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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of Ser. No. PCT/DK96/00107 filed Mar. 18, 1996 which is a continuation-in-part of Ser. No. 08/448,210 filed May 23, 1995 and claims priority under 35 U.S.C. 119 of Danish application serial no. 0276/95 filed Mar. 17, 1995, the contents of which are fully incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to novel human insulin derivatives which are soluble and have a protracted profile of action, to a method of providing such derivatives, to pharmaceutical compositions containing them, and to the use of such insulin derivatives in the treatment of diabetes.
[0003] BACKGROUND OF TEE INVENTION
[0004] Many diabetic patients are treated with multiple daily insulin injections in a regimen comprising one or two daily injections of a protracted insulin to cover the basal requirement supplemented by bolus injections of a rapid acting insulin to cover the meal-related requirements.
[0005] Protracted insulin compositions are well known in the art. Thus, one main type of protracted insulin compositions comprises injectable aqueous suspensions of insulin crystals or amorphous insulin. In these compositions, the insulin compounds utilized typically are protanine insulin, zinc insulin or protamine zinc insulin.
[0006] Certain drawbacks are associated with the use of insulin suspensions. Thus, in order to secure an accurate dosing, the insulin particles must be suspended homogeneously by gentle shaking before a defined volume of the suspension is withdrawn from a vial or expelled from a cartridge. Also, for the storage of insulin suspensions, the temperature must be kept within more narrow limits than for insulin solutions in order to avoid lump formation or coagulation.
[0007] While it was earlier believed that protamines were non-immunogenic, it has now turned out that protamines can be immunogenic in man and that their use for medical purposes may lead to formation of antibodies (Samuel et al., Studies on the immunogenicity of protamines in humans and experimental animals by means of a micro-complement fixation test, Clin. Exp. Immunol. 33, pp. 252-260 (1978)).
[0008] Also, evidence has been found that the protamine-insulin complex is itself immunogenic (Kurtz et al., Circulating IgG antibody to protamine in patients treated with protamine-insulins. Diabetologica 25, pp. 322-324 (1983)). Therefore, with some patients the use of protracted insulin compositions containing protamines must be avoided.
[0009] Another type of protracted insulin compositions are solutions having a pH value below physiological pH from which the insulin will precipitate because of the rise in the pH value when the solution is injected. A drawback is that the solid particles of the insulin act as a local irritant causing inflammation of the tissue at the site of injection.
[0010] WO 91/12817 (Novo Nordisk A/S) discloses protracted, soluble insulin compositions comprising insulin complexes of cobalt(III). The protraction of these complexes is only intermediate and the bioavailability is reduced.
[0011] Human insulin has three primary amino groups: the N-terminal group of the A-chain and of the B-chain and the ε-amino group of Lys B29 . Several insulin derivatives which are substituted in one or more of these groups are known in the prior art. Thus, U.S. Pat. No. 3,528,960 (Eli Lilly) relates to N-carboxyaroyl insulins in which one, two or three primary amino groups of the insulin molecule has a carboxyaroyl group. No specifically N εB29 -substituted insulins are disclosed.
[0012] According to GB Patent No. 1.492.997 (Nat. Res. Dev. Corp.), it has been found that insulin with a carbamyl substitution at N εB29 has an improved profile of hypoglycaemic effect.
[0013] P laid-open patent application No. 1-254699 (Kodama Co., Ltd.) discloses insulin wherein a fatty acid is bound to the amino group of Phe B1 or to the ε-amino group of Lys B29 or to both of these. The stated purpose of the derivatisation is to obtain a pharmacologically acceptable, stable insulin preparation.
[0014] Insulins, which in the B30 position has an amino acid having at least five carbon atoms which cannot necessarily be coded for by a triplet of nucleotides, are described in JP laid-open patent application No. 57-067548 (Shionogi). The insulin analogues are claimed to be useful in the treatment of diabetes mellitus, particularly in patients who are insulin resistant due to generation of bovine or swine insulin antibodies.
[0015] U.S. Pat. No. 5,359,030 (Ekwuribe, Protein Delivery, Inc.) describes conjugation-stabilized polypeptide compositions for oral or parenteral administration comprising a polypeptide covalently coupled with a polymer including a linear polyalkylene moiety and a lipophilic moiety, said moieties being arranged so relative to each other that the polypeptide has an enhanced in vivo resistance to enzymatic degradation.
[0016] EP 511600 A2 relates i.a. to protein derivatives of the formula [protein][Z] n wherein [protein] represents a protein having n amino residues each derivable from an amino group by removal of one of its hydrogen atoms, in stead of amino groups, [Z] is a residue represented by the formula —CO—W—COOH wherein W is a divalent long chain hydrocarbon group which may also contain certain hetero atoms and n represents an average of the number of amide bonds between [Z] and [protein]. It is mentioned that the protein derivatives of the invention have an extremely prolonged serum half-life as compared with the proteins from which they are derived and that they exhibit no antigenicity. It is also mentioned, that insulin is one of the proteins from which derivatives according to the invention can be made, but no specific insulin derivatives are disclosed in EP 511600 nor is there any indication of a preferred [Z] or (a) preferred position(s) in which [Z] should be introduced in order to obtain useful insulin derivatives.
[0017] In the present specification, whenever the term insulin is used in a plural or a generic sense it is intended to encompass both naturally occurring insulins and insulin analogues and derivatives thereof. By “insulin derivative” as used herein is meant a polypeptide having a molecular structure similar to that of human insulin including the disulphide bridges between Cys A7 and Cys B7 and between Cys A20 and Cys B19 and an internal disulphide bridge between CyS A6 and Cys A11 , and which have insulin activity.
[0018] However, there still is a need for protracted injectable insulin compositions which are solutions and contain insulins which stay in solution after injection and possess minimal inflammatory and immunogenic properties.
[0019] One object of the present invention is to provide human insulin derivatives, with a protracted profile of action, which are soluble at physiological pH values.
[0020] Another object of the present invention is to provide a pharmaceutical composition comprising the human insulin derivatives according to the invention.
[0021] It is a further object of the invention to provide a method of making the human insulin derivatives of the invention.
SUMMARY OF THE INVENTION
[0022] Surprisingly, it has turned out that certain insulin derivatives, wherein either the amino group of the N-terminal amino acid of the B-chain has a lipophilic substituent comprising from 12 to 40 carbon atoms attached, or wherein the carboxylic acid group of the C-terminal amino acid of the B-chain has a lipophilic substituent comprising from 12 to 40 carbon atoms attached, have a protracted profile of action and are soluble at physiological pH values.
[0023] Accordingly, in its broadest aspect, the present invention relates to an insulin derivative having the following sequence:
[0024] wherein
[0025] Xaa at position A21 is any codable amino acid except Lys, Arg and Cys;
[0026] Xaa at positions B1, B2, B3, B26, B27, B28 and B29 are, independent of each other, any codable amino acid except Cys or deleted;
[0027] Xaa at position B30 is any codable amino acid except Cys, a dipeptide comprising no Cys or Arg, a tripeptide comprising no Cys or Arg, a tetrapeptide comprising no Cys or Arg or deleted; and either the amino group of the N-terminal amino acid of the B-chain has a lipophilic group, W, attached to it which group has from 12 to 40 carbon atoms and optionally contains a group which can be negatively charged or the carboxyl group of the C-terminal amino acid of the B-chain has a lipophilic group, Z, attached to it which group has from 12 to 40 carbon atoms and optionally contains a group which can be negatively charged with the proviso that if one or more of the amino acids at position B1, B2 and B3 is (are) deleted then the number of the N-terminal amino acid is found by counting down from Cys B7 which is always assigned the number 7 and that
[0028] (a) when B1-B2-B3 is Phe-Val-Asn and A21 is Asn and B26-B27-B28-B29-B30 is Tyr-Thr-Pro-Lys-Thr (SEQ ID NO:3) or Tyr-Thr-Pro-Lys-Ala (SEQ ID NO:4), then said W or Z always contains a group which can be negatively charged; and
[0029] (b) when B29 and B30 are deleted and a group Z as defined above is present at the C-terminal amino acid of the B-chain and neither B1, B2 nor B3 is deleted then B1-B2 is different from Phe-Val or B26-B27-B28 is different from Tyr-Thr-Pro or both B1-B2 and B26-B27-B28- are different from said sequences; and
[0030] (c) when B29 and B30 are deleted and a group Z as defined above is present at the C-terminal amino acid of the B-chain and one of B1, B2 or B3 is deleted then the N-terminal amino acid of the B-chain is different from Val or the sequence B26-B27-B28 is different from Tyr-Thr-Pro or both the N-terminal amino acid of the B-chain and the sequence B26-B27-B28 are different from Val and Tyr-Thr-Pro respectively.
[0031] In a preferred embodiment, the present invention relates to an insulin derivative having the following sequence:
[0032] wherein
[0033] Xaa at position A21 is any codable amino acid except Lys, Arg and Cys;
[0034] Xaa at positions B1, B2, B3, B26, B27, B28, B29 and B30 are, independent of each other, any codable amino acid except Cys or deleted; and either the amino group of the N-terminal amino acid of the B-chain has a lipophilic group, W, attached to it which group has from 12 to 40 carbon atoms and optionally contains a group which can be negatively charged or the carboxyl group of the C-terminal amino acid of the B-chain has a lipophilic group, Z, attached to it which group has from 12 to 40 carbon atoms and optionally contains a group which can be negatively charged with the proviso that if one or more of the amino acids at position B1, B2 and B3 is (are) deleted then the number of the N-terminal amino acid is found by counting down from Cys B7 which is always assigned the number 7 and that
[0035] (a) when B1-B2-B3 is Phe-Val-Asn and A21 is Asn and B26-B27-B28-B29-B30 is Tyr-Thr-Pro-Lys-Thr or Tyr-Thr-Pro-Lys-Ala, then said W or Z always contains a group which can be negatively charged; and
[0036] (b) when B29 and B30 are deleted and a group Z as defined above is present at the C-terminal amino acid of the B-chain and neither B1, B2 nor B3 is deleted then B1-B2 is different from Phe-Val or B26-B27-B28 is different from Tyr-Thr-Pro or both B1-B2 and B26-B27-B28 are different from said sequences; and
[0037] (c) when B29 and B30 are deleted and a group Z as defined above is present at the C-terminal amino acid of the B-chain and one of B1, B2 or B3 is deleted then the N-terminal amino acid of the B-chain is different from Val or the sequence B26-B27-B28 is different from Tyr-Thr-Pro or both the N-terminal amino acid of the B-chain and the sequence B26-B27-B28 are different from Val and Tyr-Thr-Pro respectively.
[0038] When a lipophilic group, W, is attached to the α-amino group of the N-terminal amino acid of the B-chain, then the bond between the α-amino group and W is preferably an amide bond in which the N-terminal amino group of the B-chain constitutes the amine moiety and a group contained in W constitutes the carboxyl moiety.
[0039] When a lipophilic group, Z, is attached to the carboxyl group of the C-terminal amino acid of the B-chain, then the bond between the carboxyl group and Z is preferably an amide bond in which the C-terminal carboxyl group constitutes the carboxyl moiety and an amino group contained in Z constitutes the amine moiety.
[0040] In another preferred embodiment, the invention relates to an insulin derivative as described above wherein a lipophilic group, W, is attached to the α-amino group of the N-terminal amino acid of the B-chain.
[0041] In another preferred embodiment, the invention relates to a insulin derivative as described above wherein a lipophilic group, Z, is attached to the carboxyl group of the C-terminal amino acid of the B-chain.
[0042] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position A21 is selected from the group comprising Ala, Asn, Gln, Glu, Gly and Ser.
[0043] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B1 is Phe.
[0044] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B1 is deleted.
[0045] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B2 is selected from the group comprising Ala and Val.
[0046] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B3 is selected from the group comprising Asn, Gln, Glu and Thr.
[0047] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B26 is Tyr.
[0048] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B27 is Thr.
[0049] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B28 is Pro.
[0050] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B29 is Lys or Thr.
[0051] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B28 is Lys and the amino acid at position B29 is Pro.
[0052] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B30 is Thr or ε-acylated Lys.
[0053] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the dipeptide Thr-Lys.
[0054] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the dipeptide Gly-Lys.
[0055] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the tripeptide Glu-Ser-Lys.
[0056] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the tripeptide Thr-Gly-Lys.
[0057] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the tetrapeptide Thr-Gly-Gly-Lys.
[0058] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the tetrapeptide Thr-Glu-Gly-Lys.
[0059] In another preferred embodiment, the invention relates to an insulin derivative wherein Xaa at position 30 in SEQ ID NO:2 designates the tetrapeptide Gly-Asp-Thr-Lys.
[0060] In another preferred embodiment, the invention relates to an insulin derivative wherein the C-terminal amino acid of the B-chain is ε-acylated Lys and the amino acid next to the C-terminal amino acid is Gly.
[0061] In another preferred embodiment, the invention relates to an insulin derivative wherein the parent insulin is a des(B30) insulin.
[0062] In another preferred embodiment, the invention relates to an insulin derivative wherein the parent insulin is des(B30) human insulin.
[0063] In another preferred embodiment, the invention relates to an insulin derivative wherein the parent insulin is a des(B28-B30) insulin.
[0064] In another preferred embodiment, the invention relates to an insulin derivative wherein the parent insulin is a des(B27-B30) insulin.
[0065] In another preferred embodiment, the invention relates to an insulin derivative wherein the parent insulin is a des(B26-B30) insulin.
[0066] In another preferred embodiment, the invention relates to an insulin derivative wherein the amino acid at position B28 is Pro and the amino acid at position B29 is Thr.
[0067] In another preferred embodiment, the invention relates to an insulin derivative which has a group, W, as mentioned above, attached to the N-terminal α-amino group of its B-chain, W being a group of the general formula CH 3 (CH 2 ) n CH(COOH)NH—CO(CH 2 ) 2 CO— wherein n is an integer from 9 to 15.
[0068] In another preferred embodiment, the invention relates to an insulin derivative which has a group, W, as mentioned above, attached to the N-terminal α-amino group of its B-chain, W being a group of the general formula CH 3 (CH 2 ) r CO—NHCH(COOH)(CH 2 ) 2 CO— wherein r is an integer from 9 to 15.
[0069] In another preferred embodiment, the invention relates to an insulin derivative which has a group, W, as mentioned above, attached to the N-terminal α-amino group of its B-chain, W being a group of the general formula CH 3 (CH 2 ) 3 CO—NHCH((CH2) 2 COOH)CO— wherein s is an integer from 9 to 15.
[0070] In another preferred embodiment, the invention relates to an insulin derivative which has a group, Z, as mentioned above, attached to the C-terminal amino acid of its B-chain, wherein Z is a group of the general formula —NHCH(COOH)(CH 2 ) 4 NH—CO(CH 2 ) m CH 3 wherein m is an integer from 8 to 18, that is, Z is a N ε -acylated lysine residue.
[0071] In another preferred embodiment, the invention relates to an insulin derivative which has a group, Z, as mentioned above, attached to the C-terminal amino acid of its B-chain, wherein Z is a group of the general formula —NHCH(COOH)(CH 2 ) 4 NH—COCH((CH 2 ) 2 COOH)NH—CO(CH 2 ) p CH 3 wherein p is an integer from 10 to 16.
[0072] In another preferred embodiment, the invention relates to an insulin derivative which has a group, Z, as mentioned above, attached to the C-terminal amino acid of its B-chain, wherein Z is a group of the general formula —NHCH(COOH)(CH 2 ) 4 NH—CO(CH 2 ) 2 CH(COOH)NH—CO(CH 2 ) q CH 3 wherein q is an integer from 10 to 16.
[0073] In another preferred embodiment, the invention relates to an insulin derivative which has a group, Z, as mentioned above, which comprises a partly or completely hydrogenated cyclopentanophenanthrene skeleton.
[0074] In another preferred embodiment, the invention relates to an insulin derivative which has a group, Z, as mentioned above, which is an acylated amino acid, in particular acylated lysine.
[0075] In another preferred embodiment, the invention relates to Thr B29 human insulin with a group Z as described above attached to the C-terminal amino acid of its B-chain.
[0076] In another preferred embodiment, the invention relates to des(B28-B30) human insulin with a group Z as described above attached to the C-terminal amino acid of its B-chain.
[0077] In another preferred embodiment, the invention relates to des(B27-B30) human insulin with a group Z as described above attached to the C-terminal amino acid of its B-chain.
[0078] In another preferred embodiment, the invention relates to des(B26-B30) human insulin with a group Z as described above attached to the C-terminal amino acid of its B-chain.
[0079] In another preferred embodiment, the invention relates to the use of an insulin derivative according to the invention for the preparation of a medicament for treating diabetes.
[0080] In another preferred embodiment, the invention relates to a pharmaceutical composition for the treatment of diabetes in a patient in need of such a treatment comprising a therapeutically effective amount of an insulin derivative according to the invention together with a pharmaceutically acceptable carrier.
[0081] In another preferred embodiment, the invention relates to a pharmaceutical composition for the treatment of diabetes in a patient in need of such a treatment comprising a therapeutically effective amount of an insulin derivative according to the invention, in mixture with an insulin or an insulin analogue which has a rapid onset of action, together with a pharmaceutically acceptable carrier.
[0082] In another preferred embodiment, the invention relates to a pharmaceutical composition comprising an insulin derivative according to the invention which is soluble at physiological pH values.
[0083] In another preferred embodiment, the invention relates to a pharmaceutical composition comprising an insulin derivative according to the invention which is soluble at pH values in the interval from about 6.5 to about 8.5.
[0084] In another preferred embodiment, the invention relates to a protracted pharmaceutical composition comprising an insulin derivative according to the invention.
[0085] In another preferred embodiment, the invention relates to a pharmaceutical composition which is a solution containing from about 120 nmol/ml to about 1200 nmol/ml, preferably about 600 nmol/ml of an insulin derivative according to the invention.
[0086] In another preferred embodiment, the invention relates to a method of treating diabetes in a patient in need of such a treatment comprising administering to the patient a therapeutically effective amount of an insulin derivative according to this invention together with a pharmaceutically acceptable carrier.
[0087] In another preferred embodiment, the invention relates to a method of treating diabetes in a patient in need of such a treatment comprising administering to the patient a therapeutically effective amount of an insulin derivative according to this invention, in mixture with an insulin or an insulin analogue which has a rapid onset of action, together with a pharmaceutically acceptable carrier.
[0088] Examples of preferred insulin derivatives according to the present invention are the following:
[0089] (N εB30 -tetradecanoyl) Thr B29 .Lys B30 human insulin,
[0090] (N εB28 -tetradecanoyl) Lys B28 des(B29,B30) human insulin,
[0091] (N εB27 -tetradecanoyl) LyS B27 des(B28-B30) human insulin and
[0092] (N εB26 -tetradecanoyl) Lys B26 des(B27-B30) human insulin.
[0093] (N εB32 -tetradecanoyl) Glu B30 ,Ser B31 ,Lys B32 human insulin.
[0094] (N εB29 -acetyl,N εB32 -tetradecanoyl) Glu B30 ,Ser B31 ,Lys B32 human insulin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0095] The present invention is further illustrated with reference to the appended drawing wherein:
[0096] [0096]FIG. 1 shows the construction of the plasmids pKV153, pKV159, pJB173, pJB174 and pJB175;
[0097] [0097]FIG. 2 a which is continued in FIG. 2 b shows the sequence of pMT742, position 907 to 1500, and the oligonucleotides #94, #593, #2371 and #3075 used for PCR1A, PCR1B and PCR1C of Example 1. The 138 amino acid sequence corresponding to the MF alpha prepro-leader (amino acids Nos. 1-85) and an insulin precursor which has the amino acid sequence B(1-29)AlaAlaLysA(1-21) wherein A(1-21) is the A chain of human insulin and B(1-29) is the B chain of human insulin in which Thr(B30) is missing, is shown below the coding sequence (amino acids Nos. 86-138).
DETAILED DESCRIPTION OF THE INVENTION
[0098] Terminology
[0099] The three letter codes and one letter codes for the amino acid residues used herein are those stated in J. Biol. Chem. 243, p. 3558 (1968).
[0100] In the DNA sequences, A is adenine, C is cytosine, G is guanine, and T is thymine. The following acronyms are used:
[0101] DMSO for dimethyl sulphoxide,
[0102] DMF for dimethylformamide,
[0103] Boc for tert-butoxycarbonyl,
[0104] NMP for 1-methyl-2-pyrrolidone,
[0105] TFA for trifluoroacetic acid,
[0106] X-OSu for an N-hydroxysuccinimid ester,
[0107] X for an acyl group,
[0108] RP-HPLC for reversed phase high performance liquid chromatography.
[0109] Preparation of Lipophilic Insulin Derivatives
[0110] The insulin derivatives according to the present invention can be prepared i.a. as described in the following:
[0111] 1. Insulin Derivatives Featuring in Position B30 an Amino Acid Residue Which can be Coded for by the Genetic Code, e.g. Threonine (Human Insulin) or Alanine (Porcine Insulin).
[0112] 1.1 Insulins Modified by Attachment of a Lipophilic Group, W, to the N-Terminal Amino Group, Starting from Human Insulin.
[0113] Human insulin is treated with a Boc-reagent (e.g. di-tert-butyl dicarbonate) to form (A1,B29)-diBoc human insulin, i.e., human insulin in which the N-terminal end of the A-chain and the ε-amino group of Lys B29 are protected by a Boc-group. After an optional purification, e.g. by HPLC, an acyl group is introduced in the α-amino group of Phe B1 by allowing the product to react with a N-hydroxysuccinimide ester of the formula W-OSu wherein W is an acyl group as defined in the above to be introduced at the N-terminal α-amino group of the B-chain. In the final step, TFA is used to remove the Boc-groups and the product, N αB1 -W human insulin, is isolated.
[0114] 2. Insulin Derivatives with no Amino Acid Residue in Position B30. i.e. des(B30) Insulins.
[0115] 2.1 Starting from Human Insulin or Porcine Insulin.
[0116] On treatment with carboxypeptidase A in ammonium buffer, human insulin and porcine insulin both yield des(B30) insulin. After an optional purification, the des(B30) insulin is treated with a Boc-reagent (e.g. di-tert-butyl dicarbonate) to form (A1,B29)-diBoc des(B30) insulin. After an optional purification, e.g. by HPLC, an acyl group is introduced in the α-amino group of the amino acid in position B1 by allowing the product to react with a N-hydroxysuccinimide ester of the formula W-OSu wherein W is the acyl group to be introduced. In the final step, TFA is used to remove the Boc-groups and the product, (N αB1 -W) des(B30) insulin, is isolated.
[0117] 2.2 Starting from a Single Chain Human Insulin Precursor.
[0118] A single chain human insulin precursor, which is extended in position B1 with an extension (Ext) which is connected to B1 via an arginine residue and which has a bridge from a C-terminal lysine in position B26, B27, B28 or B30 to A1 can be a used as starting material. Preferably, the bridge is a peptide of the formula Y n -Arg, where Y is a codable amino acid except cysteine, lysine and arginine, and n is zero or an integer between 1 and 35. When n>1, the Y's may designate different amino acids. Preferred examples of the bridge from Lys in position B26, B27, B28 or B30 to A1 are: AlaAlaArg, SerArg, SerAspAspAlaArg (SEQ ID NO:5) and Arg (European Patent No. 163529). Treatment of such a precursor of the general formula Ext-Arg-B(1-Q)-Y n -Arg-A(1-21), wherein Q is 26, 27, 28 or 30, with a lysyl endopeptidase, e.g. Achromobacter lyticus protease, yields Ext-Arg-B(1-Q) Y n -Arg-A(1-21) insulin. Acylation of this intermediate with a N-hydroxysuccinimide ester of the general formula X-OSu wherein X is an acyl group, introduces the acyl group X in the ε-amino group of Lys BQ , and in the N-terminal amino group of the A-chain and the B-chain to give (N εBQ -X) X-Ext-Arg-B(1-Q) X-Y n -Arg-A(1-21) insulin. This intermediate on treatment with trypsin in mixture of water and a suitable organic solvent, e.g. DMF, DMSO or a lower alcohol, gives the desired derivative, Z-human insulin wherein Z is Lys εBQ -X.
[0119] Pharmaceutical Compositions
[0120] Pharmaceutical compositions containing a human insulin derivative according to the present invention may be administered parenterally to patients in need of such a treatment. Parenteral administration may be performed by subcutaneous, intramuscular or intravenous injection by means of a syringe, optionally a pen-like syringe. Alternatively, parenteral administration can be performed by means of an infusion pump. A further option is a composition which may be a powder or a liquid for the administration of the human insulin derivative in the form of a nasal spray.
[0121] Pharmaceutical compositions containing a compound of the present invention may be prepared by conventional techniques, e.g. as described in Remington's Pharmaceutical Sciences, 1985.
[0122] Thus, the injectable human insulin compositions of the invention can be prepared using the conventional techniques of the pharmaceutical industry which involves dissolving and mixing the ingredients as appropriate to give the desired end product.
[0123] Thus, according to one procedure, the human insulin derivative is dissolved in an amount of water which is somewhat less than the final volume of the composition to be prepared. An isotonic agent, a preservative and a buffer is added as required and the pH value of the solution is adjusted—if necessary—using an acid, e.g. hydrochloric acid, or a base, e.g. aqueous sodium hydroxide as needed. Finally, the volume of the solution is adjusted with water to give the desired concentration of the ingredients.
[0124] Examples of isotonic agents are sodium chloride, mannitol and glycerol.
[0125] Examples of preservatives are phenol, m-cresol, methyl p-hydroxybenzoate and benzyl alcohol.
[0126] Examples of suitable buffers are sodium acetate and sodium phosphate.
[0127] Preferred pharmaceutical compositions of the particular insulins of the present invention are solutions hexameric complexes. Typically the hexameric complexes are stabilized by two or more zinc ions and three or more molecules of a phenolic compound like phenol or meta-cresol or mixtures thereof per hexamer.
[0128] In a particular embodiment, a composition is provided which contains two different insulins, one having a protracted profile of action and one having a rapid onset of action, in the form of soluble hexameric complexes. Typically the hexameric complexes are stabilized by two or more zinc ions and three or more molecules of a phenolic compound like phenol or meta-cresol or mixtures thereof per hexamer. The complexes are mixtures of hexamers of the particular insulins and mixed hexamers in which the ratio between the two different insulins is from 1:5 to 5:1.
[0129] A composition for nasal administration of an insulin derivative according to the present invention may, for example, be prepared as described in European Patent No. 272097 (to Novo Nordisk A/S).
[0130] The insulin compositions of this invention can be used in the treatment of diabetes. The optimal dose level for any patient will depend on a variety of factors including the efficacy of the specific human insulin derivative employed, the age, body weight, physical activity, and diet of the patient, on a possible combination with other drugs, and on the severity of the case of diabetes. It is recommended that the daily dosage of the human insulin derivative of this invention be determined for each individual patient by those skilled in the art in a similar way as for known insulin compositions.
[0131] Where expedient, the human insulin derivatives of this invention may be used in mixture with other types of insulin, e.g. human insulin or porcine insulin or insulin analogues with a more rapid onset of action. Examples of such insulin analogues are described e.g. in the European patent applications having the publication Nos. EP 214826 (Novo Nordisk is A/S), EP 375437 (Novo Nordisk A/S) and EP 383472 (Eli Lilly & Co.).
[0132] The present invention is further illustrated by the following examples which, however, are not to be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the following examples may, both separately and in any combination thereof, be material for realizing the invention in diverse forms thereof.
EXAMPLES
[0133] Plasmids and DNA Material
[0134] All expression plasmids are of the cPOT type. Such plasmids are described in EP patent application No. 171 142 and are characterised in containing the Schizosaccharomyces pombe triose phosphate isomerase gene (POT) for the purpose of plasmid selection and stabilisation. A plasmid containing the POT-gene is available from a deposited E. coli strain (ATCC 39685). The plasmids furthermore contain the S. cerevisiae triose phosphate isomerase promoter and terminator (P TPI and T TPI ). They are identical to pMT742 (Egel-Mitani, M et al., Gene 73 (1988) 113-120) (see FIG. 1) except for the region defined by the EcoRI-XbaI restriction sites encompassing the coding region for MF alpha prepro leader/product. The EcoRI/XbaI fragment of pMT742 itself encodes the Mating Factor (MF) alpha prepro-leader sequence of Saccharomyces cerevisiae followed by the insulin precursor MI3 which has a Ala-Ala-Lys bridge connecting B29 and A1 (i.e. B(1-29)-Ala-Ala-Lys-A(1-21)) (see FIG. 2)
[0135] Synthetic DNA fragments were synthesised on an automatic DNA synthesizer (Applied Biosystems model 380A) using phosphoramidite chemistry and commercially available reagents (Beaucage, S. L. and Caruthers, M. H., Tetrahedron Letters 22 (1981) 1859-1869).
[0136] All other methods and materials used common state of the art knowledge (see, e.g. Sambrook, J., Fritsch, E. F. and Maniatis, T. Molecular Cloning: A Laboratory Manual , Cold Spring Harbour Laboratory Press, New York, 1989).
[0137] Analytical
[0138] Molecular masses of insulin precursors prepared were obtained by mass spectroscopy (MS), either by plasma desorption mass spectrometry (PDMS) using Bio-Ion 20 instrument (Bio-Ion Nordic AB, Uppsala, Sweden) or electrospray mass spectrometry (ESMS) using an API III Biomolecular Mass Analyzer (Perkin Elmer Sciex Instruments, Thornhill, Canada).
[0139] The lipophilicity of an insulin derivative relative to human insulin, k′ rel , was measured on a LiChrosorb® RP18 (5 μm, 250×4 mm) HPLC column by isocratic elution at 40° C. using mixtures of A) 0.1 M sodium phosphate buffer, pH 7.3, containing 10% acetonitrile, and B) 50% acetonitrile in water. The elution was monitored by the absorption of the eluate at 214 nm. Void time, t 0 , was found by injecting 0.1 mM sodium nitrate. Retention time for human insulin, t human , was adjusted to at least 2t 0 by varying the ratio between the A and B solutions. k′ rel is defined as (t derivative −t 0 )/(t hyman −t 0 ).
[0140] As a measure of the protraction of the compounds of the invention, the disappearance rate in pigs was studied and T 50% was determined. T 50% is the time when 50% of the A14 Tyr( 125 I)-labeled analogue has disappeared from the site of injection as measured with an external γ-counter (Ribel, U et al., The Pig as a Model for Subcutaneous Absorption in Man. In: M. serrano-Rios and P. J. Lefebre (Eds): Diabetes 1985; Proceedings of the 12th Congress of the International Diabetes Federation, Madrid, Spain, 1985 (Excerpta Medica, Amsterdam, (1986) 891-96).
EXAMPLE 1
[0141] Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-29)-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor (SEQ ID NO:6-B(1-29)-SEQ ID NO:5-A(1-21)) from yeast strain yKV153 using the S.cerevisiae MF alpha prepro-leader.
[0142] The following oligonucleotides were synthesised:
(SEQ ID NO:9) #593 5′-CCAAGTACAAAGCTTCAACCAAGTGGGAACCGCACAAGTGT TGGTTAACGAATCTTGTAGCCTTTGGTTCAGCTTCAGCTTCAGC TTCTTCTCTTTTATCCAAAGAAACACC-3′ (SEQ ID NO:10) #94 5′-TAAATCTATAACTACAAAAAACACATA-3′ (SEQ ID NO:11) #3075 5′-TTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGGTTT CTTCTACAGTCCTAAGTCTGACGATGCTAGAGGTATTG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0143] The following two Polymerase Chain Reactions (PCR) were performed using Gene Amp PCR reagent kit (Perkin Elmer, 761 Main Avewalk, Conn., USA) according to the manufacturer's instructions (see FIG. 2).
[0144] PCR1A:
[0145] 0.2 μl of pMT742 plasmid template
[0146] 4.0 μl of oligonucleotide #593 (100 pmol)
[0147] 4.0 μl of oligonucleotide #94 (100 pmol)
[0148] 10.0 μl of 1O×PCR buffer
[0149] 10.0 μl of 2.5 Mm dNTP
[0150] 0.5 μl of Taq polymerase enzyme
[0151] 71.3 μl of water
[0152] PCR1B:
[0153] 0.2 μl of pMT742 plasmid template
[0154] 4.0 μl of oligonucleotide #3075 (100 pmol)
[0155] 4.0 μl of oligonucleotide #2371 (100 pmol)
[0156] 10.0 μl of 1O×PCR buffer
[0157] 10.0 μl of 2.5 mM dNTP
[0158] 0.5. μl of Taq polymerase enzyme
[0159] 71.3 μl of water
[0160] In both cases two cycles were performed at 94° C. for 1 min., 45° C. for 1 min. and 72° C. for 1 min. and subsequently followed by 11 cycles: 94° C. for 1 min., 55° C. for 1 min., 72° C. for 1 min.
[0161] 20 μl of each PCR mixture was loaded onto a 2% agarose gel and subjected to electrophoresis using standard techniques (Sambrook et al., Molecular cloning, Cold Spring Harbour Laboratory Press, 1989). Resulting DNA fragments (452 bp from PCR1A and 170 bp from PCR1B) were cut out of the agarose gel and isolated using the Gene Clean kit (Bio101 Inc., PO BOX 2284, La Jolla, Calif., USA) according to the manufacturer's instructions. The purified DNA fragments were dissolved in 100 μl of water.
[0162] The following PCR was performed
[0163] PCR1C:
[0164] 1.0 μl of DNA fragment from PCR1A
[0165] 1.0 μL of DNA fragment from PCR1B
[0166] 10.0 μl of 1O×PCR buffer
[0167] 10.0 μl of 2.5 mM dNTP
[0168] 0.5 μl of Taq polymerase enzyme
[0169] 69.5 μl of water
[0170] Two cycles were performed at 94° C. for 1 min., 45° C. for 1 min. and 72° C. for 1 min.
[0171] Subsequently 4 μl of oligonucleotide #94 (100 pmol) and 4.0 μl of oligonucleotide #2371 (100 pmol) was added and 15 cycles were performed at 94° C. for 1 min., 55° C. for 1 min. and 72° C. for 1 min.
[0172] The PCR mixture was loaded onto a 1% agarose gel and the resulting 594 bp fragment was purified using the Gene Clean kit as described. The purified PCR DNA fragment was dissolved in 20 μl of water and restriction endonuclease buffer and cut with the restriction endonucleases EcoRI and XbaI (New England Biolabs, Inc. Mass., USA). The resulting 550 bp EcoRI/XbaI restriction fragment was run on agarose gel and isolated and purified using the Gene clean kit.
[0173] In two separate restriction endonuclease digestions the plasmid pMT742 was cut with i) restriction endonucleases ApaI and XbaI and ii) with restriction endonucleases ApaI and EcoRI. From these digestions the 8.6 kb ApaI/XbaI restriction fragment and the 2.1 kb ApaI/EcoRI restriction fragment was isolated.
[0174] The three fragments (i.e. the 550 bp EcoRI/XbaI restriction fragment from PCR1C and the 8.6 kb ApaI/XbaI restriction fragment and 2.1 kb ApaI/EcoRI restriction fragment from pMT742) were ligated together using T4 DNA ligase and standard conditions (Sambrook et al., Molecular cloning, Cold Spring Harbour Laboratory Press, 1989)(see FIG. 1). The ligation mixture was transformed into competent E. coli cells (Ap r− ) followed by selection for ampicillin resistance. Plasmids were isolated from the resulting E. coli colonies using standard DNA miniprep technique (Sambrook et al., Molecular cloning, Cold Spring Harbour Laboratory Press, 1989) and checked with appropriate restriction endonucleases (i.e. EcoRI, ApaI and XbaI). The selected plasmid designated pKV153 was shown by DNA sequencing analysis (using the Sequenase kit from U.S. Biochemical Corp, according to the manufacturer's recommendations) to contain the correct sequence encoding the MF alpha prepro-leader/Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-29)-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor.
[0175] pKV153 was transformed into S. cerevisiae strain MT663 and selected for growth on glucose as described in European patent application having the publication No. 214826.
[0176] The resulting yeast strain was designated yKV153 and was verified to produce Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-29)-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor (SEQ ID NO:6-B(1-29)-SEQ ID NO:5-A(1-21)) in the culture media by HPLC and mass spectroscopy.
EXAMPLE 2
[0177] Synthesis of Lys B30 (N ε -tetradecanoyl) Thr B29 Human Insulin.
[0178] 2a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-28)-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) (SEQ ID NO:6-B(1-29)-SEQ ID NO:5-A(1-21)) Insulin Precursor from Yeast Strain yKV159 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0179] The following oligonucleotides were synthesised:
(SEQ ID NO:13) #388 5′-TTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGGTT TCTTCTACACTCCTACCAAGTCTGACGATGCTAGAGGTATTGT CG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′ (SEQ ID NO:14) #627 5′-CACTTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAG GTTTCTTCTACACTAAGTCTGACGATGCTAG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0180] The following Polymerase Chain Reaction (PCR) was performed using Gene Amp PCR reagent kit as described above.
[0181] PCR2:
[0182] 0.2 μl of pKV153 plasmid template (from Example 1)
[0183] 4.0 μl of oligonucleotide #3881 (100 pmol)
[0184] 4.0 μl of oligonucleotide #2371 (100 pmol)
[0185] 10.0 μl of 1O×PCR buffer
[0186] 10.0 μl of 2.5 mM dNTP
[0187] 0.5 μl of Taq polymerase enzyme
[0188] 71.3 μl of water
[0189] Two cycles were performed at 94° C. for 1 min., 45° C. for 1 min. and 72° C. for 1 min. and subsequently followed by 11 cycles at 94° C. for 1 min., 55° C. for 1 min., 72° C. for 1 min.
[0190] The PCR mixture was loaded onto a 2% agarose gel and the resulting 174 bp fragment was purified using the Gene Clean kit as described. The purified PCR DNA fragment was dissolved in 20 μl of water and restriction endonuclease buffer and cut with the restriction endonucleases HindIII and XbaI. The resulting 153 bp HindIII/XbaI restriction fragment was run on agarose gel and isolated and purified using the Gene Clean kit.
[0191] In two separate restriction endonuclease digestions pMT742 was cut with restriction endonucleases ApaI and XbaI whereas pKV153 (from Example 1) was cut with restriction endonucleases ApaI and EcoRI. From this digestions the 8.6 kb ApaI/XbaI restriction fragment from pMT742 and the 2.1 kb ApaI/EcoRI restriction fragment from pKV153 was isolated.
[0192] The three fragments (i.e. the 550 bp EcoRI/XbaI restriction fragment from PCR2 and the 8.6 kb ApaI/XbaI restriction fragment from pMT748 and the 2.1 kb ApaI/EcoRI restriction fragment from pKV153) were ligated together using T4 DNA ligase as described above (see FIG. 1). The ligation mixture was transformed into competent E. coli cells (Ap r− ) followed by selection for ampicillin resistance. Plasmids were isolated from the resulting E. coli colonies and checked for appropriate restriction endonucleases (i.e. HindIII, ApaI and XbaI) as described.
[0193] The selected plasmid designated pKV159 was shown by DNA sequencing analysis to contain the correct sequence encoding the MF alpha prepro-leader/Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-28)-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor (SEQ ID NO:6-B(1-28)-SEQ ID NO:7- A(1-21)).
[0194] pKV159 was transformed into S. cerevisiae strain MT663 and selected for growth on glucose as described.
[0195] The resulting yeast strain was designated yKV159 and was verified to produce Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-28)-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor (SEQ ID NO:6-B(1-29)-SEQ ID NO:5- A(1-21)) in the culture media by HPLC and mass spectroscopy.
[0196] 2b. Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-28)-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor.
[0197] The yKV159 strain was fermented for 72 hours and five litres of broth were collected. Yeast cells were removed by centrifugation, the pH value was adjusted to 3.0 using sulphuric acid and the insulin precursor was concentrated on a Pharmacia Strealine® 50 column packed with 300 ml of Streamline® SP ion exchanger. After wash with 25 mM citrate buffer, pH value 3.6, the precursor was eluted by 0.5 M NH 3 and the fraction from 300 to 600 ml was collected. The pH value was adjusted to 2.5 and the precursor was purified by RP-HPLC using 15μ spherical C18 silica of 100 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 as buffer, and using a gradient from 23 to 33% acetonitrile. The precursor eluted at about 27-28% acetonitrile. The pool containing the central major peak of the precursor was desalted by gel filtration on Sephadex® G-50 F in 0.5 M acetic acid, and the precursor isolated by lyophilization. Yield: 486 mg.
[0198] 2c. Synthesis of Ala-Thr-Arg-B(1-28)-Thr-Lys, Ser-Asp-Asp-Ala-Arg-A(1 -21) Insulin.
[0199] The 486 mg of single-chain precursor obtained as described above were dissolved in 30 ml of 0.05 M glutamate buffer at pH 9.0, and 3 ml of immobilized A. lyticus protease gel were added (see PCT/DK94/00347, page 45). After gentle stirring for 5 hours at 30° C., the gel was removed by filtration and the double-chain, extended insulin was crystallized by the addition of 10 ml of ethanol, 845 mg of trisodium citrate dihydrate and 78 mg of zinc chloride. After adjustment of the pH value to 6.1 and storage at 4° C. overnight the crystals were collected by centrifugation, washed twice with isopropanol and dried in vacuo. Yield: 450 mg.
[0200] 2d. Synthesis of N αA−5 ,N αB−3 ,N εB30 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-28)-Thr-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0201] 450 mg of the double-chain, extended insulin, obtained as described above, were dissolved in a mixture of 3.15 ml of DMSO and 0.69 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.69 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 2 hours at 15° C., the reaction was stopped by addition of 112 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0202] 2e. Synthesis of Lys B30 (N ε -tetradecanoyl) Thr B29 Human Insulin.
[0203] To the solution from the previous step was added 5 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 16 hours, the gel was removed by filtration, the pH value was adjusted to 9.0 and the solution was applied to a 2.5×25 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 17.3 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with NH 3 .
[0204] The title compound emerged from the column after 650 ml, and a pool from 650 to 754 ml was collected. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration on Sephadex® G-50 Fine, and the product isolated in the dry state by lyophilization. Yield: 91 mg.
[0205] Molecular mass of the title compound, found by MS: 6020±6, theory: 6018.
[0206] Molecular mass of the B-chain, found by MS: 3642±5, theory: 3640.
[0207] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease, found by MS: 1326±2, theory: 1326.
[0208] Relative lipophilicity, k′ rel =113.
[0209] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 20.3±5.2 hours (n=6).
EXAMPLE 3
[0210] Synthesis of LyS B28 (N ε -tetradecanoyl) des(B29-B30) Human Insulin.
[0211] 3a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor (SEQ ID NO:6-B(1-27)-SEQ ID NO:8-A(1-21)) from Yeast Strain yJB173 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0212] The following oligonucleotides were synthesised:
(SEQ ID NO:14) #627 5′-CACTTGGTTGAAGGTTTGTACTTGGTTTGCGGTGAAAGAGG TTTCTTCTACACTAAGTCTGACGATGCTAG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0213] The DNA encoding Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21)(SEQ ID NO:6-B(1-27)-SEQ ID NO:8-A(1-21))was constructed in the same manner as described in Example 2 by substituting oligonucleotide #3881 with oligonucleotide #627.
[0214] The resulting plasmid was designated pJB173 and the yeast strain expressing Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) (SEQ ID NO:6-B(1-27)-SEQ ID NO:8-A(1-21)) was designated yJB173.
[0215] 3b . Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) insulin precursor.
[0216] The yJB173 strain was fermented for 72 hours and 4.8 litres of broth were collected. Yeast cells were removed by centrifugation and the pH value was adjusted to 3.0 using sulphuric acid. The conductivity was 7.8 mS/cm. The insulin precursor was concentrated using a Pharmacia Streamline® 50 column packed with 300 ml of Streamline® SP ion exchanger. After wash with 25 mM citrate buffer, pH value 3.6, the precursor was eluted by 0.5 M NH 3 and the fraction from 300 to 600 ml was collected. Free ammonia was evaporated in vacuo at room temperature and the pH value of the resulting 280 ml of solution was adjusted to 9.0 with hydrochloric acid.
[0217] 3c. Synthesis of Ala-Thr-Arg-B(1-27)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0218] To the 280 ml of solution containing 118 mg of the single-chain precursor, obtained as described above, were added 3 ml of immobilized A. lyticus protease gel (see PCT/DK94/00347, page 45). After gentle stirring for 24 hours at 30° C. the gel was removed by filtration. The pH value was adjusted to 3.5 and the solution was filtered though a Milipore® 0.45μ filter. The double-chain, extended insulin was purified in 2 runs by RP-HPLC using a 2×20 cm column packed with 15μ spherical C18 silica of 100 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 , pH 3.5 as buffer, and using a gradient from 23 to 33% acetonitrile at a rate of 4 ml/min and a column temperature of 40° C. The double-chain, extended insulin eluted at about 30-31% acetonitrile. The acetonitrile was removed from the combined pools of 70 ml by evaporation in vacuo, and salts were removed by gelfiltration using a 5×47 cm column of Sephadex G-25 in 0.5 M acetic acid. The double-chain, extended insulin was isolated by lyophilization. Yield: 110 mg.
[0219] 3d. Synthesis of N αA−5 ,N αB−3 ,N εB28 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-27)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0220] 110 mg of the double-chain, extended insulin obtained as described above were dissolved in a mixture of 0.84 ml of DMSO and 0.275 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.185 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 2 hour at 15° C., the reaction was stopped by addition of 32.5 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0221] 3e. Synthesis of Lys B28 (N ε -tetradecanoyl) des(B29-B30) Human Insulin.
[0222] To the resulting solution from the previous step was added 1.5 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 18 hours, the gel was removed by filtration, the pH value adjusted to 9.0 and the solution applied to a 1.5×21 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 10 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with NH 3 . The title compound emerged from the column after 250-390 ml, peaking at 330 ml. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration using Sephadex® G-50 Fine, and the product was isolated in the dry state by lyophilization. Yield: 47 mg.
[0223] Molecular mass of the title compound, found by MS: 5820±2, theory: 5819.
[0224] Molecular mass of the B-chain, found by MS: 3444±4, theory: 3442.
[0225] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease, found by MS: 1128±2, theory: 1128.
[0226] Relative lipophilicity, k′ rel =121.
[0227] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 19.6±3.6 h (n=4).
EXAMPLE 4
[0228] Synthesis of Lys B27 (N ε -tetradecanoyl) des(B28-B30) Human Insulin.
[0229] 4a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-26)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor (SEQ ID NO:6-B(1-26)-SEQ ID NO:8-A(1-21)) from Yeast Strain yJB174 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0230] The following oligonucleotides were synthesised:
(SEQ ID NO:15) #628 5-′CACTTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGG TTTCTTCTACAAGTCTGACGATGCTAG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0231] The DNA encoding Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-26)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21)(SEQ ID NO:6-B(1-26)-SEQ ID NO:8- A(1-21)) was constructed in the same manner as described in Example 2 by substituting oligonucleotide #3881 with oligonucleotide #628.
[0232] The resulting plasmid was designated pJB174 and the yeast strain expressing Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-26)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) (SEQ ID NO:6- B(1-26)-SEQ ID NO:8-A(1-21)) was designated yJB174.
[0233] 4b. Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-26)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor.
[0234] The yJB174 strain was fermented for 72 hours and 3.5 litres of broth were collected. Yeast cells were removed by centrifugation, the pH value was adjusted to 3.0 using sulphuric acid and the solution was diluted with water to 8 litres in order to decrease the salt concentration. The resulting conductivity was 7.9 mS/cm. The insulin precursor was concentrated using a Pharmacia Streamline® 50 column packed with 300 ml of Streamline® SP ion exchanger. After wash with 25 mM citrate buffer, pH 3.6, the precursor was eluted by 0.5 M NH 3 and the fraction from 300 to 600 ml was collected. Free ammonia was evaporated in vacuo at room temperature and the pH value of the resulting 280 ml was adjusted to 9.0 with hydrochloric acid.
[0235] 4c. Synthesis of Ala-Thr-Arg-B(1-26)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0236] To the 280 ml of solution of the single-chain precursor obtained as described above was added 3 ml of immobilized A. lyticus protease gel (see PCT/DK94/00347, page 45). After gentle stirring for 13 hours at 30° C. the gel was removed by filtration. The pH value was adjusted to 2.5 and the solution was filtered though a Milipore® 0.45μ filter. The double-chain, extended insulin was purified in 4 runs by RP-HPLC using a 2×20 cm column packed with 15μ spherical C18 silica of 100 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 , pH 2.5 as buffer, and using a gradient from 24 to 33% acetonitrile. The double-chain, extended insulin eluted at about 30-31% acetonitrile. The acetonitrile was removed from the combined pools by evaporation in vacuo, and the salts were removed by gelfiltration using a 5×47 cm column of Sephadex G-25 in 0.5 M acetic acid. The double-chain, extended insulin was isolated by lyophilization. Yield: 69 mg.
[0237] 4d. Synthesis of N αA−5 ,N αB−3 ,N εB27 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-26)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0238] 62 mg of the double-chain, extended insulin obtained as described under 4e was dissolved in a mixture of 0.44 ml of DMSO and 0.15 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.096 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 2 hours at 15° C. the reaction was stopped by addition of 17 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0239] 4e. Synthesis of Lys B27 (N ε -tetradecanoyl) des(B28-B30) Human Insulin.
[0240] To the solution from the previous step was added 1 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 26 hours, the gel was removed by filtration, the pH value adjusted to 9.0 and the solution applied to a 1.5×25.5 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 17.3 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with NH 3 . The title compound emerged from the column after 360 ml, and a pool from 272 to 455 ml was collected. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration on Sephadex® G-50 Fine, and the product isolated in the dry state by lyophilization. Yield: 38 mg.
[0241] Molecular mass of the title compound, found by MS: 5720±6, theory: 5718.
[0242] Molecular mass of the B-chain, found by MS: 3342±4, theory: 3340.
[0243] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease, found by MS: 1027±2, theory: 1027.
[0244] Relative lipophilicity, k′ rel =151.
[0245] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 15.2±2.2 h (n=5).
EXAMPLE 5
[0246] Synthesis of Lys B26 (N ε -tetradecanoyl) des(B27-B30) Human Insulin.
[0247] 5a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-25)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor (SEQ ID NO:6-B(1-26)-SEQ ID NO:8- A(1-21)) from Yeast Strain yJB175 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0248] The following oligonucleotides were synthesised:
(SEQ ID NO:16) #629 5′-CACTTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGG TTTCTTCAAAGTCTGACGATGCTAG-3′ (SEQ ID NO:12) #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0249] The DNA encoding Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-25)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21)(SEQ ID NO:6-B(1-26)-SEQ ID NO:8-A(1-21))was constructed in the same manner as described in Example 2 by substituting oligonucleotide #3881 with oligonucleotide #629.
[0250] The resulting plasmid was designated pJB175 and the yeast strain expressing Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-25)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) (SEQ ID NO:6-B(1-26)-SEQ ID NO:8-A(1-21)) was designated yJB175.
[0251] 5b. Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-25)-Lys-Ser-Asp-Asp-Ala-Arg-A(1-2 1) Insulin Precursor.
