabolite - 4787
61
0.1533
0.0688
−84%
Metabolite - 4117-possible-propranolol-or-2-
61
0.1541
0.0689
39%
heptyl-3-hydroxy-quinolone
Metabolite - 1573
61
0.1548
0.069
56%
beta-nicotinamide-adenine-dinucleotide
61
0.1581
0.0702
352%
alpha-D-ribose-5-phosphate
50
0.1585
0.0702
−29%
Metabolite - 1593
61
0.16
0.0707
−56%
glycine
50
0.1614
0.0711
20%
glutarate
61
0.1633
0.0717
73%
succinate
50
0.1697
0.074
84%
Metabolite - 1113-possible-acetylcarnitine-
61
0.1697
0.074
30%
or-isopentyl-adenine
Metabolite - 3034
50
0.1726
0.0751
38%
Metabolite - 3848
61
0.1771
0.0767
−29%
Metabolite - 5228
50
0.1777
0.0767
22%
Metabolite - 3099
50
0.1779
0.0767
−25%
GABA
50
0.1788
0.0768
−35%
serine
50
0.1792
0.0768
−13%
Metabolite - 4133
50
0.1803
0.077
64%
Metabolite - 2036
61
0.1835
0.078
246%
Metabolite - 2824
61
0.1838
0.078
98%
possible-ISOBAR-DL-aspartic acid-
50
0.1848
0.0782
−29%
maltose
50
0.1852
0.0782
504%
Metabolite - 4503
50
0.1887
0.0794
335%
Metabolite - 2827
61
0.1937
0.0813
−56%
Metabolite - 3129
61
0.1989
0.0832
−13%
Metabolite - 1616
61
0.1999
0.0834
−64%
Metabolite - 3604
61
0.2032
0.0845
−40%
Metabolite - 5128
61
0.2076
0.0861
−72%
Isobar-5-includes-asparagine-ornithine
61
0.2092
0.0865
30%
1-7-dihydro-6h-purin-6-one
61
0.2113
0.0867
14%
1-methyladenine
50
0.2113
0.0867
−83%
Metabolite - 4030-possible-glutethimide-or-
61
0.2115
0.0867
−28%
securinine
ornithine
50
0.2134
0.0872
−20%
Metabolite - 1679
61
0.2163
0.0881
56%
methionine
61
0.218
0.0886
17%
biotin
61
0.2198
0.0891
−35%
Metabolite - 4116
61
0.2206
0.0892
−13%
Metabolite - 1963
61
0.229
0.0923
−27%
Metabolite - 1575
61
0.2338
0.0938
−37%
S-adenosyl-l-homocysteine
61
0.234
0.0938
22%
dethiobiotin
50
0.2429
0.0971
−11%
Metabolite - 1216
61
0.2446
0.0975
36%
Metabolite - 1455
61
0.2458
0.0977
206%
Metabolite - 4080
50
0.2467
0.0977
−39%
biliverdin
61
0.2525
0.0998
−25%
Metabolite - 5226
50
0.2569
0.1012
50%
25-hydroxycholesterol
50
0.258
0.1014
−6%
Metabolite - 2129
61
0.2623
0.1028
−44%
N-acetylneuraminate
61
0.265
0.1036
29%
Metabolite - 2109
61
0.2658
0.1036
27%
Metabolite - 3517
61
0.2721
0.1057
67%
Metabolite - 4667
61
0.2746
0.1064
−22%
cytidine-5-monophosphate
61
0.2754
0.1064
27%
Metabolite - 4003
61
0.276
0.1064
−19%
Metabolite - 3074
50
0.2779
0.1069
80%
Metabolite - 2774
61
0.2815
0.1079
34%
Metabolite - 5170
61
0.2827
0.1081
−98%
Metabolite - 2768
61
0.285
0.1087
−99%
dihydroxyacetone-phosphate
61
0.295
0.1122
−22%
glucarate
50
0.3014
0.1144
−73%
Metabolite - 2055
61
0.303
0.1145
27%
Metabolite - 2368
61
0.3043
0.1145
−87%
pyridoxamine-phosphate
61
0.3047
0.1145
−24%
phosphoenolpyruvate
50
0.3051
0.1145
−43%
fructose
50
0.3065
0.1148
−44%
Metabolite - 5227
50
0.3077
0.1149
740%
Metabolite - 1088
61
0.3104
0.1155
−36%
2-deoxy-D-ribose
61
0.311
0.1155
17%
phytonadione
50
0.3221
0.1194
−11%
Metabolite - 1609
61
0.3244
0.1199
−33%
malic acid
50
0.3288
0.1212
17%
Metabolite - 4796
50
0.3315
0.1218
26%
6-phosphogluconic acid
61
0.3322
0.1218
16%
benzoic acid
50
0.333
0.1218
13%
Metabolite - 1211
61
0.3356
0.1224
10%
Metabolite - 4806
50
0.3385
0.1232
18%
2-deoxyuridine
61
0.3422
0.1237
31%
cholesterol
50
0.3424
0.1237
−9%
Metabolite - 3545
61
0.3426
0.1237
51%
Isobar-1-includes-mannose-fructose-
61
0.3458
0.1246
−17%
glucose-galactose-alpha-L-sorbopyranose-
Inositol-D-allose
Metabolite - 2056
61
0.3473
0.1248
18%
3-hydroxy-3-methylglutarate
50
0.3496
0.1253
22%
4-hydroxy-2-quinolinecarboxylic acid
61
0.3526
0.1261
−14%
Metabolite - 1653
61
0.3592
0.1277
−25%
xylitol
50
0.3596
0.1277
35%
Metabolite - 2348
61
0.3597
0.1277
48%
Metabolite - 3401
61
0.3637
0.1287
41%
Isobar-40-includes-Maltotetraose-stachyose
61
0.3704
0.1308
−36%
hippuric acid
61
0.3719
0.131
−29%
glutamic acid
50
0.3743
0.1315
17%
Metabolite - 2232
61
0.3753
0.1315
−36%
Metabolite - 4362
50
0.381
0.1332
−21%
Isobar-4-includes-Gluconic acid-DL-
61
0.3854
0.1344
−23%
arabinose-D-ribose-L-xylose-DL-lyxose-D-
xylulose
Metabolite - 3430
61
0.3874
0.1348
29%
Metabolite - 2313
61
0.3923
0.1361
14%
5-6-dihydrouracil
61
0.3941
0.1361
31%
Metabolite - 1104
61
0.3943
0.1361
−23%
Metabolite - 4355
50
0.3949
0.1361
−10%
Metabolite - 2074
61
0.4055
0.1394
45%
Metabolite - 2981
50
0.4071
0.1396
8%
Metabolite - 3094
50
0.4099
0.1402
−8%
Metabolite - 5189
61
0.4199
0.1433
−42%
Metabolite - 2194
61
0.4272
0.1454
43%
Metabolite - 2558
61
0.4305
0.146
35%
Metabolite - 4514
50
0.4309
0.146
17%
alpha-keto-glutarate
61
0.4325
0.1461
56%
Metabolite - 5211
50
0.4333
0.1461
−47%
cytidine
61
0.4411
0.1482
39%
Isobar-30-includes-maltotetraose-stachyose
61
0.4415
0.1482
−24%
Metabolite - 2198
61
0.4438
0.1486
−14%
Metabolite - 2389
61
0.447
0.1493
−10%
histamine
61
0.4668
0.1556
−12%
Metabolite - 3952
61
0.4773
0.1584
−19%
ascorbic acid
50
0.4775
0.1584
31%
Metabolite - 3694
61
0.4868
0.1611
−28%
Isobar-17-includes-arginine-N-alpha-acetyl-
61
0.4925
0.1625
−15%
ornithine
Metabolite - 1187
61
0.4931
0.1625
−24%
Metabolite - 4931
61
0.4969
0.1633
16%
Metabolite - 2319
61
0.5011
0.1643
−27%
Metabolite - 3189
61
0.5094
0.1667
39%
Metabolite - 3752
61
0.5167
0.1687
43%
Metabolite - 5215
50
0.5182
0.1688
−10%
Metabolite - 3484
61
0.5253
0.1707
32%
Metabolite - 3365
61
0.5283
0.171
−22%
Isobar-21-includes-gamma-aminobutyryl-L-
61
0.5285
0.171
−20%
histidine-L-anserine
Metabolite - 4272
50
0.5403
0.1742
−13%
Metabolite - 2185
61
0.5423
0.1742
19%
Metabolite - 3755
61
0.5431
0.1742
10%
Metabolite - 4497
50
0.5432
0.1742
−14%
orotidine-5-phosphate
61
0.5557
0.1777
−20%
Metabolite - 3051
61
0.5569
0.1777
26%
N-5-aminocarbonyl-L-ornithine
50
0.5705
0.1813
18%
Metabolite - 3317
61
0.5709
0.1813
19%
Metabolite - 2041
61
0.5719
0.1813
16%
Metabolite - 2846
61
0.5851
0.1844
−25%
cystine
50
0.5862
0.1844
−11%
Metabolite - 4032
50
0.5865
0.1844
26%
azelaic acid
61
0.5881
0.1844
16%
Metabolite - 3475
61
0.5881
0.1844
−17%
o-phosphoethanolamine
50
0.5905
0.1847
18%
cysteine
50
0.5935
0.1853
21%
Metabolite - 1911
61
0.5982
0.1861
22%
Metabolite - 4053
50
0.5988
0.1861
15%
galactose
50
0.6145
0.1906
−10%
Metabolite - 1183
61
0.6174
0.191
−22%
Metabolite - 2212
61
0.6301
0.1946
31%
hypotaurine
50
0.6325
0.1949
18%
Metabolite - 3957
61
0.6423
0.1975
11%
Metabolite - 1286
61
0.646
0.1982
−6%
Isobar-22-includes-glutamic acid-O-acetyl-L-
61
0.6499
0.199
6%
serine
Metabolite - 4616
61
0.6537
0.1997
−16%
Isobar-32-includes-N-acetyl-D-glucosamine-
61
0.659
0.2009
−8%
N-acetyl-D-mannosamine
Metabolite - 2407
61
0.6631
0.2017
−8%
N-N-dimethylarginine
61
0.6691
0.2031
13%
Metabolite - 4354
50
0.6766
0.2049
−8%
Metabolite - 4510
50
0.6881
0.2076
11%
tyramine
50
0.6893
0.2076
5%
Metabolite - 4632
50
0.6898
0.2076
6%
Metabolite - 4271
50
0.6928
0.2081
22%
Metabolite - 3994
61
0.6964
0.2087
−16%
Metabolite - 1085-possible-isolobinine-or-4-
61
0.6977
0.2087
−8%
aminoestra-1-3-5-10-triene-3-17beta-diol
Metabolite - 4448
61
0.7093
0.2117
−6%
Metabolite - 2064
61
0.7138
0.2126
7%
glutamine
50
0.7211
0.2143
12%
guanine
50
0.7322
0.2172
−14%
Metabolite - 2279
61
0.7424
0.2195
−10%
4-methyl-2-oxopentanoate
61
0.7432
0.2195
12%
Metabolite - 3040
50
0.7523
0.2217
−7%
Metabolite - 2691
61
0.7568
0.2226
11%
Isobar-18-includes-D-fructose-1-phosphate-
61
0.7623
0.2233
−9%
beta-D-fructose-6-phosphate
Metabolite - 4523
50
0.7627
0.2233
6%
Metabolite - 3027
50
0.7639
0.2233
10%
Metabolite - 4043
50
0.7735
0.2254
4%
dulcitol
50
0.7743
0.2254
−6%
beta-D-lactose
50
0.7821
0.2272
11%
Metabolite - 1975
61
0.7859
0.2279
11%
5-oxoproline
50
0.7882
0.2281
5%
Metabolite - 3813
61
0.7998
0.2306
14%
3-nitro-L-tyrosine
50
0.8003
0.2306
8%
Metabolite - 4002
50
0.815
0.2344
5%
Metabolite - 4238
61
0.8303
0.2383
8%
Metabolite - 2388
61
0.8374
0.2399
−4%
Metabolite - 3783
61
0.8416
0.2406
−6%
Metabolite - 4084
50
0.849
0.2422
1%
Metabolite - 3778
61
0.8508
0.2423
−8%
Metabolite - 3476
61
0.8527
0.2423
−6%
Metabolite - 1979-Cl-adduct-of-C6H10O5
61
0.8564
0.2426
−5%
Metabolite - 1980
61
0.8571
0.2426
9%
Metabolite - 2005
61
0.8602
0.243
5%
alpha-amino-adipate
50
0.862
0.243
7%
Metabolite - 5213
50
0.8674
0.2441
−4%
glucose-6-phosphate
50
0.8781
0.2461
−4%
Metabolite - 2174
61
0.8781
0.2461
5%
Metabolite - 5147
61
0.881
0.2464
−14%
Metabolite - 4020
50
0.8947
0.2493
3%
adenine
50
0.8948
0.2493
−4%
Metabolite - 3176-possible-creatine
61
0.9158
0.2547
−1%
Metabolite - 2180
61
0.937
0.26
3%
Metabolite - 3576
61
0.9487
0.2624
2%
2-deoxyuridine-5-triphosphate
61
0.9491
0.2624
−2%
L-histidinol
61
0.9545
0.2629
1%
Metabolite - 4096-gamma-glu-gly-leu-
61
0.9545
0.2629
−1%
Metabolite - 2753
61
0.9699
0.2664
1%
Isobar-31-includes-maltotriose-melezitose
61
0.9712
0.2664
1%
glucono-gamma-lactone
50
0.9791
0.2681
1%
uridine-5-monophosphate
61
0.9814
0.2682
0%
asparagine
50
0.9893
0.2695
0%
mannose
50
0.9898
0.2695
0%
2-deoxy-D-glucose
50
0.9996
0.2716
0%
Example 2
Cancer Vs. Non-Cancer
[0115] Biomarkers were discovered by (1) analyzing plasma and/or urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0116] The plasma and/or urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer and 48 individuals with prostate cancer. After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0117] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Prostate cancer vs. Control plasma, Prostate cancer vs. Control urine).
Biomarkers:
[0118] As listed below in Table 4, biomarkers were discovered that were differentially present between plasma samples from subjects with prostate cancer and Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 5 lists biomarkers that were discovered that were differentially present between urine samples from subjects with prostate cancer and Control subjects (i.e. not diagnosed with prostate cancer).
[0119] Tables 4 and 5 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 4) and the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 5). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.
[0000]
TABLE 4
Prostate Cancer Biomarkers from Plasma from subjects with
Prostate Cancer compared to Plasma from Control subjects.
% Change
COMPOUND
Library
p-value
q-value
in PCA
Metabolite - 3377
35
0
0.0043
192%
Metabolite - 2329
35
1.00E−04
0.0144
73%
Metabolite - 3305
35
1.00E−04
0.0138
144%
palmitoleic acid
50
4.00E−04
0.0313
67%
Metabolite - 3327
35
5.00E−04
0.0313
111%
Metabolite - 1127
35
6.00E−04
0.0313
54%
DL-indole-3-lactic acid
50; 35
7.00E−04
0.0325
33%
Metabolite - 3322
35
8.00E−04
0.0325
84%
Metabolite - 1185
35
0.0012
0.045
−41%
elaidic acid
50
0.0021
0.0665
54%
Metabolite - 3603
35
0.0022
0.0665
−29%
lactate
50
0.0035
0.0882
17%
Metabolite - 2141
35
0.0036
0.0882
126%
Metabolite - 5349
50
0.0037
0.0882
−19%
Metabolite - 2711
35
0.0046
0.1028
27%
caffeine
35
0.0049
0.1041
104%
N-acetyl-L-valine
35
0.0061
0.1135
−18%
monosaccharide
50
0.0063
0.1135
−18%
Metabolite - 2108
35
0.0069
0.1135
65%
Metabolite - 3402
35
0.007
0.1135
59%
Metabolite - 2407
35
0.0071
0.1135
−34%
n-hexadecanoic acid
50
0.0078
0.1191
19%
Metabolite - 3030
50
0.0082
0.1196
−18%
Metabolite - 1988
35
0.01
0.1398
43%
alpha-keto-glutarate
35
0.0104
0.1398
81%
Metabolite - 1121
35
0.0123
0.1555
−24%
Isobar-17-includes-arginine-N-alpha-
35
0.0125
0.1555
−27%
acetyl-ornithine
Metabolite - 1104
35
0.0155
0.1863
20%
Metabolite - 1116
35
0.0183
0.2034
78%
Metabolite - 1286
35
0.0188
0.2034
−15%
Metabolite - 1713
35
0.0189
0.2034
54%
Metabolite - 3088
50
0.0199
0.2034
−30%
Metabolite - 3977
35
0.0207
0.2034
20%
theobromine-theophylline
35
0.0212
0.2034
74%
Metabolite - 1839
35
0.0223
0.2034
85%
valine
50
0.0224
0.2034
16%
tartaric acid
35
0.0225
0.2034
61%
Metabolite - 3033
50
0.0244
0.2034
−13%
Metabolite - 1085-possible-isolobinine-or-
35
0.0247
0.2034
−17%
4-aminoestra-1-3-5-10-triene-3-17beta-
diol
glycerol
50
0.0247
0.2034
16%
3-methylglutaric acid
35
0.0249
0.2034
22%
Metabolite - 1831-possible-Cl-adduct-of-
35
0.0253
0.2034
160%
citrulline
Metabolite - 3303
35
0.0278
0.2179
19%
Metabolite - 3900
35
0.0294
0.2256
16%
octadecanoic acid
50
0.0337
0.2512
11%
Metabolite - 3843
35
0.0346
0.2512
22%
Metabolite - 2978
50
0.035
0.2512
−22%
Metabolite - 2005
35
0.0359
0.252
35%
aspartate
50
0.041
0.2818
34%
3-hydroxybutanoic acid
50
0.0434
0.2924
81%
Metabolite - 3832-possible-phenol-sulfate
35
0.0475
0.314
97%
phenylalanine
35
0.05
0.3241
7%
Metabolite - 3040
50
0.0517
0.329
−21%
alpha-tocopherol
50
0.0529
0.3301
91%
Metabolite - 3002
50
0.0539
0.3305
27%
creatinine
35
0.0563
0.3392
11%
dethiobiotin
50; 35
0.0603
0.3565
30%
linoleic acid
50
0.0622
0.3598
17%
L-homoserine
50
0.063
0.3598
−16%
Metabolite - 3309
35
0.066
0.3707
37%
Metabolite - 4147
50
0.0676
0.3735
32%
3-chloro-L-tyrosine
50
0.0704
0.3747
23%
isoleucine
50
0.072
0.3747
15%
Metabolite - 1834
35
0.0729
0.3747
54%
Metabolite - 3781-possible-Na-adduct-of-
35
0.073
0.3747
−9%
Isobar-21
Metabolite - 2390
35
0.0735
0.3747
38%
3-amino-isobutyrate
50
0.0756
0.3747
−13%
Metabolite - 3098
50
0.0761
0.3747
−24%
Metabolite - 2389
35
0.0767
0.3747
−65%
Metabolite - 3178-possible-NH3-adduct-
35
0.0803
0.3786
16%
of-isobar-42
Metabolite - 4031-possible-
35
0.0804
0.3786
14%
norlevorphenol-isobutylphendienamide-
amprolium
alanine
50
0.0821
0.3786
18%
leucine
50
0.0833
0.3786
15%
Metabolite - 1817
35
0.084
0.3786
−20%
Metabolite - 3146
35
0.0842
0.3786
49%
Metabolite - 3830
35
0.0863
0.3791
31%
alpha-4-dihydroxybenzenepropanoic acid
50
0.0866
0.3791
36%
Metabolite - 1829
35
0.0881
0.3809
−13%
Metabolite - 3534
35
0.0918
0.3827
43%
Metabolite - 4511
50
0.0925
0.3827
37%
Metabolite - 2285
35
0.0932
0.3827
217%
D-quinic acid
50
0.094
0.3827
72%
Isobar-6-includes-valine-betaine
35
0.0949
0.3827
8%
Metabolite - 3707
35
0.0965
0.3827
−52%
Metabolite - 3837
35
0.0965
0.3827
30%
Metabolite - 3813
35
0.0991
0.3855
38%
Metabolite - 2130
35
0.1005
0.3855
−43%
Metabolite - 3014
50
0.1016
0.3855
19%
Metabolite - 1836
35
0.1036
0.3855
39%
tryptophan
50; 35
0.1049
0.3855
12%
Metabolite - 3772
35
0.1052
0.3855
16%
Metabolite - 3138
35
0.1056
0.3855
31%
4-methyl-2-oxopentanoate
50
0.1063
0.3855
20%
glycine
50
0.1082
0.386
19%
Metabolite - 3314
35
0.1088
0.386
28%
Metabolite - 2254
35
0.112
0.3897
70%
Metabolite - 2974
50
0.1132
0.3897
−13%
p-acetamidophenyl-beta-D-glucuronide
35
0.1133
0.3897
392%
Metabolite - 3489
35
0.1178
0.4011
54%
Metabolite - 4362
50
0.1232
0.4152
−19%
carnosine
35
0.1257
0.4163
24%
melatonin
50
0.1259
0.4163
−11%
Metabolite - 3758
35
0.1279
0.4163
62%
Metabolite - 1609
35
0.1285
0.4163
23%
Metabolite - 2698
35
0.1297
0.4163
42%
trans-4-hydroxyproline
35; 50
0.1352
0.4205
−22%
Metabolite - 2391
35
0.1363
0.4205
15%
Metabolite - 4769
50
0.1368
0.4205
−15%
Metabolite - 3074
50
0.1368
0.4205
70%
Metabolite - 3067
50
0.1372
0.4205
13%
adenosine-5-monophosphate
35
0.142
0.4314
22%
Metabolite - 2287
35
0.1436
0.4322
−78%
Metabolite - 2388
35
0.1466
0.4372
−10%
cholesterol
50
0.1481
0.4372
11%
Metabolite - 1975
35
0.15
0.4372
−35%
Metabolite - 3016
50
0.1504
0.4372
10%
heptanedioic acid
35
0.1522
0.4378
−33%
glyceric acid
50
0.1532
0.4378
−16%
Metabolite - 2506
35
0.1556
0.4395
63%
azelaic acid
35
0.1571
0.4395
12%
Metabolite - 3143
35
0.1583
0.4395
21%
Metabolite - 5419
50
0.159
0.4395
29%
Metabolite - 2867
35
0.1608
0.4408
100%
Metabolite - 2056
35
0.1623
0.4412
17%
Isobar-13-includes-5-keto-D-gluconic
35
0.1646
0.4439
24%
acid-2-keto-L-gulonic acid-D-glucuronic
acid
glutamic acid
50
0.1716
0.4557
22%
Metabolite - 2924
50
0.1732
0.4557
20%
Metabolite - 3073
50
0.1743
0.4557
−19%
Isobar-5-includes-asparagine-ornithine
35
0.1744
0.4557
−14%
benzoic acid
50; 35
0.176
0.4557
−19%
tyramine
50
0.1771
0.4557
14%
Metabolite - 2255
35
0.183
0.459
−58%
glucose-6-phosphate
50
0.1835
0.459
6%
Metabolite - 1977
35
0.1838
0.459
14%
Metabolite - 2316
35
0.1841
0.459
−36%
2-keto-L-gulonic acid
50
0.1863
0.459
5%
n-dodecanoate
50
0.187
0.459
14%
Metabolite - 3474
35
0.189
0.459
−19%
ornithine
50
0.1892
0.459
22%
L-beta-imidazolelactic acid
50; 35
0.1952
0.4677
10%
5-oxoproline
50
0.1956
0.4677
10%
carnitine
35
0.197
0.4678
−9%
glutamine
50
0.1993
0.4698
16%
Metabolite - 3216
35
0.2052
0.4785
21%
Metabolite - 2212
35
0.2067
0.4785
−17%
fructose
50
0.2072
0.4785
29%
Metabolite - 3091
50
0.2097
0.481
−32%
Metabolite - 3109
50
0.216
0.4901
−25%
Metabolite - 2507
35
0.2166
0.4901
54%
histidine
50
0.2197
0.4937
13%
Metabolite - 5403
50
0.2235
0.4991
−11%
Metabolite - 1113-possible-
35
0.2254
0.5
14%
acetylcarnitine-or-isopentyl-adenine
catechol
35
0.2295
0.5058
53%
Metabolite - 3019
50
0.232
0.508
−10%
Metabolite - 4032
50
0.2399
0.5217
23%
Metabolite - 2898
35
0.2417
0.5223
57%
Metabolite - 3017
50
0.2449
0.5245
−13%
5-6-Dimethylbenzimidazole
50
0.2458
0.5245
25%
Metabolite - 1211
35
0.2482
0.5261
−67%
Metabolite - 2111
35
0.2497
0.5261
25%
Metabolite - 3160
35
0.2544
0.5298
18%
Metabolite - 4767
50
0.2546
0.5298
−19%
threonine
50
0.2588
0.5353
9%
Metabolite - 4042
50
0.2647
0.5433
8%
Metabolite - 2269-
35
0.2698
0.5433
−25%
Metabolite - 4078
35
0.2704
0.5433
23%
Metabolite - 3215
35
0.2706
0.5433
15%
Metabolite - 3624
35
0.2708
0.5433
23%
Metabolite - 3085
50
0.2758
0.5438
13%
Metabolite - 2914
50
0.2774
0.5438
−2%
Metabolite - 1110
35
0.2792
0.5438
−31%
Metabolite - 4167
35
0.2792
0.5438
20%
Metabolite - 3752
35
0.282
0.5438
−60%
Metabolite - 3877
35
0.2832
0.5438
28%
Metabolite - 3165
35
0.2842
0.5438
7%
glucono-gamma-lactone
50
0.2848
0.5438
7%
Metabolite - 3578
35
0.2855
0.5438
−24%
Metabolite - 3102
50
0.2897
0.5449
9%
Metabolite - 3131
35
0.2901
0.5449
−23%
Metabolite - 2027
35
0.2909
0.5449
18%
Metabolite - 3972
35
0.2949
0.5488
−13%
Metabolite - 1188
35
0.3012
0.5488
−17%
Metabolite - 2279
35
0.3017
0.5488
36%
arachidonic acid
50
0.304
0.5488
16%
Metabolite - 3089
50
0.3056
0.5488
23%
DL-cystathionine
35
0.3083
0.5488
−11%
trans-2-3-4-trimethoxycinnamic acid
35
0.3128
0.5488
−26%
p-hydroxybenzaldehyde
35
0.3129
0.5488
10%
Metabolite - 3576
35
0.3151
0.5488
−17%
Metabolite - 5489
50
0.3161
0.5488
−9%
Metabolite - 4795
50
0.3168
0.5488
−18%
Metabolite - 4504
50
0.3207
0.5488
16%
Metabolite - 3025
50
0.321
0.5488
−9%
fumaric acid
50
0.3213
0.5488
12%
Isobar-36-includes-D-sorbitol-6-
35
0.3219
0.5488
16%
phosphate-mannitol-1-phosphate
Metabolite - 1203-possible-
35
0.3221
0.5488
33%
acetylbrowniine-tricornine-germine-or-
veracevine
Metabolite - 3023
50
0.3225
0.5488
−9%
xylitol
35; 50
0.3244
0.5488
−16%
Metabolite - 2592
35
0.3264
0.5488
71%
methyl-indole-3-acetate
35
0.3269
0.5488
14%
Metabolite - 3313
35
0.3272
0.5488
61%
Metabolite - 1498
35
0.3289
0.549
−13%
Metabolite - 3184
35
0.3345
0.5509
15%
serine
50
0.3365
0.5509
7%
succinate
50
0.3397
0.5509
−7%
GABA
50
0.3397
0.5509
12%
Metabolite - 3027
50
0.3399
0.5509
−8%
Metabolite - 1656
35
0.341
0.5509
−14%
Metabolite - 3086
50
0.3429
0.5509
−19%
malic acid
35
0.3478
0.5509
26%
Metabolite - 4196
50
0.3484
0.5509
26%
Metabolite - 5906
50
0.3494
0.5509
35%
allantoin
35
0.351
0.5509
9%
L-alpha-glycerophosphorylcholine
35
0.3514
0.5509
22%
L-allo-threonine
50
0.3516
0.5509
7%
Metabolite - 2347
35
0.3533
0.5509
−23%
3-methyl-L-histidine
35
0.3568
0.5509
6%
Metabolite - 1914
35
0.3578
0.5509
−25%
3-phospho-d-glycerate
35
0.3582
0.5509
16%
Isobar-20-includes-fumaric acid-3-methyl-
35
0.3628
0.5509
−17%
2-oxobutanoate
urea
50
0.3643
0.5509
−6%
4-hydroxyphenylacetate
35; 50
0.3644
0.5509
5%
Metabolite - 4611
50
0.3655
0.5509
7%
Metabolite - 3807
35
0.366
0.5509
5%
pyridoxal-phosphate
35
0.3699
0.5528
−4%
Metabolite - 4361
50
0.3706
0.5528
−15%
adonitol
50
0.3737
0.5551
5%
N-N-dimethylarginine
35
0.3769
0.5553
9%
pantothenic acid
35
0.3772
0.5553
20%
Metabolite - 3012
50
0.384
0.5609
−7%
DL-pipecolic acid
35
0.3851
0.5609
11%
Isobar-4-includes-Gluconic acid-DL-
35
0.3861
0.5609
−12%
arabinose-D-ribose-L-xylose-DL-lyxose-
D-xylulose
Metabolite - 4355
50
0.389
0.5609
24%
DL-homocysteine
35
0.3893
0.5609
13%
25-hydroxycholesterol
50
0.3953
0.5642
4%
Metabolite - 4272
50
0.3955
0.5642
13%
Metabolite - 3130
35
0.3968
0.5642
18%
diaminopimelic acid
50; 35
0.3989
0.5642
−8%
Metabolite - 1835
35
0.4018
0.5642
−11%
Metabolite - 2281
35
0.403
0.5642
39%
Metabolite - 3498
35
0.4042
0.5642
−9%
Metabolite - 4084
50
0.405
0.5642
22%
proline
35; 50
0.4097
0.5684
8%
Metabolite - 3058
50
0.4147
0.573
−13%
Metabolite - 2888-possible-sulfated-
35
0.4195
0.5751
−11%
Rosiglitazone
Metabolite - 3078
50
0.4196
0.5751
−8%
Metabolite - 1911
35
0.4221
0.5761
−20%
inositol
50
0.4245
0.577
5%
citrulline
50
0.428
0.5795
−6%
Metabolite - 3055-possible-NH3-adduct-
35
0.4333
0.5828
−19%
of-hippuric acid
Metabolite - 4134
50
0.4339
0.5828
−6%
Metabolite - 2546
35
0.4358
0.583
15%
mannose
50
0.4399
0.5862
4%
Metabolite - 4516
50
0.4457
0.5899
−6%
Metabolite - 5437
50
0.4462
0.5899
27%
Metabolite - 3955
35
0.4482
0.5902
−23%
phosphoenolpyruvate
35
0.453
0.5922
10%
Metabolite - 4234
35
0.4546
0.5922
9%
Metabolite - 5847
50
0.455
0.5922
20%
citric acid
50
0.4573
0.5922
4%
Metabolite - 2915
50
0.4585
0.5922
−6%
Metabolite - 3125
35
0.4693
0.6021
7%
Metabolite - 3081
50
0.4697
0.6021
9%
Metabolite - 3370
35
0.4719
0.6026
9%
Metabolite - 4096-possible-gamma-glu-
35
0.4808
0.6117
−16%
gly-leu-
4-amino-5-methyl-2-1H-pyrimidinone
35
0.4852
0.6129
9%
Metabolite - 5427
50
0.4874
0.6129
4%
Metabolite - 4163
35
0.4882
0.6129
13%
Metabolite - 1216
35
0.489
0.6129
8%
nonanate
50
0.4925
0.6137
−3%
oxitryptan
35
0.4933
0.6137
10%
Metabolite - 2139
35
0.4964
0.6153
−8%
methionine
35
0.499
0.6163
4%
Metabolite - 3783
35
0.5036
0.6193
−11%
galactose
50
0.5059
0.6193
−6%
sn-Glycerol-3-phosphate
50
0.5069
0.6193
5%
Metabolite - 1208
35
0.5108
0.6218
19%
Metabolite - 2250
35
0.5155
0.6239
−15%
dulcitol
50
0.5164
0.6239
−6%
Metabolite - 4133
50
0.5194
0.6239
−7%
Metabolite - 2849-related-to-citric acid-
35
0.52
0.6239
−6%
dopamine
50
0.5264
0.6251
13%
Metabolite - 2386
35
0.5265
0.6251
17%
Metabolite - 4986
50
0.5287
0.6251
−14%
Metabolite - 3044
35
0.5288
0.6251
9%
Metabolite - 3094
50
0.5302
0.6251
7%
Metabolite - 2387
35
0.5328
0.6256
49%
gamma-L-glutamyl-L-tyrosine
35
0.5344
0.6256
−4%
Isobar-2-includes-3-amino-isobutyrate-2-
35
0.5412
0.6289
18%
amino-butyrate-4-aminobutanoic acid-
dimethylglycine-choline-
L-homoserine-lactone
35
0.5419
0.6289
−13%
Isobar-19-includes-D-saccharic acid-2-
35
0.5463
0.6289
−10%
deoxy-D-galactose-2-deoxy-D-glucose-L-
fucose-L-rhamnose
gamma-L-glutamyl-L-glutamine
35
0.5465
0.6289
−11%
Metabolite - 2567
35
0.5492
0.6289
−6%
Metabolite - 1086
35
0.5505
0.6289
11%
Metabolite - 4275
50
0.5511
0.6289
−6%
Metabolite - 3077
50
0.5522
0.6289
−6%
gamma-glu-leu
35
0.5551
0.6291
5%
Metabolite - 3320-possible-pimpinellin-or-
35
0.5561
0.6291
27%
tetrahydroxybenzophenone
Metabolite - 3992-possible-Cl-adduct-of-
35
0.56
0.6314
−4%
Formate-dimer
Metabolite - 1389-possible-glucuronide-
35
0.5643
0.6335
14%
form-of-Metabolite - 1359
Metabolite - 3020
50
0.5697
0.6335
−6%
guanosine-5-diphosphate
35
0.5698
0.6335
9%
Metabolite - 3426
35
0.5712
0.6335
2%
Metabolite - 2185
35
0.5746
0.6335
−5%
orotidine-5-phosphate
35
0.5748
0.6335
12%
Metabolite - 3951
35
0.575
0.6335
5%
biliverdin
35
0.5834
0.6407
9%
Metabolite - 2313
35
0.5904
0.6449
7%
Metabolite - 3056
35
0.5918
0.6449
5%
normetanephrine
50
0.593
0.6449
−6%
Metabolite - 2100
35
0.6011
0.6511
−4%
tyrosine
50
0.6026
0.6511
4%
Metabolite - 1142-possible-5-
35
0.611
0.6582
12%
hydroxypentanoate-or-beta-
hydroxyisovaleric acid
Metabolite - 1597
35
0.6293
0.6744
−3%
Metabolite - 3441
35
0.6319
0.6744
6%
glycochenodeoxycholic
35
0.6334
0.6744
14%
acid/glycodeoxycholic acid
Metabolite - 5346
50
0.6341
0.6744
5%
Metabolite - 3765
35
0.6389
0.6774
12%
Metabolite - 2249
35
0.6409
0.6774
7%
Metabolite - 4593
50
0.6542
0.6824
−2%
hippuric acid
35
0.6581
0.6824
10%
Metabolite - 3022
50
0.6591
0.6824
−5%
niacinamide
35
0.6593
0.6824
11%
phytonadione
50
0.6599
0.6824
4%
5-methoxytryptamine
50
0.6645
0.6824
−6%
Metabolite - 2486
35
0.6655
0.6824
9%
N-6-trimethyl-l-lysine
35
0.6657
0.6824
6%
Metabolite - 2753
35
0.6692
0.6824
5%
Metabolite - 3670
35
0.6697
0.6824
4%
Metabolite - 1465
35
0.67
0.6824
6%
Metabolite - 3604
35
0.6701
0.6824
−11%
Metabolite - 3075
50
0.6739
0.6824
−6%
Metabolite - 3879
35
0.6755
0.6824
−20%
Metabolite - 4148
50
0.6761
0.6824
−7%
Isobar-21-includes-gamma-aminobutyryl-
35
0.6781
0.6824
−7%
L-histidine-L-anserine
N-acetyl-L-leucine
35
0.6834
0.6858
13%
D-allose
50
0.6934
0.6906
−5%
Metabolite - 3181
35
0.6944
0.6906
5%
Metabolite - 3099
50
0.697
0.6906
8%
Metabolite - 2688
35
0.6986
0.6906
−8%
3-nitro-L-tyrosine
50; 35
0.7005
0.6906
8%
Metabolite - 3653-Possible-stachydrine-
35
0.7021
0.6906
−12%
Metabolite - 2392
35
0.7026
0.6906
18%
Metabolite - 3132
35
0.7104
0.695
3%
Isobar-25-includes-L-gulono-1-4-lactone-
35
0.7112
0.695
8%
glucono-gamma-lactone-
Metabolite - 1323-possible-4-sulfobenzyl-
35
0.7154
0.6971
3%
alcohol
heneicosanoic acid-methyl-ester
50
0.7198
0.6975
−4%
guanidineacetic acid
35
0.7202
0.6975
−5%
Metabolite - 1215
35
0.7223
0.6975
−11%
hypoxanthine
35
0.7241
0.6975
5%
Metabolite - 3134
35
0.7323
0.7008
13%
Isobar-30-includes-maltotetraose-
35
0.7345
0.7008
5%
stachyose
Metabolite - 2853
35
0.7345
0.7008
7%
Metabolite - 1244
35
0.7359
0.7008
6%
Metabolite - 1342-possible-
35
0.7405
0.7032
−7%
phenylacetylglutamine-or-formyl-N-acetyl-
5-methoxykynurenamine
Metabolite - 3135
35
0.7437
0.7043
−11%
pyrophosphate
35; 50
0.7499
0.7082
9%
ethyl-3-indoleacetate
50
0.7704
0.7186
3%
Metabolite - 3476
35
0.7739
0.7186
7%
Metabolite - 1183
35
0.778
0.7186
−8%
Isobar-9-includes-sucrose-beta-D-lactose-
35
0.7787
0.7186
5%
D-trehalose-D-cellobiose-D-Maltose-
palatinose-melibiose-alpha-D-lactose
Metabolite - 4503
50
0.7819
0.7186
9%
L-kynurenine
35
0.7838
0.7186
3%
Metabolite - 3093
50
0.7844
0.7186
6%
Metabolite - 4365
50
0.7869
0.7186
5%
Metabolite - 3698
35
0.7885
0.7186
6%
oxalacetic acid
35
0.7896
0.7186
5%
inosine
35
0.7915
0.7186
−9%
Metabolite - 1573
35
0.7953
0.7186
5%
uric acid
35
0.7956
0.7186
1%
vitamin-B6
50
0.7962
0.7186
2%
Metabolite - 4020
50
0.7967
0.7186
1%
Metabolite - 1351
35
0.7988
0.7186
3%
alphahydroxybenzeneacetic acid
35
0.8012
0.7186
−3%
Metabolite - 1915
35
0.8026
0.7186
−13%
Metabolite - 3994
35
0.8031
0.7186
7%
Metabolite - 3218
35
0.8059
0.7186
4%
phenyl-beta-glucopyranoside
50
0.8076
0.7186
−4%
Metabolite - 1289
35
0.8079
0.7186
5%
histamine
35
0.81
0.7186
−5%
Metabolite - 2370
35
0.8174
0.7197
−4%
Metabolite - 2053
35
0.818
0.7197
4%
Metabolite - 5907
50
0.8229
0.7197
−2%
hydroxyacetic acid
50
0.8232
0.7197
−4%
maltose
50
0.8234
0.7197
−4%
Metabolite - 3761
35
0.824
0.7197
5%
tryptamine
50
0.8298
0.7229
−3%
Metabolite - 2809
35
0.8365
0.7257
5%
Metabolite - 4768
50
0.8383
0.7257
6%
Metabolite - 2256
35
0.8395
0.7257
4%
Metabolite - 2973
50
0.8416
0.7257
−1%
Metabolite - 3245
35
0.8492
0.7286
4%
Metabolite - 2129
35
0.8493
0.7286
5%
Metabolite - 4274
50
0.8535
0.7303
2%
Metabolite - 1974
35
0.8572
0.7316
−4%
Metabolite - 1220
35
0.8619
0.7331
−5%
pyridoxamine-phosphate
35
0.8654
0.7331
−2%
thyroxine
35
0.8659
0.7331
−2%
N-acetylserotonin
50
0.868
0.7331
1%
Metabolite - 3968
35
0.8698
0.7331
4%
Metabolite - 3108
50
0.8722
0.7333
−1%
Metabolite - 2055
35
0.8779
0.7362
−2%
D-alanyl-D-alanine
35
0.8819
0.7378
2%
Metabolite - 4791
50
0.8875
0.7401
5%
Metabolite - 3816
35
0.8926
0.7401
2%
Metabolite - 3167
35
0.8948
0.7401
3%
4-Guanidinobutanoic acid
35
0.895
0.7401
2%
glycocholic acid
35
0.8957
0.7401
5%
Isobar-1-includes-mannose-fructose-
35
0.8978
0.7401
2%
glucose-galactose-alpha-L-
sorbopyranose-Inositol-D-allose
3-hydroxyphenylacetate
35
0.9038
0.7415
1%
Metabolite - 3004
50
0.9114
0.7415
2%
noradrenaline
50
0.9121
0.7415
2%
Metabolite - 2074
35
0.9154
0.7415
−2%
Metabolite - 2686
35
0.9155
0.7415
−1%
Metabolite - 3436
35
0.916
0.7415
−2%
Metabolite - 4091-possible-gamma-
35
0.9173
0.7415
1%
glutamyl-glutamic acid
3-methoxy-L-tyrosine
50
0.9174
0.7415
0%
7-8-dihydrofolic acid
35
0.9197
0.7415
−4%
Metabolite - 4238
35
0.9224
0.7415
−2%
glucarate
50
0.9243
0.7415
2%
phosphate
50
0.9259
0.7415
1%
Metabolite - 1979-Cl-adduct-of-C6H10O5
35
0.9351
0.7426
−1%
Metabolite - 1335
35
0.9375
0.7426
−1%
Metabolite - 3166
35
0.9387
0.7426
2%
xanthine
35
0.9416
0.7426
−2%
3-hydroxypropanoate
50
0.9424
0.7426
1%
Metabolite - 4015
50
0.9455
0.7426
0%
Metabolite - 3183-possible-gamma-L-
35
0.946
0.7426
−1%
glutamyl-L-phenylalanine-or-aspartame
Metabolite - 1111-possible-
35
0.9467
0.7426
−1%
methylnitronitrosoguanidine-or-ethyl-
thiocarbamoylacetate
Metabolite - 1843
35
0.9471
0.7426
−1%
Metabolite - 3615
35
0.9529
0.7437
−1%
octopamine
50
0.9564
0.7447
1%
Isobar-18-includes-D-fructose-1-
35
0.9652
0.7498
0%
phosphate-beta-D-fructose-6-phosphate
Metabolite - 3003
50
0.9736
0.7546
0%
Metabolite - 5366
50
0.983
0.757
0%
Metabolite - 4360
50
0.9831
0.757
−1%
Metabolite - 3097
50
0.9839
0.757
−1%
Metabolite - 1392
35
0.9857
0.757
1%
Metabolite - 3129
35
0.9973
0.7602
0%
Metabolite - 1133-possible-Na-adduct-of-
35
0.9981
0.7602
0%
EDTA
Metabolite - 3243
35
0.9986
0.7602
0%
Metabolite - 1349
35
0.9989
0.7602
0%
[0000]
TABLE 5
Prostate Cancer Biomarkers from Urine from subjects with
Prostate Cancer compared to Urine from Control subjects.