[0252] The yJB175 strain was fermented for 72 hours and 3.7 litres of broth were collected. Yeast cells were removed by centrifugation, the pH value was adjusted to 3.0 using sulphuric acid and the solution was diluted with water to 8.5 litres in order to decrease the salt concentration. The resulting conductivity was 7.7 mS/cm. The insulin precursor was concentrated using a Pharmacia Strealine® 50 column packed with 300 ml of Streamline® SP ion exchanger. After wash with 25 mM citrate buffer, pH 3.6, the precursor was eluted by 0.5 M ammonia and the fraction from 300 to 600 ml was collected. Free ammonia was evaporated in vacuo at room temperature and the pH value of the resulting 270 ml of solution was adjusted to 9.0 with hydrochloric acid.
[0253] 5c. Synthesis of Ala-Thr-Arg-B(1-25)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0254] To the 270 ml solution of the single-chain precursor obtained as described above was added 3 ml of immobilized A. lyticus protease gel (see PCT/DK94/00347, page 45). After gentle stirring for 23 hours at 30° C., the gel was removed by filtration. The pH value was adjusted to 2.5 and the solution was filtered though a Milipore® 0.45μ filter. The double-chain, extended insulin was purified in 4 runs by RP-HPLC using a 2×20 cm column packed with 15μ spherical C18 silica of 100 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 , pH 3.5 as buffer, and using a gradient from 24 to 33% acetonitrile. The double-chain, extended insulin eluted at about 29-31% acetonitrile. The acetonitrile was removed from the combined pools by evaporation in vacuo, and the salts were removed by gelfiltration using a 5×47 cm column of Sephadex® G-25 in 0.5 M acetic acid. The double-chain, extended insulin was isolated by lyophilization. Yield: 81 mg.
[0255] 5d. Synthesis of N αA−5 ,N αB−3 ,N εB26 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-25)-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0256] 80 mg of the double-chain, extended insulin was dissolved in a mixture of 0.56 ml of DMSO and 0.19 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.124 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 2 hour at 15 ° C. the reaction was stopped by addition of 21.8 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0257] 5e. Synthesis of LyS B26 (N ε -tetradecanoyl) des(B27-B30), Human Insulin.
[0258] To the solution from the previous step was added 1 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 23 hours the gel was removed by filtration, the pH value was adjusted to 9.0 and the solution applied to a 1.5×25.5 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 19.3 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with ammonia. The title compound emerged from the column after 320 ml, and a fraction from 320 to 535 ml was collected. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration on Sephadex® G-50 Fine, and the product isolated in the dry state by lyophilization. Yield: 25 mg.
[0259] Molecular mass of the title compound found by MS. 5555±6, theory: 5555.
[0260] Molecular mass of the B-chain found by MS: 3179±4, theory: 3178.
[0261] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease found by MS: 864±1, theory: 863.5.
[0262] Relative lipophilicity, k′ rel =151.
[0263] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 14.4±1.5 h (n=5).
EXAMPLE 6
[0264] Synthesis of (N(1-carboxytridecyl)-2-amidosuccinyl)-Phe αB1 des(B30) Human Insulin.
[0265] A1,B29-diBoc-des(B30) human insulin (200 mg, 0.033 mmol) was dissolved in DMF (15 ml) and triethylamine (20 μl) was added. N(1-carbomethoxytridecyl)-2-amidosuccinic acid N-hydroxysuccinimide ester (16 mg, 0.033 mmol) was added and after 4 hours at room temperature the reaction mixture was evaporated in vacuo to dryness. The Boc groups were removed by treatment for 30 min at room temperature with trifluoroacetic acid (5 ml). The trifluoroacetic acid was removed by evaporation in vacuo. The residue was dissolved at 0° C. in 0.1 N NaOH (20 ml). The saponification of the methyl ester was accomplished after 1 hour at 0° C. The pH value of the reaction mixture was adjusted to 5.0 by acetic acid and ethanol (5 ml) was added. The precipitate formed was isolated by centrifugation. The title compound was purified from the precipitate by ion exchange chromatography using a 2.5×27 cm column of QAE-Sephadex® A25.
[0266] The precipitate was dissolved ethanol/water (60:40, v/v) (25 ml) by adjustment of the pH value to 9.8 using ammonia and the solution was applied to the column. Elution was carried out in NH 3 /NH 4 Cl buffers at pH 9.0, using a linear gradient from 0.12 to 0.18 M NH 4 Cl in ethanol/water (60:40, v/v) and a total of 1000 ml of eluent. The UV absorbance of the eluate was monitored at 280 nm and fractions of 10 ml were collected. The title compound emerged from the column in fractions 62 to 72. The title compound was precipitated by diluting the pool with 2 volumes of water and adjusting the pH value to 5.0. After centrifugation the precipitate was washed with water and after a second centrifugation the product was dried in vacuo. Yield: 10 mg.
[0267] Molecular weight, found by PDMS: 6032, theory: 6032.
[0268] Relative lipophilicity, k′ rel =140.
[0269] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 8.65±11.65 hours (n=5).
EXAMPLE 7
[0270] Phe αB1 -tetradecanoyl-glutamyl-glycyl des(B30) Human Insulin.
[0271] A1,B29-diBoc des(B30) human insulin (200 mg, 0.033 mmol) was dissolved in DMF (15 ml) and triethylamine (100 μl) was added. Myristoyl-Glu(γ-OtBu)-Gly N-hydroxysuccinimide ester (95 mg, 0.17 mmol) was added and after 4 hours at room temperature the reaction mixture was evaporated to dryness in vacuo. The Boc and tBu groups were removed by treatment for 30 min at room temperature with trifluoroacetic acid (5 ml). The trifluoroacetic acid was removed by evaporation in vacuo. The title compound was purified from the precipitate by RP-HPLC using a C18 silica column and eluting with a linear gradient from 16 to 64% acetonitrile in a 50 mM Tris/phosphate buffer containing 75 mM (NH 4 ) 2 SO 4 at pH 7. The title compound emerged from the column at about 50% acetonitrile. The acetonitrile was evaporated in vacuo, and ethanol was added to 20% (v/v). Adjustment of the pH value to 5.0 caused the product to precipitate. After centrifugation the precipitate was dissolved in 10 mM NH 4 HCO 3 , desalted by gel filtration using Sephadex G-25 and lyophilized. Yield: 97 mg.
[0272] Molecular mass, found by PDMS: 6105, theory: 6104.
EXAMPLE 8
[0273] Synthesis of Gly B28 ,Thr B29 ,Lys B30 (N ε -tetradecanoyl) Human Insulin
[0274] 8a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor from Yeast Strain yKV195 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0275] The following oligonucleotides were synthesised:
#4790 5′-TTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGGTT TCTTCTAGACTGGTACCAAGTCTGACGATGCTAGAGGTATTGT CG-3′ #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0276] The DNA encoding Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) was constructed in the same manner as described in Example 2 by substituting oligonucleotide #3881 with oligonucleotide #4790.
[0277] The resulting plasmid was designated pKV195 and the yeast strain expressing Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) was designated yKV195.
[0278] 8b. Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor.
[0279] The yKV195 strain was fermented for 72 hours and 4.4 litres of broth were collected. Yeast cells were removed by centrifugation, the pH value was adjusted to 3.0 using sulphuric acid and 3.6 litres of water were added to dilute salts to a conductivity of 7.7 mS/cm. The insulin precursor was concentrated using a Pharmacia Strealine® 50 column packed with 300 ml of Streamline® SP ion exchanger. After wash with 3 litres of 25 mM citrate buffer, pH 3.6, the precursor was eluted using 0.5 M ammonia and the fraction from 300 to 600 ml was collected. Free ammonia was evaporated in vacuo at room temperature and the pH value of the resulting 280 ml was adjusted to 9.0 with hydrochloric acid.
[0280] 8c. Synthesis of Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0281] To the 280 ml of solution containing 300 mg of the single-chain precursor were added 3 ml of immobilized A. lyticus protease gel (see PCT/DK94/00347, page 45). After gentle stirring for 17 hours at 30° C. the gel was removed by filtration. The pH value was adjusted to 3.5 and the solution was filtered though a Milipore® 0.45μ filter. The double-chain, extended insulin was purified in 3 runs by RP-HPLC using a 2×20 cm column packed with 10μ spherical C18 silica of 120 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 , pH 3.5 as buffer, and using a gradient from 23 to 33% acetonitrile at a rate of 4 ml/min and a column temperature of 40° C. The double-chain, extended insulin eluted at about 30-31% acetonitrile. The acetonitrile was removed from the combined pools of 70 ml by evaporation in vacuo, and the salt were removed by gelfiltration using a 5×47 cm column of Sephadex® G-25 and 0.5 M acetic acid. The double-chain, extended insulin was isolated by lyophilization. Yield: 176 mg.
[0282] 8d. Synthesis of N αA−5 ,N αB−3 ,N εB30 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-27)-Gly-Thr-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0283] 176 mg of the double-chain, extended insulin was dissolved in a mixture of 1.4 ml of DMSO and 0.275 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.963 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 20 hour at 15° C. the reaction was stopped by addition of 50 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0284] 8e. Synthesis of Gly B28 ,Thr B29 ,Lys B30 (N ε -tetradecanoyl) Human Insulin.
[0285] To the solution from the previous step was added 2.5 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 5 hours, the gel was removed by filtration; the pH value adjusted to 9.0 and the solution applied to a 1.5×26.5 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 9.3 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with ammonia. The title compound emerged from the column after 325-455 ml, peaking at 380 ml. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration using Sephadex® G-50 Fine, and the product isolated in the dry state by lyophilization. Yield: 50 mg.
[0286] Molecular mass of the title compound, found by MS: 5979±6, theory: 5977.
[0287] Molecular mass of the B-chain, found by MS: 3600±4, theory: 3600.
[0288] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease, found by MS: 1286±2, theory: 1286.
[0289] Relative lipophilicity, k′ rel =103.
[0290] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 17±2 h (n =4).
EXAMPLE 9.
[0291] Synthesis of Gly B28 ,Lys B29 (N ε -tetradecanoyl) Human Insulin.
[0292] 9a. Synthesis of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor from Yeast Strain yKV196 Using the S. cerevisiae MF Alpha Prepro-Leader.
[0293] The following oligonucleotides were synthesised:
#4791 5′-TTGGTTGAAGCTTTGTACTTGGTTTGCGGTGAAAGAGGTTT CTTCTACACCGGTAAGTCTGACGATGCTAGAGGTATTGTCG-3′ #2371 5′-TTAATCTTAGTTTCTAGAGCCTGCGGG-3′
[0294] The DNA encoding Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) was constructed in the same manner as described in Example 2 by substituting oligonucleotide #3881 with oligonucleotide #4791.
[0295] The resulting plasmid was designated pKV196 and the yeast strain expressing Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) was designated yKV196.
[0296] 9b. Isolation of Glu-Glu-Ala-Glu-Ala-Glu-Ala-Glu-Pro-Lys-Ala-Thr-Arg-B(1-27)-Gly-Lys-Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin Precursor.
[0297] The yKV196 strain was fermented for 72 hours and 3.6 litres of broth were collected. Yeast cells were removed by centrifugation, the pH value was adjusted to 3.0 using sulphuric acid and 3.4 litres of water were added to dilute salts to a conductivity of 7.7 mS/cm. The insulin precursor was concentrated to 300 ml using the procedure described in Example 8b.
[0298] 9c. Synthesis of Ala-Thr-Arg-B(1-27)-Gly-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0299] To the 300 ml solution at pH 9.0 containing 390 mg of the single-chain precursor were added 5 ml of immobilized A. lyticus protease gel (see PCT/DK94/00347, page 45). After gentle stirring for 40 hours at 30° C., the gel was removed by filtration. The pH value was adjusted to 3.5 and the solution was filtered though a Milipore® 0.45μ filter. The double-chain, extended insulin was purified in 3 runs by RP-HPLC using a 2×20 cm column packed with 10μ spherical C18 silica of 120 Å pore size and 0.2 M Na 2 SO 4 , 0.04 M H 3 PO 4 , pH 3.5 as buffer, and using a gradient from 23 to 33% acetonitrile at a rate of 4 ml/min and a column temperature of 40° C. The double-chain, extended insulin eluted at about 29% acetonitrile. The acetonitrile was removed from the combined pools of 60 ml by evaporation in vacuo, and the salt were removed by gelfiltration using a 5×47 cm column of Sephadex® G-25 and 0.5 M acetic acid. The double-chain, extended insulin was isolated by lyophilization. Yield: 154 mg.
[0300] 9d. Synthesis of N αA−5 ,N αB−3 ,N εB29 -tris(tetradecanoyl) Ala-Thr-Arg-B(1-27)-Gly-Lys, Ser-Asp-Asp-Ala-Arg-A(1-21) Insulin.
[0301] 154 mg of the double-chain, extended insulin was dissolved in a mixture of 1.05 ml of DMSO and 0.329 ml of 2 M diisopropylethylamine in NMP. The solution was cooled to 15° C. and 0.22 ml of 0.3 M tetradecanoic acid N-hydroxysuccinimide ester in DMSO/NMP (1:1, v/v) was added. After 2 hour at 15° C., the reaction was stopped by addition of 40 ml of 0.01 M glycine buffer in ethanol/water (60:40, v/v) and the pH value adjusted to 10.0. The triacylated intermediate was not isolated.
[0302] 9e. Synthesis of Gly B28 ,Lys B29 (N ε -tetradecanoyl) Human Insulin.
[0303] To the solution from the previous step was added 1.5 ml of immobilized trypsin gel (see PCT/DK94/00347, page 46). After gentle stirring at 15° C. for 21 hours, the gel was removed by filtration, the pH value adjusted to 9.0 and the product in 43 ml solution was applied to a 1.5×26.0 cm column of QAE-Sephadex® A-25. Isocratic elution was performed at a rate of 9:5 ml/h using a 0.12 M NH 4 Cl buffer in ethanol/water (60:40, v/v) adjusted to pH 9.0 with ammonia. The title compound emerged from the column after 190-247 ml, is peaking at 237 ml. Finally, the buffer was changed to 0.01 M NH 4 HCO 3 by gel filtration using Sephadex® G-50 Fine, and the product isolated in the dry state by lyophilization. Yield: 67 mg.
[0304] Molecular mass of the title compound, found by MS: 5877±2, theory: 5876.
[0305] Molecular mass of the B-chain, found by MS: 3499±3, theory: 3499.
[0306] Molecular mass of the C-terminal fragment of B-chain digested by V8 protease, found by MS: 1184±2, theory: 1185.
[0307] Relative lipophilicity, k′ rel =118.5.
[0308] Disappearance half-life, T 50% , after subcutaneous injection in pigs: 25±9 h (n=4).
1
26
21 amino acids
amino acid
single
linear
1
Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu
1 5 10 15
Glu Asn Tyr Cys Xaa
20
30 amino acids
amino acid
single
linear
2
Xaa Xaa Xaa Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr
1 5 10 15
Leu Val Cys Gly Glu Arg Gly Phe Phe Xaa Xaa Xaa Xaa Xaa
20 25 30
5 amino acids
amino acid
single
linear
3
Tyr Thr Pro Lys Thr
1 5
5 amino acids
amino acid
single
linear
4
Tyr Thr Pro Lys Ala
1 5
5 amino acids
amino acid
single
linear
5
Ser Asp Asp Ala Arg
1 5
13 amino acids
amino acid
single
linear
6
Glu Glu Ala Glu Ala Glu Ala Glu Pro Lys Ala Thr Arg
1 5 10
5 amino acids
amino acid
single
linear
7
Ser Asp Asp Ala Arg
1 5
7 amino acids
amino acid
single
linear
8
Thr Lys Ser Asp Asp Ala Arg
1 5
6 amino acids
amino acid
single
linear
9
Lys Ser Asp Asp Ala Arg
1 5
112 base pairs
nucleic acid
single
linear
10
CCAAGTACAA AGCTTCAACC AAGTGGGAAC CGCACAAGTG TTGGTTAACG AATCTTGTAG 60
CCTTTGGTTC AGCTTCAGCT TCAGCTTCTT CTCTTTTATC CAAAGAAACA CC 112
27 base pairs
nucleic acid
single
linear
11
TAAATCTATA ACTACAAAAA ACACATA 27
79 base pairs
nucleic acid
single
linear
12
TTGGTTGAAG CTTTGTACTT GGTTTGCGGT GAAAGAGGTT TCTTCTACAC TCCTAAGTCT 60
GACGATGCTA GAGGTATTG 79
27 base pairs
nucleic acid
single
linear
13
TTAATCTTAG TTTCTAGAGC CTGCGGG 27
85 base pairs
nucleic acid
single
linear
14
TTGGTTGAAG CTTTGTACTT GGTTTGCGGT GAAAGAGGTT TCTTCTACAC TCCTACCAAG 60
TCTGACGATG CTAGAGGTAT TGTCG 85
71 base pairs
nucleic acid
single
linear
15
CACTTGGTTG AAGCTTTGTA CTTGGTTTGC GGTGAAAGAG GTTTCTTCTA CACTAAGTCT 60
GACGATGCTA G 71
68 base pairs
nucleic acid
single
linear
16
CACTTGGTTG AAGCTTTGTA CTTGGTTTGC GGTGAAAGAG GTTTCTTCTA CAAGTCTGAC 60
GATGCTAG 68
66 base pairs
nucleic acid
single
linear
17
CACTTGGTTG AAGCTTTGTA CTTGGTTTGC GGTGAAAGAG GTTTCTTCAA AGTCTGACGA 60
TGCTAG 66
594 base pairs
nucleic acid
double
linear
CDS
109..522
18
CTTAAATCTA TAACTACAAA AAACACATAC AGGAATTCCA TTCAAGAATA GTTCAAACAA 60
GAAGATTACA AACTATCAAT TTCATACACA ATATAAACGA TTAAAAGA ATG AGA TTT 117
Met Arg Phe
1
CCT TCT ATT TTT ACT GCT GTT TTA TTC GCT GCT TCC TCC GCT TTA GCT 165
Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser Ala Leu Ala
5 10 15
GCT CCA GTC AAC ACT ACC ACT GAA GAT GAA ACG GCT CAA ATT CCA GCT 213
Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala
20 25 30 35
GAA GCT GTC ATC GGT TAC TCT GAT TTA GAA GGT GAT TTC GAT GTT GCT 261
Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala
40 45 50
GTT TTG CCA TTT TCC AAC TCC ACC AAT AAC GGT TTA TTG TTT ATC AAT 309
Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn
55 60 65
ACT ACT ATT GCC TCC ATT GCT GCT AAA GAA GAA GGT GTT TCT TTG GAT 357
Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Asp
70 75 80
AAA AGA TTC GTT AAC CAA CAC TTG TGC GGT TCC CAC TTG GTT GAA GCT 405
Lys Arg Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala
85 90 95
TTG TAC TTG GTT TGC GGT GAA AGA GGT TTC TTC TAC ACT CCT AAG GCT 453
Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Ala
100 105 110 115
GCT AAG GGT ATT GTC GAA CAA TGC TGT ACC TCC ATC TGC TCC TTG TAC 501
Ala Lys Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr
120 125 130
CAA TTG GAA AAC TAC TGC AAC TAGACGCAGC CCGCAGGCTC TAGAAACTAA 552
Gln Leu Glu Asn Tyr Cys Asn
135
GATTAATATA ATTATATAAA AATATTATCT TCTTTTCTTT AT 594
138 amino acids
amino acid
linear
protein
19
Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser
1 5 10 15
Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln
20 25 30
Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe
35 40 45
Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu
50 55 60
Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val
65 70 75 80
Ser Leu Asp Lys Arg Phe Val Asn Gln His Leu Cys Gly Ser His Leu
85 90 95
Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr
100 105 110
Pro Lys Ala Ala Lys Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys
115 120 125
Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn
130 135
4 amino acids
amino acid
single
linear
None
20
Thr Gly Gly Lys
1
4 amino acids
amino acid
single
linear
None
21
Thr Glu Gly Lys
1
4 amino acids
amino acid
single
linear
None
22
Gly Asp Thr Lys
1
8 amino acids
amino acid
single
linear
None
23
Gly Thr Lys Ser Asp Asp Ala Arg
1 5
7 amino acids
amino acid
single
linear
None
24
Gly Lys Ser Asp Asp Ala Arg
1 5
85 base pairs
nucleic acid
single
linear
25
TTGGTTGAAG CTTTGTACTT GGTTTGCGGT GAAAGAGGTT TCTTCTACAC TGGTACCAAG 60
TCTGACGATG CTAGAGGTAT TGTCG 85
82 base pairs
nucleic acid
single
linear
cDNA
26
TTGGTTGAAG CTTTGTACTT GGTTTGCGGT GAAAGAGGTT TCTTCTACAC CGGTAAGTCT 60
GACGATGCTA GAGGTATTGT CG 82
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The present invention relates to insulin derivatives in which a lipophilic group having from 12 to 40 carbon atoms is attached to the α-amino group of the N-terminal amino acid in the B-chain or to the carboxy group of the C-terminal amino acid in the B-chain have a protracted profile of action.
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BACKGROUND OF THE INVENTION
[0001] The present invention relates generally to systems and methods for detecting light, and more particularly to systems and methods for large dynamic range light detection.
[0002] It is often desirable to detect (and possibly quantify)light emitted from light emitting samples or substances. Such detection capability is useful in various assays, such as, for example, DNA sequencing assays where different fluorescent substances may be attached to different amino acids. For certain assays it is also desirable to quantify the light emitted by a sample. However, light emitted by a light emitting sample, such as a sample containing a fluorescent substance, may be in a 6 decade (10 6 ) range of intensity for a given stimulation intensity. Samples may be distributed over an area that is stimulated by a stationary or scanned point light source of a single color, with the emitted light directed to a point optical detector, and the detector's electrical output quantized to a digital value representing the optical power detected in a given time interval. The set of values may be organized into a 2-dimensional array representing fluorescent emission over the sample area, where a given sample detection time corresponds to a given point in the sample area. Alternatively, the data may be collected serially, in time, and arranged in any way that correlates a particular sample with a particular reading.
[0003] In certain applications requiring an optical detection power range of roughly 0.3 pW to 300 nW, for example, and the requirement of a signal-to-noise ratio of about 10 at 50 pW in a time interval of 5 us, a PMT (photomultiplier tube) detector must be used. The PMT's practical dynamic range for this time interval is between 3 and 4 decades, limited at the low end by signal-to-noise and at the high end by PMT anode current rating. The PMT gain may be adjusted for 300 nW at maximum anode current but 0.3 pW will not be detected, or for usable signal-to-noise at 0.3 pW but 300 nW will be above the PMT anode current rating. In prior art implementations, multiple scans with different stimulation intensities or PMT responsivities were required to be carried out for 6 decade detection, consuming extra time and possibly degrading the sample due to increased light exposure.
[0004] Therefore it is desirable to provide systems and methods that overcome the above and other problems.
BRIEF SUMMARY OF THE INVENTION
[0005] The present invention provides systems and method for detecting and measuring light emitted from a sample and having a large dynamic range, e.g., a range of luminous intensity covering six or more orders of magnitude, that may be difficult to fully detect using a single detector with a limited detection range.
[0006] In certain embodiments, simultaneous measurement of the emitted light in two intensity ranges is performed using two detectors, one including a photomultiplier tube (PMT) and the other including a solid state detector such as a photodiode. A beam splitting element directs light emitted from a sample under investigation to both detectors simultaneously such that most of the light impinges on the PMT and a smaller portion of the light impinges on the solid-state detector. A processor receives output signals from the two detectors and provides an output representing the luminous intensity of the sample over a detection range greater than the detection range of each individual detector, thereby providing a detection system having an enhanced dynamic range (ratio between maximum and minimum detectable light). In certain aspects, for example when the detection system is used in a scanning detection system, the processor scales and combines data from each detector into one data value per sample acquisition time with a continuous dynamic range of at least six decades (six orders of magnitude).
[0007] According to one embodiment, a scanning fluorescence detector system is provided that stimulates a sample point with light of a single color at a given instant in time, and a single intensity over the total scan area, and which detects emitted light using two detectors and a beamsplitter. The beamsplitter directs most of the light to a first detector element, such as a PMT, which detects the lower power range and directs the rest of the light to a second detector element such as a solid-state sensor, typically an APD (avalanche photodiode) or a PIN or PN (positive-intrinsic-negative, positive-negative) photodiode, which detects the higher power range. The responsivity of the detectors and the beamsplitter ratio are chosen so that the detected light will always be within the dynamic range of at least one of the two detectors.
[0008] Embodiments of the invention advantageously allow an area containing fluorescent samples of a given (emission) color to be scanned only once for all available data. A uniform scan intensity helps ensure uniform photobleaching for minimal effect on subsequent scans with the same color. This uniform exposure also has the benefit of not requiring linearity in response of the sample (i.e., the light-to-response of the sample itself is not required to be linear). This has advantages in systems containing mixtures or in samples where the linearity of response is not valid, or even known. Signal and data processing provide a data set representative of a single detector with 6 decades of dynamic range. In one aspect, data from only one detector may be taken, for example, where it is known a priori that the dynamic range of emitted light will be within the detection range of a single detector.
[0009] According to one aspect of the present invention, a light detection system with large dynamic range detection capability is provided. The system typically includes a first light detection element capable of detecting incident light over a first intensity range, and a second light detection element of a different type than the first light detection element, wherein the second light detection element is capable of detecting incident light over a second intensity range different than the first intensity range. The system also typically includes a beamsplitting element configured to transmit a first portion of incident light from a light emitting sample to the first light detection element and direct a second portion of the incident light to the second light detection element, wherein the first and second light detection elements simultaneously detect the incident light from the sample.
[0010] According to another aspect of the present invention, a method is provided for detecting light emitted from a sample using a detection system proximal to the sample. The detection system typically includes a beam splitting element configured to transmit a first portion of incident emitted light to a first detector element and to direct a second portion of the incident emitted light to a second detector element, wherein the first detector element is of a different type than the second detector element. The method typically includes the steps of simultaneously detecting the first portion of the emitted light with the first detector and detecting the second portion of the emitted light with the second detector, and providing output signals from each of the first and second detectors, each output signal representing a dynamic range that is different from the other. The method further typically includes processing the output signals from the first and second detectors to produce a combined output signal representing a dynamic range greater than the dynamic range of each of the detector output signals.
[0011] Reference to the remaining portions of the specification, including the drawings and claims, will realize other features and advantages of the present invention. Further features and advantages of the present invention, as well as the structure and operation of various embodiments of the present invention, are described in detail below with respect to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar elements.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 illustrates a light detection system according to one embodiment.
[0013] FIG. 2 illustrates a layout of the elements of a scanning detection system including a detection system of FIG. 1 according to one embodiment.
DETAILED DESCRIPTION OF THE INVENTION
[0014] The present invention provides wide dynamic range light detection systems and methods using two (or more) detectors in which part of the received light is directed to a low intensity light sensor, and part of the light is directed to a high intensity light sensor. The sensor outputs are merged into a single output representing the luminous intensity of the sample over a detection range greater than the detection range of each individual detector.
[0015] According to one embodiment as shown in FIG. 1 , a light detection system 10 includes a first detector 15 , a second detector 20 and a beamsplitting element 30 configured to direct a portion of the light emitted from a sample 5 toward detector 20 and to allow a portion of the emitted light (e.g., photoluminescent emission such as fluorescent emission) to pass to detector 15 . Sample 5 may be excited by illumination from a light source (not shown) such as a laser or other source of coherent or incoherent light. In a scanning system, for example, sample 5 may be illuminated with light of a single color at a given instant in time, and a single intensity over the total scan area. Useful light sources include lasers (e.g., gas lasers, diode lasers, excimer lasers, E-beam pumped lasers, etc), arc lamps, LEDs, OLEDs, resonant phosphor structures, etc, or any light source having a suitable emission spectrum.
[0016] In one embodiment, the beamsplitter 30 is configured to direct most of the light to a first detector element configured to detect the lower power range, such as a photomultiplier tube (PMT) or other electro-optic detector having similar or equivalent range and signal-to-noise characteristics. Beamsplitter 30 is also configured to direct the remainder of the light to a second detector element configured to detect the higher power range, such as a solid-state sensor, typically a photodiode. Examples of useful photodiodes include an APD (avalanche photodiode) a PIN (positive-intrinsic-negative) photodiode, and a PN (positive-negative) photodiode. For example, in the embodiment as shown in FIG. 1 , beamsplitter element 30 is configured to direct (e.g., reflect) most (i.e., >50%) of the light toward detector 20 , which includes a PMT, whereas the remainder of the light is allowed to pass to detector 15 , which includes a solid-state detector. Thus, in one embodiment, the ratio of light transmission vs. reflection of the beamsplitter is less than 1:1. In one specific embodiment, for example, beamsplitter 30 directs 75% of the light toward detector 20 and allows up to 25% of the light to pass to detector 15 . It should be appreciated that detector 15 may include a PMT and that detector 20 may include a solid-state detector. In this case, the ratio of light allowed to pass versus the light directed/reflected by beamsplitter 30 should be greater than 1:1 so that most of the light passes to the PMT. In certain aspects, the beamsplitter ratio may vary from about 4:1 to about 1:4 depending, in part, on the positions of the low-power and high-power light detection elements relative to the beamsplitter. In certain aspects, the beamsplitter ratio may have values up to 1:10 or 1:20 or more. In certain aspects, the responsivity of the detection elements and the beamsplitter ratio are chosen so that the detected light will always be within the dynamic range of at least one of the two detection elements.
[0017] In one aspect, beamsplitter 30 includes an optically passive element such as a dichroic cube beamsplitter or other passive element(s). Beamsplitter 30 , in certain aspects, includes an electro-optical device to facilitate adjustment of the beamsplitting ratio, e.g., under control of microprocessor 40 , an external intelligence module, or by a user. It should also be appreciate that additional optical elements may be included to control (e.g., collect, steer and image) the emitted light and/or to condition the light. Such optical elements might include focusing lenses and pinholes (apertures) as may be commonly used in confocal microscopy systems.
[0018] Processor module 40 receives as input the output signals from detector 15 and detector 20 . The signals from detectors 15 and 20 may be provided to microprocessor module 40 as analog or digital signals. In either case, in one aspect, an analog-to-digital (A/D) converter is used to convert the analog signals to digital signals for processing by microprocessor module 40 . For example, microprocessor module 40 may include an A/D converter coupled with its input(s) and/or a detector may include an A/D converter coupled with its output. It should be appreciated that processor module 40 may include an intelligence module (e.g., processor executing instructions) resident in a data acquiring device or system such as a microarray scanner system, where the data signals (detector output) is provided to the intelligence module in real time as the signals are generated, or module 40 may be a separate stand alone system such as a desktop computer system or other computer system, coupled via a network connection (e.g., LAN, VPN, intranet, Internet, etc.) or direct connection (e.g., USB or other direct wired or wireless connection) to the acquiring device. The data signals may also be converted and stored in a memory unit or buffer or on a portable medium such as a CD, DVD, floppy disk or the like and provided to the intelligence module for processing after the experiment has been completed.
[0019] In one aspect, the signals from the two detectors are processed before conversion to digital data by pulse counters, current-to-voltage converters or charge integrators. Such processing may introduce a time delay that may be significantly different between the two detectors and which may need to be compensated for, either before or after conversion, so that a given sample time corresponds to a given point in the sample area to within a specific tolerance. In one aspect, therefore, the processor module 40 includes circuit elements to perform scaling and combining of the data from the two detectors into one data value per sample time with a continuous dynamic range of at least 6 decades, taking into account the differences in signal processing time delay and responsivity in the signal paths of the two detectors. The digital data is then processed into one data value per sample time with a continuous dynamic range of at least 6 decades. This may require color-dependent scaling as the detected color, and therefore the detector responsivities, may change from scan to scan. For example, in one aspect, digitized data values from the two detectors are stored in separate numerical arrays in the processor's memory with each value time-indexed. Data for the net detector responsivities is known from prior calibration and from the set beamsplitter ratio and detection wavelength and is stored in the processor. The time delay in each detector is also known from prior calibration and stored. Each detector has a defined and stored dynamic range corresponding to a minimum and maximum numerical value. A computing algorithm executed in the processor 1) adjusts the time indices for one or both of the arrays based on the calibration data for the closest practical delay matching, then 2) for each new time index chooses a value from the array within usable dynamic range, or the value nearest maximum if values from both arrays are within range, and 3) scales the chosen value with the matching responsivity calibration data to arrive at the final optical power value.
[0020] In some cases, the detection dynamic range is known or expected to be within the dynamic range of one of the detectors, in which case only data from that detector is taken. In these cases, in one aspect, the detector responsivity is adjusted electrically to match the expected dynamic range of the sample area.
[0021] In one aspect, a solid-state detector is used as a responsivity calibration reference for a PMT in the portion of the dynamic range where both detectors have linear responses. This requires that the responsivity of the solid-state detector has better stability with time and temperature than the PMT. For an APD, this would require a low APD gain or APD temperature stabilization.
[0022] According to one embodiment, a method of light detection using a scanning fluorescence detector system includes positioning the detector system proximal to a sample or array of samples to be investigated, stimulating the sample area with a single color and a single intensity over the total sample area or scan area with a beamsplitter directing most of the detected light to a PMT and the rest of the light to a solid-state point detector, such as a photodiode or avalanche photodiode. One typical solid state detector is the Advanced Photonix P/N 012-70-62-541, 0.3 mm active area diameter avalanche photodiode. A typical PMT is a Hamamatsu R3896 PMT. The low-end light detector 20 can be any other detector with similar power range and signal-to-noise performance. In one aspect, a sample array is scanned sequentially, first with one color illuminating the sample area, then with another color, etc. FIG. 2 illustrates a layout of the elements of a scanning detection system 100 including a detection system 10 according to one embodiment. As shown, two excitation sources 110 provide excitation light to sample 105 (e.g., single sample, or array of samples) via scanning element 125 . Scanning element 125 may include a scanning mirror and a lens coupled to a translation stage. Light emitted by the sample is reflected back and guided to detection system 10 .
[0023] Embodiments of the invention advantageously allow an area containing fluorescent samples of a given color to be scanned only once for all available data. A uniform scan intensity helps ensure uniform photobleaching for minimal effect on subsequent scans with the same color. This uniform exposure also has the benefit of not requiring linearity in response of the sample (i.e., the light-to-response of the sample itself is not required to be linear). This has advantages in systems containing mixtures or in samples where the linearity of response is not valid, or even known. Signal and data processing provide a data set representative of a single detector with 6 decades of dynamic range. In one aspect, data from only one detector may be taken, for example where it is know a priori that the intensity range of a signal to be detected will be within the detection range of one of the detectors. In one aspect, the detector responsivity is adjusted to match the known or expected dynamic range of light emitted from the sample area.
[0024] While the invention has been described by way of example and in terms of the specific embodiments, it is to be understood that the invention is not limited to the disclosed embodiments. To the contrary, it is intended to cover various modifications and similar arrangements as would be apparent to those skilled in the art. Therefore, the scope of the appended claims should be accorded the broadest interpretation so as to encompass all such modifications and similar arrangements.
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Systems and method for detecting and measuring light emitted from a sample and having a large dynamic range, e.g., a range of luminous intensity covering six or more orders of magnitude, that may be difficult to fully detect using a single detector with a limited detection range. Simultaneous measurement of the emitted light in two intensity ranges is performed using two detectors, e.g., one including a photomultiplier tube (PMT) and the other including a solid state detector such as a photodiode. A beam splitting element directs light emitted from a sample under investigation to both detectors simultaneously such that a portion of the light impinges on the first detector and a second portion of the light impinges on the second detector. A processor receives output signals from the two detectors and provides an output representing the luminous intensity of the sample over a detection range greater than the detection range of each individual detector, thereby providing a detection system having an enhanced dynamic range.
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This application claims the benefit of U.S. Provisional Application(s) Ser. No(s). 60/072,713, filed on Jan. 13, 1998.
TECHNICAL FIELD
The present invention relates, in general, to a paint roller frame having a cage assembly attached thereto and, more particularly, to a paint roller frame and cage assembly which securely retains a paint roller cover thereon during painting and which permits the paint roller cover to be easily removed therefrom after usage or for replacement purposes.
BACKGROUND ART
There are numerous types of paint roller frames and cage assemblies that permit the removal of the roller cover therefrom for replacement purposes. Such removal and/or replacement entails varying degrees of difficulty since if it is relatively easy to remove the roller cover from the cage assembly, the roller cover is usually not positively retained in place on the cage assembly and thus can move longitudinally relative thereto during painting. Conversely, if the roller cover is securely retained on the cage assembly, it is relatively difficult to remove it therefrom for replacement purposes or at the time painting has been completed. Such is the case with the paint roller frame disclosed in U.S. Pat. No. 5,345,648 (Graves) wherein the paint roller cover is retained on the cage assembly by a Belleville type washer having a plurality of radially extending prongs which grip the inner surface of the roller cover. Since the prongs become embedded in the inner surface of the roller cover, it is extremely difficult to remove the roller cover from the cage assembly in this case.
Another inherent disadvantage of most paint roller frames is that the cage assemblies used to support the roller cover include areas where paint may become entrapped, thus making the cage assemblies difficult to clean. Also, some cage assemblies do not provide uniform support for the roller cover permitting the roller cover to develop flat spots or become out of round making the roller cover less effective in spreading paint.
Because of the foregoing inherent disadvantages associated with presently available paint roller frames, it has become desirable to develop a paint roller frame which positively retains the roller cover thereon during painting while allowing the roller cover to be quickly and easily removed therefrom for replacement purposes or when painting has been completed. Furthermore, the resulting paint roller frame should be easy to clean and should provide substantial uniform support to the surface of the roller cover.
SUMMARY OF THE INVENTION
The present invention solves the problems associated with the prior art paint roller frames and other problems by providing a paint roller frame having a cage assembly which positively retains the roller cover thereon during painting and still permits the roller cover to be easily removed therefrom when desired. The cage assembly includes a cage body comprising a plurality of circumferentially spaced-apart, longitudinally extending roller cover support bars joined together by a plurality of arcuate ribs interposed between the support bars. An outboard end cap is received over the outboard end of the cage body while an inboard end cap is received over the inboard end thereof. A centrally located bore is provided in the hub portions of each of the aforementioned end caps permitting the shaft portion of the paint roller frame to be received therethrough allowing rotation of the cage assembly about the shaft of the paint roller frame. The inboard end cap has a plurality of circumferentially spaced-apart longitudinally extending ribs which grippingly engage the inner surface of the inboard end of the roller cover to securely retain the roller cover on the cage assembly. When painting has been completed or when it is desired to replace the roller cover, the paint roller frame with the roller cover thereon can be oriented vertically with the outboard end cap being located lower than the inboard end cap and by rapping the inboard side of the paint roller frame against a solid surface, the weight of the paint roller cover, with the paint retained therein, causes the roller cover to become disengaged from the longitudinally extending ribs on the inboard end cap resulting in the roller cover dropping from the cage assembly.
Accordingly, an object of the present invention is to provide a paint roller frame which securely retains the roller cover thereon during painting and still permits the roller cover to be quickly and easily removed therefrom for replacement purposes or after painting has been completed.
Another object of the present invention is to provide a paint roller frame having a structure which permits paint to easily drain therefrom and which minimizes the amount of paint entrapped therein.
Still another object of the present invention is to provide a paint roller frame which provides substantial uniform support for the paint roller cover over the length thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the paint roller frame and cage assembly of the present invention.
FIG. 2 is a front elevational view of the paint roller frame and cage assembly of the present invention with a roller cover received thereon.
FIG. 3 is a cross-sectional view of the inboard end cap of the cage assembly taken across section-indicating lines 3 — 3 in FIG. 2 .
FIG. 3A is an enlarged cross-sectional view of the inboard end cap shown in FIG. 3 and illustrates a longitudinally extending rib thereon.
FIG. 3B is a cross-sectional view taken across section-indicating lines 3 B— 3 B in FIG. 3 A.
FIG. 4 is a cross-sectional view of the cage assembly taken across section-indicating lines 4 — 4 in FIG. 2 .
FIG. 5 is a cross-sectional view of the outboard end cap of the cage assembly taken across section-indicating lines 5 — 5 in FIG. 2 .
FIG. 6 is a cross-sectional view of the paint roller frame and cage assembly taken across section-indicating lines 6 — 6 in FIG. 2 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings where the illustrations are for the purpose of describing the preferred embodiment of the present invention and are not intended to limit the invention described herein, FIG. 1 is a perspective view of a paint roller frame 10 with a cage assembly, shown generally by the numeral 12 , attached thereto. The frame 10 is formed from heavy gauge wire or rod that is bent so as to provide a handle portion 14 at one end thereof and the shaft portion 16 at the other end thereof for rotatably supporting the cage assembly 12 thereon. Typically, a hand grip (not shown), which may be made of plastic or wood, is attached to the end of the handle portion 14 to assist in gripping the paint roller frame 10 with one hand. A threaded socket (not shown) may be provided in the outer end of the hand grip to permit attachment of an extension pole, if desired.
The cage assembly for the present invention can be any structure that can support a roller cover thereon. For illustration purposes only, as shown in FIG. 2, the cage assembly 12 may be molded of a nylon material, such as Delrin or the like, and includes a substantially rigid one-piece cage body 18 having a substantially circular cross-section and comprised of a plurality of circumferentially spaced, longitudinally extending roller cover support bars 20 joined together at a plurality of axially spaced-apart locations by arcuate ribs 22 interposed between the support bars 20 . The support bars 20 are substantially straight and of uniform height over their entire length, the height of the ribs 22 corresponding to the height of the support bars 20 , and the ribs 22 are joined to the bars 20 forming axially spaced annular rings 24 each having an outer diameter that is slightly less than the inner diameter of a paint roller cover resulting in the outer diameter of the cage body 18 being slightly less than the inner diameter of the paint roller cover to be received thereon.
As shown in FIG. 6, the cage body 18 has an axial opening 26 therethrough to receive the shaft portion 16 of the frame 10 . The outboard end of the cage body 18 is provided with a longitudinally extending circumferential surface 28 terminating in a chamfered surface 30 . A circumferential groove 32 is provided in the longitudinally extending circumferential surface 28 . The inboard end of the cage body 20 is similarly provided with a longitudinally extending circumferential surface 34 terminating in a chamfered surface 36 . As in the case of the outboard end of the cage body 18 , a circumferential groove 38 is also provided in the longitudinally extending circumferential surface 34 .
An end cap 50 , which may also be molded of a nylon material, such as Delrin or the like, and having a substantially circular cross-section with an outer diameter approximating the inner diameter of the paint roller cover to be received thereon, is provided to cover the outboard end of the cage body 18 . The end cap 50 has an annular recess 52 formed therein. The diameter of circumferential surface 54 defining annular recess 52 approximates the outer diameter of the longitudinally extending circumferential surface 28 on cage body 18 . An inwardly directed circumferential lip 56 , having a configuration complementary to circumferential groove 32 in the longitudinally extending circumferential surface 28 on cage body 18 , is provided on the circumferential surface 54 of end cap 50 . The inner diameter of the inwardly directed circumferential lip 56 approximates the root diameter of circumferential groove 32 . A centrally located bore 58 is provided in hub portion 60 of end cap 50 and terminates in a blind bore 62 on the outboard side of end cap 50 . End cap 50 is received over the longitudinally extending circumferential surface 28 on cage body 18 permitting the longitudinally extending circumferential surface 28 to be received in annular recess 52 in end cap 50 and allowing inwardly directed circumferential lip 56 to be received in circumferential groove 32 on the longitudinally extending circumferential surface 28 . In this manner, end cap 50 is lockingly engaged with longitudinally extending circumferential surface 28 on cage body 18 . Chamfered surface 30 on the end of longitudinally extending surface 28 on cage body 18 acts as a pilot surface for the receipt of end cap 50 thereon. The shaft portion 16 of the frame 10 is received through bore 58 in hub portion 60 of end cap 50 so that its end is positioned in blind bore 62 . A cap nut 64 is received on the end of shaft portion 16 of frame 10 and is positioned within blind bore 62 and abuts the surface 66 which defines the bottom of blind bore 62 . A cap (not shown) may be provided to cover the opening to blind bore 62 .
Similarly, an end cap 70 , which may also be formed of Delrin or the like and having a substantially circular cross-section, is provided to cover the inboard end of the cage body 18 . The end cap 70 has an annular recess 72 therein. The diameter of circumferential surface 74 defining annular recess 72 approximates the outer diameter of the longitudinally extending circumferential surface 34 on cage body 18 . An inwardly directed circumferential lip 76 , having a configuration complementary to circumferential groove 38 in the longitudinally extending surface 34 on cage body 18 , is provided on circumferential surface 74 of end cap 70 . The inner diameter of inwardly directed lip 76 approximates the root diameter of the circumferential groove 38 . A bore 78 is provided in hub portion 80 of end cap 70 . End cap 70 is received over the longitudinally extending circumferential surface 34 on cage body 18 permitting the longitudinally extending circumferential surface 34 to be received within annular recess 72 in end cap 70 and allowing inwardly directed circumferential lip 76 to be received in circumferential groove 38 on longitudinally extending circumferential surface 34 . In this manner, end cap 70 is lockingly engaged with longitudinally extending circumferential surface 34 on cage body 18 . Chamfered surface 36 on the end of longitudinally extending surface 34 on cage body 18 acts as a pilot surface for the receipt of end cap 70 thereon. The shaft portion 16 of the frame 10 is received through bore 78 in hub portion 80 and is staked outwardly thereof forming oppositely disposed ears 82 . A washer 84 is received over shaft portion 16 of frame 10 and is interposed between oppositely disposed ears 82 and end 86 of end cap 70 .
End 86 of inboard end cap 70 is provided with an outwardly directed circumferential flange 88 . As shown in FIG. 3, the outer surface of inboard end cap 70 is provided with four (4) circumferentially spaced-apart longitudinally extending ribs 90 which originate adjacent the inboard end of end cap 70 and terminate at the outwardly directed circumferential flange 88 . The diameter across oppositely positioned longitudinally extending ribs 90 is slightly greater than the inner diameter of the paint roller cover to be received thereon. The diameter across oppositely disposed longitudinally extending ribs 90 should be sufficient to tightly and frictionally engage the paint roller cover to be received thereon, yet allow an easy disengagement during the removal process. Typically, the diameter across oppositely disposed longitudinally extending ribs 90 is at least 0.020 inches greater than the inner diameter of the paint roller cover.
In order to install a paint roller cover 100 on paint roller frame 10 , the paint roller cover 100 is slidingly received over outboard end cap 50 , roller cover support bars 20 , and inboard end cap 70 until the end 102 of paint roller cover 100 abuts outwardly directed circumferential flange 88 on end cap 70 . When the paint roller cover 100 is so installed on paint roller frame 10 , the longitudinally extending ribs 90 on end cap 70 engage the inner surface of the paint roller cover 100 preventing the roller cover 100 from becoming disengaged from the frame 10 . When painting has been completed, the paint roller frame 10 , with the paint roller cover 100 thereon, is oriented vertically with outboard end cap 50 being positioned so as to be located lower than inboard end cap 70 . By rapping the inboard side of the shaft portion 16 of the paint roller frame against a solid surface, the weight of the paint roller cover 100 , with the paint retained therein, causes the roller cover 100 to become disengaged from the longitudinally extending ribs 90 and to drop from the roller frame 10 . Since the ribs 90 are oriented in the same direction as longitudinal axis of the roller cover 100 , and thus, in the direction of motion of the roller cover 100 during the removal process, the paint roller cover 100 , with the paint retained therein, can be easily removed from frame 10 for disposal purposes without the painter touching the roller cover 100 .
Certain modifications and improvements will occur to those skilled in the art upon reading the foregoing. It should be understood that all such modifications and improvements have not been expressly set forth herein for the sake of conciseness and readability, but are properly within the scope of the following claims.
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A paint roller frame which securely retains a paint roller cover thereon during painting and which permits the roller cover to be easily removed therefrom is disclosed. The paint roller frame includes a cage assembly comprising a cage body and oppositely disposed end caps having bores therein permitting the passage of the paint roller frame therethrough. The inboard end cap includes a plurality of circumferentially spaced-apart longitudinally extending ribs which securely engage the inner surface of the paint roller cover during the painting process and which permit the easy removal of the roller cover therefrom when painting has been completed or when the roller cover needs replacement.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is based upon and claims the benefit of priority of the prior Japanese Patent Application No. 2009-123524, filed on May 21, 2009, the entire contents of which are incorporated herein by reference.
FIELD
[0002] The embodiments discussed herein are related to an apparatus and method for controlling an open amount of a plurality of air transfer grilles.
BACKGROUND
[0003] Data centers may be configured to supply cold air to server racks bearing information technology (IT) devices from the under floor space through air transfer grilles (grilles) have been used. In the above-described data center, there has been a tendency for the calorific value of each of the server racks to increase with an increase in the heat generation density of the IT devices borne on the server racks. Consequently, a hotspot or the like occurs due to the infiltration of exhaust from the IT devices.
[0004] Here, the air flows that are observed in the data center will be described with reference to FIG. 17 . As shown in FIG. 17 , the air flows that are observed in the data center include the flow of air that is blown out from an air conditioner and that is sucked into the rack (see I shown in FIG. 17 ), the flow of air that is blown out from the air conditioner and that is sucked into the air conditioner (see II shown in FIG. 17 ), the flow of air that is discharged from the rack and that is sucked into the air conditioner (see III shown in FIG. 17 ), and the flow of air that is discharged from the rack and that is sucked into the rack (see IV shown in FIG. 17 ).
[0005] When a large volume of air is exhausted from the rack and is passed to a path leading to the rack so that the air is sucked into the rack 21 , the hotspot occurs due to the infiltration of exhaust from the IT devices. The method of reducing the temperature of air sent from an air conditioner and/or the method of adding facilities to the data center have been available as the method of reducing the above-described hotspot (see Japanese Laid-open Patent Publication No. 2008-185271, Japanese Laid-open Patent Publication No. 2006-046671, and Japanese Laid-open Patent Publication No. 2002-6992). For example, the method of adding an air conditioning system to reduce the temperature of air sent from an air conditioner to reduce the temperature of the entire room and/or the method of adding a partition to the side part of a row of racks and/or the upper part of the rack has been used to reduce the hotspot occurring due to the exhaust infiltration.
[0006] Incidentally, since the above-described method of reducing the temperature of the air sent from the air conditioner and/or the above-described method of adding the facility to the data center allows for reducing the air temperature, a large amount of power is consumed. Further, since providing the additional facilities costs money, it has been difficult to cool the racks with efficiency.
SUMMARY
[0007] According to an aspect of the embodiments, an apparatus for controlling an open amount of a plurality of air transfer grilles which are installed in a room, each of the air transfer grilles blowing air cooled by an air conditioner, the room accommodating a plurality of computers, each of the computers having a inlet and controlling the amount of intake air on the basis of an internal temperature of each of the computers, the apparatus includes, a memory for storing first information including a plurality of relations, each of the relations being relation between one of the air transfer grilles and at least one of the computers inhaling air from the one grille;
an obtaining unit for obtaining second information corresponding to an amount of intake air of each of the computers, a determining unit for determining a plurality of first target amounts of blowing to each of the computers on the basis of the second information, for determining a plurality of second target amount of blowing from each of the air transfer grilles on the basis of the plurality of first target amounts and the first information stored in the memory so that each of air of the first target amounts are blown to each of the computer, and for determining a plurality of open amounts of the plurality of each of the air transfer grilles on the basis of the plurality of second target amounts so that each of the amounts of blowing from each of the grilles becomes each of the second target amounts, a controller for controlling each of the open amount on the basis of the each of the determined open amounts.