% Change
COMPOUND
Library
p-value
q-value
in PCA
Metabolite - 2974
50
0.0023
0.1555
−32%
2-amino-butyrate
50
0.0035
0.1555
−27%
guanidineacetic acid
35
0.0048
0.1555
−65%
citrulline
50
0.006
0.1555
−43%
Metabolite - 2752
35
0.0063
0.1555
−38%
adenosine
35
0.0067
0.1555
−46%
Metabolite - 2242
35
0.0068
0.1555
170%
3-methoxy-4-hydroxyphenylacetate
50
0.0096
0.1555
−41%
Metabolite - 4504
50
0.0118
0.1555
−36%
N-acetyl-D-glucosamine
50
0.012
0.1555
−53%
Metabolite - 2978
50
0.012
0.1555
−29%
Metabolite - 1573
35
0.013
0.1555
−28%
Metabolite - 2181
35
0.0134
0.1555
−34%
Metabolite - 4522
50
0.0149
0.1555
−35%
serine
50
0.016
0.1555
−38%
methionine
35
0.0162
0.1555
−32%
catechol
35
0.0163
0.1555
−60%
Metabolite - 3215
35
0.0164
0.1555
−31%
Metabolite - 4593
50
0.0167
0.1555
−36%
Isobar-9-includes-sucrose-beta-D-
35
0.017
0.1555
−49%
lactose-D-trehalose-D-cellobiose-D-
Maltose-palatinose-melibiose-alpha-D-
lactose
Metabolite - 2567
35
0.0188
0.1611
−33%
uracil
50
0.0194
0.1611
−36%
Metabolite - 3020
50
0.0217
0.1611
−41%
Metabolite - 3807
35
0.0225
0.1611
−25%
arabinose
50
0.0227
0.1611
−47%
histamine
35
0.0249
0.1611
−37%
Metabolite - 3761
35
0.026
0.1611
−31%
Metabolite - 3443
35
0.0262
0.1611
100%
DL-homocysteine
35
0.0263
0.1611
−43%
Metabolite - 2271
35
0.0264
0.1611
−47%
Metabolite - 4503
50
0.0264
0.1611
−38%
glycine
50
0.0284
0.1641
−37%
Isobar-4-includes-Gluconic acid-DL-
35
0.0297
0.1641
−33%
arabinose-D-ribose-L-xylose-DL-lyxose-
D-xylulose
adenosine-3-5-cyclic-monophosphate
35
0.0301
0.1641
−24%
citric acid
50
0.0304
0.1641
−38%
dopamine
50
0.0317
0.1641
−30%
Metabolite - 1974
35
0.0347
0.1641
−42%
N-acetylneuraminate
50
0.0348
0.1641
−32%
Metabolite - 3381
35
0.0352
0.1641
−35%
adenine
50
0.0359
0.1641
−37%
Metabolite - 2051
35
0.0361
0.1641
−22%
serotonin
35
0.0364
0.1641
−33%
Metabolite - 4636
50
0.0396
0.1641
−44%
Isobar-19-includes-D-saccharic acid-2-
35
0.0416
0.1641
−58%
deoxy-D-galactose-2-deoxy-D-glucose-
L-fucose-L-rhamnose
L-allo-threonine
50
0.0421
0.1641
−31%
Metabolite - 1349
35
0.0426
0.1641
−36%
N-6-trimethyl-l-lysine
35
0.0433
0.1641
−38%
Metabolite - 3370
35
0.0481
0.1641
−35%
Metabolite - 3056
35
0.0489
0.1641
−29%
Metabolite - 3803
35
0.049
0.1641
−41%
1-methyladenosine
35
0.0501
0.1641
−34%
N-tigloylglycine
35
0.0501
0.1641
−31%
tyrosine
50
0.0503
0.1641
−31%
threonine
50
0.0516
0.1641
−31%
Metabolite - 3951
35
0.0518
0.1641
−25%
carnosine
35
0.0542
0.1641
−37%
xylitol
35; 50
0.055
0.1641
−35%
caffeine
35
0.0555
0.1641
79%
Metabolite - 2277
35
0.0558
0.1641
−28%
Metabolite - 1979-Cl-adduct-of-
35
0.0565
0.1641
−45%
C6H10O5
heptanedioic acid
35
0.0573
0.1641
−28%
orotic acid
50
0.0584
0.1641
−44%
Metabolite - 1342-possible-
35
0.0596
0.1641
−29%
phenylacetylglutamine-or-formyl-N-
acetyl-5-methoxykynurenamine
beta-hydroxyisovaleric acid
50
0.0598
0.1641
−34%
Metabolite - 1911
35
0.0613
0.1641
−50%
ornithine
50
0.0615
0.1641
−34%
Metabolite - 4499
50
0.0619
0.1641
−36%
Metabolite - 4519
50
0.0619
0.1641
−55%
Metabolite - 2390
35
0.0635
0.1641
−43%
Metabolite - 3329
35
0.064
0.1641
−59%
7-8-dihydrofolic acid
35
0.0648
0.1641
−26%
Metabolite - 4251
50
0.0652
0.1641
−40%
Metabolite - 1655
35
0.0659
0.1641
−51%
Metabolite - 3955
35
0.0663
0.1641
−43%
N-acetyl-L-valine
35
0.0669
0.1641
−51%
3-ureidopropionic acid
35
0.0672
0.1641
−49%
erythrose-4-phosphate
50
0.0681
0.1641
−45%
Metabolite - 3033
50
0.0691
0.1641
−35%
gluconic acid
50
0.0697
0.1641
−46%
succinate
50
0.0704
0.1641
−41%
2-acetamido-1-amino-1-2-dideoxy-beta-
50
0.0705
0.1641
−36%
D-glucopyranose
fructose
50
0.072
0.1641
−43%
Metabolite - 3327
35
0.0729
0.1641
−46%
5-6-Dihydrothymine
35
0.0731
0.1641
−34%
Metabolite - 3908
35
0.0744
0.1641
−39%
Metabolite - 3305
35
0.0747
0.1641
−43%
Metabolite - 4502
50
0.0748
0.1641
−5%
phenylalanine
35
0.0753
0.1641
−25%
Metabolite - 3055-possible-NH3-adduct-
35
0.0765
0.1641
46%
of-hippuric acid
pyrophosphate
35; 50
0.0783
0.1641
−53%
Metabolite - 3183-possible-gamma-L-
35
0.079
0.1641
−37%
glutamyl-L-phenylalanine-or-aspartame
guanine
35
0.0803
0.1641
−30%
Metabolite - 3970
35
0.0804
0.1641
−31%
Metabolite - 3246-possible-Ala-GLy-
35
0.0816
0.1641
−38%
glycyl-sarcosine-or-ureido-butyric acid
5-6-Dimethylbenzimidazole
50
0.0818
0.1641
−47%
urocanic acid
35
0.0821
0.1641
−35%
Metabolite - 3813
35
0.083
0.1641
−32%
Metabolite - 4523
50
0.0831
0.1641
−30%
Metabolite - 2285
35
0.084
0.1641
−34%
5-hydroxyindoleacetate
50
0.0847
0.1641
−35%
Isobar-29-includes-R—S-hydroorotic
35
0.0847
0.1641
−81%
acid-5-6-dihydroorotic acid
valine
50
0.0849
0.1641
−23%
leucine
50
0.0862
0.1651
−37%
Metabolite - 4639
50
0.0905
0.1703
−52%
4-hydroxy-3-methoxymandelate
50
0.0906
0.1703
−33%
Metabolite - 1656
35
0.0927
0.1726
−52%
Metabolite - 2781
35
0.0965
0.1752
−22%
3-phospho-d-glycerate
35
0.0989
0.1752
−33%
N-acetyl-L-leucine
35
0.099
0.1752
−33%
Metabolite - 4505
50
0.0997
0.1752
−49%
Metabolite - 4002
50
0.0999
0.1752
−35%
Metabolite - 4112
35
0.1002
0.1752
−33%
4-acetominophen-sulfate
35
0.1013
0.1755
−35%
cellobiose
50
0.1027
0.1765
−48%
Metabolite - 1829
35
0.1037
0.1767
−22%
Metabolite - 3489
35
0.1062
0.1794
102%
DL-beta-hydroxyphenylethylamine
35
0.1082
0.1813
−29%
Metabolite - 4628
50
0.1098
0.182
−57%
4-hydroxymandelate
50
0.1115
0.182
−39%
5-oxoproline
50
0.1124
0.182
−29%
4-acetamidobutyric acid
35
0.1142
0.182
−28%
4-Guanidinobutanoic acid
35
0.1143
0.182
−28%
Metabolite - 2546
35
0.1157
0.182
−23%
histidine
50
0.1191
0.182
−38%
cysteine
50
0.1196
0.182
−52%
Metabolite - 4516
50
0.1197
0.182
−53%
L-beta-imidazolelactic acid
50; 35
0.1201
0.182
−25%
Metabolite - 2293-possible-O-
35
0.1215
0.182
−32%
desmethylvenlafaxine-glucuronide
Metabolite - 1383-possible-salicyluric-
35
0.1218
0.182
−52%
glucuronide
Metabolite - 4027
50
0.1224
0.182
−28%
Metabolite - 2807
35
0.1228
0.182
−44%
Metabolite - 3576
35
0.1229
0.182
−44%
cis-aconitic acid
50
0.124
0.182
−43%
Metabolite - 3322
35
0.1266
0.182
−39%
N—N-dimethylarginine
35
0.1269
0.182
−23%
Metabolite - 3828
35
0.1273
0.182
−32%
noradrenaline
50
0.1276
0.182
−43%
Metabolite - 4638
50
0.1281
0.182
−49%
creatinine
35
0.1327
0.1866
−17%
Metabolite - 4618
50
0.1343
0.1868
−32%
Metabolite - 4629
50
0.1347
0.1868
−31%
Metabolite - 3800
35
0.1366
0.1881
−40%
3-hydroxybutanoic acid
50
0.1415
0.1926
92%
Metabolite - 3817
35
0.1418
0.1926
−30%
methylmalonic acid
50
0.143
0.193
−42%
Metabolite - 4595
50
0.1443
0.1932
−23%
Metabolite - 4637
50
0.1468
0.1932
−54%
Metabolite - 3830
35
0.1474
0.1932
−40%
Metabolite - 4624
50
0.1475
0.1932
−24%
xanthine
35
0.148
0.1932
−43%
Metabolite - 3805
35
0.1504
0.195
−26%
Metabolite - 4635
50
0.1599
0.1957
−56%
folic acid
35
0.1603
0.1957
−37%
diaminopimelic acid
50; 35
0.1608
0.1957
−26%
Metabolite - 2973
50
0.1618
0.1957
29%
Metabolite - 3973
35
0.1629
0.1957
−65%
Metabolite - 3605
35
0.163
0.1957
−44%
N-formyl-L-methionine
35
0.1643
0.1957
−35%
urea
50
0.1643
0.1957
−21%
riboflavine
35
0.1654
0.1957
−73%
Metabolite - 1289
35
0.1665
0.1957
−16%
Metabolite - 3380
35
0.1674
0.1957
−29%
Metabolite - 4611
50
0.1674
0.1957
−26%
Metabolite - 4511
50
0.1685
0.1957
−38%
(1′R-1′S)_biopterin
35
0.1687
0.1957
−25%
1-methyladenine
50
0.1694
0.1957
−45%
4-hydroxy-2-quinolinecarboxylic acid
50
0.17
0.1957
−41%
Metabolite - 3994
35
0.1716
0.1957
−32%
Metabolite - 2550
35
0.1717
0.1957
−44%
Metabolite - 3898
35
0.1721
0.1957
−16%
Metabolite - 3103
50
0.1723
0.1957
43%
possible-L-homocysteine-thiolactone-
50
0.1735
0.1959
−30%
identical-to-homocysteine
Metabolite - 1122
35
0.1757
0.1972
−23%
tryptophan
50; 35
0.1769
0.1972
−20%
Metabolite - 1335
35
0.1775
0.1972
−23%
Metabolite - 2557-possible-
35
0.1812
0.2002
−34%
Pantoprazole-metabolite
asparagine
50
0.1833
0.2014
−32%
Metabolite - 3837
35
0.1862
0.2025
−33%
Metabolite - 3659
35
0.1878
0.2025
−26%
mannitol
50
0.1883
0.2025
−39%
D-alanyl-D-alanine
35
0.1885
0.2025
−23%
3-amino-isobutyrate
50
0.1894
0.2025
−39%
Metabolite - 4498
50
0.1936
0.2059
−27%
hypoxanthine
35
0.1978
0.2093
−36%
Isobar-24-includes-L-arabitol-adonitol
35
0.2001
0.2095
−8%
hydroxyacetic acid
50
0.2012
0.2095
−21%
Metabolite - 1843
35
0.2013
0.2095
−18%
Metabolite - 3216
35
0.2022
0.2095
−8%
Metabolite - 2175
35
0.2045
0.2108
−49%
alanine
50
0.2058
0.211
−27%
Metabolite - 2366
35
0.2076
0.2118
40%
Metabolite - 3873
35
0.2143
0.2124
−23%
Metabolite - 4046
50
0.2165
0.2124
−73%
Metabolite - 1455
35
0.2166
0.2124
−18%
Metabolite - 3708
35
0.2167
0.2124
−63%
Metabolite - 3843
35
0.217
0.2124
−30%
Metabolite - 3886
35
0.2177
0.2124
−21%
Metabolite - 2174
35
0.2178
0.2124
−23%
4-8-dihydroxyquinoline-2-carboxylic
50
0.2182
0.2124
−31%
acid
Metabolite - 3387
35
0.2183
0.2124
−23%
Metabolite - 4271
50
0.2193
0.2124
−30%
tyramine
50
0.2204
0.2124
−42%
Metabolite - 4496
50
0.2215
0.2124
−15%
normetanephrine
50
0.2223
0.2124
−13%
Metabolite - 1679
35
0.2229
0.2124
−22%
trans-4-hydroxyproline
35; 50
0.2281
0.2163
−24%
Metabolite - 2703
35
0.2307
0.2174
−14%
Metabolite - 3169
35
0.2314
0.2174
−62%
Metabolite - 4634
50
0.2337
0.2185
−28%
Metabolite - 3221
35
0.2367
0.2196
−25%
alpha-4-dihydroxybenzenepropanoic
50
0.237
0.2196
−48%
acid
uric acid
35
0.243
0.2227
−6%
Metabolite - 3841
35
0.2435
0.2227
−32%
Metabolite - 4500
50
0.2437
0.2227
−62%
Metabolite - 3667
35
0.2468
0.2245
−20%
Metabolite - 4495
50
0.2517
0.228
−22%
Metabolite - 3706
35
0.2536
0.2286
−17%
D-lyxose
50
0.2626
0.2336
−26%
glutamine
50
0.2629
0.2336
−28%
Metabolite - 3014
50
0.2637
0.2336
−21%
Metabolite - 3802
35
0.2638
0.2336
−34%
Metabolite - 2591
35
0.2717
0.2375
32%
Metabolite - 3178-possible-NH3-adduct-
35
0.2724
0.2375
−28%
of-isobar-42
Metabolite - 2607
35
0.2727
0.2375
−38%
L-kynurenine
35
0.2729
0.2375
−76%
gamma-L-glutamyl-L-tyrosine
35
0.2752
0.2385
−23%
Metabolite - 3832-possible-phenol-
35
0.2771
0.2391
66%
sulfate
hippuric acid
35
0.2825
0.2427
−21%
4-hydroxyphenylacetate
35; 50
0.2898
0.2469
−24%
Metabolite - 3108
50
0.2898
0.2469
−34%
Metabolite - 3834
35
0.2916
0.2473
−33%
allantoin
35
0.2933
0.2478
−19%
Metabolite - 2118
35
0.2957
0.2488
−19%
Metabolite - 3440
35
0.2986
0.2501
192%
ascorbic acid
50
0.3011
0.2502
−70%
Metabolite - 1498
35
0.3011
0.2502
−40%
Metabolite - 4509
50
0.3032
0.2508
−38%
Isobar-6-includes-valine-betaine
35
0.3058
0.2519
−16%
Metabolite - 2150
35
0.312
0.2556
−24%
Metabolite - 3911
35
0.3148
0.2556
−14%
1-5-diaminopentane
50
0.3158
0.2556
−40%
proline
35; 50
0.3161
0.2556
−29%
salicyluric acid
35
0.3167
0.2556
−71%
Metabolite - 4494
50
0.3178
0.2556
14%
porphobilinogen
35
0.3208
0.2569
−20%
Metabolite - 3804
35
0.3263
0.2589
−21%
pantothenic acid
35
0.3273
0.2589
−36%
Metabolite - 3099
50
0.3281
0.2589
−25%
Metabolite - 3660
35
0.3284
0.2589
−39%
Metabolite - 3090
50
0.3345
0.2598
−11%
Metabolite - 4632
50
0.3356
0.2598
−45%
Isobar-2-includes-3-amino-isobutyrate-
35
0.3373
0.2598
183%
2-amino-butyrate-4-aminobutanoic acid-
dimethylglycine-choline-
Metabolite - 3309
35
0.3374
0.2598
−18%
Metabolite - 1110
35
0.3379
0.2598
−17%
Metabolite - 3493
35
0.3384
0.2598
−17%
Metabolite - 3163-possible-
35
0.3387
0.2598
−15%
methylcytidine-benserazide-or-Pyr-Gln-
OH
N-alpha-acetyl-L-ornithine-
50
0.345
0.2637
−16%
Metabolite - 1465
35
0.3552
0.2705
−14%
Metabolite - 1834
35
0.3614
0.2729
53%
3-methyl-L-histidine
35
0.3622
0.2729
−14%
carnitine
35
0.3625
0.2729
32%
Metabolite - 1338
35
0.3638
0.2729
25%
dulcitol
50
0.3732
0.2789
−36%
glutamic acid
50
0.3771
0.2808
−15%
Metabolite - 2259
35
0.3795
0.2815
−42%
S-adenosyl-l-homocysteine
35
0.3841
0.2839
−19%
D-allose
50
0.3895
0.2858
−21%
Metabolite - 4234
35
0.3895
0.2858
−51%
Metabolite - 3091
50
0.3975
0.2906
−27%
2-deoxy-D-glucose
50
0.4016
0.292
−26%
Metabolite - 3963
35
0.4038
0.292
−54%
Metabolite - 2292
35
0.4038
0.292
23%
isoleucine
50
0.4077
0.2936
−15%
Metabolite - 2893-possible-
35
0.4115
0.2936
−21%
demethylated-Rosiglitazone
glucose-6-phosphate
50
0.4136
0.2936
189%
2-keto-L-gulonic acid
50
0.4138
0.2936
194%
Metabolite - 1496
35
0.4148
0.2936
−31%
theobromine-theophylline
35
0.418
0.2944
41%
Metabolite - 3131
35
0.42
0.2944
−19%
Metabolite - 3085
50
0.4202
0.2944
38%
Metabolite - 3893
35
0.4258
0.2971
−15%
Metabolite - 2686
35
0.4273
0.2971
−15%
Metabolite - 2386
35
0.4286
0.2971
−13%
Metabolite - 2108
35
0.432
0.2981
55%
Metabolite - 2249
35
0.4331
0.2981
−30%
Metabolite - 3604
35
0.4379
0.3004
−16%
Metabolite - 3543
35
0.4474
0.3041
−42%
Metabolite - 3878
35
0.4474
0.3041
25%
Metabolite - 4507
50
0.4492
0.3041
−21%
Metabolite - 3771
35
0.4493
0.3041
−28%
3-nitro-L-tyrosine
50; 35
0.4548
0.3062
−20%
lactate
50
0.4554
0.3062
14%
Metabolite - 3668
35
0.4624
0.3084
12%
Metabolite - 2506
35
0.4645
0.3084
−18%
Metabolite - 2254
35
0.4659
0.3084
69%
Isobar-13-includes-5-keto-D-gluconic
35
0.4661
0.3084
−34%
acid-2-keto-L-gulonic acid-D-glucuronic
acid
Metabolite - 3909
35
0.4663
0.3084
55%
Metabolite - 1682
35
0.4794
0.3142
−16%
dethiobiotin
50; 35
0.4799
0.3142
−39%
alpha-L-sorbopyranose
50
0.482
0.3142
−29%
beta-D-lactose
50
0.4838
0.3142
−21%
Metabolite - 2329
35
0.4846
0.3142
−11%
Metabolite - 4520
50
0.4866
0.3145
32%
Metabolite - 1114
35
0.4884
0.3147
−21%
malic acid
35
0.49
0.3147
−15%
Metabolite - 4501
50
0.4979
0.3188
−19%
Metabolite - 3436
35
0.5088
0.3247
−11%
Metabolite - 1351
35
0.5117
0.3255
−21%
Metabolite - 3806
35
0.5173
0.3281
−24%
Metabolite - 2726
35
0.519
0.3281
−12%
Metabolite - 4518
50
0.5282
0.3329
−32%
Metabolite - 3409
35
0.5303
0.3331
−17%
Metabolite - 4133
50
0.5446
0.341
−21%
Metabolite - 3952
35
0.547
0.3415
−20%
Metabolite - 3879
35
0.5531
0.3442
−27%
Metabolite - 3113
50
0.5631
0.3488
17%
Metabolite - 3433
35
0.5639
0.3488
−9%
tartaric acid
35
0.5703
0.3517
−20%
Metabolite - 2698
35
0.5772
0.3549
38%
Metabolite - 2056
35
0.5849
0.3582
−8%
Metabolite - 3670
35
0.5873
0.3582
−9%
Metabolite - 3786
35
0.5899
0.3582
−14%
Metabolite - 2853
35
0.5908
0.3582
−16%
Metabolite - 3981
35
0.5931
0.3582
−21%
Metabolite - 3564
35
0.5948
0.3582
−23%
Metabolite - 3781-possible-Na-adduct-
35
0.5951
0.3582
−12%
of-Isobar-21
Metabolite - 1186
35
0.5992
0.3585
−11%
2-isopropylmalic acid
50
0.5992
0.3585
37%
Isobar-1-includes-mannose-fructose-
35
0.6073
0.3623
26%
glucose-galactose-alpha-L-
sorbopyranose-Inositol-D-allose
Metabolite - 1101
35
0.6174
0.3672
−10%
Metabolite - 4167
35
0.6297
0.3734
−10%
Metabolite - 2005
35
0.6452
0.3814
−9%
sn-Glycerol-3-phosphate
50
0.65
0.3814
−13%
3-methylglutaric acid
35
0.6501
0.3814
9%
Metabolite - 3992-possible-Cl-adduct-
35
0.6507
0.3814
−5%
of-Formate-dimer
mercaptopyruvate
35
0.6565
0.383
−12%
homogentisate
35
0.6586
0.383
−9%
azelaic acid
35
0.6592
0.383
18%
Metabolite - 4510
50
0.6672
0.3866
−13%
3-hydroxyphenylacetate
35
0.674
0.3883
−10%
Metabolite - 3127
35
0.6771
0.3883
−9%
phosphoenolpyruvate
35
0.6772
0.3883
−17%
Metabolite - 3138
35
0.6779
0.3883
−10%
agmatine
35
0.6825
0.3898
−15%
Metabolite - 3402
35
0.6861
0.3899
−6%
alpha-keto-glutarate
35
0.7074
0.4
−11%
Metabolite - 4512
50
0.7083
0.4
−17%
Metabolite - 2323
35
0.7136
0.4012
−9%
Metabolite - 3701
35
0.7145
0.4012
−10%
Metabolite - 3016
50
0.73
0.4068
4%
Metabolite - 2272
35
0.7302
0.4068
−17%
DL-pipecolic acid
35
0.7319
0.4068
−12%
Metabolite - 4633
50
0.7325
0.4068
−8%
niacinamide
35
0.7378
0.4086
8%
Metabolite - 3123
35
0.7434
0.41
−8%
galactose
50
0.7512
0.41
−13%
pyridoxamine-phosphate
35
0.752
0.41
5%
Metabolite - 3101
50
0.7539
0.41
−7%
o-phosphoethanolamine
50
0.756
0.41
−8%
Metabolite - 3516
35
0.7584
0.41
−7%
DL-indole-3-lactic acid
50; 35
0.76
0.41
11%
Metabolite - 1126
35
0.7615
0.41
−9%
Metabolite - 1981
35
0.7617
0.41
−6%
Metabolite - 3986
35
0.7628
0.41
−8%
Metabolite - 4598
50
0.7687
0.4121
−7%
Metabolite - 4514
50
0.775
0.4127
9%
Metabolite - 3507
35
0.7759
0.4127
−7%
Metabolite - 1216
35
0.776
0.4127
4%
Metabolite - 3053
35
0.788
0.4172
−12%
L-rhamnose
50
0.7886
0.4172
5%
Metabolite - 2389
35
0.7912
0.4175
6%
Metabolite - 1368
35
0.7964
0.4191
−11%
alphahydroxybenzeneacetic acid
35
0.7995
0.4196
−4%
benzoic acid
50; 35
0.809
0.4235
6%
N-acetyl-L-alanine
35
0.8203
0.4259
−4%
Metabolite - 4517
50
0.8203
0.4259
−6%
Metabolite - 4092
35
0.8218
0.4259
−6%
Metabolite - 3977
35
0.8221
0.4259
−8%
Isobar-38-includes-N-acetyl-L-
35
0.8281
0.428
4%
methionine-5-hydroxy-1H-indole-3-
acetic acid
Metabolite - 2706
35
0.8316
0.4284
6%
Metabolite - 3311-possible-Zolpidem-in-
35
0.8367
0.4284
7%
humans-
Metabolite - 4010
50
0.8374
0.4284
−6%
Metabolite - 3773
35
0.8375
0.4284
−5%
Metabolite - 2897
35
0.847
0.4322
5%
Metabolite - 3364
35
0.8537
0.434
5%
Metabolite - 3231
35
0.8549
0.434
−4%
Metabolite - 3957
35
0.8591
0.435
−3%
Metabolite - 2269-
35
0.8619
0.4353
−3%
Metabolite - 3754
35
0.873
0.4398
5%
Metabolite - 2387
35
0.8782
0.4414
−5%
Metabolite - 3377
35
0.8819
0.4421
−6%
Metabolite - 2319
35
0.8913
0.445
−3%
suberic acid
35
0.8921
0.445
3%
oxalacetic acid
35
0.8946
0.4451
−2%
Metabolite - 3876
35
0.8969
0.4451
−6%
Metabolite - 2348
35
0.8988
0.4451
−4%
Metabolite - 1839
35
0.9015
0.4453
5%
Metabolite - 1113-possible-
35
0.9057
0.4462
−4%
acetylcarnitine-or-isopentyl-adenine
3-methyl-2-oxovaleric acid
35
0.9096
0.4469
−4%
melibiose
50
0.9114
0.4469
4%
Metabolite - 1364
35
0.9316
0.4557
3%
Metabolite - 4524
50
0.9364
0.4569
4%
thymidine
35
0.9412
0.4581
2%
Metabolite - 3755
35
0.9473
0.46
−1%
Metabolite - 3855
35
0.9504
0.4604
−1%
Metabolite - 3058
50
0.966
0.4638
2%
Metabolite - 1116
35
0.9663
0.4638
−1%
Metabolite - 3847
35
0.9693
0.4638
−1%
Metabolite - 3313
35
0.9709
0.4638
−1%
5-s-methyl-5-thioadenosine
35
0.9714
0.4638
1%
Metabolite - 3887
35
0.9799
0.4668
−1%
Metabolite - 3824
35
0.9839
0.4676
0%
Metabolite - 3457
35
0.9863
0.4676
−1%
Metabolite - 1283
35
0.9995
0.4728
0%
Example 3
Distinguish Lower Grade from Higher Grade/Metastatic Prostate Cancer in Subjects Using Plasma
[0120] Biomarkers were discovered by (1) analyzing plasma samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0121] The plasma samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, higher grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0122] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/Higher Grade Prostate cancer vs. Lower Grade Prostate cancer).
Biomarkers:
[0123] As listed below in Table 6, biomarkers were discovered that were differentially present between plasma samples from subjects with lower grade prostate cancer and plasma samples from Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 7 lists biomarkers that were discovered that were differentially present between plasma samples from subjects with metastatic/high grade prostate cancer and plasma samples from Control subjects with biopsy negative prostates (i.e. not diagnosed with prostate cancer). Table 8 lists biomarkers that were discovered that were differentially present between plasma samples from subjects with metastatic/high grade prostate cancer and plasma from subjects with lower grade prostate cancer.
[0124] Tables 6-8 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 6), the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 7), and the metastatic/high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 8). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.
[0125] Biomarkers were discovered by (1) analyzing plasma samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0126] The plasma samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0127] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).
[0000]
TABLE 6
Plasma Metabolite Biomarkers to distinguish
Non-cancer vs. Lower Grade PCA
% Change
COMP_ID
COMPOUND
LIB_ID
pvalue
qvalue
in PCA
53
glutamine
50
0.9855
0.9993
−1%
54
tryptophan
50
0.6455
0.9851
3%
57
glutamic acid
50
0.5953
0.9851
−6%
59
histidine
50
0.4258
0.9478
−9%
60
leucine
50
0.2512
0.9478
8%
63
cholesterol
50
0.8251
0.9851
−1%
64
phenylalanine
35
0.61
0.9851
−2%
513
creatinine
35
0.0047
0.5749
−10%
527
lactate
50
0.6496
0.9851
−1%
528
alpha - keto-glutarate
35
0.0081
0.5749
−40%
541
4-hydroxyphenylacetate
35
0.2553
0.9478
−5%
542
3-hydroxybutanoic acid
50
0.748
0.9851
11%
569
caffeine
35
0.0542
0.7407
61%
577
fructose
50
0.2415
0.9478
−26%
581
glucose
50
0.254
0.9478
−4%
584
mannose
50
0.9209
0.9993
1%
594
niacinamide
35
0.7471
0.9851
10%
597
phosphoenolpyruvate
35
0.5253
0.9851
−6%
1105
linoleic acid
50
0.6374
0.9851
3%
1107
allantoin
50
0.6861
0.9851
−8%
1110
arachidonic acid
50
0.4338
0.9478
−6%
1121
heptadecanoic acid
50
0.0432
0.7407
12%
1123
inosine
35
0.8138
0.9851
8%
1125
isoleucine
50
0.2856
0.9478
7%
1126
alanine
50
0.8973
0.9993
−1%
1284
threonine
50
0.9044
0.9993
−1%
1299
tyrosine
50
0.2074
0.9478
8%
1302
methionine
35
0.9843
0.9993
0%
1303
malic acid
35
0.5347
0.9851
−9%
1336
n-hexadecanoic acid
50
0.4029
0.9478
5%
1358
octadecanoic acid
50
0.05
0.7407
7%
1365
tetradecanoic acid
50
0.4504
0.9478
6%
1366
trans-4-hydroxyproline
50
0.8095
0.9851
1%
1413
3-hydroxyphenylacetate
35
0.4804
0.9659
−3%
1414
3-phospho-d-glycerate
35
0.9448
0.9993
−1%
1415
4-amino-5-methyl-2-1H-
35
0.6722
0.9851
3%
pyrimidinone
1431
(p-Hydroxyphenyl)lactic acid
50
0.598
0.9851
6%
1432
alphahydroxybenzeneacetic
35
0.8582
0.9851
−2%
acid
1437
succinate
50
0.6649
0.9851
−2%
1444
DL-pipecolic acid
35
0.3051
0.9478
−10%
1480
guanidineacetic acid
35
0.3889
0.9478
7%
1493
ornithine
50
0.9114
0.9993
1%
1494
5-oxoproline
50
0.5882
0.9851
4%
1498
N-6-trimethyl-l-lysine
35
0.2178
0.9478
−11%
1507
palmitoleic acid
50
0.5998
0.9851
8%
1508
pantothenic acid
35
0.4151
0.9478
20%
1519
sucrose
50
0.6854
0.9851
6%
1557
3-methylglutaric acid
35
0.1656
0.9478
−9%
1561
alpha - tocopherol
50
0.0145
0.6753
−50%
1564
citric acid
50
0.6977
0.9851
2%
1570
oleic acid
50
0.8649
0.9851
−2%
1572
glyceric acid
50
0.7217
0.9851
2%
1574
histamine
35
0.5568
0.9851
8%
1584
methyl-indole-3-acetate
35
0.9677
0.9993
0%
1587
N-acetyl-L-leucine
35
0.3101
0.9478
31%
1591
N-acetyl-L-valine
35
0.0094
0.5749
20%
1604
uric acid
35
0.9975
0.9993
0%
1643
fumaric acid
50
0.5347
0.9851
−3%
1645
n-dodecanoate
50
0.7836
0.9851
3%
1648
serine
50
0.2503
0.9478
8%
1649
valine
50
0.3429
0.9478
7%
1670
urea
50
0.5816
0.9851
4%
1708
7-8-dihydrofolic acid
35
0.3763
0.9478
30%
1898
proline
50
0.6963
0.9851
−3%
2078
pyrophosphate
35
0.97
0.9993
0%
2092
catechol
35
0.9928
0.9993
0%
2132
citrulline
50
0.7476
0.9851
−3%
2730
gamma - L-glutamyl-L-
35
0.8715
0.9852
−3%
glutamine
2734
gamma - L-glutamyl-L-
35
0.2947
0.9478
6%
tyrosine
2832
adenosine-5-monophosphate
35
0.661
0.9851
−4%
2848
guanosine-5-diphosphate
35
0.9286
0.9993
1%
3127
hypoxanthine
35
0.6226
0.9851
−6%
3138
pyridoxamine-phosphate
35
0.1559
0.9478
16%
3147
xanthine
35
0.4283
0.9478
−10%
4966
xylitol
35
0.6274
0.9851
5%
5280
biliverdin
35
0.2685
0.9478
33%
5331
pyridoxal-phosphate
35
0.2348
0.9478
−5%
5618
Metabolite - 1085-possible-
35
0.4282
0.9478
4%
isolobinine-or-4-aminoestra-
1-3-5-10-triene-3-17beta-diol
5628
Metabolite - 1086
35
0.8863
0.9931
−2%
5669
Metabolite - 1104
35
0.7565
0.9851
−1%
5687
Metabolite - 1110
35
0.8421
0.9851
5%
5689
Metabolite - 1111-possible-
35
0.1327
0.9478
11%
methylnitronitrosoguanidine-
or-ethyl-thiocarbamoylacetate
5697
acetylcarnitine-
35
0.8273
0.9851
−2%
5717
Metabolite - 1121
35
0.2772
0.9478
10%
5733
Metabolite - 1127
35
0.0093
0.5749
−18%
5765
Metabolite - 1142-possible-5-
35
0.7839
0.9851
9%
hydroxypentanoate-or-beta-
hydroxyisovaleric acid
5788
Metabolite - 1183
35
0.3488
0.9478
145%
5792
Metabolite - 1185
35
0.001
0.3826
35%
5800
Metabolite - 1188
35
0.0412
0.7407
36%
6112
Metabolite - 1203-HXGXX-
35
0.3191
0.9478
53%
in-MTRX
6130
Metabolite - 1208
35
0.7504
0.9851
7%
6136
Metabolite - 1211-possible-
35
0.0416
0.7407
287%
IHWESASLLR-
6144
Metabolite - 1215
35
0.9559
0.9993
2%
6147
Metabolite - 1216
35
0.6032
0.9851
8%
6155
Metabolite - 1220
35
0.8003
0.9851
3%
6171
Metabolite - 1244
35
0.3509
0.9478
11%
6266
Metabolite - 1286
35
0.3935
0.9478
5%
6278
Metabolite - 1289
35
0.1436
0.9478
−16%
6362
Metabolite - 1323-possible-p-
35
0.3987
0.9478
17%
cresol-sulfate
6398
Metabolite - 1335
35
0.9275
0.9993
−1%
6413
Metabolite - 1342-possible-
35
0.3835
0.9478
16%
phenylacetylglutamine-or-
formyl-N-acetyl-5-
methoxykynurenamine
6437
Metabolite - 1349-possible-N-
35
0.9654
0.9993
1%
acetyl-8-O-methyl-Neuraminic
acid
6443
Metabolite - 1351
35
0.9312
0.9993
−1%
6537
Metabolite - 1389-possible-
35
0.3189
0.9478
308%
gemfibrozil-glucuronide-
6549
Metabolite - 1392
35
0.4102
0.9478
12%
6787
Metabolite - 1465
35
0.7835
0.9851
5%
6852
Metabolite - 1498
35
0.1492
0.9478
−14%
6987
Metabolite - 1573
35
0.8168
0.9851
−2%
7029
Metabolite - 1597
35
0.0206
0.7407
10%
7081
Metabolite - 1609
35
0.3186
0.9478
8%
7177
Metabolite - 1656
35
0.8442
0.9851
2%
7359
n-acetyl-L-aspartic acid
35
0.7069
0.9851
−2%
7446
p-hydroxybenzaldehyde
35
0.3568
0.9478
−6%
7595
Metabolite - 1817
35
0.6472
0.9851
3%
7639
oxalic acid
35
0.7835
0.9851
2%
7644
Metabolite - 1831-possible-Cl-
35
0.2483
0.9478
−29%
adduct-of-citrulline
7650
Metabolite - 1834
35
0.6754
0.9851
−8%
7652
Metabolite - 1835
35
0.031
0.7407
25%
7654
Metabolite - 1836
35
0.7242
0.9851
−3%
7660
Metabolite - 1839
35
0.8404
0.9851
−4%
7672
Metabolite - 1843
35
0.7507
0.9851
3%
7933
Metabolite - 1911
35
0.0739
0.7639
48%
7935
paraxanthine
35
0.1117
0.9478
38%
7941
Metabolite - 1914
35
0.8081
0.9851
6%
7944
Metabolite - 1915
35
0.3455
0.9478
55%
7957
trans-2-3-4-
35
0.8125
0.9851
5%
trimethoxycinnamic acid
8091
glycocholic acid
35
0.2546
0.9478
30%
8176
Metabolite - 1974
35
0.4143
0.9478
10%
8189
Metabolite - 1977
35
0.8558
0.9851
2%
8196
Metabolite - 1979-Cl-adduct-
35
0.5336
0.9851
−5%
of-isobar-19
8217
Metabolite - 1983
35
0.1187
0.9478
410%
8300
Metabolite - 1988
35
0.1698
0.9478
−14%
8336
Metabolite - 2005
35
0.8806
0.9897
−2%
8404
Metabolite - 2027
35
0.6346
0.9851
−4%
8649
Metabolite - 2053
35
0.2084
0.9478
17%
8669
Metabolite - 2055
35
0.9233
0.9993
1%
8677
Metabolite - 2056
35
0.5835
0.9851
6%
8796
Metabolite - 2074
35
0.8013
0.9851
−2%
8959
Metabolite - 2100
35
0.4481
0.9478
5%
9007
Metabolite - 2108
35
0.9789
0.9993
0%
9024
Metabolite - 2111
35
0.6202
0.9851
−5%
9092
Metabolite - 2129
35
0.5701
0.9851
−9%
9106
Metabolite - 2130
35
0.4394
0.9478
−12%
9130
Metabolite - 2139
35
0.7305
0.9851
3%
9137
Metabolite - 2141
35
0.5077
0.9851
12%
9491
Metabolite - 2185
35
0.0387
0.7407
18%
9748
Metabolite - 2212
35
0.3479
0.9478
−9%
10087
Metabolite - 2249
35
0.6712
0.9851
−4%
10092
Metabolite - 2250
35
0.0564
0.7407
63%
10122
Metabolite - 2254
35
0.4991
0.9851
−15%
10143
Metabolite - 2255-
35
0.0474
0.7407
89%
hydroxyproline-form-of-
bradykinin
10145
Metabolite - 2256
35
0.1134
0.9478
−18%
10245
Metabolite - 2269-
35
0.7452
0.9851
8%
10317
Metabolite - 2279
35
0.2635
0.9478
32%
10327
Metabolite - 2281
35
0.5771
0.9851
34%
10378
Metabolite - 2287
35
0.395
0.9478
59%
10438
gamma-glu-leu
35
0.4307
0.9478
4%
10461
Metabolite - 2313
35
0.71
0.9851
−4%
10476
Metabolite - 2316
35
0.456
0.9478
−13%
10544
Metabolite - 2329
35
0.8979
0.9993
1%
10551
Metabolite - 2347
35
0.6776
0.9851
8%
10604
Metabolite - 2370
35
0.6853
0.9851
4%
10629
Metabolite - 2386
35
0.8269
0.9851
−4%
10644
Metabolite - 2387
35
0.5459
0.9851
52%
10655
Metabolite - 2388
35
0.7697
0.9851
−1%
10667
Metabolite - 2389
35
0.318
0.9478
20%
10672
Metabolite - 2390
35
0.4169
0.9478
23%
10692
Metabolite - 2391
35
0.397
0.9478
−6%
10698
Metabolite - 2392
35
0.7279
0.9851
−9%
10737
Isobar-1-includes-mannose-
35
0.7112
0.9851
4%
fructose-glucose-galactose-
alpha - L-sorbopyranose-
Inositol-D-allose-D--altrose-D-
psicone
10739
Metabolite - 2407
35
0.9869
0.9993
0%
10741
Isobar-2-includes-2-
35
0.6711
0.9851
−10%
aminoisobutyric acid-3-amino-
isobutyrate-2-amino-butyrate-
4-aminobutanoic acid-
dimethylglycine-choline-
10743
Isobar-4-includes-Gluconic
35
0.8686
0.9851
−2%
acid-DL-arabinose-D-ribose-L-
xylose-DL-lyxose-D-xylulose
10744
Isobar-5-includes-asparagine-
35
0.7225
0.9851
4%
ornithine-gly-gly
10746
Isobar-6-includes-valine-
35
0.1667
0.9478
5%
betaine
10753
Isobar-9-includes-galactinol-
35
0.6051
0.9851
−7%
dihydrate-turanose-kojibiose-
D-leucrose-lactulose-
sophorose-sucrose-beta-D-
lactose-D-trehalose-D-
cellobiose-D-Maltose-
palatinose-melibiose-alpha -
D-lactose
10782
Metabolite - 2486
35
0.5968
0.9851
8%
10785
Metabolite - 2506
35
0.9224
0.9993
2%
10787
Metabolite - 2507
35
0.6105
0.9851
−13%
10825
Metabolite - 2546
35
0.9993
0.9993
0%
11053
Metabolite - 2567
35
0.1285
0.9478
9%
11111
Metabolite - 2592
35
0.4637
0.9582
54%
11219
Metabolite - 2686
35
0.5844
0.9851
3%
11222
Metabolite - 2688
35
0.163
0.9478
14%
11323
Metabolite - 2711
35
0.9889
0.9993
0%
11438
phosphate
50
0.8104
0.9851
0%
11499
Metabolite - 2753
35
0.4215
0.9478
7%
11777
glycine
50
0.3338
0.9478
−8%
11813
Metabolite - 2809
35
0.8323
0.9851
3%
12035
nonanate
50
0.7544
0.9851
1%
12109
Metabolite - 2853
35
0.0277
0.7407
39%
12298
Metabolite - 2867
35
0.1237
0.9478
−45%
12478
Metabolite - 2898
35
0.0495
0.7407
−51%
12532
Metabolite - 2914
50
0.1166
0.9478
2%
12533
Metabolite - 2915
50
0.2615
0.9478
−7%
12543
2-hydroxy-butanoic acid
50
0.1956
0.9478
17%
12562
Metabolite - 2955
50
0.279
0.9478
3%
12593
Metabolite - 2973
50
0.9818
0.9993
0%
12594
Metabolite - 2974
50
0.9799
0.9993
0%
12601
Metabolite - 2978
50
0.6254
0.9851
3%
12625
Metabolite - 3002
50
0.9162
0.9993
−2%
12626
Metabolite - 3003
50
0.1382
0.9478
−9%
12627
Metabolite - 3004
50
0.5311
0.9851
−5%
12639
Metabolite - 3012
50
0.4723
0.9653
5%
12641
meso-erythritol
50
0.3847
0.9478
−7%
12644
Metabolite - 3016
50
0.1293
0.9478
−7%
12645
Metabolite - 3017
50
0.0303
0.7407
18%
12647
Metabolite - 3019
50
0.2488
0.9478
7%
12648
Metabolite - 3020
50
0.4953
0.9851
6%
12650
Metabolite - 3022
50
0.9679
0.9993
0%
12656
Metabolite - 3025
50
0.195
0.9478
8%
12658
Metabolite - 3026
50
0.3559
0.9478
7%
12663
Metabolite - 3030
50
0.0934
0.9247
9%
12666
Metabolite - 3033
50
0.8631
0.9851
−1%
12673
Metabolite - 3040
50
0.3373
0.9478
10%
12682
Metabolite - 3044
35
0.1918
0.9478
12%
12719
Metabolite - 3055
35
0.741
0.9851
5%
12720
Metabolite - 3056
35
0.5288
0.9851
−4%
12726
Metabolite - 3058
50
0.727
0.9851
3%
12739
1-5-anhydro-D-glucitol
50
0.2751
0.9478
−8%
12751
Metabolite - 3073
50
0.921
0.9993
1%
12753
Metabolite - 3074
50
0.3835
0.9478
−22%
12754
Metabolite - 3075
50
0.2497
0.9478
−7%
12756
Metabolite - 3077
50
0.9463
0.9993
1%
12757
Metabolite - 3078
50
0.8351
0.9851
−2%
12761
Metabolite - 3081
50
0.0685
0.7493
−9%
12765
inositol
50
0.4516
0.9478
−5%
12768
Metabolite - 3088
50
0.1228
0.9478
−15%
12769
Metabolite - 3089
50
0.0654
0.7493
16%
12771
Metabolite - 3091
50
0.25
0.9478
21%
12773
Metabolite - 3093
50
0.4676
0.961
9%
12774
Metabolite - 3094
50
0.9437
0.9993
0%
12777
Metabolite - 3097
50
0.2879
0.9478
16%
12780
Metabolite - 3098
50
0.1558
0.9478
12%
12781
Metabolite - 3099
50
0.0718
0.7631
26%
12784
Metabolite - 3102
50
0.8378
0.9851
−1%
12790
Metabolite - 3108
50
0.6368
0.9851
2%
12876
Metabolite - 3125
35
0.4896
0.9793
−4%
12912
Metabolite - 3129
35
0.4506
0.9478
9%
12924
Metabolite - 3131
35
0.6823
0.9851
5%
12931
DL-hexanoyl-carnitine
35
0.6978
0.9851
3%
12960
Metabolite - 3134
35
0.9924
0.9993
0%
12969
Metabolite - 3135
35
0.5304
0.9851
13%
13018
Metabolite - 3138
35
0.0971
0.9247
−16%
13038
Metabolite - 3143
35
0.9259
0.9993
1%
13065
Metabolite - 3146
35
0.8545
0.9851
4%
13104
Metabolite - 3160
35
0.2622
0.9478
−10%
13142
Metabolite - 3165
35
0.3363
0.9478
−5%
13146
Metabolite - 3166
35
0.8043
0.9851
4%
13148
Metabolite - 3167
35
0.044
0.7407
21%
13179
possible-Metabolite - 3176-
35
0.7152
0.9851
5%
possible-creatine
13208
Metabolite - 3181
35
0.354
0.9478
−9%
13211
Metabolite - 3182
35
0.9963
0.9993
0%
13214
Metabolite - 3183-possible-
35
0.7525
0.9851
2%
gamma-L-glutamyl-L-
phenylalanine
13217
Metabolite - 3184
35
0.1642
0.9478
−11%
13249
Metabolite - 3215
35
0.6878
0.9851
−4%
13251
Metabolite - 3216
35
0.2268
0.9478
−13%
13257
Metabolite - 3218
35
0.5081
0.9851
5%
13342
Metabolite - 3243
35
0.5847
0.9851
10%
13448
Metabolite - 3303
35
0.0978
0.9247
−9%
13459
Metabolite - 3305
35
0.3143
0.9478
−19%
13484
Metabolite - 3309
35
0.0626
0.7493
−25%
13505
Metabolite - 3313
35
0.5629
0.9851
−23%
13509
Metabolite - 3314
35
0.2956
0.9478
−8%
13534
Metabolite - 3320-possible-
35
0.7791
0.9851
10%
pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
0.2266
0.9478
16%
13589
Metabolite - 3327
35
0.831
0.9851
−4%
13775
Metabolite - 3370
35
0.8025
0.9851
1%
13803
Metabolite - 3377
35
0.2963
0.9478
−17%
13904
Metabolite - 3402
35
0.3454
0.9478
−15%
14027
Metabolite - 3426
35
0.1435
0.9478
−3%
14084
Metabolite - 3436
35
0.2313
0.9478
13%
14117
Metabolite - 3441
35
0.2102
0.9478
−10%
14239
Metabolite - 3474
35
0.3092
0.9478
−9%
14249
Metabolite - 3476
35
0.3874
0.9478
−16%
14368
Metabolite - 3489
35
0.383
0.9478
−19%
14439
Metabolite - 3498
35
0.7901
0.9851
3%
14495
Metabolite - 3534
35
0.2653
0.9478
13%
14595
Metabolite - 3576
35
0.6382
0.9851
−5%
14608
Metabolite - 3578
35
0.243
0.9478
13%
14639
Metabolite - 3603
35
0.04
0.7407
19%
14640
Metabolite - 3604
35
0.2069
0.9478
30%
14672
Metabolite - 3615
35
0.275
0.9478
15%
14715
Metabolite - 3653-possible-
35
0.6884
0.9851
−12%
stachydrine-
14766
Metabolite - 3670
35
0.1501
0.9478
8%
14785
isobar-glycochenodeoxycholic
35
0.3915
0.9478
18%
acid-glycodeoxycholic acid
14787
Metabolite - 3698
35
0.3714
0.9478
−11%
14837
Metabolite - 3707
35
0.4795
0.9659
18%
14961
Metabolite - 3752
35
0.0597
0.7407
228%
15000
Metabolite - 3758
35
0.3269
0.9478
−23%
15017
Metabolite - 3761
35
0.6023
0.9851
−5%
15032
Metabolite - 3765
35
0.0289
0.7407
43%
15063
Metabolite - 3772
35
0.573
0.9851
−4%
15113
Metabolite - 3783
35
0.983
0.9993
0%
15122
glycerol
50
0.7135
0.9851
−2%
15128
DL-homocysteine
35
0.1339
0.9478
−14%
15129
D-alanyl-D-alanine
35
0.0165
0.6833
23%
15211
Metabolite - 3807
35
0.3174
0.9478
−5%
15220
Metabolite - 3813
35
0.6421
0.9851
−5%
15227
Metabolite - 3816
35
0.9802
0.9993
0%
15251
Metabolite - 3830
35
0.262
0.9478
20%
15253
Metabolite - 3832-possible-
35
0.0596
0.7407
−45%
phenol-sulfate
15278
Metabolite - 3843
35
0.0092
0.5749
−16%
15319
DL-phenyllactic acid
35
0.2331
0.9478
32%
15326
Metabolite - 3879
35
0.5692
0.9851
13%
15328
azelaic acid
35
0.7398
0.9851
−2%
15336
tartaric acid
35
0.9993
0.9993
0%
15365
sn-Glycerol-3-phosphate
50
0.4116
0.9478
3%
15389
Metabolite - 3900
35
0.5829
0.9851
3%
15500
carnitine
35
0.528
0.9851
3%
15529
Metabolite - 3951
35
0.0399
0.7407
−11%
15535
Metabolite - 3955
35
0.5955
0.9851
−7%
15606
Metabolite - 3968
35
0.761
0.9851
−5%
15612
Metabolite - 3972
35
0.2908
0.9478
8%
15626
Metabolite - 3977
35
0.2184
0.9478
−7%
15677
3-methyl-L-histidine
35
0.1203
0.9478
−8%
15681
4-Guanidinobutanoic acid
35
0.2211
0.9478
−14%
15683
4-methyl-2-oxopentanoate
50
0.4541
0.9478
5%
15704
heptanedioic acid
35
0.8664
0.9851
−2%
15744
N-N-dimethylarginine
35
0.6586
0.9851
3%
15753
hippuric acid
35
0.6181
0.9851
10%
15991
L-alpha -
35
0.8467
0.9851
−3%
glycerophosphorylcholine
16002
Metabolite - 3992-possible-Cl-
35
0.874
0.9852
−1%
adduct-of-Formate-dimer
16016
Metabolite - 3994
35
0.7041
0.9851
−8%
16071
Metabolite - 4020
50
0.3935
0.9478
5%
16091
Metabolite - 4031-possible-
35
0.94
0.9993
−1%
norlevorphenol-
isobutylphendienamide-
amprolium
16107
lysine
50
0.8238
0.9851
2%
16137
Metabolite - 4078
35
0.5038
0.9851
−12%
16161
gamma - glutamyl-glutamic
35
0.5112
0.9851
8%
acid
16186
Metabolite - 4096-possible-
35
0.2257
0.9478
18%
gamma - glu-gly-leu-
16226
Isobar-28-includes-L-
35
0.6861
0.9851
3%
threonine-L-allothreonine-L-
homoserine-S-4-amino-2-
hydroxybutyric acid
16231
Isobar-20-includes-fumaric
35
0.2502
0.9478
18%
acid-3-methyl-2-oxobutanoate
16232
Isobar-17-includes-arginine-N-
35
0.9455
0.9993
−1%
alpha - acetyl-ornithine
16233
Isobar-13-includes-5-keto-D-
35
0.799
0.9851
3%
gluconic acid-2-keto-L-gulonic
acid-D-glucuronic acid-D-
galacturonic acid
16235
Isobar-19-includes-D-saccharic
35
0.8329
0.9851
3%
acid-1-5-anhydro-D-glucitol-2-
deoxy-D-galactose-2-deoxy-D-
glucose-L-fucose-L-rhamnose
16237
Isobar-25-includes-L-gulono-1-
35
0.8393
0.9851
−3%
4-lactone-glucono-gamma -
lactone-
16241
Isobar-30-includes-
35
0.282
0.9478
11%
maltotetraose-stachyose
16243
L-kynurenine
35
0.6848
0.9851
2%
16244
Isobar-21-includes-gamma -
35
0.0676
0.7493
−21%
aminobutyryl-L-histidine-L-
anserine
16246
Isobar-18-includes-D-fructose-
35
0.6754
0.9851
5%
1-phosphate-beta - D-fructose-
6-phosphate
16279
Isobar-36-includes-D-sorbitol-
35
0.0432
0.7407
18%
6-phosphate-mannitol-1-
phosphate
16290
Metabolite - 4133
50
0.1746
0.9478
−9%
16308
Metabolite - 4147
50
0.6922
0.9851
−4%
16330
Metabolite - 4163
35
0.4304
0.9478
−10%
16337
Metabolite - 4167
35
0.7076
0.9851
−3%
16462
Metabolite - 4234
35
0.4466
0.9478
−5%
16471
Metabolite - 4238
35
0.5384
0.9851
10%
16508
Metabolite - 4272
50
0.1526
0.9478
−11%
16621
Metabolite - 4355
50
0.3937
0.9478
−17%
16653
Metabolite - 4361
50
0.0994
0.9247
21%
16666
Metabolite - 4365
50
0.2946
0.9478
−10%
16824
iminodiacetic acid
50
0.7755
0.9851
−3%
16829
Metabolite - 4503
50
0.9392
0.9993
−1%
16848
Metabolite - 4511
50
0.8497
0.9851
−2%
16952
Metabolite - 4593
50
0.3035
0.9478
4%
17028
Metabolite - 4611
50
0.3813
0.9478
−5%
17328
Metabolite - 4768
50
0.4803
0.9659
13%
17330
Metabolite - 4769
50
0.2485
0.9478
14%
17359
Metabolite - 4791
50
0.8127
0.9851
−5%
17388
Metabolite - 4795
50
0.2822
0.9478
11%
17614
Metabolite - 4966
50
0.33
0.9478
9%
17627
Metabolite - 4986
50
0.0582
0.7407
28%
18118
Metabolite - 5346
50
0.4123
0.9478
6%
18146
Metabolite - 5366
50
0.0108
0.5749
40%
18232
Metabolite - 5403
50
0.3291
0.9478
6%
18316
Metabolite - 5437
50
0.1177
0.9478
30%
18335
D-quinic acid
50
0.6344
0.9851
10%
18349
DL-indole-3-lactic acid
50
0.6042
0.9851
−4%
18868
Metabolite - 5847
50
0.8544
0.9851
3%
18926
Metabolite - 5906
50
0.9154
0.9993
4%
18929
Metabolite - 5907
50
0.2112
0.9478
8%
[0000]
TABLE 7
Plasma Metabolite Biomarkers to distinguish Non-cancer from Higher Grade PCA.