[0009] The object and advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not restrictive of the invention, as claimed.
BRIEF DESCRIPTION OF DRAWINGS
[0010] FIG. 1 is a block diagram showing the configuration of an open amount controlling apparatus according to a first embodiment.
[0011] FIG. 2 is a block diagram showing the configuration of an open amount controlling apparatus according to a second embodiment.
[0012] FIG. 3 shows an exemplary arrangement of racks 21 and grilles 23 .
[0013] FIG. 4 shows the positional relationship of racks 21 and grilles 23 .
[0014] FIG. 5 also shows the positional relationship of racks 21 and grilles 23 .
[0015] FIG. 6 also shows the positional relationship of racks 21 and grilles 23 .
[0016] FIG. 7 shows the grille volume determined by exemplary calculation.
[0017] FIG. 8 shows an exemplary target air volume of each grille 23 .
[0018] FIG. 9A and 9B show that a simulation are repeated at each change in the grille aperture ratio to cause the simulation air volume to approach the target grille volume.
[0019] FIG. 10 is a flowchart illustrating all of processing procedures performed through the open amount controlling apparatus according to the second embodiment.
[0020] FIG. 11 is a flowchart illustrating target grille-calculating processing procedures performed through the open amount controlling apparatus according to the second embodiment.
[0021] FIG. 12 is a flowchart illustrating target-grille volume-achievement-determination processing performed through the open amount controlling apparatus according to the second embodiment.
[0022] FIG. 13 shows the rack 21 temperature obtained when the grille aperture ratios is not improved.
[0023] FIG. 14 shows the rack 21 temperature obtained when the grille aperture ratios is improved.
[0024] FIG. 15 shows a comparison of the rack 21 intake air temperature obtained when the grille aperture ratio is improved and that obtained when the grille aperture ratio is not improved.
[0025] FIG. 16 shows a computer executing a grille aperture ratio-calculating program.
[0026] FIG. 17 shows the air flow observed in an air conditioning system.
DESCRIPTION OF EMBODIMENTS
[0027] Hereinafter, an open amount controlling apparatus, a grille aperture ratio-calculating method, and a grille aperture ratio-calculating program according to each embodiment will be described in detail with reference to the attached drawings.
First Embodiment
[0028] In each of the following embodiments, the configuration and processing of an open amount controlling apparatus 1 according to a first embodiment will be described and the advantages of the first embodiment will be described at the end.
[0029] First, the configuration of the open amount controlling apparatus 1 according to the first embodiment will be described with reference to a block diagram shown in FIG. 1 .
[0030] The open amount controlling apparatus 1 according to the first embodiment calculates the aperture ratio of a grille provided to supply cooling air to cool racks 21 . Particularly, the open amount controlling apparatus 1 includes a target-grille air volume-calculating unit 2 , a simulation unit 3 , and a grille aperture ratio-calculating unit 4 .
[0031] The target-grille air volume-calculating unit 2 calculates information about the target grille air volume appropriate to cool the racks 21 regarding cooling air which is sent through a grille to cool the racks 21 .
[0032] The simulation unit 3 sets a specified grille aperture ratio, performs a simulation based on the specified grille aperture ratio, and calculates the simulation-grille air volume information indicating the volume of air sent from the grille to the rack 21 as the simulation result.
[0033] The grille aperture ratio-calculating unit 4 calculates the target grille aperture ratio based on the difference between the target-grille air volume information calculated through the target-grille air volume-calculating unit 2 and the simulation-grille air volume information calculated through the simulation unit 3 .
[0034] Thus, the grille aperture ratio-calculating unit 1 calculates the target-grille air volume information indicating the air volume which is appropriate to cool the racks 21 regarding the cooling air which is sent through the grille to cool the racks 21 . Further, the open amount controlling apparatus 1 sets the specified grille aperture ratio, performs the simulation based on the specified grille aperture ratio information, and calculates the simulation-grille air volume information indicating the volume of air sent from the grille to the racks 21 as the simulation result. Then, the open amount controlling apparatus 1 calculates the target grille aperture ratio based on the difference between the target-grille air volume information and the simulation-grille air volume information.
[0035] Therefore, the open amount controlling apparatus 1 calculates the appropriate grille aperture ratio and performs the layout optimization by adjusting the grille arrangement, the grille aperture ratio, etc. so that the cooling air is appropriately sent to the racks 21 . Consequently, the racks 21 can be cooled with efficiency.
Second Embodiment
[0036] Hereinafter, the configuration and processing flow of an open amount controlling apparatus 10 according to a second embodiment will be described in sequence and the advantages of the second embodiment will be described at the end. Further, in the following second embodiment, the target grille volumes indicating the air volume which is appropriate to cool the racks 21 is calculated for each grille 23 in a data center having under floor space provided to supply cooling air from an air conditioner 22 to racks 21 , for example.
[0037] [The Configuration of the Open Amount Controlling Apparatus]
[0038] First, the configuration of the open amount controlling apparatus 10 will be described with reference to a block diagram shown in FIG. 2 . As shown in FIG. 2 , the above-described open amount controlling apparatus 10 includes an input unit 11 , an output unit 12 , a control unit 13 , and a storage unit 14 . Hereinafter, the processing performed through each of the above-described units will be described.
[0039] The input unit 11 is provided to transmit the rack 21 arrangement information, the grille 23 arrangement information, information about the air volume of each rack 21 , information about the calorific value of each rack 21 , information about the gross air volume of the racks 21 , information about the gross calorific value of the racks 21 , information about the gross air volume of the air conditioners 22 , etc, and includes a keyboard, a mouse, a microphone, and so forth. Further, the output unit 12 externally transmits information about the grille aperture ratio.
[0040] The storage unit 14 stores data and/or programs used to execute various types of processing through the control unit 13 , and particularly includes an initial-grille aperture ratio-storage unit 14 a configured to store information about a specified grille aperture ratio used to perform the first simulation as the initial value.
[0041] The control unit 13 includes an internal memory provided to store programs specifying various types of processing procedures and appropriate data. The control unit 13 performs various types of processing based on the above-described appropriate data and programs, and particularly includes a target-grille air volume-calculating unit 13 a, a simulation unit 13 b, an air volume-determining unit 13 c, a set-grille aperture ratio-calculating unit 13 d, and a grille aperture ratio-calculating unit 13 e.
[0042] The target-grille air volume-calculating unit 13 a calculates the target grille volume which is appropriate to cool the racks 21 regarding the cooling air which is sent through the grille 23 to cool the racks 21 . More specifically, the input unit 11 transmits the rack 21 arrangement information, the grille 23 arrangement information, the air volume information of each rack 21 , the calorific value information of each rack 21 , the gross air volume information of the racks 21 , the gross calorific value information of the racks 21 (and/or the gross air volume information of the air conditioners 22 ), etc. to the target-grille air volume-calculating unit 13 a. Then, the target-grille air volume-calculating unit 13 a calculates the target grille volume based on the transmitted information.
[0043] Here, processing performed to calculate the target grille volume will be specifically described with reference to FIGS. 3 , 4 , 5 , 6 , 7 , and 8 . First, the target-grille air volume-calculating unit 13 a calculates the number of racks 21 to which each of the grilles 23 corresponds. For example, the target-grille air volume-calculating unit 13 a determines the rack coordinates a[j, l] indicating the coordinates of a rack 21 , the grille coordinates b[i, l] indicating the coordinates of a grille 23 , and the rack volume x[i, l] indicating the air volume of each of the racks 21 .
[0044] For example, in the case where an exemplary data center shown in FIG. 3 is used, the coordinates a[ 1 , l], a[ 2 , l], a[ 3 , l], etc. are set as the rack coordinates indicating the coordinates of a row of racks 21 . Further, the coordinates b[ 1 , l], b[ 2 , l], b[ 3 , l] . . . , b[ 6 , l] are set as the grille coordinates indicating the coordinates of a row of grilles 23 . FIG. 3 shows an exemplary arrangement of racks 21 and that of grilles 23 . Here, FIG. 3 is a top view of a data center where cooling air sent from an air conditioner 22 flows from the under floor space and passes through the grilles 23 so that the cooling air is supplied to the racks 21 .
[0045] Then, the target-grille air volume-calculating unit 13 a calculates the number “k” of at least a single set of the rack coordinates a[j, l] shown between the grille coordinates b[i, l] and b[i+1, l] that are determined in regard to the value “i” for each of the grilles 23 .
[0046] Here, the positional relationship of the racks 21 and the grilles 23 will be described with reference to FIGS. 4 , 5 , and 6 . When the equation “k”=“0” holds, as shown in FIG. 4 , there is not any set of the rack coordinates between the grille coordinates b[i, l] and b[i+1, l]. Further, when the equation “k”=“1” holds, there is a single set of the rack coordinates between the grille coordinates b[i, l] and b[i+1, l].
[0047] In an example shown in FIG. 5 , there are at least two sets of the rack coordinates between the grille coordinates of both ends of a grille 23 B[ 0 , 1 ] so that the inequality “k”≧“2” holds. Further, since there is a single set of the rack coordinates between the grille coordinates of both ends of a grille 23 B[ 1 , 1 ], the equality “k”=“1” holds. Further, there are at least two sets of the rack coordinates between the grille coordinates of both ends of a grille 23 B[ 2 , 1 ] so that the inequality “k”≧“2” holds.
[0048] Likewise, in an example shown in FIG. 6 , there is a single set of the rack coordinates between the grille coordinates of both ends of each of grilles 23 B[ 0 , 1 ], B[ 1 , 1 ], B[ 3 , 1 ], B[ 4 , 1 ], and B[ 6 , 1 ] so that the equality “k”=“1” holds. Further, since there is not any set of the rack coordinates between the grille coordinates of both ends of each of grilles 23 B[ 2 , 1 ] and B[ 5 , 1 ], the equality “k”=“0” holds.
[0049] Here, the target-grille air volume-calculating unit 13 a selects a calculation formula appropriate to calculate the target grille 23 based on the value of “k” and performs the target grille 23 calculation processing. For example, when the value of “k” is “0”, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] according to the following expression (1).
[0000] y[j,l]={ ( b[j+ 1, l]−b[j,l ])/( a [SUP+1, l]−a [INF, l ])}*( Tc/Tr )* x[i,l] (1)
[0050] Namely, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] based on the ratio between the grille 23 width observed between the grille coordinates (the grille coordinates b[i, l] and b[i+1, l] in FIG. 4 ) and the rack 21 width observed between the rack coordinates of both ends (the rack coordinates a[INF, l] and a[SUP, l] in FIG. 4 ). Here, the sign “Tc” indicates information about the gross air volume of the air conditioners 22 and the sign “Tr” indicates information about the gross air volume of the racks 21 .
[0051] Here, the above-described configurations will be specifically described based on an example shown in FIG. 7 . The method of calculating the target volume air of a grille 23 having the grille coordinates b[ 6 , 0 ] and b[ 5 , 0 ] of both ends, where the value of “k” is “0”, will be described. FIG. 7 is provided to illustrate the grille volume determined by exemplary calculation. As shown in FIG. 7 , the target-grille air volume-calculating unit 13 a calculates the ratio between the rack 21 width “0.6 m” shown between the rack coordinates a[ 4 , 0 ] and a[ 3 , 0 ] and the grille 23 width “0.4 m” shown between the grille coordinates b[ 6 , 0 ] and b[ 5 , 0 ].
[0052] Further, the ratio between the gross rack—air volume “130.32 m 3 /min” and the gross air conditioner—air volume “200 m m 3 /min” is calculated. The values of the above-described ratios are multiplied by the rack volume “10.86 m 3 /min” so that the target grille volume “10.60 m 3 /min” is calculated.
[0053] Further, when the value of “k” is “1”, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] according to the following expression (2). Here, the target-grille air volume-calculating unit 13 a searches for the rack coordinates matching the condition of the rack coordinates shown between the grille coordinates of both ends, which is shown as “b[i, l]<a[t, l]<b[i+1, l]”. When the value of “k” is “1”, the constant t has a single value and the equation MID=t holds
[0000] y[j,l ]={( a [MID, l]−b[j,l ])/( a [MID, l]−a [MID−1 ,l ])}*( Tc/Tr )* x [MID−1 ,l ]+{( a [MID, l]−b[j+ 1 ,l ])/( a [MID+1, l]−a [MID, l ])}*( Tc/Tr )* x [MID, l] (2)
[0054] Namely, the target-grille air volume-calculating unit 13 a calculates the ratio between the rack 21 width and the grille 23 width for each of the two racks 21 corresponding to the rack coordinates (the rack coordinates a[MID, l] in FIG. 4 ) shown between the grille coordinates of both ends (the grille coordinates b[i, l] and b[i+1, l] in FIG. 4 ), and calculates the target grille volume y[j, l] based on the sum total of the ratios.
[0055] Here, the above-described configurations will be specifically described based on the example shown in FIG. 7 . The method of calculating the target air volume of a grille 23 having the grille coordinates b[ 4 , 0 ] and b[ 5 , 0 ] of both ends, where the value of “k” is “1”, will be described. As shown in FIG. 7 , the target-grille air volume-calculating unit 13 a calculates the ratio between the rack 21 width and the grille 23 width for each of the two racks 21 corresponding to the rack coordinates a[ 3 , 0 ] shown between the grille coordinates b[ 4 , 0 ] and b[ 5 , 0 ] of both ends. The ratios are shown as “0.2 m/0.6 m” and “0.2/0.6 m”, respectively.
[0056] Then, the target-grille air volume-calculating unit 13 a multiplies the ratio “0.2 m/0.6 m” by the ratio between the gross rack volume 130.32 m 3 /min and the gross air conditioner—air volume 200 m 3 /min, and the rack volume “10.86 m3/min”. Further, the target-grille air volume-calculating unit 13 a multiplies the ratio “0.2 m/0.6 m” by the ratio between the gross rack volume “130.32 m3/min ” and the gross air conditioner—air volume 200 m3/min, and the rack volume “21.72 m3/min”. Then, the target-grille air volume-calculating unit 13 a sums the values obtained through the multiplications to calculate the target grille volume “16.39 m3/min”.
[0057] Further, when the value of “k” is “2” or more, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] according to the following expression (3). Here, the target-grille air volume-calculating unit 13 a searches for the rack coordinates matching the condition of the rack coordinates shown between the grille coordinates of both ends, which is shown as “b[i, l]<a[t, l]<b[i+1, l]”. When the value of “k” is “2” or more, the constant t has two values. In that case, the maximum value of the constant t is indicated by the sign “MAX” and the minimum value of the constant t is indicated by the sign “MIN”.
[0000] y[j,l]={{|a [MIN, l]−b[j,l ]|/( a [MIN, l]−a [MIN−1 , l ])}* x [MIN−1 ,l]+ . . . x [MIN, l]+ . . . +x [MAX−1, l]+ . . . +{|a [MAX, l]−b[j+ 1 ,l ]|/( a [MAX+1 ,l]−a [MAX, l ])}* x [MAX, l ]}*( Tc/Tr ) (3)
[0058] Namely, according to the example shown in FIG. 4 , the target-grille air volume-calculating unit 13 a determines the minimum rack coordinates a[MIN, l] and the maximum rack coordinates a[MAX, l] that are shown between the grille coordinates b[i, l] and b[i+1, l] of both ends. Then, the target-grille air volume-calculating unit 13 a multiplies the ratio between the rack 21 width corresponding to the minimum rack coordinates a[MIN, l] and the coordinates a[MIN−1, l] adjacent thereto, and a width observed between the grille coordinates b[i, l] and the rack coordinates a[MIN, l] by the rack volume x[MIN−1, l].
[0059] Then, the target-grille air volume-calculating unit 13 a multiplies the ratio between the rack 21 width corresponding to the maximum rack coordinates a[MAX, l] and the coordinates a[MAX+1, l] adjacent thereto, and a width observed between the grille coordinates b[i+1, l] and the rack coordinates a[MAX, l] by the rack volume x[MAX, l]. Then, the target-grille air volume-calculating unit 13 a sums the two values obtained through the multiplications and the rack volume x[MAX, l]˜ the rack volume x[MAX−1, l]. Then, the target-grille air volume-calculating unit 13 a multiplies the result of the above-described sum by Tc/Tr to calculate the target grille volume y[j, l].
[0060] Thus, as shown in FIG. 8 , the target-grille air volume-calculating unit 13 a calculates and sets the target grille volume for each of the grilles 23 . FIG. 8 shows an exemplary target air volume of each of the grilles 23 . Further, FIG. 8 is a top view of a data center where cooling air sent from an air conditioner 22 flows from the under floor space and passes through the grilles 23 so that the cooling air is supplied to the racks 21 .
[0061] The simulation unit 13 b sets a specified grille aperture ratio, performs a simulation based on the specified grille aperture ratio information, and calculates the simulation air volume indicating the volume of air sent from the grille 23 to the racks 21 , as a result of the simulation. Further, the simulation unit 13 b performs the simulation again based on the grille aperture ratio calculated through the set-grille aperture ratio-calculating unit 13 d that will be described later, and calculates the simulation air volume indicating the volume of air passing through the grille 23 , as a result of the simulation.
[0062] More specifically, the simulation unit 13 b sets the grille aperture ratio, where data of the above-described grille aperture ratio is stored in the initial-grille aperture ratio-storage unit 14 a, as the initial value, performs a simulation, and calculates the grille volume as the simulation result. Then, the simulation unit 13 b calculates the pressure loss ΔP based on the grille volume obtained as the simulation result according to the following expression (4).
[0000] Δ P[j,l]={r*K ( O[j,l ])*( y[j,l ]/( S*O[j,l ]))̂2}/2 (4)
[0063] Here, the sign “O[j, l]” denotes the grille aperture ratio obtained when the air volume y[j, l] is attained through the grille 23 B[j, l]. The sign “r” denotes the air density, the sign “S” denotes the grille 23 area, and the sign K(O) denotes a resistance coefficient determined based on the grille aperture ratio O. When a perforated plate is used, the resistance coefficient is calculated according to the following expression (5).
[0000] K ( x )=(1 x̂ 2)*{0.707*(1 −x )̂0.375+1− x }̂2 (5)
[0064] Upon receiving information about the grille aperture ratio O used to perform the next simulation, the information being transmitted from the set-grille aperture ratio-calculating unit 13 d, the simulation unit 13 b performs the simulation again based on the transmitted grille aperture ratio information.
[0065] The air volume-determining unit 13 c determines whether or not the value of the difference between the target grille volume and the calculated simulation air volume is greater than or equal to a specified threshold value. More specifically, the air volume-determining unit 13 c compares the target grille volume calculated through the target-grille air volume-calculating unit 13 a and the simulation air volume calculated through the simulation unit 13 b, and determines whether or not the value of the difference between the simulation air volume and the target grille volume is greater than or equal to the specified threshold value.
[0066] For example, as processing performed to determine whether or not the value of the difference between the simulation air volume and the target grille volume is greater than or equal to the specified threshold value, the air volume-determining unit 13 c calculates the average of differences between the target grille volume and the simulation air volume according to the following expression (6), and determines whether or not the calculated value is greater than or equal to the specified threshold value.
[0000] Σ j,l<|y[j,l]−y{tilde over ( )}[j,l ]|/{( y[j,l]+y{tilde over ( )}[j,l] )/2}>/{( n− 1)*( L− 1)} (6)
[0067] When the result of the above-described determination shows that the value of the difference between the target grille volume and the simulation air volume is greater than or equal to the specified threshold value, the air volume-determining unit 13 c notifies the set-grille aperture ratio-calculating unit 13 d that the simulation shall be performed again. Further, when the result of the above-described determination shows that the value of the difference between the target grille volume and the simulation air volume is smaller than the threshold value, the air volume-determining unit 13 c notifies the grille aperture ratio-calculating unit 13 e that the grille aperture ratio information shall be calculated.
[0068] When it is determined that the value of the difference between the target grille volume and the simulation air volume is greater than or equal to the specified threshold value, the set-grille aperture ratio-calculating unit 13 d calculates the grille aperture ratio information set for the next simulation based on the target-grille volume information and the simulation air volume information. Namely, upon receiving the notification that the simulation shall be performed again, the notification being transmitted from the air volume-determining unit 13 c, the set-grille aperture ratio-calculating unit 13 d calculates the grille aperture ratio O used to perform the next simulation according to the following expression (7), and notifies the simulation unit 13 b of the calculation result. More specifically, the set-grille aperture ratio-calculating unit 13 d substitutes the grille aperture ratio information set through the simulation, the simulation air volume information indicating the simulation result, and the target grille air volume into the expression (7) to calculate the grille aperture ratio information set for the next simulation. Here, the sign “O[j, l]” denotes the grille aperture ratio obtained when the air volume y[j, l] is attained through the grille 23 B[j, l], and the air volume y˜[j, l] indicates the target grille volume, and the sign “O˜[j, l]” indicates the grille aperture ratio set for the next simulation.
[0000] { r*K ( O[j,l ])*( y[j,l ]/( S*O[j,l ]))̂2}/2={ r*K ( O{tilde over ( )}[j,l] )*( y{tilde over ( )}[j,l ]/( S*O{tilde over ( )}[j,l] ))̂2}/2 (7)
[0069] Namely, the set-grille aperture ratio-calculating unit 13 d calculates the grille aperture ratio appropriate to achieve the target grille volume according to a calculation formula including the variables corresponding to the simulation air volume, the target grille volume, and the current grille aperture ratio.
[0070] Here, according to processing described in FIG. 9A and 9B , a simulation is repeated to cause the simulation air volume to approach the target grille volume. Namely, FIG. 9A and 9B show that the grille aperture ratio is changed and the simulation is repeated to cause the simulation air volume to approach the target grille volume. As shown in FIG. 9A and 9B , the simulation unit 13 b sets the initial value of the grille aperture ratio (the grille aperture ratio stands at 55.3% in FIG. 9 ), where the data of the initial value is stored in the initial-grille aperture ratio-storage unit 14 a , and performs the first simulation.
[0071] Then, the simulation unit 13 b calculates the simulation air volume (shown as the simulation value in FIG. 9A and 9B ) as the simulation result. For example, the simulation unit 13 b determines the simulation air volume of a grille 23 E 7 to be “8.76 m3/min” by calculation.
[0072] Next, the set-grille aperture ratio-calculating unit 13 d substitutes the simulation air volume, the target grille volume, and the current grille aperture ratio into the above-described expression (7) to calculate the grille aperture ratio used to perform the next simulation. For example, the set-grille aperture ratio-calculating unit 13 d determines the grille aperture ratio used to perform the next simulation of the grille 23 E 7 to be “0.65” by calculation.
[0073] The grille aperture ratio-calculating unit 13 e calculates the target grille aperture ratio based on the difference between the target-grille volume information and the simulation-air volume information. More specifically, upon receiving an instruction to calculate the grille aperture ratio information, the instruction being transmitted from the air volume-determining unit 13 c, the grille aperture ratio-calculating unit 13 e externally transmits the grille aperture ratio information set for the simulation as the target aperture ratio information.
[0074] After that, the simulation unit 13 b optimizes the grille aperture ratio by repeating the simulation to cause the simulation air volume to approach the target grille volume. As indicated by the graphs shown in the lower part of FIG. 9 , the simulation air volume approaches the target grille volume as the simulation is repeated.
[0075] Then, when the value of the difference between the target grille volume and the simulation air volume becomes smaller than the threshold value during the fourth simulation, the grille aperture ratio-calculating unit 13 e externally transmits data of the grille aperture ratio used for the fourth simulation as data of the target aperture ratio. For example, the grille aperture ratio-calculating unit 13 e externally transmits data shown as “0.74” as the target aperture ratio of the grille 23 E 7 .
[0076] [Processing Performed Through the Open Amount Controlling Apparatus]
[0077] Next, processing performed through the open amount controlling apparatus 10 according to the first embodiment will be described with reference to FIGS. 10 , 11 , and 12 . FIG. 10 is a flowchart illustrating all of processing procedures performed through the open amount controlling apparatus according to the second embodiment. FIG. 11 is a flowchart illustrating the target grille-calculating processing procedures performed through the open amount controlling apparatus according to the second embodiment. FIG. 12 is a flowchart illustrating the target-grille volume-achievement-determination processing procedures performed through the open amount controlling apparatus according to the second embodiment.
[0078] As shown in FIG. 10 , the open amount controlling apparatus 10 transmits information about, for example, the heat quantity of a rack 21 (operation S 101 ) and calculates the target grille volume indicating the air volume appropriate to cool the racks 21 regarding cooling air sent through the grille 23 to cool the racks 21 (operation S 102 ), which will be described later with reference to FIG. 11 .
[0079] Then, the open amount controlling apparatus 10 sets the grille aperture ratio, where data of the grille aperture ratio is stored in the initial grille aperture ratio-storage unit 14 a, as the initial value (operation S 103 ), and performs a simulation (operation S 104 ). Then, the open amount controlling apparatus 10 performs the target-grille volume-achievement-determination processing (operation S 105 ) to determine whether or not the value of the difference between the simulation air volume obtained as the simulation result and the target grille volume is greater than or equal to the specified threshold value, which will be described later with reference FIG. 12 , and determines whether or not the simulation processing may be finished (operation S 106 ).
[0080] When it is determined, as a consequence, that the value of the difference between the simulation air volume and the target grille volume is smaller than the specified threshold value and the simulation processing may be continued (No at operation S 106 ), the open amount controlling apparatus 10 calculates the grille aperture ratio appropriate to achieve the target grille volume according to a calculation formula including the simulation air volume, the target grille volume, and the current grille aperture ratio as variables (operation S 107 ). Then, the open amount controlling apparatus 10 performs the simulation again based on the calculated grille aperture ratio (operation S 104 ).
[0081] Further, when it is determined that the value of the difference between the simulation air volume obtained as the simulation result and the target grille volume is greater than or equal to the specified threshold value and the simulation processing may be finished (Yes at operation S 106 ), the open amount controlling apparatus 10 externally transmits the grille aperture ratio information used to perform the simulation as the target-aperture ratio information (operation S 108 ).
[0082] Then, the target grille - calculation processing performed through the open amount controlling apparatus 10 will be described with reference to FIG. 11 . As shown in FIG. 11 , the target-grille air volume-calculating unit 13 a of the open amount controlling apparatus 10 transmits information about the rack coordinates, the grille coordinates, and the rack volume (operation S 201 ) and determines that the equations i=0 and k=0 hold, as the initialization processing (operation S 202 ).
[0083] Then, the target-grille air volume-calculating unit 13 a determines whether or not the value “i” is smaller than or equal to the value “m−2” obtained by subtracting “2” from the total number of racks 21 , which is indicated by the sign “m” (operation S 203 ). Namely, when the value “i” is greater than the value “m−2” (No at operation S 203 ), the target-grille air volume-calculating unit 13 a determines that the number “k” is calculated for each of the grilles 23 and terminates the processing.
[0084] Further, when the value “i” is smaller than the value “m−2”, the target-grille air volume-calculating unit 13 a determines that the equations LOW =b[i, l] and HIGH=b[i+1, l] hold (operation S 204 ), and determines that the equation j=0 holds (operation S 205 ). Then, the target-grille air volume-calculating unit 13 a determines whether or not the value “j” is smaller than or equal to the value “n−2” obtained by subtracting “2” from the total number of grilles 23 , which is indicated by the sign “n” (operation S 206 ).
[0085] When the result of the above-described determination shows that the value “j” is smaller than or equal to the value “n−2” (Yes at operation S 206 ), the target-grille air volume-calculating unit 13 a determines whether or not the inequality LOW≦a[j, l]≦HIGH holds (operation S 207 ). Namely, the target-grille air volume-calculating unit 13 a determines whether or not the rack coordinates a[j, l] fall within the range of the equation LOW=b[i, l] to the equation HIGH=b[i+1, l].
[0086] When the result of the above-described determination shows that the inequality LOW≦a[j, l]≦HIGH holds (Yes at operation S 207 ), the target-grille air volume-calculating unit 13 a adds the value of the number “k” (operation S 208 ), adds the value “j” (operation S 209 ), and repeats the processing performed to determine whether or not the inequality LOW≦a[j, l]≦HIGH holds (from operation S 206 to operation S 209 ).
[0087] Further, when the value “j” exceeds the value “n−2” (No at operation S 206 ), the target-grille air volume-calculating unit 13 a determines that the number “k” of the racks 21 corresponding to a single grille 23 is calculated and performs the target grille-calculation processing.
[0088] The target-grille air volume-calculating unit 13 a determines whether or not the equation “k” =“ 0 ” holds (operation S 210 ). When it is determined that the equation “k” =“ 0 ” holds (Yes at operation S 210 ), the target-grille air volume-calculating unit 13 a sets the maximum number INF for the constant t where the inequality a[t, l]<b[i, l] holds and the minimum number SUP for the constant t where the inequality a[t, l]<b[i, l] holds (operation S 211 ). Then, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] corresponding to the ratio between the grille 23 width observed between the grille coordinates and the rack 21 width observed between the rack coordinates of both ends according to the above-described expression (1) (operation S 212 ).
[0089] When it is determined that the equation “k”=“0” does not hold (No at operation S 210 ), the target-grille air volume-calculating unit 13 a determines whether or not the equation “k”=“1” holds (operation S 213 ). Then, the target-grille air volume-calculating unit 13 a searches for the rack coordinates a[t, l] matching the condition of the rack coordinates shown between the grille coordinates of both ends, which is shown as “b[i, l]<a[t, l]<b[i+1, l]”, and sets the value of the constant t as MID (operation S 214 ). After that, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] according to the above-described expression (2) (operation S 215 ).
[0090] Further, when it s determined that the equation “k”=“1” does not hold (No at operation S 213 ), the target-grille air volume-calculating unit 13 a determines that the inequality “k”≧“2” holds (operation S 216 ). Then, the target-grille air volume-calculating unit 13 a determines the maximum value of the constant t to be MAX and the minimum value of the constant t to be MIN (operation S 217 ). After that, the target-grille air volume-calculating unit 13 a calculates the target grille volume y[j, l] according to the above-described expression (3) (operation S 218 ).
[0091] After that, the target-grille air volume-calculating unit 13 a externally transmits data of the target grille volume y[j, l] (operation S 219 ), adds the value “i”, and returns to operation S 203 . Here, when the value “i” exceeds the value “m−2” (No at operation S 203 ), the target-grille air volume-calculating unit 13 a determines that the number “k” is calculated for each of the grilles 23 and terminates the processing. The above-described operations are performed for each row l (where the inequality 0≦1≦L−1 holds). Here, the sign “L” denotes the total number of rack 21 rows.
[0092] Next, the target-grille volume-achievement determination processing will be described with reference to FIG. 12 . As shown in FIG. 12 , the simulation unit 13 b of the open amount controlling apparatus 10 performs the N-th simulation (operation S 301 ), and externally transmits information about the simulation air volume as the simulation result, where the simulation air volume indicates the volume of air sent from the grille 23 to the racks 21 (operation S 302 ).
[0093] Then, the air volume-determining unit 13 c compares the target grille air volume with the simulation air volume and determines whether or not the value of the difference between the simulation air volume and the target grille volume is greater than or equal to the specified threshold value (operation S 303 ).
[0094] When the result of the above-described determination shows that the value of the difference between the target grille volume and the simulation grille air volume is greater than or equal to the specified threshold value (Yes at operation S 303 ), the simulation unit 13 b sets the grille aperture ratio used to perform the next simulation, increments the value N by “1” (operation S 304 ), and returns to operation S 301 . Further, when it is determined that the value of the difference between the target grille volume and the simulation grille air volume is smaller than the specified threshold value, the target-grille volume-achievement determination processing is terminated.
Advantages of First Embodiment
[0095] As described above, the open amount controlling apparatus 10 calculates the target-grille air volume information indicating the air volume appropriate to cool the rack 21 regarding cooling air which is sent through the grille to cool the racks 21 . Further, the open amount controlling apparatus 10 determines a specified grille aperture ratio, performs a simulation based on the specified grille aperture ratio, and calculates the simulation-grille air volume information indicating the volume of air sent from the grille to the racks 21 as the simulation result. Then, the open amount controlling apparatus 10 calculates the target grille aperture ratio based on the difference between the target-grille air volume information and the simulation-grille air volume information.
[0096] Therefore, the open amount controlling apparatus 10 calculates the appropriate grille aperture ratios and performs the layout optimization by adjusting the grille 23 arrangement, the grille aperture ratios, etc. so that the cooling air is appropriately distributed among the racks 21 . Consequently, the racks 21 can be cooled with efficiency.
[0097] Here, the rack 21 temperature obtained through the layout optimization including the adjustment of the grille 23 arrangement, the grille aperture ratios, and so forth will be described with reference to FIGS. 13 and 14 . FIG. 13 shows the rack 21 temperatures obtained in an air conditioning system where the grille aperture ratios is not improved, and FIG. 14 shows the rack 21 temperatures obtained in an air conditioning system where the grille aperture ratios is improved. The blow off temperature and the air volume of the air conditioning system exemplarily shown in FIG. 13 are the same as those of the air conditioning system exemplarily shown in FIG. 14 . However, the temperature of the rack s shown in FIG. 14 is lower than that of the rack s shown in FIG. 13 . Namely, the racks shown in FIG. 14 are cooled with efficiency. More specifically, as exemplarily shown in FIG. 15 , the rack 21 temperature obtained at the time when the target grille volumes is achieved is lower than that obtained before the above-described improvement, which means that the racks 21 are cooled with efficiency.
[0098] Further, according to the first embodiment, the open amount controlling apparatus 10 determines whether or not the value of the difference between the target-grille air volume information and the simulation-grille air volume information is greater than or equal to the specified threshold value. When it is determined that the value of the difference between the target-grille air volume information and the simulation-grille air volume information is greater than or equal to the specified threshold value, the open amount controlling apparatus 10 calculates the grille aperture ratio information set for the next simulation based on the target-grille air volume information and the simulation-grille air volume information. After that, the open amount controlling apparatus 10 performs the simulation again based on the calculated grille aperture ratio and calculates the simulation-grille air volume information indicating the volume of air sent from the grille to the racks 21 as the simulation result. When it is determined that the value of the difference between the calculated target-grille air volume information and the simulation-grille air volume information is smaller than the specified threshold value, the set grille aperture ratio information is determined to be the target aperture ratio information by calculation.
[0099] Therefore, the open amount controlling apparatus 10 repeats the simulation until the simulation grille air volume approaches the target grille air volume to calculate a more appropriate grille aperture ratio. Consequently, the layout optimization including the adjustment of the grille 23 arrangements, the grille aperture ratios, and so forth is attained so that cooling air is appropriately distributed among the racks 21 . As a result, the racks 21 are cooled with efficiency.
[0100] Further, according to the first embodiment, the open amount controlling apparatus 10 calculates the target grille air volume based on the rack 21 arrangement information, the grille arrangement information, information about the air volume of each of the racks 21 , information about the calorific value of each of the racks 21 , information about the gross air volume of the racks 21 , information about the gross calorific value of the racks 21 (and/or information about the gross air volume of the air conditioners 22 ), etc., so that the appropriate target grille air volume can be calculated.
[0101] Further, according to the first embodiment, the open amount controlling apparatus 10 calculates the target grille volume based on the ratio between the rack 21 width and the grille 23 width so that the appropriate target grille air volume can be calculated based on the rack 21 arrangement, the racks 21 ize , the grille 23 arrangement, and the grilles 23 ize.
[0102] (1) Conditions for Terminating Simulation Processing
[0103] In the above-described second embodiment, the target grille air volume and the simulation air volume are compared with each other, and the simulation processing is terminated when the value of the difference between the simulation air volume and the target grille volumes is smaller than or equal to the specified threshold value. However, the third embodiment is achieved without being limited to the second embodiment.
[0104] For example, the open amount controlling apparatus 10 may terminate the simulation processing when the value of the difference between the pressure loss calculated based on the grille volume obtained as the simulation result and the pressure loss calculated based on the grille volume obtained as the previous simulation result.
[0105] Further, the open amount controlling apparatus 10 may terminate the simulation processing when the value of the difference between the grille aperture ratios used to perform the simulation and that used to perform the previous simulation is smaller than or equal to the specified threshold value.
[0106] Thus, when it is determined that the value of the difference between the pressure loss calculated based on the target-grille air volume information and that calculated based on the simulation-grille air volume information is greater than or equal to the specified threshold value, the open amount controlling apparatus 10 calculates the grille aperture ratio information set for the next simulation based on the target-grille air volume information and the simulation-grille air volume information. Therefore, the simulation is repeated until the appropriate pressure loss is obtained so that a more appropriate grille aperture ratio can be determined by calculation.
[0107] Thus, when the value of the difference between the grille aperture ratio used to perform the simulation and that used to perform the previous simulation is smaller than or equal to the specified threshold value, the open amount controlling apparatus 10 calculates the grille aperture ratio information set for the next simulation based on the target-grille air volume information and the simulation-grille air volume information. Therefore, the simulation is repeated until a change in the grille aperture ratio becomes insignificant so that a more appropriate grille aperture ratio can be determined by calculation.
[0108] (2) Target Grille Volume-Calculations
[0109] Further, the target grille volumes may be calculated in consideration of the grille 23 position and/or the rack 21 position. For example, since the exhaust infiltration often occurs in the racks 21 provided at the four corners of the rack 21 row, the target grille volume may be increased for the above-described racks 21 .
[0110] Thus, the target grille volumes is calculated in consideration of the grille 23 position and/or the rack 21 position, which makes it possible to calculate the appropriate target grille volume.
[0111] (3) System Configuration, Etc.
[0112] The components of each of the devices are functionally and conceptually illustrated in the attached drawings, and may not be configured as physically as shown in the drawings. Namely, the specific form of distribution and/or integration of the devices is not limited to those shown in the drawings, and all or part of the devices may be distributed and/or integrated functionally and/or physically in an arbitrary unit based on various loads and/or service conditions. For example, the target-grille air volume-calculating unit 13 a and the simulation unit 13 b may be integrated. Further, all or arbitrary part of the processing functions performed in the devices may be achieved through a CPU and/or a program which is analyzed and executed through the CPU, or may be achieved as hardware attained based on wired logic.
[0113] Further, of the processing procedures clarified in the above-described embodiment, all or part of the automatically performed processing procedures may be manually performed. Otherwise, all or part of the manually performed processing procedures may be automatically performed according to a known method. Further, the processing procedures, the control procedures, the specific names, and the information including various data and/or parameters that are shown in the above-described embodiments and/or the attached drawings may be arbitrarily changed apart from specified cases.
[0114] (4) Programs
[0115] Incidentally, the various processing procedures clarified in the above-described embodiments may be achieved through a computer executing a predetermined program. Hereinafter, therefore, an exemplary computer executing a program having the same functions as those of the above-described embodiments will be described with reference to FIG. 16 . More specifically, FIG. 16 shows a computer executing a grille aperture ratio-calculating program.
[0116] As shown in FIG. 16 , a computer 600 provided as the open amount controlling apparatus includes an HDD 610 , a RAM 620 , a ROM 630 , and a CPU 640 that are connected to one another via a bus 650 .
[0117] The ROM 630 stores a grille aperture ratio-calculating program having the same functions as those of the above-described embodiments. Namely, as shown in FIG. 16 , a target-grille air volume-calculating program 631 , a simulation program 632 , an air volume-determining program 633 , a set grille aperture ratio-calculating program 634 , and a grille aperture ratio-calculating program 635 are stored in the ROM 630 in advance. Here, the programs 631 , 632 , 633 , 634 , and 635 may be integrated and/or distributed as appropriate as is the case with the components of the open amount controlling apparatus 10 shown in FIG. 2 .
[0118] Further, when the CPU 640 executes the above-described programs 631 to 635 that are read from the ROM 630 , the programs 631 to 635 function as a target-grille air volume-calculating process 641 , a simulation process 642 , an air volume-determining process 643 , a set-grille aperture ratio-calculating process 644 , and a grille aperture ratio-calculating process 645 , as shown in FIG. 16 . The processes 641 to 645 correspond to the respective target-grille air volume-calculating unit 13 a, simulation unit 13 b, air volume-determining unit 13 c, set-grille aperture ratio-calculating unit 13 d, and grille aperture ratio-calculating unit 13 e that are shown in FIG. 2 .
[0119] Further, initial-grille aperture ratio data 611 is stored in the HDD 610 as shown in FIG. 16 . The initial-grille aperture ratio data 611 corresponds to the initial-grille aperture ratio storage unit 14 a shown in FIG. 2 .
[0120] In the embodiments that described above, the aperture rate is calculated. However it may calculate another open amount (for example, opening space for each of the air transfer grilles).
[0121] All examples and conditional language recited herein are intended for pedagogical purposes to aid the reader in understanding the invention and the concepts contributed by the inventor to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions, nor does the organization of such examples in the specification relate to a showing of the superiority and inferiority of the invention. Although the embodiments of the present invention have been described in detail, it should be understood that the various changes, substitutions, and alterations could be made hereto without departing from the spirit and scope of the invention.
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An apparatus for controlling an open amount of a plurality of air transfer grilles which are installed in a room, includes a determining unit for determining first target amounts of blowing to each of the racks, for determining second target amounts of blowing from each of the air transfer grilles on the basis of the first target amounts so that each of air of the first target amounts are blown to each of the racks, and for determining open amounts for each of the air transfer grilles on the basis of the plurality of second target amounts so that each of the amounts of blowing from each of the grilles becomes each of the second target amounts, and a controller for controlling each of the open amounts of the air transfer grilles on the basis of the each of the determined open amounts.
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BACKGROUND OF THE INVENTION
The present invention relates to load-bearing structures. More particularly, the present invention relates to a load-bearing structural member having a fluid chamber, which is capable of absorbing an applied load and, when the load is removed, returning the structure to its original configuration.
The types and varieties of load bearing structures are vast. Load bearing structures are commonly used in the framework and base construction of buildings, roads and bridges in order to not only support the weight of the structure and the loads placed thereon, but also to allow the structure to move somewhat due to thermal expansion, wind, earthquakes and other external forces. Load-bearing structures are also used in automobiles, submarines, and a myriad of other devices upon which load and pressure forces are applied.
In some devices, the use of flexible materials do not negatively affect the performance of the device. In others, strong, rigid materials must necessarily be used. The methods and materials used to create load bearing structures in buildings, roads and bridges have traditionally included the use of strong construction materials such as steel and reinforced concrete. As these materials allow limited flexibility, expansion spaces or members are typically employed. Oftentimes, resilient materials such as coils, elastomers and foams are used within the load-bearing structure. However, after a traumatic event, such as an earthquake, the resilient material may be crushed or otherwise damaged. These materials also tend to lose their resiliency due to the constant forces acting on them over time. The loss of resiliency causes the structure to remain in the displaced or compacted state instead of returning to its original configuration.
Therefore, what is needed is a load-bearing structural member which is capable of supporting a wide range of loads and then returning to its original state on removal of an applied load, even after a traumatic event. Such a load-bearing structural member is needed which will not lose its resiliency over time. The present invention fulfills these needs and provides other related advantages.
SUMMARY OF THE INVENTION
The present invention resides in a load-bearing structural member disposed between a selected base and a load bearing element, and which is capable of bearing forces from loads of various magnitudes while granting flexibility and resiliency to a structure. Generally, the load-bearing structural member comprises a housing fixed to the selected base and having a resilient wall defining an inner cavity and a first open end, a flexible partition joined to a surface of the resilient wall adjacent to the first open end, a displaceable closure member fitting within the first open end to define an inner fluid containing chamber between the cavity and the flexible partition, and a shaft interconnected between the closure member and the load bearing element. The flexible partition preferably comprises a low-friction elastomer, and several load-bearing structural members may be interconnected as needed for specific applications.
A load transmitted to the shaft via the load bearing element displaces the closure member and acts on the fluid within the inner chamber. The closure member is replaced to its original position when the contents of the fluid chamber reach a state of equilibrium. A port is formed through the housing wall in order to access the inner chamber. The fluid in the inner chamber may be comprised of a compressible gas or a liquid. When a liquid is placed in the chamber, the walls of the housing are deformably resilient to absorb applied loads. The fluid contents of the inner chamber may be under a negative pressure to create a vacuum-effect when the closure member is displaced away from the chamber, acting to pull the closure member back to its original position.
In one alternative form of the present invention the displaceable closure member includes an aperture over which the flexible partition is stretched to create a deformably resilient diaphragm. The diaphragm temporarily deforms through the aperture in reaction to the displacement of the closure member. When the load is removed, the diaphragm and the closure member return to their original positions.
In another form, the housing has a second open end in addition to the first open end and is constricted about a mid-portion. A second flexible partition is joined to an inner surface of the housing adjacent the second open end and a second shaft is interconnected between a load transmitting element and a second displaceable closure member fitting within the second open end. The inner fluid chamber extends between the opposing flexible partitions.
Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings illustrate the invention. In such drawings:
FIG. 1 is a cross-sectional view of a load-bearing structural member embodying the present invention disposed between a load transmitting element and a casing;
FIG. 2 is a cross-sectional view of multiple load-bearing structures of FIG. 1 attached side by side to form a structural support;
FIG. 3 is a cross-sectional view of another embodiment of the load-bearing structural member of the present invention, having a diaphragm stretched across an aperture of a closure member;
FIG. 4 is a cross-sectional view of the load-bearing structural member of FIG. 3, illustrating deformation of the diaphragm;
FIG. 5 is a cross-sectional view of another embodiment of the load-bearing structural member having two open ends;
FIG. 6 is a cross-sectional view of multiple load-bearing structural members of FIG. 5 connected end to end to form a structural support;
FIG. 7 is a cross-sectional view of multiple load-bearing structural members of FIG. 5 and modified load-bearing structural members of FIG. 1, connected to one another and configured to form a structural support for a closed-system bridge; and
FIG. 8 is a cross-sectional view of multiple load-bearing structural members of FIG. 5 and modified load-bearing structural members of FIG. 1, connected to one another in a lattice configuration to form a structural support.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As shown in the drawings for purposes of illustration, the present invention is concerned with a load-bearing structural member, generally illustrated in FIGS. 1-2 and 7 - 8 by the reference number 10 , in FIGS. 3 and 4 by the reference number 12 , and in FIGS. 5-8 by the reference number 14 . In the following description, functionally equivalent elements found in each of the illustrated embodiments will be given the same reference numbers.
The load-bearing structural members 10 - 14 each include a housing 16 having a wall 18 which defines an inner cavity 20 and an open end 22 . The wall 18 may be comprised of a rigid, strong material such as steel, but is preferably comprised of a strong yet resilient material which can withstand the external forces applied to the structural member 10 - 14 while retaining its shape. A flexible partition 24 is joined to an inner surface of the wall 18 of the housing 16 near the open end 22 . The flexible partition 24 is preferably comprised of a low-friction elastomer material. A displaceable rigid closure member 26 is fitted within the open end 22 under the flexible partition 24 to form an inner chamber 28 which typically contains a fluid between the flexible partition 24 and the cavity 20 .
The fluid may be either a compressed gas or a liquid. The closure member 26 may be attached to the flexible partition 24 . A shaft 30 is interconnected between the closure member 26 and a load bearing element 32 . A stop 34 may be attached to or formed at the open end 22 of the housing 16 to limit the downward travel of the closure member 26 . A port 36 is formed through the wall 18 of the housing 16 in order to gain access to the cavity 20 and inner fluid chamber 28 . Preferably, the port 36 comprises a one-way valve for removing fluid from the chamber to allow greater movement of the shaft 30 , closure member 26 and flexible partition 24 . The port 36 may be used to create a negative pressure or a vacuum within the inner chamber 28 as necessary. The port 36 can be closed off to prevent the escape of fluid from the chamber 28 when in use. Several ports 36 may be formed in the wall 18 as needed.
The load-bearing structural member 10 - 14 may be very small or very large depending on its application and the magnitude of loads to be bom. When a load is applied to the load bearing element 32 , the force of the load is transferred to the shaft 30 which displaces the closure member 26 . The closure member 26 moves either towards or away from the inner fluid chamber 28 acting upon the fluid contents of the inner chamber 28 .
When the inner fluid chamber 28 contains a compressible gas and the closure member 26 compresses the gas by moving towards the inner fluid chamber 28 in response to a load applied to the structural member 10 - 14 , the compressed gas exerts a force on the displaceable closure member 26 urging it back to its original position. When the chamber is full of liquid, the liquid serves to act as a shock absorber. However, when the inner chamber 28 contains a liquid, the dosure member 26 is restricted in its displacement to the deformability of the resilient walls 18 comprising the housing 16 and/or the empty space remaining in the inner fluid chamber 28 . In either event, the movable flexible partition 24 absorbs some of the force applied by moving either towards the wall 18 or collapsing upon itself within the chamber 28 .
When the displaceable closure member 26 moves away from the inner fluid chamber 28 in response to a load exerted upon the shaft 30 through the load bearing element 32 , a negative pressure is formed within the inner chamber 28 so as to cause the closure member 26 to be pulled back towards the inner chamber 28 . This vacuum-effect is particularly acute when the inner fluid chamber 28 contains liquid. The effect is even more pronounced when the contents of the inner chamber 28 are placed under a negative pressure before any loads or forces are applied to the structural member 10 - 14 .
A first embodiment of the load-bearing structural member 10 of the present invention is illustrated in FIGS. 1 and 2. The structural member 10 is disposed within a casing 38 which is attachable to the selected base. The selected base may take many forms of a structure or ground support such as end points of a bridge, the hull of a submarine, or the ground beneath a roadway, to name only a few. The housing 16 of the structural member 10 may be attached to the casing 38 , or the walls 18 of the housing 16 may be formed with the casing 38 so as to comprise a wall of the housing 16 . As illustrated in FIG. 1, the load transmitting element 32 typically attaches to the shaft 30 within the casing 38 and extends outside of the casing 38 through guide apertures 40 .
The load bearing element 32 may also be stabilized with the use of a guide track into which guide members 42 move vertically. A platform 50 is preferably connected to the load bearing element 32 to more evenly spread the forces applied to the load bearing element 32 . As illustrated in FIG. 2, the casings 38 may be joined together to form a surface support structure. Such a support structure would be particularly applicable where loads or forces are applied over a broad surface area.
Referring now to FIGS. 3 and 4, a second embodiment of the present invention is illustrated. In this particular embodiment, the closure member 26 of the structural member 12 has an aperture 44 through a central portion of the closure member 26 . A flexible partition 24 comprised of a resiliently deformable material is stretched over the closure member 26 , creating a diaphragm 46 over the closure member aperture 44 . The shaft 30 is typically cylindrical in order to attach to and support the outer edges of the closure member 26 . The contents of the inner fluid chamber 28 are preferably under a negative pressure. The shaft 30 ′ moves in response to a load being applied to it, causing the closure member 26 to become displaced. The displacement of the closure member 26 in one vertical direction causes the diaphragm 46 to deform and expand through the aperture 44 . As well as the compression and vacuum-effects on the contents of the fluid within the inner chamber 28 discussed above, the resiliency of the diaphragm 46 creates forces opposed to the forces acting upon the shaft 30 ′. These opposing forces counteract the load forces applied to the structural member 12 and replace the closure member 26 to its original position as the load acting on the shaft 30 ′ is lessened. Although not shown, the housing 16 of this embodiment may be interconnected to others to form support structures.