%
Change
COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA
53
glutamine
50
0.1993
0.3977
−14%
54
tryptophan
50
0.1049
0.3151
−10%
57
glutamic acid
50
0.1716
0.3828
−18%
59
histidine
50
0.2197
0.4209
−11%
60
leucine
50
0.0833
0.2916
−13%
63
cholesterol
50
0.1481
0.3699
−10%
64
phenylalanine
35
0.05
0.245
−7%
513
creatinine
35
0.0563
0.2564
−10%
527
lactate
50
0.0035
0.0655
−15%
528
alpha - keto-glutarate
35
0.0099
0.0976
−45%
541
4-hydroxyphenylacetate
35
0.3644
0.481
−5%
542
3-hydroxybutanoic acid
50
0.0434
0.221
−45%
569
caffeine
35
0.0049
0.0777
−51%
577
fructose
50
0.0544
0.2523
−41%
581
glucose
50
0.1835
0.3851
−6%
584
mannose
50
0.9521
0.6641
0%
594
niacinamide
35
0.6135
0.59
−11%
597
phosphoenolpyruvate
35
0.4146
0.5151
−9%
1105
linoleic acid
50
0.0622
0.2681
−14%
1107
allantoin
50
0.4785
0.5344
−14%
1110
arachidonic acid
50
0.3429
0.481
−12%
1121
heptadecanoic acid
50
0.0029
0.0624
−19%
1123
inosine
35
0.7999
0.6385
10%
1125
isoleucine
50
0.072
0.2829
−13%
1126
alanine
50
0.0821
0.2916
−16%
1284
threonine
50
0.2588
0.4682
−9%
1299
tyrosine
50
0.6026
0.5883
−4%
1302
methionine
35
0.499
0.5413
−4%
1303
malic acid
35
0.343
0.481
−21%
1336
n-hexadecanoic acid
50
0.0078
0.0976
−16%
1358
octadecanoic acid
50
0.0337
0.1829
−10%
1365
tetradecanoic acid
50
0.0076
0.0976
−17%
1366
trans-4-hydroxyproline
50
0.0164
0.1319
−14%
1413
3-hydroxyphenylacetate
35
0.9038
0.6568
−1%
1414
3-phospho-d-glycerate
35
0.3849
0.4882
−13%
1415
4-amino-5-methyl-2-1H-
35
0.4688
0.5282
−8%
pyrimidinone
1431
(p-Hydroxyphenyl)lactic acid
50
0.0618
0.2681
−22%
1432
alphahydroxybenzeneacetic acid
35
0.9337
0.6641
1%
1437
succinate
50
0.3397
0.481
7%
1444
DL-pipecolic acid
35
0.3851
0.4882
−10%
1480
guanidineacetic acid
35
0.7214
0.6178
5%
1493
ornithine
50
0.1892
0.3889
−18%
1494
5-oxoproline
50
0.1956
0.3977
−9%
1498
N-6-trimethyl-l-lysine
35
0.6864
0.6107
−6%
1507
palmitoleic acid
50
4.00E−04
0.0178
−40%
1508
pantothenic acid
35
0.3718
0.481
−17%
1519
sucrose
50
0.8433
0.6512
4%
1557
3-methylglutaric acid
35
0.0249
0.1479
−18%
1561
alpha -tocopherol
50
0.0158
0.1319
−53%
1564
citric acid
50
0.4573
0.5239
−4%
1570
oleic acid
50
0.0021
0.0503
−35%
1572
glyceric acid
50
0.1532
0.3719
20%
1574
histamine
35
0.8493
0.6519
4%
1584
methyl-indole-3-acetate
35
0.28
0.4695
−13%
1587
N-acetyl-L-leucine
35
0.71
0.6136
−10%
1591
N-acetyl-L-valine
35
0.0093
0.0976
21%
1604
uric acid
35
0.7956
0.6385
−1%
1643
fumaric acid
50
0.4015
0.5016
−9%
1645
n-dodecanoate
50
0.187
0.3875
−12%
1648
serine
50
0.3365
0.481
−7%
1649
valine
50
0.0224
0.1466
−14%
1670
urea
50
0.3643
0.481
7%
1708
7-8-dihydrofolic acid
35
0.9239
0.6628
4%
1898
proline
50
0.1339
0.3538
−19%
2078
pyrophosphate
35
0.7732
0.6377
−7%
2092
catechol
35
0.259
0.4682
−31%
2132
citrulline
50
0.4546
0.5239
6%
2730
gamma - L-glutamyl-L-
35
0.552
0.5628
12%
glutamine
2734
gamma - L-glutamyl-L-tyrosine
35
0.5344
0.5577
4%
2832
adenosine-5-monophosphate
35
0.1631
0.3779
−17%
2848
guanosine-5-diphosphate
35
0.5329
0.5577
−8%
3127
hypoxanthine
35
0.7241
0.6178
−5%
3138
pyridoxamine-phosphate
35
0.8654
0.6522
2%
3147
xanthine
35
0.9538
0.6641
2%
4966
xylitol
35
0.3179
0.481
18%
5280
biliverdin
35
0.4282
0.5189
−11%
5331
pyridoxal-phosphate
35
0.3699
0.481
4%
5618
Metabolite - 1085-possible-
35
0.0247
0.1479
21%
isolobinine-or-4-aminoestra - 1-
3-5-10-triene-3-17beta - diol
5628
Metabolite - 1086
35
0.5566
0.5628
−10%
5669
Metabolite - 1104
35
0.0086
0.0976
−15%
5687
Metabolite - 1110
35
0.2792
0.4695
45%
5689
Metabolite - 1111-possible-
35
0.9467
0.6641
1%
methylnitronitrosoguanidine-or-
ethyl-thiocarbamoylacetate
5697
acetylcarnitine-
35
0.2254
0.4256
−12%
5717
Metabolite - 1121
35
0.0166
0.1319
29%
5733
Metabolite - 1127
35
6.00E−04
0.0178
−35%
5765
Metabolite - 1142-possible-5-
35
0.611
0.59
−11%
hydroxypentanoate-or-beta -
hydroxyisovaleric acid
5788
Metabolite - 1183
35
0.7587
0.6319
10%
5792
Metabolite - 1185
35
0.0012
0.034
68%
5800
Metabolite - 1188
35
0.2872
0.4722
18%
6112
Metabolite - 1203-HXGXX - in-
35
0.3875
0.4889
−20%
MTRX
6130
Metabolite - 1208
35
0.5109
0.547
−15%
6136
Metabolite - 1211-possible-
35
0.2482
0.4551
204%
IHWESASLLR-
6144
Metabolite - 1215
35
0.7273
0.6178
12%
6147
Metabolite - 1216
35
0.4342
0.5189
−8%
6155
Metabolite - 1220
35
0.8726
0.6522
3%
6171
Metabolite - 1244
35
0.7307
0.6186
−6%
6266
Metabolite - 1286
35
0.021
0.1462
16%
6278
Metabolite - 1289
35
0.8015
0.6385
−4%
6362
Metabolite - 1323-possible-p-
35
0.5645
0.5664
17%
cresol-sulfate
6398
Metabolite - 1335
35
0.9375
0.6641
1%
6413
Metabolite - 1342-possible-
35
0.7405
0.6228
7%
phenylacetylglutamine-or-
formyl-N-acetyl-5-
methoxykynurenamine
6437
Metabolite - 1349-possible-N-
35
0.9989
0.6849
0%
acetyl-8-O-methyl-Neuraminic
acid
6443
Metabolite - 1351
35
0.7988
0.6385
−3%
6537
Metabolite - 1389-possible-
35
0.5683
0.5664
−11%
gemfibrozil-glucuronide-
6549
Metabolite - 1392
35
0.8385
0.6512
−5%
6787
Metabolite - 1465
35
0.7433
0.6231
−4%
6852
Metabolite - 1498
35
0.3324
0.481
15%
6987
Metabolite - 1573
35
0.8266
0.6482
−4%
7029
Metabolite - 1597
35
0.6293
0.6006
3%
7081
Metabolite - 1609
35
0.118
0.327
−16%
7177
Metabolite - 1656
35
0.3641
0.481
15%
7359
n-acetyl-L-aspartic acid
35
0.0139
0.1266
−23%
7446
p-hydroxybenzaldehyde
35
0.3129
0.481
−9%
7595
Metabolite - 1817
35
0.0951
0.3035
24%
7639
oxalic acid
35
0.0942
0.3035
14%
7644
Metabolite - 1831-possible-Cl-
35
0.026
0.1507
−61%
adduct-of-citrulline
7650
Metabolite - 1834
35
0.0722
0.2829
−35%
7652
Metabolite - 1835
35
0.4205
0.5151
11%
7654
Metabolite - 1836
35
0.0891
0.295
−28%
7660
Metabolite - 1839
35
0.0218
0.1462
−45%
7672
Metabolite - 1843
35
0.9787
0.6778
−1%
7933
Metabolite - 1911
35
0.4204
0.5151
25%
7935
paraxanthine
35
0.0203
0.1462
−41%
7941
Metabolite - 1914
35
0.3503
0.481
32%
7944
Metabolite - 1915
35
0.8018
0.6385
15%
7957
trans-2-3-4-trimethoxycinnamic
35
0.3149
0.481
35%
acid
8091
glycocholic acid
35
0.9047
0.6568
−5%
8176
Metabolite - 1974
35
0.8572
0.6522
4%
8189
Metabolite - 1977
35
0.1838
0.3851
−12%
8196
Metabolite - 1979-Cl-adduct-of-
35
0.9459
0.6641
1%
isobar-19
8217
Metabolite - 1983
35
0.3016
0.481
246%
8300
Metabolite - 1988
35
0.01
0.0976
−30%
8336
Metabolite - 2005
35
0.0359
0.1905
−26%
8404
Metabolite - 2027
35
0.1676
0.3788
−14%
8649
Metabolite - 2053
35
0.7092
0.6136
−5%
8669
Metabolite - 2055
35
0.8342
0.6512
4%
8677
Metabolite - 2056
35
0.1623
0.3779
−15%
8796
Metabolite - 2074
35
0.9322
0.6641
2%
8959
Metabolite - 2100
35
0.6011
0.5883
4%
9007
Metabolite - 2108
35
0.0055
0.0777
−29%
9024
Metabolite - 2111
35
0.3265
0.481
−15%
9092
Metabolite - 2129
35
0.8607
0.6522
−4%
9106
Metabolite - 2130
35
0.0964
0.3035
72%
9130
Metabolite - 2139
35
0.5099
0.547
7%
9137
Metabolite - 2141
35
0.0052
0.0777
−43%
9491
Metabolite - 2185
35
0.6878
0.6107
4%
9748
Metabolite - 2212
35
0.2255
0.4256
19%
10087
Metabolite - 2249
35
0.6409
0.6006
−6%
10092
Metabolite - 2250
35
0.4987
0.5413
18%
10122
Metabolite - 2254
35
0.1171
0.327
−39%
10143
Metabolite - 2255-
35
0.1844
0.3851
139%
hydroxyproline-form-of-
bradykinin
10145
Metabolite - 2256
35
0.862
0.6522
−3%
10245
Metabolite - 2269-
35
0.2698
0.4695
34%
10317
Metabolite - 2279
35
0.3109
0.481
−24%
10327
Metabolite - 2281
35
0.4355
0.5189
−24%
10378
Metabolite - 2287
35
0.1438
0.3664
346%
10438
gamma - glu-leu
35
0.4822
0.5344
−6%
10461
Metabolite - 2313
35
0.5649
0.5664
−6%
10476
Metabolite - 2316
35
0.2043
0.4036
51%
10544
Metabolite - 2329
35
1.00E−04
0.0086
−42%
10551
Metabolite - 2347
35
0.3563
0.481
30%
10604
Metabolite - 2370
35
0.8174
0.6449
4%
10629
Metabolite - 2386
35
0.516
0.5502
−14%
10644
Metabolite - 2387
35
0.5362
0.5577
−32%
10655
Metabolite - 2388
35
0.1466
0.3699
11%
10667
Metabolite - 2389
35
0.0776
0.291
186%
10672
Metabolite - 2390
35
0.0718
0.2829
−27%
10692
Metabolite - 2391
35
0.0982
0.3052
−12%
10698
Metabolite - 2392
35
0.6996
0.6131
−15%
10737
Isobar-1-includes-mannose-
35
0.8978
0.6568
−2%
fructose-glucose-galactose-alpha -
L-sorbopyranose-Inositol-D-
allose-D--altrose-D-psicone
10739
Metabolite - 2407
35
0.0093
0.0976
48%
10741
Isobar-2-includes-2-
35
0.5412
0.5606
−15%
aminoisobutyric acid-3-amino-
isobutyrate-2-amino-butyrate-4-
aminobutanoic acid-
dimethylglycine-choline-
10743
Isobar-4-includes-Gluconic
35
0.3542
0.481
14%
acid-DL-arabinose-D-ribose-L-
xylose-DL-lyxose-D-xylulose
10744
Isobar-5-includes-asparagine-
35
0.1653
0.3788
17%
ornithine-gly-gly
10746
Isobar-6-includes-valine-betaine
35
0.0606
0.2681
−8%
10753
Isobar-9-includes-galactinol-
35
0.7716
0.6377
−6%
dihydrate-turanose-kojibiose-D-
leucrose-lactulose-sophorose-
sucrose-beta - D-lactose-D-
trehalose-D-cellobiose-D-
Maltose-palatinose-melibiose-
alpha - D-lactose
10782
Metabolite - 2486
35
0.6665
0.6048
−8%
10785
Metabolite - 2506
35
0.1515
0.3712
−39%
10787
Metabolite - 2507
35
0.2156
0.4171
−34%
10825
Metabolite - 2546
35
0.4358
0.5189
−13%
11053
Metabolite - 2567
35
0.5492
0.5628
6%
11111
Metabolite - 2592
35
0.3309
0.481
−41%
11219
Metabolite - 2686
35
0.9155
0.6628
1%
11222
Metabolite - 2688
35
0.6923
0.6112
6%
11323
Metabolite - 2711
35
0.0036
0.0655
−21%
11438
phosphate
50
0.9259
0.6628
−1%
11499
Metabolite - 2753
35
0.6692
0.6048
−5%
11777
glycine
50
0.1082
0.3168
−16%
11813
Metabolite - 2809
35
0.7365
0.6215
−7%
12035
nonanate
50
0.4925
0.5413
3%
12109
Metabolite - 2853
35
0.6348
0.6006
−8%
12298
Metabolite - 2867
35
0.1809
0.3851
−47%
12444
Metabolite - 2888-possible-
35
0.3955
0.4965
13%
sulfated-Rosiglitazone
12478
Metabolite - 2898
35
0.2404
0.4472
−36%
12532
Metabolite - 2914
50
0.2774
0.4695
2%
12533
Metabolite - 2915
50
0.4585
0.5239
7%
12543
2-hydroxy-butanoic acid
50
0.1732
0.3828
−17%
12562
Metabolite - 2955
50
0.8848
0.6555
1%
12593
Metabolite - 2973
50
0.8416
0.6512
1%
12594
Metabolite - 2974
50
0.1138
0.3224
11%
12601
Metabolite - 2978
50
0.0765
0.291
23%
12625
Metabolite - 3002
50
0.0539
0.2523
−21%
12626
Metabolite - 3003
50
0.9736
0.6761
0%
12627
Metabolite - 3004
50
0.9538
0.6641
−1%
12639
Metabolite - 3012
50
0.384
0.4882
7%
12641
meso-erythritol
50
0.1016
0.3119
−16%
12644
Metabolite - 3016
50
0.1504
0.3712
−9%
12645
Metabolite - 3017
50
0.2449
0.4523
15%
12647
Metabolite - 3019
50
0.232
0.4348
11%
12648
Metabolite - 3020
50
0.5697
0.5664
7%
12650
Metabolite - 3022
50
0.6591
0.6042
5%
12656
Metabolite - 3025
50
0.3225
0.481
9%
12658
Metabolite - 3026
50
0.321
0.481
10%
12663
Metabolite - 3030
50
0.0082
0.0976
22%
12666
Metabolite - 3033
50
0.0244
0.1479
14%
12673
Metabolite - 3040
50
0.0517
0.2487
27%
12682
Metabolite - 3044
35
0.5288
0.5577
−8%
12719
Metabolite - 3055
35
0.4505
0.5239
21%
12720
Metabolite - 3056
35
0.7025
0.6131
−3%
12726
Metabolite - 3058
50
0.4992
0.5413
12%
12739
1-5-anhydro-D-glucitol
50
0.3236
0.481
−12%
12751
Metabolite - 3073
50
0.1743
0.3828
23%
12753
Metabolite - 3074
50
0.136
0.3538
−39%
12754
Metabolite - 3075
50
0.6421
0.6006
6%
12756
Metabolite - 3077
50
0.5522
0.5628
6%
12757
Metabolite - 3078
50
0.4196
0.5151
9%
12761
Metabolite - 3081
50
0.4686
0.5282
−8%
12765
inositol
50
0.2758
0.4695
−12%
12768
Metabolite - 3088
50
0.0202
0.1462
38%
12769
Metabolite - 3089
50
0.2713
0.4695
−14%
12771
Metabolite - 3091
50
0.2132
0.4171
48%
12773
Metabolite - 3093
50
0.7501
0.6267
−5%
12774
Metabolite - 3094
50
0.5302
0.5577
−7%
12777
Metabolite - 3097
50
0.9998
0.6849
0%
12780
Metabolite - 3098
50
0.0769
0.291
31%
12781
Metabolite - 3099
50
0.8957
0.6568
2%
12784
Metabolite - 3102
50
0.3579
0.481
−7%
12790
Metabolite - 3108
50
0.8722
0.6522
1%
12876
Metabolite - 3125
35
0.4287
0.5189
−6%
12912
Metabolite - 3129
35
0.9973
0.6849
0%
12924
Metabolite - 3131
35
0.2901
0.4739
29%
12931
DL-hexanoyl-carnitine
35
0.7104
0.6136
−3%
12960
Metabolite - 3134
35
0.6932
0.6112
−11%
12969
Metabolite - 3135
35
0.7666
0.6364
10%
13018
Metabolite - 3138
35
0.1116
0.3215
−20%
13038
Metabolite - 3143
35
0.1583
0.3769
−17%
13065
Metabolite - 3146
35
0.0835
0.2916
−33%
13104
Metabolite - 3160
35
0.1779
0.3843
−15%
13142
Metabolite - 3165
35
0.2842
0.4702
−7%
13146
Metabolite - 3166
35
0.9041
0.6568
−3%
13148
Metabolite - 3167
35
0.9239
0.6628
1%
13179
possible-Metabolite - 3176-
35
0.1352
0.3538
28%
possible-creatine
13208
Metabolite - 3181
35
0.5937
0.5841
−6%
13211
Metabolite - 3182
35
0.649
0.6015
11%
13214
Metabolite - 3183-possible-
35
0.946
0.6641
1%
gamma - L-glutamyl-L-
phenylalanine
13217
Metabolite - 3184
35
0.3141
0.481
−13%
13249
Metabolite - 3215
35
0.2706
0.4695
−13%
13251
Metabolite - 3216
35
0.2161
0.4171
−16%
13257
Metabolite - 3218
35
0.8158
0.6449
−4%
13342
Metabolite - 3243
35
0.9895
0.6834
0%
13448
Metabolite - 3303
35
0.0146
0.128
−17%
13459
Metabolite - 3305
35
1.00E−04
0.0086
−59%
13484
Metabolite - 3309
35
0.0639
0.2681
−27%
13505
Metabolite - 3313
35
0.3298
0.481
−38%
13509
Metabolite - 3314
35
0.1312
0.3519
−19%
13534
Metabolite - 3320-possible-
35
0.556
0.5628
−21%
pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
5.00E−04
0.0178
−39%
13589
Metabolite - 3327
35
5.00E−04
0.0178
−52%
13775
Metabolite - 3370
35
0.4705
0.5282
−7%
13803
Metabolite - 3377
35
0
0.0026
−64%
13904
Metabolite - 3402
35
0.0047
0.0777
−38%
14027
Metabolite - 3426
35
0.5712
0.5664
−2%
14084
Metabolite - 3436
35
0.8882
0.6558
2%
14117
Metabolite - 3441
35
0.4955
0.5413
−6%
14239
Metabolite - 3474
35
0.168
0.3788
20%
14249
Metabolite - 3476
35
0.7254
0.6178
−8%
14368
Metabolite - 3489
35
0.1059
0.3151
−35%
14439
Metabolite - 3498
35
0.4571
0.5239
9%
14495
Metabolite - 3534
35
0.1123
0.3215
−23%
14595
Metabolite - 3576
35
0.3216
0.481
19%
14608
Metabolite - 3578
35
0.3148
0.481
23%
14639
Metabolite - 3603
35
0.0022
0.0503
40%
14640
Metabolite - 3604
35
0.6656
0.6048
12%
14672
Metabolite - 3615
35
0.8695
0.6522
3%
14715
Metabolite - 3653-possible-
35
0.7021
0.6131
13%
stachydrine-
14766
Metabolite - 3670
35
0.5739
0.5668
−5%
14785
isobar-glycochenodeoxycholic
35
0.6413
0.6006
−12%
acid-glycodeoxycholic acid
14787
Metabolite - 3698
35
0.798
0.6385
−4%
14837
Metabolite - 3707
35
0.0965
0.3035
108%
14961
Metabolite - 3752
35
0.2823
0.4701
145%
15000
Metabolite - 3758
35
0.123
0.3334
−38%
15017
Metabolite - 3761
35
0.8844
0.6555
−2%
15032
Metabolite - 3765
35
0.6458
0.6006
−11%
15063
Metabolite - 3772
35
0.0788
0.291
−15%
15113
Metabolite - 3783
35
0.4349
0.5189
12%
15122
glycerol
50
0.0247
0.1479
−14%
15128
DL-homocysteine
35
0.3684
0.481
−11%
15129
D-alanyl-D-alanine
35
0.8683
0.6522
−2%
15211
Metabolite - 3807
35
0.2961
0.4806
−6%
15220
Metabolite - 3813
35
0.0871
0.295
−23%
15227
Metabolite - 3816
35
0.8378
0.6512
−3%
15251
Metabolite - 3830
35
0.0863
0.295
−24%
15253
Metabolite - 3832-possible-
35
0.0475
0.2374
−49%
phenol-sulfate
15278
Metabolite - 3843
35
0.0309
0.1711
−17%
15319
DL-phenyllactic acid
35
0.2786
0.4695
−22%
15326
Metabolite - 3879
35
0.6363
0.6006
28%
15328
azelaic acid
35
0.1571
0.3769
−10%
15336
tartaric acid
35
0.0214
0.1462
−38%
15365
sn-Glycerol-3-phosphate
50
0.5069
0.547
−5%
15389
Metabolite - 3900
35
0.0294
0.1667
−14%
15500
carnitine
35
0.197
0.3977
10%
15529
Metabolite - 3951
35
0.6687
0.6048
−3%
15535
Metabolite - 3955
35
0.4421
0.5216
27%
15606
Metabolite - 3968
35
0.8468
0.6519
−4%
15612
Metabolite - 3972
35
0.3503
0.481
11%
15626
Metabolite - 3977
35
0.0207
0.1462
−17%
15677
3-methyl-L-histidine
35
0.3568
0.481
−6%
15681
4-Guanidinobutanoic acid
35
0.8904
0.6558
−2%
15683
4-methyl-2-oxopentanoate
50
0.1063
0.3151
−16%
15704
heptanedioic acid
35
0.1218
0.3334
47%
15744
N-N-dimethylarginine
35
0.3455
0.481
−8%
15753
hippuric acid
35
0.6581
0.6042
−9%
15991
L-alpha -
35
0.3514
0.481
−18%
glycerophosphorylcholine
16002
Metabolite - 3992-possible-Cl-
35
0.643
0.6006
3%
adduct-of-Formate-dimer
16016
Metabolite - 3994
35
0.7835
0.6385
−8%
16071
Metabolite - 4020
50
0.7967
0.6385
−1%
16091
Metabolite - 4031-possible-
35
0.0804
0.2916
−12%
norlevorphenol-
isobutylphendienamide-
amprolium
16107
lysine
50
0.1771
0.3843
−12%
16137
Metabolite - 4078
35
0.2647
0.4695
−19%
16161
gamma - glutamyl-glutamic acid
35
0.9512
0.6641
0%
16186
Metabolite - 4096-possible-
35
0.4824
0.5344
19%
gamma-glu-gly-leu-
16226
Isobar-28-includes-L-threonine-
35
0.1998
0.3977
14%
L-allothreonine-L-homoserine-
S-4-amino-2-hydroxybutyric
acid
16231
Isobar-20-includes-fumaric
35
0.5237
0.5561
12%
acid-3-methyl-2-oxobutanoate
16232
Isobar-17-includes-arginine-N-
35
0.0125
0.1175
36%
alpha - acetyl-ornithine
16233
Isobar-13-includes-5-keto-D-
35
0.1598
0.3771
−19%
gluconic acid-2-keto-L-gulonic
acid-D-glucuronic acid-D-
galacturonic acid
16235
Isobar-19-includes-D-saccharic
35
0.5502
0.5628
11%
acid-1-5-anhydro-D-glucitol-2-
deoxy-D-galactose-2-deoxy-D-
glucose-L-fucose-L-rhamnose
16237
Isobar-25-includes-L-gulono-1-
35
0.7148
0.6154
−8%
4-lactone-glucono-gamma-
lactone-
16241
Isobar-30-includes-
35
0.6804
0.6106
−6%
maltotetraose-stachyose
16243
L-kynurenine
35
0.7838
0.6385
−3%
16244
Isobar-21-includes-gamma-
35
0.6805
0.6106
7%
aminobutyryl-L-histidine-L-
anserine
16246
Isobar-18-includes-D-fructose-
35
0.8566
0.6522
4%
1-phosphate-beta - D-fructose-6-
phosphate
16279
Isobar-36-includes-D-sorbitol-6-
35
0.3438
0.481
−13%
phosphate-mannitol-1-phosphate
16290
Metabolite - 4133
50
0.6833
0.6107
5%
16308
Metabolite - 4147
50
0.0642
0.2681
−24%
16330
Metabolite - 4163
35
0.4532
0.5239
−12%
16337
Metabolite - 4167
35
0.2792
0.4695
−17%
16462
Metabolite - 4234
35
0.4546
0.5239
−8%
16471
Metabolite - 4238
35
0.9246
0.6628
2%
16508
Metabolite - 4272
50
0.3504
0.481
−12%
16621
Metabolite - 4355
50
0.3773
0.4856
−17%
16653
Metabolite - 4361
50
0.3706
0.481
17%
16666
Metabolite - 4365
50
0.7897
0.6385
−4%
16824
iminodiacetic acid
50
0.041
0.213
−26%
16829
Metabolite - 4503
50
0.8049
0.639
−7%
16848
Metabolite - 4511
50
0.0692
0.2829
−25%
16952
Metabolite - 4593
50
0.6542
0.604
2%
17028
Metabolite - 4611
50
0.3655
0.481
−6%
17328
Metabolite - 4768
50
0.7791
0.6385
−7%
17330
Metabolite - 4769
50
0.1385
0.3566
17%
17359
Metabolite - 4791
50
0.8812
0.6555
−5%
17388
Metabolite - 4795
50
0.3033
0.481
22%
17614
Metabolite - 4966
50
0.3248
0.481
11%
17627
Metabolite - 4986
50
0.6096
0.59
12%
18118
Metabolite - 5346
50
0.6124
0.59
−6%
18146
Metabolite - 5366
50
0.6449
0.6006
7%
18232
Metabolite - 5403
50
0.2718
0.4695
10%
18316
Metabolite - 5437
50
0.4383
0.5195
−19%
18335
D-quinic acid
50
0.0891
0.295
−42%
18349
DL-indole-3-lactic acid
50
5.00E−04
0.0178
−25%
18868
Metabolite - 5847
50
0.4666
0.5282
−15%
18926
Metabolite - 5906
50
0.3425
0.481
−27%
18929
Metabolite - 5907
50
0.8229
0.6473
2%
[0000]
TABLE 8
Plasma Metabolite Biomarkers to distinguish Lower Grade PCA from
Higher Grade PCA.
%
Change
in Higher
COMP_ID
COMPOUND
LIB_ID
p-value
q-value
PCA
53
glutamine
50
0.2081
0.4944
−13%
54
tryptophan
50
0.0734
0.3431
−13%
57
glutamic acid
50
0.3386
0.6063
−13%
59
histidine
50
0.742
0.7437
−3%
60
leucine
50
0.015
0.154
−19%
63
cholesterol
50
0.19
0.4682
−9%
64
phenylalanine
35
0.1602
0.4579
−5%
513
creatinine
35
0.9764
0.7893
0%
527
lactate
50
0.0062
0.0915
−14%
528
alpha - keto-glutarate
35
0.6988
0.7368
−9%
541
4-hydroxyphenylacetate
35
0.9884
0.7893
0%
542
3-hydroxybutanoic acid
50
0.1111
0.4081
−50%
569
caffeine
35
6.00E−04
0.0433
−70%
577
fructose
50
0.0966
0.3887
−20%
581
glucose
50
0.6171
0.7298
−2%
584
mannose
50
0.9074
0.7713
−1%
594
niacinamide
35
0.4972
0.666
−18%
597
phosphoenolpyruvate
35
0.7347
0.7434
−4%
1105
linoleic acid
50
0.0404
0.2538
−17%
1107
allantoin
50
0.7673
0.7448
−6%
1110
arachidonic acid
50
0.6643
0.7368
−6%
1121
heptadecanoic acid
50
0
0.0036
−27%
1123
inosine
35
0.972
0.7891
1%
1125
isoleucine
50
0.0129
0.1407
−19%
1126
alanine
50
0.0951
0.3887
−15%
1284
threonine
50
0.3138
0.5918
−8%
1299
tyrosine
50
0.1559
0.4579
−11%
1302
methionine
35
0.5223
0.687
−4%
1303
malic acid
35
0.5527
0.712
−13%
1336
n-hexadecanoic acid
50
0.0024
0.0649
−20%
1358
octadecanoic acid
50
9.00E−04
0.0464
−16%
1365
tetradecanoic acid
50
0.0017
0.0613
−22%
1366
trans-4-hydroxyproline
50
0.0035
0.0738
−15%
1413
3-hydroxyphenylacetate
35
0.6788
0.7368
2%
1414
3-phospho-d-glycerate
35
0.4156
0.6338
−12%
1415
4-amino-5-methyl-2-1H-
35
0.3
0.5825
−10%
pyrimidinone
1431
(p-Hydroxyphenyl)lactic
50
0.0035
0.0738
−27%
acid
1432
alphahydroxybenzeneacetic
35
0.8113
0.751
3%
acid
1437
succinate
50
0.2184
0.5028
9%
1444
DL-pipecolic acid
35
0.9642
0.7862
0%
1480
guanidineacetic acid
35
0.8726
0.7585
−2%
1493
ornithine
50
0.1811
0.4682
−19%
1494
5-oxoproline
50
0.0231
0.2124
−12%
1498
N-6-trimethyl-l-lysine
35
0.7026
0.7368
5%
1507
palmitoleic acid
50
7.00E−04
0.0433
−44%
1508
pantothenic acid
35
0.182
0.4682
−31%
1519
sucrose
50
0.9548
0.7862
−2%
1557
3-methylglutaric acid
35
0.19
0.4682
−10%
1561
alpha - tocopherol
50
0.8757
0.759
−6%
1564
citric acid
50
0.2758
0.5606
−6%
1570
oleic acid
50
0.0045
0.0866
−34%
1572
glyceric acid
50
0.2114
0.4945
17%
1574
histamine
35
0.8416
0.7585
−4%
1584
methyl-indole-3-acetate
35
0.2877
0.569
−13%
1587
N-acetyl-L-leucine
35
0.2729
0.5593
−31%
1591
N-acetyl-L-valine
35
0.9102
0.7713
1%
1604
uric acid
35
0.813
0.751
−1%
1643
fumaric acid
50
0.5872
0.7241
−6%
1645
n-dodecanoate
50
0.1214
0.4111
−15%
1648
serine
50
0.0574
0.3133
−14%
1649
valine
50
0.0074
0.1041
−19%
1670
urea
50
0.6012
0.7257
3%
1708
7-8-dihydrofolic acid
35
0.5075
0.673
−20%
1898
proline
50
0.221
0.5048
−16%
2078
pyrophosphate
35
0.7583
0.7448
−7%
2092
catechol
35
0.2733
0.5593
−31%
2132
citrulline
50
0.3254
0.5955
9%
2730
gamma-L-glutamyl-L-
35
0.4725
0.6556
16%
glutamine
2734
gamma-L-glutamyl-L-
35
0.7177
0.7423
−2%
tyrosine
2832
adenosine-5-monophosphate
35
0.3158
0.5918
−14%
2848
guanosine-5-diphosphate
35
0.445
0.6491
−9%
3127
hypoxanthine
35
0.948
0.7855
1%
3138
pyridoxamine-phosphate
35
0.4558
0.6552
−12%
3147
xanthine
35
0.6472
0.73
13%
4966
xylitol
35
0.463
0.6556
13%
5280
biliverdin
35
0.1482
0.4503
−33%
5331
pyridoxal-phosphate
35
0.0379
0.2538
9%
5618
Metabolite - 1085-possible-
35
0.0709
0.3425
16%
isolobinine-or-4-aminoestra-
1-3-5-10-triene-3-17beta-
diol
5628
Metabolite - 1086
35
0.6001
0.7257
−8%
5669
Metabolite - 1104
35
0.0196
0.1865
−14%
5687
Metabolite - 1110
35
0.3645
0.6113
37%
5689
Metabolite - 1111-possible-
35
0.4217
0.6338
−9%
methylnitronitrosoguanidine-
or-ethyl-
thiocarbamoylacetate
5697
acetylcarnitine-
35
0.262
0.559
−11%
5717
Metabolite - 1121
35
0.1136
0.4081
17%
5733
Metabolite - 1127
35
0.0695
0.3413
−20%
5765
Metabolite - 1142-possible-
35
0.5859
0.7241
−18%
5-hydroxypentanoate-or-
beta-hydroxyisovaleric
acid
5788
Metabolite - 1183
35
0.3872
0.6303
−55%
5792
Metabolite - 1185
35
0.0919
0.3869
24%
5800
Metabolite - 1188
35
0.4258
0.6338
−13%
6112
Metabolite - 1203-HXGXA
35
0.1905
0.4682
−48%
in-MTRX
6130
Metabolite - 1208
35
0.3544
0.6113
−20%
6136
Metabolite - 1211-possible-
35
0.6994
0.7368
−22%
IHWESASLLR-
6144
Metabolite - 1215
35
0.7751
0.7448
10%
6147
Metabolite - 1216
35
0.3347
0.6063
−15%
6155
Metabolite - 1220
35
0.9929
0.7893
0%
6171
Metabolite - 1244
35
0.3205
0.5918
−15%
6266
Metabolite - 1286
35
0.1856
0.4682
11%
6278
Metabolite - 1289
35
0.4585
0.6556
14%
6362
Metabolite - 1323-possible-
35
0.9961
0.7893
0%
p-cresol-sulfate
6398
Metabolite - 1335
35
0.8918
0.766
2%
6413
Metabolite - 1342-possible-
35
0.7003
0.7368
−8%
phenylacetylglutamine-or-
formyl-N-acetyl-5-
methoxykynurenamine
6437
Metabolite - 1349-possible-
35
0.9819
0.7893
−1%
N-acetyl-8-O-methyl-
Neuraminic acid
6443
Metabolite - 1351
35
0.871
0.7585
−2%
6537
Metabolite - 1389-possible-
35
0.302
0.5825
−78%
gemfibrozil-glucuronide-
6549
Metabolite - 1392
35
0.4157
0.6338
−15%
6787
Metabolite - 1465
35
0.649
0.73
−8%
6852
Metabolite - 1498
35
0.0777
0.3524
33%
6987
Metabolite - 1573
35
0.9489
0.7855
−1%
7029
Metabolite - 1597
35
0.4038
0.6338
−6%
7081
Metabolite - 1609
35
0.0305
0.2368
−23%
7177
Metabolite - 1656
35
0.4157
0.6338
13%
7359
n-acetyl-L-aspartic acid
35
0.0437
0.2628
−21%
7446
p-hydroxybenzaldehyde
35
0.6766
0.7368
−4%
7595
Metabolite - 1817
35
0.153
0.4554
21%
7639
oxalic acid
35
0.2078
0.4944
11%
7644
Metabolite - 1831-possible-
35
0.0691
0.3413
−44%
Cl-adduct-of-citrulline
7650
Metabolite - 1834
35
0.1156
0.4081
−30%
7652
Metabolite - 1835
35
0.4281
0.6338
−11%
7654
Metabolite - 1836
35
0.147
0.4503
−25%
7660
Metabolite - 1839
35
0.0387
0.2538
−42%
7672
Metabolite - 1843
35
0.7808
0.7448
−3%
7933
Metabolite - 1911
35
0.5335
0.6956
−16%
7935
paraxanthine
35
0.0019
0.0613
−58%
7941
Metabolite - 1914
35
0.4757
0.6556
25%
7944
Metabolite - 1915
35
0.6141
0.7297
−26%
7957
trans-2-3-4-
35
0.4257
0.6338
28%
trimethoxycinnamic acid
8091
glycocholic acid
35
0.4181
0.6338
−27%
8176
Metabolite - 1974
35
0.7599
0.7448
−5%
8189
Metabolite - 1977
35
0.0864
0.3689
−14%
8196
Metabolite - 1979-Cl-
35
0.6427
0.73
6%
adduct-of-isobar-19
8217
Metabolite - 1983
35
0.6235
0.73
−32%
8300
Metabolite - 1988
35
0.0635
0.3225
−19%
8336
Metabolite - 2005
35
0.0395
0.2538
−25%
8404
Metabolite - 2027
35
0.3196
0.5918
−10%
8649
Metabolite - 2053
35
0.1695
0.4624
−19%
8669
Metabolite - 2055
35
0.9053
0.7713
3%
8677
Metabolite - 2056
35
0.0608
0.3144
−20%
8796
Metabolite - 2074
35
0.7798
0.7448
4%
8959
Metabolite - 2100
35
0.9464
0.7855
−1%
9007
Metabolite - 2108
35
0.0164
0.1608
−29%
9024
Metabolite - 2111
35
0.5873
0.7241
−10%
9092
Metabolite - 2129
35
0.8698
0.7585
5%
9106
Metabolite - 2130
35
0.0606
0.3144
95%
9130
Metabolite - 2139
35
0.6874
0.7368
5%
9137
Metabolite - 2141
35
0.0058
0.0915
−49%
9491
Metabolite - 2185
35
0.1596
0.4579
−12%
9748
Metabolite - 2212
35
0.0811
0.355
31%
10087
Metabolite - 2249
35
0.8331
0.7585
−3%
10092
Metabolite - 2250
35
0.2327
0.5235
−27%
10122
Metabolite - 2254
35
0.3765
0.6227
−29%
10143
Metabolite - 2255-
35
0.6393
0.73
27%
hydroxyproline-form-of-
bradykinin
10145
Metabolite - 2256
35
0.4476
0.6495
18%
10245
Metabolite - 2269-
35
0.4123
0.6338
24%
10317
Metabolite - 2279
35
0.0505
0.2916
−42%
10327
Metabolite - 2281
35
0.3395
0.6063
−44%
10378
Metabolite - 2287
35
0.2325
0.5235
180%
10438
gamma-glu-leu
35
0.245
0.5351
−10%
10461
Metabolite - 2313
35
0.7899
0.7448
−3%
10476
Metabolite - 2316
35
0.1189
0.4081
74%
10544
Metabolite - 2329
35
0
0.0014
−42%
10551
Metabolite - 2347
35
0.5251
0.6877
20%
10604
Metabolite - 2370
35
0.9852
0.7893
0%
10629
Metabolite - 2386
35
0.5977
0.7257
−11%
10644
Metabolite - 2387
35
0.3024
0.5825
−55%
10655
Metabolite - 2388
35
0.1144
0.4081
12%
10667
Metabolite - 2389
35
0.1156
0.4081
138%
10672
Metabolite - 2390
35
0.0817
0.355
−41%
10692
Metabolite - 2391
35
0.3467
0.6113
−7%
10698
Metabolite - 2392
35
0.8622
0.7585
−7%
10737
Isobar-1-includes-mannose-
35
0.6822
0.7368
−6%
fructose-glucose-galactose-
alpha-L-sorbopyranose-
Inositol-D-allose-D--altrose-
D-psicone
10739
Metabolite - 2407
35
0.0119
0.1402
48%
10741
Isobar-2-includes-2-
35
0.6689
0.7368
−7%
aminoisobutyric acid-3-
amino-isobutyrate-2-amino-
butyrate-4-aminobutanoic
acid-dimethylglycine-
choline-
10743
Isobar-4-includes-Gluconic
35
0.3076
0.5847
16%
acid-DL-arabinose-D-
ribose-L-xylose-DL-lyxose-
D-xylulose
10744
Isobar-5-includes-
35
0.2642
0.559
13%
asparagine-ornithine-gly-gly
10746
Isobar-6-includes-valine-
35
0.0032
0.0738
−12%
betaine
10753
Isobar-9-includes-
35
0.9571
0.7862
1%
galactinol-dihydrate-
turanose-kojibiose-D-
leucrose-lactulose-
sophorose-sucrose-beta-D-
lactose-D-trehalose-D-
cellobiose-D-Maltose-
palatinose-melibiose-alpha-
D-lactose
10782
Metabolite - 2486
35
0.427
0.6338
−15%
10785
Metabolite - 2506
35
0.1333
0.4318
−41%
10787
Metabolite - 2507
35
0.354
0.6113
−25%
10825
Metabolite - 2546
35
0.4672
0.6556
−13%
11053
Metabolite - 2567
35
0.7367
0.7434
−3%
11111
Metabolite - 2592
35
0.1638
0.4579
−62%
11219
Metabolite - 2686
35
0.7815
0.7448
−2%
11222
Metabolite - 2688
35
0.6332
0.73
−7%
11323
Metabolite - 2711
35
0.0047
0.0866
−21%
11438
phosphate
50
0.7922
0.7448
−1%
11499
Metabolite - 2753
35
0.3071
0.5847
−11%
11777
glycine
50
0.355
0.6113
−9%
11813
Metabolite - 2809
35
0.5982
0.7257
−10%
12035
nonanate
50
0.6366
0.73
2%
12109
Metabolite - 2853
35
0.0251
0.2202
−34%
12298
Metabolite - 2867
35
0.9249
0.7787
−4%
12478
Metabolite - 2898
35
0.4273
0.6338
30%
12532
Metabolite - 2914
50
0.8816
0.7596
0%
12533
Metabolite - 2915
50
0.1622
0.4579
14%
12543
2-hydroxy-butanoic acid
50
0.0286
0.2334
−29%
12562
Metabolite - 2955
50
0.5565
0.7129
−2%
12593
Metabolite - 2973
50
0.8623
0.7585
1%
12594
Metabolite - 2974
50
0.1248
0.4179
11%
12601
Metabolite - 2978
50
0.1299
0.4252
19%
12625
Metabolite - 3002
50
0.0819
0.355
−20%
12626
Metabolite - 3003
50
0.4436
0.6491
9%
12627
Metabolite - 3004
50
0.6919
0.7368
5%
12639
Metabolite - 3012
50
0.8549
0.7585
2%
12641
meso-erythritol
50
0.163
0.4579
−9%
12644
Metabolite - 3016
50
0.6845
0.7368
−3%
12645
Metabolite - 3017
50
0.7813
0.7448
−3%
12647
Metabolite - 3019
50
0.6788
0.7368
4%
12648
Metabolite - 3020
50
0.9322
0.7826
1%
12650
Metabolite - 3022
50
0.6859
0.7368
5%
12656
Metabolite - 3025
50
0.9228
0.7787
1%
12658
Metabolite - 3026
50
0.7257
0.7423
3%
12663
Metabolite - 3030
50
0.114
0.4081
12%
12666
Metabolite - 3033
50
0.0152
0.154
15%
12673
Metabolite - 3040
50
0.2695
0.5593
15%
12682
Metabolite - 3044
35
0.1443
0.4503
−18%
12719
Metabolite - 3055
35
0.5731
0.7241
15%
12720
Metabolite - 3056
35
0.9358
0.7834
1%
12726
Metabolite - 3058
50
0.6191
0.7298
9%
12739
1-5-anhydro-D-glucitol
50
0.7986
0.7448
−4%
12751
Metabolite - 3073
50
0.1953
0.4717
22%
12753
Metabolite - 3074
50
0.3904
0.6321
−22%
12754
Metabolite - 3075
50
0.2559
0.5505
15%
12756
Metabolite - 3077
50
0.5804
0.7241
5%
12757
Metabolite - 3078
50
0.2799
0.5648
11%
12761
Metabolite - 3081
50
0.8489
0.7585
1%
12765
inositol
50
0.5387
0.6992
−7%
12768
Metabolite - 3088
50
0.0017
0.0613
63%
12769
Metabolite - 3089
50
0.0293
0.2334
−26%
12771
Metabolite - 3091
50
0.4809
0.6576
22%
12773
Metabolite - 3093
50
0.4029
0.6338
−13%
12774
Metabolite - 3094
50
0.4972
0.666
−7%
12777
Metabolite - 3097
50
0.3855
0.6303
−14%
12780
Metabolite - 3098
50
0.2867
0.569
17%
12781
Metabolite - 3099
50
0.1762
0.4679
−19%
12784
Metabolite - 3102
50
0.3989
0.6338
−6%
12790
Metabolite - 3108
50
0.8644
0.7585
−1%
12876
Metabolite - 3125
35
0.7646
0.7448
−2%
12912
Metabolite - 3129
35
0.4822
0.6576
−8%
12924
Metabolite - 3131
35
0.3961
0.6338
23%
12931
DL-hexanoyl-carnitine
35
0.487
0.6583
−6%
12960
Metabolite - 3134
35
0.6922
0.7368
−11%
12969
Metabolite - 3135
35
0.9108
0.7713
−3%
13018
Metabolite - 3138
35
0.7404
0.7437
−4%
13038
Metabolite - 3143
35
0.1276
0.4226
−18%
13065
Metabolite - 3146
35
0.0976
0.3887
−35%
13104
Metabolite - 3160
35
0.6297
0.73
−6%
13142
Metabolite - 3165
35
0.7536
0.7448
−2%
13146
Metabolite - 3166
35
0.7532
0.7448
−7%
13148
Metabolite - 3167
35
0.217
0.5028
−16%
13179
possible-Metabolite - 3176-
35
0.1906
0.4682
22%
possible-creatine
13208
Metabolite - 3181
35
0.7725
0.7448
3%
13211
Metabolite - 3182
35
0.6544
0.7332
11%
13214
Metabolite - 3183-possible-
35
0.8943
0.766
−1%
gamma-L-glutamyl-L-
phenylalanine
13217
Metabolite - 3184
35
0.8706
0.7585
−2%
13249
Metabolite - 3215
35
0.4668
0.6556
−9%
13251
Metabolite - 3216
35
0.7987
0.7448
−4%
13257
Metabolite - 3218
35
0.5009
0.6678
−8%
13342
Metabolite - 3243
35
0.6378
0.73
−9%
13448
Metabolite - 3303
35
0.2433
0.5351
−9%
13459
Metabolite - 3305
35
0.0084
0.1083
−50%
13484
Metabolite - 3309
35
0.8307
0.7585
−4%
13505
Metabolite - 3313
35
0.3577
0.6113
−20%
13509
Metabolite - 3314
35
0.3672
0.6113
−12%
13534
Metabolite - 3320-possible-
35
0.4843
0.6576
−28%
pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
0
0.0014
−47%
13589
Metabolite - 3327
35
0.0057
0.0915
−50%
13775
Metabolite - 3370
35
0.3669
0.6113
−8%
13803
Metabolite - 3377
35
0.006
0.0915
−57%
13904
Metabolite - 3402
35
0.0721
0.3428
−26%
14027
Metabolite - 3426
35
0.7318
0.7434
1%
14084
Metabolite - 3436
35
0.6058
0.7257
−10%
14117
Metabolite - 3441
35
0.7013
0.7368
5%
14239
Metabolite - 3474
35
0.0599
0.3144
31%
14249
Metabolite - 3476
35
0.7249
0.7423
9%
14368
Metabolite - 3489
35
0.3626
0.6113
−20%
14439
Metabolite - 3498
35
0.5688
0.7241
6%
14495
Metabolite - 3534
35
0.0262
0.2202
−32%
14595
Metabolite - 3576
35
0.2107
0.4945
26%
14608
Metabolite - 3578
35
0.6691
0.7368
9%
14639
Metabolite - 3603
35
0.1163
0.4081
18%
14640
Metabolite - 3604
35
0.5838
0.7241
−13%
14672
Metabolite - 3615
35
0.6102
0.728
−10%
14715
Metabolite - 3653-possible-
35
0.473
0.6556
28%
stachydrine-
14766
Metabolite - 3670
35
0.147
0.4503
−13%
14785
isobar-
35
0.3213
0.5918
−25%
glycochenodeoxycholic
acid-glycodeoxycholic acid
14787
Metabolite - 3698
35
0.7067
0.7385
8%
14837
Metabolite - 3707
35
0.1711
0.4624
76%
14961
Metabolite - 3752
35
0.639
0.73
−25%
15000
Metabolite - 3758
35
0.1668
0.4593
−19%
15017
Metabolite - 3761
35
0.8791
0.7596
3%
15032
Metabolite - 3765
35
0.0335
0.2531
−38%
15063
Metabolite - 3772
35
0.1466
0.4503
−11%
15113
Metabolite - 3783
35
0.4353
0.6413
12%
15122
glycerol
50
0.056
0.3133
−13%
15128
DL-homocysteine
35
0.728
0.7423
3%
15129
D-alanyl-D-alanine
35
0.0754
0.3472
−21%
15211
Metabolite - 3807
35
0.8721
0.7585
−1%
15220
Metabolite - 3813
35
0.1744
0.4672
−20%
15227
Metabolite - 3816
35
0.8542
0.7585
−3%
15251
Metabolite - 3830
35
0.0126
0.1407
−36%
15253
Metabolite - 3832-possible-
35
0.7773
0.7448
−8%
phenol-sulfate
15278
Metabolite - 3843
35
0.8645
0.7585
−1%
15319
DL-phenyllactic acid
35
0.0478
0.2816
−41%
15326
Metabolite - 3879
35
0.7977
0.7448
13%
15328
azelaic acid
35
0.2378
0.5309
−9%
15336
tartaric acid
35
0.0388
0.2538
−38%
15365
sn-Glycerol-3-phosphate
50
0.2692
0.5593
−8%
15389
Metabolite - 3900
35
0.0079
0.1061
−16%
15500
carnitine
35
0.344
0.6106
7%
15529
Metabolite - 3951
35
0.2451
0.5351
9%
15535
Metabolite - 3955
35
0.3382
0.6063
37%
15606
Metabolite - 3968
35
0.9659
0.7862
1%
15612
Metabolite - 3972
35
0.7724
0.7448
2%
15626
Metabolite - 3977
35
0.1527
0.4554
−10%
15677
3-methyl-L-histidine
35
0.5533
0.712
3%
15681
4-Guanidinobutanoic acid
35
0.3014
0.5825
15%
15683
4-methyl-2-oxopentanoate
50
0.0405
0.2538
−20%
15704
heptanedioic acid
35
0.1181
0.4081
51%
15744
N—N-dimethylarginine
35
0.1838
0.4682
−11%
15753
hippuric acid
35
0.3545
0.6113
−17%
15991
L-alpha-
35
0.4761
0.6556
−16%
glycerophosphorylcholine
16002
Metabolite - 3992-possible-
35
0.586
0.7241
4%
Cl-adduct-of-Formate-dimer
16016
Metabolite - 3994
35
0.9895
0.7893
0%
16071
Metabolite - 4020
50
0.3655
0.6113
−6%
16091
Metabolite - 4031-possible-
35
0.1019
0.4004
−11%
norlevorphenol-
isobutylphendienamide-
amprolium
16107
lysine
50
0.1647
0.4579
−14%
16137
Metabolite - 4078
35
0.7185
0.7423
−8%
16161
gamma-glutamyl-glutamic
35
0.5784
0.7241
−8%
acid
16186
Metabolite - 4096-possible-
35
0.9805
0.7893
1%
gamma-glu-gly-leu-
16226
Isobar-28-includes-L-
35
0.2869
0.569
11%
threonine-L-allothreonine-
L-homoserine-S-4-amino-2-
hydroxybutyric acid
16231
Isobar-20-includes-fumaric
35
0.7914
0.7448
−5%
acid-3-methyl-2-
oxobutanoate
16232
Isobar-17-includes-arginine-
35
0.01
0.1225
38%
N-alpha-acetyl-ornithine
16233
Isobar-13-includes-5-keto-
35
0.1191
0.4081
−21%
D-gluconic acid-2-keto-L-
gulonic acid-D-glucuronic
acid-D-galacturonic acid
16235
Isobar-19-includes-D-
35
0.6445
0.73
8%
saccharic acid-1-5-anhydro-
D-glucitol-2-deoxy-D-
galactose-2-deoxy-D-
glucose-L-fucose-L-
rhamnose
16237
Isobar-25-includes-L-
35
0.821
0.756
−5%
gulono-1-4-lactone-glucono-
gamma-lactone-
16241
Isobar-30-includes-
35
0.2512
0.5443
−15%
maltotetraose-stachyose
16243
L-kynurenine
35
0.6009
0.7257
−5%
16244
Isobar-21-includes-gamma-
35
0.1351
0.4326
36%
aminobutyryl-L-histidine-L-
anserine
16246
Isobar-18-includes-D-
35
0.9657
0.7862
−1%
fructose-1-phosphate-beta-
D-fructose-6-phosphate
16279
Isobar-36-includes-D-
35
0.0397
0.2538
−26%
sorbitol-6-phosphate-
mannitol-1-phosphate
16290
Metabolite - 4133
50
0.1945
0.4717
16%
16308
Metabolite - 4147
50
0.1066
0.4081
−21%
16330
Metabolite - 4163
35
0.866
0.7585
−3%
16337
Metabolite - 4167
35
0.4046
0.6338
−14%
16462
Metabolite - 4234
35
0.7831
0.7448
−4%
16471
Metabolite - 4238
35
0.7117
0.741
−8%
16508
Metabolite - 4272
50
0.939
0.7839
−1%
16621
Metabolite - 4355
50
0.9609
0.7862
−1%
16653
Metabolite - 4361
50
0.8571
0.7585
−3%
16666
Metabolite - 4365
50
0.6891
0.7368
7%
16824
iminodiacetic acid
50
0.0261
0.2202
−23%
16829
Metabolite - 4503
50
0.839
0.7585
−7%
16848
Metabolite - 4511
50
0.0959
0.3887
−23%
16952
Metabolite - 4593
50
0.7253
0.7423
−2%
17028
Metabolite - 4611
50
0.7939
0.7448
−2%
17328
Metabolite - 4768
50
0.414
0.6338
−17%
17330
Metabolite - 4769
50
0.8061
0.7493
3%
17359
Metabolite - 4791
50
0.9964
0.7893
0%
17388
Metabolite - 4795
50
0.6053
0.7257
10%
17614
Metabolite - 4966
50
0.866
0.7585
2%
17627
Metabolite - 4986
50
0.4496
0.6495
−13%
18118
Metabolite - 5346
50
0.2656
0.559
−11%
18146
Metabolite - 5366
50
0.0574
0.3133
−23%
18232
Metabolite - 5403
50
0.6472
0.73
4%
18316
Metabolite - 5437
50
0.0382
0.2538
−38%
18335
D-quinic acid
50
0.0437
0.2628
−48%
18349
DL-indole-3-lactic acid
50
0.0021
0.0633
−22%
18868
Metabolite - 5847
50
0.3783
0.6227
−18%
18926
Metabolite - 5906
50
0.4724
0.6556
−29%
18929
Metabolite - 5907
50
0.5093
0.673
−6%
Example 4
Distinguish Lower Grade from Higher Grade, Urine
[0128] Biomarkers were discovered by (1) analyzing urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0129] The urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0130] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).
Biomarkers:
[0131] As listed below in Table 9, biomarkers were discovered that were differentially present between urine samples from subjects with lower grade prostate cancer and urine samples from Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 10 lists biomarkers that were discovered that were differentially present between urine samples from subjects with metastatic/high grade prostate cancer and urine samples from Control subjects with biopsy negative prostates (i.e. not diagnosed with prostate cancer). Table 11 lists biomarkers that were discovered that were differentially present between urine samples from subjects with metastatic/high grade prostate cancer and urine from subjects with lower grade prostate cancer.
[0132] Tables 9-11 include, for each listed biomarker, the p-value and q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 9), the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 10), and the metastatic/high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 11). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.
[0133] Biomarkers were discovered by (1) analyzing urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
[0134] The urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
[0135] T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).
[0000]
TABLE 9
Urine Metabolite Biomarkers to distinguish Non-cancer vs. Lower Grade PCA
% Change
COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA
53
glutamine
50
0.796
0.9846
5%
54
tryptophan
35
0.1502
0.9846
−15%
57
glutamic acid
50
0.855
0.9846
−3%
59
histidine
50
0.4545
0.9846
17%
60
leucine
50
0.7145
0.9846
8%
64
phenylalanine
35
0.6419
0.9846
−6%
418
guanine
50
0.9595
0.9875
1%
512
asparagine
50
0.4606
0.9846
−9%
513
creatinine
35
0.1826
0.9846
−10%
521
homogentisate
50
0.8571
0.9846
−5%
527
lactate
50
0.3716
0.9846
−9%
528
alpha-keto-glutarate
35
0.1009
0.9846
35%
531
3-hydroxy-3-
50
0.9687
0.9875
0%
methylglutarate
541
4-hydroxyphenylacetate
50
0.4362
0.9846
25%
542
3-hydroxybutanoic acid
50
0.6851
0.9846
27%
554
adenine
50
0.2417
0.9846
23%
555
adenosine
35
0.9098
0.9875
2%
563
alpha-L-sorbopyranose
50
0.9777
0.9875
−1%
569
caffeine
35
0.4377
0.9846
21%
575
arabinose
50
0.5366
0.9846
10%
577
fructose
50
0.4858
0.9846
31%
581
glucose
50
0.3339
0.9846
−77%
587
gluconic acid
50
0.5172
0.9846
14%
594
niacinamide
35
0.8901
0.9875
1%
597
phosphoenolpyruvate
35
0.4537
0.9846
−20%
605
uracil
50
0.4138
0.9846
15%
607
urocanic acid
35
0.2858
0.9846
39%
608
vitamin-B6
35
0.1525
0.9846
112%
1101
3-methoxy-4-
50
0.9705
0.9875
1%
hydroxyphenylacetate
1107
allantoin
50
0.6965
0.9846
6%
1125
isoleucine
50
0.4588
0.9846
−12%
1126
alanine
50
0.9256
0.9875
1%
1284
threonine
50
0.7919
0.9846
5%
1299
tyrosine
50
0.8374
0.9846
4%
1302
methionine
35
0.6757
0.9846
−6%
1303
malic acid
35
0.81
0.9846
6%
1366
trans-4-hydroxyproline
50
0.2618
0.9846
22%
1413
3-hydroxyphenylacetate
35
0.8047
0.9846
−4%
1417
kynurenic acid
50
0.9471
0.9875
−1%
1418
5-6-Dihydrothymine
35
0.9664
0.9875
−1%
1419
5-s-methyl-5-thioadenosine
35
0.2486
0.9846
−15%
1431
(p-Hydroxyphenyl)lactic
50
0.1211
0.9846
32%
acid
1432
alphahydroxybenzeneacetic
35
0.8358
0.9846
−2%
acid
1437
succinate
50
0.0633
0.9846
42%
1444
DL-pipecolic acid
35
0.9345
0.9875
−4%
1480
guanidineacetic acid
35
0.0371
0.9846
42%
1493
ornithine
50
0.2975
0.9846
54%
1494
5-oxoproline
50
0.4228
0.9846
14%
1498
N-6-trimethyl-l-lysine
35
0.2734
0.9846
18%
1505
orotic acid
50
0.2172
0.9846
26%
1508
pantothenic acid
35
0.9729
0.9875
−1%
1519
sucrose
50
0.3449
0.9846
95%
1557
3-methylglutaric acid
35
0.8338
0.9846
3%
1558
4-acetamidobutyric acid
35
0.3994
0.9846
−13%
1559
5-6-dihydrouracil
50
0.2764
0.9846
14%
1560
L-methyldopa
35
0.3931
0.9846
19%
1564
citric acid
50
0.4898
0.9846
13%
1566
3-amino-isobutyrate
50
0.3393
0.9846
41%
1567
4-hydroxy-3-
50
0.8926
0.9875
−3%
methoxymandelate
1568
4-hydroxymandelate
50
0.6452
0.9846
11%
1569
DL-beta-
35
0.4562
0.9846
16%
hydroxyphenylethylamine
1574
histamine
35
0.892
0.9875
−3%
1580
noradrenaline
50
0.6485
0.9846
11%
1585
N-acetyl-L-alanine
35
0.5936
0.9846
−8%
1587
N-acetyl-L-leucine
35
0.7574
0.9846
5%
1591
N-acetyl-L-valine
35
0.2762
0.9846
34%
1592
N-acetylneuraminic acid
50
0.9603
0.9875
−1%
1598
N-tigloylglycine
35
0.434
0.9846
13%
1604
uric acid
35
0.8166
0.9846
1%
1640
ascorbic acid
50
0.5353
0.9846
113%
1648
serine
50
0.448
0.9846
10%
1649
valine
50
0.8355
0.9846
4%
1708
7-8-dihydrofolic acid
35
0.3057
0.9846
10%
1778
gamma-glu-cys
35
0.9805
0.9875
−1%
1827
riboflavine
35
0.3791
0.9846
29%
1860
3-nitro-L-tyrosine
35
0.3596
0.9846
26%
1868
cysteine
50
0.3622
0.9846
69%
1898
proline
50
0.806
0.9846
−5%
1899
quinolinic acid
50
0.8475
0.9846
3%
2078
pyrophosphate
50
0.3881
0.9846
44%
2092
catechol
35
0.9299
0.9875
3%
2132
citrulline
50
0.1077
0.9846
29%
2183
thymidine
35
0.6528
0.9846
−7%
2245
Metabolite - 294
35
0.1857
0.9846
32%
2342
serotonin
35
0.631
0.9846
6%
2734
gamma-L-glutamyl-L-
35
0.1668
0.9846
−24%
tyrosine
2829
N-formyl-L-methionine
35
0.3164
0.9846
19%
2831
adenosine-3-5-cyclic-
35
0.4814
0.9846
−8%
monophosphate
3127
hypoxanthine
35
0.8698
0.9875
3%
3138
pyridoxamine-phosphate
35
0.3482
0.9846
−9%
3147
xanthine
35
0.3736
0.9846
10%
3155
3-ureidopropionic acid
35
0.3809
0.9846
17%
4966
xylitol
50
0.3043
0.9846
38%
5493
Metabolite - 1059
35
0.7607
0.9846
4%
5495
Metabolite - 1060
35
0.0016
0.6911
−17%
5514
Metabolite - 1081
35
0.904
0.9875
0%
5538
Metabolite - 1101
35
0.5358
0.9846
−21%
5664
Metabolite - 1101
35
0.506
0.9846
25%
5687
Metabolite - 1110
35
0.7134
0.9846
−6%
5697
acetylcarnitine-
35
0.6634
0.9846
12%
5702
Metabolite - 1114
35
0.4207
0.9846
−23%
5711
2-hydroxybutyric acid
35
0.7116
0.9846
7%
5719
Metabolite - 1122
35
0.5481
0.9846
11%
5727
Metabolite - 1126
35
0.541
0.9846
10%
5797
Metabolite - 1186
35
0.3318
0.9846
−14%
6137
Metabolite - 1212
35
0.2597
0.9846
−50%
6147
Metabolite - 1216
35
0.5806
0.9846
4%
6238
normetanephrine
50
0.8045
0.9846
−3%
6253
Metabolite - 1283
35
0.0674
0.9846
−25%
6278
Metabolite - 1289
35
0.7974
0.9846
4%
6329
urea
50
0.903
0.9875
2%
6362
Metabolite - 1323-possible-
35
0.4176
0.9846
18%
p-cresol-sulfate
6398
Metabolite - 1335
35
0.4128
0.9846
12%
6405
Metabolite - 1338
35
0.741
0.9846
−6%
6413
Metabolite - 1342-possible-
35
0.4637
0.9846
10%
phenylacetylglutamine-or-
formyl-N-acetyl-5-
methoxykynurenamine
6421
Metabolite - 1345
35
0.5336
0.9846
20%
6437
Metabolite - 1349-possible-
35
0.5691
0.9846
10%
N-acetyl-8-O-methyl-
Neuraminic acid
6443
Metabolite - 1351
35
0.3894
0.9846
23%
6477
Metabolite - 1364
35
0.3757
0.9846
167%
6486
Metabolite - 1368
35
0.5104
0.9846
−22%
6493
salicyluric acid
35
0.2953
0.9846
888%
6528
Metabolite - 1383-possible-
35
0.2172
0.9846
287%
salicyluric-glucuronide
6760
Metabolite - 1455
35
0.0407
0.9846
−22%
6764
Metabolite - 1459
35
0.1583
0.9846
36%
6777
Metabolite - 1463
35
0.172
0.9846
161%
6787
Metabolite - 1465
35
0.848
0.9846
−3%
6847
Metabolite - 1496
35
0.2291
0.9846
24%
6852
Metabolite - 1498
35
0.6978
0.9846
13%
6987
Metabolite - 1573
35
0.1323
0.9846
18%
7132
Metabolite - 1667
35
0.3324
0.9846
256%
7175
Metabolite - 1655
35
0.3706
0.9846
14%
7177
Metabolite - 1656
35
0.0404
0.9846
68%
7272
Metabolite - 1679
35
0.4554
0.9846
−10%
7286
Metabolite - 1682
35
0.363
0.9846
15%
7359
n-acetyl-L-aspartic acid
35
0.7265
0.9846
−6%
7639
oxalic acid
35
0.842
0.9846
2%
7650
Metabolite - 1834
35
0.6964
0.9846
−16%
7660
Metabolite - 1839
35
0.9696
0.9875
−1%
7672
Metabolite - 1843
35
0.5216
0.9846
−6%
7933
Metabolite - 1911
35
0.219
0.9846
41%
8176
Metabolite - 1974
35
0.4332
0.9846
20%
8196
Metabolite - 1979-Cl-
35
0.0901
0.9846
96%
adduct-of-isobar-19
8210
Metabolite - 1981
35
0.7764
0.9846
5%
8336
Metabolite - 2005
35
0.3343
0.9846
23%
8644
Metabolite - 2051
35
0.0878
0.9846
18%
8677
Metabolite - 2056
35
0.3734
0.9846
−12%
9007
Metabolite - 2108
35
0.2858
0.9846
−44%
9038
Metabolite - 2118
35
0.5665
0.9846
−7%
9113
Metabolite - 2133
35
0.1426
0.9846
−18%
9165
Metabolite - 2150
35
0.9275
0.9875
1%
9333
Metabolite - 2174
35
0.4734
0.9846
13%
9334
Metabolite - 2175
35
0.8327
0.9846
13%
9458
Metabolite - 2181
35
0.8365
0.9846
−3%
10058
Metabolite - 2242
35
0.3634
0.9846
427%
10087
Metabolite - 2249
35
0.3102
0.9846
−22%
10122
Metabolite - 2254
35
0.4777
0.9846
−40%
10136
Metabolite - 2034
35
0.8375
0.9846
−5%
10156
Metabolite - 2259
35
0.836
0.9846
−7%
10240
4-acetominophen-sulfate
35
0.2026
0.9846
34%
10245
Metabolite - 2269-
35
0.8222
0.9846
−2%
10247
Metabolite - 2270
35
0.6261
0.9846
15%
10252
Metabolite - 2271
35
0.2147
0.9846
30%
10286
Metabolite - 2272
35
0.4099
0.9846
−34%
10309
Metabolite - 2277
35
0.3674
0.9846
−12%
10347
Metabolite - 2285
35
0.8582
0.9846
4%
10407
Metabolite - 2059
35
0.663
0.9846
−6%
10424
Metabolite - 2292
35
0.1432
0.9846
30%
10433
Metabolite - 2293-possible-
35
0.3141
0.9846
1403%
O-desmethylvenlafaxine-
glucuronide
10490
Metabolite - 2319
35
0.83
0.9846
−4%
10526
Metabolite - 2323
35
0.8463
0.9846
4%
10544
Metabolite - 2329
35
0.9805
0.9875
1%
10555
Metabolite - 2348
35
0.2902
0.9846
65%
10570
Metabolite - 2366
35
0.1258
0.9846
−37%
10629
Metabolite - 2386
35
0.7455
0.9846
−4%
10644
Metabolite - 2387
35
0.3475
0.9846
−24%
10667
Metabolite - 2389
35
0.2017
0.9846
22%
10672
Metabolite - 2390
35
0.9346
0.9875
1%
10737
Isobar-1-includes-
35
0.4849
0.9846
−26%
mannose-fructose-glucose-
galactose-alpha-L-
sorbopyranose-Inositol-D-
allose-D--altrose-D-
psicone
10741
Isobar-2-includes-2-
35
0.356
0.9846
−61%
aminoisobutyric acid-3-
amino-isobutyrate-2-
amino-butyrate-4-
aminobutanoic acid-
dimethylglycine-choline-
10743
Isobar-4-includes-Gluconic
35
0.986
0.9883
0%
acid-DL-arabinose-D-
ribose-L-xylose-DL-
lyxose-D-xylulose
10746
Isobar-6-includes-valine-
35
0.8873
0.9875
4%
betaine
10785
Metabolite - 2506
35
0.6703
0.9846
7%
10825
Metabolite - 2546
35
0.3625
0.9846
13%
10872
Metabolite - 2550
35
0.5812
0.9846
−11%
10906
Metabolite - 2557-possible-
35
0.0411
0.9846
64%
Pantoprazole-metabolite
11053
Metabolite - 2567
35
0.7296
0.9846
5%
11085
Metabolite - 2588
35
0.2272
0.9846
25%
11110
Metabolite - 2591
35
0.4451
0.9846
17%
11173
Metabolite - 2607
35
0.2724
0.9846
42%
11219
Metabolite - 2686
35
0.4501
0.9846
13%
11264
Metabolite - 2698
35
0.6617
0.9846
27%
11271
Metabolite - 2700
35
0.1367
0.9846
48%
11292
Metabolite - 2703
35
0.6289
0.9846
−6%
11299
Metabolite - 2706
35
0.2913
0.9846
−22%
11390
Metabolite - 2726
35
0.3521
0.9846
−14%
11411
Metabolite - 2746
35
0.2543
0.9846
−21%
11438
phosphate
50
0.5453
0.9846
11%
11484
Metabolite - 2752
35
0.245
0.9846
18%
11661
Metabolite - 2781
35
0.7701
0.9846
−4%
11777
glycine
50
0.5674
0.9846
10%
11808
Metabolite - 2807
35
0.0487
0.9846
62%
11851
Metabolite - 2811
35
0.0085
0.9846
161%
12025
cis-aconitic acid
50
0.3727
0.9846
58%
12055
galactose
50
0.6975
0.9846
11%
12102
o-phosphoethanolamine
50
0.6267
0.9846
−13%
12104
Metabolite - 2852
35
0.5159
0.9846
29%
12109
Metabolite - 2853
35
0.9627
0.9875
1%
12129
beta-hydroxyisovaleric
50
0.8271
0.9846
4%
acid
12300
Metabolite - 2868
35
0.7519
0.9846
−16%
12358
(1′R,1′S)_biopterin
35
0.2306
0.9846
26%
12426
Metabolite - 2416
35
0.4534
0.9846
20%
12463
Metabolite - 2893-possible-
35
0.4566
0.9846
18%
demethylated-
Rosiglitazone
12474
Metabolite - 2897
35
0.2372
0.9846
−17%
12593
Metabolite - 2973
50
0.0377
0.9846
−25%
12641
meso-erythritol
50
0.9483
0.9875
−2%
12644
Metabolite - 3016
50
0.3011
0.9846
−8%
12648
Metabolite - 3020
50
0.8127
0.9846
5%
12666
Metabolite - 3033
50
0.8413
0.9846
3%
12711
Metabolite - 3053
35
0.5017
0.9846
24%
12720
Metabolite - 3056
35
0.5412
0.9846
8%
12765
inositol
50
0.4102
0.9846
−27%
12770
Metabolite - 3090
50
0.1121
0.9846
−11%
12771
Metabolite - 3091
50
0.2399
0.9846
−25%
12795
Metabolite - 3113
50
0.3928
0.9846
−14%
12856
Metabolite - 3123
35
0.4327
0.9846
17%
12902
Metabolite - 3127
35
0.765
0.9846
−4%
12904
Metabolite - 2457
35
0.0497
0.9846
66%
12924
Metabolite - 3131
35
0.7354
0.9846
−7%
12938
Metabolite - 2459
35
0.9267
0.9875
−1%
13018
Metabolite - 3138
35
0.9748
0.9875
0%
13136
Metabolite - 3163-possible-
35
0.9502
0.9875
1%
methylcytidine-
benserazide-Pyr-Gln-OH-
or-glycerophosphocholine-
13153
Metabolite - 3169
35
0.6836
0.9846
13%
13179
Metabolite - 3176
35
0.8382
0.9846
−13%
13214
Metabolite - 3183-possible-
35
0.6928
0.9846
8%
gamma-L-glutamyl-L-
phenylalanine
13217
Metabolite - 3184
35
0.3549
0.9846
10%
13249
Metabolite - 3215
35
0.8582
0.9846
3%
13251
Metabolite - 3216
35
0.3024
0.9846
−7%
13265
Metabolite - 3221
35
0.9343
0.9875
−2%
13297
Metabolite - 3231
35
0.9212
0.9875
−2%
13318
DL-indole-3-lactic acid
35
0.4237
0.9846
−19%
13356
Metabolite - 3246-possible-
35
0.5345
0.9846
−8%
Ala-GLy-glycyl-sarcosine-
or-ureido-butyric acid
13459
Metabolite - 3305
35
0.483
0.9846
16%
13484
Metabolite - 3309
35
0.8589
0.9846
3%
13493
Metabolite - 3311-
35
0.1888
0.9846
56%
13505
Metabolite - 3313
35
0.5469
0.9846
−13%
13534
Metabolite - 3320-possible-
35
0.6718
0.9846
13%
pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
0.393
0.9846
−14%
13589
Metabolite - 3327
35
0.2554
0.9846
26%
13594
Metabolite - 3329
35
0.9464
0.9875
−2%
13704
Metabolite - 3355
35
0.2556
0.9846
20%
13744
Metabolite - 3364
35
0.2659
0.9846
19%
13775
Metabolite - 3370
35
0.5874
0.9846
12%
13791
Metabolite - 3373
35
0.985
0.9883
0%
13803
Metabolite - 3377
35
0.5535
0.9846
−22%
13817
Metabolite - 3380
35
0.3112
0.9846
−11%
13820
beta-nicotinamide-
35
0.8355
0.9846
4%
mononucleotide
13847
Metabolite - 3387
35
0.7957
0.9846
4%
13904
Metabolite - 3402
35
0.3187
0.9846
71%
13968
Metabolite - 3409
35
0.3858
0.9846
18%
14036
Metabolite - 3427
35
0.7015
0.9846
8%
14066
Metabolite - 3433
35
0.7142
0.9846
−4%
14084
Metabolite - 3436
35
0.5508
0.9846
10%
14115
Metabolite - 3440
35
0.3104
0.9846
−64%
14125
Metabolite - 3443
35
0.5809
0.9846
11%
14170
Metabolite - 3457
35
0.6752
0.9846
12%
14220
Metabolite - 3470
35
0.8918
0.9875
4%
14249
Metabolite - 3476
35
0.0695
0.9846
82%
14368
Metabolite - 3489
35
0.3569
0.9846
−27%
14406
Metabolite - 3493
35
0.818
0.9846
3%
14453
Metabolite - 3507
35
0.5637
0.9846
14%
14471
Metabolite - 3516
35
0.2008
0.9846
34%
14506
Metabolite - 3543
35
0.5679
0.9846
−18%
14539
Metabolite - 3564
35
0.1262
0.9846
−38%
14595
Metabolite - 3576
35
0.4931
0.9846
9%
14640
Metabolite - 3604
35
0.1561
0.9846
20%
14641
Metabolite - 3605
35
0.1604
0.9846
44%
14731
Metabolite - 3659
35
0.4077
0.9846
18%
14732
Metabolite - 3660
35
0.2255
0.9846
31%
14733
Metabolite - 3661
35
0.7777
0.9846
−9%
14759
Metabolite - 3667
35
0.2647
0.9846
19%
14762
Metabolite - 3668
35
0.57
0.9846
−5%
14766
Metabolite - 3670
35
0.5103
0.9846
12%
14769
Metabolite - 3691
35
0.6776
0.9846
−8%
14808
Metabolite - 3701
35
0.0336
0.9846
−31%
14835
Metabolite - 3706
35
0.9101
0.9875
2%
14840
Metabolite - 3708
35
0.8511
0.9846
−6%
14907
Metabolite - 3734
35
0.3113
0.9846
16%
14983
Metabolite - 3754
35
0.9005
0.9875
−2%
14984
Metabolite - 3755
35
0.3521
0.9846
154%
15017
Metabolite - 3761
35
0.1689
0.9846
21%
15057
Metabolite - 3771
35
0.1457
0.9846
52%
15064
Metabolite - 3773
35
0.4225
0.9846
−10%
15096
N-acetyl-D-glucosamine
50
0.612
0.9846
10%
15121
Metabolite - 3786
35
0.3986
0.9846
20%
15124
porphobilinogen
35
0.8882
0.9875
2%
15125
(2-
35
0.1453
0.9846
14%
Aminoethyl)phosphonate
15128
DL-homocysteine
35
0.0781
0.9846
46%
15129
D-alanyl-D-alanine
35
0.9606
0.9875
1%
15130
diaminopimelic acid
35
0.4317
0.9846
−9%
15131
dethiobiotin
35
0.7544
0.9846
−6%
15187
Metabolite - 3800
35
0.7143
0.9846
−8%
15197
Metabolite - 3802
35
0.701
0.9846
8%
15201
Metabolite - 3803
35
0.3018
0.9846
16%
15202
Metabolite - 3804
35
0.213
0.9846
−22%
15203
Metabolite - 3805
35
0.9354
0.9875
−2%
15207
Metabolite - 3806
35
0.1744
0.9846
−33%
15211
Metabolite - 3807
35
0.8708
0.9875
2%
15220
Metabolite - 3813
35
0.3635
0.9846
17%
15228
Metabolite - 3817
35
0.5239
0.9846
−12%
15240
Metabolite - 3824
35
0.8028
0.9846
−7%
15249
Metabolite - 3828
35
0.8756
0.9875
3%
15251
Metabolite - 3830
35
0.0975
0.9846
39%
15253
Metabolite - 3832-possible-
35
0.2712
0.9846
−41%
phenol-sulfate
15258
Metabolite - 3834-Peptide
35
0.4949
0.9846
18%
15275
Metabolite - 3840
35
0.6594
0.9846
5%
15276
Metabolite - 3841
35
0.3623
0.9846
58%
15278
Metabolite - 3843
35
0.8581
0.9846
−4%
15284
Metabolite - 3847
35
0.9705
0.9875
0%
15294
Metabolite - 3855
35
0.8089
0.9846
5%
15312
Metabolite - 3873
35
0.609
0.9846
−8%
15315
Metabolite - 3876
35
0.379
0.9846
29%
15324
Metabolite - 3878
35
0.3307
0.9846
−18%
15326
Metabolite - 3879
35
0.9133
0.9875
−3%
15328
azelaic acid
35
0.1572
0.9846
−33%
15335
mannitol
50
0.123
0.9846
50%
15336
tartaric acid
35
0.2935
0.9846
−26%
15356
Metabolite - 3886
35
0.5807
0.9846
8%
15359
Metabolite - 3887
35
0.7867
0.9846
−5%
15365
sn-Glycerol-3-phosphate
50
0.8503
0.9846
−7%
15374
Metabolite - 3893
35
0.8837
0.9875
2%
15382
Metabolite - 3898
35
0.6325
0.9846
4%
15410
Metabolite - 3908
35
0.5194
0.9846
10%
15411
Metabolite - 3909
35
0.6385
0.9846
−23%
15418
Metabolite - 3911
35
0.4593
0.9846
8%
15496
agmatine
35
0.0364
0.9846
34%
15500
carnitine
35
0.7459
0.9846
10%
15529
Metabolite - 3951
35
0.9957
0.9957
0%
15532
Metabolite - 3952
35
0.4244
0.9846
−16%
15535
Metabolite - 3955
35
0.9603
0.9875
1%
15541
Metabolite - 3957
35
0.8287
0.9846
−3%
15599
Metabolite - 3963
35
0.3146
0.9846
24%
15610
Metabolite - 3970
35
0.4461
0.9846
17%
15620
Metabolite - 3973
35
0.3553
0.9846
44%
15626
Metabolite - 3977
35
0.1456
0.9846
−35%
15636
Metabolite - 3981
35
0.5962
0.9846
−16%
15641
Metabolite - 3986
35
0.6453
0.9846
−6%
15650
1-methyladenosine
35
0.8651
0.9875
−2%
15667
2-isopropylmalic acid
50
0.6338
0.9846
−24%
15676
3-methyl-2-oxovaleric acid
35
0.4947
0.9846
16%
15677
3-methyl-L-histidine
35
0.046
0.9846
−23%
15679
xanthurenic acid
50
0.5776
0.9846
14%
15681
4-Guanidinobutanoic acid
35
0.8135
0.9846
4%
15704
heptanedioic acid
35
0.7689
0.9846
−3%
15716
L-beta-imidazolelactic acid
50
0.5938
0.9846
18%
15730
suberic acid
35
0.2788
0.9846
−13%
15737
hydroxyacetic acid
50
0.5729
0.9846
−9%
15743
N-N-dimethylarginine
35
0.7457
0.9846
4%
15753
hippuric acid
35
0.4325
0.9846
14%
15778
benzoic acid
35
0.1887
0.9846
63%
15804
maltose
50
0.428
0.9846
64%
15835
L-xylose
50
0.7767
0.9846
10%
15948
S-adenosyl-l-homocysteine
35
0.6109
0.9846
−11%
15964
D-arabitol
50
0.9713
0.9875
1%
16002
Metabolite - 3992-possible-
35
0.1682
0.9846
16%
Cl-adduct-of-Formate-
dimer
16016
Metabolite - 3994
35
0.1703
0.9846
−24%
16034
Metabolite - 4002
50
0.1968
0.9846
30%
16071
Metabolite - 4020
50
0.6192
0.9846
8%
16082
Metabolite - 4027
50
0.7798
0.9846
5%
16107
lysine
50
0.2773
0.9846
145%
16175
Metabolite - 4092
35
0.4841
0.9846
−13%
16197
Metabolite - 4112
35
0.8282
0.9846
4%
16217
Metabolite - 4116
35
0.8574
0.9846
−6%
16230
Isobar-29-includes-R-S-
35
0.0326
0.9846
114%
hydroorotic acid-5-6-
dihydroorotic acid
16232
Isobar-17-includes-
35
0.7984
0.9846
5%
arginine-N-alpha-acetyl-
ornithine
16233
Isobar-13-includes-5-keto-
35
0.7037
0.9846
−8%
D-gluconic acid-2-keto-L-
gulonic acid-D-glucuronic
acid-D-galacturonic acid
16235
Isobar-19-includes-D-
35
0.1465
0.9846
66%
saccharic acid-1-5-
anhydro-D-glucitol-2-
deoxy-D-galactose-2-
deoxy-D-glucose-L-fucose-
L-rhamnose
16243
L-kynurenine
35
0.5787
0.9846
−8%
16276
Isobar-38-includes-N-
35
0.4495
0.9846
19%
acetyl-L-methionine-5-
hydroxy-1H-indole-3-
acetic acid
16278
Isobar-35-includes-D-
35
0.1346
0.9846
20%
arabinose-5-phosphate-D-
ribulose-5-phosphate-
alpha-D-ribose-5-
phosphate
16290
Metabolite - 4133
50
0.4411
0.9846
35%
16337
Metabolite - 4167
35
0.633
0.9846
12%
16338
Metabolite - 4168
35
0.6584
0.9846
20%
16457
Metabolite - 4233
35
0.4705
0.9846
21%
16462
Metabolite - 4234
35
0.1194
0.9846
57%
16496
Metabolite - 4251
50
0.1706
0.9846
−16%
16506
Metabolite - 4271
50
0.2282
0.9846
31%
16816
Metabolite - 4494
50
0.938
0.9875
−1%
16818
Metabolite - 4495
50
0.3478
0.9846
18%
16819
Metabolite - 4496
50
0.4825
0.9846
6%
16821
Metabolite - 4498
50
0.2269
0.9846
34%
16822
Metabolite - 4499
50
0.5555
0.9846
11%
16823
Metabolite - 4500
50
0.3974
0.9846
63%
16824
iminodiacetic acid
50
0.1445
0.9846
−23%
16827
Metabolite - 4502
50
0.6363
0.9846
−1%
16829
Metabolite - 4503
50
0.2869
0.9846
23%
16831
Metabolite - 4504
50
0.7348
0.9846
6%
16834
Metabolite - 4505
50
0.6099
0.9846
15%
16837
Metabolite - 4507
50
0.2767
0.9846
26%
16848
Metabolite - 4511
50
0.3715
0.9846
33%
16851
Metabolite - 4512
50
0.1504
0.9846
59%
16859
Metabolite - 4516
50
0.6517
0.9846
8%
16860
Metabolite - 4517
50
0.7046
0.9846
10%
16861
Metabolite - 4518
50
0.9422
0.9875
1%
16862
Metabolite - 4519
50
0.7079
0.9846
−11%
16863
Metabolite - 4520
50
0.9455
0.9875
−2%
16864
Metabolite - 4521
50
0.8773
0.9875
−5%
16865
Metabolite - 4522
50
0.6761
0.9846
7%
16866
Metabolite - 4523
50
0.7153
0.9846
6%
16867
Metabolite - 4524
50
0.2787
0.9846
−31%
16952
Metabolite - 4593
50
0.2049
0.9846
18%
16959
Metabolite - 4595
50
0.7468
0.9846
3%
17028
Metabolite - 4611
50
0.872
0.9875
3%
17050
Metabolite - 4618
50
0.2699
0.9846
72%
17064
Metabolite - 4624
50
0.3903
0.9846
13%
17072
Metabolite - 4628
50
0.2516
0.9846
81%
17074
Metabolite - 4629
50
0.6487
0.9846
9%
17080
Metabolite - 4632
50
0.8257
0.9846
7%
17083
Metabolite - 4634
50
0.7731
0.9846
6%
17084
Metabolite - 4635
50
0.3361
0.9846
134%
17085
Metabolite - 4636
50
0.5178
0.9846
18%
17086
Metabolite - 4637
50
0.834
0.9846
7%
17087
Metabolite - 4638
50
0.2699
0.9846
44%
17088
Metabolite - 4639
50
0.3228
0.9846
32%
[0000]
TABLE 10
Urine Metabolite Biomarkers to distinguish Non-cancer from Higher Grade PCA.