A third embodiment of the present invention is shown in FIGS. 5 and 6. This form of the load-bearing structural member 14 has two open ends 22 and two flexible partitions 24 attached the inner surface of the wall 18 near each respective open end 22 . Two closure members 26 are fitted within respective open ends so as to oppose one another, creating a inner fluid chamber 28 between the two flexible partitions 24 and the cavity 20 of the housing 16 . The wall 18 of the housing 16 is conStdcted near the mid-portion of the housing 16 . The constriction 48 acts as a barrier to prevent the closure members 26 from traveling past it. The restricted movement of the closure members 26 allows the vacuum-effect to be created when load forces initially push both closure members 26 in the same direction until one of the closure members 26 is stopped by the constriction 48 and the other closure member 26 continues to move away from the constriction 48 . The constriction 48 also enhances the vacuum-effect when the closure members 26 are pulled away from each other, creating such a negative pressure as to replace both closure members 26 to their original positions. The flexibility or tightness of the attached structural members 14 can be controlled by altering the distance that the shaft 30 and closure member 26 are allowed to traverse. Travel is limited by increasing the negative pressure within the chamber 28 .
Referring specifically now to FIG. 6, the housings 16 of the load-bearing structural members 14 may be connected end to end on a horizontal plane and interconnected to opposing vertical bases for lateral support. The connected structural members 14 may also be connected vertically end to end to create a pillar structural support member. Although the end to end connection mainly provides load bearing support in one plane, the deformably resilient walls 18 of the structural members 14 also provide a limited load beam support and flexibility in the other plane.
To enhance the load bearing support in both planes, a combination of the first and third structural members 10 and 14 having single and dual open ends, respectively, may be interconnected and configured to create a support structure such as the closed system bridge illustrated in FIG. 7 . In fact, a lattice of connected load-bearing structural members 10 - 14 may be created, as illustrated in FIG. 8, in order to provide support from a variety of angles. Although several embodiments have been described in detail for purposes of illustration, various modifications may be made without departing from the spirit and scope of the invention. Accordingly, the invention is not to be limited, except as by the appended claims.
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A load-bearing structural member is disposed between a selected base and a load bearing element and is capable of bearing loads of various magnitudes while granting flexibility and resiliency to a structure. The structural member includes a housing fixed to the base and having a resilient wall which defines an inner cavity and a first open end, a flexible partition joined to an inner surface of the wall adjacent to the first open end, a displaceable stiff closure member fitting within the first open end to define an inner fluid containing chamber between the cavity and the flexible partition, and a shaft interconnected between the closure member and the load bearing element. The load-bearing structural members may be interconnected and configured such to act as a support structure.
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This application is a 35 U.S.C. §371 national stage application of PCT/CN2012/071129, which was filed Feb. 14, 2012 and claimed the benefit of CN20110239124.1, filed Aug. 19, 2011, both of which are incorporated herein by reference as if fully set forth.
FIELD OF THE INVENTION
The present invention provides a pressurized metered dose inhaler composition with pharmaceuticals and a preparing method thereof, wherein the pressurised metered dose inhaler is a medicine used for treating respiratory diseases such as asthma and chronic obstructive pulmonary disease.
BACKGROUND OF THE INVENTION
Pressurized metered dose inhaler (pMDI) can make the inhaled pharmaceuticals topically and rapidly present the activity of the medicine, and has lower systemic adverse reaction when compared with an oral drug. The pMDI and dry powder inhaler (DPI) are the most general administrations for asthma or chronic obstructive pulmonary disease (COPD), which are used to administer the composition being one selected from a group consisting of a corticosteroid drug, a beta-2 agonist, an anticholinergics and a combination thereof.
Since 1995, Company 3M developed a product of pMDI with chlorofluorocarbons (CFC) as a propellant, and the product has become most popular administration for treating asthma or COPD. Compared with the oral drug, the pMDI may present activity more rapidly and provide lower systemic adverse reaction of the medicine. Typical components for treating such diseases include a corticosteroid drug, a beta-2 agonist, an anticholinergics, or a pharmaceutical composition being a dose inhaler and consisting of the mentioned drugs.
In the 1970s, it is found that the propellant of CFC may result in environmental protection problems in destroying ozonosphere, and thus the CFC is confronted by the situation of global restriction. In the end of 1980s, a substitute product of the DPI was developed, but the substitute product can not completely replace the pMDI with the CFC propellant all along, since the product tends to suffer moisture and the patient needs enough speed of inhaling when using the product to be efficiently administered. Until now, Company Riker of 3M firstly develops a substitute propellant for replacing the CFC propellant, i.e. the propellant of hydrofluoroalkanes (HFA), which includes 1,1,1,2-tetrafluoroethane (HFA 134a, HFC 134a) or 1,1,1,2,3,3,3-heptafluoro-n-propane (HFC 227ea, HFC 227, HFA227). However, because there are some problems, such as techniques of preparation and drug safety, to be overcome, the first product of the formulation of HFA MDI did not enter into the market until 1996, and was booming in 2004, which results in the complete restriction on producing the CFC MDI after 2010.
In the U.S. Pat. Nos. 5,225,183, 5,439,670, 5,695,743, 5,766,573, 5,836,299 and 6,352,684 owned by Company Riker/3M, the patented formulation including HFA 134a has been disclosed. The formulation includes components of β-2-adrenergic agonists including such as salbutamol, corticosteroid such as beclomethasone dipropionate, adrenergic components, choline and anti-histamine or anti-inflammatory drugs, and uses 1-50% ethanol compound as a solubilizer, and the surfactant, which may be the derivatives such as oleic acid, polyethylene glycol 400(PEG 400) or Span, is added with a weight ratio less than 5%. In the U.S. Pat. No. 6,743,413, HFA 134a and micronized drugs are used as main components without other excipients. The U.S. Pat. No. 5,776,432 discloses that HFA 134a, HFA 227, or a combination thereof is used as the propellant, and 2%-12% ethanol is used as the solubilizer of the main drug component, beclomethasone 17, 21 dipropionate, without any surfactant.
The U.S. Pat. No. 5,474,759 owned by Company Schering discloses that HFA 227 is used as the propellant, and propylene glycol diester with a long chain is used as the surfactant, wherein the main components thereof include compounds such as albuterol, albuterol sulfate, beclomethasone dipropionate, or mometasone furoate.
In the U.S. Pat. Nos. 5,653,962, 5,658,549 and 5,744,123 owned by Company GSK, the patented formulation including HFA has been disclosed. The formulation includes main components such as salmeterol, salbutamol and fluticasone propionate, but does not have co-solvent, and uses the surfactant less than 0.001%. The subsequent patents thereof relate to the modification of drug delivery uniformity. The U.S. Pat. Nos. 6,315,173 and 6,510,969 relate to the improvement of the sprinkle-nozzle. The U.S. Pat. No. 6,479,035 uses Fluticasone and 7-20% alcohol as the solubilizer, and uses 0.5-3% glycerol or PEG as the surfactant. In the U.S. Pat. Nos. 5,736,124, 5,817,293, 5,916,540, 5,922,306, 6,333,023, 6,200,549 and 6,222,339, the main component of formoterol has been disclosed, and 0.01-5% ethanol is adopted. The U.S. Pat. Nos. 6,303,103 and 6,238,647 disclose that salmeterol and anti-cholinergics are incorporated, and the excipient used thereby is less than 0.0001%. The U.S. Pat. No. 6,013,245 relates to beclomethasone and salbutamol, uses HFA 227 and does not use the surfactant. The U.S. Pat. No. 5,833,950 discloses beclomethasone, and uses HFA and the excipient less than 0.0001%.
Company Aeropharm has disclosed a patented formulation including HFA. The U.S. Pat. No. 5,891,419 discloses flunisolide with an addition of 0.5%-2% ethanol only. The U.S. Pat. No. 5,891,420 discloses triamcinolone acetonide with an addition of 1%-3% ethanol. The U.S. Pat. No. 6,458,338 relates to a metered dose formulation with amino acid as the stabilizer. In the U.S. Pat. Nos. 6,447,750, 6,540,982, 6,540,983, 6,548,049 and 6,645,468, a metered dose formulation of a main component of a drug treating diabetes has been disclosed. The U.S. Pat. No. 6,464,959 discloses a metered dose formulation of a main component of a drug treating diabetes, which is incorporated with amino acid as the stabilizer.
The U.S. Pat. No. 6,004,537 owned by Company Baker Norton (now TEVA) discloses that HFA is used as the propellant, and uses 10%-40% (w/w) ethanol as the solubilizer to dissolve the main components of Budesonide and Formoterol.
The U.S. Pat. No. 6,123,924 owned by Fisons discloses main components such as β 2 -receptor agonist: fenoterol hydrobromide, procaterol hydrochloride, salbutamol sulphate, terbutaline sulphate, anabolic steroid or steroid components; beclomethasone dipropionate, fluticasone propionate, tipredane, anti-histamine, anti-inflammation or acetyl-β-methylcholine bromide; cholinergic components: pentamidine isoethionate, tipredanene, docromil sodium, sodium cromoglycate, clemastine, budesonide and so on, which are distributed in HFA, and uses of polyvinylpyrrolidone (PVP) of 0.0000˜10% w/w as the suspending agent and PEG 400-3000 as the lubricating agent.
The TW Patent Application No. 200303767 owned by Company Chiesi discloses formoterol superfine formulation, which includes 0.003-0.192% w/v of (R,R)-(±)-formoterol fumarate, wherein the combination technique of pressurized metered inhaler formulation is used and 10˜20% ethanol and HCl are used to adjust pH value. It is emphasized that the ratio of particles equal to or less than 1.1 micrometer is larger than or equal to 30%. In the U.S. Pat. No. 7,223,381, the formulation is consisting of Budesonide, HFA propellant, and co-solvents of 13% ethanol and 0.2˜2% glycerol.
The U.S. Pat. No. 6,638,495 owned by Company Nektar relates to a formulation combination technique where the phospholipid is used as the excipient to form a microstructure and materials having biological activities are distributed in the pressurized metered inhaler.
The U.S. Pat. No. 6,932,962 owned by Company AstraZeneca relates to HFA atomization dose including fatty acid or a salt thereof, bile salts, phospholipid or alkyl glycosides as the surfactant, wherein the amount of the ethanol used thereby can be 5-20%.
The U.S. Pat. No. 7,481,995 owned by University College Cardiff Consultants Limited relates to a HFA MDI formulation technique which uses amino acid as the suspending excipient.
When observing the mentioned prior arts based on the pressurized metered dose inhaler prescription, in addition to the medicine and HFA gas, the techniques can be classified according to using conditions of the ethanol as follows.
1). Without any additives, as represented by Company GSK, which provides the medicine completely presented by a suspending solution mode, while such medicine has a problem that it is more difficult to make the administration uniform.
2). Without the use of ethanol and a simple use of an excipient, such as PVP or propanediol bischloroacetate.
3). Large amount of ethanol (more than 10%), which would completely dissolve the medicine, and other excipients may be added or not. In this case, the advantage is good uniformity of the administration, and the disadvantage are possibly worse stability of the medicine and the rare delicacy of alcohol that has bad acceptance for patients.
4). Medium-low amount of ethanol (about 1% to 10%) collocated with other excipients, in which the medicine is in a condition of partially being dissolved and partially without being dissolved. It has bigger effect on the stability of the formula that the particle diameter of the medicine would be caused to change with passing of the preserving time.
5). Extreme-low amount of ethanol (about 0.2% to 2%), such as the formula of Company Valois. In this case, the advantage is the better stability of the medicine since it is in a suspending solution station without being dissolved, while the disadvantage is the bad uniformity of the administration and thus the assistance of other excipients may be needed. Moreover, it may have more difficulty in the manufacturing process.
Although Valois SAS has published the formula about Budesonide HFA MDI, which uses 0.1-5% of PEG 300 and 0.2-2% of ethanol (referring to Indian Journal of Pharmaceutical Science, Vol. 69, No. 5, P. 722-724, September-October 2007). However, in order to reduce the absorption of the container with the drug and increase the uniformity of the administration, the mentioned formula needs a use of a special surface-anodized container, such as a standard anodized aluminum canister, to be filled therewith. When it is used in an scale-up production or a general container, such as an aluminum canister, some problems about quality would be generated. Accordingly, when actually mass producing the mentioned formula in pharmaceutical industry, even though the formula components are the same, the differences of quality would still be resulted from different mixture orders of components and different ways and equipments of filling. The examples of the differences of quality are insufficient amount of the main component, cohering of the particles of the medicine, bad uniformity and so on. Particularly, the mentioned conditions would occur more easily when a product contains two kinds of main components, since there are differences of physical and chemical characteristics as well as ratio of content existing between said two main components. Therefore, a change of the producing process in combining the excipient with the contents of the formula, especially the application in mixture orders and homogenizing methods of the main components with the propellant and other excipients, may generate a pressurized metered dose inhaler with stable, safer and more efficacious qualities.
SUMMARY OF THE INVENTION
Lung is a tender tissue, and thus it is necessary to consider making harm to lung as low as possible when performing a pulmonary administration. Although surface cells of lung have motor fibers capable of excluding the inhaled foreign body, the excluding function is limited. Therefore, when designing the dose inhaler formula, it shall use excipients as few as possible or those with lower toxicity. Although the use of large amount of solubilizer may cause the product to present a better uniformity, the stability thereof would reduce correspondingly. Accordingly, the policy of HFA MDI formula is researched in the present invention, which intends to prepare a safe and efficient suspending solution dose with fewest excipient and solubilizer, to achieve good uniformity of administration and long stability of products, and to provide the patients with efficient dose (<5 micrometer) capable of entering into the lung. However, the reducing of amounts of the excipient and solubilizer in the patented HFA formula would easily reduce the stability and uniformity of the produced medicines, especially when the product contains two main components, such as beta-2 agonists and corticosteroids. Besides, large difference of dosages and different physical and chemical characteristics between the two main components would more easily result in the phenomenon of worse uniformity and stability of the main components in the dose. Moreover, because the main components cannot be uniformly mixed the excipient during the producing process of the suspending solution dose, the particles of medicine may easily cohere again, which results in the phenomenon of significant reducing of efficiently inhaled dose (fine particle dose).
The present invention provides a method of preparing a metered dose inhaler composition, comprising steps of:
a) mixing 0.05%-10% (w/w %) alcohol with a surfactant to form a first mixture;
b) dispersing a beta-2 agonist in the first mixture to form a second mixture;
c) adding a hydrofluoroalkane (HFA) propellant into the second mixture to form a third mixture;
d) dispersing a corticosteroid in the third mixture; and
e) performing a filling step.
According to the mentioned concept, a stable and well-mixed suspending solution dose is formed in the present invention by using an inhaled medicine with proper producing process. The medicine includes a beta-2 agonist such as procaterol, salbutamol, formoterol and salmeterol, a corticosteroid such as budesonide, fluticasone, ciclesonide and beclomethasone, or a combination thereof. The hydrofluoroalkanes (HFA) propellant includes one of 1,1,1,2-tetrafluoroethane (HFA 134a, HFC 134a) or 1,1,1,2,3,3,3-heptafluoro-n-propane (HFC 227ea, HFC 227, HFA227), and the mentioned two HFA propellants may be mixed for use if necessary. The surfactant includes a polyethylene glycol (PEG) excipient for stabilizing the formula or lubricating the metering valve of container to prevent blocking, and the addition amount thereof is ranged from 0.01%-2.50% (w/w %), preferably 0.05%-1.50% (w/w %). Generally, the PEG having the mentioned concentration would not affect the solubility of the main components that results in reduction of stability. The PEG preferably has a molecular weight ranged from 100 to 6000, and in addition to the function of helping suspending, the PEG may be deemed as a corrector for particle diameter since the modification of the addition amount thereof may change the distribution of particle diameters. The ethanol absolute is added and the addition percent thereof is ranged from 0.05%-10.0% (w/w %), preferably 0.25%-2% (w/w %). With the mentioned concentration, the ethanol absolute may not only assistant in the dissolution of PEG, but also improve the phenomenon that the particles of the main component aggregate, which results from the HFA evaporated from the sprinkle-nozzle of the spray dose in the sprinkling moment. Furthermore, the surfactant, i.e. PEG 100-6000 molecular weight, used in the present invention is a commercially available product, and the needed viscidity can be adjusted by the amount of ethanol.
According to the mentioned concept, the present invention specifically provides a method of preparing a metered dose inhaler composition, comprising steps of:
a) using 0.05%-10% (w/w %) alcohol as an alcohol solvent to be mixed with a surfactant to form a mixture solution;
b) dispersing a beta-2 agonist in the mixture solution to form a uniform solution;
c) adding HFA into the uniform solution;
d) dispersing a corticosteroid in the uniform solution; and
e) performing a freeze filling step or a pressure filling step.
In the producing process of the spray dose provided in the present invention, a step of uniformly dispersing PEG in HFA is an important step for controlling the uniformity of particles of the main component. Firstly, little amount of alcohol is uniformly mixed with PEG. Because the particles of drug of inhaling type are very fine, the particles are apt to aggregate. For uniformly dispersing the particles by PEG, it is necessary to perform the mixing step by ultrasonic vibration for forming a concentrated solution. The viscosity and volume of the mixture solution of alcohol and PEG may be changed with the quantity and property of the main component, while the amount thereof shall not be larger than 2% (w/w %) of the total amount of the formula. However, if the quantity of the main component medicine is more and the appeared volume is much larger than the volume of the mixture solution of alcohol and PEG, it is not necessary to mix the alcohol with PEG in advance. Next, the mentioned concentrated solution or the mixture solution of alcohol and PEG would be homogenizedly stirred with HFA to for a homogenized solution, and then the main component with large quantity is slowly added into and mixed with the homogenized solution. In the abovementioned process, the order of adding the excipient and the way of mixing have significant effect. Particularly, when in a scale-up production, there are distinct improvements in the extent of uniformly dispersing of drug particles and the quantity of the main component medicine stained in the mixing tank. Finally, the freeze filling or pressure filling steps is performed.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Evaluation of Delivery Dose Uniformity:
The drug efficacy and safety of spray dose are affected by delivery dose uniformity, which includes:
1. the suspending solution is dispersed uniformly and quickly when shaking the bottle;
2. the uniformly suspending state is maintained at least 5 seconds after shaking; and
3. the tolerance range of the sprinkle-nozzle of the spray (the USA Food and Drug Administration requires that a qualified range is that an average of a group of sprinkle-nozzles is the target value ±10%, and the respective sprinkle-nozzle is the target value ±15%).
For obtaining a credible uniformity test, a dose unit sampling apparatus (DUSA) as required by United States Pharmacopeia (USP) is used with glass fiber filter (1 μm). After performing a spray sampling under a required air-extracting flow rate (28.3 L/min), the quantities of drugs in the actuator (or mouthpiece) and the sampling/drug-collecting apparatus are measured respectively by high-efficient chromatography. The initial three sprayings, medium four sprayings and final indicated three sprayings of a bottle are respectively tested for a single dosage. The specification requires that the main components in a single spraying shall be less than 25% of the indicated dosage according to the requirements of the Pharmacopeia, and an average amount of the main components of all ten sprayings shall be less than 15% of the indicated dosage. Moreover, the delivery dose uniformity is evaluated under the conditions of 40, relative humidity 75% and maintenance of six-months storing period for facilitating the stability.
Evaluation of Particle Size Distribution:
For determining the condition of particle size distribution of the drugs, a spray sampling is performed under an air-extracting flow rate (30.0 L/min) required by USP, and the analysis of particle size of the drugs in the spray sampling is performed by using Next Generation Cascade Impactor. The distribution and changing circumstances of the particles in every level when using Next Generation Cascade Impactor are observed under the conditions of 40, relative humidity 75% and maintenance of six-months storing period for facilitating the stability, so as to evaluate the stability of the drug particles suspending in the formula solution.
The delivery dose uniformity is analyzed for the spray according to Formula Example I of the process of the spray dose provided in the present invention. As shown in FIG. 1 where Budesonide in the first spraying has an indicated dosage of 180 mcg, after the six-months test of facilitating stability (40 and relative humidity 75%), every bottle of the sprays including totally ten sprayings of delivery dosages is complying with the requirement that the main component in a single spraying shall be less than 25% of the indicated dosage and an average value shall be less than 15% of the indicated dosage according to the Pharmacopeia. As shown in FIG. 2 where Procaterol HCl in the first spraying has an indicated dosage of 10 mcg, after the six-months test of facilitating stability (40 and relative humidity 75%), every bottle of the sprays including totally ten sprayings of delivery dosages is complying with the requirement that the main component in a single spraying shall be less than 25% of the indicated dosage and an average value shall be less than 15% of the indicated dosage according to the Pharmacopeia.
As shown in FIG. 3 illustrating the analysis of particle size distribution, after the six-months test of facilitating stability (40 and relative humidity 75%), Budesonide is analyzed by using Next Generation Cascade Impactor for all levels, which include actuator, L-throat, Stage 1, Stage 2, Stage 3, Stage 4, Stage 5, Stage 6, Stage 7 and micro-orifice collector (MOC). There are no significant differences (ANOVA test, p>0.05) in quantity of Budesonide, when compared with that at initial time point, among the products in every level.
As shown in FIG. 4 illustrating the analysis of particle size distribution, after the six-months test of facilitating stability (40 and relative humidity 75%), Procaterol HCl is analyzed by using Next Generation Cascade Impactor for every level, and there are no significant differences (ANOVA test, p>0.05) in quantity of Procaterol HCl, when compared with that at initial time point, among the products in every level.
FIG. 5 illustrates the analysis of the delivery dose uniformity for Fluticasone in the spray of Formula Example VII, wherein the Fluticasone in the first spraying has an indicated dosage of 250 mcg. After the six-months test of facilitating stability (40 and relative humidity 75%), every bottle of the sprays including totally ten sprayings of delivery dosages is complying with the requirement that the main component in a single spraying shall not be over 25% of the indicated dosage and an average value shall not be over 15% of the indicated dosage according to the Pharmacopeia.
FIG. 6 illustrates the analysis of particle size distribution for Fluticasone in the spray of Formula Example VII. After the six-months test of facilitating stability (40 and relative humidity 75%), it is analyzed by using Next Generation Cascade Impactor for every level, and there are no significant differences (ANOVA test, p>0.05) in quantity of Fluticasone, when compared with that at initial time point, among the products in every level.
FIG. 7 illustrates the analysis of the delivery dose uniformity for Albuterol sulfate in the spray of Formula Example IX, wherein the Albuterol sulfate in the first spraying has an indicated dosage of 250 mcg. After the six-months test of facilitating stability (40 and relative humidity 75%), every bottle of the sprays which includes totally ten sprayings of delivery dosages is complying with the requirement that the main component in a single spraying shall not be over 25% of the indicated dosage and an average value shall not be over 15% of the indicated dosage according to the Pharmacopeia.
FIG. 8 illustrates the analysis of particle size distribution for Albuterol sulfate. After the six-months test of facilitating stability (40 and relative humidity 75%), it is analyzed by using Next Generation Cascade Impactor for every level, and there are no significant differences (ANOVA test, p>0.05) in quantity of Albuterol sulfate, when compared with that at initial time point, among the products in every level.
The object of the present invention is to promote the stability of amounts, the delivery dose uniformity and the stability of quality when producing the pressurized metered spray dose in the scale-up production. The formula applied to the producing process would deeply have industrial value especially when two main components having much differences in relative physical and chemical properties are combined in the product. Accordingly, the present invention is sought to be protected by operation of law. The “process of preparing metered dose inhaler for treating respiratory diseases” provided in the present invention will become more readily apparent to those ordinarily skilled in the art after reviewing the following examples. However, it is to be understood that the invention needs not be limited to the disclosed embodiments. The person skilled in the art could derive various embodiments according to the spirit of the disclosed embodiments, all of which shall belong to the scope of the appended claims in the present invention.
Process Example I
Procaterol HCl
0.014%
W/W %
Budesonide
0.252%
W/W %
HFA 227
98.984%
W/W %
ethanol absolute
0.500%
W/W %
PEG 6000
0.250%
W/W %
Total Amount
100.000%
W/W %
Descriptions for Process
PEG 6000 is completely dissolved in the ethanol absolute to form a mixture solution, and then Procaterol HCl is poured into the mixture solution and dissolved by ultrasonic vibration to form an homogenized solution. After homogenizedly mixing HFA 227 with the homogenized solution, Budesonide is slowly added thereinto. Finally, freeze filling or pressure filling is performed.
Process Example II
Fluticasone propionate
0.350%
W/W %
HFA 134a
98.900%
W/W %
ethanol absolute
0.500%
W/W %
PEG 400
0.250%
W/W %
Total Amount
100.000%
W/W %
Descriptions for Process
PEG 400 is completely dissolved in the ethanol absolute to form a mixture solution. After homogenizedly mixing HFA 134a with the mixture solution, Fluticasone is slowly added thereinto. Finally, freeze filling or pressure filling is performed.
Process Example III
Albuterol sulfate
0.168%
W/W %
Fluticasone propionate
0.322%
W/W %
HFA 134a
97.510%
W/W %
ethanol absolute
1.000%
W/W %
PEG 100
1.000%
W/W %
Total Amount
100.000%
W/W %
Descriptions for Process
PEG 100 is completely dissolved in the ethanol absolute to form a mixture solution, and then Albuterol sulfate is poured into the mixture solution and dissolved by ultrasonic vibration to form an homogenized solution. After homogenizedly mixing HFA 227 with the homogenized solution, Fluticasone propionate is slowly added thereinto. Finally, freeze filling or pressure filling is performed.
Process Example IV
Procaterol
0.014%
W/W %
HFA 227
99.286%
W/W %
ethanol absolute
0.500%
W/W %
PEG 2000
0.200%
W/W %
Total Amount
100.000%
W/W %
Descriptions for Process
PEG 2000 is completely dissolved in the ethanol absolute to form a mixture solution, and then Procaterol HCl is poured into the mixture solution and dissolved by ultrasonic vibration to form an homogenized solution. HFA 227 is homogenizedly mixed with the homogenized solution. Finally, freeze filling or pressure filling is performed.
Formula Example I
Procaterol HCl
0.014%
W/W %
Budesonide
0.280%
W/W %
HFA 134a
98.906%
W/W %
alcohol
0.500%
W/W %
PEG 2000
0.300%
W/W %
Total Amount
100.000%
W/W %
Formula Example II
Procaterol HCl
0.014%
W/W %
Fluticasone propionate
0.350%
W/W %
HFA 227
98.886%
W/W %
alcohol
0.250%
W/W %
PEG 400
0.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example III
Albuterol sulfate
0.168%
W/W %
Fluticasone propionate
0.322%
W/W %
HFA 227
97.510%
W/W %
ethanol absolute
1.500%
W/W %
PEG 400
0.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example IV
Procaterol
0.014%
W/W %
HFA 134a
97.986%
W/W %
alcohol
1.000%
W/W %
PEG 100
1.000%
W/W %
Total Amount
100.000%
W/W %
Formula Example V
Procaterol HCl
0.014%
W/W %
Budesonide
0.333%
W/W %
HFA 134a
98.903%
W/W %
alcohol
0.250%
W/W %
PEG 400
0.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example VI
Budesonide
0.330%
W/W %
HFA 227
99.530%
W/W %
alcohol
1.500%
W/W %
PEG 2000
0.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example VII
Fluticasone propionate
0.351%
W/W %
HFA 227
97.899%
W/W %
alcohol
1.500%
W/W %
PEG 6000
0.250%
W/W %
Total Amount
100.000%
W/W %
Formula Example VIII
Procaterol HCl
0.014%
W/W %
Ciclesonide
0.286%
W/W %
HFA 227
98.950%
W/W %
alcohol
0.500%
W/W %
PEG 100
1.000%
W/W %
Total Amount
100.000%
W/W %
Formula Example IX
Albuterol sulfate
0.396%
W/W %
HFA 134a
96.604%
W/W %
alcohol
2.500%
W/W %
PEG 6000
0.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example X
Albuterol sulfate
0.168%
W/W %
Beclomethasone dipropionate
0.286%
W/W %
HFA 134a
96.546%
W/W %
alcohol
1.500%
W/W %
PEG 100
1.500%
W/W %
Total Amount
100.000%
W/W %
Formula Example XI
Procaterol HCl
0.014%
W/W %
Beclomethasone dipropionate
0.286%
W/W %
HFA 227
98.950%
W/W %
alcohol
0.250%
W/W %
PEG 400
0.500%
W/W %
Total Amount
100.000%
W/W %
EMBODIMENTS
1. A method of preparing a metered dose inhaler composition, comprising steps of:
a) mixing 0.05%-10% (w/w %) alcohol with a surfactant to form a first mixture;
b) dispersing a beta-2 agonist in the first mixture to form a second mixture;
c) adding a hydrofluoroalkane (HFA) propellant into the second mixture to form a third mixture;
d) dispersing a corticosteroid in the third mixture; and
e) performing a filling step.
2. A method of preparing a metered dose inhaler composition, comprising steps of:
a) mixing 0.05%-10% (w/w %) alcohol with a surfactant to form a first mixture;
b) dispersing a beta-2 agonist in the first mixture to form a second mixture;
c) adding HFA into the second mixture to form a third mixture; and
d) dispersing a corticosteroid in the third mixture.
3. A method of preparing a metered dose inhaler composition, comprising steps of:
a) mixing 0.05%-0.25% (w/w %) alcohol with a surfactant to form a first mixture;
b) dispersing a beta-2 agonist in the first mixture to form a second mixture; and
c) adding HFA into the second mixture to form a third mixture.
4. A method of embodiment 1, wherein the corticosteroid includes one selected from a group consisting of budesonide, fluticasone, beclomethasone, ciclesonide, fluticasone propionate, beclomethasone dipropionate and a combination thereof.
5. A method of embodiment 1, wherein the beta-2 agonist includes one selected from a group consisting of albuterol, procaterol, formoterol, albuterol sulfate, procaterol hydrochloride, formoterol fumarate and a combination thereof.
6. A method of embodiment 1, wherein the alcohol solvent is ethanol absolute.
7. A method of embodiment 1, wherein the mixing step is performed by ultrasonic vibration.
8. A method of embodiment 5, wherein the alcohol solvent preferably has an addition percent ranged from 0.25%-2% (w/w %).
9. A method of embodiment 1, wherein the surfactant includes a polyethylene glycol (PEG) having a molecular weight ranged from 100 to 6000.
10. A method of embodiment 9, wherein the surfactant preferably has an addition percent ranged from 0.01%-2.5% (w/w %).
11. A method of embodiment 9, wherein the surfactant preferably has an addition percent ranged from 0.05%-1.5% (w/w %).
12. A method of embodiment 1, wherein the HFA propellant includes one of HFA 134a and HFA 227.
13. A method of embodiment 12, wherein the HFA propellant may include a combination of HFA 134a and HFA 227.
14. A metered dose inhaler composition prepared according to the method as claimed in embodiment 1, wherein the composition is used as one of an emergency drug for a subject suffering an asthma attack and a drug during an eccentric therapy for the subject, wherein the subject has one of asthma and chronic obstructive pulmonary disease, and the drug in the eccentric therapy is administrated to the subject when the subject is in a condition being one of before and after sleeping.
While the invention has been described in terms of what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention needs not be limited to the disclosed embodiments. On the contrary, it is intended to cover various modifications and similar arrangements included within the spirit and scope of the appended claims which are to be accorded with the broadest interpretation so as to encompass all such modifications and similar structures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram illustrating the analysis of the delivery dose uniformity for Budesonide of Formula Example I.
FIG. 2 is a diagram illustrating the analysis of the delivery dose uniformity for Procaterol HCl of Formula Example I.
FIG. 3 is a diagram illustrating the analysis of particle size distribution for Budesonide of Formula Example I.
1: actuator 2: L-throst 3: Stage 1+Stage 2 4: Stage 3 5: Stage 4 6: Stage 5 7: Stage 6+Stage 7+micro-orifice collector (MOC)
FIG. 4 is a diagram illustrating the analysis of particle size distribution for Procaterol HCl of Formula Example I.
1: actuator 2: L-throst 3: Stage 1+Stage 2 4: Stage 3 5: Stage 4 6: Stage 5 7: Stage 6+Stage 7+micro-orifice collector (MOC)
FIG. 5 is a diagram illustrating the analysis of the delivery dose uniformity for Fluticasone of Formula Example VII.
FIG. 6 is a diagram illustrating the analysis of particle size distribution for Fluticasone of Formula Example VII.
1: actuator 2: L-throst 3: Stage 1 4: Stage 2 5: Stage 3 6: Stage 4 7: Stage 5 8: Stage 6 9: Stage 7 10: micro-orifice collector (MOC)
FIG. 7 is a diagram illustrating the analysis of the delivery dose uniformity for Albuterol sulfate of Formula Example IX.
FIG. 8 is a diagram illustrating the analysis of particle size distribution for Albuterol sulfate of Formula Example IX.
1: actuator 2: L-throst 3: Stage 1 4: Stage 2 5: Stage 3 6: Stage 4 7: Stage 5 8: Stage 6 9: Stage 7 10: micro-orifice collector (MOC)
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The present invention is related to metered dose inhalation formulas and manufacturing process. The active pharmaceutical ingredient can be beta-2 agonists, corticosteroids, or a combination thereof. The inhalation formulas are homogenized suspensions with hydrofluoroalkane (HFA) propellant, minimal amount of ethanol and polyetheleneglycol (PEG) as suspending and particle size modifying agents.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related to U.S. patent application Ser. No. ______, entitled “Cable Stranding Apparatus Employing a Hollow-Shaft Guide Member Driver,” filed on the same day of ______, and which is assigned to the same Assignee as the present application, and which is incorporated by reference herein.
FIELD
[0002] The present disclosure relates to methods for stranding together strand and core members to form stranded cables with an alternating twist direction, and in particular to such methods that employ a hollow-shaft guide member driver.
BACKGROUND
[0003] Cable stranding machines are used in cable manufacturing to form cables with multiple strand elements (“strands”) having an alternating twist direction. Such cables are called “SZ” cables because the strands periodically helically twist in opposing “S” and “Z” directions. The SZ stranding configuration eliminates the need for the strand storage containers to be rotated around the cable core member, thereby resulting in less complex, faster-operating stranding machinery.
[0004] The strands, which can be wire, optical fibers, buffer tubes, etc., are stored in storage containers (e.g., spools or “packages”) and pass through a stationary guide or “layplate.” The layplate keeps the strands locally spaced apart as they pass through to a downstream SZ cable-stranding apparatus. Prior art SZ cable-stranding apparatus employ a series of axially arranged and mechanically coupled guides typically in the form of non-stationary (i.e., rotatable) plates called “layplates” similar if not identical to the stationary layplate. The rotatable layplates also serves to keep the strands locally spaced apart during the stranding process to ensure that the strands do not become entangled with each other or the core member as the layplates rotate through their motion profiles.
[0005] In the process of forming an SZ-stranded cable, the layplates are mechanically coupled and driven in alternating rotational directions at progressively slower rates towards the upstream stationary plate as the strands move through the layplates. An SZ-stranded assembly, consisting of the strands wound around the central core member, emerges from the most downstream rotatable layplate.
[0006] In the simplest form of SZ cable-stranding apparatus, tension in the strands provides the mechanical coupling that rotates the layplates. However, this results in poor tension control with a limited range of layplate rotation. More complex and expensive approaches use a series of shafts from a drive member (“prime mover”) and belts and/or gears to synchronize the motion of the rotating layplates to generate the required rotation rate for each layplate. An example of this type of SZ cable-stranding apparatus uses an elastic shaft running parallel to the axis of the oscillator. The torsion of the shaft, in combination with an arrangement of belts, pulleys and/or gears, drives the layplates.
[0007] Generally, mechanically based SZ cable-stranding apparatus are expensive and difficult to maintain. Furthermore, the added rotational inertia of the mechanical components limits the maximum rate at which the rotatable layplates can reverse directions, thereby limiting both line speed and performance. In addition, the mechanical components limit the relative speed differences between successive layplates. This makes it difficult if not impossible to decouple the operation of the individual layplates to optimize the layplate rotational speeds to achieve the smoothest possible SZ stranding operation.
SUMMARY
[0008] An aspect of the disclosure is a method of stranding strand elements in an SZ configuration to form an SZ-stranded assembly. The method comprises passing, through at least one guide member, initially spaced apart strand elements through respective guide holes and at least one core member through a generally central location of the guide member. The method also includes actuating a controller that controls the rotation of the guide member and rotating the guide member to form the SZ-stranded assembly.
[0009] Another aspect of the disclosure is a method of forming an apparatus for controlling strand elements and at least one core member in a stranding apparatus. The method includes providing at least one motor having an associated rotating guide member driver. The method also includes providing and operably disposing a guide member at least partially within the rotating guide member driver so that the guide member rotates with the guide member driver, wherein the guide member is configured to receive and individually guide the strand elements and pass the at least one core member.
[0010] Another aspect of the disclosure a method of forming a cable stranding apparatus that strands strand elements about at least one core member in an SZ configuration to form a SZ-stranded assembly. The method includes providing a plurality of motors each having a guide member driver, and aligning the guide member drivers along an apparatus axis. The method also includes providing a plurality of guide members configured to locally spatially separate the individual strand elements and pass the at least one core member. The method further includes disposing and holding stationary one of the guide members upstream of the plurality of motors. The method additionally includes disposing the remaining guide members at least partially within respective guide member drivers so that they rotate with the respective guide member drivers.
[0011] These and other advantages of the disclosure will be further understood and appreciated by those skilled in the art by reference to the following written specification, claims and appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] A more complete understanding of the present disclosure may be had by reference to the following detailed description when taken in conjunction with the accompanying drawings, wherein:
[0013] FIG. 1 is a perspective view of an example SZ cable-stranding apparatus according to the present disclosure;
[0014] FIG. 2 is a perspective view of an example hollow-shaft motor showing an exploded view of a guide member attached to the hollow shaft via set screws;
[0015] FIG. 3 is a front-on view and FIG. 4 is a cross-sectional view of an example guide member of FIG. 2 in the form of a layplate having a central hole sized to pass the at least one core member, surrounding strand guide holes, and peripheral set-screw holes;
[0016] FIG. 5 is a schematic diagram of an example electronic configuration of the SZ cable-stranding apparatus; and
[0017] FIG. 6 is a schematic overall view of a SZ cable-forming system that includes the SZ cable-stranding apparatus of the present disclosure.
DETAILED DESCRIPTION
[0018] Reference is now made to embodiments of the disclosure, exemplary embodiments of which are illustrated in the accompanying drawings. In the description below, like elements and components are assigned like reference numbers or symbols. Also, the terms “upstream” and “downstream” are relative to the direction in which the SZ-stranded cable is formed, starting upstream with the various unstranded strand elements and optional at least one core member, and ending downstream with the formed SZ-stranded assembly and SZ-stranded cable.
[0019] FIG. 1 is a perspective view of an example SZ cable-stranding apparatus (“apparatus”) 10 according to the present disclosure. Apparatus 10 has an upstream input end 11 and a downstream output end 13 . Apparatus 10 includes along an axis A 1 in order from an upstream to a downstream direction as indicated by arrow 12 , a stationary guide member 20 S and at least one hollow-shaft motor 100 that includes a rotatable guide member 20 R operably disposed therein. Here, the term “rotatable” refers to the fact that motor 100 causes the guide member to rotate, as described in greater detail below. FIG. 1 shows an example configuration of apparatus 10 having a plurality of axially aligned motors 100 . An example type of motor 100 is a high-precision motor such as a servo motor.
[0020] In an example embodiment, adjacent motors 100 are spaced apart by respective distances S, which in many cases is governed by space constraints and the fact that larger guide-member separations result in lower tension variation in the strands. A typical spacing S between motors 100 is between 0.1 m and 2 m, and in an example embodiment the spacing is adjustable, as described below. In some example embodiments, the spacing S is equal between all motors 100 , while in other example embodiments the spacing S is equal between some motors, while in other example embodiments the spacing S is not equal between any of the motors. Providing a variable spacing S between motors 100 may be used to adjust the stranding process. For example, a large spacing downstream helps minimize tension variation while a short spacing upstream shortens the overall length of apparatus 10 with little impact on tension variation.
[0021] FIG. 2 is a perspective view of an example motor 100 . Motor 100 includes a guide member driver in the form of a hollow shaft 102 defined by an axial shaft hole 104 formed therein. An example size of shaft hole 104 is between 1 and 3 inches in diameter, with 2 inches being a commonly available size suitable for use in forming many types of SZ cables. The term “hollow shaft” as used herein in connection with motor 100 is intended to include a motor that contains a through passage concentric with and contained within the rotating structure of the motor. For example, certain types of servo-motors suitable for use herein and discussed in greater detail below include inductively driven rotors that surround and drive a hollow shaft.
[0022] Each motor 100 includes the aforementioned rotatable guide member 20 R operably disposed within shaft hole 104 (see FIG. 1 ) so that the guide member rotates with the rotation of the hollow shaft. In an example embodiment, rotatable guide member 20 R is disposed in shaft hole 104 and is fixed to hollow shaft 102 by, for example, by set screws (as described below), an adhesive, a flexible or rigid mounting member or fixture, or other known fixing means.
[0023] Each motor 100 includes a position feedback device 106 , such as an optical encoder (see FIG. 5 , introduced and discussed below). Positional feedback device 106 provides information (in the form of an electrical signal S 3 ) about the rotational position and speed of hollow shaft 102 and thus rotatable guide member 20 R. An example maximum rotational speed of motor 100 is 3,600 rpm and an example maximum theoretical acceleration is 21,582 rad/s 2 . A typical operating rotational speed for motor 100 used in producing SZ cable is about 1,500 rpm with an angular acceleration of about 8,000 rad/s 2 . An exemplary motor 100 for use in apparatus 10 is one of the model nos. CM-4000 hollow-shaft inductively driven servo motors made by Computer Optical Products, Inc., Chatsworth, Calif. Another exemplary motor 100 for use in apparatus 10 is a hollow-shaft gear-based motor, such as those available from Bodine Electric Company, Chicago, Ill.
[0024] FIG. 3 is a face-on view and FIG. 4 is a cross-sectional view of an example guide member 20 that can be used as stationary guide member 20 S and/or as rotatable guide member 20 R. The example guide member 20 is in the form of a round plate (“layplate”) having a central hole 24 with peripherally arranged smaller guide holes (e.g., eyelets) 28 (six guide holes are shown by way of example). Central hole 24 is sized to pass at least one core member 30 while guide holes 28 are sized to pass individual strand elements (“strands”) 40 . Core member 30 includes, for example, a strength element and/or a cable core member. An example strength element is glass-reinforced plastic (GRP), steel or like strength elements presently used in SZ cables. Example cable core members 30 include buffer tubes, optical fibers, optical fiber cables, conducting wires, insulating wires, and like core members presently used in SZ cables. Example strands 40 include optical fibers, buffer tubes, wires, thread, copper twisted pairs, etc.
[0025] Guide member 20 is arranged in apparatus 10 so that central hole 24 is centered on axis A 1 , and in an example embodiment peripheral guide holes 28 are arranged symmetrically about the central hole. Guide member 20 is configured to maintain the at least one core member 30 and individual strands 40 in a locally spaced apart configuration as the core member and individual strands pass through their respective holes. An example guide member 20 is formed from aluminum. Guide member 20 optionally includes hole liners 44 that line central hole 24 and/or guide holes 28 in a manner that facilitates the passing of core member 30 and/or strands 40 through the guide member. Example materials for hole liners 44 include ceramic, plastic, TEFLON, and like materials. Hole liners 44 preferably have rounded edges that reduce the possibility of core member 30 and/or strands 40 from being snagged, abraded, nicked or cut as they pass through their respective holes. In another example embodiment, central hole 24 and guide holes 28 are provided with rounded edges.
[0026] With reference to FIG. 2 through FIG. 4 , in an example embodiment, rotatable guide member 20 R includes peripheral set-screw holes 25 , and hollow shaft 102 includes matching screw holes 25 ′ configured so that the rotatable guide member is attached to the hollow shaft via corresponding set screws 27 .
[0027] In an example embodiment, rotatable guide member 20 R is the same as or is similar to stationary guide member 20 S, and further in an example embodiment are both in the form of layplates such as shown in FIG. 3 and FIG. 4 . Motors 100 are axially aligned so that shaft hole 104 and the rotatable guide member 20 R operably disposed therein are centered on axis A 1 .
[0028] With reference again to FIG. 1 , in an example embodiment, stationary guide member 20 S and each motor 100 are mounted to respective base fixtures 120 , which in turn are mounted to a common platform 130 , such as a base plate or tabletop. In an example embodiment, base fixtures 120 are configured to be fixed in place to platform 130 , while in another example embodiment they are also configured to be positionally adjustable relative to platform 130 . In one example, the positional adjustability is achieved by slidably mounting base fixtures 120 to rails 140 , which allows for axial adjustability of each motor 100 . Movable motors 100 can be axially moved along rails 140 and placed together for “thread up,” i.e., threading the at least one core member 30 and strands 40 through their respective holes 24 and 28 in the various rotatable guide members 20 R, and then axially moved again along the rails to be spaced apart and fixed at select positions during the SZ stranding operation, as discussed below. The positional adjustability of motors 100 allows for the spacings S to be changed so that apparatus 10 can be reconfigured for forming different types of SZ cables or to tune the cable-forming process. In an example embodiment, base fixtures 120 and platform 130 (and optional rails 140 ) are configured so that motors 100 can be added or removed from apparatus 10 .
[0029] With continuing reference to FIG. 1 and also to the schematic diagram of FIG. 5 , an example apparatus 10 includes at least one servo driver 150 electrically connected to the corresponding at least one motor 100 . Each servo driver 150 is in turn operably connected to a controller 160 . An example controller 160 is a programmable logic controller (PLC), or a microcontroller. An example controller 160 includes a processor 164 and a memory unit 166 , which constitutes a computer-readable medium for storing instructions, such as a rotation relationship embodied as an electronic gearing profile, to be carried out by the processor in controlling the operation of apparatus 10 . An exemplary controller 160 suitable for use in the present disclosure is Model No. PiC900 PLC made by Giddings and Lewis, LLC, Fond du Lac, Wis.
[0030] Apparatus 10 also includes a linespeed monitoring device 172 operably arranged to measure the speed at which the SZ-stranded assembly 226 or core member 30 travels through the apparatus. Example locations for linespeed monitoring device 172 include downstream of the most downstream motor 100 and adjacent SZ-stranded assembly 226 as shown, or upstream of stationary guide member 20 S and adjacent core member 30 . Intermediate locations can also be used. Linespeed monitoring device 172 is electrically connected to controller 160 and provides a linespeed signal SL thereto. An example linespeed monitoring device 172 is the BETA QUADRATRAK II linespeed monitor, available from Beta LaserMike USA, Inc., Dayton, Ohio.
[0031] In an example embodiment, controller 160 includes instructions (i.e., is programmed with instructions stored in memory unit 166 ) that control the rotational speed and the reversal of rotation of each motor 100 according to a rotation relationship. This rotation relationship between motors 100 is accomplished via motor control signals S 1 provided by controller 160 to the corresponding servo drivers 150 . In an example embodiment, the rotation relationship is embodied as electronic gearing. In response thereto, each servo driver 150 provides its corresponding motor 100 with a power signal S 2 that powers the motor and drives it at a select speed and rotation direction according to the rotation relationship. Position feedback device 106 provides a position signal S 3 that in an example embodiment includes incremental positional information, speed information, and an absolute (reference) position. The reference position is typically a start position of hollow shaft 102 , while the incremental position tracks its rotational position on a regular basis (e.g., 36,000 counts per rotation). The rotational speed of hollow shaft 102 is the change in rotational position with time and is obtained from the position information contained in signal S 3 . Linespeed signal SL provides linespeed information, which is useful for comparing to the rotational speeds of motors 100 to ensure that the rotational speed and linespeed are consistent with the operational parameters of apparatus 10 and the particular SZ-cable being fabricated.
[0032] For apparatus 10 having a plurality of motors 100 , each motor has a different rotational speed, with less rotational speed the farther upstream the motor resides. For an SZ stranded cable, the number n of “turns between reversals'” can vary, with a typical number being n=8. For this example number of turns between reversals, apparatus 10 starts at a neutral point (n=0) where all of the strands 30 and the rotational and stationary guide members 20 R and 20 S are aligned. Controller 160 , through the operation of servo drivers 150 , then causes motors 100 to execute four turns clockwise, and then reverse and execute eight turns counterclockwise. Note that after the first four counterclockwise turns, apparatus 10 returns to and then passes through the neutral point. After the eight counterclockwise turns, apparatus 10 reverses and performes eight clockwise turns. In this way, n=8 turns between reversals is obtained, with rotatable guide members 20 R turning four turns around the neutral point in each direction.
[0033] For apparatus 10 designed to operate with a maximum angular deviation of 120° between two successive rotatable guide members 20 R, the 120° needs to be divided between four turns, or 30° per turn. Thus, as the “first” or most downstream rotatable guide member 20 R undergoes its first revolution, the second (i.e., second most downstream rotatable guide member) must lag the first by 30°, i.e., it only turns 11/12 (i.e., 0.92) of a revolution. This defines the base rotation ratio R, i.e., the range of rotation between the second and first most downstream motors.
[0034] Consider an example for n=+/−4 turns and a maximum angular displacement between two rotatable guide members 20 R of θ MAX =120°. The first rotatable guide member turns a total angle of θ T =1440° (n*360), the second turns 1320°, the third 1200° and so on. The second rotatable guide member 20 R is then driven at a ratio R 2 =1320/1440=0.92. The third guide member 20 R is driven at a ratio R 3 =1200/1320 or 0.91. Generally, for j=the rotatable guide member number, θ MAX =the separation angle, θ T =the total angular rotation (n*360°) for the first guide member, the rotation ratio R j of guide member j=2, 3, . . . relative to the first guide member is given by R j =1−(j−1)*θ MAX /θ T .
[0035] Example rotation relationships for motors 100 are carried out in a similar manner for different numbers n of turns between reversals, a different total number m of motors, and a different maximum angular deviation θ MAX between adjacent guide members. The number m of motors 100 needed in apparatus 10 generally depends on the type of SZ cable being formed and related factors, such as the maximum number n of turns between reversals, and θ MAX , which in turn depends on the guide member diameter, the size of the core member 30 and the size of strands 40 . A typical number m of motors 100 ranges from 1 to 20, with between 5 and 12 being a common number for a wide range of SZ cable applications.
[0036] Apparatus 10 can be configured and operated in a number of ways. For example, rather than controller 160 controlling each individual servo driver 150 , in one embodiment the servo drivers are linked together via a communication line 178 and receive information about the rotation of the most downstream motor 100 via an electrical signal S 4 . The upstream servo drivers 150 then calculate the required motor signals S 2 needed to provide the appropriate rotation relationship (e.g., via electronic gearing) to their respective motors 100 . Thus, controller 160 transmits information via signal S 1 about the stranding profile (n turns between reversals, the laylength, etc. . . . ) to the first (i.e., most downstream) servo driver 150 . Each upstream servo driver 150 receives a master/slave profile (e.g. a gear ratio=R) for the motor 100 immediately in front of it via respective signals S 4 . Thus, the upstream servo drivers 150 are slaved to the most downstream servo driver. In this embodiment, controller 160 is mainly for initiating and then monitoring the operation of apparatus 10 . Linespeed information is provided to the most downstream servo driver 150 through controller 160 (i.e., from linespeed monitoring device 178 to controller 160 and then to the most downstream servo driver).