% Change
COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA
53
glutamine
50
0.2634
0.2182
39%
54
tryptophan
35
0.1769
0.1876
25%
57
glutamic acid
50
0.3771
0.2666
18%
59
histidine
50
0.1191
0.1705
61%
60
leucine
50
0.0862
0.1546
58%
64
phenylalanine
35
0.0753
0.1546
33%
418
guanine
50
0.0722
0.1546
56%
512
asparagine
50
0.1886
0.1931
45%
513
creatinine
35
0.1327
0.1736
21%
521
homogentisate
50
0.1389
0.1744
59%
527
lactate
50
0.4598
0.2867
−11%
528
alpha-keto-glutarate
35
0.7074
0.3708
12%
531
3-hydroxy-3-
50
0.378
0.2666
24%
methylglutarate
541
4-hydroxyphenylacetate
50
0.2908
0.2279
32%
542
3-hydroxybutanoic acid
50
0.1308
0.1723
−48%
554
adenine
50
0.0464
0.1546
55%
555
adenosine
35
0.0068
0.1546
84%
563
alpha-L-sorbopyranose
50
0.2249
0.2026
92%
569
caffeine
35
0.0527
0.1546
−43%
575
arabinose
50
0.0227
0.1546
88%
577
fructose
50
0.4822
0.2929
41%
581
glucose
50
0.4136
0.2782
−65%
587
gluconic acid
50
0.0697
0.1546
86%
594
niacinamide
35
0.6385
0.3496
−8%
597
phosphoenolpyruvate
35
0.6788
0.3622
20%
605
uracil
50
0.0194
0.1546
55%
607
urocanic acid
35
0.0836
0.1546
54%
608
vitamin-B6
35
0.0887
0.1575
79%
1101
3-methoxy-4-
50
0.0139
0.1546
57%
hydroxyphenylacetate
1107
allantoin
50
0.0457
0.1546
83%
1125
isoleucine
50
0.3971
0.272
16%
1126
alanine
50
0.2068
0.1964
36%
1284
threonine
50
0.0516
0.1546
45%
1299
tyrosine
50
0.0503
0.1546
45%
1302
methionine
35
0.0169
0.1546
45%
1303
malic acid
35
0.5118
0.3041
18%
1366
trans-4-hydroxyproline
50
0.229
0.2026
32%
1413
3-hydroxyphenylacetate
35
0.671
0.36
12%
1417
kynurenic acid
50
0.172
0.1874
66%
1418
5-6-Dihydrothymine
35
0.0782
0.1546
44%
1419
5-s-methyl-5-
35
0.9786
0.4388
0%
thioadenosine
1431
(p-Hydroxyphenyl)lactic
50
0.2483
0.2111
87%
acid
1432
alphahydroxybenzeneacetic
35
0.7995
0.3952
4%
acid
1437
succinate
50
0.0769
0.1546
62%
1444
DL-pipecolic acid
35
0.728
0.3756
13%
1480
guanidineacetic acid
35
0.0049
0.1546
184%
1493
ornithine
50
0.062
0.1546
52%
1494
5-oxoproline
50
0.1124
0.1698
42%
1498
N-6-trimethyl-l-lysine
35
0.0433
0.1546
62%
1505
orotic acid
50
0.0559
0.1546
74%
1508
pantothenic acid
35
0.3273
0.2426
56%
1519
sucrose
50
0.102
0.1641
95%
1557
3-methylglutaric acid
35
0.6501
0.3538
−9%
1558
4-acetamidobutyric acid
35
0.1142
0.1698
39%
1559
5-6-dihydrouracil
50
0.0325
0.1546
44%
1560
L-methyldopa
35
0.2445
0.2093
36%
1564
citric acid
50
0.0304
0.1546
62%
1566
3-amino-isobutyrate
50
0.1884
0.1931
64%
1567
4-hydroxy-3-
50
0.0913
0.1595
48%
methoxymandelate
1568
4-hydroxymandelate
50
0.1129
0.1698
62%
1569
DL-beta-
35
0.1404
0.1744
36%
hydroxyphenylethylamine
1574
histamine
35
0.0267
0.1546
57%
1580
noradrenaline
50
0.1426
0.1744
67%
1585
N-acetyl-L-alanine
35
0.8018
0.3953
5%
1587
N-acetyl-L-leucine
35
0.1032
0.1641
49%
1591
N-acetyl-L-valine
35
0.0682
0.1546
101%
1592
N-acetylneuraminic acid
50
0.035
0.1546
46%
1598
N-tigloylglycine
35
0.0515
0.1546
46%
1604
uric acid
35
0.243
0.2093
6%
1640
ascorbic acid
50
0.3011
0.2324
228%
1648
serine
50
0.016
0.1546
60%
1649
valine
50
0.0849
0.1546
31%
1708
7-8-dihydrofolic acid
35
0.0656
0.1546
36%
1778
gamma-glu-cys
35
0.4751
0.2914
45%
1827
riboflavine
35
0.1656
0.1865
264%
1860
3-nitro-L-tyrosine
35
0.4409
0.2848
25%
1868
cysteine
50
0.1193
0.1705
108%
1898
proline
50
0.3203
0.2413
39%
1899
quinolinic acid
50
0.0925
0.1595
44%
2078
pyrophosphate
50
0.0839
0.1546
107%
2092
catechol
35
0.0165
0.1546
151%
2132
citrulline
50
0.0064
0.1546
73%
2183
thymidine
35
0.8414
0.4032
−4%
2245
Metabolite - 294
35
0.1285
0.1705
89%
2342
serotonin
35
0.0389
0.1546
41%
2734
gamma-L-glutamyl-L-
35
0.3139
0.2394
26%
tyrosine
2829
N-formyl-L-methionine
35
0.1969
0.195
46%
2831
adenosine-3-5-cyclic-
35
0.0306
0.1546
32%
monophosphate
3127
hypoxanthine
35
0.1978
0.195
56%
3138
pyridoxamine-phosphate
35
0.752
0.3841
−5%
3147
xanthine
35
0.148
0.1787
77%
3155
3-ureidopropionic acid
35
0.069
0.1546
96%
4966
xylitol
50
0.7869
0.3926
−5%
5493
Metabolite - 1059
35
0.9512
0.4306
1%
5495
Metabolite - 1060
35
0.1027
0.1641
−19%
5514
Metabolite - 1081
35
0.008
0.1546
11%
5538
Metabolite - 1101
35
0.6862
0.363
26%
5664
Metabolite - 1101
35
0.7561
0.3849
6%
5687
Metabolite - 1110
35
0.4575
0.2863
16%
5697
acetylcarnitine-
35
0.9057
0.4171
4%
5702
Metabolite - 1114
35
0.477
0.2917
27%
5711
2-hydroxybutyric acid
35
0.9468
0.4297
2%
5719
Metabolite - 1122
35
0.1964
0.195
24%
5727
Metabolite - 1126
35
0.7746
0.3891
8%
5797
Metabolite - 1186
35
0.6024
0.3354
12%
6137
Metabolite - 1212
35
0.479
0.2919
−32%
6147
Metabolite - 1216
35
0.7457
0.3827
−5%
6238
normetanephrine
50
0.2267
0.2026
13%
6253
Metabolite - 1283
35
0.9728
0.4373
1%
6278
Metabolite - 1289
35
0.1762
0.1876
17%
6329
urea
50
0.1643
0.1865
27%
6362
Metabolite - 1323-
35
0.0787
0.1546
84%
possible-p-cresol-sulfate
6398
Metabolite - 1335
35
0.1991
0.195
25%
6405
Metabolite - 1338
35
0.3289
0.2426
−21%
6413
Metabolite - 1342-
35
0.0596
0.1546
40%
possible-
phenylacetylglutamine-
or-formyl-N-acetyl-5-
methoxykynurenamine
6421
Metabolite - 1345
35
0.1218
0.1705
105%
6437
Metabolite - 1349-
35
0.0435
0.1546
54%
possible-N-acetyl-8-O-
methyl-Neuraminic acid
6443
Metabolite - 1351
35
0.5184
0.3061
26%
6477
Metabolite - 1364
35
0.8749
0.413
−6%
6486
Metabolite - 1368
35
0.7964
0.3952
13%
6493
salicyluric acid
35
0.3168
0.2401
243%
6528
Metabolite - 1383-
35
0.1243
0.1705
97%
possible-salicyluric-
glucuronide
6760
Metabolite - 1455
35
0.1951
0.195
23%
6764
Metabolite - 1459
35
0.386
0.2688
54%
6777
Metabolite - 1463
35
0.3817
0.2674
79%
6787
Metabolite - 1465
35
0.3552
0.2553
16%
6847
Metabolite - 1496
35
0.4314
0.2831
43%
6852
Metabolite - 1498
35
0.2973
0.2314
67%
6987
Metabolite - 1573
35
0.0136
0.1546
38%
7132
Metabolite - 1667
35
0.9013
0.4171
−3%
7175
Metabolite - 1655
35
0.0662
0.1546
103%
7177
Metabolite - 1656
35
0.0932
0.1595
106%
7272
Metabolite - 1679
35
0.2252
0.2026
28%
7286
Metabolite - 1682
35
0.4881
0.2937
19%
7359
n-acetyl-L-aspartic acid
35
0.0973
0.1641
56%
7639
oxalic acid
35
0.1037
0.1641
28%
7650
Metabolite - 1834
35
0.3481
0.2512
−34%
7660
Metabolite - 1839
35
0.9015
0.4171
−4%
7672
Metabolite - 1843
35
0.2013
0.1955
21%
7933
Metabolite - 1911
35
0.0604
0.1546
100%
8176
Metabolite - 1974
35
0.0348
0.1546
71%
8196
Metabolite - 1979-Cl-
35
0.0609
0.1546
77%
adduct-of-isobar-19
8210
Metabolite - 1981
35
0.7647
0.3861
6%
8336
Metabolite - 2005
35
0.6452
0.3522
10%
8644
Metabolite - 2051
35
0.041
0.1546
27%
8677
Metabolite - 2056
35
0.5849
0.3294
9%
9007
Metabolite - 2108
35
0.4471
0.2848
−34%
9038
Metabolite - 2118
35
0.3323
0.2426
20%
9113
Metabolite - 2133
35
0.6941
0.3651
8%
9165
Metabolite - 2150
35
0.3174
0.2401
30%
9333
Metabolite - 2174
35
0.2248
0.2026
29%
9334
Metabolite - 2175
35
0.2046
0.1961
95%
9458
Metabolite - 2181
35
0.0134
0.1546
52%
10058
Metabolite - 2242
35
0.0104
0.1546
−55%
10087
Metabolite - 2249
35
0.4419
0.2848
39%
10122
Metabolite - 2254
35
0.4675
0.2896
−41%
10136
Metabolite - 2034
35
0.4115
0.2778
35%
10156
Metabolite - 2259
35
0.3889
0.2693
71%
10240
4-acetominophen-sulfate
35
0.1068
0.1675
54%
10245
Metabolite - 2269-
35
0.8384
0.4028
3%
10247
Metabolite - 2270
35
0.2488
0.2111
−42%
10252
Metabolite - 2271
35
0.0323
0.1546
79%
10286
Metabolite - 2272
35
0.7248
0.375
19%
10309
Metabolite - 2277
35
0.0567
0.1546
39%
10347
Metabolite - 2285
35
0.0852
0.1546
50%
10407
Metabolite - 2059
35
0.4659
0.2896
14%
10424
Metabolite - 2292
35
0.3819
0.2674
−17%
10433
Metabolite - 2293-
35
0.1642
0.1865
35%
possible-O-
desmethylvenlafaxine-
glucuronide
10490
Metabolite - 2319
35
0.8212
0.3991
4%
10526
Metabolite - 2323
35
0.713
0.372
11%
10544
Metabolite - 2329
35
0.4846
0.2934
12%
10555
Metabolite - 2348
35
0.8929
0.4163
5%
10570
Metabolite - 2366
35
0.2076
0.1964
−29%
10629
Metabolite - 2386
35
0.4286
0.2831
14%
10644
Metabolite - 2387
35
0.8787
0.4132
6%
10667
Metabolite - 2389
35
0.7983
0.3952
−5%
10672
Metabolite - 2390
35
0.0662
0.1546
70%
10737
Isobar-1-includes-
35
0.4454
0.2848
−28%
mannose-fructose-
glucose-galactose-alpha-
L-sorbopyranose-Inositol-
D-allose-D--altrose-D-
psicone
10741
Isobar-2-includes-2-
35
0.3313
0.2426
−65%
aminoisobutyric acid-3-
amino-isobutyrate-2-
amino-butyrate-4-
aminobutanoic acid-
dimethylglycine-choline-
10743
Isobar-4-includes-
35
0.0302
0.1546
48%
Gluconic acid-DL-
arabinose-D-ribose-L-
xylose-DL-lyxose-D-
xylulose
10746
Isobar-6-includes-valine-
35
0.3058
0.2341
19%
betaine
10785
Metabolite - 2506
35
0.6343
0.3485
11%
10825
Metabolite - 2546
35
0.119
0.1705
29%
10872
Metabolite - 2550
35
0.1693
0.1865
77%
10906
Metabolite - 2557-
35
0.1732
0.1874
51%
possible-Pantoprazole-
metabolite
11053
Metabolite - 2567
35
0.0188
0.1546
49%
11085
Metabolite - 2588
35
0.2532
0.2129
105%
11110
Metabolite - 2591
35
0.2696
0.2198
−24%
11173
Metabolite - 2607
35
0.2777
0.2216
59%
11219
Metabolite - 2686
35
0.4301
0.2831
18%
11264
Metabolite - 2698
35
0.5771
0.3274
−27%
11271
Metabolite - 2700
35
0.116
0.1705
91%
11292
Metabolite - 2703
35
0.2307
0.2026
17%
11299
Metabolite - 2706
35
0.8211
0.3991
−6%
11390
Metabolite - 2726
35
0.5251
0.308
13%
11411
Metabolite - 2746
35
0.1037
0.1641
−29%
11438
phosphate
50
0.0685
0.1546
42%
11484
Metabolite - 2752
35
0.0063
0.1546
60%
11661
Metabolite - 2781
35
0.1145
0.1698
25%
11777
glycine
50
0.0284
0.1546
58%
11808
Metabolite - 2807
35
0.1406
0.1744
64%
11851
Metabolite - 2811
35
0.026
0.1546
235%
12025
cis-aconitic acid
50
0.1274
0.1705
76%
12055
galactose
50
0.7432
0.3824
14%
12102
o-phosphoethanolamine
50
0.7644
0.3861
8%
12104
Metabolite - 2852
35
0.1765
0.1876
285%
12109
Metabolite - 2853
35
0.6347
0.3485
15%
12129
beta-hydroxyisovaleric
50
0.066
0.1546
49%
acid
12300
Metabolite - 2868
35
0.4388
0.2848
76%
12358
(1′R,1′S)_biopterin
35
0.1576
0.1865
30%
12426
Metabolite - 2416
35
0.1652
0.1865
72%
12463
Metabolite - 2893-
35
0.4067
0.2755
27%
possible-demethylated-
Rosiglitazone
12474
Metabolite - 2897
35
0.8628
0.4093
−4%
12593
Metabolite - 2973
50
0.1595
0.1865
−22%
12641
meso-erythritol
50
0.3364
0.2437
28%
12644
Metabolite - 3016
50
0.72
0.3736
−4%
12648
Metabolite - 3020
50
0.0217
0.1546
69%
12666
Metabolite - 3033
50
0.0719
0.1546
51%
12711
Metabolite - 3053
35
0.788
0.3926
14%
12720
Metabolite - 3056
35
0.0489
0.1546
41%
12765
inositol
50
0.4194
0.2789
−27%
12770
Metabolite - 3090
50
0.3345
0.2432
12%
12771
Metabolite - 3091
50
0.3988
0.2721
37%
12795
Metabolite - 3113
50
0.5631
0.3223
−15%
12856
Metabolite - 3123
35
0.7525
0.3841
8%
12902
Metabolite - 3127
35
0.6832
0.363
10%
12904
Metabolite - 2457
35
0.169
0.1865
83%
12924
Metabolite - 3131
35
0.4335
0.2834
22%
12938
Metabolite - 2459
35
0.6893
0.3637
10%
13018
Metabolite - 3138
35
0.669
0.36
12%
13136
Metabolite - 3163-
35
0.2764
0.2216
19%
possible-methylcytidine-
benserazide-Pyr-Gln-OH-
or-
glycerophosphocholine-
13153
Metabolite - 3169
35
0.2308
0.2026
162%
13179
Metabolite - 3176
35
0.8221
0.3991
14%
13214
Metabolite - 3183-
35
0.0768
0.1546
57%
possible-gamma-L-
glutamyl-L-phenylalanine
13217
Metabolite - 3184
35
0.0416
0.1546
51%
13249
Metabolite - 3215
35
0.0164
0.1546
45%
13251
Metabolite - 3216
35
0.2086
0.1964
9%
13265
Metabolite - 3221
35
0.2654
0.2182
31%
13297
Metabolite - 3231
35
0.8602
0.4091
4%
13318
DL-indole-3-lactic acid
35
0.7643
0.3861
−9%
13356
Metabolite - 3246-
35
0.0822
0.1546
62%
possible-Ala-GLy-glycyl-
sarcosine-or-ureido-
butyric acid
13459
Metabolite - 3305
35
0.0755
0.1546
71%
13484
Metabolite - 3309
35
0.3911
0.2698
17%
13493
Metabolite - 3311-
35
0.837
0.4028
−6%
13505
Metabolite - 3313
35
0.9682
0.4363
1%
13534
Metabolite - 3320-
35
0.4164
0.2789
51%
possible-pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
0.1275
0.1705
63%
13589
Metabolite - 3327
35
0.085
0.1546
74%
13594
Metabolite - 3329
35
0.0641
0.1546
145%
13704
Metabolite - 3355
35
0.1883
0.1931
33%
13744
Metabolite - 3364
35
0.8656
0.4096
−3%
13775
Metabolite - 3370
35
0.0505
0.1546
51%
13791
Metabolite - 3373
35
0.3231
0.2424
1137%
13803
Metabolite - 3377
35
0.882
0.4132
7%
13817
Metabolite - 3380
35
0.1975
0.195
36%
13820
beta-nicotinamide-
35
0.0287
0.1546
51%
mononucleotide
13847
Metabolite - 3387
35
0.2135
0.2001
28%
13904
Metabolite - 3402
35
0.6861
0.363
6%
13968
Metabolite - 3409
35
0.5164
0.3059
22%
14036
Metabolite - 3427
35
0.0743
0.1546
72%
14066
Metabolite - 3433
35
0.5622
0.3223
7%
14084
Metabolite - 3436
35
0.5088
0.3032
13%
14115
Metabolite - 3440
35
0.2994
0.232
−66%
14125
Metabolite - 3443
35
0.0258
0.1546
−49%
14170
Metabolite - 3457
35
0.9959
0.4445
0%
14220
Metabolite - 3470
35
0.0581
0.1546
91%
14249
Metabolite - 3476
35
0.0267
0.1546
66%
14368
Metabolite - 3489
35
0.1102
0.1698
−48%
14406
Metabolite - 3493
35
0.3257
0.2426
21%
14453
Metabolite - 3507
35
0.774
0.3891
8%
14471
Metabolite - 3516
35
0.7774
0.3894
6%
14506
Metabolite - 3543
35
0.4448
0.2848
73%
14539
Metabolite - 3564
35
0.5935
0.3317
29%
14595
Metabolite - 3576
35
0.1252
0.1705
78%
14640
Metabolite - 3604
35
0.4348
0.2834
20%
14641
Metabolite - 3605
35
0.1679
0.1865
78%
14731
Metabolite - 3659
35
0.182
0.1904
34%
14732
Metabolite - 3660
35
0.3269
0.2426
64%
14733
Metabolite - 3661
35
0.5283
0.308
17%
14759
Metabolite - 3667
35
0.2604
0.217
24%
14762
Metabolite - 3668
35
0.473
0.2914
−11%
14766
Metabolite - 3670
35
0.6732
0.3602
8%
14769
Metabolite - 3691
35
0.0229
0.1546
116%
14808
Metabolite - 3701
35
0.716
0.3725
11%
14835
Metabolite - 3706
35
0.2566
0.2148
21%
14840
Metabolite - 3708
35
0.2166
0.2008
166%
14907
Metabolite - 3734
35
0.0383
0.1546
73%
14983
Metabolite - 3754
35
0.9142
0.4199
−3%
14984
Metabolite - 3755
35
0.9378
0.4275
1%
15017
Metabolite - 3761
35
0.029
0.1546
40%
15057
Metabolite - 3771
35
0.4518
0.2856
38%
15064
Metabolite - 3773
35
0.8169
0.3991
5%
15096
N-acetyl-D-glucosamine
50
0.016
0.1546
100%
15121
Metabolite - 3786
35
0.5899
0.3306
17%
15124
porphobilinogen
35
0.2695
0.2198
25%
15125
(2-
35
0.0023
0.1546
42%
Aminoethyl)phosphonate
15128
DL-homocysteine
35
0.0263
0.1546
76%
15129
D-alanyl-D-alanine
35
0.1999
0.195
28%
15130
diaminopimelic acid
35
0.1669
0.1865
36%
15131
dethiobiotin
35
0.4736
0.2914
64%
15187
Metabolite - 3800
35
0.1387
0.1744
68%
15197
Metabolite - 3802
35
0.2646
0.2182
50%
15201
Metabolite - 3803
35
0.049
0.1546
69%
15202
Metabolite - 3804
35
0.3305
0.2426
26%
15203
Metabolite - 3805
35
0.18
0.1894
29%
15207
Metabolite - 3806
35
0.5382
0.3128
31%
15211
Metabolite - 3807
35
0.0225
0.1546
33%
15220
Metabolite - 3813
35
0.083
0.1546
48%
15228
Metabolite - 3817
35
0.14
0.1744
43%
15240
Metabolite - 3824
35
0.9991
0.4448
1%
15249
Metabolite - 3828
35
0.1281
0.1705
48%
15251
Metabolite - 3830
35
0.1474
0.1787
67%
15253
Metabolite - 3832-
35
0.2771
0.2216
−40%
possible-phenol-sulfate
15258
Metabolite - 3834-Peptide
35
0.2916
0.2279
50%
15275
Metabolite - 3840
35
0.419
0.2789
17%
15276
Metabolite - 3841
35
0.2765
0.2216
39%
15278
Metabolite - 3843
35
0.2183
0.2008
42%
15284
Metabolite - 3847
35
0.9603
0.4337
2%
15294
Metabolite - 3855
35
0.9398
0.4275
2%
15312
Metabolite - 3873
35
0.2025
0.1956
30%
15315
Metabolite - 3876
35
0.8981
0.4171
7%
15324
Metabolite - 3878
35
0.4489
0.2848
−19%
15326
Metabolite - 3879
35
0.5546
0.3194
36%
15328
azelaic acid
35
0.6594
0.3573
−15%
15335
mannitol
50
0.1881
0.1931
65%
15336
tartaric acid
35
0.5703
0.3245
24%
15356
Metabolite - 3886
35
0.2185
0.2008
26%
15359
Metabolite - 3887
35
0.9902
0.443
0%
15365
sn-Glycerol-3-phosphate
50
0.6605
0.3573
14%
15374
Metabolite - 3893
35
0.4206
0.2789
18%
15382
Metabolite - 3898
35
0.1721
0.1874
19%
15410
Metabolite - 3908
35
0.0752
0.1546
65%
15411
Metabolite - 3909
35
0.4575
0.2863
−35%
15418
Metabolite - 3911
35
0.2886
0.2274
16%
15496
agmatine
35
0.5278
0.308
25%
15500
carnitine
35
0.3618
0.2584
−24%
15529
Metabolite - 3951
35
0.0523
0.1546
34%
15532
Metabolite - 3952
35
0.5521
0.319
25%
15535
Metabolite - 3955
35
0.0719
0.1546
72%
15541
Metabolite - 3957
35
0.8591
0.4091
3%
15599
Metabolite - 3963
35
0.4048
0.2752
114%
15610
Metabolite - 3970
35
0.0812
0.1546
45%
15620
Metabolite - 3973
35
0.1635
0.1865
179%
15626
Metabolite - 3977
35
0.8247
0.3993
7%
15636
Metabolite - 3981
35
0.6037
0.3354
25%
15641
Metabolite - 3986
35
0.9057
0.4171
2%
15650
1-methyladenosine
35
0.0502
0.1546
51%
15667
2-isopropylmalic acid
50
0.5859
0.3294
−27%
15676
3-methyl-2-oxovaleric
35
0.8809
0.4132
5%
acid
15677
3-methyl-L-histidine
35
0.3622
0.2584
16%
15679
xanthurenic acid
50
0.2292
0.2026
43%
15681
4-Guanidinobutanoic acid
35
0.1143
0.1698
38%
15704
heptanedioic acid
35
0.0573
0.1546
38%
15716
L-beta-imidazolelactic
50
0.2314
0.2026
55%
acid
15730
suberic acid
35
0.9187
0.421
−3%
15737
hydroxyacetic acid
50
0.2051
0.1961
26%
15743
N-N-dimethylarginine
35
0.1269
0.1705
30%
15753
hippuric acid
35
0.2825
0.2245
26%
15778
benzoic acid
35
0.8138
0.3991
6%
15804
maltose
50
0.8907
0.4163
−6%
15835
L-xylose
50
0.3032
0.233
61%
15948
S-adenosyl-l-
35
0.3769
0.2666
24%
homocysteine
15964
D-arabitol
50
0.0555
0.1546
53%
16002
Metabolite - 3992-
35
0.6621
0.3573
6%
possible-Cl-adduct-of-
Formate-dimer
16016
Metabolite - 3994
35
0.1773
0.1876
44%
16034
Metabolite - 4002
50
0.0999
0.1641
53%
16071
Metabolite - 4020
50
0.0376
0.1546
55%
16082
Metabolite - 4027
50
0.1234
0.1705
39%
16107
lysine
50
0.2204
0.2015
72%
16175
Metabolite - 4092
35
0.8448
0.4038
6%
16197
Metabolite - 4112
35
0.1002
0.1641
50%
16217
Metabolite - 4116
35
0.6325
0.3485
22%
16230
Isobar-29-includes-R-S-
35
0.0858
0.1546
404%
hydroorotic acid-5-6-
dihydroorotic acid
16232
Isobar-17-includes-
35
0.502
0.3001
−19%
arginine-N-alpha-acetyl-
ornithine
16233
Isobar-13-includes-5-
35
0.4534
0.2856
49%
keto-D-gluconic acid-2-
keto-L-gulonic acid-D-
glucuronic acid-D-
galacturonic acid
16235
Isobar-19-includes-D-
35
0.0455
0.1546
103%
saccharic acid-1-5-
anhydro-D-glucitol-2-
deoxy-D-galactose-2-
deoxy-D-glucose-L-
fucose-L-rhamnose
16243
L-kynurenine
35
0.2729
0.2215
316%
16276
Isobar-38-includes-N-
35
0.8281
0.3999
−4%
acetyl-L-methionine-5-
hydroxy-1H-indole-3-
acetic acid
16278
Isobar-35-includes-D-
35
0.585
0.3294
16%
arabinose-5-phosphate-D-
ribulose-5-phosphate-
alpha-D-ribose-5-
phosphate
16290
Metabolite - 4133
50
0.5451
0.3159
26%
16337
Metabolite - 4167
35
0.6297
0.3485
11%
16338
Metabolite - 4168
35
0.2445
0.2093
239%
16457
Metabolite - 4233
35
0.0367
0.1546
160%
16462
Metabolite - 4234
35
0.3867
0.2688
105%
16496
Metabolite - 4251
50
0.0612
0.1546
68%
16506
Metabolite - 4271
50
0.2168
0.2008
42%
16816
Metabolite - 4494
50
0.3938
0.2707
−8%
16818
Metabolite - 4495
50
0.2517
0.2126
28%
16819
Metabolite - 4496
50
0.1967
0.195
17%
16821
Metabolite - 4498
50
0.1936
0.195
37%
16822
Metabolite - 4499
50
0.0625
0.1546
57%
16823
Metabolite - 4500
50
0.2443
0.2093
159%
16824
iminodiacetic acid
50
0.5004
0.3001
23%
16827
Metabolite - 4502
50
0.0748
0.1546
5%
16829
Metabolite - 4503
50
0.0266
0.1546
60%
16831
Metabolite - 4504
50
0.012
0.1546
56%
16834
Metabolite - 4505
50
0.1015
0.1641
93%
16837
Metabolite - 4507
50
0.4492
0.2848
27%
16848
Metabolite - 4511
50
0.1687
0.1865
62%
16851
Metabolite - 4512
50
0.7087
0.3708
20%
16859
Metabolite - 4516
50
0.1197
0.1705
111%
16860
Metabolite - 4517
50
0.8131
0.3991
7%
16861
Metabolite - 4518
50
0.5277
0.308
47%
16862
Metabolite - 4519
50
0.0624
0.1546
120%
16863
Metabolite - 4520
50
0.4865
0.2937
−24%
16864
Metabolite - 4521
50
0.5658
0.3229
−21%
16865
Metabolite - 4522
50
0.0149
0.1546
54%
16866
Metabolite - 4523
50
0.0831
0.1546
43%
16867
Metabolite - 4524
50
0.9395
0.4275
−3%
16952
Metabolite - 4593
50
0.0167
0.1546
56%
16959
Metabolite - 4595
50
0.1416
0.1744
30%
17028
Metabolite - 4611
50
0.1674
0.1865
35%
17050
Metabolite - 4618
50
0.1343
0.1744
47%
17064
Metabolite - 4624
50
0.1424
0.1744
29%
17072
Metabolite - 4628
50
0.1106
0.1698
133%
17074
Metabolite - 4629
50
0.1355
0.1744
44%
17080
Metabolite - 4632
50
0.2873
0.2274
75%
17083
Metabolite - 4634
50
0.2324
0.2026
39%
17084
Metabolite - 4635
50
0.1653
0.1865
120%
17085
Metabolite - 4636
50
0.0414
0.1546
77%
17086
Metabolite - 4637
50
0.1528
0.1833
114%
17087
Metabolite - 4638
50
0.1281
0.1705
97%
17088
Metabolite - 4639
50
0.0915
0.1595
109%
[0000]
TABLE 11
Urine Metabolite Biomarkers to distinguish
Lower Grade PCA from Higher Grade PCA.
% Change
in Higher
COMP_ID
COMPOUND
LIB_ID
p-value
q-value
PCA
53
glutamine
50
0.3616
0.4198
32%
54
tryptophan
35
0.0325
0.3021
47%
57
glutamic acid
50
0.3185
0.411
21%
59
histidine
50
0.2782
0.3951
37%
60
leucine
50
0.1497
0.3451
46%
64
phenylalanine
35
0.0392
0.3021
42%
418
guanine
50
0.0948
0.3377
54%
512
asparagine
50
0.1243
0.3401
60%
513
creatinine
35
0.0268
0.3021
34%
521
homogentisate
50
0.1224
0.3401
67%
527
lactate
50
0.9146
0.6009
−2%
528
alpha-keto-glutarate
35
0.5059
0.468
−17%
531
3-hydroxy-3-
50
0.3917
0.4342
24%
methylglutarate
541
4-hydroxyphenylacetate
50
0.8452
0.5813
6%
542
3-hydroxybutanoic acid
50
0.2058
0.3499
−59%
554
adenine
50
0.2549
0.3783
25%
555
adenosine
35
0.0081
0.3021
81%
563
alpha-L-sorbopyranose
50
0.1978
0.3499
94%
569
caffeine
35
0.029
0.3021
−53%
575
arabinose
50
0.0415
0.3021
72%
577
fructose
50
0.8863
0.591
7%
581
glucose
50
0.061
0.3283
52%
587
gluconic acid
50
0.1217
0.3401
64%
594
niacinamide
35
0.5535
0.4815
−9%
597
phosphoenolpyruvate
35
0.3699
0.4225
50%
605
uracil
50
0.1162
0.3401
35%
607
urocanic acid
35
0.7279
0.5417
11%
608
vitamin-B6
35
0.7072
0.5385
−15%
1101
3-methoxy-4-
50
0.0137
0.3021
55%
hydroxyphenylacetate
1107
allantoin
50
0.0607
0.3283
73%
1125
isoleucine
50
0.1449
0.3451
32%
1126
alanine
50
0.2233
0.3499
35%
1284
threonine
50
0.094
0.3377
38%
1299
tyrosine
50
0.0817
0.3308
39%
1302
methionine
35
0.0101
0.3021
54%
1303
malic acid
35
0.627
0.5038
11%
1366
trans-4-hydroxyproline
50
0.7014
0.5382
9%
1413
3-hydroxyphenylacetate
35
0.5846
0.4923
17%
1417
kynurenic acid
50
0.1657
0.3499
68%
1418
5-6-Dihydrothymine
35
0.075
0.3283
46%
1419
5-s-methyl-5-
35
0.3383
0.411
17%
thioadenosine
1431
(p-Hydroxyphenyl)lactic
50
0.4665
0.4614
42%
acid
1432
alphahydroxybenzeneacetic
35
0.7224
0.5417
6%
acid
1437
succinate
50
0.6047
0.497
13%
1444
DL-pipecolic acid
35
0.749
0.5497
18%
1480
guanidineacetic acid
35
0.0242
0.3021
99%
1493
ornithine
50
0.9781
0.6148
−1%
1494
5-oxoproline
50
0.3008
0.4095
24%
1498
N-6-trimethyl-l-lysine
35
0.1516
0.3464
37%
1505
orotic acid
50
0.2192
0.3499
38%
1508
pantothenic acid
35
0.3229
0.411
57%
1519
sucrose
50
0.9951
0.6181
0%
1557
3-methylglutaric acid
35
0.5659
0.4828
−11%
1558
4-acetamidobutyric acid
35
0.026
0.3021
60%
1559
5-6-dihydrouracil
50
0.1436
0.3451
26%
1560
L-methyldopa
35
0.597
0.497
14%
1564
citric acid
50
0.1013
0.3377
44%
1566
3-amino-isobutyrate
50
0.6838
0.5331
16%
1567
4-hydroxy-3-
50
0.0688
0.3283
53%
methoxymandelate
1568
4-hydroxymandelate
50
0.2224
0.3499
45%
1569
DL-beta-
35
0.4431
0.4524
17%
hydroxyphenylethylamine
1574
histamine
35
0.0188
0.3021
61%
1580
noradrenaline
50
0.2067
0.3499
50%
1585
N-acetyl-L-alanine
35
0.5273
0.4762
14%
1587
N-acetyl-L-leucine
35
0.1465
0.3451
41%
1591
N-acetyl-L-valine
35
0.2387
0.3625
50%
1592
N-acetylneuraminic acid
50
0.0338
0.3021
48%
1598
N-tigloylglycine
35
0.1685
0.3499
29%
1604
uric acid
35
0.3873
0.4336
5%
1640
ascorbic acid
50
0.6695
0.5267
54%
1648
serine
50
0.0526
0.3216
45%
1649
valine
50
0.1421
0.3451
26%
1708
7-8-dihydrofolic acid
35
0.1975
0.3499
23%
1778
gamma-glu-cys
35
0.4675
0.4614
47%
1827
riboflavine
35
0.2142
0.3499
183%
1860
3-nitro-L-tyrosine
35
0.974
0.6137
−1%
1868
cysteine
50
0.6881
0.534
23%
1898
proline
50
0.2767
0.395
46%
1899
quinolinic acid
50
0.1071
0.3377
40%
2078
pyrophosphate
50
0.3706
0.4225
44%
2092
catechol
35
0.018
0.3021
145%
2132
citrulline
50
0.0991
0.3377
35%
2183
thymidine
35
0.8751
0.5877
3%
2245
Metabolite - 294
35
0.3345
0.411
43%
2342
serotonin
35
0.0762
0.3283
34%
2734
gamma-L-glutamyl-L-
35
0.0437
0.3021
66%
tyrosine
2829
N-formyl-L-methionine
35
0.4526
0.4591
23%
2831
adenosine-3-5-cyclic-
35
0.008
0.3021
43%
monophosphate
3127
hypoxanthine
35
0.2239
0.3499
51%
3138
pyridoxamine-phosphate
35
0.8095
0.5733
5%
3147
xanthine
35
0.207
0.3499
60%
3155
3-ureidopropionic acid
35
0.1334
0.3451
67%
4966
xylitol
50
0.2152
0.3499
−31%
5493
Metabolite - 1059
35
0.8769
0.5877
−3%
5495
Metabolite - 1060
35
0.8529
0.5835
−2%
5514
Metabolite - 1081
35
0.026
0.3021
11%
5538
Metabolite - 1101
35
0.471
0.4614
59%
5664
Metabolite - 1101
35
0.6342
0.505
−15%
5687
Metabolite - 1110
35
0.306
0.411
23%
5697
acetylcarnitine-
35
0.8627
0.5857
−6%
5702
Metabolite - 1114
35
0.2517
0.3783
65%
5711
2-hydroxybutyric acid
35
0.7942
0.5658
−5%
5719
Metabolite - 1122
35
0.4991
0.4678
12%
5727
Metabolite - 1126
35
0.9422
0.6067
−2%
5797
Metabolite - 1186
35
0.2577
0.3783
30%
6137
Metabolite - 1212
35
0.1231
0.3401
36%
6147
Metabolite - 1216
35
0.5353
0.4784
−9%
6238
normetanephrine
50
0.2336
0.3587
17%
6253
Metabolite - 1283
35
0.4722
0.4614
35%
6278
Metabolite - 1289
35
0.4075
0.4428
13%
6329
urea
50
0.2047
0.3499
24%
6362
Metabolite - 1323-
35
0.1689
0.3499
56%
possible-p-cresol-sulfate
6398
Metabolite - 1335
35
0.4993
0.4678
12%
6405
Metabolite - 1338
35
0.4624
0.4614
−16%
6413
Metabolite - 1342-
35
0.1592
0.3499
28%
possible-
phenylacetylglutamine-or-
formyl-N-acetyl-5-
methoxykynurenamine
6421
Metabolite - 1345
35
0.2195
0.3499
71%
6437
Metabolite - 1349-
35
0.1055
0.3377
40%
possible-N-acetyl-8-O-
methyl-Neuraminic acid
6443
Metabolite - 1351
35
0.9453
0.6072
2%
6477
Metabolite - 1364
35
0.3548
0.419
−65%
6486
Metabolite - 1368
35
0.4304
0.4492
45%
6493
salicyluric acid
35
0.462
0.4614
−65%
6528
Metabolite - 1383-
35
0.4273
0.4492
−49%
possible-salicyluric-
glucuronide
6760
Metabolite - 1455
35
0.0092
0.3021
58%
6764
Metabolite - 1459
35
0.7767
0.5619
13%
6777
Metabolite - 1463
35
0.5723
0.485
−31%
6787
Metabolite - 1465
35
0.2726
0.3914
20%
6847
Metabolite - 1496
35
0.7359
0.5447
15%
6852
Metabolite - 1498
35
0.4113
0.4428
49%
6987
Metabolite - 1573
35
0.2236
0.3499
16%
7132
Metabolite - 1667
35
0.3277
0.411
−73%
7175
Metabolite - 1655
35
0.1087
0.3377
77%
7177
Metabolite - 1656
35
0.5561
0.4815
23%
7272
Metabolite - 1679
35
0.1129
0.3377
42%
7286
Metabolite - 1682
35
0.8923
0.5935
4%
7359
n-acetyl-L-aspartic acid
35
0.0709
0.3283
67%
7639
oxalic acid
35
0.1367
0.3451
25%
7650
Metabolite - 1834
35
0.4803
0.464
−21%
7660
Metabolite - 1839
35
0.9276
0.6009
−3%
7672
Metabolite - 1843
35
0.1049
0.3377
30%
7933
Metabolite - 1911
35
0.2835
0.4005
42%
8176
Metabolite - 1974
35
0.1493
0.3451
43%
8196
Metabolite - 1979-Cl-
35
0.7488
0.5497
−10%
adduct-of-isobar-19
8210
Metabolite - 1981
35
0.9643
0.6134
1%
8336
Metabolite - 2005
35
0.6224
0.5032
−11%
8644
Metabolite - 2051
35
0.5497
0.4815
8%
8677
Metabolite - 2056
35
0.1235
0.3401
24%
9007
Metabolite - 2108
35
0.6911
0.534
17%
9038
Metabolite - 2118
35
0.2102
0.3499
29%
9113
Metabolite - 2133
35
0.2101
0.3499
32%
9165
Metabolite - 2150
35
0.3592
0.4194
29%
9333
Metabolite - 2174
35
0.514
0.4716
15%
9334
Metabolite - 2175
35
0.3253
0.411
73%
9458
Metabolite - 2181
35
0.0095
0.3021
56%
10058
Metabolite - 2242
35
0.3061
0.411
−91%
10087
Metabolite - 2249
35
0.2194
0.3499
79%
10122
Metabolite - 2254
35
0.9247
0.6009
−2%
10136
Metabolite - 2034
35
0.3572
0.419
42%
10156
Metabolite - 2259
35
0.331
0.411
85%
10240
4-acetominophen-sulfate
35
0.6091
0.497
15%
10245
Metabolite - 2269-
35
0.715
0.5393
5%
10247
Metabolite - 2270
35
0.135
0.3451
−49%
10252
Metabolite - 2271
35
0.2042
0.3499
38%
10286
Metabolite - 2272
35
0.1989
0.3499
80%
10309
Metabolite - 2277
35
0.0163
0.3021
59%
10347
Metabolite - 2285
35
0.1474
0.3451
44%
10407
Metabolite - 2059
35
0.3262
0.411
22%
10424
Metabolite - 2292
35
0.0485
0.3188
−36%
10433
Metabolite - 2293-
35
0.3264
0.411
−91%
possible-O-
desmethylvenlafaxine-
glucuronide
10490
Metabolite - 2319
35
0.6803
0.5319
8%
10526
Metabolite - 2323
35
0.8122
0.5733
7%
10544
Metabolite - 2329
35
0.5016
0.4678
11%
10555
Metabolite - 2348
35
0.3735
0.4225
−36%
10570
Metabolite - 2366
35
0.5627
0.4824
13%
10629
Metabolite - 2386
35
0.2987
0.4088
19%
10644
Metabolite - 2387
35
0.374
0.4225
39%
10667
Metabolite - 2389
35
0.207
0.3499
−22%
10672
Metabolite - 2390
35
0.0744
0.3283
69%
10737
Isobar-1-includes-
35
0.9075
0.6009
−4%
mannose-fructose-
glucose-galactose-alpha-
L-sorbopyranose-Inositol-
D-allose-D--altrose-D-
psicone
10741
Isobar-2-includes-2-
35
0.7125
0.5393
−9%
aminoisobutyric acid-3-
amino-isobutyrate-2-
amino-butyrate-4-
aminobutanoic acid-
dimethylglycine-choline-
10743
Isobar-4-includes-
35
0.0298
0.3021
48%
Gluconic acid-DL-
arabinose-D-ribose-L-
xylose-DL-lyxose-D-
xylulose
10746
Isobar-6-includes-valine-
35
0.5275
0.4762
14%
betaine
10785
Metabolite - 2506
35
0.886
0.591
3%
10825
Metabolite - 2546
35
0.3726
0.4225
15%
10872
Metabolite - 2550
35
0.1131
0.3377
100%
10906
Metabolite - 2557-
35
0.7733
0.5619
−8%
possible-Pantoprazole-
metabolite
11053
Metabolite - 2567
35
0.0376
0.3021
42%
11085
Metabolite - 2588
35
0.3891
0.4336
64%
11110
Metabolite - 2591
35
0.0842
0.3353
−35%
11173
Metabolite - 2607
35
0.7772
0.5619
12%
11219
Metabolite - 2686
35
0.818
0.5733
5%
11264
Metabolite - 2698
35
0.2618
0.38
−43%
11271
Metabolite - 2700
35
0.4829
0.4648
29%
11292
Metabolite - 2703
35
0.0818
0.3308
25%
11299
Metabolite - 2706
35
0.4803
0.464
21%
11390
Metabolite - 2726
35
0.1731
0.3499
31%
11411
Metabolite - 2746
35
0.6339
0.505
−9%
11438
phosphate
50
0.2251
0.3499
27%
11484
Metabolite - 2752
35
0.077
0.3283
35%
11661
Metabolite - 2781
35
0.0671
0.3283
30%
11777
glycine
50
0.0787
0.3283
44%
11808
Metabolite - 2807
35
0.9564
0.6099
2%
11851
Metabolite - 2811
35
0.497
0.4678
28%
12025
cis-aconitic acid
50
0.8152
0.5733
12%
12055
galactose
50
0.9486
0.6079
3%
12102
o-phosphoethanolamine
50
0.4724
0.4614
25%
12104
Metabolite - 2852
35
0.2242
0.3499
199%
12109
Metabolite - 2853
35
0.6302
0.5048
14%
12129
beta-hydroxyisovaleric
50
0.0907
0.3377
43%
acid
12300
Metabolite - 2868
35
0.3468
0.4142
109%
12358
(1′R,1′S)_biopterin
35
0.8705
0.5877
3%
12426
Metabolite - 2416
35
0.329
0.411
44%
12463
Metabolite - 2893-
35
0.8121
0.5733
7%
possible-demethylated-
Rosiglitazone
12474
Metabolite - 2897
35
0.5015
0.4678
16%
12593
Metabolite - 2973
50
0.8428
0.5812
3%
12641
meso-erythritol
50
0.2553
0.3783
30%
12644
Metabolite - 3016
50
0.7026
0.5382
5%
12648
Metabolite - 3020
50
0.0318
0.3021
62%
12666
Metabolite - 3033
50
0.0908
0.3377
47%
12711
Metabolite - 3053
35
0.8572
0.5835
−8%
12720
Metabolite - 3056
35
0.1203
0.3401
30%
12765
inositol
50
0.986
0.6153
−1%
12770
Metabolite - 3090
50
0.0682
0.3283
25%
12771
Metabolite - 3091
50
0.1481
0.3451
83%
12795
Metabolite - 3113
50
0.9736
0.6137
−1%
12856
Metabolite - 3123
35
0.7353
0.5447
−8%
12902
Metabolite - 3127
35
0.5559
0.4815
14%
12904
Metabolite - 2457
35
0.7826
0.5634
10%
12924
Metabolite - 3131
35
0.3436
0.4141
31%
12938
Metabolite - 2459
35
0.662
0.5223
11%
13018
Metabolite - 3138
35
0.6504
0.5163
12%
13136
Metabolite - 3163-
35
0.3216
0.411
17%
possible-methylcytidine-
benserazide-Pyr-Gln-OH-
or-
glycerophosphocholine-
13153
Metabolite - 3169
35
0.264
0.3811
132%
13179
Metabolite - 3176
35
0.4698
0.4614
30%
13214
Metabolite - 3183-
35
0.1413
0.3451
45%
possible-gamma-L-
glutamyl-L-phenylalanine
13217
Metabolite - 3184
35
0.1112
0.3377
37%
13249
Metabolite - 3215
35
0.0274
0.3021
40%
13251
Metabolite - 3216
35
0.0408
0.3021
17%
13265
Metabolite - 3221
35
0.2155
0.3499
34%
13297
Metabolite - 3231
35
0.7164
0.5393
6%
13318
DL-indole-3-lactic acid
35
0.7541
0.5513
12%
13356
Metabolite - 3246-
35
0.0524
0.3216
76%
possible-Ala-GLy-glycyl-
sarcosine-or-ureido-
butyric acid
13459
Metabolite - 3305
35
0.1936
0.3499
47%
13484
Metabolite - 3309
35
0.491
0.4678
13%
13493
Metabolite - 3311-
35
0.1657
0.3499
−40%
13505
Metabolite - 3313
35
0.6134
0.4974
17%
13534
Metabolite - 3320-
35
0.559
0.4815
34%
possible-pimpinellin-or-
tetrahydroxybenzophenone
13545
Metabolite - 3322
35
0.0622
0.3283
90%
13589
Metabolite - 3327
35
0.2577
0.3783
37%
13594
Metabolite - 3329
35
0.0616
0.3283
149%
13704
Metabolite - 3355
35
0.6078
0.497
11%
13744
Metabolite - 3364
35
0.2939
0.4065
−19%
13775
Metabolite - 3370
35
0.1617
0.3499
35%
13791
Metabolite - 3373
35
0.3232
0.411
1137%
13803
Metabolite - 3377
35
0.4791
0.464
37%
13817
Metabolite - 3380
35
0.094
0.3377
53%
13820
beta-nicotinamide-
35
0.0454
0.3059
45%
mononucleotide
13847
Metabolite - 3387
35
0.3384
0.411
23%
13904
Metabolite - 3402
35
0.3627
0.4198
−38%
13968
Metabolite - 3409
35
0.9107
0.6009
4%
14036
Metabolite - 3427
35
0.1123
0.3377
58%
14066
Metabolite - 3433
35
0.4093
0.4428
12%
14084
Metabolite - 3436
35
0.8736
0.5877
2%
14115
Metabolite - 3440
35
0.8294
0.575
−5%
14125
Metabolite - 3443
35
0.0154
0.3021
−54%
14170
Metabolite - 3457
35
0.6072
0.497
−11%
14220
Metabolite - 3470
35
0.0626
0.3283
84%
14249
Metabolite - 3476
35
0.7481
0.5497
−9%
14368
Metabolite - 3489
35
0.1826
0.3499
−28%
14406
Metabolite - 3493
35
0.4363
0.4492
17%
14453
Metabolite - 3507
35
0.8289
0.575
−5%
14471
Metabolite - 3516
35
0.3193
0.411
−21%
14506
Metabolite - 3543
35
0.3275
0.411
111%
14539
Metabolite - 3564
35
0.2138
0.3499
107%
14595
Metabolite - 3576
35
0.1745
0.3499
63%
14640
Metabolite - 3604
35
0.9887
0.6156
0%
14641
Metabolite - 3605
35
0.5637
0.4824
24%
14731
Metabolite - 3659
35
0.5691
0.4839
14%
14732
Metabolite - 3660
35
0.627
0.5038
25%
14733
Metabolite - 3661
35
0.4336
0.4492
28%
14759
Metabolite - 3667
35
0.828
0.575
4%
14762
Metabolite - 3668
35
0.7262
0.5417
−6%
14766
Metabolite - 3670
35
0.8506
0.5835
−4%
14769
Metabolite - 3691
35
0.0162
0.3021
135%
14808
Metabolite - 3 701
35
0.1711
0.3499
61%
14835
Metabolite - 3706
35
0.353
0.419
19%
14840
Metabolite - 3708
35
0.202
0.3499
184%
14907
Metabolite - 3734
35
0.1065
0.3377
49%
14983
Metabolite - 3754
35
0.9841
0.6153
−1%
14984
Metabolite - 3755
35
0.3568
0.419
−60%
15017
Metabolite - 3761
35
0.3351
0.411
15%
15057
Metabolite - 3771
35
0.7946
0.5658
−9%
15064
Metabolite - 3773
35
0.4963
0.4678
17%
15096
N-acetyl-D-glucosamine
50
0.0305
0.3021
81%
15121
Metabolite - 3786
35
0.9216
0.6009
−3%
15124
porphobilinogen
35
0.3291
0.411
22%
15125
(2-
35
0.0419
0.3021
25%
Aminoethyl)phosphonate
15128
DL-homocysteine
35
0.4331
0.4492
20%
15129
D-alanyl-D-alanine
35
0.2018
0.3499
27%
15130
diaminopimelic acid
35
0.0787
0.3283
49%
15131
dethiobiotin
35
0.4377
0.4492
74%
15187
Metabolite - 3800
35
0.1005
0.3377
82%
15197
Metabolite - 3802
35
0.3395
0.411
40%
15201
Metabolite - 3803
35
0.1397
0.3451
45%
15202
Metabolite - 3804
35
0.0505
0.3216
62%
15203
Metabolite - 3805
35
0.1828
0.3499
32%
15207
Metabolite - 3806
35
0.1977
0.3499
95%
15211
Metabolite - 3807
35
0.0352
0.3021
30%
15220
Metabolite - 3813
35
0.3153
0.411
26%
15228
Metabolite - 3817
35
0.0645
0.3283
62%
15240
Metabolite - 3824
35
0.837
0.5787
8%
15249
Metabolite - 3828
35
0.176
0.3499
43%
15251
Metabolite - 3830
35
0.5535
0.4815
20%
15253
Metabolite - 3832-
35
0.9729
0.6137
1%
possible-phenol-sulfate
15258
Metabolite - 3834-Peptide
35
0.5236
0.476
27%
15275
Metabolite - 3840
35
0.5876
0.4932
12%
15276
Metabolite - 3841
35
0.7884
0.5652
−12%
15278
Metabolite - 3843
35
0.1684
0.3499
48%
15284
Metabolite - 3847
35
0.9363
0.6044
2%
15294
Metabolite - 3855
35
0.9278
0.6009
−2%
15312
Metabolite - 3873
35
0.1113
0.3377
41%
15315
Metabolite - 3876
35
0.6801
0.5319
−17%
15324
Metabolite - 3878
35
0.9543
0.6099
−1%
15326
Metabolite - 3879
35
0.5214
0.4756
40%
15328
azelaic acid
35
0.5573
0.4815
27%
15335
mannitol
50
0.7785
0.5619
10%
15336
tartaric acid
35
0.1794
0.3499
69%
15356
Metabolite - 3886
35
0.3988
0.4403
17%
15359
Metabolite - 3887
35
0.8182
0.5733
6%
15365
sn-Glycerol-3-phosphate
50
0.5348
0.4784
23%
15374
Metabolite - 3893
35
0.4706
0.4614
15%
15382
Metabolite - 3898
35
0.287
0.4018
14%
15410
Metabolite - 3908
35
0.1311
0.3451
50%
15411
Metabolite - 3909
35
0.559
0.4815
−17%
15418
Metabolite - 3911
35
0.6533
0.517
7%
15496
agmatine
35
0.8254
0.575
−7%
15500
carnitine
35
0.191
0.3499
−31%
15529
Metabolite - 3951
35
0.0572
0.3283
34%
15532
Metabolite - 3952
35
0.3275
0.411
49%
15535
Metabolite - 3955
35
0.0891
0.3377
71%
15541
Metabolite - 3957
35
0.7242
0.5417
5%
15599
Metabolite - 3963
35
0.5152
0.4716
72%
15610
Metabolite - 3970
35
0.3254
0.411
24%
15620
Metabolite - 3973
35
0.2969
0.4084
94%
15626
Metabolite - 3977
35
0.2082
0.3499
65%
15636
Metabolite - 3981
35
0.3746
0.4225
49%
15641
Metabolite - 3986
35
0.6892
0.534
9%
15650
1-methyladenosine
35
0.0431
0.3021
54%
15667
2-isopropylmalic acid
50
0.9286
0.6009
−3%
15676
3-methyl-2-oxovaleric
35
0.7554
0.5513
−9%
acid
15677
3-methyl-L-histidine
35
0.0247
0.3021
50%
15679
xanthurenic acid
50
0.428
0.4492
25%
15681
4-Guanidinobutanoic acid
35
0.1785
0.3499
33%
15704
heptanedioic acid
35
0.0437
0.3021
42%
15716
L-beta-imidazolelactic
50
0.4297
0.4492
31%
acid
15730
suberic acid
35
0.5965
0.497
13%
15737
hydroxyacetic acid
50
0.1005
0.3377
38%
15743
N-N-dimethylarginine
35
0.1977
0.3499
25%
15753
hippuric acid
35
0.6063
0.497
11%
15778
benzoic acid
35
0.2541
0.3783
−35%
15804
maltose
50
0.4101
0.4428
−43%
15835
L-xylose
50
0.4221
0.4492
47%
15948
S-adenosyl-l-
35
0.1118
0.3377
40%
homocysteine
15964
D-arabitol
50
0.0578
0.3283
52%
16002
Metabolite - 3992-
35
0.5021
0.4678
−9%
possible-Cl-adduct-of-
Formate-dimer
16016
Metabolite - 3994
35
0.0348
0.3021
90%
16034
Metabolite - 4002
50
0.5041
0.468
17%
16071
Metabolite - 4020
50
0.0755
0.3283
44%
16082
Metabolite - 4027
50
0.1596
0.3499
33%
16107
lysine
50
0.6063
0.497
−30%
16175
Metabolite - 4092
35
0.4353
0.4492
22%
16197
Metabolite - 4112
35
0.122
0.3401
43%
16217
Metabolite - 4116
35
0.5789
0.4891
30%
16230
Isobar-29-includes-R-S-
35
0.2117
0.3499
135%
hydroorotic acid-5-6-
dihydroorotic acid
16232
Isobar-17-includes-
35
0.4014
0.4413
−23%
arginine-N-alpha-acetyl-
ornithine
16233
Isobar-13-includes-5-keto-
35
0.3895
0.4336
63%
D-gluconic acid-2-keto-L-
gulonic acid-D-glucuronic
acid-D-galacturonic acid
16235
Isobar-19-includes-D-
35
0.5538
0.4815
22%
saccharic acid-1-5-
anhydro-D-glucitol-2-
deoxy-D-galactose-2-
deoxy-D-glucose-L-
fucose-L-rhamnose
16243
L-kynurenine
35
0.2602
0.3798
353%
16276
Isobar-38-includes-N-
35
0.3469
0.4142
−19%
acetyl-L-methionine-5-
hydroxy-1H-indole-3-
acetic acid
16278
Isobar-35-includes-D-
35
0.874
0.5877
−3%
arabinose-5-phosphate-D-
ribulose-5-phosphate-
alpha-D-ribose-5-
phosphate
16290
Metabolite - 4133
50
0.8566
0.5835
−7%
16337
Metabolite - 4167
35
0.9854
0.6153
−1%
16338
Metabolite - 4168
35
0.2875
0.4018
183%
16457
Metabolite - 4233
35
0.0702
0.3283
115%
16462
Metabolite - 4234
35
0.7005
0.5382
30%
16496
Metabolite - 4251
50
0.0239
0.3021
99%
16506
Metabolite - 4271
50
0.7894
0.5652
9%
16816
Metabolite - 4494
50
0.4086
0.4428
−7%
16818
Metabolite - 4495
50
0.7053
0.5385
8%
16819
Metabolite - 4496
50
0.4299
0.4492
10%
16821
Metabolite - 4498
50
0.9186
0.6009
3%
16822
Metabolite - 4499
50
0.132
0.3451
42%
16823
Metabolite - 4500
50
0.5079
0.4682
59%
16824
iminodiacetic acid
50
0.1695
0.3499
60%
16827
Metabolite - 4502
50
0.0356
0.3021
6%
16829
Metabolite - 4503
50
0.1744
0.3499
30%
16831
Metabolite - 4504
50
0.0255
0.3021
47%
16834
Metabolite - 4505
50
0.1844
0.3499
68%
16837
Metabolite - 4507
50
0.9737
0.6137
1%
16848
Metabolite - 4511
50
0.5473
0.4815
22%
16851
Metabolite - 4512
50
0.5346
0.4784
−25%
16859
Metabolite - 4516
50
0.1479
0.3451
95%
16860
Metabolite - 4517
50
0.9134
0.6009
−3%
16861
Metabolite - 4518
50
0.5481
0.4815
45%
16862
Metabolite - 4519
50
0.0417
0.3021
147%
16863
Metabolite - 4520
50
0.49
0.4678
−23%
16864
Metabolite - 4521
50
0.5999
0.497
−17%
16865
Metabolite - 4522
50
0.0317
0.3021
45%
16866
Metabolite - 4523
50
0.1397
0.3451
35%
16867
Metabolite - 4524
50
0.4657
0.4614
41%
16952
Metabolite - 4593
50
0.1068
0.3377
32%
16959
Metabolite - 4595
50
0.206
0.3499
26%
17028
Metabolite - 4611
50
0.191
0.3499
30%
17050
Metabolite - 4618
50
0.7146
0.5393
−14%
17064
Metabolite - 4624
50
0.4442
0.4524
15%
17072
Metabolite - 4628
50
0.6112
0.4971
29%
17074
Metabolite - 4629
50
0.2339
0.3587
32%
17080
Metabolite - 4632
50
0.3386
0.411
64%
17083
Metabolite - 4634
50
0.2892
0.402
32%
17084
Metabolite - 4635
50
0.9283
0.6009
−6%
17085
Metabolite - 4636
50
0.1467
0.3451
50%
17086
Metabolite - 4637
50
0.1763
0.3499
99%
17087
Metabolite - 4638
50
0.4336
0.4492
37%
17088
Metabolite - 4639
50
0.2348
0.3587
58%
Example 5
Random Forest Analysis for the Classification of Tissue Samples
[0136] The data obtained in Example 1 concerning the tissue samples was used to create a random forest model. Random Forest Analysis was carried out on the data obtained from tissue samples in Example 1 to classify them as Normal (N), Localized (i.e. lower grade) cancer tumor (T) or Metastatic tumor (M). The first analysis resulted in 90.5% correct classification of the three tissue types. The metastatic tumors were correctly classified 100% of the time while the normal tissue and the localized prostate cancer tumors were correctly classified 87% and 83%, respectively (Table 12).
[0000]
TABLE 12
Confusion matrix for metastatic (M), normal prostate (N)
and localized prostate cancer tumor (T) tissue types.
Predicted Tissue Type
Metastatic
Normal
Localized
Tumor
Tissue
Tumor
error
Actual
Metastatic Tumor (M)
14
0
0
0.00
Tissue
Normal Tissue (N)
0
14
2
0.13
Type
Localized Tumor (T)
0
2
10
0.17
OOB Error = 9.5%
[0137] Based on the OOB Error rate of 9.5%, the Random Forest model that was created could be used to predict whether a subject has a metastatic tumor (M), a localized tumor (T), or normal tissue (N) with about 90.5% accuracy from analysis of the levels of the biomarkers in samples from the subject.
[0138] The importance plot is shown in FIG. 1 . The important metabolites for this classification are listed in Table 13.
[0000]
TABLE 13
Most important biomarker metabolites to distinguish N, T, M tissue
types.
Metabolite
Library
n-hexadecanoic acid (palmitate)
50
tetradecanoic acid (myristate)
50
inosine
61
octadecanoic acid
50
(stearate(3-amino-isobutyrate
50
n-dodecanoate (laurate)
50
(2-aminoethyl)phosphonate
61
Metabolite - 3778
61
glycerol
50
(p-hydroxyphenyl)lactic acid
50
palmitoleic acid
50
N-acetyl-D-galactosamine
50
Metabolite - 3102
50
meso-erythritol
50
Metabolite - 1597
61
uracil
50
uridine
61
Metabolite - 4075
50
Isobar-24 includes L-arabitol & adonitol
61
Metabolite - 2867
61
Metabolite - 4620
61
sn-glycerol-3-phosphate
50
Metabolite - 4117 (possible-propranolol or 2-
61
heptyl-3-hydroxy-quinolone
Metabolite - 1114
61
DL-homocysteine
61
leucine
50
xanthine
61
Metabolite - 1576
61
Metabolite - 2973
50
Metabolite - 3810
61
[0139] Based on this analysis one sample appeared to be an outlier. Sample T3, which was reported as localized prostate tumor tissue, appears to be an outlier. From the random forest comparing all three tissue types, 80% of the trees in the random forest classified T3 as an “N” or normal while only 17% correctly classed it as “T” and only 3% classified it as “M” or metastatic. This result indicates that the sample may be a mixture of normal and cancerous tissue or that the sample is at an early stage of cancer.
[0140] Random Forest Analysis was also carried out on the tissue samples from the prostate to classify them as Normal prostate (N) or Localized prostate cancer tumor (T). This analysis resulted in 86% correct classification of the two tissue types. The normal tissue and the localized prostate cancer tumors were correctly classified 87% and 83% respectively (Table 14).
[0000]
TABLE 14
Confusion matrix comparing Normal prostate tissue (N) with
Localized prostate tumor tissue (T).
Predicted
Tissue Type
Normal
Localized
Tissue
Tumor
error
Actual
Normal Tissue (N)
14
2
0.13
Tissue
Localized Tumor
2
10
0.17
Type
(T)
OOB Error = 14%
[0141] Based on the OOB Error rate of 14%, the Random Forest model that was created could be used to predict whether a subject has normal tissue (N), or localized tumor (T) tissue with about 86% accuracy from analysis of the levels of biomarkers in samples from the subject.
[0142] The important metabolites for this classification are listed in Table 15 and shown in the importance plot in FIG. 2 .
[0000]
TABLE 15
Most important biomarker metabolites to distinguish Normal prostate
tissue (N) and Cancerous prostate tumor tissue (T).
Metabolite
Library
N-acetyl-D-galactosamine
50
Metabolite - 3778
61
uridine
61
Metabolite - 4117 possible propanolol or 2-
61
heptyl-3-hydroxy-quinolone
Metabolite - 1114
61
Metabolite - 3810
61
DL-homocysteine
61
Metabolite - 3094
50
Metabolite - 4616
61
Metabolite - 1576
61
Metabolite - 3139
61
sn-glycerol-3-phospate
50
Metabolite - 2973
50
carnitine
61
Metabolite - 2041
61
Isobar 3 includes inositol-1-phosphate,
61
mannose-6-phospate, glucose-6-phosphate, D-
mannose-1-phoaphate, alpha-D-glucose-1-
phosphate
kynurenic acid
61
n-hexadecanoic acid (palmitate)
50
cysteine
50
Metabolite - 4027
50
Metabolite - 3027
50
glutamic acid
50
Metabolite - 2688
61
Metabolite - 1111 possible
61
methylnitronitrosoguanidine or ethyl-
thiocarbamoylacetate
Metabolite - 2055
61
Metabolite - 3176 possible creatine
61
uracil
50
glycine
50
Metabolite - 3165
61
Metabolite - 1595 possible glutathione-
61
metabolite
[0143] Since the metastatic tumors were obtained from sites distal to the prostate, we determined if these tissues were distinguished from the normal and cancerous prostate tissue due to the metastasis or due to the location of the tumor. To test this, the metastatic tumor tissue samples from liver were compared with the non-liver metastatic tumor tissues using Random Forest. The confusion matrix resulting from this analysis is provided in Table 16 and the results are essentially random chance; the liver and non-liver origins of the tumors appear to be indistinguishable. Thus, the classification of the metastatic tumor tissue is based on the metabolite biomarkers for metastasis and not on the source tissue of the metastatic tumor.
[0000]
TABLE 16
Confusion matrix comparing metastatic tumors from liver tissue with
metastatic tumors from non-liver tissue.
Predicted
Tissue Source
Liver
Non-liver
error
Actual
Liver
5
3
0.38
Tissue
Non-
5
5
0.50
Source
liver
OOB Error = 43%
[0144] Based on the OOB Error rate of 43%, the Random Forest model that was created could be used to predict whether a subject has a metastatic tumor from liver tissue, compared to non-liver tissue, with about 57% accuracy from analysis of the levels of biomarkers in liver tissue samples from the subject, but the Error Rate may essentially be random chance and may indicate that the source (i.e. liver or non-liver) of the tumor tissue is not predicted by these biomarkers.
Example 6
Random Forest Analysis for the Classification of Urine Samples from Control Subjects, Subjects with Low Grade PCA and Subjects with High Grade PCA
[0145] Random Forest Analysis was carried out on the data obtained from urine samples in Example 4 to classify them as Non-cancer (Control) or Prostate cancer. The control samples were urine obtained from subjects with a Gleason score (major) of 0 or from prostate cancer (PCA) subjects with a Gleason score (major)>=4. The analysis resulted in 63% correct classification of the urine sample types. The control subjects were correctly classified 62% of the time while the subjects with prostate cancer (PCA) were correctly classified 64% of the time (Table 17).
[0000]
TABLE 17
Confusion matrix for control vs PCA in Urine.
Predicted
Control
PCA
error
Actual
Control
33
20
0.38
PCA
5
9
0.36
OOB Error = 37%
[0146] Based on the OOB Error rate of 37%, the Random Forest model that was created could be used to predict whether a subject has prostate cancer (PCA), compared to being cancer-free, with about 63% accuracy from analysis of the levels of biomarkers in urine from the subject.
[0147] The importance plot is shown in FIG. 3 . The important metabolites for this classification are listed in Table 18.
[0000]
TABLE 18
Most important urine biomarker metabolites to distinguish Control
from PCA.
Metabolite
Library
(2-aminoethyl)phosphonate
35
Metabolite - 2051
35
Metabolite - 3805
35
Guanidineacetic acid
35
catechol
35
N-acetyl-L-valine
35
DL-beta-hydroxyphenylethylamine
35
N-acetyl-D-glucosamine
50
Metabolite - 1974
35
Metabolite - 4636
50
Metabolite - 2811
35
Metabolite - 3176
35
Metabolite - 1979
35
histamine
35
alpha-L-sorbopyranose
50
xylitol
50
Metabolite - 4504
50
Metabolite - 2285
35
3-methoxy-4-hydroxyphenylacetate
50
Metabolite - 2181
35
Metabolite - 1455
35
adenosine
35
Isobar 6: includes valine & betaine
35
Metabolite - 3169
35
Metabolite - 3470
35
Metabolite - 4502
50
Metabolite - 2746
35
Metabolite - 4503
50
Metabolite - 3476
35
Metabolite - 3443
35
[0148] Random Forest Analysis was also carried out on the biomarkers identified in Example 4 from urine samples to classify them as lower grade prostate cancer (Gleason score major 3) or higher grade prostate cancer (Gleason score major>=4). In this analysis resulted in 61% correct classification of the two cancer grades. The lower grade and the higher grade prostate cancers were correctly classified 58% and 71% respectively (Table 19).
[0000]
TABLE 19
Confusion matrix comparing urine from subjects with lower grade
prostate cancer and higher grade prostate cancer.
Predicted
Grade
Low
High
error
Actual
Low
25
18
0.42
Grade
High
4
10
0.29
OOB Error = 39%
[0149] Based on the OOB Error rate of 39%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or a higher grade prostate cancer with about 61% accuracy from analysis of the levels of biomarkers in urine from the subject.
[0150] The importance plot is shown in FIG. 4 . The important metabolites for this classification are listed in Table 20.
[0000]
TABLE 20
Most important urine biomarker metabolites to distinguish subjects
with lower grade prostate cancer and higher grade prostate cancer.
Metabolite
Library
Metabolite - 3805
35
Histamine
35
Metabolite - 1455
35
Catechol
35
xylitol
50
Metabolite - 4636
50
Metabolite - 3691
35
Adenosine
35
Glycine
50
Metabolite - 3661
35
Metabolite - 3955
35
Methionine
35
Isobar 6 includes valine, betaine
35
guanidineacetic acid
35
Metabolite - 3817
35
N-acetyl-D-glucosamine
50
Metabolite - 3806
35
Metabolite - 2277
35
3-methoxy-4-hydroxyphenylacetate
50
Metabolite - 4502
50
Metabolite - 4519
50
Guanine
50
Metabolite - 2181
35
Alpha-L-sorbopyranose
50
Metabolite - 2270
35
Metabolite - 1498
35
Metabolite - 3443
35
tryptophan
35
Metabolite - 2051
35
gamma-L-glutamy-L-tyrosine
35
Example 7
Random Forest Analysis for the Classification of Plasma Samples from Control Subjects, Subjects with Lower Grade PCA and Subjects with Higher Grade PCA
[0151] Random Forest Analysis was carried out on data obtained in Example 3 from plasma samples to classify them as Non-cancer (Control) or Prostate cancer. The control samples were plasma obtained from subjects with a Gleason score (major) of 0 or from prostate cancer (PCA) subjects with a Gleason score (major) 3 . The analysis resulted in 65% correct classification of the plasma sample types. The control subjects were correctly classified 68% of the time while the subjects with prostate cancer (PCA) were correctly classified 60% of the time (Table 21).
[0000]
TABLE 21
Confusion matrix for Control vs Lower Grade PCA in Plasma.
Predicted
Control
PCA
error
Actual
Control
36
17
0.32
PCA
17
26
0.40
OOB Error = 35%
[0152] Based on the OOB Error rate of 35%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or does not have prostate cancer with about 65% accuracy from analysis of the levels of biomarkers in plasma from the subject.
[0153] The importance plot is shown in FIG. 5 . The important metabolites for this classification are listed in Table 22.
[0000]
TABLE 22
Most important plasma biomarker metabolites to distinguish Control
from Lower Grade PCA.
Metabolite
Library
Metabolite - 1185
35
5-oxoproline
50
IHWESASLLR
35
Metabolite - 3765
35
Metabolite - 2753
35
Hydroxyproline form of bradykinin
35
D-alany-D-alanine
35
Metabolite - 5437
50
Metabolite - 2256
35
Metabolite - 5366
50
Metabolite - 4611
50
Alpha keto glutarate
35
Metabolite - 3167
35
Alpha-tocopherol
50
Metabolite - 3377
35
Metabolite - 1127
35
Iminodiacetic acid
50
Trans-4-hydroxyproline
50
Metabolite - 2111
35
Metabolite - 2853
35
Metabolite - 2185
35
Metabolite - 3030
50
Metabolite - 3017
50
Metabolite - 1083
35
N-acetyl-L-valine
35
Metabolite - 1597
35
Creatinine
35
Isobar 36 includes D-sorbitol-6-phosphate,
35
mannitol-1-phosphate
Metabolite - 2914
50
Pyridoxal-phosphate
35
[0154] Random Forest Analysis was also carried out on the biomarkers from plasma samples in Example 3 to classify them as control (Gleason score major 0) or higher grade prostate cancer (Gleason score major>=4, PCA). In this analysis resulted in 73% correct classification of the plasma sample types. The control and the higher grade prostate cancers were correctly classified 58% and 71% respectively (Table 23).
[0000]
TABLE 23
Confusion matrix comparing plasma from subjects without prostate
cancer (Control) and with higher grade prostate cancer (High PCA).
Predicted
High
Control
PCA
error
Actual
Control
36
17
0.32
High PCA
2
13
0.07
OOB Error = 27%
[0155] Based on the OOB Error rate of 27%, the Random Forest model that was created could be used to predict whether a subject has a higher grade prostate cancer or does not have prostate cancer with about 63% accuracy from analysis of the levels of biomarkers in plasma from the subject.
[0156] The importance plot is shown in FIG. 6 . The important biomarker metabolites for this classification are listed in Table 24.
[0000]
TABLE 24
Most important plasma biomarker metabolites to distinguish subjects
without prostate cancer from those with higher grade prostate cancer.
Metabolite
Library
Metabolite - 1185
35
Metabolite - 3377
35
Metabolite - 2329
35
Metabolite - 3603
35
Metabolite - 1127
35
Metabolite - 3305
35
Metabolite - 2389
35
Metabolite - 3088
50
Trans-4-hydroxyproline
50
Metabolite - 1104
35
Isobar 17 includes arginine, N-alpha-acetyl-
35
ornithine
Metabolite - 4769
50
Metabolite - 2141
35
Metabolite - 3030
50
Metabolite - 2867
35
Metabolite - 3707
35
Metabolite - 3098
50
Palmitoleic acid
50
Metabolite - 2711
35
Tetradecanoic acid
50
Metabolite - 2287
35
Metabolite - 2407
35
DL-indole-3-lactic acid
50
Metabolite - 1286
35
Heptadecanoic acid
50
Metabolite - 3033
50
5-oxoproline
50
Metabolite - 3576
35
Tartaric acid
35
Metabolite - 1831 possible Cl adduct of
35
citrulline
[0157] Random Forest Analysis was also carried out on the biomarkers from plasma samples to classify them as lower grade prostate cancer (Gleason score major 3) or higher grade prostate cancer (Gleason score major>=4). This analysis resulted in 67% correct classification of the two cancer grades. The lower grade and the higher grade prostate cancers were correctly classified 65% and 71% respectively (Table 25).
[0000]
TABLE 25
Confusion matrix classifying plasma from subjects with lower grade
prostate cancer and higher grade prostate cancer.
Predicted
Grade
Low
High
error
Actual
Low
28
15
0.35
Grade
High
4
10
0.29
OOB Error = 33%
[0158] Based on the OOB Error rate of 33%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or a higher grade prostate cancer with about 67% accuracy from analysis of the levels of biomarkers in plasma from the subject.
[0159] The importance plot is shown in FIG. 7 . The important metabolites for this classification are listed in Table 26.
[0000]
TABLE 26
Most important plasma biomarker metabolites to distinguish subjects
with lower grade prostate cancer and higher grade prostate cancer.
Metabolite
Library
Metabolite - 2329
35
Heptadecanoic acid
50
Metabolite - 3088
50
Metabolite - 3322
35
Palmitoleic acid
50
Isobar 6 includes valine and betaine
35
Tetradecanoic acid
50
Pyridoxal-phosphate
35
4-methyl-2-oxopentanoate
50
Metabolite - 3534
35
Metabolite - 2711
35
Isobar 17 includes arginine, N-alpha-acetyl-
35
ornithine.
Octadecanoic acid
50
Caffeine
35
Metabolite - 2389
35
Metabolite - 3377
35
Metabolite - 3305
35
Leucine
50
Metabolite - 2407
35
Metabolite - 3900
35
Metabolite - 3992 possible Cl adduct of formate
35
dimmer
Metabolite - 3089
50
Trans-4-hydroxypyruvate
50
Metabolite - 5437
50
N-hexadecanoic acid
50
Paraxanthine
35
Metabolite - 3603
35
M2130
35
Oleic acid
50
Metabolite - 1286
35
Example 8
Analytical Characterization of Unnamed Biomarkers Compounds
[0160] Table 27 below includes analytical characteristics of each of the isobars and the unnamed metabolites listed in Tables 1-26 above. The table includes, for each listed Isobar and Metabolite, the retention time (RT), retention index (RI), mass, quant mass, and polarity obtained using the analytical methods described above. “Mass” refers to the mass of the C12 isotope of the parent ion used in quantification of the compound. The values for “Quant Mass” give an indication of the analytical method used for quantification: “Y” indicates GC-MS and “1” indicates LC-MS. “Polarity” indicates the polarity of the quantitative ion as being either positive (+) or negative (−).
[0000]
TABLE 27
Analytical Characteristics of Isobars and Unnamed Metabolites.
COMPOUND
RT
RI
MASS
QUANT_MASS
Polarity
Isobar 1 includes mannose,
1.45
1481.0
215
1
−
fructose, glucose, galactose,
alpha-L-sorbopyranose, Inositol,
D-allose
Isobar 13 includes 5-keto-D-
1.40
1530.0
193.1
1
−
gluconic acid, 2-keto-L-gulonic
acid, D-glucuronic acid
Isobar 17 includes arginine, N-
1.49
1620.0
175.2
1
+
alpha-acetyl-ornithine
Isobar 18 includes D-fructose 1-
1.33
1475.0
259.1
1
−
phosphate, beta-D-fructose 6-
phosphate
Isobar 19 includes D-saccharic
1.55
1700.0
209
1
−
acid, 2-deoxy-D-galactose, 2-
deoxy-D-glucose, L-fucose, L-
rhamnose
Isobar 2 includes 3-amino-
1.60
1671.0
104.1
1
+
isobutyrate, 2-amino-butyrate, 4-
aminobutanoic acid,
dimethylglycine, choline
Isobar 20 includes fumaric acid,
4.45
4800.0
160.9
1
−
3-methyl-2-oxobutanoate
Isobar 21 includes gamma-
1.59
1620.0
263.1
1
+
aminobutyryl-L-histidine, L-
anserine
Isobar 22 includes glutamic acid,
1.55
1635.0
148
1
+
O-acetyl-L-serine
Isobar 24 includes L-arabitol,
1.43
1545.0
153.1
1
+
adonitol
Isobar 25 includes L-gulono-1,4-
1.67
1615.0
222.9
1
−
lactone, glucono-gamma-lactone
Isobar 27 includes L-kynurenine,
8.23
8470.0
209.1
1
+
alpha-2-diamino-gamma-
oxobenzenebutanoic acid
Isobar 29 includes R,S-
2.17
2095.0
157.1
1
−
hydroorotic acid, 5,6-
dihydroorotic acid
Isobar 3 includes inositol 1-
1.45
1467.0
304.7
1
−
phosphate, mannose 6-
phosphate, glucose 6-phosphate,
D-mannose 1-phosphate, alpha-
D-glucose 1-phosphate, alpha-D-
galactose 1 phosphate
Isobar 30 includes maltotetraose,
1.67
1770.0
710.8
1
−
stachyose
Isobar 31 includes maltotriose,
1.64
1752.0
548.8
1
−
melezitose
Isobar 32 includes N-acetyl-D-
1.57
1685.0
222
1
+
glucosamine, N-acetyl-D-
mannosamine
Isobar 36 includes D-sorbitol 6-
1.37
1470.0
261.1
1
−
phosphate, mannitol-1-phosphate
Isobar 38 includes N-acetyl-L-
9.12
9220.0
192
1
+
methionine, 5-hydroxy-1H-indole-
3-acetic acid
Isobar 4 includes Gluconic acid,
1.52
1587.0
195
1
−
DL-arabinose, D-ribose, L-xylose,
DL-lyxose, D-xylulose
Isobar 40 includes Maltotetraose,
1.67
2282.0
710.8
1
−
stachyose
Isobar 5 includes asparagine,
1.50
1395.0
133.1
1
+
ornithine
Isobar 6 includes valine, betaine
2.13
2160.0
118.1
1
+
Isobar 9 includes sucrose, beta-
1.60
1605.0
386.9
1
−
D-lactose, D-trehalose, D-
cellobiose, D-Maltose, palatinose,
melibiose, alpha-D-lactose
Metabolite - 1069-possible
12.55
14450.0
367.2
1
−
dehydroepiandrosterone sulfate
Metabolite - 1070
9.00
9169.0
378.3
1
+
Metabolite - 1085-possible
15.82
15964.0
288.1
1
+
isolobinine or 4-aminoestra-
1,3,5(10)-triene-3,17beta-diol
Metabolite - 1086
4.56
4811.0
294.1
1
+
Metabolite - 1088
13.12
14225.0
369.1
1
−
Metabolite - 1104
2.43
2410.0
201
1
−
Metabolite - 1110
11.66
11841.0
269.1
1
−
Metabolite - 1111 - possible
2.69
2700.0
148.1
1
+
methylnitronitrosoguanidine or
ethyl thiocarbamoylacetate
Metabolite - 1113 - possible
4.91
5290.0
204.2
1
+
acetylcarnitine
Metabolite - 1114
2.19
2198.0
104.1
1
+
Metabolite - 1116
4.20
4780.0
103.4
1
−
Metabolite - 1121
16.29
16429.0
303.3
1
+
Metabolite - 1122
4.45
4701.0
233.1
1
+
Metabolite - 1126
3.04
3188.0
175.1
1
+
Metabolite - 1127
12.18
12369.0
363.1
1
+
Metabolite - 1129
5.16
5419.0
260.1
1
+
Metabolite - 1133 - retired Na
1.63
1636.0
315
1
+
adduct of EDTA
Metabolite - 1142 - possible 5-
8.54
8739.0
163
1
−
hydroxypentanoate or beta-
hydroxyisovaleric acid
Metabolite - 1183
8.56
8765.0
365.8
1
+
Metabolite - 1185
8.70
9150.0
506.8
1
+
Metabolite - 1186
8.83
9000.0
529.6
1
+
Metabolite - 1187
8.80
9017.0
559.9
1
+
Metabolite - 1188
8.83
9017.0
619.9
1
+
Metabolite - 1203 - possible
9.11
9288.0
510.2
1
+
HXGXA
Metabolite - 1208
15.33
15494.0
319.4
1
−
Metabolite - 1211 - possible
9.90
9800.0
606.5
1
+
IHWESASLLR
Metabolite - 1215
8.96
9390.0
550.1
1
+
Metabolite - 1216
1.60
1631.4
343.9
1
−
Metabolite - 1220
15.24
15402.5
319.2
1
+
Metabolite - 1244
15.28
15436.8
343.4
1
−
Metabolite - 1248 - possible
8.06
8275.4
302.3
1
+
avermectin aglycone
Metabolite - 1283
9.04
9244.5
434.8
1
+
Metabolite - 1286
14.41
14579.8
229
1
+
Metabolite - 1288
2.11
2120.5
302
1
−
Metabolite - 1289
8.96
9139.7
338.4
1
+
Metabolite - 1303
9.01
9178.0
527.8
1
+
Metabolite - 1323 - possible p-
9.31
10000.0
187
1
−
cresol sulfate
Metabolite - 1327 - possible
13.22
13300.0
585.4
1
+
bilirubin
Metabolite - 1329
2.69
2791.0
210.1
1
+
Metabolite - 1330
10.67
11097.7
436.3
1
+
Metabolite - 1333
3.05
3794.0
321.9
1
+
Metabolite - 1335
8.74
9162.2
367.2
1
+
Metabolite - 1338
10.76
11193.0
241.1
1
−
Metabolite - 1342 - possible
9.04
9459.4
265.2
1
+
phenylacetylglutamine or formyl-
N-acetyl-5-methoxykynurenamine
Metabolite - 1349
3.50
3876.0
323.9
1
+
Metabolite - 1351
1.77
1936.5
177.9
1
+
Metabolite - 1364
10.35
10765.1
397.2
1
+
Metabolite - 1368
8.18
8607.4
184.1
1
+
Metabolite - 1383 - possible
8.66
9077.9
370.1
1
−
salicyluric glucuronide
Metabolite - 1389 - possible
13.62
14111.3
425.3
1
−
glucuronide form of X-1359
Metabolite - 1392
10.90
11350.3
415.2
1
+
Metabolite - 1394 - possible
12.28
12752.0
423.2
1
+
Losartan
Metabolite - 1455
2.38
2350.0
131.1
1
+
Metabolite - 1457
1.59
1675.0
188.2
1
+
Metabolite - 1465
3.45
3600.0
162.1
1
+
Metabolite - 1496
1.53
1562.0
133
1
−
Metabolite - 1497
13.87
14031.5
332.2
1
+
Metabolite - 1498
1.56
1650.0
143.1
1
−
Metabolite - 1573
1.63
1669.0
170.9
1
−
Metabolite - 1575
2.25
2243.5
219.1
1
+
Metabolite - 1576
2.51
2530.0
247.1
1
+
Metabolite - 1593
2.67
2690.0
395.9
1
−
Metabolite - 1594
3.15
3325.0
263.1
1
+
Metabolite - 1595 - possible
3.14
3400.0
290.1
1
+
glutathione metabolite
Metabolite - 1596
3.66
3902.0
185
1
−
Metabolite - 1597
3.66
4100.0
265.9
1
+
Metabolite - 1608
8.08
8253.0
348.1
1
−
Metabolite - 1609
8.31
8529.0
378
1
+
Metabolite - 1616
12.73
12910.3
331.2
1
+
Metabolite - 1653
16.84
16977.0
454.3
1
+
Metabolite - 1655
1.31
1374.0
107
1
+
Metabolite - 1656
1.46
1509.0
154.9
1
−
Metabolite - 1679
8.52
8705.8
283.1
1
−
Metabolite - 1680
8.50
8681.0
851.1
1
+
Metabolite - 1682
8.78
8961.0
339.1
1
−
Metabolite - 1713
2.73
3050.0
174
1
−
Metabolite - 1718
8.43
8390.0
457.9
1
+
Metabolite - 1817
1.37
1552.3
252
1
+
Metabolite - 1819
1.36
1539.6
244.8
1
−
Metabolite - 1829
1.43
1600.0
135
1
−
Metabolite - 1831 - possible Cl
1.46
1638.7
209.9
1
−
adduct of citrulline
Metabolite - 1834
1.64
1960.0
104
1
−
Metabolite - 1835
1.86
1999.3
152.1
1
−
Metabolite - 1836
2.10
2215.5
205.9
1
−
Metabolite - 1911
11.42
11799.6
464.1
1
+
Metabolite - 1914
10.35
10719.8
239.1
1
+
Metabolite - 1915
14.37
14798.6
507.2
1
−
Metabolite - 1963
13.15
13550.8
464.1
1
+
Metabolite - 1970
12.88
13271.2
852.9
1
+
Metabolite - 1974
5.93
6300.0
160.2
1
+
Metabolite - 1975
5.95
6093.0
344
1
+
Metabolite - 1977
3.56
4060.0
260.9
1
+
Metabolite - 1979 - Cl adduct of
1.52
1690.3
199
1
−
isobar 19
Metabolite - 1980
13.20
13250.0
391.1
1
+
Metabolite - 1981
7.94
8150.0
158.1
1
+
Metabolite - 1988
11.14
11515.0
190.1
1
+
Metabolite - 2005
8.62
9048.0
232.1
1
+
Metabolite - 2027
1.56
1729.3
184.1
1
+
Metabolite - 2036
14.30
14300.0
616.3
1
+
Metabolite - 2041
13.84
14198.1
246.3
1
+
Metabolite - 2051
1.45
1634.0
309
1
+
Metabolite - 2053
1.35
1482.3
324.9
1
−
Metabolite - 2055
1.37
1502.0
269.9
1
+
Metabolite - 2056
1.37
1499.0
165.1
1
−
Metabolite - 2064
8.00
8312.0
193.2
1
+
Metabolite - 2072
1.57
1736.1
273.7
1
−
Metabolite - 2074
2.24
2380.9
280.1
1
+
Metabolite - 2075
2.71
2728.0
134.1
1
+
Metabolite - 2099
7.82
8135.9
469.2
1
+
Metabolite - 2100
1.33
1532.9
499
1
+
Metabolite - 2105
8.15
8442.0
433.6
1
+
Metabolite - 2108
8.76
8800.0
277.1
1
+
Metabolite - 2109
8.99
9266.0
321.1
1
+
Metabolite - 2111
9.19
9442.3
365.1
1
+
Metabolite - 2118
13.10
13367.8
547.1
1
+
Metabolite - 2121
14.18
14467.4
561.2
1
+
Metabolite - 2129
15.83
16363.2
526.3
1
+
Metabolite - 2130
16.28
16625.5
792.4
1
+
Metabolite - 2139
8.09
8500.0
218.1
1
+
Metabolite - 2141
9.39
9605.0
409.1
1
+
Metabolite - 2143
10.11
10327.0
585.1
1
+
Metabolite - 2150
13.27
13616.5
466.1
1
+
Metabolite - 2174
2.50
2569.0
250.1
1
+
Metabolite - 2175
3.84
4148.4
144
1
+
Metabolite - 2180
8.32
8663.0
490
1
+
Metabolite - 2181
8.37
8715.5
298
1
+
Metabolite - 2185
9.22
9499.4
246.2
1
+
Metabolite - 2194
13.65
13961.3
544.2
1
+
Metabolite - 2198
13.97
14284.8
530.1
1
+
Metabolite - 2212
15.96
16271.0
478.2
1
+
Metabolite - 2232
2.26
2318.0
754.8
1
−
Metabolite - 2237
10.14
10039.0
453.1
1
+
Metabolite - 2242
11.61
11926.0
254.3
1
+
Metabolite - 2249
14.21
14570.9
267.2
1
−
Metabolite - 2250
14.26
14668.4
286.3
1
+
Metabolite - 2254
1.53
1687.6
217.2
1
+
Metabolite - 2255 -
9.08
9394.0
539.1
1
+
hydroxyproline form of bradykinin
Metabolite - 2256
9.93
9867.0
460.8
1
+
Metabolite - 2259
11.25
11586.0
383.2
1
−
Metabolite - 2269
10.36
10727.0
255.1
1
−
Metabolite - 2271
12.95
13348.8
413.2
1
−
Metabolite - 2272
7.96
8377.0
189.1
1
−
Metabolite - 2277
10.07
10457.0
201.1
1
−
Metabolite - 2279
12.38
12781.0
490.1
1
+
Metabolite - 2281
13.93
14325.1
505.2
1
−
Metabolite - 2285
2.00
2146.0
699.6
1
−
Metabolite - 2287
12.95
13335.6
502.8
1
+
Metabolite - 2292
2.40
2900.0
343.9
1
−
Metabolite - 2293 - possible O-
8.86
9084.0
440.1
1
+
desmethylvenlafaxine
glucuronide
Metabolite - 2313
1.56
1685.6
352.9
1
−
Metabolite - 2316
8.82
9163.6
100.1
1
+
Metabolite - 2319
12.24
12626.0
367.2
1
−
Metabolite - 2323
7.55
7796.0
188.9
1
−
Metabolite - 2329
11.76
12177.6
541.2
1
−
Metabolite - 2347
13.65
14091.0
450.1
1
+
Metabolite - 2348
13.91
14293.5
448.3
1
+
Metabolite - 2366
8.47
8870.2
271
1
+
Metabolite - 2368
9.27
9615.5
573.2
1
−
Metabolite - 2370
16.13
16561.2
476.4
1
−
Metabolite - 2386
11.94
12320.3
539.2
1
−
Metabolite - 2387
8.55
9050.0
182.1
1
−
Metabolite - 2388
16.16
16900.0
259.1
1
−
Metabolite - 2389
1.49
1641.5
314.9
1
−
Metabolite - 2390
6.09
6410.0
517.4
1
+
Metabolite - 2391
10.14
10485.7
159.1
1
+
Metabolite - 2392
13.08
13460.4
379
1
−
Metabolite - 2406
14.69
15063.0
274.4
1
+
Metabolite - 2407
15.72
16127.6
637.3
1
+
Metabolite - 2466
9.19
8760.0
624.8
1
+
Metabolite - 2486
1.52
1667.0
635.7
1
−
Metabolite - 2506
14.05
14437.5
624.4
1
−
Metabolite - 2507
14.44
14843.0
481.4
1
−
Metabolite - 2546
1.63
1747.3
129.1
1
+
Metabolite - 2548 - possible Cl
5.97
6430.0
202.9
1
−
adduct of uric acid
Metabolite - 2550 - possible
11.09
11490.0
411.1
1
+
Riluzole glucuronide
Metabolite - 2557 - possible
11.79
11968.1
354.2
1
+
Pantoprazole metabolite
Metabolite - 2558 - possible N1-
8.14
8800.0
153.1
1
+
methyl-2-pyridone-5-carboxamide
and others
Metabolite - 2567
7.79
8464.7
247.1
1
+
Metabolite - 2591
9.99
10189.4
279.3
1
+
Metabolite - 2592
10.59
10600.0
697.4
1
−
Metabolite - 2607
10.01
10354.0
578.2
1
+
Metabolite - 2686
1.40
1593.0
219
1
−
Metabolite - 2688
1.42
1614.0
182
1
−
Metabolite - 2690
1.62
1786.2
441.1
1
+
Metabolite - 2691
1.69
1835.8
294.1
1
−
Metabolite - 2698
3.88
4500.0
157
1
+
Metabolite - 2703
8.86
9054.8
384.1
1
+
Metabolite - 2706
10.20
10428.3
247.2
1
+
Metabolite - 2711
2.22
2300.0
123
1
+
Metabolite - 2724
4.12
4499.3
206.1
1
+
Metabolite - 2726
8.30
8854.0
375.2
1
+
Metabolite - 2752
2.92
3200.0
189.1
1
+
Metabolite - 2753
3.38
3750.0
147
1
+
Metabolite - 2766
8.09
8395.0
397
1
+
Metabolite - 2768
9.13
9340.0
322.8
1
−
Metabolite - 2774
3.53
3796.0
230.9
1
+
Metabolite - 2778
7.97
8251.5
376.1
1
+
Metabolite - 2781
10.01
10224.6
202.2
1
−
Metabolite - 2806
1.38
1491.0
185.1
1
+
Metabolite - 2807
8.74
8920.3
380.8
1
+
Metabolite - 2809
8.74
8923.5
699.8
1
+
Metabolite - 2821
6.80
7680.0
119.1
1
+
Metabolite - 2824
12.72
12903.0
773.2
1
+
Metabolite - 2827
8.70
8877.0
419.5
1
+
Metabolite - 2846
9.19
9369.8
596.6
1
+
Metabolite - 2849 - related to
3.17
3375.0
482.6
1
−
citric acid?