[0037] In a related embodiment, controller 160 transmits the aforementioned stranding profile information via signal S 1 to first servo driver 150 , while each upstream servo driver receives a master/slave profile (e.g. a gear ratio=R) that synchronizes them to the downstream servo driver. Since each upstream servo driver 150 is slaved to the most downstream servo driver, each servo driver requires the position feedback data from the first motor 100 . Linespeed information is provided to the first servo driver 150 through controller 160 .
[0038] In another related embodiment, controller 160 transmits the aforementioned stranding profile information to the first servo driver 150 . Controller 160 also calculates an individualized stranding profile for each upstream motor 100 based on the complete stranding profile that will result in a desired operation for apparatus 10 . In this case, there are no rotational master/slave relationships between motors 100 . Since each motor 100 operates independently of the others, each requires linespeed feedback from linespeed monitoring device 178 and only its own position information. In an example embodiment, the linespeed feedback is provided via controller 160 .
[0039] Thus, in one embodiment, each motor 100 is programmed to rotate with a select speed that is not necessarily slaved of off the “base” rotation ratio R. In an example embodiment, the rotation relationship between the motors has a non-linear form selected to optimize the SZ stranding process. The rotation relationship between two adjacent rotatable guide members 20 R can best be visualized as a function of the angular position θ M of a “master” guide member 20 R and the angular position θ S of a corresponding “slave” guide members. Thus, for a prior art mechanical system where the rotation ratio R is fixed, the angular position θ S of the slave guide member is determined by the function θ S =R*θ M , which is a linear function in θ. In contrast, the rotation relationship programmed into controller 160 can allow for a much more complex functional relationships between the angular positions and rotation speeds of guide members 20 . A non-linear rotation relationship is useful, for example, to minimize tension spikes that can occur during the SZ stranding operation.
[0040] FIG. 6 is a schematic diagram of an example SZ cable-forming system (“system”) 200 that includes apparatus 10 of the present disclosure. System 200 includes strand storage containers 210 , typically in the form of spools or “packages” that respectively hold and pay off individual strands 40 and optionally one or more individual core members 30 .
[0041] System 200 include a strand-guide device 220 arranged immediately downstream of strand storage containers 210 . In an example embodiment, strand-guide device 220 includes a series of pulleys (not shown) that collect and distribute the strands 40 and the at least one core member 30 . SZ cable-stranding apparatus 10 is arranged immediately downstream of strand-guide device 220 and receives at its input end 11 the strands 40 and the at least one core member 30 outputted from the strand-guide device. Apparatus 10 then performs SZ-stranding of the strands about the at least one core member 30 , as described above. Strands 40 and the optional core member 30 exit apparatus 10 at output end 13 as an SZ-stranded assembly 226 , as shown in the close-up view of inset A of FIG. 6 (see also FIG. 1 ). SZ-stranded assembly 226 consists of strands 40 wound around the at least one core member 30 in an SZ configuration.
[0042] System 200 includes a coating unit 228 arranged immediately downstream of apparatus 10 . Coating unit includes an extrusion station 230 configured to receive the SZ-stranded assembly 226 and form a protective coating 229 thereon, as shown in the close-up view of inset B in FIG. 6 , thereby forming the final SZ cable 232 . In an example embodiment, extrusion station 230 includes a cross-head die (not shown) configured to combine the protective coating extrusion material with the SZ-stranded assembly. Example coatings 228 include polyethylene (PE), polyvinyl chloride (PVC), Poly Vinyl Diene Fluorine (PVDF), Nylon, Poly Tetra Flouro Ethylene (PTFE), etc. Coating unit 228 also includes a cooling and drying station 240 is arranged immediately downstream of extrusion station and cools and dries coating 228 . The final SZ cable 232 emerges from coating unit 228 and is received by a take-up unit 250 that tensions the SZ cable and winds it around a take-up spool 260 .
[0043] Apparatus 10 of the present disclosure eliminates the mechanical coupling between rotatable guide members 20 R and in this sense is a gearless and shaftless apparatus. Note that the strands 40 passing through the rotatable guide members 20 R do not establish a mechanical coupling between the guide members because the strands are not used to drive the rotation of the guide members. Without the added rotational inertia and bearing friction associated with mechanical components, faster reversal times and thus higher line speeds are possible for a given lay length. Gear-based SZ cable-stranding apparatus are also subject to extremely high dynamic loads during the reversals. This puts a great deal of stress on the power transmission gears, resulting in frequent maintenance issues. The gearless/shaftless SZ cable-stranding apparatus 10 eliminate these types of maintenance and reliability issues.
[0044] Because the motion of rotatable guide members 20 R is electronically controlled, their rotational velocities in relation to other plates is programmable according to a rotation relationship to carry out rotation profiles (including complex rotation profiles) that result in smoother operation and lower tension variations on strands 40 and the at least on core member 30 . The prior art mechanical approaches limit the rotation profiles of the rotatable guide members, which causes unwanted variations in strand tension.
[0045] It will be apparent to those skilled in the art that various modifications to the present embodiment of the disclosure as described herein can be made without departing from the spirit or scope of the disclosure as defined in the appended claims. Thus, the disclosure covers the modifications and variations provided they come within the scope of the appended claims and the equivalents thereto.
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Cable-stranding methods for performing SZ-stranding of strand elements about at least one core member are disclosed. One method includes passing initially spaced apart strand elements through peripheral guide holes and passing at least one core member through a generally central location of at least one guide member. The method also includes actuating a controller that controls the rotation of the at least one guide member and rotating the at least one guide member to form the SZ-stranded assembly.
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TECHNICAL FIELD
[0001] The present disclosure provides examples in the field of semi-automation and/or automation of machines, in particular, asphalt pavers.
BACKGROUND
[0002] Asphalt road paving machines (or asphalt pavers) include a tractor with a hopper for receiving asphalt paving material located at the front of the paver, and a feeder conveyor for delivering the asphalt paving material to the rear of the paver to a spreader auger. The auger distributes the asphalt laterally behind the tractor to the road surface in front of the screed.
[0003] Asphalt pavers include a screed, a heavy assembly drawn behind the paving machine by a pair of pivotally mounted tow arms for smoothing out and compressing the asphalt material. Pavers may include a screed extender frame for adjusting screed width, which may be hydraulically adjustable.
[0004] Road mat thickness is determined in part by asphalt material composition, machine specifics, as well as by the volume of the asphalt material pile placed in front of the screed. Asphalt material composition and screed specifics are typically constants with a specific machine and mix; however, the height of the material pile must be continuously provided by the conveyor and auger as the paver moves forward. Material pile height should remain constant to pave an even surface. Variables affecting a current material pile size include the conveyor speed, and the auger speed.
[0005] Sensors mounted on the end of the screed or screed extender help determine the amount of material in front of the screed. The machine operator may manually set estimated material height, or provide an estimated control gain by using a marked dial or digital input on the control panel, to direct the machine to regulate the material pile to a target size using the auger and conveyor systems.
[0006] Too much material placed in front of the screed results in a ridge once the machine is adjusted to the proper material pile height. Too little material placed in front of the screed results in a dip once the machine is adjusted to the proper material pile height. Some paving machines utilize manual knobs that an operator turns to adjust the gain for a paver to set the target material pile height. This gain signals to an electronic control module (ECM) as to the material height setting, and thus, the conveyor and auger speed.
[0007] U.S. Pat. No. 5,575,583 to Grembowicz et al. describes an apparatus for controlling a material feed system. The apparatus includes a sensor that monitors the amount of material at the edge of the screed and responsively produces a target material height signal, which the operator matches using a rotary switch. It is desirable to provide a system that can provide the proper settings from initial paving. It may also be desirable to automate the process to reduce variability due to operator subjectivity.
SUMMARY
[0008] The present disclosure generally relates to automating material feed for a paver to maintain a material pile size.
[0009] In a first embodiment, the paver includes a system for regulating material feed including a screed, a conveyor and an auger. One sensor, or a pair of sensors on the screed measures the amount of material placed in front of the asphalt screed. These sensors may be contact based, sonic based, or may employ another technology. The sensors measure the size of the material pile in front of the screed, and for example, slightly beyond the auger width.
[0010] A sensor measures the initial distance from its position to the feed material adjacent the screed, and transmit this information to an ECM. The ECM uses this initial distance information to calibrate the paver by setting a target pile size to determine a conveyor and auger speed. As the paver and material feed system operates, the sensor continues to monitor the pile, and the ECM continues to determine, set, and adjust a rotational conveyor speed and a rotational auger speed to maintain the target pile size.
[0011] Upon paver initialization, the ECM transmits this auger speed, and conveyor speed, which may be determined by a ratio of the auger speed, to the auger control and the conveyor control. An algorithm within the ECM calculates information such as gains necessary to maintain the pile size, using feedback information provided by the sensor. The calibration and paving process may be initiated with a signal, which may be produced from a button, switch, or upon machine initialization, which signals the ECM to receive the target pile size input from the sensor. The step of guessing a material height or gain with a variable dial may be eliminated. Upon the start of paving, the ECM will compare the current pile size to the target pile size to control the rotational conveyor speed and the rotational auger speed ratio to maintain the target pile size. This auto-calibration option may replace, or be present in addition to manual dials.
[0012] A sensor produces a first target material height signal indicative of an initial material height at the edge of the screed, and transmit this signal to an ECM. The ECM calculates or sets a gain corresponding to the target material height. As the paver moves and material is delivered by the conveyor and auger, the sensors continue to detect an actual material height at the edge of the screed. This signal is transmitted to the ECM, which compares the actual and target material height signals, and determines a target rotational speed of the auger and conveyor to maintain the target material height.
[0013] The paver continuously senses and transmits the material pile height information to the ECM, which adjusts the auger and conveyor speeds accordingly. A machine which has been auto-calibrated may begin paving with the proper speeds and speed ratio.
[0014] The feed conveyors and spreader augers may be mechanically or electronically coupled together, and accordingly, the rotational speed may be expressed by a ratio between the conveyor rotations per minute (RPM) and the auger RPM. In an alternate embodiment, a second pair of sensors measures the amount of material deposited by the conveyor to the auger. When sensors are employed to detect the amount of material delivered by the conveyor to the auger, the conveyor speed is be independent of the auger speed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings.
[0016] In the drawings:
[0017] FIG. 1 is a side view, showing the general construction of an asphalt paving machine including an example apparatus of the present disclosure;
[0018] FIG. 2 is a schematic representation of an example system;
[0019] FIG. 3 shows an example operator control panel;
[0020] FIG. 4 shows an example screed station control panel, all arranged in accordance with at least some embodiments of the present disclosure; and
[0021] FIG. 5 is a flow chart, illustrating an example method of the present disclosure.
DETAILED DESCRIPTION
[0022] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, may be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.
[0023] The present disclosure relates to apparatus and methods of calibrating an initial or target pile size, and maintaining that pile size. The present disclosure contemplates using sensors, e.g. paddle, acoustic, ultrasonic sensors or other types of sensors, to measure the material pile size during calibration and throughout the paving process. Example systems may eliminate the manual adjustment of knobs for gains, and instead, auto-calibrate the pile size.
[0024] Prior designs required manual estimations and settings, i.e. a gain to be manually set for each job to create the target material pile size. Because the setting of these manual settings by the rotary switch requires some training and experience for consistency, there is a high probability that it will be incorrectly set at the beginning of paving job, resulting in inconsistent material height regulation when the gain is adjusted to the proper setting. Traditional pavers require close monitoring by the screed operator when paving commences until it is adjusted to the proper setting. Example systems of the present disclosure allow a paver to initialize with the proper gain and settings.
[0025] FIG. 1 shows an example paver 010 . Tow arms 130 , one located on each side of paver 010 , pull the screed 100 and screed extender 110 . An auger 300 is located in front of the screed 100 .
[0026] FIG. 2 depicts a schematic representation of an example system that includes an asphalt paving machine 010 of the type with which an example method may be implemented. It will be appreciated that the present disclosure may be useful for automatic calibration with other types of earth moving machines, and with similar machines that operate with a sensor as part of the machine control system.
[0027] Asphalt paver 010 includes rotatable conveyor 200 , which feeds material 040 to rotatable auger 300 . Auger 300 is adapted to receive asphalt 040 discharged from the conveyor 200 and spread asphalt 040 in front of screed 100 to form material volume 050, which the screed 100 compresses into laid asphalt road mat 025.
[0028] A sensor 400 is mounted on the screed extender 110 , and while FIG. 2 only shows one sensor 400 at the end of screed extender 110 , a second sensor may be mounted on the other end of screed extender 110 . Sensor 400 should be adjusted to be pointed to a spot on pile 050 which should be maintained at a relatively constant height to create an even road mat 025. For example, a good spot to point sensor 400 would be just beyond the auger 300 edge. Operator station 700 and screed station 750 provide control over the paving process.
[0029] A second sensor 475 may be associated with paver 010 . The second sensor 475 senses the amount of asphalt material 050 placed by conveyor 200 to the auger 300 and transmits corresponding signals in response to respective sensed excesses and deficiencies of asphalt material 040. Sensor 475 measures the material 050 in front of the auger 300 to vary the speed of the conveyor 200 to increase or decrease the material 040 delivered to auger 300 . By using a second set of sensors 475 to detect the amount of material 040 delivered to the auger 300 by conveyor 200 , the speeds of the auger 300 and the conveyor 200 can be independently adjusted. Without this sensor 475 , it would be difficult to determine the independent conveyor 200 and auger 300 speed, and thus they could be tied together by an adjustable ratio. Thus, sensor 475 may replace a conveyor speed and auger speed ratio knob. Regardless, knobs on tractor control station 700 and screed control station 750 may still be retained for a manual setting or override of the target pile size calibration and application.
[0030] As paver 010 moves and pulls screed 100 , sensor 400 transmits the material size information to ECM 450 , which adjusts conveyor 200 and/or auger 300 speeds accordingly to ensure target pile size is maintained.
[0031] Referring to FIG. 3 , an example tractor operator station 700 is shown. Operator station 700 is generally located on the tractor at the rear of the machine 010 , and has independent controls for the conveyor 200 and the auger control 300 . The left and right sides of station 700 perform the same functions for each respective side of the conveyor 200 and auger 300 . For example, conveyor panel 709 controls the right side of conveyor 200 with reverse button 708 , auto button 707 , and manual override button 706 . These buttons 706 - 708 operate in the same manner for left conveyor panel 702 . Furthermore, buttons 706 - 708 operate in a similar manner for auger panel 703 , including reverse, auto, and manual settings as indicated by the respective symbols. In one embodiment, the dials 701 on panel 704 are to adjust the target amount of material 040 the conveyor 200 delivers to the auger 300 when sensor 475 is employed. Panel 704 is used when button 707 on panel 709 or its corresponding button in panel 702 is activated to the “Automatic” or “Auto” mode. The left and right dials on panel 704 control the amount of material 040 delivered by the conveyor 200 to the auger 300 . The manual buttons are “Manual Overrides” which momentarily activate the conveyors or augers at a fixed high speed.
[0032] In an alternate embodiment, the magnitude of the conveyor ratio signal may be adjusted by the relative position of the conveyor ratio dials 701 in panel 704 . For example, “slow” or “−” represents a minimum speed ratio of the conveyor speed to the auger speed, while “fast” or “+” represents a maximum speed ratio of the conveyor speed to the auger speed. Thus, the conveyor speed may be calculated as a ratio of the auger speed. Left and right side of auger 300 may be controlled by left and right sides of panel 703 .
[0033] Referring to FIG. 4 , screed station 750 is located on the screed 100 of FIG. 2 . A signal producing switch or button 715 initiates the program of calibrating the target material height at the edge of the screed 110 . A material height dial 710 is turned to adjust the target height of material 050, at the edge of the screed 100 . The material height dial 710 adjusts a signal indicative of a target amount of asphalt material 050 at the edge of the screed. The magnitude of the material height signal is adjusted by the relative direction and increments of the dial 710 . For example, “low” or “−” represents a lesser amount of material, while “high” or “+” represents a greater amount of material 040 at the end of the screed.
[0034] In an alternate embodiment, a separate auto-calibrate button 715 may not be present. Upon starting the paver 010 , the ECM's auto-calibrate function immediately senses the pile size 050, and sets the target height of material to be controlled by auger 300 and conveyor 200 .
[0035] Conveyors 200 may be controlled by conveyor panel 712 and auger 300 may be controlled by auger panel 713 , or conveyor 200 and auger 300 may be controlled simultaneously with panel 714 , on the screed station 750 . In addition to reverse and manual override buttons, screed station 750 panels 712 and 713 each have a pause button 711 .
[0036] After setting up the prefill to a desired volume 050, as determined by calculation or experimentation, an operator initiates the disclosed method with auto button 707 or its corresponding button on left conveyor panel 702 , on operator station 700 , and then presses the Auto Calibrate button 715 on screed station 750 . Sensor 400 continuously measures a distance x and send the distance information signal to an ECM 450 . ECM 450 uses the distance (material height) information and paver 010 properties, and determines a conveyor 200 speed and an auger 300 speed to maintain that material height. The ECM 450 transmits this to the conveyor control 705 and auger control 350 . When paver 010 is initiated to start paving, paver 010 commences at these determined speeds, or in an alternate embodiment, initializing the machine 010 automatically begins the calibration process, followed by paving.
[0037] FIG. 5 is a flow chart outlining the method 501 of the disclosure. A prefill material volume 050 created in front of the screed 100 is measured with a sensor 400 , as in operation 510 . In operation 520 , this material pile information is sent to the ECM 450 , and set as a target pile size in operation 230 . Before paving commences, in operation 540 , the ECM 450 determines an auger and a conveyer speed, and in operation 550 , transmits this information to the auger and conveyor controller. Upon starting the paver, the auger 300 and conveyor 200 turn at the determined speeds. During paving, as the conveyor and auger deposit material in front of the screed, the pile height varies and shifts. Thus the sensor periodically or continuously (e.g. seconds, or milliseconds, or any time interval) monitors the current pile size (i.e., detected pile size), and sends the information to the ECM, as in operation 560 . In operation 570 , the ECM compares the detected pile size to the target pile size, and transmits the appropriate signals to the conveyor and auger controls to adjust the conveyor and auger speeds, as in operation 580 , to maintain the target pile size.
[0038] In an automatic mode, the ECM 450 increases the auger rotational speed in response to the actual material height being less than the target material height, i.e., the amount of asphalt material near the edge of the screed being below that of the target amount of material. This target material height is automatically determined by the sensor and the calibration program. Alternately, the control 450 reduces the auger rotational speed in response to the actual material height being greater than the target material height, i.e., the amount of asphalt material near the edge of the screed being greater than that of the target amount of material.
INDUSTRIAL APPLICABILITY
[0039] This system may be used in asphalt pavers to reduce, minimize, and/or restrict operator variability. Example systems may allow an asphalt paver to accurately distribute material for the screed for the entire project.
[0040] The present system may be used when paving a road, parking lot, or other asphalt or aggregate surfaces. One advantage of the present disclosure lies in the commencing of the initial paving process; the operator does not have to guess an initial gain or auger and/or conveyor speed. The operator is not required to set a dial or guess the prefill material amount that the paver attempts to replicate; the paver measures a prefill material, and adjusts the auger and/or conveyor in response to the detected prefill material.
[0041] A prefill material pile size may be created in front of the screed, as typical in the industry. This prefill material to be created is determined before paver initialization, so the paver has a beginning frame of reference.
[0042] The prefill material pile volume is measured with a sensor and sent to the ECM, as a target pile size. As paving commences, the ECM determines an auger and a conveyer speed, and transmits this information to the auger and conveyor controller. Thus, upon starting the paver, the auger and conveyor turn at the appropriate speeds to deliver an accurate amount of feed material. During paving, the sensor periodically monitors the current pile size, and the ECM transmits the appropriate signals to the conveyor and auger controls to adjust the conveyor and auger speeds to maintain the target pile size.
[0043] The paver may be automated to reduce operator error, but retains manual override features.
[0044] While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.
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A method and apparatus is disclosed for controlling material feed for asphalt pavers. The material feed system includes a screed, feeder conveyor and a spreader auger. A sensor measures a material volume and transmits this information to an electronic control module (ECM). This information may be used as the target material volume, which the ECM may use to calculate a corresponding conveyor speed and auger speed. The sensor monitors the material volume as paving commences, and the ECM maintains the initial calibrated target size by adjusting the auger and conveyor rotational speeds.
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BACKGROUND OF THE INVENTION
The invention described in this application was made at least in part with the support of funds from the National Cancer Institute (Grant No. CA28218) and the National Heart, Lung and Blood Institute (Grant No. 32034). The U.S. Government may have rights in this invention.
This invention relates to amplification of a gene and enhancing production of a desired gene product.
Organisms use gene amplification, i.e., increasing the number of copies of a specific gene sequence, as a cellular regulatory mechanism used occasionally to overproduce a particular gene product in the normal course of their growth and development or to respond to certain drugs or disease states [Stark and Wahl (1984) Gene amplification. Ann. Rev. Biochem. 53:447-491]. Amplification of specific genes can enable an organism to resist the lethal effects of several toxic substances [Schimke et al (1978) Science 202:1051-1055; Wahl et al (1979) J. Biol. Chem. 254:8679-8689].
Biswas and Hanes [(1982) Nucleic Acid Res. 10: 3995-4008]disclose that the thymidine analog 5-bromodeoxyuridine (BrdUrd) induces amplification of the gene encoding the hormone prolactin (PRL) in a clonal strain of the rat pituitary tumor cell line designated "GH 1 2C 1 " that does not normally produce PRL, that is, the cell line is ordinarily PRL - . BrdUrd-induced gene amplification is accompanied by PRL synthesis in the PRL - GH strain [Biswas et al (1977) Cell 11:431-439]. A specific length of DNA (about 20kb), including all of the rat prolactin gene sequence plus about 3kb upstream from the 5' end thereof and about 7kb downstream from the 3' end thereof, is amplified by BrdUrd. The BrdUrd-induced PRL + phenotype reverts to PRL - upon withdrawal of the drug [Wilson et al. (1983) DNA 2:237-242].
Harvard Medical Area Focus, Jan. 12, 1984 reports that Dr. Biswas and colleagues have derived a strain of rat pituitary cells which produce prolactin only upon exposure to 5-bromodeoxyuridine (BrdUrd), accompanied by a 50 to 100 fold increase in the gene encoding prolactin. This gene amplification is reported to be reversible upon withdrawal of BrdUrd. The report says,:
"The precise mechanisms of gene amplification in higher organisms are still unresolved . . . `The trick is in getting hold of the DNA sequence that carries the information for responding to the drug, ` [Dr. Biswas] said. `If we can isolate it and put it in close association with other genes, it is possible that we might be able to amplify those genes.`"
The article further discloses that a viral gene was joined to a DNA segment which included part of the prolactin gene from a BrdUrd-inducible rat cell and a region adjacent to that gene. The viral gene is amplified by BrdUrd.
Chien and Thompson [(1980) Proc. Nat. Acad. Sci. U.S.A. 77:4583-4587] report making overlapping cDNA clones of the rat prolactin gene.
Enquist et al. (1979) Gene 7:335-342 disclose the use of the herpes simplex virus themidine kinase gene as a selectable marker in an E. coli plasmid.
SUMMARY OF THE INVENTION
The invention features a hybrid DNA capable of effecting controlled amplification in a host cell of a heterologous gene that determines a specific function. The hybrid DNA has the following three different DNA regions: (1) an "amplicon" that is inducible by an external stimulus; (2) the heterologous gene (or a site for its insertion); and (3) a selectable marker enabling isolation of the transformed host cells. As used in this patent application, the term amplicon means a DNA segment that effects an increase in the number of copies of at least one other DNA sequence associated with the amplicon. A heterologous gene is a gene that does not naturally occur in association with the amplicon so as to be amplified by it. In order to make a desired compound coded by the heterologous gene: a vehicle including the hybrid DNA is introduced, e.g. by transfection into a host cell; host cells are grown to a desired population; the external stimulus is controlled to effect amplification of the gene in members of the population; cells containing amplified gene are cultured, and the compound is recovered.
In preferred embodiments, the external stimulus is 5-bromodeoxyuridine; the amplicon is derived from DNA associated with a rat prolactin gene, and specifically from DNA substantially similar to (or identical to) a segment of the 10.3 kb at the 5' end of a rat prolactin gene. The heterologous gene codes for human growth hormone, and the host cell is a eucaryotic (most preferably a mammalian) cell.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiment and from the claims.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Brief Description of the Drawing
I. Drawings
FIG. 1 is a diagrammatic representation of a hybrid DNA sequence.
II. The Hybrid DNA
FIG. 1 is a diagram of a hybrid DNA sequence that contains the amplicon. Specifically, the hybrid DNA sequence includes (reading 5' to 3'): (1) a marker gene, in this case a 3.5 kb gene coding for thymidine kinase which enables transformants to grow in a HAT selection medium; (2) an amplicon, in this case the amplicon is contained within a 10.3 kb sequence from the 5' end of the rPRL gene of a GH cell line; and (3) a 2.6 kb human growth hormone (hGH) gene sequence that is representative of the heterologous gene coding for a desired protein.
An important element of the hybrid for purposes of this invention is the amplicon portion of the 10.3 kb rPRL-related sequence. The amplicon is capable of controlled amplification of gene sequences that are adjacent either to its 5' or its 3' end. While the entire 10.3 kb DNA segment is used in the hybrid DNA described here, amplicon function may reside in a shorter sub-segment within that 10.3 kb seqment, and, in that case, one skilled in the art will readily perceive that the 10.3 kb segment can be divided into restriction fragments that can be tested for amplicon activity and re-divided and retested to provide smaller sub-fragments retaining the activity. The invention covers constructions and methods using such sub-fragments.
While the specific embodiment includes a specific marker gene and a specific heterologous gene, the invention covers other markers (e.g., antibiotic resistance) and other heterologous genes.
Applicant has deposited with the American Type Culture Collection in Rockville, MD, a virus comprising the above-described amplicon portion of the rPRL-related sequence. The deposit has been given accession number ATCC 40187. Applicant's assignee acknowledges its responsibility to replace this deposit should the deposit become non-viable before the end of the term of a patent issued hereon, and its responsibility to notify the ATCC of the issuance of such a patent, at which time the deposits will be made available to the public. Until that time the deposits will be made available to the Commissioner of Patents under the terms of 37 CFR §1.14 and 35 USC §112.
A suitable amplicon for use in hybrid DNA can be obtained by digesting the lambda DNA from the deposit with EcoRI and separating the resulting fragments on a 1% agarose electrophoresis gel. In addition to the lambda DNA, the gel will reveal three primary brands representing the rPRL-related sequence: at about 2.0 kb, 4.4 kb, and 11.0 kb. The 11.0 kb segment represents a suitable amplicon.
Alternatively, the hybrid DNA can be constructed as described below and illustrated in FIG. 1 from the elements A-C below.
A. Thymidine Kinase
A thymidine kinase gene from any of a number of known sources can be used. For example, a plasmid containing a herpes simplex type I thymidine kinase gene (HSVITk) can be obtained by the technique generally described by Enguist et al. (1979) Gene 7:335-340. The HSVlTk gene is recovered by digesting the plasmid with a suitable restriction enzyme (e.g. BamH1) and then performing various isolation techniques, such as described in Wilson et al. (1983) DNA 2:237-242.
B. The Amplicon
The amplicon is contained in a 10.3 kb sequence 5' to the rPRL gene of a PRL-nonproducing BrdUrd-inducible (PRL - ) rat pituitary tumor cell line. Such cell lines can be obtained by growing rat pituitary tumor cells in gradually increasing concentrations of BrdUrd, using the general technique described by Biswas et al. (1977) Cell 11:431-439. Specifically, suitable PRL - cell lines (GH 1 2C 1 ) can be obtained from rat pituitary tumors, and then subjected to gradually increasing doses of BrdUrd to yield a more resistant strain (e.g. F 1 BGH 1 2C 1 ). A specific starting cell line that could be used for such a procedure is GH 3 (ATCC CCL 82.1).
High molecular weight DNA from such cell lines (designated, e.g., GH 3 /F 1 BGH 1 2C 1 )) is obtained by the general method of Gross-Ballard (1973) J. Biochem. 36:32. That DNA is digested with EcoRI, and the fragments are separated on a 1 percent low-melting agarose gel. The 11-kb fragments of the genomic DNA are extracted from the gel and cloned in an EcoRI site of a suitable vehicle such as the λ Charon 4A described in Blattner et al. (1977) Science 196:161, yielding "λ104".
The 11.2 kb 5' end rPRL DNA sequences accordingly represent the specific region of the BrdUrd-inducible PRL gene in transformed rat pituitary cells (λ104). The 11.2 kb EcoRI DNA fragment isolated from λ104 is digested with restriction endonuclease BamH1, which generates two DNA fragments (0.9 kb and 10.3 kb). These are separated by low melt agarose (1 percent) gel electrophoresis and extraction as described above. The amplicon is contained within the 10.3 kb segment.
C. The hGH gene
The hGH gene sequence is recovered using similar techniques from the plasmid hGH pBR322 described by DeNote et al. (1981) Nucleic Acid Research 9:3719-3730.
D. Assembling the Hybrid DNA
The 10.3-5' rPRL gene sequence is ligated to HSV1Tk and hGH DNA sequences using standard recombinant DNA techniques. The hybrid DNA (16.4 kb) is separated from the rest of unreacted DNA fragments by electrophoresis on a low melt agarose gel, and the high molecular weight DNA is extracted from agarose and characterized by Southern blot analysis.
In FIG. 1, the top sketch shows the amplified (solid area) and unamplified (open area) regions of the PRL gene and its neighboring sequences in BrdUrd-treated cells. The second sketch from the top shows the organization of rPRL gene. Solid blocks are exons and the regions designated by letters A to D are the introns in the rPRL gene. The last sketch shows the organization of the "Hybrid DNA". The numbers under HSV1Tk, hGH and the Hybrid DNA designate the length (kilobases) of the specific DNA sequence. The arrows show the recognition sites of the indicated restriction endonucleases.
The hybrid DNA can be characterized by Southern blot analysis. The DNA is separated according to its electrophoretic mobility and the identity of fragments thus separated is verified by radiolabeled hybridization probes.
III. Transfer of Hybrid DNA into Mouse Cells
The transfer of the HSV1Tk-10.3-5' rPRL-hGH hybrid DNA into Tk - mouse L cells is executed according to the method of Wigler et al. (1977) Cell 11:223-232. The selection of the transfectants is carried out on the basis of the transfer of HSV1Tk gene as indicated by the HAT-resistant [Szybalska et al. (1962) Proc. Nat'l. Acad. Sci. (USA) 48:2026-2048] phenotype of the cells (Table-1). About 25-32 HAT resistant transfectants per 10 6 recipient cells are obtained in these series of transfections. Transfer of the sequences of the hybrid DNA into the mouse cell is verified by dot hybridization analysis of transfectant DNA as described by Wilson et al. (1983) cited above.
Transfectants retain the original orientation of the hybrid DNA (5' to 3'): HSV1Tk-rPRL 10.3-5' rPRL-hGH, as can be demonstrated by Xba I digestion to generate three fragments of about 3.8 kb, 6.6 kb, and 9.4 kb respectively. The latter fragment hybridizes to the 32 P-labeled HSV1Tk and the 6.6 kb fragment hybridizes with 32 P-labeled hGH DNA. The smaller fragment does not hybridize with either probe. These results suggest that the HSV1Tk DNA is still attached to the 5' end of the 10.3 kb DNA in the transfectant chromosone. The 6.6 kb fragment is composed of 2.7 kb×ba I fragment of rPRL 10.3 kb and 2.6 kb hGH DNA, demonstrating that the 3' end structure of the 10.3 kb rPRL DNA is attached to the hGH DNA.
IV. Amplification of the Hybrid DNA Sequence in Transfectants
The levels of hybrid DNA sequences in control and BrdUrd treated transfectants are examined to demonstrate amplification of the hybrid specific sequences in these cells. The transfectants are found to be sensitive to BrdUrd and to grow only on concentrations of the drug lower than 10 μg/ml.
To study the BrdUrd-induced amplification of specific DNA sequences, the transfectants are grown in the presence of 10 μg/ml of the drug for 7-10 days. Results of dot hybridization analysis of the DNA isolated from control and drug treated cells show that levels of HSV1Tk and rPRL-10.3 kb DNA sequences are higher in equal amounts of BrdUrd-treated cell DNA of transfectants carrying the 10.3 kb DNA fragment (λ104) from BrdUrd-inducible cells. BrdUrd treatment of the transfectants carrying control DNA [i.e., 10.3 kb fragment from non-inducible PRL + GH cells] does not affect the level of either HSV1Tk or rPRL 10.3 kb sequences in the transfectants.
Similarly the levels of hGH sequence in one of the transfectants of each series is determined after treatment of the cells with BrdUrd (10 μg/ml, 7d). Dot hybridization analysis of the transfectant DNA again reveals that the [ 32 P]hGH-hybridizable sequence is significantly greater in the drug-treated transfectant which carries the hybrid DNA with 10.3 kb from BrdUrd-inducible cells, whereas the BrdUrd treatment does not affect the levels of hGH sequence in transformants with control DNA.
The amplification of the hybrid DNA sequence in the transfectants carrying the 10.3 kb from BrdUrd-inducible cells is further verified by Southern blot analysis of the transfectant cell DNA. DNA from untreated and BrdUrd-treated inducible transfectants is digested with Xba I and the fractioned DNA is hybridized with 32 P-labelled 11.2 kb DNA sequence. The levels of all three Xba I fragments of the hybrid DNA are greater in BrdUrd treated cells. These results further substantiate that the hybrid DNA sequences, including HSV1Tk and hGH sequences, are all amplified following treatment of the cells with BrdUrd. More specifically, in order to demonstrate amplification, the levels of specific regions of hybrid DNA sequence in transfectants are determined using dot hybridization and labeled probes as described by Wilson et al. (1983) DNA 2:237-242.
Without being bound to any particular theory, it appears that the above-described gene amplification is different from previously recognized gene amplification phenomena such as: (1) amplification of genes that occurs during normal developmental processes, such as amplification of rRNA genes during oogenesis as reported by Brown et al. (1968) Science(160:272-280); or (2) the stable and permanent acquisition of a trait such as toxin resistance.
Amplification is limited to 20 kb length of DNA in the neighborhood of rat PRL gene sequences in GH cells, and this DNA sequence is flanked by unamplified sequences at both ends thus designating a unit of amplification. The DNA sequence effecting the BrdUrd-inducible gene amplification is located in 10.3 kb 5' end rPRL gene sequence. Transfectants carrying this DNA segment from the BrdUrd-inducible cells induces amplification of both the 3' and 5' end neighbouring sequences.
PRL gene amplification observed in this GH cell strain in response to the drug BrdUrd is a true induction phenomenon. The onset and the termination of the phenomenon can be controlled by an externally administered agent.
Other embodiments are within the following claims.
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Hybrid DNA capable of effecting controlled amplification in a host cell of a heterologous gene that determines a specific function. The hybrid DNA has the following three different regions of DNA: (1) an "amplicon" that is inducible by an external stimulus; (2) the heterologous gene (or a site for its insertion); and (3) a selectable marker enabling isolation of the transformed host cells. In order to make a desired compound coded by the heterologous gene, a vehicle including the hybrid DNA is introduced into a host cell is transformed with the vector, transformed host cells are grown to a desired population, the external stimulus is controlled to effect amplification of the gene in members of the population, cells containing amplified gene are cultured, and the compound is recovered.
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BACKGROUND OF THE INVENTION
This invention relates in general to a sealing ring construction and more particularly to the components of fluid seal assemblies used to provide inner diameter and outer diameter sealing on oil field equipment.
It is common practice to use seal assemblies to form a fluid barrier on the inner diameter or exterior diameter of oil field equipment, such as gas lift valves, safety valves, and circulating tools. Typically, a seal assembly includes a center element, one or more sealing rings, and one or more backup rings. The sealing rings typically are V-shaped or Chevron type packing rings, which have a concave, V-shaped bottom surface, a convex top surface and straight sides. Such rings are commonly known as V-rings. An example of such an assembly is shown in U.S. Pat. No. 4,811,959. Multiple V-rings may be necessary to provide a sufficient number of sealing surfaces for an effective seal.
The service conditions for seal assemblies can vary widely in temperature, pressure and the type of liquid or gas being sealed. Temperatures can range from -70° F. to 400° F., with pressures from atmosphere to 20,000 psi. To accommodate the varying service conditions, various materials and combinations of rings and backup rings are used. U.S. Pat. No. 4,811,959 describes a large variety of ring materials including fabric impregnated with rubber, asbestos with a plastic binder or elastomeric material, wire mesh, asbestos cord, ceramic fibers, and elastomeric materials wrapped with tetrafluoroethylene-propylene copolymer or terpolymer.
Multiple non-elastomeric backup rings may be used to give strength to the sealing rings in order to accommodate high pressures. Often, when the seal assembly is taken apart and reassembled for repair or other reasons, the backup rings are inadvertently left out or too few backup rings are replaced. Error in installation of the backup rings can result in excessive deformation and destruction of the V-rings and substantial wear, inefficient operation and leakage of the seal.
In view of the foregoing, a need exists for a seal assembly which can accommodate high pressures without the need for backup rings. Also, a need exists for a seal assembly which reduces the number of sealing rings necessary to provide an effective seal.
SUMMARY OF THE INVENTION
The present invention alleviates to a great extent the deficiencies of the prior art by providing a sealing ring comprising an elastomeric body and a reinforced face such that a portion of the ring is less flexible than the remainder of the ring.
In another aspect of the invention, the sealing ring has a waisted cross section such that the ring provides two distinct sealing surfaces on both the inner and outer diameters. Additionally, the two sealing surfaces can be provided by the elastomeric body and the reinforced face to create surfaces with different characteristics.
In another aspect of the invention, a plurality of sealing rings according to the present invention are stacked to provide a sealing assembly.
Therefore, it is an object of this invention to provide a sealing ring which can be used in high pressure situations without the need for backup rings. It is another object of the present invention to provide a sealing ring which requires fewer rings to provide an effective seal.
With these and other objects, advantages and features of the invention that may become apparent, the nature of the invention may be more clearly understood by reference to the following detailed description of the invention, the appended claims and the several drawings attached hereto.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-section view of a sealing ring according to a preferred embodiment of the present invention.
FIG. 2 is a cross-section view of a preferred embodiment of a seal assembly according to the present invention using the sealing ring of FIG. 1.
FIG. 3 is a cross-section view of a second preferred embodiment of a seal assembly according to the present invention using the sealing ring of FIG. 1.
FIG. 4 is a cross-section view of a sealing ring according to a second preferred embodiment of the present invention.
FIG. 5 is a cross-section view of a sealing ring according to a third preferred embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Referring now in detail to the drawings, there is illustrated in FIG. 1 a cross-section of a sealing ring 20 according to a preferred embodiment of the present invention. The sealing ring 20 is generally in the shape for V-ring type seals; it is formed of an elastomeric material with a V-shaped concave bottom 28 and a rounded convex top 26. The sealing ring 20 has a waisted crosssection, which means that both the inner surface 22 and the outer surface 24 of the sealing ring 20 are concave, so that the middle section has a smaller width than either the top or bottom.
The sealing ring 20 consists of two portions, an elastomeric body 40 and a reinforced face 30, which define its shape. The reinforced face 30 is attached at its bottom surface 38 to the top surface 46 of the elastomeric body 40. The reinforced face 30 provides a portion of the sealing ring 20 which is less flexible than the remainder of the sealing ring 20 formed by the elastomeric body 40. Additionally, the reinforced face 30 has a lower coefficient of friction than the body 40. Preferably, the reinforced face 30 is formed of molded polytetrafluoroethylene ("PTFE") and is adhered to the body 40 to be integral with the body 40.
The inner surface 22 of the sealing ring 20 is defined by the inner surface 32 of the reinforced face 30 and the inner surface 42 of the elastomeric body 40. Similarly, the outer surface 24 of the sealing ring is defined by the outer surface 34 of the reinforced face 30 and the outer surface 44 of the elastomeric body 40. The waisted cross section of the sealing ring 20 provides two ring-shaped contact areas on both the inner surface 21, 25 and the outer surface 23, 27. The combination of the reinforced face 30 and the waisted cross section creates contact areas with different characteristics on both the inner surface 22 and the outer surface 24 of the sealing ring 20. The top contact areas 21, 23 are formed by the reinforced face 30. The bottom contact areas 25, 27 are formed by the elastomeric body. The use of two inner and outer sealing surfaces and the different characteristics of the sealing surfaces reduces the number of sealing rings needed to provide an effective seal.
When compressed, the reinforced face 30, which is less flexible, is subject to less deformation than the elastomeric body. The shape of the ring is maintained without the need for backup rings. Further, the deformation causes the contact areas 21, 23, 25, 27 to press against the sealed pipes or tools, which provides more surface contact and a stronger seal.
Physical properties of the two materials complement each other such that the lower coefficient of friction of the face can allow a greater force to be applied to the inner diameter and or outer diameter to the equipment being sealed by the face without increasing the actuating drag between the components. This allows more surface contact and a stronger seal for gases and fluids with one arrangement. Therefore, the sealing ring according to the present invention can withstand greater pressures.
FIG. 2 illustrates a cross-section of a seal assembly composed of sealing rings according to a preferred embodiment of the present invention. The seal assembly is disposed between an inner tool 90 and an outer tool 10 to form a fluid barrier. The inner tool and outer tool can be parts of a gas lift valve, safety valve, well pump, circulating tool or other oil field equipment. Depending upon the type of tools, the seal assembly is maintained in position by supports on either the inner or outer tool. As illustrated in FIG. 2, the inner tool includes a seal assembly support 96 created by an area of reduced width on the inner tool. The seal assembly is also bounded by a second seal assembly support formed by the upper surface of a nut 80 attached to a threaded portion 97 of the inner tool. In this construction, the inner tool 90 and seal assembly, can slide or rotate within a bore 12 of the outer tool 10. The seal assembly supports could also be formed by or attached to the outer tool 10. Alternatively, if the inner tool 90 and outer tool 10 do not move relative to each other, seal supports could be located on both tools.
As in general construction, the seal assembly consists of a header 70, a plurality of sealing rings 20 and a plurality of followers 50, 60. The header 70 forms a central element of the seal assembly and is generally of a metallic or other non-elastomeric material. The header top 76 and header bottom 78 are rounded or V-shaped so as to fit within the sealing ring bottom 28.
A plurality of sealing rings 20 according to the present invention are stacked on either side of the header 70. The body 40 of each ring contacts the reinforced face 30 of an adjacent ring. The sealing rings on one side of the header 70 are oriented oppositely to the sealing rings on the other side of the header.
A metallic follower 50 is interposed between the last sealing ring on one side of the seal assembly and the seal assembly support 96. The follower 50 has a concave bottom surface 58 to contact the convex top 26 of the sealing ring. A second metallic follower 60 is interposed between the last sealing ring on the other side of the seal assembly and the seal assembly support 86 of the nut 80. The top 66 of this follower is concave to contact the convex top 26 of the inverted sealing ring 20.
No backup rings are necessary between the sealing rings 20 and the metallic followers 50, 60. The reinforced faces 30 of the sealing rings 20 function similar to backup rings to increase the pressure capability of the sealing assembly. When under pressure, the top contact areas 21, 23 which are part of the reinforced face 30 spread out against the inner tool 90 and the outer tool 10. The elastomeric body is, therefore, prevented from extending past the reinforced face 30. This eliminates the possibility of installation errors regarding the use of backup rings, which can prevent proper operation of the seal assembly.
FIG. 3 illustrates a cross-section of a second seal assembly composed of sealing rings according to a preferred embodiment of the present invention. Again, the seal assembly is disposed between an inner tool 90 and an outer tool 10. The seal assembly is bounded by supports 96, 86 formed by or attached to the inner tool 90 or the outer tool 10. As illustrated in FIG. 3, the seal assembly header 100 has a flat top 106 which rests against the upper seal assembly support 96. The header bottom 108 is rounded or V-shaped to fit within the sealing ring bottom 28. A plurality of sealing rings 20 are stacked on one side of the header so that the body 10 of each ring contacts the reinforced face 40 of the adjacent ring. A single metallic follower 60, which has a concave top 66, contacts the reinforced face 30 of the last ring 20 opposite the header 100. This seal assembly functions in a similar manner to the seal assembly illustrated in FIG. 2 and, thus, no backup rings are necessary.
The dimensions of the sealing ring would depend upon the inner and outer diameters of the tools being sealed. However, by way of example, in a preferred embodiment, a sealing ring, as shown in FIG. 1, having an inner diameter of 0.719 inches and an outer diameter of 1.031 inches has a width of approximately 0.180 inches at its widest points 620, 630 and a total height 605 of 0.204 inches. The distance 610 between the top contact areas 21, 23 and the bottom contact areas 25, 27 is approximately 0.1609 inches. The sides 22, 24 of the sealing ring which form the waisted cross section are defined by an arc 690 having a radius of curvature of 0.2216 inches. The outer surface 36 and inner surface 38 of the reinforced face 30 are parallel curves 640, 641, each having a radius of curvature of approximately 0.1 inches. The bottom 28 of the sealing ring is defined by two angled side portions at angles 660 of approximately 45 degrees. The center of the bottom 670, defined by the area between points approximately 0.051 inches from each side, is defined by an arc 680 having a radius of curvature of approximately 0.05 inches. Naturally, these dimensions would be adjusted based upon the width and height of the sealing ring.
FIGS. 4 and 5 illustrate additional embodiments of sealing rings according to the present invention having slightly different cross-sectional shapes and dimensions. In FIG. 4, the lower contact areas 242, 244 are defined by flat sections along the sides 202, 204 of the sealing ring. In this embodiment, with a sealing ring of dimensions similar to those illustrated with respect to FIG. 1, the contact areas 242, 244 would be approximately 0.03 inches 612. Similarly, the top contact areas 232, 234 of the reinforced face 2 also have flat sections along the sides 202, 204 of the sealing ring of approximately 0.03 inches 613. The flat sections defining the top contact areas 232, 234 and the bottom contact areas 242, 244 are separated by a distance 611 of approximately 0.1679 inches. The sealing ring has a total height 606 of 0.262 inches. In the area between the flat sections, the waisted cross section of the sealing ring has a concave side defined by an arc 691 having a radius of curvature of approximately 0.242 inches. The reinforced face 230 has an outer surface 236 and an inner surface 238 which are parallel and each are defined by arcs 642, 643 each having a radius of curvature of approximately 0.125 inches. The bottom 228 of the sealing ring is formed like the embodiment illustrated in FIG. 1. Two angled side portions 222, 224 are at angles 661 of 45 degrees. The center section 228, which covers an area between points 0.051 inches from each side 675, is defined by an arc 681 having a radius of curvature of 0.05 inches.
FIG. 5 illustrates a third embodiment which is similar to the embodiment of FIG. 4 on the top and sides. This embodiment has a notched portion 350 in the bottom of the sealing ring. The top contact areas 332, 334 and bottom contact areas 342, 344 have flat sections along the sides 302, 304 of the sealing ring. On the bottom of the sealing ring, two angled side portions 322 and 324 are formed at angles 661 of 45 degrees. These side portions end approximately 0.051 inches from the bottom contact areas 675. Two parallel side walls 323, 325 extend into the body 340 of the sealing ring approximately 0.039 inches 700. The side walls are connected by a semicircular center section 328 having a radius 710 of 0.035 inches to complete the bottom of the sealing ring. In this embodiment, the bottom contact areas are spread further apart to press against the walls of the inner tool and outer tool as the reinforced face 330 of the ring below presses into the notched portion of the bottom of the sealing ring.
Although preferred embodiments are specifically illustrated and described herein, it will be appreciated that modifications and variations of the present invention are covered by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention.
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A sealing ring for a seal assembly used in oil field equipment including an elastomeric body and a reinforced face. The reinforced face is of molded polytetrafluoroethylene and is integral with the elastomeric body to provide improved pressure capability for the seal without the need for backup rings. The elastomeric body is formed to have a waisted cross section with a narrower portion in the middle and a wider portion at each end. The wider ends provide multiple sealing surfaces and allow fewer rings to be used.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
In many processes which have one or more steps requiring the distribution of fibrous or particulate material it has proven convenient and economical to use a liquid vehicle, particularly water, for this distribution. Subsequent removal of the liquid vehicle (drying) in such cases becomes an important consideration. While drying usually can be accomplished simply by exposure to the atmosphere and evaporation, speed of operation and other economic factors in most cases dictate the use of accelerated drying techniques. Examples of these techniques are well-known and include contact with a hot surface such as a steam heated dryer drum, contact with a gas stream which may be heated such as air, and contact with a solvent in which the liquid to be removed is highly soluble, causing it to be drawn from the material being dried and concentrated into the solvent.
Since solvent-drying is usually more expensive due to additional chemical costs and often capital costs for solvent recovery equipment, its use is primarily limited to processes which require its unique advantages. Contact with a hot drum in most cases results in an ironing out or flattening of the dried material, and air drying of fibrous materials frequently imparts a harsh stiffness to the material. Solvent-drying, on the other hand, can result in a soft, relatively uncompressed, dried product.
2. Description of the Prior Art
In conventional solvent-drying steps, the material to be dried is usually drawn in web or fiber form through a solvent bath. The liquid to be removed is exchanged in the bath leaving the web or filament drier as it emerges from the solvent bath. In some cases it has proven desirable to employ multiple solvent baths to increase the rate of liquid removal or where different solvents are required to remove more than one liquid, for example. In copending and co-assigned U.S. patent application Ser. No. 402,311 to Frederick O. Lassen entitled "Filaments of Chemically Modified Cellulose Fibers, Method of Making Such Filaments and Webs and Products Formed Therefrom" there is disclosed a solvent-drying process wherein multiple solvent baths are utilized with the result that solvent renewal requirements can be substantially reduced.
It is a characteristic of solvent-drying steps that periodic changing of the solvent bath is required. The evaporation of the solvent combined with the build-up of the liquid being renewed will eventually render the drying properties of the bath ineffective. In most cases it is necessary to separate the liquid removed from the solvent in order that the solvent can be reused. This presents a problem of substantial economic importance in virtually all processes utilizing a solvent-drying step. The entire bath volume must be treated by distillation or other separation techniques which inherently causes a considerable loss of solvent. It can be readily seen, that a significant amount of the expense of solvent-drying is occasioned by the solvent regeneration or reconcentration step. The present invention is directed at a method of solvent-drying which greatly facilitates solvent renewal and reduces the solvent losses.
SUMMARY OF THE INVENTION
In accordance with the present invention, a solvent or solvent mixture is used as the drying medium which forms layers one of which favors the concentration of the liquid being removed. More specifically, the solvent mixture is one that forms two or more immiscible layers, one of which has an equilibrium concentration substantially richer in the liquid being removed than the one or more others. When contacted with the solvent medium in accordance with the invention, the liquid being removed is concentrated in the layer of the solvent mixture in which it is richest with a minimum depletion of the solvent medium. In treating the solvent, it is therefore necessary only to withdraw the liquid-rich layer and purify the solvent by azeotropic distillation to an extent that it can be returned to the drying bath. Preferably, the liquid-rich layer comprises only a minor portion by volume of the solvent mixture, and drying of the material takes place in a different layer.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates schematically an embodiment of the method of the invention for a two layer system with drying in the top layer; and
FIG. 2 schematically illustrates an alternative embodiment utilizing a three layer system with drying in the bottom layer; and
FIG. 3 illustrates schematically a third embodiment providing for temperature control of the bath and separator contents.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
While the invention will be described in connection with preferred embodiments, it will be understood that it is not intended to limit the invention to those embodiments. On the contrary, it is intended to cover all alternatives, modifications, and equivalents as may be included within the spirit and the broad scope of the invention as defined by the appended claims.
The azeotrope-forming mixtures which can be used in accordance with the process of the invention will depend on a number of factors including the specific liquid to be removed, the amount to be removed, and the desired speed of the drying step. When an azeotrope-forming mixture includes two solvents, it is only essential that they form immiscible layers, one of which includes a major portion of the liquid being removed and that the other layer be effective in removing the liquid from the material being dried. As used herein the term "azeotrope" refers generally to the mixed solvent systems that distill universally at a constant composition at a given temperature and pressure. The layer that tends to be rich in the liquid being removed preferably is maintained as a minor portion of the total volume of the solvent bath. The liquid to be removed will be distributed into a solvent drying system, the partition coefficients of which favor the concentration of this liquid in one of the separate, immiscible layers. Examples of mixtures which favor such distribution include the following: butanol-water, methanol-chloroform-water, and 2,3-dichloropropanol-water. Others will be apparent to those skilled in this art.
Turning to FIG. 1, a preferred embodiment of the method of the invention will be described. Wet web 10 travels over guide roll 12 into tank 14 which contains the solvent drying medium divided into layers 16 and 18. Layer 18 is preferably similar in volume and richer in the liquid being removed than is layer 16. Web 10 preferably contacts only layer 16 and is drawn over guide roll 20 out of the tank 14. If web 10 is so light as to float, means may be provided such as guide bars (not shown) to maintain immersion in layer 16. If desired, the web may be air dried in chamber 22 before being wound or further processed.
Solvent renewal takes place by withdrawing the liquid rich layer 18 from bath 14 and directing it to distillation column 24. Preferably this layer undergoes azeotropic distillation producing a distillate which proportionally is significantly lower in the liquid than is the original liquid-rich layer of the bath being distilled. Where condensation takes place in the column 24, the condensate may be returned to the bath as indicated by the dashed arrow. Alternatively, the vapors may be condensed at 26 for collection, and the solvent-rich distillate can be returned to tank 14. In certain cases, if economically feasible, a mechanical separation step can be carried out between condensation 26 and bath 14 to further purify the solvent. Additionally, in some cases it may be practical to direct the exhaust from air drying chamber 22 to condenser 26 to increase solvent recovery.
Thus a virtually closed system is presented that requires treatment of only a fraction of the solvent volume. The layer 16 will remain relatively free of the liquid being removed as this liquid will transfer to layer 18.
FIG. 2 illustrates a similar arrangement for use in a solvent system where the liquid-rich layer forms on top. In this case the solvent system is shown as separating into three layers 28, 30, and 32 in which the first two of are relatively liquid-rich and the bottom layer solvent rich. The web 10 is drawn into the lower solvent rich layer 32 under idler roll 34, and baffle 36 prevents contact between web 10 and the liquid-rich upper layers 28 and 30 as the web is withdrawn.
Solvent renewal is as described with respect to FIG. 1 except that liquid rich composition is drawn from the top of tank 14.
FIG. 3 illustrates a third embodiment wherein the bath contents 42 are directed through cooler 36 and to separator 24 and heater 38 before returning to bath 42. Bath 42 is provided with stirrer 44 and heater 46. In this manner separation takes place only in the separator and a single layer drying bath is maintained under desired temperature conditions.
EXAMPLE 1
An arrangement corresponding to the schematic diagram of FIG. 1 was assembled for the binary azeotrope-forming solvent system including butanol and water. A solution containing 45 percent water and 55 percent butanol (w/w) was placed in a separatory funnel where it formed a two layer system wheren the bottom layer was about 28-29 percent of the total volume and was composed of 7.7 percent butanol and 92.3 percent water, (w/w). Twenty milliliters of distilled water were added, and the layers were allowed to separate. A slight decrease in the volume of the upper layer and a large volume increaase in the lower layer were observed demonstrating that the drying process requires only a minor fraction of the total solvent composition. The lower, water rich layer was removed and distilled at a constant temperature (about 93°C) which was lower than the boiling point of either of the components water (BP 100°C) and butanol (BP 117°C). The condensate was returned to the separatory funnel, and the volume of the remaining water measured after cooling. Volumes in the funnel returned to their original values, and approximately 20 milliliters of water remained in the still.
The amount of water added to the system was concentrated in the lower layer and remained in the still after azeotropic distillation of the butanol with the result that the solvent bath composition was unchanged after completion of the cycle.
EXAMPLE 2
The process of the present invention was applied to dewater webs of phosphorylated cellulose fibers produced in accordance with Example 1 of the above-mentioned Lassen application Ser. No. 402,311. Thus, Northern Spruce pulpboards (air dried) were soaked for one-half hour at 70°C in a solution of 50 percent urea, 32 percent orthophosphoric acid and 18 percent water by weight for a solution pickup of 138 percent by weight based on airdried pulp weight. They were then cured for 2 hours at about 180° to 190°C in a forced draft oven. Following a water wash, the fibers were treated for 1 hour with 3.7 percent HCL (w/w) at 60°-70°C. Following a second water wash, the fibers were soaked in 5-10 percent sodium carbonate (w/w) for one-half hour at room temperature. Then following a third water wash, the fibers were refined in a standardized Valley beater, being hydrorefined for 30 minutes and mechanically refined for 3 minutes with 5 pounds pressure on the beater blade. Following adjustment of the pH to 7.5 with dilute hydrochloric acid, the unbound interfiber water was removed from the refined fibers by centrifugation at approximately 37,000 g. using a Sharpless Model M-41-24 ultra-centrifuge. The resulting swollen fibrous mass contained about 96 percent water by weight and was extruded through a 20 gauge (I.D. about 0.022 inch) syringe needle into a solvent bath. In accordance with the present invention and as illustrated schematically in FIG. 2, the solvent bath comprised a tertiary azeotropic mixture, chloroform-methanol-water. In this system, the water partitioned between the two layers of chloroform and methanol wherein the water content of the upper and lower layers, respectively, were 20 percent (w/w) and 3 percent (w/w). The upper water-rich layer represented only 3 percent of the volume of the solvents used. The extruded filaments of cellulosic fibers were dried in the lower layer illustrating that only a portion of the bath was required for the actual drying step.
EXAMPLE 3
An arrangement corresponding to FIG. 1 was assembled in a beaker as in Example 1. The total weight of the butanol-water solution after preparation was 150 grams. After assembling this solvent-drying system, phosphorylated pulp extrudate prepared in a manner similar to that of Example 2 and containing 94 percent water (w/w) was extrusion formed on a wire mesh and dried in the upper layer of the solvent-drying system. It was then removed from the solvent bath and the remaining solvent evaporated off in a hot air stream from a laboratory-type Sargent-Welch electric forced air dryer at a temperature of about 115°C measured about 8 to 10 inches from the dryer.
The result was a soft, white web sample weighing 0.11 grams. To illustrate the effect of long term drying of material in the solvent-system, 50 grams of water were added to the system and allowed to come to equilibrium for 2 minutes. Following this, another extrusion formed sample of the same phosphorylated pulp extrudate was dried in the upper layer of the solvent system yielding a soft white sample similar in quality to the first sample, showing that the solvent system still was an effective drying medium.
The solvent system was then placed in a separatory funnel and the lower layer separated off. The lower layer, approximately 100 milliliters in volume, was then placed in a laboratory distillation apparatus, and distillation of the liquid was carried out until the distillation temperature rose to the boiling point of water (approximately 100°C) at which time distillation was terminated.
Condensate in an amount of 33.5 grams had been collected during the distillation and was returned to the beaker along with the upper layer from the separatory funnel. Another extrusion-formed phosphorylated pulp sample was dried in the upper layer yielding a soft, white, dry web of comparable quality to the samples described above and weighing 0.07 gram, showing that the solvent system utilizing the recycled condensate from the distillation still was an effective drying medium. Following the drying of this last sample, the solvent mixture from the drying bath was weighed and found to be 123 grams.
The liquid remaining in the distillation flask was also weighed and found to be 68 grams. The liquid was assumed to be pure water after it was shown that the liquid had no alcohol odor, and did not decolorize hot aqueous KMnO 4 solution or cause the color change of hot aqueous K 2 Cr 2 O 7 solution characteristics of alcohols and specifically butanol.
Evaluation of the above data showed that a total of 204.6 grams of liquid had been added to the mixture during the experiment as follows:
150 grams original drying mixture
50 grams water to simulate long term use 4.6 grams water in the gel dried for the web samples.
After the conclusion of the experiment, 123 grams of liquid was left in the drying bath and 68 grams of water had been removed in recycling the lower layer for a total of 191 grams. Thus, all but 12 grams of the liquid was accounted for, with the loss probably due to carry-out with the dried web before final hot-air evaporation and in adherence to the walls of the various vessels used in carrying out the experiment.
EXAMPLE 4
This example demonstrates the advantages obtained through the use of controlled temperature conditions. As illustrated in FIG. 3, the apparatus for this example included a bath with heating and stirring means, a cooler for bath effluent, peristaltic pumping means (Masterflex Model No. 7015), separator, and means for heating solvent and returning it to the bath. As in FIGS. 1 and 2 means were also provided for handling the web.
In operation, the drying bath was charged with 2000 milliliters of n-butanol and the separator with 150 milliliters of n-butanol. A phosphorylated pulp web as in Example 2 was dried, and then 400 milliliters water were added to the drying bath to saturate the solvent with water at room temperature while maintaining a single layer.
The pumps were started to initiate circulation, and heat was applied to the bath. At a bath temperature of 35°C and separator contents temperature of 22°C (ΔT = 13°C) a single layer was maintained in both the drying bath and the separator. An additional 100 milliliters water were added to the drying bath. With a pumping rate of 20 milliliters per minute, a single layer was maintained in the drying bath while two distinct layers formed and were separated in the separator. After one-half hour of continuous circulation the drying bath temperature had risen gradually to 44°C and the temperature in the separator had dropped to 19°C (ΔT = 25°C). At this point a second web sample was dried successfully utilizing the bath.
An additional 100 milliliters water were added to the drying bath, and after only a momentary existence of two layers in the bath, the bath took the form of a single layer again while two distinct layers continued to separate out in the separator. After 1 hour from drying the previous sample, a third similar web sample was successfully dried using the bath. The solutions were then allowed to equilibrate at room temperature.
After drying the third web all of the solution used could be accounted for except for 410 grams which were lost during the 3 hours by evaporation, carryout on the web samples, and adherence to the containers. The remaining solution included 31 milliliters as a water-rich lower layer, and the rest formed the butanol-rich upper layer.
This example illustrates that selection of operating conditions resulting in an appropriate ΔT between the solvent drying bath and the separator will allow drying to take place in a single-layer solvent bath while separation of the solvent takes place at the lower temperature in a separate container. In general, the upper temperature is that at which the liquid being removed, in this case water, is removed most efficiently without boiling while the lower temperature may be as low as can be attained, without freezing the liquid being removed, for improved separation. Depending on factors such as heating and cooling costs, the ΔT may range from about 10C° and preferably is at least about 25C° for improved results. The drying and separation steps are thus greatly facilitated.
The previous examples demonstrate that the use of this method allows purification and recycling of the drying solvents while handling a minor fraction of the solvents used in the drying process. The resulting dried product was characteristic of the solvent-dried materials in terms of softness, color, absorbency, and other physical properties as described in the above-mentioned Lassen application.
In further illustration of the present invention, the butanol-water system will be described in terms of a numerical theoretical example with reference to FIG. 1. Assuming at A, a wet web 10 mass of 50,000 grams composed of 2,000 grams fiber and 48,000 grams water, i.e. consistency 96 percent, and utilizing published azeotropic data, the upper layer 16 will maintain a concentration of 79.9 percent butanol and 20.1 percent water with the bottom layer 18 maintaining a concentration of 7.7 percent butanol and 92.3 water based on partition coefficients as described, for example, in "Handbook of Chemistry and Physics", R. C. West, Ed., 48th edition, The Chemical Rubber Co., Cleveland, Ohio, 1967, p. D5. Changes in total bath concentration resulting from drying of the web will be accomodated by variations in relative volumes of the upper layer 16 and bottom layer 18. Further assuming a 9 to 1 carry-out, the solvent-dry web at B will have a mass of 20,000 grams composed of 2,000 grams fiber and 18,000 grams of layer 16 composition including 14,382 grams of butanol and 3,618 grams of water. The draw-off from bottom layer 18 at C will have layer 18 composition and a mass of 51,531.4 grams including 3,967.9 grams of butanol and 47,563.5 grams of water. By distilling the azeotrope until the butanol is depleted, 44,382 grams of water will be discarded at D and a product obtained at E of 3,967.2 grams butanol and 3,181.5 grams water for a concentration of 55.5 percent butanol and 44.5 percent water. After condensing at condenser 26, this product will be returned to the bath. While those calculations assume efficiencies of 100 percent, except for recovery of vapors from the air dryer, they demonstrate that, to remove the 48,000 g. of water, only 51,531.4 g. of the water rich layer need be treated and no recycling of the solvent-rich layer is necessary. If the air dryer vapors are returned to condenser 26, again assuming 100 percent efficiency, corresponding numbers at C are 55,732 grams total including 4,291.4 grams butanol and 51,440.6 grams water; at D, 48,000 grams water; at E, 4,291.4 grams bultanol and 3,440.6 grams water; and at F, 25,732 grams will be recycled including 18,673.4 grams butanol and 7,058.6 grams water to be returned to the bath with the condensed stream at E.
It will be apparent to those skilled in the art that the process of the present invention is useful for drying a wide variety of materials with a great number of multiple-layer azeotrope producing solvent systems. Thus, wherever the quantity of liquid to be removed is sufficient to make solvent renewal advantageous, the benefits of the present invention can be used to simplify and reduce the cost of solvent renewal. Specifically, examples of other solvent-drying processes which can be improved in accordance with this invention include pulp, gelable starches, fabrics, staple fibers, water-formed nonwovens and wool. These examples are representative only and are not to be considered as limiting the present invention.
To obtain maximum benefits, the solvent drying system should be chosen so that the concentration of the solvent in the liquid-rich layer is as low as practical. Specifically, the liquid content of the solvent-rich layer should be lower than the liquid content of the azeotrope for the respective drying system. Conversely, the liquid concentration of the liquid-rich layer should be greater than the liquid content of this azeotrope.
Thus, it is apparent that there has been provided, in accordance with the invention, a solvent-drying process that fully satisfies the objects, aims, and advantages set forth above. While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modifications, and variations as fall within the spirit and broad scope of the appended claims.
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Solvent-drying, particularly of water-wetted materials, is accomplished through the use of specific azeotropic mixed-solvent systems. The azeotropic systems used in the method of the invention are those which form two or more separate layers, in which the water distribution equilibrium favors the concentration of water or other liquid being removed in one layer over the other. The water or other liquid, therefore, concentrates in one layer facilitating removal by separation of the layers. Drying of the material takes place in the other layer which maintains a constant liquid concentration sufficiently low so as to produce a substantially dried product. Temperature control of the solvent bath and separator contents results in a single-layer drying bath and facilitates separation in a preferred embodiment.
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BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention relates to the distribution of clock signals in circuits where the synchronization between data and clock signals cannot be guaranteed.
2. Relevant Background
In digital circuits of increasing complexity, it is a challenge to maintain synchronization between data and clock signals throughout the circuits, essentially because of increasing parasitic capacitive influences due to decreasing distances between tracks. In order to prevent data loss, clock trees need to be carefully designed in order to approach synchronization between data and clock signals in sections of a circuit. The clock signal of a “branch” assigned to a specific section of the circuit is generated from a reference clock by delay elements that are sized to match the worst-case data delay situation in that section.
FIG. 1 schematically illustrates a typical example where synchronization between a clock signal and data signals is needed. Data signals on a data bus composed of n parallel data lines S 1 , S 2 . . . Sn arrive at the input of a latch 10 . Latch 10 is clocked by a clock signal CK.
When clock CK is low, the content of latch 10 tracks the values of signals S 1 -Sn as they appear at the input of the latch. At the subsequent rising edge of clock CK, the data then present in the latch is held until the next falling edge of the clock.
It is essential that the data in the latch be stable when the clock's rising edge appears. If the data is not stable when the rising edge appears, the data subsequently held in the latch will take a random value. Therefore, care should be taken in the layout of the clock line so that the rising edge at the clock input of the latch always occurs between two consecutive edges at each data input of the latch.
At an origin of data signals S 1 –Sn and clock CK, the data is assumed to be synchronous with clock CK, i.e. the transitions of signals S 1 –Sn occur simultaneously with transitions of clock CK. The data lines and clock line will usually be designed to have substantially the same length, and thus have similar capacitive and delay characteristics.
However, as the number of data lines S 1 –Sn increases, and the distance between the data lines decreases, the influence of parasitic capacitances 12 between the lines becomes significant. The clock line will usually not run close enough to the data lines to be affected in the same manner. As a result the transitions of the data signals will inevitably be delayed with respect to the clock signal.
As shown in FIG. 2 , a conventional solution to prevent data loss in latch 10 is to delay the clock signal by inserting a buffer 14 in the clock line. Buffer 14 will be sized to insert a delay corresponding to the worst-case delay in lines S 1 –Sn.
This solution is however very dependent on the particular layout of the various lines and the technology used, i.e. each such buffer needs to be individually sized for every section of lines between two latches and for each technology the circuit is implemented in.
FIG. 3A is a solution for delaying the clock line that is less layout and technology dependent. The clock line CK runs between two parallel lines 16 and 18 that are connected to a fixed voltage, such as ground GND. The distance between the clock line and each of the ground lines 16 and 18 is substantially equal to the distance between two data lines S 1 –Sn. This distance will often be the minimal distance between tracks allowed by the technology.
With this arrangement, the transitions of the clock signal CK will be delayed by the two parasitic capacitances 12 ′ present between the clock line and each of the ground lines, in a similar way any of the middle data signals S 1 –Sn will be delayed by two parasitic capacitances 12 .
However, as will be explained below with reference to FIG. 3B , this solution is not fully satisfactory and will require additional elements that make it layout and technology dependent.
What is needed, therefore, is a clock delay arrangement accounting for the worst-case delay situation of the data signals, which is independent of the layout and technology.
SUMMARY OF THE INVENTION
According to the invention, this need is satisfied by a circuit comprising a main clock line; two dummy clock lines, each arranged parallel to the main clock line, and the main clock line disposed between the two dummy clock lines; and a clock source coupled to the main clock line and the two dummy clock lines, adapted to drive said dummy clock lines in phase opposition with respect to the main clock line.
A storage element is usually coupled to the main clock line and adapted to store data in sequence with transitions on said main clock line.
Preferably, the main clock line and the dummy clock lines run parallel to each other over a distance substantially equal to the length of said data lines.
The distance between main and dummy clock lines is preferably substantially equal to a minimum distance between data lines.
According to an embodiment of the invention, the clock source comprises a transmission gate coupling each of the dummy clock lines to a reference clock signal, and an inverter coupling the main clock line to the reference clock signal.
BRIEF DESCRIPTION OF THE DRAWING
The invention is illustrated in the accompanying drawing, in which:
FIG. 1 is a schematic diagram of parallel data lines and a clock line coupled to a latch, where delays in the data lines need to be accounted for.
FIG. 2 illustrates a common solution to insert a delay in a clock signal to account for the delays in the data lines.
FIG. 3A illustrates an improved solution to create a delay in a clock signal.
FIG. 3B is a timing diagram illustrating the worst-case delay situation for parallel data lines.
FIG. 4 is a schematic diagram of parallel data lines coupled to a latch, and an embodiment of the invention for delaying a clock signal.
FIGS. 5A and 5B are schematic diagrams of circuitry for generating required clock signals in the arrangement of FIG. 4 .
FIG. 6 is a schematic diagram of an embodiment of the invention applied to only two data lines.
FIG. 7 is a schematic diagram of a pipeline network search engine in which the present invention may advantageously be used.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As previously mentioned, the clock delay arrangement of FIG. 3A does not fully account for the worst-case delay situation in the data lines of FIG. 1 .
FIG. 3B illustrates why. The worst-case situation is when one of the middle data lines of FIG. 1 , say S 2 , transitions in phase opposition to its immediate surrounding lines S 1 and S 3 . Indeed, in this situation, each of the two parasitic capacitances 12 coupled to line S 2 is first discharged and then charged in opposite direction. For instance, if Vdd is the voltage swing of signals S 1 –Sn, each of the two capacitances 12 sees a 2Vdd voltage swing. As a result, the transition of signal S 2 is delayed twice as much as in the situation of clock CK in FIG. 3A , where the surrounding lines 16 and 18 are at a fixed voltage and the parasitic capacitances only see a Vdd voltage swing.
To compensate for this worst-case situation, delay elements will still need to be inserted in the clock line of FIG. 3A , whereby the clock delay solution of FIG. 3A remains technology and layout dependent.
FIG. 4 is a schematic diagram of a latch 10 receiving parallel data lines S 1 –Sn and clocked by a main clock signal CK. Similarly to FIG. 1 , the data lines S 1 –Sn and clock line CK are approximately of same length between latch 10 and a synchronous source 20 of signals S 1 –Sn and CK.
According to an embodiment of the invention, two dummy clock lines 22 and 24 run parallel, on either side, of main clock line CK. Each of these dummy clock lines bears a clock signal that is opposite in phase to main clock signal CK.
With this arrangement, upon each transition of clock signal CK, each of the dummy clock lines transitions in opposite direction, reproducing the worst-case situation of FIG. 3B , where the parasitic capacitances between the lines see a voltage swing of 2Vdd.
The length of dummy clock lines 22 , 24 along the clock line CK is preferably equal to, or greater than the length of the data lines S 1 –Sn between source 20 and latch 10 . The distance between each of the dummy clock lines and the main clock line CK is preferably equal to, or smaller than the smallest distance between the data lines.
In this manner, whatever the lengths of the lines, the distance between them, and the technology used, clock signal CK will always track the worst-case situation of delay in the data lines S 1 –Sn.
FIG. 5A is a schematic diagram of an exemplary source 20 providing the clock signals to main line CK and dummy lines 22 , 24 . The main clock signal CK is provided from a reference clock signal CK 0 through an inverter 26 and a buffer 28 . Each of the dummy clock signals is provided from the same reference clock CK 0 through a transmission gate 30 and a buffer 32 . The transmission gates 30 are permanently set to a pass state, and their role is to insert substantially the same delay as inverter 26 .
Of course, the same results as the circuit of FIG. 5A are obtained by substituting the inverter by a transmission gate, and the transmission gates by inverters, as shown in FIG. 5B .
FIG. 6 schematically illustrates an embodiment of the invention applied to the case of only two data lines S 1 , S 2 . The worst-case situation is when signals S 1 and S 2 transition in opposite directions, whereby the parasitic capacitance between the lines sees a voltage swing of 2Vdd.
This situation would be compensated by using the clock delay arrangement of FIG. 3A . Indeed, the delay introduced when swinging the voltage by Vdd across two capacitors, as in FIG. 3A , is equivalent to the delay introduced when swinging the voltage across one capacitor by 2Vdd. The solution would be technology and layout independent in this particular case. It however requires 3 lines for the clock.
According to the embodiment of the invention shown in FIG. 6 , only two clock lines are required, one bearing the clock signal CK fed to the latch 10 , the other 24 bearing the opposite phase clock signal.
FIG. 7 depicts a system having a pipeline network search engine 102 in which the present invention may be used advantageously. This search engine is fully described in US Patent Publication 2004/0109451, incorporated herein by reference. It includes: a network processor unit interface 200 coupling the search engine to a system controller 101 ; an arbiter 201 ; a central processor unit (CPU) 202 with associated memory (SRAM) 203 containing the programs executed by CPU 202 ; an SRAM controller 204 coupling the search engine to external memory 103 ; and an array of pipeline logic units 205 a – 205 n and a corresponding set of configurable memory blocks 206 a – 206 n forming a series of virtual memory banks, with pipeline logic units 205 a – 205 n and memory blocks 206 a – 206 n coupled by a meshed crossbar 207 enabling the virtual bank configurations.
Crossbar 207 will typically, upon command, effect a point-to-point connection of any one of the pipeline logic units 205 to any one of the memory banks 206 . The point-to-point connection will include as many data lines as the data width of the memory banks, address lines, and a clock line. The data, address and clock lines are depicted as bidirectional buses B between each of the pipeline units 205 , memory banks 206 and the crossbar 207 . These lines may cross several latches in the crossbar 207 , depending on the number of stages in the crossbar. The delay problems caused by the lengths of the lines will arise between latches in the crossbar, and between the crossbar, the pipeline units, and the memory banks.
Advantageously, the present invention will be used for the clock lines in such a system, overcoming the need for the designer to take specific care in adjusting the delays of the clock lines.
Although the invention has been described and illustrated with a certain degree of particularity, it is understood that the present disclosure has been made only by way of example, and that numerous changes in the combination and arrangement of parts can be resorted to by those skilled in the art without departing from the spirit and scope of the invention, as hereinafter claimed. For instance, although a latch is described as being driven by the main clock line, any element having a data storage function may be used instead of the latch.
Although an exemplary embodiment of a system has been shown in FIG. 7 , it is understood that the present invention may be utilized in any number of systems for distributing clock and data signals within the system.
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The invention provides a clock delay arrangement accounting for the worst-case delay situation of data signals, which is independent of the layout and technology. It comprises a main clock line; two dummy clock lines, each arranged parallel to the main clock line, and the main clock line disposed between the two dummy clock lines; and a clock source coupled to the main clock line and the two dummy clock lines, adapted to drive said dummy clock lines in phase opposition with respect to the main clock line.
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BACKGROUND
[0001] The invention relates to a camshaft drive for an internal combustion engine with a camshaft adjuster.
[0002] From DE 689 04 842 T2, a camshaft drive is known for adjusting and fixing the relative rotational angle position of a camshaft relative to a crankshaft of an internal combustion engine by means of a camshaft adjuster. The camshaft adjuster has a housing, which carries on its outer surface a belt pulley. The housing of the camshaft adjuster is closed in a hermetic and airtight way by an end cover on the end opposite the camshaft. The camshaft adjuster is supplied with a fluid, which is used as a work fluid and which takes on lubricating properties, from an oil pan via a motor oil pump.
[0003] From DE 102 48 355 A1, a camshaft adjuster is known, which has an adjusting gear mechanism embodied as a triple-shaft gear mechanism with a double-eccentric plate. In this case, the camshaft drive has a toothed chain as a traction mechanism. The camshaft adjuster is integrated into a cylinder head. Also, a control drive is integrated into the cylinder head under a seal. Contact surfaces of components of the camshaft adjuster and anti-friction bearings moving relative to each other are lubricated by means of lubricant present in the cylinder head.
[0004] The camshaft adjuster according to DE 100 38 354 C2, which includes a swash-plate gear mechanism, is likewise driven via a toothed chain and integrated into a cylinder head, so that lubrication is realized by means of lubricant present in the cylinder head.
SUMMARY
[0005] The invention is based on the objective of providing a camshaft drive, for which the camshaft adjuster can be lubricated in a simple way and for a long service life.
[0006] According to the invention, the objective is met by the features of the independent Claim 1 .
[0007] Accordingly, the camshaft adjuster features lifetime lubrication. Such lifetime lubrication must be introduced once, e.g., with the production of the camshaft adjuster, into the camshaft adjuster and does not need to be renewed within given maintenance intervals, but instead provides sufficient lubrication for a predefined service life of the camshaft adjuster or the internal combustion engine. The lifetime lubrication involves any selected lubricant, especially grease or oil, which is suitable for this purpose.
[0008] Leakage of the lifetime lubrication from the camshaft adjuster, which would lead to a short or long term negative effect on the function of the camshaft adjuster, is prevented according to the invention, in that the camshaft adjuster has a housing, which is sealed from the surroundings and in which the lifetime lubrication is arranged. In this sense, the seal is understood to be any seal that is sufficient to prevent the lubricant from escaping from the housing. The suitable measures for sealing the housing are here to be adapted to the viscosity of the lubricant. In addition, the sealed housing prevents foreign matter such as pollutant particles from entering into the camshaft adjuster.
[0009] An essential advantage of the invention is that with the tight housing and the lifetime lubrication, the necessity of connecting the housing to other lubricant circuits is eliminated. Instead, the camshaft adjuster represents, in terms of lubrication, a separate and autonomous component. This has advantages for assembly and disassembly of the camshaft adjuster, because any connections to other lubricant circuits do not have to be taken into account. As another advantage, it is to be noted that if there are ruptures, changes, or contamination in a lubricant circuit of this construction according to the invention, there are no repercussions on the function of the camshaft adjuster. Conversely this means that any negative effects on the function of the camshaft adjuster, which lead to contamination of the lubricant of the camshaft adjuster, cannot lead to a negative effect on a different lubricant circuit. In this way, severe consequential damages, for example, in the area of the cylinder head, can be avoided.
[0010] Furthermore, according to the invention it is allowed that the camshaft adjuster does not absolutely have to be arranged in a cylinder head of the internal combustion engine, but instead can be arranged outside of this cylinder head. In this way, expanded structural possibilities are given. For example, such a camshaft adjuster can now be used in connection with a belt drive.
[0011] According to a refinement of the camshaft drive according to the invention, the housing has an inner space that is open on at least one side. By means of such a housing, there is easy access for assembly and/or disassembly via the one or more open sides of the inner space. During operation, a seal is realized with a sealing cover, which closes the housing from the outside. Such a sealing cover involves, in particular, a pressed-in or clipped-in sealing cover. The sealing cover can here satisfy only one sealing function at one or more sealing positions, so that this seal can be constructed with small wall thicknesses or non-resistant to bending. Alternatively, such a sealing cover can satisfy other functions in addition to the function of sealing, for example, the support of components of the camshaft adjuster.
[0012] For guaranteeing the seal, any components known for this purpose can be used. In particular, it can involve an O-ring, a labyrinth seal, a diaphragm seal, and/or a radial shaft sealing ring. Such sealing measures can guarantee a sufficient sealing function both between stationary components, such as, for example, the housing and a sealing cover, and also between components that move relative to each other. A suitable sealing measure is selected according to the occurring relative velocities, the viscosity of a lubricant, and the sealing position. For example, for sealing positions in the area surrounding rotating components there are, under some circumstances, lower sealing demands due to the centrifugal forces exerted on the lubricant than for sealing positions between components that do not move relative to each other.
[0013] According to another construction according to the invention, a camshaft projects from a cylinder head with one end region under a seal. Due to this seal, the camshaft adjuster can be constructed separately from the cylinder head. The housing of the camshaft adjuster is sealed, on the side facing the cylinder head, from the cylinder head, the end area of the camshaft, or a component rotating with the camshaft. In this way, it is guaranteed that no lubricant can escape from the housing of the camshaft adjuster in the direction of the cylinder head and no foreign matter can enter into the housing. For the case that the camshaft can be locked in rotation with a rotating component of the camshaft adjuster projecting from the housing of the camshaft adjuster, it is advantageous when the housing of the camshaft adjuster is sealed from this component. In such a case, the camshaft is sealed separately, for example, from the cylinder head. In this case, the camshaft adjuster is also sealed on the side facing the cylinder head for disassembly of the camshaft. Likewise, the camshaft is sealed from the cylinder head on the outside independent of the assembly of the camshaft adjuster. On the side facing away from the cylinder head, the housing of the camshaft adjuster is sealed from an adjustment shaft of a servo motor (or from a component rotating with the adjustment shaft). In this way, the housing, optionally with sealing covers, the adjustment shaft, and the camshaft, forms an inner space, which is sealed from the outside and in which the gear mechanism of the camshaft adjuster with lifetime lubrication is arranged.
[0014] Advantageous refinements emerge from the subordinate claims, the description, and the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Additional features of the invention emerge from the following description and the associated drawings, in which embodiments of the invention are illustrated schematically. Shown are:
[0016] FIG. 1 half-sectional view of a camshaft drive with a housing sealed by means of a sealing cover;
[0017] FIG. 2 a front view of the camshaft drive according to FIG. 1 in a three-dimensional representation;
[0018] FIG. 3 a rear view of the camshaft drive according to FIG. 1 in a three-dimensional representation.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] In the camshaft drive 10 according to the invention, a camshaft adjuster 13 is used for adjusting the angular position between a drive element 11 driven by a traction mechanism, for example, by a chain or a belt, and a camshaft 12 according to a control device, which determines a suitable control signal for adjusting the camshaft adjuster 13 , in particular, under consideration of power output demands of the driver, emission requirements, fuel-conservation requirements, and engine, operating, and environmental parameters.
[0020] In the camshaft drive 10 , any camshaft adjuster can be used, which works on the basis of a superposition gear mechanism or a triple-shaft gear mechanism. In such a gear mechanism, the transmission ratio of the drive movement of the drive element 11 to the camshaft 12 depends on the movement of the adjustment shaft 14 , which is drivingly connected to a control drive.
[0021] In the embodiment shown in FIG. 1 , the gear mechanism involves a double-eccentric gear mechanism. In this embodiment, the adjustment shaft 14 enters into a central bore of a double-eccentric shaft 15 through a drive connection, or optionally through an elastic coupling element 41 . In the end region of the double-eccentric shaft 15 projecting past the end of the adjustment shaft 14 , there are two axially offset, eccentric peripheral surfaces 16 , 17 , which each carry an anti-friction bearing 18 , 19 . The two extremities (regions of maximum distance of the peripheral surfaces 16 , 17 from a longitudinal axis X-X of the camshaft adjuster) of the peripheral surfaces 16 , 17 are offset by 180° relative to each other in the peripheral direction.
[0022] The anti-friction bearings 18 , 19 each carry intermediate gears 20 , 21 on their outer surfaces. The intermediate gears 20 , 21 have several bores 22 , 23 distributed in the peripheral direction. A common connecting piece 24 passes through each bore 22 , 23 , with this connecting piece extending parallel to the longitudinal axis X-X of the camshaft adjuster 13 . The connecting piece 24 is supported in its end regions and outside of the intermediate gears 20 , 21 in circular ring-shaped support elements 25 , 26 . The double-eccentric shaft 15 passes with play through the inner bore of the support element 25 . The support element 26 is locked in rotation with the camshaft 12 on the inside in the radial direction. For this purpose, the support element 26 is connected with the camshaft 12 via a tensioning screw 27 , which is screwed into one end of the camshaft 12 .
[0023] A housing 28 of the camshaft adjuster 13 has a hollow cylindrical wall 29 , which carries on the outside in the radial direction the drive element 11 , in particular a belt pulley, and which forms on the inside in the radial direction a ring gear 30 . In the region of the extremities of the double-eccentric shaft 15 , that is, on opposite peripheral regions, the intermediate gears 20 , 21 each mesh with the ring gear 30 . In the embodiment shown in FIG. 1 , for the intermediate gear 20 , the extremity of the peripheral surface 16 is shown, so that the intermediate gear here engages with the ring gear 30 . The extremity for the peripheral surface 17 lies in the half-plane not shown in FIG. 1 , so that the gearing of the intermediate gear 21 in the shown region does not engage with the internal gearing of the ring gear 30 . The bores 22 , 23 have an over-dimension relative to the diameters of the connecting pieces, such that relative movements caused by the extremity are possible between the intermediate gears 20 , 21 and the connecting piece 24 .
[0024] Another anti-friction bearing, here a needle bearing 31 , is connected between the head of the tensioning screw 27 and the double-eccentric shaft 15 . The camshaft 12 emerges from a cylinder head 33 under a seal through a sealing element 32 .
[0025] The support elements 25 , 26 are guided via suitable sliding bearings relative to the housing 28 and are supported on the step for the ring gear 30 on the inside and also in the direction of the X-X axis on the outside by means of suitable securing elements 34 .
[0026] If the adjustment shaft 14 is driven by the control drive at an angular velocity that deviates from the angular velocity of the camshaft 12 , then the extremity and thus the contact point between the intermediate gears 20 , 21 travels in the peripheral direction relative to the ring gear 30 . In this way, the angle between the drive element 11 and the camshaft 12 is changed.
[0027] In terms of additional principle details of the construction of the camshaft adjuster with double-eccentric gear mechanisms, refer to the publication DE 102 48 355 A1 by the applicant.
[0028] The contact surfaces moving relative to each other and rolling in opposite directions and also the anti-friction bearings 18 , 19 , 31 are provided with lifetime lubrication. Leakage of such lifetime lubrication from the housing 28 is prevented by the use of sealing covers 36 , 37 , which close both openings of the wall 29 .
[0029] For the embodiment shown in FIG. 1 , the sealing covers 36 , 37 rotate with the housing 28 . The sealing cover 36 is snapped into a suitable groove of the housing 28 . On the inside in the radial direction, a sealing element 38 is connected between the sealing cover 36 and the adjustment shaft 14 .
[0030] A sealing element 39 is connected between the sealing cover 37 and the housing 28 . On the inside in the radial direction, the sealing cover 37 has a collar, on which on the inside in the radial direction a sealing element 40 is supported, which is actively connected with the cylinder head 33 on the outside in the radial direction.
[0031] For the contact regions of the sealing covers 36 , 37 with the adjacent components both on the inside and also on the outside in the radial direction, for example, the following solutions are conceivable alternatively or cumulatively:
The sealing covers 36 , 37 can be inserted or snapped into the adjacent components with a non-positive connection. Here, the sealing covers 36 , 37 are pressed against the adjacent components through the elasticity of the sealing covers 36 , 37 themselves or additional elastic elements, whereby a sealing effect is produced. Furthermore, the sealing covers can be held by the adjacent components with a positive connection, for example, in a groove. A sealing element, such as, for example, a sealing ring or a radial shaft sealing ring can be connected between sealing covers 36 , 37 and adjacent components. Furthermore, a diaphragm seal or labyrinth seal can be used, which is adapted to the special operating requirements, such as, rotational speeds, centrifugal forces, and a viscosity of the lifetime lubrication, as well as the occurring temperatures.
[0036] The sealing cover 36 is preferably supported in the end region on the outside in the radial direction against the wall 29 . Alternatively, a support relative to the support element 25 is possible, wherein in this case an additional seal must be provided between the support element 25 and the wall 29 .
[0037] On the inside in the radial direction, the sealing cover 36 is supported against the adjustment shaft 14 . Alternatively, it is also possible that the sealing cover 36 is supported against the double-eccentric shaft 15 . In this case, it is to be guaranteed that the connection between the adjustment shaft 14 and the double-eccentric shaft 15 has a tight construction.
[0038] The sealing cover 37 is supported on the outside in the axial direction against the wall 29 . Alternatively, it is possible that the sealing cover 37 is supported against the support element 26 , wherein in this case, a seal between the support element 26 and wall 29 is to be provided. On the inside in the radial direction, the sealing cover 37 is supported against the cylinder head 33 or the camshaft 12 .
[0039] For the case that the camshaft 12 and/or the adjustment shaft 14 does not project into the camshaft adjuster 13 , but instead is coupled outside of this adjuster to a shaft projecting out of the camshaft adjuster, a seal from this projecting shaft can be realized.
[0040] The sealing covers 36 , 37 preferably have an inherently stiff construction, for example, as a sheet-metal part. Alternatively, the sealing covers can have a construction that is at least partially not resistant to bending, especially as a sealing bellows, or the like. The sealing covers 36 , 37 can be completely left out for a different embodiment of the invention, as long as there is a seal between the housing 28 , support element 25 , connecting piece 24 , double-eccentric shaft 15 , and adjustment shaft 14 or housing 28 , support element 26 , connecting piece 24 , and camshaft 12 .
[0041] According to another construction according to the invention, a rubber-elastic form element 41 is connected between the adjustment shaft 14 and double-eccentric shaft 15 . In this case, a seal of a sealing cover 36 from the rubber-elastic form element 41 or from the adjustment shaft can be realized. In some circumstances, it is sufficient in this case to provide a diaphragm seal here, because the lifetime lubrication is accelerated outwards in the radial direction due to centrifugal force.
[0042] The camshaft adjuster used according to the invention can involve a camshaft adjuster of any type. For example, as a control unit, a construction with a BLDC motor with rare-earth magnet and fixed stator, preferably with bipolar triggering, can be used. Any other motor, for example, a brush-type direct-current motor, is also conceivable.
[0043] Furthermore, camshaft adjuster units, for which the motor rotates with the gear mechanism, can also be used.
[0044] A rubber-elastic form element 41 can be integrated into the adjustment shaft 14 as a coupling element between the adjustment shaft 14 and the electric motor, wherein, however, other possibilities, for example, a feather key or a splined shaft profile, can be used. In addition to the described double internal eccentric gear mechanism, other gear mechanisms, for example, single internal eccentric gear mechanisms, swash-plate gear mechanisms, shaft gear mechanisms, planetary gear mechanisms, and other high transmission ratio gear mechanisms can be used in a known way for belt-driven internal combustion engines.
[0045] The lifetime lubrication is preferably embodied as a lifetime grease filling. Other lifetime lubrications, such as motor oil (such as the type for gear mechanisms with chain-driven motors) are also conceivable, wherein in this case, increased sealing requirements are to be set.
LIST OF REFERENCE SYMBOLS
[0000]
10 Camshaft drive
11 Drive element
12 Camshaft
13 Camshaft adjuster
14 Adjustment shaft
15 Double-eccentric shaft
16 Peripheral surface
17 Peripheral surface
18 Anti-friction bearing
19 Anti-friction bearing
20 Intermediate gear
21 Intermediate gear
22 Bore
23 Bore
24 Connecting piece
25 Support element
26 Support element
27 Tensioning screw
28 Housing
29 Wall
30 Ring gear
31 Needle bearing
32 Sealing element
33 Cylinder head
34 Securing element
36 Sealing cover
37 Sealing cover
38 Sealing element
39 Sealing element
40 Sealing element
41 Elastic coupling element
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A camshaft adjusting device for an internal combustion engine is provided. A functionally reliable camshaft adjusting device designed for a long-lasting operation is obtained when the camshaft adjuster ( 13 ) has a lifelong lubrication located in the housing ( 28, 36, 37 ) sealed from the surrounding area be sealing covers ( 36, 37 ). The camshaft adjuster is not required to be mounted inside the cylinder head ( 33 ), but can be mounted as a separate unit on the cylinder head ( 33 ) of the internal combustion engine independent of the lubricating oil circuit. This expands, in particular, the range of possibilities for use of the camshaft adjuster ( 13 ) with a belt drive.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a 35 U.S.C. 371 US national phase application of PCT international application s/n PCT/US2012/033583, filed on Apr. 13, 2012, and is herein incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention is related generally to the method steps of three dimensional molding, and in particular to a process of molding simple or complex micro and/or nanopatterned features on a wide array of molded objects and both planar and non-planar surfaces. It also relates to the molded objects and surfaces resulting from these method steps as well as the molded objects produced with micro and/or nanopatterned features.
BACKGROUND OF THE INVENTION
[0003] There is a need in the current technology to incorporate simple or complex micro and/or nanoscale structures on surfaces of many different mass-produced molded parts. One example application of this invention is in the area of mass-production of solar panel clamping brackets with biologically-inspired adhesive microfibers on the glass-contacting surface to simplify the assembly of solar panel racking systems and improve their clamping ability with respect to non micropatterned alternative products. Incorporating biologically-inspired adhesive surfaces on molded parts may have a broader range of applications in the healthcare, defense, apparel, sporting good, and household good industries. For example, highly adhesive surfaces can be incorporated into the skin-contacting interfaces of sleep apnea masks or personal safety masks to improve the seal of the mask to the face and improve customer satisfaction or safety when using the products. Beyond the range of geometries of biologically-inspired fibrillar adhesives, this invention may be used to apply different micro and/or nanoscale structures to products which have applications in optics, fog resistance, pressure sensing, tissue engineering, microfluidics, and other applications known to those familiar in this field which could benefit from micro and/or nanoscale patterning.
SUMMARY OF THE INVENTION
[0004] There are two primary advantages of the present invention when compared with present technology of molding simple or complex micro and/or nanopatterned features on both planar or non-planar molded objects and surfaces. The first is that it allows for creating micro and/or nanostructures on either planar or non-planar three-dimensional surfaces in a single molding step, eliminating the need for secondary manufacturing processes after the part is removed from the mold. The second advantage is that it allows for the molded production of complex high-aspect ratio micro and/or nanostructures, not merely cylinders, conical structures, low aspect-ratio channels, bumps, or posts. An example of such a complex structure are high aspect ratio pillars with enlarged “mushroom-shaped” tips which demonstrate enhanced, repeatable adhesion and shear strength on a variety of substrates when compared with other micro and/or nanostructures and unstructured materials. The mold of such a material requires an “undercut” feature that cannot be produced using existing mass production micro/nano-molding techniques.
[0005] The present invention can be applied to fabricating micro and/or nanopatterned surfaces to enhance adhesion and friction for a variety of three dimensional injection molded products, including industrial clamps, skin contacting surfaces in the healthcare, personal safety, defense, and cosmetics industries, tissue contacting surfaces for medical device applications, materials to replace traditional “hook and loop” closures for clothing and sports apparel, athletic gloves for enhanced grip for activities like football, soccer, rock climbing, golf, and baseball. Future applications may extend beyond adhesive applications to the fabrication of micro- or nano-electronic devices, micro/nano sensors, tissue engineering scaffolds, etc.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] For the present invention to be easily understood and readily practiced, the invention will now be described, for the purposes of illustration and not limitation, in conjunction with the following figures, wherein:
[0007] FIG. 1 are illustrations of the mold fabrication process of the present invention; and
[0008] FIGS. 2A-G are pictorial representations of embodiments of the present invention to fabricate a product with micro and/or nanopatterned features.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The present invention describes a process to incorporate simple or complex, three-dimensional, high aspect ratio micro and/or nanopatterned features onto surfaces of small batch or mass-produced molded parts, which includes: (1) a method for replicating micro and/or nanostructures fabricated through well-established micro/nanofabrication techniques onto thin, flexible, compliant backings; (2) a method to incorporate the patterned micro and/or nanostructures onto planar or non-planar surfaces of a molding tool with an additional surface modification molding step performed on the tool; (3) A molded part which incorporates micro and/or nanopatterned features produced using a tool modified through step (2) above. With the present invention, mass-production of injection molded parts with planar or non-planar surfaces patterned with either simple or complex, high-aspect ratio micro and/or nanostructures in a single step at extremely low cost becomes possible. Micro and/or Nanopatterned features means a cluster or grouping of multiple micro and/or nanoscale elements in a predetermined arrangement. Various patterned embodiments can be configured where adjacent sections of clustered groups can have different patterns of varying element characteristic lengths, element characteristic outer diameters, and characteristic recess or void depths and widths. The term “characteristic” refers to a representative length, diameter, depth or width where the feature may not have uniform dimensions. For example, an elliptical cross-section is non-circular but it can have a characteristic diameter determined by well known mathematical expressions.
[0010] The application refers to the following terms, words, and phrases that have particular meaning with regards to the present invention. A geometric feature being micro or microscale means that at least one of the characteristic lengths of the feature in any 3D direction should be between 0.5-500 micrometers in length. Micropatterned surfaces are surfaces which have at least one microscale feature on them. A geometric feature being nano or nanoscale means that at least one of the characteristic lengths of the feature in any 3D direction should be between 0.2-500 nanometers in length. Nanopatterned surfaces are surfaces which have at least one nanoscale feature on them. Micro and nanopatterned surfaces refer to surfaces with any combination and quantity of microscale (0.5-500 micrometers in length) and nanoscale (0.2-500 nanometers in length) features on them. The characteristic diameters of the micro and nanopatterned features can range from 0.2-500 micrometers and 0.2-500 nanometers for microscale and nanoscale features, respectively. Therefore, surfaces of the present invention can contain only microscale features, only nanoscale features, or both microscale and nanoscale features.
[0011] Though injection molding is described herein as one possible approach to manufacturing the molded part, other molding approaches include, but are not limited to, compression molding, blow molding, vacuum molding, extrusion molding, injection compression molding, extrusion compression molding, rotational molding, thermoforming, casting, pultruding, stamping, forging, or any combination thereof.
[0012] FIG. 1 shows the steps to replicate micro and/or nanostructures onto a rigid 12 A or compliant 12 B backing material. The first step in the process is to start with the base material 10 with actual micro and/or nanoscale features that are to be produced on molded parts 14 A (on a planar molded surface), 14 B (on a non-planar molded surface) using one of the molding processes described below, but not limited to:
[0013] A. Injection molding: Injection over molding, Co-injection molding, Gas assist injection molding, Tandem injection molding, Ram injection molding, Micro-injection molding, Vibration assisted molding, Multiline molding, Counter flow molding, Gas counter flow molding, Melt counter flow molding, Structural foam molding, Injection-compression molding, Oscillatory molding of optical compact disks, Continuous injection molding, Reaction injection molding (Liquid injection molding, Soluble core molding, Insert molding), and Vacuum Molding;
[0014] B. Compression molding: Transfer molding, and Insert molding;
[0015] C. Thermoforming: Pressure forming, Laminated sheet forming, Twin sheet thermoforming, and Interdigitation;
[0016] D. Casting: Encapsulation, Potting, and impregnation;
[0017] E. Coating Processes: Spray coating, Powder coatings, Vacuum coatings, Microencapsulation coatings, Electrode position coatings, Floc coatings, and Dip coating;
[0018] F. Blow molding: Injection blow molding, Stretch blow molding, and Extrusion blow molding;
[0019] F. Vinyl Dispersions: Dip molding, Dip coatings, Slush molding, Spray coatings, Screened inks, and Hot melts; and
[0020] G. Composite manufacturing techniques involving molds: Autoclave processing, Bag molding, Hand lay up, and Matched metal compression.
[0021] The second step is to attach bottom surface 11 of starting material 10 described in step 1 onto a rigid planar backing 12 A or flexible backing 12 B to form product 18 A, 18 B, such that the actual micro and/or nanoscale features 10 A are facing outward opposing the backing 12 A, 12 B.
[0022] The third step is to prepare planar 16 A or non-planar 16 B tool surface of tooling 17 A, 17 B using one of the methods described below, but not limited to:
[0023] A. Plasma treatment;
[0024] B. Silane adhesion promoters and coupling agents;
[0025] C. Acid etching;
[0026] D. Mechanical abrasion;
[0027] E. Chlorinated polypropylene treatment, and
[0028] F. No treatment necessary
[0029] Another embodiment of the present invention includes a tool surface that is partially planar and partially non-planar (not shown).