Metabolite - 2853
8.74
8923.5
578.4
1
+
Metabolite - 2867
9.65
9908.0
235.3
1
+
Metabolite - 2888 - possible
9.87
10153.9
452
1
−
sulfated Rosiglitazone
Metabolite - 2893 - possible
9.99
10292.8
344.1
1
+
demethylated Rosiglitazone
Metabolite - 2897
10.96
10100.0
245.2
1
−
Metabolite - 2898
11.17
11463.3
213.1
1
−
Metabolite - 2900
13.35
13544.7
621.8
1
+
Metabolite - 2914
3.75
1096.1
214
Y
+
Metabolite - 2915
3.77
1099.0
174
Y
+
Metabolite - 2924 2-hydroxy
4.38
1170.7
130.9
Y
+
butanoic acid
Metabolite - 2973
4.74
1213.4
281
Y
+
Metabolite - 2974
4.76
1215.6
187
Y
+
Metabolite - 2978
5.01
1244.1
261.8
Y
+
Metabolite - 2981
5.21
1265.2
210.9
Y
+
Metabolite - 3002
6.74
1440.8
296.1
Y
+
Metabolite - 3003
6.79
1446.6
218.1
Y
+
Metabolite - 3004
6.81
1449.0
210.9
Y
+
Metabolite - 3012
7.17
1489.8
232
Y
+
Metabolite - 3014 - meso
7.43
1520.6
217.1
Y
+
erythritol
Metabolite - 3016
7.58
1537.5
186
Y
+
Metabolite - 3017
7.61
1541.4
246.1
Y
+
Metabolite - 3019
7.74
1556.4
260.1
Y
+
Metabolite - 3020
7.81
1564.1
292
Y
+
Metabolite - 3022
7.98
1584.9
142
Y
+
Metabolite - 3023
8.04
1590.9
274.1
Y
+
Metabolite - 3025
8.11
1600.3
274.1
Y
+
Metabolite - 3027
8.21
1610.6
142
Y
+
Metabolite - 3030
8.62
1659.7
320
Y
+
Metabolite - 3033
8.88
1689.4
116.9
Y
+
Metabolite - 3034
8.92
1694.9
299
Y
+
Metabolite - 3040
9.27
1735.7
274.1
Y
+
Metabolite - 3044
1.52
1615.3
150.1
1
+
Metabolite - 3051
8.69
8878.6
835.8
1
+
Metabolite - 3053
8.83
9042.0
170.2
1
+
Metabolite - 3055 - possible NH3
9.20
9443.0
196.8
1
+
adduct of hippuric acid
Metabolite - 3056
9.19
9432.0
185.2
1
+
Metabolite - 3058
9.70
1786.9
335.1
Y
+
Metabolite - 3064
13.80
13968.2
516.1
1
+
Metabolite - 3067
10.02
1824.2
132
Y
+
Metabolite - 3073
10.17
1838.8
362.1
Y
+
Metabolite - 3074
10.22
1844.5
204.1
Y
+
Metabolite - 3075
10.36
1857.9
204
Y
+
Metabolite - 3077
10.44
1866.2
308.1
Y
+
Metabolite - 3078
10.65
1887.0
203.1
Y
+
Metabolite - 3081
10.89
1911.5
204
Y
+
Metabolite - 3085 = Inositol 2
11.04
1926.1
217
Y
+
Metabolite - 3086
11.16
1938.5
221
Y
+
Metabolite - 3088
11.23
1946.1
372.2
Y
+
Metabolite - 3089
11.28
1951.5
116.9
Y
+
Metabolite - 3090
11.31
1955.0
243.1
Y
+
Metabolite - 3091
11.41
1966.2
232.1
Y
+
Metabolite - 3093
11.50
1975.6
204
Y
+
Metabolite - 3094
11.55
1980.6
299
Y
+
Metabolite - 3097
11.64
1990.4
204
Y
+
Metabolite - 3098
11.75
2003.0
308
Y
+
Metabolite - 3099
11.77
2005.2
204
Y
+
Metabolite - 3101
11.93
2022.2
290
Y
+
Metabolite - 3102
11.99
2028.2
217.1
Y
+
Metabolite - 3103
12.09
2039.8
290.1
Y
+
Metabolite - 3108
12.24
2056.5
246
Y
+
Metabolite - 3109
12.56
2092.6
202.1
Y
+
Metabolite - 3113
12.73
2113.5
406.2
Y
+
Metabolite - 3123
8.97
8763.0
334
1
+
Metabolite - 3125
11.88
12095.0
187.1
1
+
Metabolite - 3127
8.61
8812.0
260.1
1
−
Metabolite - 3129
8.80
9012.0
337.1
1
+
Metabolite - 3130
9.09
9328.0
158.2
1
+
Metabolite - 3131
10.49
10770.0
192.9
1
+
Metabolite - 3132
10.14
10177.0
260.2
1
+
Metabolite - 3134
14.33
14487.3
483.1
1
+
Metabolite - 3135
14.96
15107.7
467.2
1
+
Metabolite - 3138
8.63
8749.0
229.2
1
+
Metabolite - 3139
8.82
8934.5
176.1
1
+
Metabolite - 3143
9.81
10070.0
160.1
1
+
Metabolite - 3146
14.96
15105.0
499.1
1
−
Metabolite - 3160
12.11
12247.3
361
1
+
Metabolite - 3163 - possible
4.57
4837.5
258
1
+
methylcytidine, benserazide, Pyr-
Gln-OH, or
glycerophosphocholine
Metabolite - 3165
8.38
8472.2
265
1
+
Metabolite - 3166
8.69
8850.0
394.2
1
+
Metabolite - 3167
8.86
8929.0
197.1
1
+
Metabolite - 3169
9.27
9384.5
250
1
+
Metabolite - 3176 - possible
1.42
1750.0
132
1
+
creatine
Metabolite - 3178 - possible NH3
3.15
3670.0
210
1
+
adduct of isobar 42
Metabolite - 3180
4.14
4500.0
139
1
+
Metabolite - 3181
8.59
8621.4
165.1
1
+
Metabolite - 3183 - possible
9.37
9441.0
295.2
1
+
gamma-L-glutamyl-L-
phenylalanine
Metabolite - 3184
10.28
10364.4
223
1
+
Metabolite - 3189
12.06
12190.0
391
1
+
Metabolite - 3215
1.67
1733.8
173.8
1
+
Metabolite - 3216
1.68
1743.8
405.7
1
+
Metabolite - 3218
2.20
2257.0
148.1
1
+
Metabolite - 3220
3.73
4044.1
233.1
1
+
Metabolite - 3221
7.97
8050.0
204.1
1
+
Metabolite - 3231
3.08
3287.0
104.1
1
+
Metabolite - 3238
11.77
11827.4
220
1
+
Metabolite - 3243
11.34
11371.0
376.8
1
+
Metabolite - 3245
2.14
2168.3
816.7
1
−
Metabolite - 3246 - possible Ala-
4.73
5260.0
147.1
1
+
GLy, glycyl sarcosine, or ureido-
butyric acid
Metabolite - 3303
9.51
9799.5
170.1
1
+
Metabolite - 3309
8.37
8686.3
512.9
1
+
Metabolite - 3311
11.27
11597.0
308.2
1
+
Metabolite - 3313
8.10
8529.6
196.9
1
−
Metabolite - 3314
8.92
9143.5
264.8
1
+
Metabolite - 3317
8.42
8702.3
429.6
1
+
Metabolite - 3320 - possible
10.74
11300.0
245
1
−
pimpinellin or
tetrahydroxybenzophenone
Metabolite - 3322
11.82
12044.0
383.2
1
−
Metabolite - 3327
11.56
11784.0
385.3
1
−
Metabolite - 3364
9.06
9172.1
189
1
−
Metabolite - 3365
1.87
2068.3
115.1
1
+
Metabolite - 3370
8.11
8529.1
226.2
1
+
Metabolite - 3377
8.86
8963.9
270.2
1
+
Metabolite - 3379
1.51
1539.0
414.1
1
+
Metabolite - 3380
8.26
8602.1
164.1
1
+
Metabolite - 3381
2.31
2775.0
335
1
+
Metabolite - 3387
9.21
9377.5
463.1
1
+
Metabolite - 3390
8.14
8800.0
595.9
1
−
Metabolite - 3401
1.73
1863.3
131.1
1
+
Metabolite - 3402
8.90
8900.0
343.2
1
+
Metabolite - 3409
10.35
10636.4
259.1
1
+
Metabolite - 3426
10.71
11051.7
163
1
+
Metabolite - 3430 - possible gly-
2.78
3319.7
189.1
1
+
leu, acetyl-lys, ala-val
Metabolite - 3433
8.41
8681.7
327.1
1
−
Metabolite - 3436
8.91
9157.1
157
1
−
Metabolite - 3440
9.99
10317.6
252.8
1
−
Metabolite - 3441
1.51
1565.4
515
1
+
Metabolite - 3443
9.23
9420.6
194.8
1
−
Metabolite - 3457
3.81
4193.3
212.9
1
+
Metabolite - 3474
15.67
16524.3
228.3
1
+
Metabolite - 3475
1.66
1711.9
365.2
1
+
Metabolite - 3476
1.65
1709.7
377
1
−
Metabolite - 3484
13.59
13710.7
983.4
1
+
Metabolite - 3489
3.26
3840.0
226
1
+
Metabolite - 3493
9.57
9912.3
335.9
1
+
Metabolite - 3498
7.80
8368.7
279.1
1
+
Metabolite - 3507
10.01
10631.8
396.2
1
+
Metabolite - 3516
10.27
10895.1
411.3
1
+
Metabolite - 3517
10.27
10891.5
382.3
1
+
Metabolite - 3522
10.38
11005.0
362.3
1
+
Metabolite - 3526
10.42
11049.9
404.3
1
+
Metabolite - 3531
10.52
11400.0
384.3
1
+
Metabolite - 3534
10.54
11174.3
426.3
1
+
Metabolite - 3539
10.62
11259.8
435.2
1
+
Metabolite - 3543
10.67
11305.2
406.5
1
+
Metabolite - 3545
10.69
11331.3
448.4
1
+
Metabolite - 3554
10.91
11547.0
521.5
1
+
Metabolite - 3564
11.15
11792.0
471.7
1
+
Metabolite - 3576
1.38
1539.7
108
1
−
Metabolite - 3578
1.36
1525.2
296
1
+
Metabolite - 3603
8.41
8971.0
313.6
1
+
Metabolite - 3604
8.99
9551.9
214.2
1
−
Metabolite - 3605
9.59
10191.4
229.9
1
−
Metabolite - 3615
13.61
14343.6
868
1
+
Metabolite - 3624
10.36
10984.4
205.1
1
+
Metabolite - 3653 - Possible
4.05
4700.0
144.1
1
+
stachydrine
Metabolite - 3659
10.28
10447.6
427.2
1
+
Metabolite - 3660
10.32
10622.4
387.1
1
+
Metabolite - 3667
9.17
9120.0
301.1
1
+
Metabolite - 3668
9.63
9536.0
379.1
1
+
Metabolite - 3670
10.23
10459.0
213
1
−
Metabolite - 3694
8.05
8483.7
364.1
1
+
Metabolite - 3698
8.31
8640.2
273.1
1
+
Metabolite - 3701
1.34
1455.6
141.2
1
+
Metabolite - 3706
9.93
9717.0
348
1
+
Metabolite - 3707
13.07
13339.5
241
1
+
Metabolite - 3708
1.66
1625.3
159.9
1
+
Metabolite - 3752
8.61
8750.4
276.1
1
+
Metabolite - 3754
9.02
9152.5
190.2
1
+
Metabolite - 3755
9.81
9800.0
418.2
1
+
Metabolite - 3756
10.02
10319.0
160.9
1
+
Metabolite - 3758
12.44
12714.0
309.1
1
−
Metabolite - 3761
8.34
8750.0
212
1
+
Metabolite - 3765
9.22
9630.0
467.8
1
+
Metabolite - 3771
1.68
1761.0
227
1
−
Metabolite - 3772
2.22
2274.0
109
1
+
Metabolite - 3773
2.26
2275.3
153
1
+
Metabolite - 3778
7.37
7200.0
307.3
1
+
Metabolite - 3783
1.37
1464.0
271.1
1
+
Metabolite - 3786
10.19
9787.3
241.2
1
−
Metabolite - 3800
2.00
2400.0
255
1
−
Metabolite - 3802
2.18
2200.0
137.1
1
+
Metabolite - 3803
2.22
2435.0
198.1
1
+
Metabolite - 3804
2.44
2694.5
259
1
+
Metabolite - 3805
2.49
2600.0
229.1
1
+
Metabolite - 3806
2.80
3155.3
212.1
1
+
Metabolite - 3808
3.28
3719.0
288.8
1
−
Metabolite - 3810
3.74
4500.0
188.1
1
−
Metabolite - 3813
3.81
4312.0
212.1
1
+
Metabolite - 3816
4.16
5310.0
173.1
1
−
Metabolite - 3817
4.73
4701.0
143.1
1
+
Metabolite - 3824
7.88
8197.7
202.1
1
+
Metabolite - 3828
8.20
8495.7
245.2
1
+
Metabolite - 3830
8.42
8725.0
189
1
−
Metabolite - 3832 - possible
8.73
8995.8
173
1
−
phenol sulfate
Metabolite - 3833
8.81
9100.0
261.1
1
−
Metabolite - 3834 - Peptide
9.20
9285.0
372
1
+
Metabolite - 3837
9.26
9466.8
212.1
1
−
Metabolite - 3841
9.45
9638.0
245.1
1
−
Metabolite - 3843
9.54
9721.9
263.1
1
+
Metabolite - 3847
9.65
9816.6
206
1
+
Metabolite - 3848
9.73
9924.4
192
1
+
Metabolite - 3855
9.94
10142.0
243
1
−
Metabolite - 3873
9.94
10142.5
219.9
1
+
Metabolite - 3876
9.99
10195.0
273
1
−
Metabolite - 3877
10.02
10227.0
211
1
−
Metabolite - 3878
10.44
10673.0
245
1
+
Metabolite - 3879
11.07
11336.5
243
1
−
Metabolite - 3886
1.77
1903.3
255
1
−
Metabolite - 3887
2.33
2576.0
224.1
1
−
Metabolite - 3893
3.26
3724.5
409
1
+
Metabolite - 3896
3.38
3868.0
245.2
1
+
Metabolite - 3898
3.57
4100.0
194.9
1
+
Metabolite - 3900
4.53
4871.7
173.1
1
−
Metabolite - 3908
7.98
8301.7
150
1
+
Metabolite - 3909
8.21
8497.8
160.1
1
+
Metabolite - 3911
8.27
8568.2
116.1
1
+
Metabolite - 3951
8.41
8705.4
367.1
1
+
Metabolite - 3952
8.70
9150.0
297.2
1
+
Metabolite - 3955
8.68
8951.7
357.1
1
−
Metabolite - 3957
9.54
9720.8
159.3
1
−
Metabolite - 3960
8.49
8744.1
417.1
1
+
Metabolite - 3963
10.53
10787.0
652.1
1
+
Metabolite - 3966
11.53
11830.0
491.2
1
+
Metabolite - 3968
1.39
1436.0
327.8
1
+
Metabolite - 3970
4.52
4906.0
226
1
+
Metabolite - 3972
6.16
6304.0
432.6
1
−
Metabolite - 3973
9.57
9765.0
296.9
1
+
Metabolite - 3974
10.12
10349.0
604.1
1
+
Metabolite - 3977
11.03
11312.0
187.1
1
−
Metabolite - 3980
8.16
8480.4
353.1
1
+
Metabolite - 3981
10.01
10234.0
431
1
+
Metabolite - 3984
12.76
13134.0
489.1
1
+
Metabolite - 3986
13.12
13514.5
489.1
1
+
Metabolite - 3992 - possible Cl
1.40
1600.0
129.2
1
−
adduct of Formate dimer
Metabolite - 3994
1.63
1640.4
427
1
+
Metabolite - 3996
5.06
1236.0
176
Y
+
Metabolite - 3997
2.87
2876.0
564.9
1
−
Metabolite - 3998
5.22
1252.7
171
Y
+
Metabolite - 4002
5.69
1305.2
174
Y
+
Metabolite - 4003
3.94
4397.0
205
1
+
Metabolite - 4010
6.80
1432.8
218.1
Y
+
Metabolite - 4013
8.05
8399.5
547
1
−
Metabolite - 4014
7.17
1474.9
252
Y
+
Metabolite - 4015
7.37
1498.4
160
Y
+
Metabolite - 4017
7.62
1527.3
174
Y
+
Metabolite - 4018
8.35
8589.3
664
1
−
Metabolite - 4019
7.68
1534.5
174
Y
+
Metabolite - 4020
7.91
1561.5
220.1
Y
+
Metabolite - 4027
8.67
1650.2
274.1
Y
+
Metabolite - 4030 - possible
11.88
12214.7
218.1
1
+
glutethimide or securinine
Metabolite - 4031 - possible
14.26
14607.0
244.2
1
+
norlevorphenol,
isobutylphendienamide,
amprolium
Metabolite - 4032
8.95
1682.6
156.1
Y
+
Metabolite - 4042
10.23
1831.9
57.9
Y
+
Metabolite - 4043 lysine
10.29
1838.6
317.2
Y
+
Metabolite - 4046
10.80
1890.5
353.1
Y
+
Metabolite - 4051
11.56
1970.2
357.1
Y
+
Metabolite - 4053
11.87
2004.6
217.1
Y
+
Metabolite - 4058
12.46
2070.6
315.1
Y
+
Metabolite - 4075
13.27
2171.5
103
Y
+
Metabolite - 4078
16.49
16789.0
663.4
1
+
Metabolite - 4080
14.02
2270.2
299
Y
+
Metabolite - 4084
14.98
2393.9
441.3
Y
+
Metabolite - 4091 - possible
2.03
2084.7
277
1
+
gamma-glutamyl-glutamic acid
Metabolite - 4092
5.23
5668.0
256.1
1
+
Metabolite - 4096 - possible
8.60
8763.6
318.2
1
+
gamma-glu-gly-leu
Metabolite - 4112
8.46
8643.5
254.2
1
+
Metabolite - 4116
10.26
10582.0
272.2
1
+
Metabolite - 4117-possible
14.70
15040.2
260.3
1
+
propranolol or 2-heptyl-3-
hydroxy-quinolone
Metabolite - 4133
4.35
1108.9
198
Y
+
Metabolite - 4134
5.51
1239.0
60.9
Y
+
Metabolite - 4147
10.07
1767.1
290.2
Y
+
Metabolite - 4148
10.23
1786.3
249.2
Y
+
Metabolite - 4150
11.34
1910.4
306.3
Y
+
Metabolite - 4163
1.35
1444.1
225.3
1
+
Metabolite - 4167
11.03
10920.4
286.2
1
+
Metabolite - 4168
13.69
13793.3
686.4
1
+
Metabolite - 4196
12.14
2000.4
290.2
Y
+
Metabolite - 4234
10.57
10467.0
564.4
1
+
Metabolite - 4235
10.91
10789.1
652.3
1
+
Metabolite - 4238
9.29
9192.0
828.5
1
+
Metabolite - 4251
4.09
1130.7
217
Y
+
Metabolite - 4271
9.69
1777.4
419.2
Y
+
Metabolite - 4272
10.28
1840.2
669.3
Y
+
Metabolite - 4274
10.37
1857.0
158.1
Y
+
Metabolite - 4275
10.68
1887.0
271.1
Y
+
Metabolite - 4331
13.95
14040.0
679
1
+
Metabolite - 4354
3.90
1074.3
110
Y
+
Metabolite - 4355
6.76
1396.9
102
Y
+
Metabolite - 4360
9.15
1678.2
347.2
Y
+
Metabolite - 4361
9.40
1706.2
232.2
Y
+
Metabolite - 4362
10.02
1779.9
319.2
Y
+
Metabolite - 4365
11.05
1892.9
204
Y
+
Metabolite - 4428
7.92
8236.5
229.2
1
+
Metabolite - 4448
9.54
9831.4
362.3
1
+
Metabolite - 4494
6.45
1363.2
221
Y
+
Metabolite - 4495
6.59
1381.0
117
Y
+
Metabolite - 4496
6.76
1398.2
204
Y
+
Metabolite - 4497
7.05
1431.6
218.1
Y
+
Metabolite - 4498
7.06
1434.9
103
Y
+
Metabolite - 4499
7.22
1453.0
189
Y
+
Metabolite - 4500
7.30
1460.7
172
Y
+
Metabolite - 4501 imino diacetic
7.96
1538.4
232.1
Y
+
acid
Metabolite - 4502
8.34
1581.3
273.1
Y
+
Metabolite - 4503
8.39
1589.0
227.2
Y
+
Metabolite - 4504
8.46
1597.1
244.1
Y
+
Metabolite - 4505
8.79
1633.4
285
Y
+
Metabolite - 4507
8.89
1644.9
245
Y
+
Metabolite - 4509
9.52
1720.6
204
Y
+
Metabolite - 4510
9.70
1740.1
254
Y
+
Metabolite - 4511
10.09
1788.4
206
Y
+
Metabolite - 4512
10.14
1790.7
345.1
Y
+
Metabolite - 4514
10.31
1812.3
342.2
Y
+
Metabolite - 4516
11.00
1886.5
217
Y
+
Metabolite - 4517
11.06
1892.7
217
Y
+
Metabolite - 4518
11.15
1902.4
295
Y
+
Metabolite - 4519
11.51
1941.8
193
Y
+
Metabolite - 4520
11.83
1978.1
325.1
Y
+
Metabolite - 4521
11.89
1983.4
383.1
Y
+
Metabolite - 4522
12.26
2025.4
217.1
Y
+
Metabolite - 4523
12.46
2047.0
258.1
Y
+
Metabolite - 4524
12.66
2071.3
210.1
Y
+
Metabolite - 4550
13.25
13286.2
568.2
1
+
Metabolite - 4567
3.50
3910.5
203.2
1
+
Metabolite - 4593
3.37
1011.1
170.9
Y
+
Metabolite - 4595
5.65
1274.4
130
Y
+
Metabolite - 4598
6.69
1392.2
169.9
Y
+
Metabolite - 4611
8.07
1546.6
292.1
Y
+
Metabolite - 4615
7.93
8250.0
222.1
1
+
Metabolite - 4617
8.39
8588.0
241.3
1
+
Metabolite - 4618
8.93
1651.1
349.2
Y
+
Metabolite - 4620
8.82
9001.0
312.1
1
+
Metabolite - 4624
10.01
1779.1
342.2
Y
+
Metabolite - 4628
10.11
1786.4
267.1
Y
+
Metabolite - 4629
10.29
1806.9
274.1
Y
+
Metabolite - 4632
10.59
1840.6
166
Y
+
Metabolite - 4633
10.69
1851.2
129
Y
+
Metabolite - 4634
11.00
1884.3
333.1
Y
+
Metabolite - 4635
11.19
1908.7
192.9
Y
+
Metabolite - 4636
11.50
1937.7
483.3
Y
+
Metabolite - 4637
11.95
1988.1
193
Y
+
Metabolite - 4638
12.25
2021.4
203.1
Y
+
Metabolite - 4639
12.87
2092.4
156.1
Y
+
Metabolite - 4649
5.33
5997.0
164.1
1
+
Metabolite - 4667
5.36
5652.8
320.1
1
−
Metabolite - 4706
8.92
9069.8
219
1
−
Metabolite - 4767
8.77
1626.2
116.9
Y
+
Metabolite - 4768
9.04
1661.7
279.1
Y
+
Metabolite - 4769
11.30
1916.4
156
Y
+
Metabolite - 4787
11.13
10895.5
289.4
1
+
Metabolite - 4791
10.29
1796.4
366.4
Y
+
Metabolite - 4795
14.83
2350.3
309
Y
+
Metabolite - 4796
3.53
1043.6
117
Y
+
Metabolite - 4806
4.20
1122.8
104.9
Y
+
Metabolite - 4866
9.18
9069.0
506.7
1
+
Metabolite - 4868 - confirmed
9.44
9356.0
531.2
1
+
Bradykinin
Metabolite - 4869
10.25
10112.8
534.5
1
+
Metabolite - 4931
1.50
1659.5
431
1
+
Metabolite - 4986
11.56
1956.4
204.1
Y
+
Metabolite - 5086
9.51
9738.3
388.2
1
+
Metabolite - 5087
9.69
9924.9
432.3
1
+
Metabolite - 5089
9.85
10075.9
476.3
1
+
Metabolite - 5107
11.87
11986.0
516.7
1
+
Metabolite - 5108
12.00
12116.5
538.7
1
+
Metabolite - 5109
12.12
12248.5
560.7
1
+
Metabolite - 5110
12.24
12350.5
582.6
1
+
Metabolite - 5126
9.78
10017.0
358.3
1
+
Metabolite - 5128
3.12
3462.8
558
1
−
Metabolite - 5147
8.21
8508.0
262.2
1
+
Metabolite - 5166
12.90
12999.4
491.5
1
+
Metabolite - 5167
12.97
13070.0
506.2
1
+
Metabolite - 5170
8.93
9156.3
279.1
1
+
Metabolite - 5186
1.55
1709.7
163.9
1
+
Metabolite - 5187
3.53
3985.5
489.1
1
+
Metabolite - 5189
16.33
16650.0
528.2
1
+
Metabolite - 5207
7.41
1493.6
151
Y
+
Metabolite - 5209
8.10
1573.6
218.2
Y
+
Metabolite - 5210
8.47
1616.4
254.1
Y
+
Metabolite - 5211
8.77
1652.1
326.2
Y
+
Metabolite - 5212
8.88
1665.1
306.1
Y
+
Metabolite - 5213
8.97
1675.3
111.1
Y
+
Metabolite - 5214
11.54
1960.0
117
Y
+
Metabolite - 5215
11.98
2008.0
163
Y
+
Metabolite - 5226
3.73
1073.9
102
Y
+
Metabolite - 5227
6.59
1398.6
151
Y
+
Metabolite - 5228
6.97
1442.5
181.1
Y
+
Metabolite - 5229
7.13
1461.6
211.1
Y
+
Metabolite - 5232
12.19
2031.5
134
Y
+
Metabolite - 5346
8.33
1573.0
202
Y
+
Metabolite - 5349
10.10
1782.2
312.1
Y
+
Metabolite - 5366
12.49
2044.7
204
Y
+
Metabolite - 5403
5.92
1300.2
319
Y
+
Metabolite - 5419
9.05
1664.1
349.2
Y
+
Metabolite - 5427
10.67
1853.0
192.9
Y
+
Metabolite - 5437
12.17
2017.4
204
Y
+
Metabolite - 5489
8.10
1550.3
247.1
Y
+
Metabolite - 5847
12.35
2040.0
288.2
Y
+
Metabolite - 5906
7.82
1541.2
313.9
Y
+
Metabolite - 5907
8.69
1643.2
229.1
Y
+
[0161] While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention. | Methods for identifying and evaluating suites of biochemical and/or gene entities useful as biomarkers for early prediction of prostate cancer, disease grading, target identification/validation, and monitoring of drug efficacy are provided. Also provided are suites of small molecule entities as biomarkers for prostate cancer. | 8 |
BACKGROUND OF THE INVENTION
This invention relates to the field of embossing machines, and is preferably used in connection with the type of embossing equipment illustrated in the U.S. patent to Bolten et al, U.S. Pat. No. 4,091,910. Since the introduction of equipment in accordance with the Bolton patent, various changes and improvements have been made to render the machine more automatic in operation and particularly to carry out the storing of blank cards or plates in a hopper, feeding them from the hopper to the embossing location, and from there to a receiver so that the entire procedure can proceed with minimum operator intervention. This equipment, known as the AM Addressograph E300 Embosser, involved first the use of a frame system arranged centrally of the machine to position a plate during embossing so that the characters are embossed in sequence on the proper line and at the proper positions along the line. The frame system was made up of an inner frame having parallel rails with grooves forming a movable track segment in which the upper and lower edges of the plate could be slidably received. This inner frame also carried means for trapping and registering the plate at a predetermined location along the movable track segment in response to its being slid into the movable track segment from the input end. The inner frame was vertically shiftable on guides carried by the outer frame, which in turn was horizontally shiftable on fixed guides running parallel to the character lines on the embossed plate. Both frames were arranged to be positioned along their guides by electrically controlled mechanism, including cables and stepping motors, in such manner as to place the plate in proper position for embossing each character thereon. The drive system for the horizontally shiftable frame had two modes of operation, one a step by step locating mode for sequential character embossing, and the other an extended travel mode for allowing the inner frame tracks to receive or discharge plates.
At the input end of the machine there was a hopper for holding a stack of unembossed plates and advancing them stackwise to a picking position, and fixed upper and lower rails forming a fixed track segment for receiving a plate picked from the stack and guiding it into the machine.
At the output end the arrangement was somewhat similar in that there was provided a fixed exit track segment and a receding stack receiver for accepting and holding the embossed plates in stacked relationship. Horizontally oscillating cursors were also provided for driving picker and pusher elements to withdraw a blank plate from the hopper and step it along through the track, finally moving an embossed plate into the receiver. These were driven in proper timed relationship by a cable system and electric motors.
The operating sequence of this mechanism called for the horizontally shiftable frame to move the track segment of the inner or vertically moving frame into close register with the fixed track segment at the input end. Then the picker slider would be activated to draw a fresh plate from the hopper stack through the input fixed track segment and to move a waiting plate onto the movable track segment where it would be trapped or latched in place. Thereafter the horizontally movable frame would carry the plate to a central location between the embossing punches and dies where the motions required during the embossing operation would be carried out by the drives for the vertically and horizontally movable frames. Upon completion of embossing, the vertically moving frame would be restored to the datum position and the horizontally moving frame would be shifted by its drive until the movable track segment on the vertically moving frame was in close register with the end of the fixed track segment on the output end, whereupon pusher elements would be activated to move the embossed plate to the fixed track segment and place another waiting card on the face of the stack in the receiving stacker.
The correct positioning of the plate on the movable track section was controlled by an inlet trapping member which normally blocked the track but could be swung aside by the incoming plate as it arrived. The trapping member was hinged to swing about a horizontal axis adjacent the upper rail, and spring pressed to return after the plate had passed. At a location about one plate length from the inlet trapping member was a retention member also positioned to block the track, hinged on a horizontal axis on the upper rail and spring urged both into blocking position and in a direction towards the plate along its hinge axis to serve as a return device to bring the plate back to its initial position after each embossment. This retention device was releasable only when the frame system was moved to release position adjacent the output track, at which time a fixed cam would displace the retention member laterally off the track to allow the pusher to move the plate onto the fixed output track segment. Because of their nature, the trapping means and the retention means would lie within the sweep of the rotary embossing heads if they were to occupy the same plane. Accordingly embossment of a narrow margin along the upper edge of a plate could not have been performed if required for any reason.
The equipment just described has operated very effectively and has given good service in usual embossing situations. Recently, however, applications have arisen in which there has been a requirement for embossing machines which can be made to accept plates of varying sizes and shapes. At the present time these applications relate primarily to automobile manufacture, but other needs for this capability undoubtedly exist. In situations where the need for embossed workpieces represents a rather low volume in comparison with such commonly embossed items as credit cards and the like, and where there are various types, sizes and shapes of plates which must be embossed, it is difficult to justify the cost of a number of highly automated embossers such as would be needed to handle several individual plate configurations. However, it has been determined that if there are a sufficiently large number of machines required at different locations it could be economically feasible to purchase or lease the machines, provided that each machine could be made to accommodate all of the various plate configurations in use by the customer, at least to the degree that a service man or a well trained operator could, with the substitution of a few readily accessible minor parts and some minor adjustment, effect a quick but fully operative conversion of the machine. No such machine has existed heretofore and customers with this particular type of requirement have had to be content with the inconveniences of embossers each designed to handle one particular configuration of workpiece with no possibility of switching from one machine to another for a particular plate configuration without undertaking a substantial rebuilding of the machine.
SUMMARY OF THE INVENTION
In accordance with this invention the conversion of embossing machines to deal with the embossing of cards or plates under circumstances where the workpiece may assume different sizes and shapes, and where the machine may be called upon from time to time to be adapted for use with any one of these sizes and shapes or to new sizes and shapes, has been reduced to a feasible and practical situation without in any way impairing the speed or effectiveness of the embossing process itself, and in a manner which permits embossing access to substantially all areas of the plate surface as is frequently required with specialized plates.
These unusual capabilities have been brought about by several interacting novel aspects of the machine construction including the following:
1. A modified mounting allows the upper track members throughout the workpiece path to be raised or lowered to accommodate the width (i.e. the height) of the plates to be used.
2. A novel hopper and plate receiver construction involving the use of repositionable supports for a fixed guide rail allows accommodation of plates of different lengths in substantially the same hopper or receiver mechanisms without in any way affecting the travel of the picker mechanism.
3. An adjustably positionable cutoff switch for the pusher drive motor provides for accommodating plates of different lengths in substantially the same hopper and receiver mechanisms without requiring any other modification of the pusher construction or plate receiver construction other than adjustment of the guide rail (mentioned in the preceding paragraph) to accommodate such differences in length of plates.
4. Provisions are made for readily adjusting the height of the picker and pusher elements to allow for so positioning them that (1) they can be brought into contact with the plate edge at the optimum point when the plate has an irregular contact edge, and (2) they can be set at an appropriate level for moving the plate through the tracks due to other variable factors (e.g. plate height vs. track contact length).
5. The plate retention means on the inner frame has been disassociated altogether from the upper rail of the trackway to allow ready adjustment of the rail to accommodate plate height. The configuration and mounting of the retention means has been wholly revised so that any portions which must necessarily fall within the sweep of the embossing heads are restructured to have a thickness only slightly greater then the plate being worked upon to thereby allow embossing access to all areas of plates of any configuration or size.
6. Plates of many unusual outlines can be readily handled in the trackway, and their accommodation in the hopper, stacker and throat areas are arranged for in a very simple manner by minimum modification to the plate stacking trays and the provision of overhead guides equipped with adjustable mounting features allowing their precise adjustment to plate configuration requirements, especially with regard to those situations involving plates with reduced lower track contact length.
7. The present invention takes into consideration the problem of embossed plates occasionally failing to stack regularly because of the interaction of the embossed portions, and provides on the trays a pressure equalizing spring means so configured as to act independently at horizontally spaced points on the plate stack. The spring means is also provided with alternate mounting devices which allow the spring to be set at various levels above the tray floor to accomodate plates of different heights or shapes.
8. Because plates may have irregularly shaped edges which would require them to be picked or pushed at locations spaced from a normal location for a rectangular plate, both the picker element and the pusher element are provided with mounting arrangement including elongate slot configurations making it possible to cause the picker and pusher strokes to be offset from the normal location by the required amount.
9. In order to simplify loading and unloading of plates a special retention means is provided to immobilize the tray-driving spring in its extended condition while a plate tray is being connected thereto or disconnected therefrom.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an overall perspective view of an embossing machine in accordance with the present invention with parts of the cover broken away;
FIG. 2 is a perspective to a larger scale of the supply hopper for holding and feeding plates, take substantially on line 2--2 of FIG. 1, with part of the plate stack broken away;
FIG. 3 is a detail section to a still larger scale taken on a vertical plane identified by the line 3--3 of FIG. 2, with a part of the plate stack broken away;
FIG. 4 is an overall perspective similar to FIG. 1 but to a somewhat larger scale and from a different direction, particularly as indicated by the arrows 4--4 in FIG. 1;
FIG. 5 is a detail perspective of the mechanism for guiding and controlling the plate on its path through the machine with particular emphasis on the input and central positioning aspects;
FIG. 6 is a view similar to FIG. 5, except that it is taken from the opposite side of the assembly as indicated by line 6--6 in FIG. 5, the picker mechanism being omitted, and one of the embossing heads included for locational reference.
FIG. 7 is a detail section taken substantially on the line 7--7 of FIG. 6;
FIG. 8 is a diagrammatic perspective to a reduced scale showing the operation of the plate moving elements;
FIG. 9 is an enlarged detail section taken substantially on line 9--9 of FIG. 5;
FIGS. 10 and 11 are reduced diagrammatic perspectives illustrating the drive mechanisms for operating the outer horizontally moving frame and the inner vertically moving frame respectively;
FIG. 12 is a partial detail perspective of the output throat and receiving tray;
FIG. 13 is a detail section taken on a horizontal plane through line 13--13 of FIG. 12;
FIG. 14 is a perspective view in detail of a supply hopper tray;
FIG. 15 is an end elevation of a supply hopper tray especially configured to accommodate an unsual plate configuration;
FIG. 16 is an end elevation of a receiving tray corresponding to the supply hopper tray of FIG. 15;
FIGS. 17A to 17F illustrate face views of few of the various types and sizes of plates which the machine of the present invention can be readily adjusted to accommodate.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The embossing machine of the present invention is shown in FIGS. 1 and 4 and is designated by the numeral 31. The rotary embossing heads are indicated by the reference characters 33 and 35 mounted for rotation in a rigid structural member of frame 37. The embossing heads 33, 35 are of the type in which corresponding punch 33A and die 35A members are radially projected to grasp a workpiece or plate P between them as they constantly rotate, and to emboss the plate P with a progressive rolling action, thereafter releasing the plate P to allow it to be returned to a reference position in readiness for the embossment of another character. These heads 33, 35 and their operation are not described in detail herein, inasmuch as their relationship to the present invention is only incidental, and the details thereof can be found in U.S. Pat. No. 4,091,910, which is hereby incorporated by reference.
The machine is shown as having a control panel 32 and a keyboard 34 for signalling the machine 31 concerning the characters to be embossed. A number of alternate sources can, of course, be used in place of the keyboard 34 shown.
For manipulating the plate P to cause placement of the embossments at required locations, there is provided at a position adjacent the embossing site, i.e. surrounding the quasi nip formed by the rotary embossing heads 33, 35, a frame assembly comprising an outer frame 39 which is mounted for horizontal sliding movement on a rod 41 whose ends are supported on bulkheads 42 and 44, and an inner frame 43 which is vertically movable on vertical rods 45, 45 fixedly connected with the frame 39. These frames 39 and 43 can be more particularly seen in FIGS. 5, 6, 10 and 11.
Running the length of the machine 31 is a trackway 47 which guides plates P from the input end 47I (at the bulkhead 42) to the output end 47O (at the bulkhead 44). This trackway 47 is discontinuous and is made up of several segments. A general designation of 47 is applied to the entire trackway although this does not appear as an independent character on all drawings. The central segment of the trackway 47C consists of upper and lower rails 47 CU and 47 CL mounted on the inner frame 43 for movement therewith, and each rail 47 CU, 47 CL has a shallow groove 41A facing the other rail 47 CU, 47 CL to guide a plate P by its upper and lower edges. The input segment consists of upper and lower rails 47 IU and 47 IL suitably mounted on the machine base 40A in alignment with rails 47 CU and 47 CL, and the output segment is similarly made up of rails 47 OU and 47 OL also mounted in alignment with the segment 47 CU, 47 CL.
The input hopper for introducing plate P into the input track segment 47 IU, 47 IL is illustrated in FIGS. 1, 2, 3, and 4, and is generally designated 49. The bulkhead 42 has a vertical inlet slot (not shown in the drawing because it is coincident with throat 54) which is framed by the throat members 51 and 53 providing between then a throat 54. The member 53 has a bracket configuration which includes as a portion thereof a projecting arm 55 which constitutes an abutment for a supply stack SI of plates P being presented for embossment. The stack SI is carried on a tray 57 which is supported for free movement on rollers 59A and 59B. Between the rollers 59A and 59B is a pair of guide rods 61 which carries a travelling block 63 having an upright pin 65. Suitable spring means 63A (preferably a NEG'ATOR® constant force spring) urges the block 63 in a direction to the right in FIG. 2 along with the tray 57 which is connected to the block 63 by a pierced tap 123 which receives the pin 65. The abovementioned spring 63A thus urges the tray 57, via the block 63, in a manner to cause the stack SI to be compressed between the abutment 55 and a head wall 57A on the tray 57 so that the foremost plate P in the stack SI is firmly held against the abutment 55 in line with the throat 54 as seen in FIG. 3.
To remove a plate P from the stack SI and bring it through the throat 54 and into the input track segment 47I, there is provided a picker element 69 which is slidable in a matching channel 71 formed in the face of the abutment 55.
As seen in FIGS. 5 and 8, the picker element 69 is carried and driven by a slide or cursor 73 which rides along the guide rods 75, 77. Its motion is brought about at the appropriate time by a stepping motor 79 which acts through an endless cable 81 to which the cursor 73 is connected.
Turning now to the output end 47O of the machine 31, the general construction is much like that at the input end 47I but differs in a few details. The rail members 47 OU and 47 OL form the exit segment of the trackway 47, and lead to a vertical outlet slot 83 in the bulkhead 44 (see FIGS. 12 and 13). An exit guide and abutment plate 85 is mounted on the exterior of the bulkhead 44 and is designed to cooperate with a receiving stacker generally indicated at 87. The receiving stacker 87 has not been shown in detail since it is substantially identical with the input hopper 49 except for being of opposite hand. The tray upon which the plates P are stacked is indicated by reference number 257 and guide flange 257D operates in a manner similar to flange 57D on the tray 57.
As seen in FIG. 13 the abutment plate 85 has a sloping section 86 which will guide the lead edge of the plate P against the face of the stack SO of already embossed plates P, it being understood that the direction of embossing is such that the embossed face of each plate P will be upwardly directed as seen in FIG. 13 so that the lead edge encounters no obstructions to its entry between the abutment plate 85 and the plate stack SO.
The pusher which causes the plate P to move onto the receiver tray 257 is indicated by reference character 91 and the abutment plate 85 is appropriately slotted as at 89 to accommodate the tip of the pusher 91.
The pusher 91 is carried and driven by a cursor 93 also slidable on the rods 75, 77 and powered by a reversible motor 95 by way of a cable transmission 97.
Referring to the frame system which is centrally located in the machine 31 and controls motion of the workpiece P during embossing, the horizontal motion of the outer frame 39 is controlled as shown in FIG. 10 by a pair of stepping motors 99 and 101 both acting on the same continuous cable system 103.
Motors 99 and 101 have pulleys 99A and 101A of diameters which differ by a small amount. When motors 99 and 101 are stepped in unison such that their effects are additive, macro movements of the frame 39 are achieved. When the motion of these motors 99, 101 are in opposite directions, such that their efforts are subtractive, small increments of motion of the frame 39 are achieved allowing the precise positioning of the frame 39 required for accurate embossing. By a combination of forward and reverse rotational steps of the two motors 99, 101, rapid frame motion over comparatively large distances is achieved for unloading and loading plates P between embossing operations; also achieved is precise positioning of the frame 39 at a selected location for accurate embossing. FIG. 11 shows the drive arrangement for raising and lowering the vertically moving frame 43, comprising the reversible stepping motor 105 acting through the cable system 107. This system 107 is not continuous and has the cable anchored on the machine frame 109A at points 109 and 111 which points are provided with adjustment means 109B to allow cable tensioning and precise location of frame 43.
As shown in FIGS. 5 to 7 there are associated with the track segment 47 CU, 47 CL certain plate locating mechanisms. The first is a plate locating abutment 113 which is so mounted as to lie across the track 47 in such a manner that an incoming plate P arriving from the left in FIG. 5 must displace it in order to move further along the track 47. Once the plate P has gone beyond this locating abutment 113, the latter is returned to original position and, when the picker 69 withdraws, the plate's trailing edge is kept from retreating along the track 47 by the restored position of the abutment 113. Retention means, including the mechanism generally indicated at 115 is provided to locate the plate P against the abutment 113 and restore it to this reference position following the embossing of each character (which involves a short transit along the track 47 away from the abutment 113 while the plate P is in the grip of the rotating embossing heads 33, 35).