[0030] If initial material described in step 1 is rigid and patterning is being performed on a non-planar surface, it will be necessary to first replicate it using one or more molding steps to reproduce the material with micro and/or nanoscale features from a compliant material listed below; as well as binding materials from Step 2 will also need to be compliant:
A. Thermosets:
[0031] i. Formaldehyde Resins (PF, RF, CF, XF, FF, MF, UF, MUF);
[0032] ii. Polyurethanes (PU);
[0033] iii. Unsaturated Polyester Resins (UP);
[0034] iv. Vinylester Resins (VE), Phenacrylate Resins, Vinylester Urethanes (VU);
[0035] v. Epoxy Resins (EP);
[0036] vi. Diallyl Phthalate Resins, Allyl Esters (PDAP);
[0037] vii. Silicone Resins (Si); and
[0038] viii. Rubbers: R-Rubbers (NR, IR, BR, CR, SBR, NBR, NCR, IIR, PNR, SIR, TOR, HNBR), M-Rubbers (EPM, EPDM, AECM, EAM, CSM, CM, ACM, ABM, ANM, FKM, FPM, FFKM), O-Rubbers (CO, ECO, ETER, PO), Q-(Silicone) Rubber (MQ, MPQ, MVQ, PVMQ, MFQ, MVFQ), T-Rubber (TM, ET, TCF), U-Rubbers (AFMU, EU, AU) Text, and Polyphosphazenes (PNF, FZ, PZ)
B. Thermoplastics
[0039] i. Polyolefins (PO), Polyolefin Derivates, and Copoplymers: Standard Polyethylene Homo- and Copolymers (PE-LD, PE-HD, PE-HD-HMW, PE-HD-UHMW, PE-LLD); Polyethylene Derivates (PE-X, PE+PSAC); Chlorinated and Chloro-Sulfonated PE (PE-C, CSM); Ethylene Copolymers (ULDPE, EVAC, EVAL, EEAK, EB, EBA, EMA, EAA, E/P, EIM, COC, ECB, ETFE; Polypropylene Homopolymers (PP, H-PP)
[0040] ii. Polypropylene Copoplymers and -Derivates, Blends (PP-C, PP-B, EPDM, PP+EPDM)
[0041] iii. Polybutene (PB, PIB)
[0042] iv. Higher Poly-α-Olefins (PMP, PDCPD)
[0043] v. Styrene Polymers: Polystyrene, Homopolymers (PS, PMS); Polystyrene, Copoplymers, Blends; Polystyrene Foams (PS-E, XPS)
[0044] vi. Vinyl Polymers: Rigid Polyvinylchloride Homopolymers (PVC-U); Plasticized (Soft) Polyvinylchloride (PVC-P); Polyvinylchloride: Copolymers and Blends; Polyvinylchloride: Pastes, Plastisols, Organosols; Vinyl Polymers, other Homo- and Copolymers (PVDC, PVAC, PVAL, PVME, PVB, PVK, PVP)
[0045] vii. Fluoropolymers: FluoroHomopolymers (PTFE, PVDF, PVF, PCTFE); Fluoro Copolymers and Elastomers (ECTFE, ETFE, FEP, TFEP, PFA, PTFEAF, TFEHFPVDF (THV), [FKM, FPM, FFKM])
[0046] viii. Polyacryl- and Methacryl Copolymers
[0047] ix. Polyacrylate, Homo- and Copolymers (PAA, PAN, PMA, ANBA, ANMA)
[0048] x. Polymethacrylates, Homo- and Copolymers (PMMA, AMMA, MABS, MBS)
[0049] xi. Polymethacrylate, Modifications and Blends (PMMI, PMMA-HI, MMA-EML Copolymers, PMMA+ABS Blends
[0050] xii. Polyoxymethylene, Polyacetal Resins, Polyformaldehyde (POM): Polyoxymethylene Homo- and Copolymers (POM-H, POM-Cop.); Polyoxymethylene, Modifications and Blends (POM+PUR)
[0051] xiii. Polyamides (PA): Polyamide Homopolymers (AB and AA/BB Polymers) (PA6, 11, 12, 46, 66, 69, 610, 612, PA 7, 8, 9, 1313, 613); Polyamide Copolymers, PA 66/6, PA 6/12, PA 66/6/610 Blends (PA+: ABS, EPDM, EVA, PPS, PPE, Rubber); Polyamides, Special Polymers (PA NDT/INDT [PA 6-3-t], PAPACM 12, PA 6-I, PA MXD6 [PARA], PA 6-T, PA PDA-T, PA 6-6-T, PA 6-G, PA 12-G, TPA-EE); Cast Polyamides (PA 6-C, PA 12-C); Polyamide for Reaction Injection Molding (PA-RIM); Aromatic Polyamides, Aramides (PMPI, PPTA)
[0052] xiv. Aromatic (Saturated) Polyesters: Polycarbonate (PC); Polyesters of Therephthalic Acids, Blends, Block Copolymers; Polyesters of Aromatic Diols and Carboxylic Acids (PAR, PBN, PEN)
[0053] xv. Aromatic Polysulfides and Polysulfones (PPS, PSU, PES, PPSU, PSU+ABS): Polyphenylene Sulfide (PPS); Polyarylsulfone (PSU, PSU+ABS, PES, PPSU)
[0054] xvi. Aromatic Polyether, Polyphenylene Ether, and Blends (PPE): Polyphenylene Ether (PPE); Polyphenylene Ether Blends
[0055] xvii. Aliphatic Polyester (Polyglycols) (PEOX, PPDX, PTHF)
[0056] xviii. Aromatic Polyimide (PI): Thermosetting Polyimide (PI, PBMI, PBI, PBO, and others); Thermoplastic Polyimides (PAI, PEI, PISO, PMI, PMMI, PESI, PARI);
[0057] xix. Liquid Crystalline Polymers (LCP)
[0058] xx. Ladder Polymers: Two-Dimensional Polyaromates and—Heterocyclenes: Linear Polyarylenes; Poly-p-Xylylenes (Parylenes); Poly-p-Hydroxybenzoate (Ekonol); Polyimidazopyrrolone, Pyrone; Polycyclone
[0059] xxi. Biopolymers, Naturally Occurring Polymers and Derivates: Cellulose- and Starch Derivates (CA, CTA, CAP, CAB, CN, EC, MC, CMC, CH, VF, PSAC); 2 Casein Polymers, Casein Formaldehyde, Artificial Horn (CS, CSF);
[0060] Polylactide, Polylactic Acid (PLA); Polytriglyceride Resins (PTP®); xix. Photodegradable, Biodegradable, and Water Soluble Polymers;
[0061] xxii. Conductive/Luminescent Polymers;
[0062] xxiii. Aliphatic Polyketones (PK);
[0063] xxiv. Polymer Ceramics, Polysilicooxoaluminate (PSIOA);
[0064] xxv. Thermoplastic Elastomers (TPE): Copolyamides (TPA), Copolyester (TPC), Polyolefin Elastomers (TPO), Polystyrene Thermoplastic Elastomers (TPS), Polyurethane Elastomers (TPU), Polyolefin Blends with Crosslinked Rubber (TPV), and Other TPE, TPZ; and
[0065] xxvi. Other materials known to those familiar with the art
[0066] The fourth step is to add liquid tool insert material 20 A, 20 B (see possible materials in listed above for step 3 to planar 16 A or non-planar 16 B tool surface.
[0067] The fifth step is to press the product 18 A, 18 B of Step 2 into tool insert material 20 A, 20 B of Step 4 and allow to cure.
[0068] The sixth step is to remove product 18 A, 18 B of Step 2 from tool insert material 20 A, 20 B for final tooling 17 A, 17 B which now has a mold surface 22 A, 22 B with the negative micro and/or nanoscale features 19 A, 19 B of the micro/nanoscale features 10 A. Herein, a negative feature is a defined as an opposite of an actual feature, such as a recess, cavity or void in a negative mold is a negative feature of a structure that projects from a surface of an actual part or product. Whereas, a structure that projects from a surface of a negative mold is a negative feature of a recess, cavity or void in an actual part or product.
[0069] The seventh step is to mold tool 17 A, 17 B produced by step 6 with a moldable part material (see above materials list for step 3). The product 14 A, 14 B of this step is a molded part with micro and/or nanoscale features 24 on one or more planar surfaces or non-planar surfaces.
[0070] Another embodiment of the present invention includes a tool surface of the molding tool having a plurality of sections (not shown). Each section of the plurality of sections includes negative micro and/or nanopatterned features having different characteristics than an adjacent section of the plurality of sections. The different characteristics include but are not limited to a recess depth, a recess inner diameter, a projection length, and a projection outer diameter.
[0071] Another embodiment of the present invention includes a removable tool insert of the molding tool having one or more planar or non-planar surfaces where at least one of these planar or non-planar surfaces includes negative micro and/or nanopatterned features produced using steps 1-6 above. This removable tool insert can be interchanged with different tool inserts with different negative micro and/or nanopatterned features should a production run require quantities of parts with various micro and/or nanopatterned features. Alternatively, these inserts may be transferred to different production sites, or to different partners or customers without transferring or being responsible for the entire molding tool.
[0072] Now turning to FIGS. 2A-C illustrating the incorporation of the micro and/or nanopatterned negative mold surface 114 into an injection molding tool. An injection molding tool with the desired part geometry, such as mold part 120 , can be fabricated from any existing tool manufacturing process such as but not limited to machining, rapid prototyping, or clamshell molding. FIG. 2A illustrates an injection molding tool using clamshell molding halves 116 , 118 to produce molded part 120 . Next, the micro and/or nanopatterned geometry 108 of master template 110 are incorporated into the micro and/or nanopatterned negative mold surface 114 using the process illustrated in FIG. 2B . The micro and/or nanopatterned negative mold surface 114 starts as a curable molding liquid such as (but not limited to) a silicone rubber or epoxy used to coat the bottom surface 124 of the bottom half of the injection molding tool 116 . Additives such as (but not limited to) primers, silanes, etc., may be used to treat the coated surface 124 to improve the binding of the curable molding liquid to the bottom half of the injection molding tool 116 . Next, the bottom surface 122 of master template 110 containing micro and/or nanopatterned geometry 108 is pressed into the curable molding liquid and a rigid backing holds the entire system in place as it cures. After curing, the rigid backing and bottom surface 122 are peeled from the bottom half injection molding 116 resulting in the final mold illustrated in FIG. 2C . Here, the molded surface of flexible negative mold 114 is patterned with the negative (female) micro and/or nanopatterned geometry. During molding with top half mold 118 in place, a molding liquid (not shown) is injected into cavity 115 to flow over and into flexible negative mold 114 to produce molded part 120 (see FIG. 2D ). This injection molding process is able to be incorporated into large scale geometry of the tool to mass produce molded part 120 with micro and/or nanopatterned geometry 126 .
[0073] Now turning to FIGS. 2E-G that illustrate uniform and non-uniform cross-sectional areas over predetermined lengths of a replicated micro and/or nanopatterned feature 128 of replicated micro and/or nanopatterned geometry 126 . Each replicated micro and/or nanoscale feature of the plurality of replicated micro and/or nanoscale features 126 comprise a predetermined length L having (i) a replicated tip 130 at a distal end 136 of the replicated feature 128 , (ii) a replicated base 132 at a proximal end 138 of the replicated feature 128 , and (iii) a plurality of replicated cross-sectional areas (see below) along the replicated feature predetermined length L. FIG. 2E illustrates one embodiment of the replicated feature 128 of replicated micro and/or nanopatterned geometry 126 having a uniform (only one) cross-sectional area A along the entire length L having a replicated flat tip 130 and a replicated base 132 , wherein replicated base 132 is attached to backing layer 134 . FIG. 2F illustrates another replicated feature stem 128 of replicated micro and/or nanopatterned geometry 126 has a substantially uniform (only one) cross-sectional area A 1 over replicated feature mid-section length L 1 , and substantially non-uniform cross-sectional Areas A 2 and A 3 over replicated fiber end lengths L 2 (tip transition) and L 3 (base transition), respectively. The present invention is not to be limited to three distinction sections (tip transition, mid-section, and base transition), but as illustrations of one possible embodiment. FIG. 2G illustrates another embodiment of the present invention can include varying cross-sectional areas (A 4 , A 5 , A 6 , A 7 ) within length L 1 (corresponding to segment lengths L 4 , L 5 , L 6 , L 7 , L 8 ). The number of segments, segment lengths, and varying cross-sectional areas can be any dimension desired by the user whether the dimensions are structured based on mathematical formulas (e.g., aspect ratios) or arbitrary selections. The present invention is not to be limited to any particular numbers of sections (e.g., tip transition, mid-section, and base transition) or any particular number of varying cross-sectional areas (e.g., A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 ), but as illustrations of possible embodiments. It should be noted that the varying cross-sectional areas can alternate between increasing and decreasing (reducing) and increasing again along length L, as shown in FIG. 2G . Another embodiment can be conically-shaped fiber with decreasing diameters from the fiber base 132 to tip 130 (not shown) or with increasing diameters from the fiber base 132 to tip 130 (not shown). Also, while the illustrations of FIGS. 2E-G illustrate replicated projecting micro and/or nanopatterned features 128 , one skilled in the art will appreciate that the replicated micro and/or nanopatterned features 128 can be represented as substantially equivalent replicated recesses micro and/or nanopatterned features of negative mold 114 . For example, a projected micro and/or nanopatterned feature characteristic that represents a fiber length is substantially equivalent to a recess depth for a recessed micro and/or nanopatterned feature characteristic. Another example is an outer diameter of the fiber is a replicated projected micro and/or nanopatterned feature characteristic that is substantially equivalent to an inner diameter of a replicated recess micro and/or nanopatterned feature characteristic.
[0074] The relationships between backing layer 134 , replicated feature 128 , and replicated tip 130 that can vary in different embodiments of the present invention. In the illustrated embodiment, replicated feature 128 can form angles 1 and 2 relative to a plane P parallel to backing layer 134 . Similarly, replicated flat surface 136 of replicated tip 130 can form angle β 1 or β 2 relative to a plane P parallel to backing layer 134 . Angles and β singularly or in combination can be defined during the fabrication process. Typically, angles and β can range between 0 and 180.
[0075] One skilled in the art understand that the description of the replicated micro and/or nanopatterned geometry 126 of the mass produce molded part 120 in FIGS. 2E-F are the same for the description of the actual micro and/or nanopatterned geometry 108 of the master template 110 illustrated in FIG. 2B , and actual micro and/or nanoscale features 10 A of material 10 and actual micro and/or nanoscale features 24 of molded parts 14 A, 14 B illustrated in FIG. 1 . Therefore, disclosures pertaining to micro and/or nanopatterned features or geometries apply to both actual and replicated micro and/or nanopatterned features or geometries, such that the actual micro and/or nanopatterned features of the material and the replicated micro and/or nanopatterned features of the product are substantially equivalent.
[0076] The present invention is capable of replicating the following microscale and/or nanoscale feature geometries:
[0000] A. Features which Protrude from the Part Surface:
[0077] i. Low aspect ratio protrusions (Feature height is approximately the same or less than the feature characteristic diameter): Bumps; Pyramids; Treads (Straight treads, Curved treads, Parallel treads, Intersecting treads, Random treads); Treads with non-uniform width (Straight, curved, parallel, intersecting or random treads with one or more enlarged areas with respect to the average tread width; Straight, curved, parallel, intersecting or random treads with one or more narrowed areas with respect to the average tread width); Solid prismatic shapes with uniform cross section (Cylindrical prisms, Elliptical prisms, Rectangular prisms, Hexagonal prisms, Pentagonal prisms, Etc. (any-sided prism shape)); Solid prismatic shapes with hollow cross section; Prismatic shapes with non-uniform cross section (Enlarged prism tip shape (Spherical tip shape, Pyramidal tip shape, Spatula tip shape, Mushroom tip shape, Conical tip shape, Convex tip shape, Concave tip shape); Modified prism base shape (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter); Prismatic shapes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0078] ii. High aspect ratio protrusions (Feature height is greater than the feature characteristic diameter): Treads (Straight treads, Curved treads, Parallel treads, Intersecting treads, Random treads), Treads with non-uniform width (Straight, curved, parallel, intersecting or random treads with one or more enlarged areas with respect to the average tread width; Straight, curved, parallel, intersecting or random treads with one or more narrowed areas with respect to the average tread width); Solid prismatic shapes with uniform cross section (Cylindrical prisms, Elliptical prisms, Rectangular prisms, Hexagonal prisms, Pentagonal prisms, Etc. (any-sided prism shape)); Solid prismatic shapes with hollow cross section; Prismatic shapes with non-uniform cross section (Enlarged prism tip shape (Spherical tip shape, Pyramidal tip shape, Spatula tip shape, Mushroom tip shape, Conical tip shape, Convex tip shape, Concave tip shape, Modified prism base shape (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Prismatic shapes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0079] iii. Parts with randomly formed protrusions;
[0080] iv. Parts with other geometrical protrusions produced using micro/nanofabrication processes;
[0081] v. Parts with geometries produced using mechanical or chemical etching or abrasion processes;
[0082] vi. Parts with more than one type of micro and/or nanofeature that protrudes from the part surface: Multiple micro and/or nanofeatures at the same length scale; Multiple micro and/or nanofeatures at different length scales.
[0000] B. Features which Recess into the Part Surface:
[0083] i. Low aspect ratio recessions (Pores, Pyramidal projections, Grooves or channels with uniform width (Straight grooves or channels, Curved grooves or channels, Parallel grooves or channels, Intersecting grooves or channels, Random grooves or channels), Grooves or channels with non-uniform width (Straight, curved, parallel, intersecting or random grooves or channels with one or more enlarged areas with respect to the average groove or channel width; Straight, curved, parallel, intersecting or random grooves or channels with one or more narrowed areas with respect to the average groove or channel width), Prismatic holes with uniform cross section (Cylindrical holes, Elliptical holes, Rectangular holes, Hexagonal holes, Pentagonal holes, Etc. (any-sided holes shape)), Hole shapes with non-uniform cross section (Enlarged hole base shape (Spherical base shape, Pyramidal base shape, Spatula base shape, Mushroom base shape, Conical base shape, Convex base shape, Concave base shape), Modified hole intersection with part surface (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Holes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0084] ii. High aspect ratio recessions: Grooves or channels with uniform width (Straight grooves, Curved grooves, Parallel grooves, Intersecting grooves, Random grooves); Grooves or channels with non-uniform width (Straight, curved, parallel, intersecting or random grooves with one or more enlarged areas with respect to the average groove or channel width; Straight, curved, parallel, intersecting or random grooves with one or more narrowed areas with respect to the average groove or channel width); Prismatic holes with uniform cross section (Cylindrical holes, Elliptical holes, Rectangular holes, Hexagonal holes, Pentagonal holes, Etc. (any-sided holes shape)); Hole shapes with non-uniform cross section (Enlarged hole base shape (Spherical base shape, Pyramidal base shape, Spatula base shape, Mushroom base shape, Conical base shape, Convex base shape, Concave base shape); Modified hole intersection with part surface (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter); Holes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0085] iii. Parts with randomly formed projections;
[0086] iv. Parts with other geometrical projections using micro and/or nanofabrication processes;
[0087] v. Parts with geometries produced using mechanical or chemical etching or abrasion processes;
[0088] vi. Parts with more than one type of micro and/or nanofeature that projects into the part surface (Multiple micro and/or nanofeatures at the same length scale, Multiple micro and/or nanofeatures at different length scales).
[0000] C. Parts with a Combination of Features that Recess into the Part Surface and Protrude from the Part Surface:
[0089] i. Multiple micro and/or nanofeatures at the same length scale;
[0090] ii. Multiple micro and/or nanofeatures at different length scales.
[0091] The present invention is capable of replicating the following undercut microscale and/or nanoscale feature geometries;
[0000] A. Features which Protrude from the Part Surface:
[0092] i. Low aspect ratio protrusions (Feature height is approximately the same or less than the feature characteristic diameter): Treads with non-uniform width (Straight, curved, parallel, intersecting or random treads with one or more enlarged areas with respect to the average tread width; Straight, curved, parallel, intersecting or random treads with one or more narrowed areas with respect to the average tread width), Prismatic shapes with non-uniform cross section (Enlarged prism tip shape (Spherical tip shape, Pyramidal tip shape, Spatula tip shape, Mushroom tip shape (see tip 130 in FIG. 2F for illustration of a mushroom tip), Conical tip shape, Convex tip shape, Concave tip shape), Modified prism base shape (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Prismatic shapes that are either enlarged or narrowed at areas that are neither the tip nor the base;
[0093] ii. High aspect ratio protrusions (Feature height is greater than the feature characteristic diameter): Treads with non-uniform width (Straight, curved, parallel, intersecting or random treads with one or more enlarged areas with respect to the average tread width; Straight, curved, parallel, intersecting or random treads with one or more narrowed areas with respect to the average tread width), Prismatic shapes with non-uniform cross section (Enlarged prism tip shape (Spherical tip shape, Pyramidal tip shape, Spatula tip shape, Mushroom tip shape, Conical tip shape, Convex tip shape, Concave tip shape), Modified prism base shape (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Prismatic shapes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0094] iii. Parts with randomly formed protrusions containing undercut features;
[0095] iv. Parts with other geometrical protrusions containing undercut features produced using micro/nanofabrication processes;
[0096] v. Parts with geometries containing undercut features produced using mechanical or chemical etching or abrasion processes;
[0097] vi. Parts with more than one type of micro and/or nanofeature that protrudes from the part surface (at least one containing an undercut feature (Multiple micro and nanofeatures at the same length scale, Multiple micro and nanofeatures at different length scales).
[0098] See tip 130 in FIG. 2F for illustration of an undercut tip, where radius 138 illustrates an undercut of the tip cross-sectional area A 2 to stem cross-sectional area A 1 . Cross-sectional area can also be represented by a characteristic diameter. In other words, one embodiment of the present invention includes the step of fabricating a radius 138 between the actual feature tip characteristic diameter D 2 and the at least one actual stem characteristic diameter D 1 of the plurality of actual stem characteristic diameters associated with cross-sectional areas A 4 , A 5 , A 6 , A 7 of FIG. 2G to form an undercut feature.
[0000] B. Features which Recess into the Part Surface:
[0099] i. Low aspect ratio projections: Grooves or channels with non-uniform width (Straight, curved, parallel, intersecting or random grooves or channels with one or more enlarged areas with respect to the average groove or channel width; Straight, curved, parallel, intersecting or random grooves or channels with one or more narrowed areas with respect to the average groove or channel width), Hole shapes with non-uniform cross section (Enlarged hole base shape (Spherical base shape, Pyramidal base shape, Spatula base shape, Mushroom base shape, Conical base shape, Convex base shape, Concave base shape), Modified hole intersection with part surface (Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Holes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0100] ii. High aspect ratio projections: Grooves or channels with non-uniform width (Straight, curved, parallel, intersecting or random grooves with one or more enlarged areas with respect to the average groove or channel width; Straight, curved, parallel, intersecting or random grooves with one or more narrowed areas with respect to the average groove or channel width), Hole shapes with non-uniform cross section (Enlarged hole base shape (Spherical base shape, Pyramidal base shape, Spatula base shape, Mushroom base shape, Conical base shape, Convex base shape, Concave base shape, Modified hole intersection with part surface, Narrowed base with respect to average prism diameter, Enlarged base with respect to average prism diameter), Holes that are either enlarged or narrowed at areas that are neither the tip nor the base);
[0101] iii. Parts with randomly formed projections containing undercut features;
[0102] iv. Parts with other geometrical projections containing undercut features fabricated using micro/nanofabrication processes;
[0103] v. Parts with geometries containing undercut features produced using mechanical or chemical etching or abrasion processes;
[0104] vi. Parts with more than one type of micro and/or nanofeature that recesses into the part surface, at least one of which is undercut (Multiple micro and/or nanofeatures at the same length scale, Multiple micro and/or nanofeatures at different length scales).
[0000] C. Parts with a Combination of Features that Recess into the Part Surface and Protrude from the Part Surface, at least One of which is Undercut:
[0105] i. Multiple micro and/or nanofeatures at the same length scale;
[0106] ii. Multiple micro and/or nanofeatures at different length scales.
[0107] While the disclosure 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 of the embodiments. Thus, it is intended that the present disclosure cover the modifications and variations of this disclosure provided they come within the scope of the appended claims and their equivalents.
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The present invention is a method that (i) allows for creating micro and/or nanostructures on either planar or non-planar three-dimensional surfaces in a single molding step, and (ii) allows for the molded production of complex high-aspect ratio micro and/or nanostructures including but not limited to cylinders, conical structures, low aspect-ratio channels, bumps, or posts. An example of such a complex structure are high aspect ratio pillars with enlarged “mushroom-shaped” or undercut tips which demonstrate enhanced, repeatable adhesion and shear strength on a variety of substrates when compared with other micro and/or nanostructures and unstructured materials. The mold of such a material requires an “undercut” feature that cannot be produced using typical micro/nano-molding processing techniques.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of patent application Ser. No. 13/176,641 filed Jul. 5, 2011, now U.S. Pat. No. 8,419,602, entitled Cartoner for Cartons Having Concave Sides, which is a continuation of patent application Ser. No. 12/885,464 filed Sep. 18, 2010, now U.S. Pat. No. 7,998,049 issued Aug. 16, 2011 entitled Cartoner for Cartons Having Concave Sides, which is a continuation of patent application Ser. No. 12/240,736 filed Sep. 29, 2008, now U.S. Pat. No. 7,819,791 issued Oct. 26, 2010, which claims priority to U.S. Provisional Patent Application Ser. No. 60/975,820 filed Sep. 28, 2007. The entire contents of all four applications/patents are incorporated by reference herein.
BACKGROUND
The present invention relates to packaging equipment. In particular the invention relates to an apparatus and methods for forming, gluing, and filling preformed cartons, particularly cartons which have concave sides.
Current systems for handling products and packages, such as cartons, commonly to use conveyors to move and assemble cartons from blanks, and to then move and transfer products into the formed, glued cartons in an inline process. The conveyors typically include elements, such as carton or product lugs, chains, gears, oscillators, and the like, all of which are typically linked together by a drive system, such as a motor driven chain drive system. The various elements which comprise the packaging equipment combine to form a piece of apparatus called a “cartoner”.
Typical cartoners are generally referred to as “horizontal” or “vertical” cartoners, the distinction being in the manner in which they operate, with horizontal cartoners typically being relatively long machines which are loaded with blank cartons at one end. As they move down the conveyor, the carton blanks are formed and glued into partially formed cartons which lie on their sides. Product is loaded into the partially formed cartons which are “horizontally” oriented, and then their flaps are tucked, glued, and sealed. The fully formed cartons, loaded with product, are then passed to a final station where they are removed for storage or shipping.
As is known by those familiar with the cartoner industry, some so-called “horizontal” cartoners, such as those made by Langen Packaging, Inc. of Mississauga, Canada, can also be “tilted” upwards to about forty-five degrees. Similarly, there are so-called “vertical” cartoners which form cartons from the blanks such that they have a vertical orientation when they are filled.
Each of the known prior art cartoners, whether horizontal, “tilted”, or vertical, is designed to form a carton from a blank, tuck in (and glue) the various flaps, and provide an area (or station) at which a partially formed carton having an open end can be filled with product, either manually or automatically. After the partially formed cartons have been filled, cartoners typically provide a further area in which the remaining flaps of the filled carton are glued and sealed, and then, ultimately removed from the machine, manually or using a conveyor system, whereby fully formed cartons, filled with product, ultimately leave the cartoner.
Based upon their design and operation, cartoners are capable of handling the foregoing operation with up to several thousand cartons being formed and filled in every shift.
As is generally understood, a standard design for a carton is a generally rectangular box, such as those used for products found on the shelves of supermarkets and other stores, filled with everything from cereals to golf balls. A problem which has existed with the cartoners of the prior art, however, is that they are generally limited to handling cartons having only a limited type of shape, while recent market studies have shown that consumers perceive certain shapes, such as a tapered carton having concave sides, as being premium packages which contain premium products.
The heretofore known cartoners have been unable to form cartons from blanks which would provide the formed cartons with such tapered, concave sides.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side schematic view of the cartoner of the present invention;
FIG. 2 is a perspective view of a “premium” carton having concave sides of the type which can be folded, formed, and filled using the present invention; and
FIGS. 3-30 are perspective views showing the invention of FIG. 1 producing the carton of FIG. 2 .
DETAILED DESCRIPTION
Referring first to FIGS. 1 and 2 , the present invention is a new cartoner 10 which can be used to form, fill, and glue a carton 12 having concave (e.g., tapered) sides 14 , 16 (See, FIG. 2 ). With continued reference to FIG. 1 , the cartoner 10 of the present invention is an elongated apparatus which includes a loading area 18 at one end. The loading area 18 includes a magazine which holds a stack of preformed carton blanks As those skilled in the art are aware, carton blanks are made by carton manufacturers who generally deliver the blanks in a collapsed form, whereby they can be stacked in a magazine located in the loading area 18 of the cartoner 10 .
With continued reference to FIG. 1 , the cartoner 10 includes means, located in the loading area 18 , for removing individual collapsed blanks from the magazine and then moving them from the loading area 18 , through a series of sections 20 , 22 , 24 , 26 , 28 of the cartoner 10 where the blanks undergo a series of operations. Thus, the cartoner 10 includes a section 20 in which the collapsed blanks are opened, and additional sections at which the flaps on one side of the blanks are closed 22 , at which product is inserted into the partially completed carton 24 , at which the remaining flaps are closed and glued 26 , and a section 28 at which completed, filled cartons are removed for storage and shipping.
Referring, now, to FIG. 3 , as is generally known in the art, the blanks 30 which are used to form the cartons 12 (See, FIG. 2 ) have already been cut, scored, adhesively bonded, and folded flat before they are placed into the magazine 32 at the loading area 18 of the cartoner 10 . From there, individual blanks 30 are pulled from the magazine 32 using rotating vacuum sucker cups 34 which are mounted on a rotating, articulating apparatus 35 , designed to reach out, and grab, a single preformed carton blank 30 at a time.
With reference to FIGS. 4 and 5 , the vacuum sucker cups 34 are driven and rotated by a system, such as an electrically operated motor (not shown) which drives a chain 38 to insure that the movements of the various elements of the cartoner 10 are synchronized. The spacing of the carton blanks 30 , as they are fed from the magazine 32 is determined by the “pitch” of the cartoner 10 . Thus, a typical cartoner will generally have a predetermined “pitch”, meaning that a carton blank 30 will follow (and be followed by) the next adjacent carton blank 30 , with the blanks separated by the “pitch” length from one another. Within the “pitch” known cartoners have so-called “lugs” which receive and retain the carton blanks 30 as they pass from the loading end 18 of the cartoner 10 to the “filled” end 28 .
The way the cartoner 10 of the present invention is able to accomplish the loading and sealing of a carton 12 having concave sides 14 , 16 requires numerous modifications to “standard” cartoner machines. In the following explanation of the present invention, a “horizontal” cartoner machine is described, although those skilled in the art will, of course, recognize that the invention is not limited solely to horizontal cartoners.
With reference to FIGS. 5-7 , in the cartoner 10 of the present invention, as well as in standard, horizontal cartoning machines, after the vacuum sucker cups 34 grab an individual blank 30 from the magazine 32 , they move the trailing edge 36 of the blank 30 (e.g., the scored edge between the bottom 42 of the carton blank 30 and the rear 44 of the carton blank 30 ) against a bar 40 which traps the blank 30 , whereby further relative movement of the blank 30 toward the bar 40 (as the vacuum sucker cups continue to rotate toward the left, as shown in FIG. 6 ) causes the carton blank 30 to open from the original flattened position it had in the magazine 32 to a more “carton-like” position in which the front 46 and rear 44 of the blank 30 are spaced apart, as shown in FIG. 7 .
At the same time, the blank 30 is positioned between a leading capture lug 48 and a trailing capture lug 50 (See, FIGS. 6-9 ). While “standard” cartoners also use lugs, those lugs are generally rectangular in cross-section, whereas the “capture lugs” 48 , 50 of the present invention are formed such that they are able to both hold the blank 30 therebetween and to squeeze the blank 30 to bow its front 46 upward and its rear 44 downward as shown in FIGS. 10-11 . In the preferred embodiment of the invention, immediately before the trailing edge 36 of the blank 30 is placed into the rear capture lug 50 , the trailing edge 36 is pressed against an angled bar 40 (See, FIG. 7 ) which urges the blank 30 to open up as the rear capture lug 50 approaches it.
The vacuum sucker cups 34 urge the leading edge of the blank 30 into the leading capture lug 48 until it is fitted into the leading capture lug 48 as shown in FIGS. 8-9 . In the preferred embodiment of the invention, rails 52 (See, FIGS. 8-9 ) assist in holding the leading edge of the blank 30 down as it is urged into position within the leading capture lug 48 . With the blank 30 fully retained by the capture lugs 48 , 50 , the blank 30 will be somewhat “bowed”, as shown in FIGS. 10-11 , the importance of which will hereafter be made clear.
With reference to FIG. 10 , the bowed blank 30 next approaches a first plow rod 54 which has an angled end 56 . As the leading distal minor flap 58 of the blank 30 makes contact with the angled end 56 of the plow rod 54 , the angled end 56 of the plow rod 54 urges the leading distal minor flap 58 to bend and close, as shown in FIGS. 11-13 .
Referring to FIGS. 13-14 , as the blank 30 moves further, a rotating rotary minor flap tucker 60 , which rotates in a counterclockwise manner when viewed from above, makes contact with, and urges the closure of, the trailing distal minor flap 62 . As will be understood by those skilled in the art, the movement of the blank 30 along the path of the cartoner 10 allows the stationary plow rod 54 to close the leading distal minor flap 58 , as the closure of the rear leading distal minor flap 58 is toward the bottom of the carton 12 . To close the trailing distal minor flap 62 , on the other hand, requires that the flap 62 be closed toward the inside of the carton 12 . Accordingly, the rotary minor flap tucker 60 has to rotate toward the leading edge of the carton blank 30 , and it must do so at a speed greater than the speed at which the blank 30 is moving along the cartoner 10 .
As the blank 30 continues to move, the elongated plow rod 54 holds both the rear leading and the rear trailing minor flaps 58 , 62 closed, as shown in FIGS. 14-15 . As will be understood by those skilled in the art, the vertical heights of the plow rod 54 and the rotary minor flap tucker 60 must be offset somewhat, whereby the rotating rotary minor flap tucker 60 does not strike the plow rod 56 . This displacement allows the plow rod 54 , which had closed the rear leading minor flap 58 to also receive the now closed rear trailing minor flap 62 , thereby holding both rear minor flaps 58 , 62 in the closed position shown in FIGS. 14-15 . At this point product can be inserted into the partially completed carton.
Referring next to FIGS. 15-17 , the blank 30 approaches another plow rod 64 which also includes an angled portion 66 , so that when the front leading minor flap 68 reaches the angled portion 66 of the plow rod 64 , as shown in FIGS. 15-16 , contact with the angled portion 66 of plow rod 64 closes the front leading minor flap 68 . This is followed shortly thereafter by the closure of the front trailing minor flap 70 by another rotating rotary minor flap tucker 72 , as shown in FIG. 17 .
With reference to FIGS. 18-22 , the blank 30 next undergoes a series of “pre-breaking” processes in which the major flaps of the blank 30 (corresponding to the sides 14 , 16 of the carton 12 ) are flexed sufficiently to cause them to bend at their score lines when subsequent bending operations are conducted. These “pre-breaking” steps are key to the successful closure of the carton, as they soften the blank 30 along the curved score lines which give the carton 12 its concave sides 14 , 16 (See, FIG. 2 ). The pre-breaking processes are accomplished by using lower secondary plow rods 74 to shape the lower inside major flaps by bowing them. As shown in FIGS. 18-19 a lower secondary angle plow 74 urges the front inside major flap 76 up as the blank 30 moves into its leading edge. A second set of plow plates 75 continues to close inside major flaps 76 , when they reach the plates 75 . Similarly, a lower secondary angle plow 74 (not shown) and plow plate 75 on the rear side urges the rear inside flap up. Next, upper secondary angle plows 78 are used to pre-break and retain the front and rear upper flaps 80 , 82 of the blank 30 inside capture lugs 48 , 50 , as shown in FIG. 20 .
Then, the partially formed carton blank 30 passes through a section of the cartoner 10 in which the inner major flaps 76 undergo a pre-breaking process while oscillators 84 , which move with the blank 30 on each side (See, FIG. 21 ) press inward and urge the major inner flaps into position creasing at the score line of the blank 30 . Once the lower major inner flaps are positioned, another set of cam track oscillators 86 which have curved metal cam operated pusher carton pre-break plates 88 (See, FIG. 22 ) hold the major inside flaps closed. As illustrated, the pusher carton prebreak plates 88 have curved cutouts 90 (See, FIGS. 22-23 ) to prevent interference with the rods which will fit into position.
Next, the major outer flaps 80 , 82 are pre-broken over the top of the carton pre-break plates 88 using rods 94 , as shown in FIGS. 23-24 . With the score lines of the carton blank 30 all having been “pre-broken”, the major outer flaps are urged into their final position as shown in FIG. 25 , by rollers 96 which are used to fully form the major flap score lines while avoiding any “marking” of the carton blank 30 .
Then the outside major flaps 80 , 82 are released from the rollers 96 . The curved metal cam operated pusher pre-break plates 88 pull away from the carton blank 30 thereby reopening pre-broken outside major flaps 80 , 82 . Rods fit into position through cutouts 90 , thereby holding the inside major flaps 76 closed.
Finally, glue (typically hot melted glue) is applied to the flaps, and the outer major flaps are reclosed by rods and rollers 97 and held in position by traveling pressure blocks 98 while the hot glue sets. As shown in FIGS. 26-30 , the pressure blocks 98 have convex outer faces 100 to fit, and mate with, the concave sides 14 , 16 of the carton 12 .
With reference to FIG. 30 , the fully formed, filled carton 12 disengages from the front capture lug 48 at the far end of the cartoner 28 (See, FIG. 1 ). Due to the manner in which the non-rectangular rear lug 50 overlays the carton 12 , it is preferable to have a conveyor meet the carton 12 as it is released by the pressure blocks 98 in order to avoid damage to the fully formed carton 12 .
While the invention has been described in connection with specific embodiments and applications, the inventor does not intend to restrict the description to the examples shown. Persons skilled in the art will recognize that the above apparatus and methods may be modified or changed without departing from the general scope of the present description, the intention of the inventor being to include all such modifications and alterations in so far as they come within the scope of the appended claims or the equivalents thereof.
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A method for assembling a blank including accessing a blank having a main panel portion and at least one flap portion coupled to the main panel portion. The method further includes positioning a plate adjacent to the blank, the plate having a curved edge, folding the flap portion relative to the main panel portion about the curved edge of the plate such that the flap portion is coupled to the main panel portion along a curved line thereof.
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TECHNICAL FIELD
The present invention relates to a construction technology of a ferrocement ribbed slab for building, and more particularly, to a method of casting in-situ a ferrocement ribbed slab through a spliced rack and a suspended formwork.
BACKGROUND
A Ferrocement ribbed slab given in the Chinese standard No. GB/T 16308-2008 is a kind of precast floor slab, which has advantages of light weight and less material consumption, has an average thickness of merely about 3 cm and hence may reduce 70% of materials compared with the ordinary in-situ cast floor slab, thus it is worth popularizing the ferrocement ribbed slab as a structured floor slab. If the ferrocement ribbed slabs are employed as floor slabs in all buildings under construction, the concrete to be saved every year would be stacked into a hill. However, the ferrocement ribbed slab needs to be precast and is difficult to transport because of its larger size. Further, due to the connection problem between the ferrocement ribbed slab and beam columns, which has a great influence on the rigidity of the whole floor slab in the building, the ferrocement ribbed slabs are not utilized widely. Moreover, due to the limitation of the existing on-site production technology level, the existing construction technology cannot meet the requirement of casting in-situ the ferrocement ribbed slab.
SUMMARY
In view of the defects existing in the prior art, an object of the present invention is to provide a method of casting in-situ a ferrocement ribbed slab with a spliced rack and a suspended formwork, such that the ferrocement ribbed slab can be formed integrally with a beam column through casting in situ, thus the ferrocement ribbed slab can be widely applied to a variety of building floor slabs.
In order to achieve the above object, the present invention proposes the following technical solution:
A method of casting in-situ ferrocement ribbed slab through a spliced rack and a suspended formwork, comprising steps of:
Step 1) of prefabricating a transverse plane truss girder 1 , an incomplete longitudinal plane truss girder 2 and an incomplete longitudinal plane truss 3 in a factory, wherein the transverse plane truss girder 1 , the incomplete longitudinal plane truss girder 2 and the incomplete longitudinal plane truss 3 are configured to be spliced to a mesh truss 4 in constructing in-situ.
A width D and a height H of the mesh truss 4 are selected according to span and load bearing requirements of a floor slab, and then fabricating the transverse plane truss girder 1 with the height H, the incomplete longitudinal plane truss girder 2 with the height H and the incomplete longitudinal plane truss 3 with the height H by using an automatic truss welding machine, where the length of the transverse plane truss girder 1 is equal to the width D.
Step 2) of making a bottom formwork:
The bottom formwork is made of light material with a good fire resistant and soundproof performance, and is reinforced for a large construction load by increasing the strength of the bottom formwork or adding a steel mesh within the bottom formwork considering requirements of the construction load.
Step 3) of splicing and constructing a mesh truss 4 on site:
Wherein, the transverse plane truss girders 1 are placed in position according to the spacing requirements of the mesh truss and fixedly connected with a beam or a wall, thereby maintaining the transverse plane truss girder 1 horizontal;
Subsequently the incomplete longitudinal plane truss girders 2 are fixed on each of the transverse plane truss girders 1 perpendicularly to the transverse plane truss girders and connected to the beam or wall, wherein the spacing between the adjacent incomplete longitudinal plane truss girders 2 are conform to the spacing requirements of a mesh truss;
Then the incomplete longitudinal plane trusses 3 are arranged below and spliced with the incomplete longitudinal plane truss girders 2 ;
Lastly, the transverse plane truss girder 1 , the incomplete longitudinal plane truss girders 2 and the incomplete longitudinal plane trusses 3 are fixedly connecting at intersections therebetween.
Step 4) of suspending the bottom formworks:
Wherein the bottom formworks are suspended and installed below the mesh truss 4 through connectors, and a gap between the bottom formworks is filled, and the spacing between the bottom formworks meets the sectional requirement of the ferrocement ribbed slab.
Step 5) of laying reinforcing mesh pieces:
Wherein the reinforcing mesh pieces are laid on both sides of the floor slab and the rib according to the structure requirements of the ferrocement ribbed slab, and then it is checked whether the structure requirements are met according to a blueprint.
Step 6) of performing in-situ casting:
Wherein self-leveling mortar, self-compacting mortar or self-compacting concrete is poured in-situ into the mesh truss 4 enclosed by the bottom formwork and the reinforcing mesh, to integrally connect the reinforcing mesh, the bottom formwork and the mesh truss 4 together, i.e., finish the in-situ construction of the in-situ ferrocement ribbed slab.
Based on the above technical solution, the transverse plane truss girder 1 includes an upper horizontal rod 11 for transverse plane truss girder and a lower horizontal rod 12 for transverse plane truss girder, a plurality of web rods 13 for transverse plane truss girder are connected between the upper horizontal rod 11 for transverse plane truss girder and the lower horizontal rod 12 for transverse plane truss girder, so that every two web rods 13 for transverse plane truss girder form a pair spliced into a triangular structure, wherein the adjacent triangular structures abut against each other.
Based on the above technical solution, the incomplete longitudinal plane truss girder 2 includes an upper horizontal rod 21 for incomplete longitudinal plane truss girder and a plurality of web rods 22 for incomplete longitudinal plane truss girder arranged below the upper horizontal rod 21 for incomplete longitudinal plane truss girder, wherein every two web rods 22 for incomplete longitudinal plane truss girder from a pair spliced into an inverted triangle structure, and the adjacent inverted triangle structures are spaced by a span of the inverted triangle structure.
Based on the above technical solution, the incomplete longitudinal plane truss 3 includes a lower horizontal rod 31 for incomplete longitudinal plane truss and a plurality of web rods 32 for incomplete longitudinal plane truss, wherein every two of the web rods 32 for incomplete longitudinal plane truss web form a pair spliced into a triangle structure, and the adjacent triangle structures are spaced by a span of the triangle structure.
Based on the above technical solution, the light material with a good fire resistant and sound proof performance which is used to make the bottom formwork is foam concrete.
Based on the above technical solution, the connector used in step 4) is embedded in advance within the bottom formwork.
The method of casting in-situ a ferrocement ribbed slab with a spliced rack and a suspended formwork has the following advantages:
1. The transverse plane truss girder 1 , the incomplete longitudinal plane truss girder 2 and the incomplete longitudinal plane truss 3 can be prefabricated in the factory.
2. The transverse plane truss girder 1 , the incomplete longitudinal plane truss girder 2 and the incomplete longitudinal plane truss 3 can form the mesh truss 4 .
3. The bottom formwork is a disposable lightweight dedicated formwork, can meet the requirement for bearing the construction load and be used to form the section of the ferrocement ribbed slab, further the bottom formwork has heat insulating, fire-resistant and soundproof functions. Thus, the bottom formwork is a multi-purpose module meeting both the construction requirement and the operating requirement.
4. The connector can be embedded in advance within the bottom formwork, so that the bottom formwork can be easily connected with the mesh truss 4 through the connector; further, the bottom formwork may be threadedly fixed to the mesh truss 4 , thereby ensuring the construction accuracy.
5. The mesh truss is fixed initially to ensure the correct relative position of the rebar inside the floor slab, which solves the problem that the accuracy of the relative position of the rebar in the existing construction technology cannot meet the requirement for the position accuracy of the rebar needed by the ferrocement ribbed slab.
6. For the splicing type mesh truss 4 , a monolithic truss can be machined in the factory, such that the vertical flatness and rigidity of the beam can be well ensured and the end support of the beam is employed during the construction (the fixed connection of the mesh 4 and the beam or well includes the support), which solves the problems that the support is uneven in the existing construction technology.
7. The use of the bottom formwork which does not need to be removed (i.e. a disposable bottom formwork) avoids the problems that the formwork needs to be removed in the existing construction technology.
8. Because the bottom formwork is produced with reference to the relative position of the rebar, the relative position between the bottom formworks and between the bottom formwork and the rebar can be ensured, thus the accuracy of the formwork for casting in-situ the ferrocement ribbed slab can reach the production accuracy of the prefabricated formwork, thereby implementing the casting in-situ of the ferrocement ribbed slab.
9. The bottom formwork has soundproof performance, and can form a composite formwork together with the in-situ cast ferrocement ribbed slab, so the composite formwork has both a light weight performance and a good soundproof performance.
10. The bottom formwork has a better heat insulation effect, which can avoid the high temperature damage to the structure in the case of a fire emergency, thereby improving the fire-resistant performance.
11. The fixed connection between the bottom formwork and the mesh truss is implemented using the connector, and is formed integrally with the cast ferrocement ribbed slab, thus avoiding the release of the bottom formwork in subsequent use.
12. Because of the use of the suspended bottom formwork and the truss, the self-leveling mortar or the self-compacting concrete is applied directly to the rebar through the bottom formwork during the construction of the floor slab, and the support does not exist, so that the floor slab will not crack under the pulling stress produced by its self-weight, and the bottom formwork and the pouring material can combine together under their self-weight, thus the time for air and oxygen to come into contact with the rebar is prolonged, that is, the service time of the floor slab is increased indirectly.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings of the present invention are as follows:
FIG. 1 is a schematic view of a transverse plane truss girder.
FIG. 2 is a schematic view of an incomplete longitudinal plane truss girder.
FIG. 3 is a schematic view of an incomplete longitudinal plane truss.
FIG. 4 is a schematic view of a spliced mesh truss.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The invention will be further described in detail with reference to the accompanying drawings.
Due to significant differences between the prefabricated production technology and the in-situ production technology, analysis shows that the in-situ production of the ferrocement ribbed slab given in the Chinese standard No. GB/T 16308-2008 is mainly limited by the following technical bottlenecks:
1. Formwork Manufacture
The ferrocement ribbed slab given in the Chinese standard No. GB/T 16308-2008 is very demanding for the formwork due to its small cross section, and particularly requires for accuracy of the formwork that is much higher than that of an in-situ produced formwork. In the prefabrication of the ferrocement ribbed slab in the factory, steel molds and a steam curing method are employed to improve a turnover rate of the formwork, which cannot be achieved in field production, or achieved at a cost much higher than the cost of the formwork per se. Thus it is unworthy popularizing the in-situ production of the formwork.
2. The Removal of the Formwork
The removal of the formwork is a big problem in the conventional construction of an in-situ cast ferroconcrete ribbed floor slab, and such problem will be more serious for the ferrocement ribbed slab, because the traditional removal method using a crowbar for example is unsuitable for the ferrocement ribbed slab due to the thin rib of the ferrocement ribbed slab. Thus, a mold release agent is used for the removal of the formwork as regulated in the Chinese standard No. GB/T 16308-2008. However, it is difficult to surely prevent the mold release agent from polluting the rebar during the in-situ construction. Once the mold release agent pollutes the rebar, the bearing capacity of the formwork is degraded directly.
3. Support
The conventional construction technology of the in-situ cast ferroconcrete ribbed floor slab generally includes: firstly installing a support, then placing a laminated wood board, binding the rebar, and lastly pouring the concrete. But this construction technology has a problem in that the horizontal accuracy of the bottom formwork is low and formwork shifting, local dent or protrusion in the ferroconcrete ribbed floor may occur, which is fatal for the ferrocement ribbed slab and affects the sectional height of the ferrocement ribbed slab directly, that is, leading to the uneven bearing capacity of the formwork.
4. Rebar Fixation
To cast in-situ a ferroconcrete ribbed floor slab, generally the rebar is manually bound on the formwork, thus it is hard to ensure a constant relative space between rebars. However, very strict requirements are applied for the relative positions of rebars in the ferrocement ribbed slab due to the small section of the ferrocement ribbed slab. Therefore, the traditional construction technology cannot meet the requirements.
In addition to the above technical problems caused by the in-situ production, there also exist the following problems in usage and functions of the ferrocement ribbed slab which block the popularization of the ferrocement ribbed slab given in the Chinese standard No. GB/T 16308-2008:
1. The ferrocement ribbed slab is very thin, and hence has an unsatisfying soundproof effect, which cannot meet the use requirements of the soundproof effect as regulated in national specifications.
2. Fire resistant performance is bad due to that the cross section of the ferrocement ribbed slab is too thin so that the heat insulation performance of the ferrocement ribbed slab is poor.
A serial of improvements must be made to promote and popularize the ferrocement ribbed slab.
Space grids (also referring to as space truss, or three-dimensional truss, or space steel truss) are largely applied to a long-span roof structure, such as ceilings of many gas stations and gyms, but not to an in-situ cast ferroconcrete structure for the reason as follows:
1. The space grid is manufactured and installed as a whole, and hence is difficult to be combined with beam columns in a multi-story building, and is unsuitable for a small-span roof.
2. The space grid has very good rigidity and a high bearing capacity, thus it is unnecessary to attach concrete to the space grid since the concrete also adds weight. As such, it is a waste of resources to embed the space grid into the concrete, because such embedding cannot improve the bearing capacity, but add the weight, thereby degrading the load grade of the space grid.