An overall view of the operation can be had by reference to FIG. 8 which illustrates the procedure diagrammatically. At the left hand end, the plates P in the hopper 49 gradually inch forward towards the picker 69 as indicated by arrow A. When a plate P reaches the abutment 55 (position P1), the next time a plate P is called for, the frame 39 is moved to its leftmost position by the motors 99, 101 and cable system 103, and the frame 43 is positioned by its drive system (stepper motor 105 and cable system 107) to align its track segment 47 CU, 47 CL with the input track segment 47 IU, 47 IL. Then the picker 69, engaging the trailing edge PTE of the plate P, moves the same in the direction of arrow B through the entry throat 54, into and through the track segment 47 IU, 47 IL, and finally into the track segment 47 CU, 47 CL where it bypasses the positioning abutment 113 and is settled in position P2 by the plate retention means 115 (FIG. 5). The picker 69 is then retracted to engage the next plate P. The motors 99, 101 and cable system 103 then return the frame 39 to a generally central position and take over the control of plate position, along with motor 105 and cable system 107, to determine character location and line spacing during the embossing operation.
When embossing is complete the motors 99, 101 and cable system 103, together with motor 105 and cable system 107, move the frame 39 to the dotted line position in FIG. 8. The plate P then occupies the position P3 and the track segment 47 CU, 47 CL is in proximity to and aligned with the output track segment 47 OU, 47 OL. At this point the pusher 91 is retracted to its leftmost position shown in broken lines in FIG. 8 where it picks up the trailing edge PTE of the plate P, and the motor 95, through cable system 97 extends the pusher 91 to move the plate P through the track segment 47 OU, 47 OL until the plate P reaches the P4 position in the receiving stacker 87, from which point it gradually recedes in the stacker 87 in the direction of the arrow C as plates P are added to the stack SO.
As stated above, the present invention is adapted to feed and process work pieces P of a wide variety of shapes and sizes and is capable of embossing upon virtually any selected area or areas of such workpieces. FIGS. 17A through 17F, which are all drawn to the same scale, illustrate a group of plates PA, PB, PC, PD, PE, PF which are currently being embossed by a machine 31 in accordance with this invention, and give a clear indication of the variety which the machine 31 can be adjusted to accept.
The features of the machine 31 which bear on providing this flexibility will appear in detail in the following discussion.
First, referring to the input hopper 49, the general organization appears in FIG. 2, and the tray 57 is shown in more detail in FIG. 14. The tray 57 is of very simple construction being basically a metal plate bent to form a head wall 57A, a floor or horizontal workpiece support 57B, an upwardly turned stop flange 57C and a downwardly turned guide flange 57D. Attached to the exterior of the headwall 57A is a U-shaped bracket 121, the lower arm or tab 123 of which is pierced and functions as previously described and as shown in FIG. 2 herein. The upper arm 125 is provided with a slot 127 whose purpose will presently appear. The support portion 57B has an elongate slot 129 running substantially its full length which provides for a settable plate clamp assembly 131 which may be used to control the plates P when the tray 57 is removed from the machine 31.
The plate clamp assembly 131 comprises a sheet of resilient metal formed into a shallow channel as seen at 133. A shaft 135 is bent at its lower end to provide a laterally extending finger 137, and has a transverse handle 139 affixed to its upper end. The handle 139 lies in contact with the upper flange of the channel 133 (except perhaps for friction reducing spacers 138) and the finger 137 is normally closely adjacent the lower flange 133A of the channel 133. A down-turned tab 141 formed from the lower flange 133A of the channel 133 rides in the slot 129 to maintain proper orientation of the channel 133 perpendicular to the slot 129. The plate clamp assembly 131 can be put into place by turning the handle 139 to orient the finger 137 parallel to the slot 129 and introducing it into the slot 129. With slight pressure the channel 133 can be deformed sufficiently to allow the finger 137 to then be turned crosswise of the slot 129. The clamp assembly 131 will then be strongly frictionally retained at the desired location to hold the plate stack SI in order. The clamp assembly 131 can be removed by turning the handle 139 until finger 137 aligns with the slot 129. Similar manipulations permit the clamp assembly 131 to be stored in the slot 127 in arm 125 when not in use.
Inasmuch as embossed plates P do not always form stacks SO which are altogether regular, perhaps because of a tendency of embossures to partially nest under certain conditions, a pressure equalizing leaf spring 143 is mounted on the head wall 57A and is so arranged that it acts independently on opposite ends of the plates P in the stack SI thereby keeping a substantially equal pressure across the plate P which is located in the abutment 55 contacting position at the throat 54 end of the stack SI. Alternate mounting means 143A are provided so that the spring 143 can be positioned at various levels above the floor 57B of the tray 57 to accommodate plates P of different heights and/or configurations.
Referring now to FIG. 2, the tray 57 is constructed in the fashion shown so that the flange 57C will provide a stop against which the plates P can be registered. The purpose of the guide flange 57D is to enter grooves 59X which are formed in the rollers 59A (i.e. the row or rollers adjacent the bulkhead 42). This provides a precise track which the tray 57 will follow.
Mounted on the bulkhead 42 by posts 147 is a guide rail 145 which, although mounted in a stationary manner on the machine 31, serves in the manner of a side flange for the tray 57. It is so positioned that when the guide flange 57D is in the roller grooves 59X, and the plates P are against the flange 57C, there is a slight clearance between the inner ends of the plates P and the rail 145. Thus as the stack SI of plates P progresses towards the input throat 54, the plates P are held accurately positioned to meet the picker 69 at the correct spot and be properly fed.
The construction just described allows plates P of varying length to be readily accommodated by merely substituting shorter support posts 147 for the rail 145 if the plate P is longer, or longer posts 147 if the plate P is shorter. The trailing edge PTE of each plate P (i.e. the edge upon which the picker 69 will act) thus remains in the same plane regardless of the length of the plate P being processed.
As previously indicated, the construction of the receiving stacker 87 is in most respects the same as that of the input hopper 49 except that the parts are of opposite hand, the upturned flange 257C being on the left side of the tray 257 and the downturned guide flange 257D on the right side when facing the head wall 257A from the tray exterior. In other words, their placement relative to the bulkhead 44, as seen in FIG. 12, is the same as for the input hopper 49. It should also be noted that the pusher 91 is acting upon the innermost end PTE of the plate P instead of the outermost end. The device of the invention also provides for using support posts 151 of various lengths to locate the guide rail 149 in a manner to accommodate varying plate lengths. This results in a slightly different operating situation inasmuch as the pusher 91 is acting upon the centrally directed end of the plate P rather than the outwardly directed end. To answer this situation, there is provided in the stepping motor 95 a cutoff switch 153, shown in FIG. 4. This switch 153 is so located that, when activated by the outwardly travelling pusher cursor 93 it de-energizes the motor 95 and terminates pusher travel in the outgoing direction, but does not interfere with energization for reverse motion. As seen in FIG. 4 the switch 153 mounting includes an elongate slot 154 so that the switch 153 can be positioned to terminate travel at a point precisely suited to bring a plate P of any particular length to rest just slightly short of contact with flange 257C of the tray 257.
Turning now particularly to FIGS. 4 through 8, the arrangements for handling, within the track 47, plates P of different heights and varying lengths will be described. In the first place, all three of the upper rails 47 IU, 47 CU, 47 OU of the trackway 47 are shown as having adjustable mountings. Rail section 47 IU is supported on upright brackets 155, 155 by posts 157 which can be clamped at the desired height in slots 159 provided in the brackets 155. Similarly rail section 47 OU has brackets 161, 161 with bracket slots 163 and adjustably positionable posts 165. In the case of rail section 47 CU, the rail is supported directly upon the inner vertically movable frame 43 which itself provides slots 167 allowing the rail section 47 CU to be clamped in a position suited to the height of the plate P. It is a simple adjustment to raise or lower the upper rail 47 IU, 47 CU, 47 OU in each case since the plate positioning devices that were positioned adjacent to the upper rail 47 CU of the inner frame 43 (in certain prior art devices such as the Model E300 embosser mentioned hereinbefore) are no longer positioned adjacent to the upper rail 47 CU.
To provide for plate P positioning, the plate locating abutment 113 is constructed in the form of a thin leaf spring mounted on a vertical structural element of the frame 43 with the slight swinging motion of its tip being in a horizontal direction. The mounting means is seen at 169 in FIG. 5. At its distal end a depending tab 171 fits a notch 173 (FIG. 6) which provides a stop normally aligning the edge of the abutment 113 precisely with the groove 41A of the track 47 so that, even though very thin, it will be an accurate and effective back stop for plates P moving in the track 47. In FIG. 9, which illustrates the operation, it will be noted that the entering plate P (under the control of picker 69), guided by the track rails 47 CU, 47 CL, cams the abutment 113 to one side to the broken line position until the plate P reaches the position marked P2, at which point the abutment 113 springs back to block the track 47 against reverse plate movement. This return movement of the abutment 113 is allowed immediately because a notch 172 is provided in the abutment 113 to accommodate the picker 69 until it can be withdrawn. The notch 172 also serves to permit access of the pusher 91 to the trailing edge PTE of the plate P after embossing is completed and the plate P is to be ejected.
As previously mentioned, a novel retention means holds the plate P against the abutment 113 and this comprises a spring pressed traveller 115 shown in the enlarged cross section of FIG. 7. A shaft 174 carries rollers 175 which travel in an elongate slot 177 in the lower rail member 47 CL. A tension spring 179 of substantial length is attached at one end to the shaft 174 and anchored at its other end to the end of the frame 43 from which the plates P approach. The spring 179 is made of maximum length permitted by the geometry of the system to permit substantial extension without unduly changing the force it applies to the shaft 174.
The plate-contacting portion of the retention means or spring pressed traveler 115 is a finger 181 which has a bell crank configuration, is pivotally mounted on the shaft 174, carries guiding rollers 183 which also ride in slot 177, and an upper extremity 181A spanning the track 47 so as to lie in contact with the plate leading edge PLE. As can be seen in FIG. 7, the roller pairs 175 and 183 straddle a central ridge with the slot 177 to keep the assembly centered with the plate track 47.
The function of the spring 179 is to cause the finger 181 to hold the plate P firmly against the abutment 113 for registration, and then to allow a slight excursion of the plate P while it is under the influence of the punch 33A and die 35A members during embossing by the rotary embossing heads 33, 35. The travel of the finger 181 permitted by the spring 179 also accommodates plates P of varying lengths.
Another feature of the finger 181, which is bifurcated and straddles the track member 47 CL to balance the loading, is that the upper tip portion is guided along a reduced section 185 of the track member 47 CL so that the tip 181A of the finger 181 can be extremely thin in the portion which lies in front of or just below the plate edge PLE. Due to this construction, coupled with the removal of plate positioning features from the upper rail area, there is no longer any chance for interference of the rail 47 CU with the approaching and receding die 35A members of the large diameter rotating embossing heads 35, and plates P can be embossed at any point including their upper and lower margins.
Bosses 187, 187 extend from the track 47 at an appropriate location and serve as stops to prevent unnecessary travel of the finger 181 in a direction towards the locating abutment 113 when a plate P is absent.
Mounted on the lower portion of the rail 47 CL is a sensor 189 which is used as a part of a circuit to detect whether or not a plate P was fed into the embossing position when called for. The sensor 189 is designed to cooperate with a flag 191 depending from one side of the finger 181 which can be positioned to affect the sensor 189. The sensor 189 is so placed that it will be activated by the flag 191 to generate a signal when a plate P is fed, but the flag 191 will not affect the sensor 189 if the finger 181 remains against the boss 187 at the time the plate P is called for. As can be seen in FIGS. 5 and 6, the lower track element 47 CL has an elongate slot 193 which allows the sensor 189 to be clamped in any desired location therealong by the bolt 195. In this manner a sensor location can be selected which gives the proper signal in relation to plates P of different lengths.
As can be seen from FIGS. 5 and 6, there are provided relief notches 197 and 199 near the output end of the lower track member 47 CL. These permit the plate P to escape from the retention means 115 when the pusher 91 is transferring it to the output track segment 47 OU, 47 OL. As the pusher 91 moves the plate P forward, the spring 179 is extended until roller 183 encounters the relief notch 197 of slot 177. As it drops into this relief notch 197, the finger 181 is allowed to pivot about shaft 174 so that the tip 181A of the finger 181 recedes into its relief notch 199 until it lies flush with the track 47 CL and the plate P overruns it, whereupon the spring 179 causes the finger 181 to emerge from the relief notch 199, erect itself, and return to ready position against the bosses 187.
Other features which provide accurate control for plates P of varying sizes and shapes are as follows.
Depending upon the height and/or shape of the plate P, the picker 69 and pusher 91 may need to be at various levels. To this end, the cursors 73 and 93 are fitted with means providing one or more alternate sets of openings 201 (FIGS. 4 and 5) to allow this change in level to be readily effected. When the picker 69 and pusher 91 levels are changed, then it will be necessary to provide a compensating adjustment at the plate locating abutment 113 which can have alternate mounting holes 169A to change its level, or preferably alternate plates notched at different levels, or, if many positions are required, combinations of both approaches may be used. As can be seen in FIGS. 17A to 17F plates PE having the shape shown in FIG. 17E, and preferable also the plate PB having the shape shown in FIG. 17B, require picking and pushing at a low level, and the plate PF shown in FIG. 17F would be picked and pushed at a higher level, and the plate PA shown in FIG. 17A practically requires such higher level picking and pushing.
FIG. 17A represents one form of plate PA exemplary of the unusual shapes which can be accommodated by the machine 31 of the present invention, and it will be noted that the plate PA has a very short bottom edge PABE and irregular end edge PAEE. In this particular case the requirement is to emboss the plate PA in such a fashion that the picker 69 and pusher 91 will be in contact with the right edge PAEE as seen in FIG. 17A.
The embossing portion of the operation on the plate PA of FIG. 17A is handled very successfully by the machine 31 as thus far described. After the upper track rails 47 IU, 47 CU, 47 OU are set for the proper height, the pusher 91 and picker 69 are adjusted to a higher position than normal to catch the vertical portion of the edge PAEE, and the finger 181 of the plate retention means 115 seats effectively against the sloping edge e beneath the plate overhang o. In order to supply and stack plates PA of this character, there are certain features required at the hopper 49 and receiver 87. As seen in FIG. 15, the supply tray 57 for the hopper 49 has added to it a side wall 203 and head restraining shelf 205 overlying the end of the plate PA which is full height, thus holding the stack SI against tilting while the tray 57 is being handled and while the plates PA are approaching the feed throat 54 during feeding. At the feed throat position, an overhead guide 207 is provided (see FIG. 2) and this is so mounted that posts 209 of varying lengths can be substituted to match plates P of various heights. The effect of this guide 207 is to hold the plates PA of FIG. 17A against cocking or tilting after they leave the tray 57 and while they are being inserted into the input track segment 47 IU, 47 IL.
As the plate P issues from the output track segment 47 OU, 47 OL under the influence of the pusher 91 it will enter a special stacker tray 257' configured like that shown in FIG. 16 which is the same as the standard stacker tray 257 except for having lengthwise of the tray 257', a ledge 211 of a height to underlie the overhanging end o of the plate PA and keep it from tilting as it departs from the track 47 and enters the tray 257'. To take care of guiding the plate P during the transition, there is also provided on the abutment 85 (see FIG. 12) an overhead guide 213 which, by way of the slot 215 and clamping bolt 217B, can be adjusted as to height to match the plates P being fed.
Another important aspect in which the machine 31 is adjustable to meet the requirements of plates of various shapes may be understood by referring to the plates PA, PB shown in FIGS. 17A and 17B. It will be noted that in each case the plate's trailing edge (for example the right hand edge PAEE in FIG. 17A) is not straight but includes a portion which does not coincide with (i.e., does not lie in line with) a normal to the base edge at PABE at its trailing end. If we assume that conditions require that the plate PA, PB be picked and/or pushed at a level higher than the base margin PABM, then we find a situation wherein the base margin PABM of the plate PA will be positioned against (in contact with) the flange 57C of the hopper tray 57, but the picking location will be substantially displaced inwardly from this contact point. While the plate PA will be accurately picked even though the picker 69 would overrun the picking edge PAEE somewhat, a problem would arise since the effective throw of the picker 69 (after encountering the plate edge PAEE) would be insufficient to allow the base margin PABM of the plate PA to clear the plate locating abutment 113, even at full travel. This problem is readily solved by the present invention by merely adjusting the picker mounting so that the range of travel of the picker 69 is displaced inwardly enough to cause the picker tip (at its outward extreme) to just pass the trailing edge of the plate PA. This causes the picker stroke to be such that the picker tip travels inwardly farther than normal (i.e., farther than the stopping point ordinarily associated with rectangular plates P) by the same amount that it was short when picking, thus allowing the projecting base margin PABM of the plate PA to clear the plate locating abutment 113 at the inner limit of travel.
Such an adjustment can be effected easily by reason of the elongate slots 201 on the picker cursor 73 which allow the picker 69 to be clamped in any of various longitudal positions to meet the shape requirement of a particular plate P.
Similar longitudal adjustment of the pusher 91 caan be used to accommodate the out-feeding operation when handling plates PA with the same edge offset characteristics as that of the picked plate PA, using the elongate slots 201 on the pusher cursor 93.
In handling the trays 57 and 257 to load the machine with blank plates P and unload embossed plates P from the machine 31, there is provided a feature which greatly facilitates these loading and unloading operations. This feature takes the form a leaf spring friction retainer 217 mounted on terminal element 217A for each of the traveling blocks 63 in the input hopper 49 and receiving stacker 87. One of the retainers 217 is seen in FIG. 2 and is so arranged that when a tray 57 is to be removed, the tray 57 is merely pushed to the fully extended position in opposition to the aforementioned spring 63A (which normally urges the block 63 towards the abutment 55 or 85). In this event, the retainer 217 engages a pin 219 extending downwardly from the block 63 with sufficient grip to oppose the force of the spring 63A which drives the block 63 and thereby prevents the block's return so that the tray 57 can merely be lifted off. To attach a replacement tray 57, the opening in the arm 123 is placed over the pin 65 and the flange 57D (or 257D) is dropped into the grooved rollers 59X. A slight manual movement of the tray 57 in the direction of the spring action releases the pin 219 from the retainer 217, and the block 63, under the control of the spring 63, again urges the tray 57 towards the corresponding abutment 55. | A machine for embossing cards or plates is provided with features which give it the capability of handling and feeding a wide variety of plate sizes both in length and height, and also make it possible to effectively process pieces which are of many unusual non-rectangular shapes. A trackway made up of several segments is arranged to have a rail of each segment readily adjustable towards and away from the other rail. Special hopper and receiver equipment is made available which can accept plates of different lengths by merely adjusting fixed side rails which cooperate with trays which are substantially standardized for the novel system. The plate holding means at the embossing station is so constructed that it can effect its retention function without inhibiting embossment on the margins or other portions of the plate regardless of its unusual size or shape limitations. Slightly modified alternate tray constructions are provided for easily accommodating, feeding and storing plates of more unusual outline. As a result a machine may be quickly modified, by simple and inexpensive adjustment or very modest part replacement, to handle any of a wide variety of workpiece configurations. | 1 |
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of Provisional U.S. Patent Application Ser. No. 60/760,406 filed Jan. 20, 2006.
FIELD OF THE INVENTION
[0002] The present invention relates to connectors for connecting optical fibers to receptacles therefor and other related equipment.
BACKGROUND OF THE INVENTION
[0003] Existing connectors for optical fibers suffer from several limitations that reduce their effectiveness for precision capture and transfer of light in optical delivery systems, particularly high power laser systems. Fundamental to any such system is the ability to precisely position the fiber at the focus of a laser beam in free space (X, Y and Z planes.).
[0004] Prior Art FIG. 1 defines the initial application of focusing light into a fiber. A focusing objective lens 100 focuses the light from a laser to a spot 102 closely matching the diameter of the core 104 of fiber 106 . This can be as small as 2 to 3 microns in diameter. The fiber then has to be positioned so the end face of the core is at the precise location of the focused spot.
[0005] Conventional methods use bulky XYZ translation stages to position the fiber and/or the lens in free space to align the fiber core with respect to the focused spot. Such stages are expensive, and are not applicable to systems where the fiber must be aligned, and semi-permanently attached.
[0006] Other methods have been employed where either the fiber is permanently attached to a lens or it is positioned at a fixed distance Z relative to the lens. The fiber/lens assembly is then manipulated and fixed relative to the laser beam in the remaining 5 planes (X, Y, pitch, yaw and roll). U.S. Pat. Nos. 4,753,510 and 4,889,406 of Omur M. Sezerman disclose a tilt-adjustable connector that can be used for such manipulation. The positioning of the fiber in the Z-plane is normally done by terminating the fiber in a conventional fiber connector (see Prior Art FIG. 2 ). The connector 108 is plugged into a receptacle 110 where it makes contact with a stop 112 . The connector ferrule 114 and sleeve 116 are manufactured to a high degree of precision, restricting the fiber in the X-Y plane. The lens 118 is precisely positioned with respect to the receptacle 110 so that the tip of the fiber is positioned at the focal plane of the lens. Assuming that the laser beam entering the lens is perfectly collimated (ie: the laser beam waist location is well within the Rayleigh distance Z R from the focusing lens), then the focused spot will be at the same distance Z from the lens as the fiber, and only adjustments in the remaining 5 planes are necessary.
[0007] Note the existence of a key 120 on the connector 108 and keyway 122 on the receptacle 110 . This feature allows one to maintain the angular orientation of the fiber (i.e: to control roll). This is necessary for certain applications, such as working with polarization maintaining fibers or with fibers with angled end faces.
[0008] The limitation of this technique is that if the laser beam is not well collimated the focused spot will not lie at the focal plane of the lens, and thus it will not lie at the tip of the fiber. Therefore for improved alignment, one needs a way to precisely adjust the distance between the fiber and lens during alignment, preferably without affecting the location of the fiber in the other five axes (X, Y, pitch, yaw, and roll).
[0009] One approach to adjust the distance is to move the lens. This suffers from two drawbacks. First the lens is between the fiber and the laser, and is often thus inaccessible. The other is that moving the lens along the Z axis usually causes unwanted motion (play) in the other planes, particularly X and Y.
[0010] Another idea is to simply mount the fiber in a threaded tube, and screw the fiber into a mating threaded receptacle. This has the drawback of being unable to control the roll of the fiber, making it unusable for polarization maintaining fiber applications.
[0011] Another issue that one wants to avoid is accidentally extending a fiber too close to a lens or other surface, possibly jamming and damaging the tip of the fiber.
[0012] An alternative to the previously described connecting systems involves the use of a compression spring within the connection device mounting the optical fiber. U.S. Pat. Nos. RE38,205E (being a reissue of U.S. Pat. No. 5,734,778) and 6,250,818 teach connectors that incorporate at least one compression spring that aids in achieving a degree of adjustment of the fiber relative to the receptacle in which it is to be received. However, in these patents the spring action is not such as to permit any compressive movement after the connector Z-position is located. This leaves open the possibility of jamming and damage to the ferrule tip should it be mated to conventional connectors or receptacles, which rely on some compressive spring action being present when mating.
SUMMARY OF THE INVENTION
[0013] The present invention provides an alternative means for adjusting the position of the fiber along the Z-axis, while enjoying the following features:
[0014] 1) The X-Y precision achieved in conventional connector methods;
[0015] 2) An optional keyway to control roll;
[0016] 3) A spring-loaded mechanism to prevent accidental jamming of the fiber;
[0017] 4) Additional features to allow access to the fiber for surface finishing;
[0018] 5) Compatibility with existing connector designs.
[0019] The present invention is available in two possible configurations: one that is compatible with an existing FC connector body standard, and another that is compatible with an existing SMA 905 connector body standard. Other designs can be constructed on similar principles.
[0020] The connector of the present invention is very useful in achieving efficient coupling with a laser to fiber coupling system such as that discussed above with reference to U.S. Pat. Nos. 4,753,510 and 4,889,406, permitting for precise adjustment of the focus. It is also very useful in fiber-to-fiber coupling systems using two collimators facing each other. As long as at least one side utilizes the connector of the present invention it is possible to achieve precise positioning in X, Y and Z planes as well as with respect to pitch and yaw, optimizing coupling and minimizing losses. The possibility of avoiding contact between fiber ends also permits the coupler to be used in high power situations where contact between fiber ends can lead to damage of the fibers. In straight fiber-to-fiber coupling systems the spring loading achievable with the invention allows the ferrule ends to mate without damage, while the adjustment feature of the invention allows for the deliberate introduction of a gap between the fiber ends, such that the coupler can function as an attenuator.
[0021] Generally speaking, the present invention may be considered as providing in one embodiment an adjustable focus connector which comprises: a ferrule holder for retaining at a distal end thereof a ferrule mounting an optical fiber therein; a lead screw member threadedly connected to the ferrule holder at a proximal end of the ferrule holder; a thrust collar surrounding the ferrule holder, the thrust collar and the ferrule holder defining a generally annular cavity therebetween; a traveler member theadedly receiving therein the lead screw member and abutting an adjacent end face of a proximal end wall of the thrust collar; a key frame secured to the thrust collar and extending away therefrom to surround the distal end of the ferrule holder; a compression spring retained within the cavity; and a coupling nut surrounding the key frame and retained thereon for connecting said connector to an FC receptacle devoid of any stop member therein.
[0022] The present invention provides in another embodiment an adjustable focus connector which comprises: a ferrule holder for retaining at a distal end thereof a ferrule mounting an optical fiber therein; a lead screw member threadedly connected to the ferrule holder at a proximal end of the ferrule holder; a thrust collar surrounding the ferrule holder, the thrust collar and the ferrule holder defining a generally annular cavity therebetween; a traveler member theadedly receiving therein the lead screw member and abutting an adjacent end face of a proximal end wall of the thrust collar; a compression spring retained within the cavity; and a coupling nut surrounding the ferrule holder for connecting the connector to an SMA receptacle devoid of any stop member therein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 illustrates a prior art arrangement for focusing light into an optical fiber.
[0024] FIG. 2 illustrates another prior art arrangement for connecting an optical fiber to a receptacle.
[0025] FIG. 3 illustrates a connector according to the present invention for use with an FC type of fiber optic connector.
[0026] FIG. 4 is a cross-sectional view taken on the line 4 - 4 of FIG. 3 .
[0027] FIG. 5 is an enlarged view of the distal end of the ferrule used in the embodiment of FIG. 3 .
[0028] FIG. 6 is a perspective view showing the components of the connector of FIG. 3 .
[0029] FIG. 7 illustrates a connector according to the present invention for use with an SMA type of fiber optic connector.
[0030] FIG. 8 is a cross-sectional view taken on the line 8 - 8 of FIG. 7 .
[0031] FIG. 9 is a perspective view showing the components of the connector of FIG. 7 .
[0032] FIG. 10 illustrates a laser-to-fiber coupler system designed for use with an adjustable focus connector of the present invention.
[0033] FIG. 11 illustrates a fiber-to-fiber coupler system designed for use with an adjustable focus connector of the present invention.
[0034] FIG. 12 illustrates a fiber having an end cap thereon with which an adjustable focus connector of the present invention is particularly useful.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0000] FC Type Fiber Optic Connector
[0035] FIGS. 3 to 6 illustrate an adjustable fiber optic connector 10 according to the present invention especially adapted for use with an FC type of connector or receptacle.
[0036] A ferrule holder 12 presents a counterbore in a distal end section thereof (right hand side in FIG. 4 ) for the mounting of any type of FC ferrule 14 . The ferrule (high power version shown) may be of any type suitable to the end user's purpose.
[0037] The high power ferrule concept is presented here as it is often seen in use with adjustable focus connector. Note that the fiber 16 is suspended in free space with a protective ring around it to prevent accidental damage to the exposed fiber. This design has two features that are advantageous. With reference to FIG. 5 it is first of all seen that the fiber tip is recessed by a distance x, only a few microns, preventing any damage to the fiber should the tip come in contact with a flat surface. The second is the presence of a notch 18 in the ring. This notch permits side inspection of the fiber, and possible access to the fiber for processes like cleaning, or surface treatment of the fiber.
[0038] The proximal end of the ferrule holder 12 (left hand side in FIG. 4 ) presents a threaded section 20 so it may be threaded into and glued permanently to the lead screw 22 .
[0039] The outside surfaces of the distal section of ferrule holder 12 define a polygonal cross-section, preferably a square section 24 ( FIG. 6 ), which passes through a mating hole in the key frame 26 .
[0040] A thrust collar 28 surrounds the ferrule holder 12 , the thrust collar having a bottom end wall 30 and, with the outer surface of the ferrule holder 12 , defining a generally annular cavity 32 . A radially outwardly directed flange 34 intermediate the length of the ferrule holder 12 is located adjacent the distal end of the cavity 32 .
[0041] A compression spring 36 is trapped in the generally annular cavity 32 defined between the bottom end wall 30 of the thrust collar 28 . This spring serves to continuously provide force on the ferrule holder/lead screw combination, acting toward the right in FIG. 4 .
[0042] A traveler member 38 , which is basically a nut with an internal thread of fine pitch (80 t.p.i.), is engaged with an external thread on the lead screw 22 . It makes contact with the external (left hand side) surface of the thrust collar bottom end wall 30 .
[0043] A spring guard 40 fits over the traveler 38 and is threaded and permanently affixed onto the thrust collar 28 .
[0044] The key frame 26 and the thrust collar 28 are glued together, confining the compression spring 34 and ferrule holder 12 inside, and confining an installation or coupling nut 42 outside.
[0045] A setscrew 44 is provided for threaded engagement with a threaded bore 46 in the traveler 38 to lock the traveler 38 and lead screw 22 together when required.
[0046] A crimp sleeve 48 is for cable jacket attachment, and is not considered part of this device.
[0000] Operation:
[0047] This male FC connector 10 is installed in the matching female receptacle by inserting the ferrule 14 into the receptacle “hole”, and engaging and tightening the installation nut 42 onto the external thread present on the receptacle. The “hole” in the receptacle, manufactured to suitable tolerances, is a close match to the diameter of the ferrule 14 , and is depended upon to prevent lateral movement of the ferrule 14 . This action is similar to all available FC connector/receptacle matchings. A key required difference is that there must not be any stop inside the receptacle. The existence of a stop would prevent forward motion of the ferrule.
[0048] With conventional fixed-length ferrule designs, no further actions to facilitate axial (in-out) movement of the ferrule are available to the user. Since the end plane of the fiber is at the outside end of the ferrule, the position of the fiber's end is fixed. The optical coupling obtained between the fiber end and the intended optical mate (lens, other fiber end, etc.) inside the receptacle depends on the manufacturing control of the ferrule length. Also, no ability to influence the accuracy of placement of the optical mate within the receptacle is available to the user of the connector, and this positioning also affects coupling efficiency.
[0049] In order to effect user control of coupling efficiency, the connector in question is able to vary the projection of the ferrule as follows:
[0050] Before installation of the connector into the receptacle, the user rotates the traveler 38 clockwise, which, by virtue of it's thrust upon the thrust collar 28 , will cause the lead screw 22 , ferrule holder 12 , ferrule 14 , and fiber end to move as a unit to the left, compressing the spring 36 . The moving items will not rotate, because of the action of the square section of the ferrule holder in the square hole in the key frame 26 . The spring 36 will eventually reach the limit of it's compression (go “solid”). This condition represents the minimum ferrule projection (fully retracted).
[0051] The connector 10 is installed to the receptacle in the conventional manner as described at the beginning of this section.
[0052] The traveler 38 is then rotated counterclockwise by the user, causing the ferrule and other associated parts to move to the right. Thus, by turning the traveler one way or the other, the user can make the ferrule move in and out, i.e. change its projection. By conducting light through the system from receptacle to connector during the adjustment, the user can measure coupling efficiency with an optical power meter, and stop the adjustment when the best coupling is achieved.
[0053] Should the user cause a collision to occur between the ferrule end and the optical mate inside the receptacle, the force transmitted by the collision is limited by the compressibility of the spring 36 , preventing damage. Also, in the case of a collision, the user will be notified by an abrupt decrease in the turning force required, since the traveler 38 will no longer be contacting the thrust collar 28 . In certain cases, causing a collision is actually desirable, since this is the position at which best coupling efficiency is obtained.
[0054] The connector can be locked against further adjustment by tightening the setscrew 44 installed in the traveler 38 , locking it against the lead screw 22 .
[0055] When this adjustment procedure has been completed, further adjustment is not possible without loosening the setscrew. Accidental adjustment is not possible.
[0056] Although the ferrule projection has been set and locked, a further safety factor exists in the form of residual spring action availability. If the connector were to be carelessly installed into any new situation whereby the existing ferrule projection was too great, and a collision with the optical mate was assured, the spring 36 can still limit the collision force, because of the ability of the traveler 38 to lift clear of the thrust collar 28 .
[0057] The subject connector thus allows for adjustable ferrule length and hence the ability to maximize optical coupling, and it retains the inherent safety feature of spring “cushioning” regardless of the length to which it has been adjusted.
[0000] SMA Style Fibre Optic Connector
[0058] Referring now to FIGS. 7 to 9 a connector 50 especially adapted to work with an SMA type of connector is illustrated
[0059] A ferrule holder 52 presents a counterbore at a distal end thereof (right hand side in FIG. 8 ) for the mounting of any type of SMA ferrule 54 . The ferrule (high power version shown) may be of any type suitable to the end user's purpose.
[0060] At the proximal end of the ferrule holder 52 there is a threaded section 56 so that it may be threaded into and glued permanently to a lead screw 58 .
[0061] A longitudinally extending intermediate section 60 of the ferrule holder 52 presents a polygonal cross-section, preferably a square section, which passes through a mating polygonal hole in a proximal end wall 62 of a thrust collar 64 that generally surrounds the ferrule holder 52 . The intermediate section 60 of the ferrule holder 52 and the surrounding thrust collar 64 define therebetween a generally annular cavity 66 .
[0062] A compression spring 68 is trapped in the cavity 66 between the inner surface or shoulder of the proximal end wall 62 of the thrust collar 64 and a radially outwardly directed flange 70 intermediate the length of the ferrule holder 52 and located generally towards the distal end of the cavity 66 . This spring serves to continuously provide force on the ferrule holder/lead screw combination, acting toward the right in FIG. 8 .
[0063] A traveler 72 , which is basically a nut with an internal thread of fine pitch (80 t.p.i.), is engaged with an external thread on the lead screw 58 . It makes contact with the external (left hand side) surface proximal end wall 62 of the thrust collar 64 .
[0064] A spring guard 74 fits over the traveler 70 and is threaded and permanently affixed onto the thrust collar 64 .
[0065] A nut retainer 76 and stop frame 78 are glued together as at 86 and are glued to the thrust collar 64 , and serve to hold captive the coupling or installation nut 80 .
[0066] A setscrew 82 is provided for threaded engagement with a threaded bore 84 in the traveler 72 to lock the traveler and lead screw together when required.
[0000] Operation:
[0067] This male SMA connector is installed in the matching female receptacle by inserting the ferrule 54 into the receptacle “hole”, and engaging and tightening the installation nut 80 onto the external thread present on the receptacle. The “hole” in the receptacle, machined to suitable tolerances, is a close match to the diameter of the ferrule, and is depended upon to prevent lateral movement of the ferrule. This action is similar to all available SMA connector/receptacle matchings. A key required difference is that there must not be any stop inside the receptacle. The existence of a stop would prevent forward motion of the ferrule.
[0068] With conventional fixed-length ferrule designs, no further actions to facilitate axial (in-out) movement of the ferrule are available to the user. Since the end plane of the fiber 88 is at the outside end of the ferrule, the position of the fiber's end is fixed. The optical coupling obtained between the fiber end and the intended optical mate (lens, other fiber end, etc.) inside the receptacle depends on the manufacturing control of the ferrule length. Also, no ability to influence the accuracy of placement of the optical mate within the receptacle is available to the user of the connector, and this positioning also affects coupling efficiency.
[0069] In order to effect user control of coupling efficiency, the connector in question is able to vary the projection of the ferrule as follows:
[0070] Before installation of the connector into the receptacle, the user rotates the traveler 72 clockwise, which, by virtue of its thrust upon the thrust collar 64 , will cause the lead screw 58 , ferrule holder 52 , ferrule 54 , and fiber end to move as a unit to the left, compressing the spring 68 . The moving items will not rotate, because of the action of the square section 60 of the ferrule holder 52 in the square hole in the proximal end wall 62 of the thrust collar 64 . The spring 68 will eventually reach the limit of its compression (go “solid”). This condition represents the minimum ferrule projection (fully retracted).
[0071] The connector is installed to the receptacle in the conventional manner as described at the beginning of this section.
[0072] The traveler 72 is then rotated counterclockwise by the user, causing the ferrule and other associated parts to move to the right. Thus, by turning the traveler 72 one way or the other, the user can make the ferrule 54 move in and out, i.e. change its projection. By conducting light through the system from receptacle to connector during the adjustment, the user can measure coupling efficiency with an optical power meter, and stop the adjustment when the best coupling is achieved.
[0073] Should the user cause a collision to occur between the ferrule end and the optical mate inside the receptacle, the force transmitted by the collision is limited by the compressibility of the spring 68 , preventing damage. Also, in the case of a collision, the user will be notified by an abrupt decrease in the turning force required, since the traveler 72 will no longer be contacting the thrust collar 64 . In certain cases, causing a collision is actually desirable, since this is the position at which best coupling efficiency is obtained.
[0074] The connector can be locked against further adjustment by tightening the setscrew 84 installed in the traveler 72 , locking it against the lead screw 58 .
[0075] When this adjustment procedure has been completed, further adjustment is not possible without loosening the setscrew. Accidental adjustment is not possible.
[0076] Although the ferrule projection has been set and locked, a further safety factor exists in the form of residual spring action availability. If the connector were to be carelessly installed into any new situation whereby the existing ferrule projection was too great, and a collision with the optical mate was assured, the spring 68 can still limit the collision force, because of the ability of the traveler 72 to lift clear of the thrust collar 64 .
[0077] The subject connector thus allows for adjustable ferrule length and hence the ability to maximize optical coupling, and it retains the inherent safety feature of spring “cushioning” regardless of the length to which it has been adjusted.
[0000] Other Applications of the Connector:
[0078] Another use of the adjustable connector is for launching light out of a fiber through a lens to focus the light. Again the position of the fiber relative to the lens needs precise adjustment while minimizing unwanted movement in the other planes. Conventional methods of moving the lens to focus the light introduce play, again mainly in the X-Y planes. By using the adjustable focus connector, with its precision sleeve, one is able to move the fiber along the Z-axis only, thus allowing one to change the position and magnification of the focused spot, while tightly constraining its position along a single axis.
[0079] FIG. 10 illustrates a coupler system for effecting laser-to-fiber coupling utilizing an adjustable focus connector of the present invention. The system provides a base member 100 having a central opening or bore 102 in which a lens 104 is mounted. The base member can be adjusted relative to the substrate to which it is secured by way of tilt adjustment screws 106 as described in the aforementioned US patents of Omur M. Sezerman. A resilient sealing member 108 is positioned between the base member and substrate to provide resistance to the adjusting screws and to hermetically seal the assembly. A receptacle 110 is secured to the base member 100 and is provided with a threaded boss 112 projecting from an outer surface thereof. A bore 114 extends through the boss and receptacle 110 and is axially aligned with the bore 102 . The receptacle 110 does not include any stop against which the ferrule of the present connector could abut; however, the receptacle may include a stop face 116 against which the end face of key frame 26 can abut to assure repeatability in the Z direction. When the connector of the present invention has been secured to the receptacle 110 the adjustment operation previously described will control the distance between the fiber end and the lens 104 in the Z direction, while adjustment of the tilt screw 106 will effect any desired adjustment of the fiber in X, Y, pitch and yaw.
[0080] FIG. 11 illustrates a system similar to that shown in FIG. 10 for a fiber-to-fiber coupling system. The assemblies 120 and 122 are similar to that shown in FIG. 10 , with each mounting a lens 124 . The base members 126 , 128 are adjustable relative to each other by adjusting screws 130 , it being noted that there is a resilient sealing member 132 positioned between the base members to provide resistance to the adjusting screws and to hermetically seal the assembly. At least one of the optical fibers secured to the coupling system is adjustably mounted to one of the receptacles 134 of the base members as described above with respect to FIG. 10 . Light from one of the fibers is collimated by its lens 124 and then focused into the other fiber by the other lens 124 . The position of the focus spot is adjusted in the XY plane by the tilt adjustment mechanism of the assembly, using the screws 130 . The position of the focus spot in the Z direction relative to the fiber pair is achieved through adjustment of the adjustable connector as described hereinabove.
[0081] FIG. 12 shows an optical fiber 140 having a piece of silica 142 fused to the end thereof, forming a window or endcap. This allows for high power handling. Light from the fiber core 144 can then expand so that when such light reaches the fused silica/air interface 146 the energy density (W/m 2 ) is greatly reduced, minimizing the risk of damage to the fiber. However, the use of an endcap prevents utilization of a conventional stop in couplers such as those of the Sezerman patents, as the location of the minimum waist no longer coincides with the end of the device. This problem is rectified when a fiber with endcap is mounted in an adjustable focus connector of the present invention since the adjustability compensates for the different light pattern resulting from the use of an endcap. | An adjustable focus connector with spring action is especially adapted for use with common FC or SMA fiber optic receptacles. The connector includes a ferrule holder which mounts a fiber-carrying ferrule at a distal end thereof. At its proximal end the ferrule holder is threadedly connected to a lead screw member. A thrust collar surrounds the ferrule holder and traps a compression spring in the cavity between the thrust collar and the ferrule holder. Because of appropriate interengagement between the components the ferrule holder cannot rotate relative to the trust collar. A traveler is threadedly connected to the lead screw and abuts against the thrust collar. A connection nut is provided at the distal end of the connector to connect it to the fiber optic receptacle. The spring action of the connector prevents damage to the fiber end during connection of the connector to the fiber optic receptacle | 6 |
FIELD OF THE INVENTION
This invention relates to a string of electrically powered ornaments such as a string of lights used for such purposes as decorating Christmas trees and other symbolic things including commercial branding, showroom displays, etc. More particularly, the invention relates to electrically wired ornament strings and provides means to assist in determining which of the various ornaments in a string has failed. In the following description, the invention is described as it applies particularly to a string of Christmas lights, but it is to be understood that this particular application of the invention is only exemplary of its many uses, and the invention is not to be so narrowly construed except as recited in the appended claims.
BACKGROUND OF THE INVENTION
Light strings frequently are made with fifty or more lights, and when a light fails generally the others remain lit. Occasionally, however, something happens to a bulb that breaks the electrical circuit and all of the lights in the string go out. When that occurs, it is necessary to check each bulb in the string to find the one that failed. When that light is replaced, the entire string will light. Light testers are available to assist in checking all the lights in a string, but it is often difficult to follow the string when it is wound about the branches of a tree and/or used in close proximity with other strings.
A primary object of the present invention is to provide means to assist a person in tracing a light string so that the bulbs may be tested in order without skipping any of the lights in a string or unknowingly retesting any of them.
Another object of the present invention is to assist a person using a light tester so that it may be used most efficiently.
SUMMARY OF THE INVENTION
In accordance with the present invention, the string of ornaments, whether they be lights or other electrically powered elements, are sequentially identified by applying indicia to each ornament in the string such as by numbering or lettering each of the ornaments in sequence. This will enable one to sequentially trace the ornaments in a particular string regardless of how the string is displayed or presented so that each ornament in the string may be tested to identify and replace the failed ornament, to reactivate all of the ornaments in the string.
These and other objects and features of the invention will be better understood and appreciated from the following detailed description of selected embodiments thereof, presented for purposes of illustration and shown in the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a typical Christmas tree illustrating how a number of intertwined or interlaced light strings are typically applied to the tree;
FIG. 2 is a diagrammatic view of a string of lights constructed in accordance with the present invention and sequentially numbered to enable the string to be traced even when wound on a tree in the manner generally suggested in FIG. 1 or in any other location;
FIG. 3 is an elevation view of a single light including both a socket and lamp carrying indicia, in this case, a letter, so as to enable a series of such lights to be traced to locate a failed bulb so that it may be replaced and thereby render the entire string operative; and
FIG. 4 is a fragmentary elevation view of a string of lights with indicia applied to tags attached to the wires connecting them in the string.
DETAILED DESCRIPTION
In FIG. 1, a Christmas tree 10 is suggested on which are hung a number of string lights 12 , 14 , 16 , . . . , each composed of a substantial number of ornaments 20 . As suggested above, while ordinarily the failure of one bulb will not effect the other lights in a string, occasionally the failure of one will cause the entire string to go dark. The single string, 22 suggested in FIG. 2 includes a plug 21 at one end for connecting the string to a power source. The plug is merely representative of a number of different electrical connectors that may be used. It is not uncommon to have fifty or more lights in a single string, and in large displays a single string may have a very large number, even exceeding 100 or more lights.
It is not difficult to appreciate that when all the lights in a string go dark, it is a difficult and time consuming task to locate the failed bulb that caused it, and this task is made more difficult because of the need to trace the string and test the bulbs in sequence. While various sophisticated circuits have been developed that will indicate where failure has occurred and so as to avoid the necessity for tracing along an entire string, they are expensive and not fully reliable.
In accordance with the present invention, sequential indicia is associated with each of the lights in a string. Thus, as FIG. 2 suggests ‘n’ lights in the string, they are consecutively numbered 1-“n”. In accordance with one aspect of the invention, the indicia may be applied to the sockets as suggested in FIGS. 2 and 3, but it should be appreciated that the indicia may alternatively be applied to the wiring adjacent each socket by an inconspicuous tag or label 30 wrapped on the wiring as in FIG. 4, or alternatively the wiring itself between adjacent sockets may be sequentially marked so as to assist a person in tracing the string from one end to the other if necessary to locate the failed bulb or other ornament. While in FIG. 2 the indicia is in the form of consecutive numbers applied to the series of lights in sequence, the numbers may be replaced by sequential letters of the alphabet or any other sequential indicia that a person will readily recognize so as to assist him or her to follow the ornaments in series in the string.
While in the foregoing description, the invention has been described as applied to a series of Christmas tree lights in a string, the lights may be replaced by any other electrically powered ornament or device.
While in the foregoing description the lights carry sequential indicia throughout the string, for convenience in manufacturing and to reduce costs, particularly in long strings, an indicia sequence may be repeated. For example in a string of 50 lights, a sequence of 1 through 10 may be repeated five times, or a different sequence may be repeated a sufficient number of times to cover the entire string. In many applications, that arrangement will be adequate to enable a person to trace the string so as to locate the failed light or other ornament.
Having described this invention in detail, those skilled in the art will appreciate that numerous modifications may be made of this invention without departing from its spirit. Therefore, it is not intended that the breadth of the invention be limited to the specific embodiment illustrated and described. Rather, the breadth of the invention should be determined by the appended claims and their equivalents. | A string of electrically powered ornaments such as lights connected in a series and sequentially identifiable indicia is applied sequentially in association with each ornament in the string to enable a person to trace the string for testing each ornament. | 8 |
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