3. The space grid, especially its nodes (e.g. spherical nodes), has high manufacture requirements, to overcome the problem of stress concentration.
Therefore, the space grid, as a load bearing structure, is used individually around the world.
This invention novelly changes the space grid into a spliced rack, which is applicable to the in-situ cast floor slab without the above-mentioned waste but saving a large number of formwork supports, to implement the incorporation and application of the prefabricated ferrocement ribbed slab technology into various in-situ cast floor slabs.
A method of casing in-situ a ferrocement ribbed slab through a spliced rack and a suspended formwork according to the present invention, as shown in FIGS. 1 to 4 , includes the following steps:
Step 1): prefabricating a transverse plane truss girder 1 , an incomplete longitudinal plane truss girder 2 and an incomplete longitudinal plane truss 3 in a factory, where the transverse plane truss girder 1 , the incomplete longitudinal plane truss girder 2 and the incomplete longitudinal plane truss 3 are configured to be spliced to a mesh truss 4 in constructing in-situ.
The width D and height H (see FIG. 4 ) of the mesh truss 4 are selected according to span and load bearing requirements of the floor slab, and the length of the mesh truss 4 can be selected as actually desired. The mesh truss 4 may have a square shape with a height H and a side length of D.
Then, a transverse plane truss girder 1 with a height H, an incomplete longitudinal plane truss girder 2 with the height H and an incomplete longitudinal plane truss 3 with the height H are fabricated by using an automatic truss welding machine, where the length of the transverse plane truss girder 1 is D.
The transverse plane truss girder 1 includes an upper horizontal rod 11 for transverse plane truss girder and a lower horizontal rod 12 for transverse plane truss girder, a plurality of web rods 13 for transverse plane truss girder are connected between the upper horizontal rod 11 for transverse plane truss girder and the lower horizontal rod 12 for transverse plane truss girder, so that every two of the web rods 13 for transverse plane truss girder form a pair spliced into a triangular structure, where adjacent triangular structures abut against each other.
The incomplete longitudinal plane truss girder 2 includes an upper horizontal rod 21 for incomplete longitudinal plane truss girder and a plurality of web rods 22 for incomplete longitudinal plane truss girder arranged below the upper horizontal rod 21 for incomplete longitudinal plane truss girder, where every two of the web rods 22 for incomplete longitudinal plane truss girder form a pair spliced into an inverted triangle structure, and the adjacent inverted triangle structures are spaced by a span of one inverted triangle structure.
The incomplete longitudinal plane truss 3 includes a lower horizontal rod 31 for incomplete longitudinal plane truss and a plurality of web rods 32 for incomplete longitudinal plane truss arranged on the lower horizontal rod 31 for incomplete longitudinal plane truss, where every two of the web rods 32 for incomplete longitudinal plane truss form a pair spliced into a triangle structure, and the adjacent triangle structures are spaced by a span of one triangle structure.
The span of the triangle structure formed with two web rods 32 for incomplete longitudinal plane truss is identical to the span of the inverted triangle structure formed with two web rods 22 for incomplete longitudinal plane truss girder.
The upper and lower horizontal rods are preferably made of twisted steel, and the web rod is preferably made of hot-rolled round steel.
Step 2): making a bottom formwork.
The bottom formwork may be made of light material with a good fire resistant and soundproof performance. Considering the requirements of the construction load, the bottom formwork should be reinforced for a large construction load by increasing the strength of the bottom formwork or adding a steel mesh within the bottom formwork.
The light material with a good fire resistant and soundproof performance which is used to make the bottom formwork may be foam concrete, which is of a low cost and thus is very advantageous for wide application.
Step 3): splicing and constructing a mesh truss 4 on site.
The transverse plane truss girders 1 are placed in position according to the spacing requirements of the mesh truss and fixedly connected with a beam or a wall (by a connection way which varies with a different beam or wall but may be implemented based on the prior art, which will not be repeated here), thereby maintaining the transverse plane truss girders 1 horizontal.
Subsequently the incomplete longitudinal plane truss girders 2 are fixed on each of the transverse plane truss girders 1 perpendicularly to the transverse plane truss girders 1 , and connected to the beam or wall, where the spacing between the adjacent incomplete longitudinal plane truss girders 2 is conform to the spacing requirements of the mesh truss.
Then the incomplete longitudinal plane trusses 3 are arranged below and spliced with the incomplete longitudinal plane truss girders 2 .
Finally, the transverse plane truss girder 1 , the incomplete longitudinal plane truss girders 2 and the incomplete longitudinal plane trusses 3 are fixedly connected at intersections therebetween.
Step 4): suspending the bottom formworks:
The bottom formworks are suspended and installed below the mesh truss 4 through connectors, and a gap between the bottom formworks is filled, where the spacing between the bottom formworks meets the sectional requirement of the ferrocement ribbed slab.
The connector may be embedded in advance within the bottom formwork.
Step 5): laying reinforcing mesh pieces:
Reinforcing mesh pieces are laid on both sides of the floor slab and the rib according to the structure requirements of the ferrocement ribbed slab, and then it is checked whether the structure requirement are met according to the blueprint.
Step 6): performing in-situ casting:
Self-levelling mortar, self-compacting mortar or self-compacting concrete is poured in-situ into the mesh truss 4 enclosed by the bottom formwork and the reinforcing mesh, to integrally connect the reinforcing mesh, the bottom formwork and the mesh truss 4 together, i.e., finish the in-situ construction of the in-situ cast ferrocement ribbed slab.
With the in-situ cast ferrocement ribbed slab fabricated with the spliced rack and the suspended formwork through the cast-in-situ construction technology, features of the light weight and less material of the prefabricated ferrocement ribbed slab are maintained, defects of bad soundproof and poor fire-resistant performance of the ferrocement ribbed slab are overcome, and the strength of nodes of the ferrocement ribbed slab with various beam columns (the node refers to a cross binding joint between a beam and a slab, a pole and a slab, or a beam and a pole, and is very important in the structure) is ensured. Moreover, the rebar of several spans of floor slabs (generally one room delimits one span, and floor slabs of several adjacent rooms are referred to as several spans of floor slabs) can be connected mutually to form a continuous two-way slab, thereby increasing the rigidity of the whole roof and improving the anti-seismic property thereof. Therefore, the ferrocement ribbed slab is more adaptable to various kinds of building floors, and may be applied more widely, saving a large quantity of building material for the country and reducing the damage to the environment.
The content which has not been described in detail in present invention generally belongs to the prior art known for those skilled in the art.
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Disclosed is a method of casting in-situ a ferrocement ribbed slab with a spliced rack and a suspended formwork. The method comprises the following specific steps: step 1: machining at a plant a transverse plane truss girder, an incomplete longitudinal plane truss girder and an incomplete longitudinal plane truss; step 2: making a bottom formwork; step 3: splicing and constructing an on-site truss in a grid shape; step 4: suspending the bottom formwork; step 5: laying reinforcing mesh pieces; and step 6: performing in-situ casting. In the present method of casting in-situ a ferrocement ribbed slab with a spliced rack and a suspended formwork, the interspaced rack becomes a spliced rack and is applied to in-situ casting of floor slabs, such that a ferrocement ribbed slab is directly cast on site, and is cast as one with beams and columns, enabling the range of use of ferrocement ribbed slabs to be extended to the floor slabs of various buildings.
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[0001] The present invention relates to electric drive systems for vehicles and more particularly, to integrated drive, regenerative braking and vehicle control systems.
BACKGROUND
[0002] The search for alternatives to a transport system largely dependent on the internal combustion engine has seen a renewed interest in electric and hybrid vehicles. Many configurations of electric motors applied for vehicle use are known but frequently require purpose built drive trains between the one or more motors and the driven wheels.
[0003] Another disadvantage of know systems is that an integrated system incorporating the modern safety and convenience aspects of vehicle control, such as anti-lock braking, traction control cruise control is usually not provided for.
[0004] It is an object of the present invention to address or ameliorate some of the above disadvantages.
Notes
[0000]
1. The term “comprising” (and grammatical variations thereof) is used in this specification in the inclusive sense of “having” or “including”, and not in the exclusive sense of “consisting only of”.
2. The above discussion of the prior art in the Background of the invention, is not an admission that any information discussed therein is citable prior art or part of the common general knowledge of persons skilled in the art in any country.
BRIEF DESCRIPTION OF INVENTION
[0007] Accordingly in one broad form of the invention there is provided an electric drive system for a vehicle; said drive system including an electric motor at least one wheel of said vehicle; said electric motor comprising an electric field source adapted to induce rotational torque in the brake disc associated with said wheel of said vehicle.
[0008] Preferably said motor includes an electric field source in the form of pairs of electromagnetic coils, wherein corresponding ones of each of said pairs of coils are disposed on opposite sides of said brake disc of said wheel.
[0009] Preferably said electromagnetic coils are provided with variable frequency alternating current; said alternating current provided via an inverter from a battery power source.
[0010] Accordingly in a further broad form of the invention there is provided an electric drive system for a vehicle; said drive system including an electric motor at each wheel of said vehicle; each said electric motor adapted to provide rotational torque to the brake disc of each wheel said vehicle.
[0011] Preferably each said motor comprises pairs of electromagnetic coils, wherein corresponding ones of each of said pairs of coils are disposed on opposite sides of a brake disc of said wheel.
[0012] Preferably said electromagnetic coils are provided with variable frequency 3-phase alternating current; said alternating current provided via an inverter from a battery power source.
[0013] Preferably each electric motor is individually supplied with said variable frequency 3-phase alternating current by a microprocessor controlled inverter.
[0014] Preferably said brake disc is a standard brake disc of a disc brake system; said brake disc mounted at the hub of each wheel of said vehicle.
[0015] Preferably said brake disc comprises a toroidal laminated core with copper or aluminium ladder bars contained radially within to form a squirrel cage.
[0016] Preferably said pairs of coils are connected in series or in parallel; said coils supplied with said 3-phase alternating current on the same phase.
[0017] Preferably said pairs of coils comprise three pairs of coils; said coils disposed within an arc of said brake disc.
[0018] Preferably said motor is adapted to replace a standard hydraulic disc brake calliper.
[0019] Preferably said motor is of similar bulk as that of said hydraulic disc brake calliper; said motor adapted for mounting to mounting points of said hydraulic brake disc calliper.
[0020] Preferably rotational velocity and direction of each said wheel is a function of said variable frequency and phases of said 3-phase alternating current.
[0021] Preferably direction of rotation torque of a said motor urges said vehicle in a first forward direction when two phases of said 3-phase alternating current are arranged in a first phase configuration.
[0022] Preferably said direction of rotation torque of a said motor is reversed when said two phases of said 3-phase alternating current are arranged in a second phase configuration.
[0023] Preferably braking of said vehicle is induced when said variable frequency is less than a frequency commensurate with a said rotational velocity.
[0024] Preferably said braking is regenerative adapted to recharging said battery power source.
[0025] Preferably a first variable braking force is applied to a said brake disc while said rotational direction is commensurate with said phases but said variable frequency is between that commensurate with said rotational velocity of said wheel and 0 Hz.
[0026] Preferably a second variable braking force is applied to said brake disc when said rotational direction is opposite to that indicated by said arranging of two phases and said variable frequency is greater than 0 Hz.
[0027] Preferably said first variable braking force and said second variable braking force are controlled through a potentiometer connected to a brake pedal of said vehicle.
[0028] Preferably said rotational velocity of each of wheel is monitored by sensors.
[0029] Preferably each said microprocessors is adapted to apply anti-lock breaking characteristics to said second variable breaking force when said sensors record disparate rotational velocities.
[0030] Preferably steering angle of said vehicle is monitored by a sensor.
[0031] Preferably each said microprocessor is adapted to apply varying rotational torques to wheels on opposite sides of said vehicle as a function of inputs from sensors monitoring rotational velocities of each wheel and said steering angle.
[0032] In a further broad form of the invention there is provided a method of imparting a torque to a wheel of a vehicle; said wheel having a brake disc rotor mechanically associated with it; said method comprising utilising said rotor as a motor rotor whereby said rotor performs a dual function of a disc brake and a motor rotor.
[0033] In a further broad form of the invention there is provided a method of providing rotational torque to the brake discs of a vehicle by the application of variable frequency 3-phase alternating current to said brake discs.
[0034] Preferably said variable 3-phase alternating current is provided to coils mounted at each of said brake discs.
[0035] Preferably said variable 3-phase alternating current is provided from a battery power source via a microprocessor controlled IGBT inverter.
[0036] Preferably said electric motors are adapted to provide regenerative braking; said regenerative braking adapted to provide a charge to said battery power source.
[0037] Preferably said method includes the steps of:
(a) monitoring rotational velocities of each of said wheels, (b) varying rotational torque inputs to brake discs as a function of said rotational velocities.
BRIEF DESCRIPTION OF DRAWINGS
[0040] Embodiments of the present invention will now be described with reference to the accompanying drawings wherein:
[0041] FIG. 1 is a schematic side view of an electric motor drive and brake unit according to a preferred embodiment of the invention,
[0042] FIG. 2 is schematic perspective view of the motor drive and brake unit of FIG. 1 ,
[0043] FIG. 3 is a schematic view of the major components of the drive system applied to a vehicle
[0044] FIG. 4 is an electrical schematic of one possible implementation of the motor drive and brake unit according to an embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
First Preferred Embodiment
[0045] In preferred forms, the invention provides for an in-wheel electric motor that can provide independent electric direct drive and brake to each wheel of a vehicle. This motor allows a single system to provide four wheel drive, traction control, regenerative braking, eddy current braking, anti-lock braking, vehicle stability control and electronic brake force distribution (brake bias). This system can also incorporate intelligent cruise control and collision avoidance.
[0046] The in-wheel motor is based on linear induction motor principles. In this case 3-phase alternating current is induced into a disc to produce rotary motion. With reference to FIGS. 1 to 3 , The disc or rotor 12 in this preferred embodiment of the motor 10 of a vehicle drive system, can be a standard motor vehicle brake disc mounted in the standard position surrounding each wheel's hub within each wheel of the vehicle (not shown). Pluralities of coils A, B and C are mounted facing each side of the brake disc separated by an air gap. Three phase AC induction motor principles are well known where copper wire wound around the outside circumference of an electric motor have a 3 phase moving AC electric current applies to them inducing an eddy current within the motors rotor that converts electrical energy into rotary torque.
[0047] For this in-wheel electric motor 10 according to preferred embodiments of the invention, as few as 3 pairs of electromagnetic coils A, B and C can be used to induce a three phase eddy current in the brake disc 12 to convert electrical energy into rotary torque. Preferably, 3 coils are mounted on each side of the disc facing each other separated by the disc. In the six coil arrangement of FIGS. 1 and 2 , pairs of coils directly facing each other are typically connected in series or parallel on the same phase. Because a relatively small number of coils can be used and the motor therefore does not have a large number of coils mounted around the 360 degrees circumference of the disc, the motor 10 can be compact and comparable in size to a hydraulic brake calliper. Typically less than half the disc circumference is within the induction field of the coils at any one time. This electric motor 10 can therefore be retrofitted in place of the hydraulic brake calliper on a vehicle using the same mounting lugs and bolts to provide brake and drive torque to each wheel.
[0048] A variable alternating current, in this case to a maximum of 336 volts, is provided to the coils in a 3-phase waveform from a DC battery power source 14 by microprocessor controlled IGBT inverters 16 . The firmware within the microprocessor controls the switch timing and configuration of the IGBT inverters to convert direct current from the battery source to 3-phase alternating current at variable frequency that is provided to the electromagnetic coils facing the in-wheel brake disc.
[0049] Motor speed which is directly proportional to wheel speed is varied by altering the AC waveform frequency. Zero Hz (cycles per second) represents zero motor speed. An increase in frequency will increase motor speed and provide torque for vehicle acceleration in response to throttle pedal inputs. Once at speed, a decrease in frequency will provide regenerative braking torque. The larger the difference between motor speed and inverter frequency, as requested by the brake pedal input, the greater the regenerative brake torque and regenerative current flow back to recharge the battery power source. Increased brake pedal input up to a predetermined point, reduces the frequency to zero Hz, stopping regenerative current and causing the application of DC direct current to stop the motor(s). Further increases in brake pedal input to apply greater braking force to the wheel motor results in the 3 phase AC signal being reversed by swapping 2 phases and increased frequency is applied to provide eddy current braking up to and equal to maximum torque of the motor. Vehicle reverse is also provided by swapping the same two phases to reverse the motors. Anti-Lock brake function is provided by high speed frequency modulation ranging between regenerative frequency, DC and eddy current brake frequency in response to wheel speed sensor input and other parameters. Brake modulation may be adjusted more than 50,000 times per second according to microprocessor frequency.
[0050] If each in-wheel motor is provided with a dedicated IGBT inverter, such as shown in FIG. 3 , motor torque can be regulated independently for each motor. When each wheel has a wheel speed sensor such as a typical Hall effect sensor commonly used in anti-lock braking systems, this provides a closed loop feedback to facilitate anti-slip traction control for drive and braking applications. With the addition of a multi-axes accelerometer input into the microprocessors, lateral stability control can be implemented in addition to high performance emergency braking algorithms. The addition of a front mounted distance measuring device such as sonar/radar on the vehicle to input into the microprocessors, allows intelligent cruise control to be implemented with fine brake and acceleration control based on the selected proximity required between following vehicles and can be used in combination with the accelerometer for emergency braking and collision avoidance algorithm input. Adding a steering wheel angle input to the microprocessor can provide input into vehicle stability algorithms and provide primary input along with accelerometer input for enhanced cornering performance varying the speed differential between inside and outside wheels while cornering by adjusting applied frequency in either brake or drive modes or regenerative torque to each wheel motor individually.
Second Preferred Embodiment
[0051] In this further preferred embodiment, the vehicle drive system again comprises an electric motor for each wheel of the vehicle, a control system and a power source. The DC power supplied by the battery power source is preferably supplied as frequency modulated alternating current to each individual wheel motor via separate IGBT inverters controlled by a microprocessor.
[0052] In this embodiment also, the microprocessor is adapted to accept various sensor inputs to monitor wheel rotation, rotation differentials, accelerator and brake pedal status and steering wheel angle. Other inputs may include cruise control settings and collision sensing means.
[0053] The electric motor at each wheel may be described as a double sided linear induction motor in which the stator is curved 180 degrees and used to produce electromagnetic induction to a rotor disc in an axial flux direction. In this embodiment, the stator core is laminated and can be made from a toroidal winding of lamination steel cut in half to form two 180 degree arcs. Coil windings are laid in slots provided within the laminated core.
[0054] As before, the disc may be the standard cast iron motor vehicle brake disc mounted in the standard position at the wheel hub of each wheel. However, for maximum efficiency, the standard brake disc may be replaced with a disc incorporating a toroidal laminated core with copper or aluminium ladder bars contained radially within to form a squirrel cage.
[0055] With reference to FIG. 4 a basic electrical schematic of the above described arrangement is illustrated. In this instance rotor 12 forms part of a motor 10 . More particularly, the disc brake rotor 12 forms the rotor of the motor 10 . Coils 50 , 51 are placed in opposed relationship to the brake disc 13 as illustrated in cross-section in FIG. 4 . Appropriate drive wave forms are applied to the coils 50 , 51 from the power electronics unit 52 thereby to induce a torque in the brake disc 12 for the purpose of either a positive drive of the vehicle wheel (not shown) to which the disc brake rotor is attached, or in the alternative, positive braking force to the same wheel. The rotor 12 may take any form as previously described in this specification. Similarly the coils 50 , 51 can be disposed as described in respect of any of the previous embodiments.
[0056] The power electronics 52 are driven by control signals 53 from micro processor 54 . Micro processor 54 derives inputs from I/O unit 55 . The control inputs can include sensor inputs 56 from the wheel as previously described and/or can include input from the engine controller 56 (particularly in the case of hybrid systems eg petrol/electric). Again as previously described brake pedal position 58 can also be an input.
[0057] Typically a program will reside in memory 57 in order to provide instructions to micro processor 54 in order to effect appropriate control of the power electronics 52 .
In Use
[0058] It will be appreciated that the system described above provides for a very flexible drive system for a vehicle. The use of individually controlled electric motors at each of the vehicle wheels allows the use of sophisticated electrical input to provide the various functions of driving and braking torque, anti-lock braking, cruise and traction control. An additional feature is that the drive system of the invention can be retrofitted to the standard suspension of an all disc-brake vehicle chassis.
[0059] Although the above described embodiments are directed at suspension and braking systems in which the brake disc is mounted at the wheel hub, it will be understood that the motors and drive system of the present invention may equally be applied to the discs of an inboard disc brake system.
[0060] Similarly, whilst the main examples concern an all wheel drive pure battery/electric system, the principles can be applied to hybrid petrol or diesel/electric systems. Furthermore having only some wheels driven is also contemplated. For example in some applications having only the two front or two rear wheels of a car may be sufficient. In the case of a motor cycle either one or both wheels may be driven.
[0061] The above describes only some embodiments of the present invention and modifications, obvious to those skilled in the art, can be made thereto without departing from the scope and spirit of the present invention.
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An electric drive system for a vehicle; said drive system including an electric motor at least one wheel of said vehicle; said electric motor comprising an electric field source adapted to induce rotational torque in the brake disc associated with said wheel of said vehicle. In an alternative form there is provided a method of imparting a torque to a wheel of a vehicle; said wheel having a brake disc rotor mechanically associated with it; said method comprising utilising said rotor as a motor rotor whereby said rotor performs a dual function of a disc brake and a motor rotor.
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BACKGROUND OF THE INVENTION
The present invention relates to the rapid rate reactive sputtering of titanium and like metallic compounds onto a substrate or workpiece. The field of this invention comprises substrate coating by cathodic magnetron sputtering and includes a substrate to be coated, a coating material mounted on a target plate, electrode plates causing gas plasma particles to strike the target to release the coating material, means to control the rate of deposition of the coating material, and means to carry the article to be coated and to expose the desired portions for coating. The prior methods for coating substrates with thin metallic films have been accomplished by vapor deposition, plasma spray processes and cathode sputtering.
Vapor deposition processes to provide a metallic thin film on a workpiece utilize the material to be plated which is heated in a suitable atmosphere, such as in a vacuum or an inert shielding gas, to such an extent that the material evaporates and is deposited as a film on a substrate. Plasma spray processes provide the material to be deposited as a fine-grained powder which is brought into a plasma arc so that the particles melt and are deposited on a substrate.
Cathode sputtering or radio-frequency ionic sputtering involves a target of the material to form the coating in a gas discharge wherein the material is sputtered by ion bombardment; the particles removed from the target being deposited on the substrate. The target becomes the cathode and an anode may be located beneath the substrate. Where a thin film of metallic compounds, such as the oxides, nitrides, carbides and the like, are to be deposited on various substrates, reactive sputtering is used wherein the target consists of the metal for the plating compound and a neutral gas, such as argon, is mixed with a reactive gas such as oxygen, nitrogen or methane. The particles that are dislodged from the target combine with the reactive gas to produce the desired compound which is plated on the substrate or workpiece.
A major problem in the sputtering process is an abrupt decrease in the deposition rate of metallic compound films during the sputtering process in a reactive gas atmosphere. The deposition rate using a reactive gas was found to be 10-20% of the rate for the deposition of pure metal in a neutral gas. A method attempting to increase the deposition rate for reactive sputtering of titanium nitride is by the pulsing of the nitrogen gas, wherein the gas is admitted to the chamber for a pulse of 2 to 3 seconds and then shut off for 2 to 3 seconds. Using this pulsing technique, the nitride film deposition rate was increased to approximately 50 to 70% of the deposition rate of the pure metal. The present invention expands on this pulsing technique to achieve a nitride deposition rate that is substantially 100% of the rate of deposition of the pure metal.
SUMMARY OF THE INVENTION
The present invention comprehends the provision of a novel method for reactive sputtering of metallic compounds on a substrate wherein the deposition rate approaches or equals the deposition rate of the pure metal. To improve the deposition rate, the reactive gas at a constant flow rate is rapidly pulsed at a rate of approximately 0.2-0.5 seconds on and off for admission of the reactive gas to the inert atmosphere in the sputtering chamber.
The present invention also comprehends the provision of a novel method for reactive sputtering wherein the inert gas supplied to the chamber is maintained at a substantially constant pressure during the deposition cycle.
Further objects, features and advantages of the present invention will be better appreciated when the following detailed description of the method thereof is taken in conjunction with the accompanying drawing.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cut-away schematic showing of a sputtering apparatus utilized for the method of the present invention.
FIG. 2 is a graph showing the power to the metal target versus the flow rate of the reactive gas.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring more particularly to the disclosure in the drawing wherein is shown in FIG. 1 an illustrative embodiment of reactive sputtering apparatus 10 for the plating of a thin film of titanium nitride (TiN) or the other group IVb metals (zirconium and hafnium) from the periodic table of elements in the form of oxides, nitrides or carbides on a suitable substrate 11. The apparatus includes an elongated chamber 12 having an elevator 13 at one end communicating with a domed loading/unloading chamber 14, a pallet 15 which is carried by the elevator to receive the substrate 11 to be coated, a pallet carrier 16 receiving the pallet from the elevator and moving the pallet into the chamber 12 for sputtering in the central portion 19 and/or etching on a platform 17 at the end 18 of the chamber opposite to the elevator.
A magnetron cathode 20 carrying the target 21 formed of the group IVb metal, such as titanium, is located in the upper wall 22 of the chamber 12, the target 21 occurring in one of two forms: (1) a generally rectangular block of material to be deposited bonded to the cathode or (2) a generally rectangular ring formed of four blocks of material clamped to the cathode, which is sold under the trademark Inset. A substantially rectangular ring of tubing 23 having a plurality of openings therein directed downwardly and inwardly for a purpose to be later described is positioned encompassing the periphery of the target. A horizontally movable shutter plate 35 having an opening or shutter 36 is positioned below the target 21 to prevent any substantial scattering of material onto other parts of the chamber, thus directing the material onto the substrate below the shutter. The tubing ring 23 is connected to an inlet 24 in the upper wall for communication with a source 25 of a reactive gas, such as nitrogen. The gas source is connected to the inlet 24 through a mass flow meter 26, a control valve 40 which passes a steady flow of the reactive gas in response to a signal from mass flow meter 26, and a pulsing valve 27, which has its on and off times regulated by a timer 43.
A source 28 of an inert gas, such as argon, communicates with an inlet 32 in the chamber end 18 through a mass flow meter 29 and a second control valve 31, which is governed by a control signal from mass flow meter 29. Also, an outlet 33 in the floor 34 of the chamber 12 is connected to a vacuum system for continuous evacuation of the chamber prior to and during etching and sputtering. A throttle 37, similar in form and operation to a metallic venetian blind structure, is positioned in outlet 33 and is regulated by throttle control valve 38.
Vacuum is continuously applied to chamber 12, and the vacuum system draws all air and other contaminants out of the chamber 12 through the outlet 33. To initiate the coating cycle, the elevator 13 is raised with a pallet 15 into the domed chamber 14 wherein a substrate 11 is loaded onto the pallet and the chamber 14 is sealed and vacuum applied. The elevator is lowered and the pallet with the substrate is transferred onto the carrier 16. The empty elevator is raised to seal the domed chamber 14 from main processing chamber 12. Valve 38 is then operated to close throttle 37. Argon gas is then admitted through the flow meter 29, control valve 31, and inlet 32 to the chamber 12 to backfill the chamber with a partial pressure of argon. The carrier 16 moves to the chamber end 18 and deposits the substrate on the etch platform 17. A potential is applied to the substrate and the argon gas ionizes, providing argon ions which bombard the substrate to clean the surface to be coated.
Once cleaned, the potential is interrupted and the carrier 16 returns to pick up the substrate and move it beneath the target 21. The shutter plate 35 is shifted to align the shutter 36 between the target and the substrate. Nitrogen gas is then admitted through inlet 24 and tubing ring 23, and a potential is applied over conductor 41 to the cathode 20, which is in contact with target 21, whereupon argon gas is ionized and the argon ions bombard the titanium target 21. The potential on conductor 41 is a negative 450 to 500 volts. A bias voltage of about minus 100 volts is applied via conductor 42 to the substrate. The titanium atoms pass through the shutter 36, and react with the nitrogen gas from the ring 23 to form titanium nitride on the cleaned substrate 11 and not on the target surface. Deposition may occur in two ways on the substrate. If the substrate is stationary beneath the shutter 36, the titanium nitride deposition will take the general outline of the shutter opening. In the alternative, the substrate may be moved or scanned under the target past the shutter to provide an even deposition of the titanium nitride on the entire surface of the substrate.
The pressure of the argon gas is manually adjusted to a substantially constant value of 8.0 millitorr, and the power supplied to the target is also adjusted to provide a substantially constant level. As seen in FIG. 2, for the pulsing rate of 0.2 second on and 0.2 second off, the optimum flow of the nitrogen gas will vary with the target power. Thus, at a target power of 5.0 kilowatts, the flow of nitrogen should be 25.4 standard cubic centimeters per minute. Toward the upper end of the scale, a target power of 11 kw requires a nitrogen flow of 53.0 sccm. If a different pulsing rate is utilized, another straight line relationship is established paralleling the line shown in the graph.
To achieve a rate of deposition of titanium nitride that is 90% to substantially 100% of the deposition rate of the pure metal, the nitrogen gas is pulsed at intervals of 0.2 to 0.5 second on and off. The flow of nitrogen through valve 40 was constant, and pulsing of valve 27--that is, setting of the on and off times--was controlled by timer 43, which includes a first control knob 43a to set the "on" time of valve 27 and a second control knob 43b to set the "off" time of this pulsing valve. If the nitrogen gas is admitted for a period of 0.2 second, it is generally shut off for the subsequent 0.2 second time period, but the on and off times need not be equal. This is a duty cycle of 50%, and best results were achieved with on and off times in the range of 0.2 to 0.5 second. Once the desired thickness of the titanium nitride has been achieved, the potential to the target is interrupted and the pallet 15, carrier 16 and substrate 11 are moved back to the elevator 13 so that the coated substrate can be removed through the domed chamber 14. Obviously, with proper entrance and exit chambers at the ends of the sputtering chamber to prevent contamination of the gas during deposition, the batch process enumerated above could be easily transformed into a continuous process for reactive sputtering of numerous substrates or workpieces in a line.
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A method of reactive sputtering of the nitride, oxide or carbide of titanium or similar materials onto a substrate from a target of the pure metal in a chamber utilizing an inert gas, such as argon, wherein the deposition rate of the metallic compound approaches substantially the deposition rate of the pure metal. A reactive gas is introduced into the chamber adjacent to the target at a constant flow and by a rapid pulsing wherein a valve is alternately opened and shut for very short time intervals.
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FIELD OF THE INVENTION
[0001] The invention relates generally to discrete resizing of power devices with parallel power combining structure for complementary metal-oxide-semiconductor (CMOS) radio frequency (RF) power amplifiers.
BACKGROUND OF THE INVENTION
[0002] In implementing fully integrated wireless transmitter systems, CMOS RF power amplifiers have been an important component block to handle RF signals carrying modulated data. To support high data-rate wireless transmission, the power amplifiers should be able to deliver very high output power to antennas while maintaining good power efficiency. Most importantly, the linearity of the power amplifiers must be good enough not to distort modulated data signals.
[0003] A power combining technique is a good means to generate high output power out of moderate output powers of individual power amplifiers. Because the required output power level for individual amplifiers can be lowered as the number of combined amplifiers increases, individual amplifiers can have more linearity margins. If the RF signal swing at the input node of transistor in the output power stage can be kept low, there will be less signal distortions by non-linear function of saturated output transistors. Discrete power controllability of multi-combined power amplifier is another advantage in terms of enhancing the power efficiency. In typical power amplifiers, overall efficiency, which is the ratio of transferred output power to DC power dissipation, drops radically as the output power level is lowered. If the number of functioning PAs is reduced by disabling part of active amplifying paths as the required output power level is lowered, overall power efficiency can be enhanced by saving DC power dissipation of the inactive PAs.
[0004] Conventional power combining techniques use multiple power transferring paths that are combined by output matching networks such as transformers. For discrete control of PA systems to improve efficiency at power back-offs, those conventional structures activate or inactivate individual power transferring paths by turning-off unnecessary PAs, so that inactive PAs are not contributing to the power combining at the output matching network (transformer in typical case). Because negative effects of idle PAs on output matching networks are negated in the conventional structures, the maximum available efficiency of the output matching networks cannot be acquired.
BRIEF SUMMARY OF INVENTION
[0005] According to an example embodiment of the invention, there may be a power amplifier system. The power amplifier system may include a plurality of unit power amplifiers in which their respective outputs are combined by a matching network. The output matching network may include variable or tunable parallel capacitors/capacitive elements and an inductively coupled transformer which may include a plurality of primary windings in parallel and a single secondary winding. Each power amplifier may have at least one output port that is connected to the output matching network to be combined to generate a system output.
[0006] According to an example embodiment of the invention, there may be a driver amplifier which delivers one or more input signals to a plurality of power amplifiers. An interstage matching network may be provided between the driver amplifier and the plurality of power amplifiers. Likewise, an input matching network may be provided at an input to the driver amplifier. The input and inter-stage matching networks can be used to maximize a signal gain at desired operating frequency and minimize return losses.
[0007] According to an example embodiment of the invention, there may be a power coupler and a power detector connected at the output port of the power amplifier system. The power coupler can samples the output power and the power detector determines levels of output power delivered by the power coupler. The power detector sends acquired information about the output power levels to a baseband modem chip/system that generates digital control signal based on the information provide by the power detector.
[0008] According to an example embodiment of the invention, there may be a mode controller that acquires multiple-bits digital control signal from the baseband modem system. The mode controller determines a required or desired operation mode of the power amplifier system via a bias controller and/or a switch controller.
[0009] According to an example embodiment of the invention, each unit power amplifier and driver amplifier may be divided into a plurality of sub-cells, where their functions are controlled by the bias/switch controllers. When required output power level varies according to transmission environment, the power coupler with the power detector at the output of the system delivers information about the power levels to the baseband modem chip/system. The multiple-bits digital control signals may be generated in the modem chip/system and provided to the mode controller, which selects the operation mode of the power amplifier system. Then, the mode controller can control the bias controller and/or the switch controller to activate or deactivate part of sub-driver-device cells and sub-power-device cells. During operation in a varying output power environment, all parallel amplifying paths still remain activated to transfer the RF signal because at least one sub-power-device cell in each power stage (power amplifying path) is in active mode, thereby fully participating or contributing to the power combining at the output transformer. Only respective part of sub-cells in each amplifying paths are simultaneously turned-off at power back-offs. By not having inactive or idle power amplifiers/power amplifying paths at the input ports of output transformer, which provides concurrent power combining, the maximum available power efficiency of the transformer can be acquired without any penalty in the performance of entire power amplifier system.
[0010] According to an example embodiment of the invention, there may be various combinations of sub-driver-device cells and sub-power-device cells, which enables continuous enhancement in efficiency at low power levels. Driving and power capability of the driver amplifier and the power amplifiers may be pre-determined by look-up table data in the mode controller, and the controller may find out the optimal device size combinations between the driver amplifier and the power amplifiers. The mode controller can operate the bias controller so that it may generate different gate bias voltages to the driver and the power amplifiers to acquire the best efficiency performance in situations of varying sub-driver-device cell and sub-power-device cell combinations. The switch controller can turn on or off sub-driver-device cells and sub-power-device cells selected by the mode controller.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Having thus described the invention in general terms, reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and wherein:
[0012] FIG. 1 illustrates an example block diagram of a power amplifier system, according to an example embodiment of the invention.
[0013] FIG. 2 illustrates an example circuit diagram of a driver amplifier and unit power amplifier describing the circuit has multiple amplifying paths which have cascode structure, according to an example embodiment of the invention.
[0014] FIG. 3A illustrates an example circuit diagram of a driver amplifier and unit power amplifier including effective total input and output capacitances, according to an example embodiment of the invention.
[0015] FIG. 3B illustrates an example circuit diagram of a driver amplifier and unit power amplifier including effective total input and output capacitances, where dotted lines are used to represent devices that are not participating in the signal amplification, according to an example embodiment of the invention.
[0016] FIG. 4 illustrates an example block diagram of concurrent combining power amplifier system using a transformer with two primary windings and one secondary winding, according to an example embodiment of the invention.
[0017] FIG. 5A illustrates an example graph of discrete switch control of sub-driver-device cells and sub-power-device cells in each amplifying path as the output power increases in accordance with an example embodiment of the invention.
[0018] FIG. 5B illustrates a graph of discrete bias control voltage versus output power in accordance with an example embodiment of the invention.
[0019] FIG. 6 illustrates example measured results for the discrete power control of an example concurrent combining power amplifier system utilizing bias control and switch control in accordance with an example embodiment of the invention
[0020] FIG. 7 illustrates example measure results for the discrete power control of an example concurrent combining power amplifier system utilizing bias control and switch control in an application of IEEE 802.11g protocol in accordance with an example embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0021] Example embodiments of the invention now will be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the invention are shown. Indeed, these inventions may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout.
[0022] Example embodiments of the invention may be directed to power amplifiers with discrete power control and concurrent power combining. In an example embodiment of the invention, each of individual power amplifiers and a driver amplifier may be comprised of multiple unit sub-device cells to support active device resizing. Indeed, instead of turning off whole power amplifier branches for discrete power control, only some part or portion of sub-power-device cells in all power amplifier branches may be turned off to save or minimize DC power dissipation or consumption. Concurrent power combining in parallel power amplifier paths may be achieved at the multi-primary transformer without having inactive power amplifier branches. The power amplifiers and their methods may prevent unnecessary energy waste in the discrete power controlled power amplifiers systems, according to an example embodiment of the invention.
[0023] FIG. 1 illustrates an example block diagram of a power amplifier system 100 in accordance with an example embodiment of the invention. The power amplifier system 100 may include an input matching network 101 , a driver amplifier 102 , an interstage matching network 103 , unit power amplifiers 104 and 105 , an output matching network 106 , a mode controller 107 , bias controller 108 , a switch controller 109 . a power coupler 114 , and a power detector 115 . The driver amplifier 102 may include multiple sub-driver-device cells (DA_ 1 to DA_k) that can be individually and/or respectively controlled (e.g., switched ON or OFF) by the switch controller 109 . Similarly, unit power amplifiers 104 and 105 may also include respective multiple sub-power-device cells (PA_ 1 to PA_k) that can be individually and/or respectively controlled (e.g., switched ON or OFF) by switch controller 109 . In the output matching network 106 , a variable capacitor block 110 may perform tuning for optimal matching points at different power modes with different power-device cell sizes, according to an example embodiment of the invention. The output transformer 111 may have two or more primary windings 112 that receive respective outputs of the respective two or more power amplifiers 104 , 105 . The two or more primary windings 112 may be inductively coupled with a secondary winding 113 . At least one of the two output ports at the secondary winding 113 may connect to or provide the system output of the entire system, which may be sampled by the power coupler 114 . The power coupler 114 may be serially connected to a power detector 115 . The power detector 115 may provide information regarding the output power levels to a baseband modem chip/system, which generates a digital control signal based on the information given by the power detector. As will be described in further detail herein, the digital control signal from the baseband modem chip/system can be provided to a mode controller 107 , which operates a bias controller 108 and/or switch controller 109 in accordance with a required or desired mode of operation of the power amplifier system.
[0024] With continued reference to FIG. 1 , a respective bias control port and/or a respective switch control port of the unit driver amplifier 102 and the unit power amplifiers 104 , 105 may be respectively controlled by a bias controller 108 and a switch controller 109 . As described herein, the power detector 115 may sample output power through the power coupler 114 and provide the sampled information for the output power level to the baseband modem chip/system. The baseband modem chip/system may perform digital signal processing to generate a digital control signal for delivery to the mode controller 107 , which controls the bias controller 108 and the switch controller 109 in accordance with the digital control signal. When the input or detected power level is lowered due to varying transmission environment, the mode controller 107 may let the switch controller 109 select one or more parts of the sub-driver-device cells (of unit driver amplifier 102 ) and/or sub-power-device cells (of unit power amplifiers 104 , 105 ) to de-activate.
[0025] For example, in the case that the maximum output power level is required, all sub-driver-device cells (DA_ 1 to DA_k) and sub-power-device cells (PA_ 1 to PA_k) may be fully activated/functioning, and two parallel power amplifier branches are provided to the respective primary windings 112 and combined at secondary winding 113 that serves as the output of transformer 111 . If some reduction of output power is needed, the switch controller 109 may deactivate one or more of sub-power-device cells in each unit power amplifier 104 , 105 concurrently, according to an example embodiment of the invention. Therefore, the two parallel power amplifier branches may include same or similar number of activated/functioning sub-power-device cells (PA_ 1 to PA_k−1) during operation. However, it will be appreciated that such symmetry in the number of activated/functioning sub-power device cells (PA_ 1 to PA_k−1) may not necessarily be required, according to an example embodiment of the invention.
[0026] The switch controller 109 may also deactivate one or more sub-driver-device cells in the driver amplifier 102 to further save DC supply current, which means that a combination of activated ones of sub-driver-device cells DA_ 1 to DA_k−1 may drive the RF signal to the power amplifiers 104 and 105 . For the minimum output power level, only sub-driver-device cell DA_ 1 (of driver amplifier 102 ) and PA_ 1 s in two parallel paths (of power amplifiers 104 , 105 ) may be active in the power amplifier system 100 , according to an example embodiment of the invention.
[0027] Because all power amplifier branches (corresponding to two or more power amplifiers 104 , 105 ) to the output matching network 106 are always functioning while having capability of discrete cell resizing, this type of combining may be illustratively referred to as “concurrent power combining” using multi-primary parallel combining transformer, according to an example embodiment of the invention. The bias controller 108 may acquire, via the mode controller 107 , information regarding the detected power level and apply increasing bias voltage to the driver amplifier 102 and each of the unit power amplifiers 104 and 105 as the input/output power level increases. With discrete cell resizing for discrete power control along with an adaptive biasing technique, the power efficiency at power back-offs can be enhanced significantly by saving DC power consumption.
[0028] In another example embodiment of the invention, there may be numerous different combinations between sub-driver-device cells and sub-power-device cells in two parallel power amplifier paths. Moreover, each sub-driver-device cell and sub-power-device cell may have different device size (gate width). For example, sub-driver-device cells of drive amplifier 102 and sub-power-device cells of power amplifiers 104 , 105 may have binary weighted device sizes such as the device size ratio of 1:2:4:8: . . . 2 k and so forth. Therefore, various combinations between sub-driver-device cells and sub-power-device cells can be flexibly achieved, generating relatively continuous output power levels, according to an example embodiment of the invention.
[0029] FIG. 2 illustrates detailed circuit diagram of a unit amplifier 200 , according to an example embodiment of the invention. The unit amplifier 200 may be an example implementation of the unit driver amplifier 102 or unit power amplifier 104 , 105 of FIG. 1 , according to an example embodiment of the invention. In FIG. 2 , the unit amplifier 200 may include multiple parallel signal amplifying paths (e.g., path_ 1 to path_k) feeding or connected to the output port of the unit amplifier 200 . Each signal amplifying path may correspond to respective a sub-device cell, and is implemented by respective transistors, including field effect transistors (FETs) such as N-channel metal-oxide-semiconductor FETs (MOSFETs), although other transistors such as bipolar junction transistors (BJTs) may be used in a same configuration. As shown in FIG. 2 , each individual signal amplifying path corresponding to respective sub-device cell may include two transistors—a gain transistor (e.g., 201 , 204 , 207 ) and a switch transistor (e.g., 202 , 205 , 208 )—in a stacked configuration. More specifically, the respective drain nodes of gain transistors 201 , 204 , 207 may be connected to the respective source nodes of switch transistors 202 , 205 , 208 . The input (gate) nodes of all gain transistors 201 , 204 207 may be tied together and connected to the signal input port. The input nodes may also be connected to the external bias controller 212 through a high-value resistor 211 that blocks RF signal leakage to the bias controller 212 . The source nodes of the gain transistors 201 , 204 , 207 may be tied together and connected to ground.
[0030] The switch transistors 202 , 205 and 208 may have respective gate nodes connected to the external switch controller 213 through high-value resistors 203 , 206 and 209 . The output (drain) nodes of all amplifying paths may be tied together and connected to DC supply (VDD) through a choke inductor 210 . The switch controller 213 may apply the appropriate DC voltage to the gate nodes of the switch transistors 202 , 205 , 208 to either activate or deactivate the respective transistors, and thus, the corresponding sub-device cell, according to an example embodiment of the invention. If the switch controller 213 turns off one of switch transistors 202 , 205 , 208 by applying zero or minimal DC voltage to the gate node of the respective transistor, the signal amplifying path that includes the deactivated switch transistor will be disabled and stop amplifying the received RF signal. The device size of gain/switch transistors in all amplifying paths may be binary weighted. The gate widths of gain/switch transistors may be doubled as the path number increases (e.g., device size ratio of 1:2:4:8 in case that there are four signal amplifying paths), according to an example embodiment of the invention.
[0031] It will be appreciated that in FIG. 2 , the activation or deactivation of the parallel sub-device cells in the respective amplifying paths can be used to increase or decrease a gain between the input port and the output port. In general, the activation of a sub-device cell may result in the respective amplifying path contributing to or increasing a gain, while a deactivation of a sub-device cell may result in a respective amplifying path not contributing to or reducing the gain, according to an example embodiment of the invention.
[0032] FIG. 3A illustrates an example circuit diagram of a driver amplifier and unit power amplifier including effective total input and output capacitances, according to an example embodiment of the invention. The unit amplifier 300 may be a detailed implementation of the unit amplifier 200 discussed with respect to FIG. 2 .
[0033] As shown in FIG. 3A , all of the amplifying cascode paths may be active, according to an example embodiment of the invention. Each amplifying path provided by unit sub-device cells 301 , 302 , 303 may include respective total parasitic input capacitances 306 , 311 , 316 at the respective input (gate) nodes of gain transistors 304 , 309 , 314 . Each unit sub-device cell 301 , 302 , 303 may also include total parasitic output capacitance 307 , 312 , 317 at the respective output (drain) nodes of switch transistors 305 , 310 , 315 . The total input parasitic capacitance may be a composite of a gate-to-source capacitance (C GS ) and a gate-to-drain capacitance (C GD ) after Miller effect accounted for gain transistors 304 , 309 , 314 . The total output parasitic capacitance may be a composite of a drain-to-body junction capacitance (C DB ) and a gate-to-drain capacitance (C GD ) for the switch transistors 305 , 310 , 315 .
[0034] FIG. 3B illustrates an example circuit diagram of a driver amplifier and unit power amplifier including effective total input and output capacitances, according to an example embodiment of the invention. In FIG. 3B , some part of the amplifying cascode paths are disabled for reduction of output power, according to an example embodiment of the invention. Indeed, in FIG. 3B , only one unit sub-device cell 320 (unit amplifying path) is activated while other sub-device cells 321 , 322 are disabled by an external switch controller (e.g., switch controller 109 ).
[0035] The switch transistors 323 , 324 in disabled amplifying paths are turned-off by zero or minimal DC voltages applied to the gates by the switch controller and are denoted by dashed lines. The amplifying paths that include disabled switch transistors 323 , 324 cannot function, and only one unit sub-device cell 320 (i.e., sub-cell_ 1 ) is contributing to the signal amplification provided in the output. However, because the gain transistors are tied at the gates each other, they are always in saturation region as long as adequate gate bias voltages are supported by an external bias controller. Therefore, effective input impedance including resistive component and reactive component mainly determined by total input capacitance may remain constant as the number of active amplifying paths varies. On the other hand, the effective output impedance may vary as the number of active amplifying paths varies because total parasitic capacitance at the drain nodes of the switch transistors 305 , 310 , 315 may vary when they switch their operational mode between linear and saturation region. Therefore, to compensate for varying output impedance, the power amplifier system as shown in FIG. 1 may utilize variable capacitive components such as variable capacitor blocks 110 in the output matching network 106 .
[0036] FIG. 4 illustrates an example of a power amplifier system 400 in accordance with an embodiment of the invention. In FIG. 4 , each of the power amplifiers 404 , 405 in respective combining paths have multiple sub-power-device cells. The driver amplifier 403 may also includes multiple sub-driver-device cells. The power amplifier system 400 may also include an input matching network 401 , an interstage matching network 403 , and combining transformer 406 at the output. The combining transformer 406 may include two primary windings coupled to respective outputs from the power amplifiers 404 , 405 . The two primary windings may be inductively coupled to a secondary winding of the transformer 406 .
[0037] According to an example embodiment of the invention, the driver amplifier 402 and the power amplifiers 404 , 405 may be implemented in differential structure each having two respective input ports and two respective output ports. The sub-divided driver amplifier 402 and power amplifiers 404 , 405 can be discretely controlled for some of sub-cells to be activated/deactivated for generating varying output power levels. In an example embodiment of the invention, this structure does not have any inactive combining path (or amplifying path) at the power back-off region. Therefore, maximum power efficiency of the output transformer can be utilized while implementing discrete cell resizing and power control.
[0038] FIG. 5A illustrates an output of the switch controller (e.g., switch controller 109 ), which represents possible example combinations between sub-driver-device cells and sub-power-device cells as output power level increases. As the arrow indicates in FIG. 5A , sub-driver-device cell DA_ 1 and sub-power-device cells PA_ 1 s are active at the minimum output power level, and other sub-driver-device cells and sub-power-device cells will be sequentially enabled as the output power level increases. For the maximum output power generation, all sub-driver-device cells and all sub-power-device cells are contributing to the power transfer. It will be appreciated that the switch controller may utilize a look-up table to determine which combinations of sub-driver-device cells and sub-power-device cells to activate, responsive to a detected input power level, to obtain a desired output power, according to an example embodiment of the invention.
[0039] FIG. 5B illustrates an output of the bias controller (e.g., bias controller 108 ). The gain transistors of driver amplifier and unit power amplifiers may be initially biased at class-AB close to class-B (which is known to use small bias current and have high efficiency but with low linearity). As the output power increases, the output of the bias controller increases and the class of the driver and power amplifier is shifted to class-AB close to class-A (which is known to use large bias current and have low efficiency but with high linearity). In an example embodiment of the invention, there are three sub-driver-device cells and three sub-power-device cells in unit driver and power amplifiers. When only sub-driver-device cell DA_ 1 and sub-power-device cells PA_ 1 s are activated, the bias voltage is at V BIAS — 1 (e.g., 0.55 V). When sub-driver-device cells DA_ 1 , DA_ 2 with sub-power-device cells PA_ 1 s , PA_ 2 s are activated, the bias voltage is at higher voltage of V BIAS — 2 (e.g., 0.6 V). When sub-driver-device cells DA_ 1 , DA_ 2 , DA_ 3 with sub-power-device cells PA_ 1 s , PA_ 2 s and PA_ 3 s are activated, the bias voltage is at a yet higher voltage of V V BIAS — 3 (e.g., 0.65 V). It will be appreciated that the example voltage values have been described herein for illustrative purposes only. Indeed, other values may be utilized without departing from example embodiments of the invention.
[0040] FIG. 6 illustrates a graph of measured results for the discrete power control of an example power amplifier system utilizing concurrent power combining with bias control in accordance with an example embodiment of the invention. The graph includes measured efficiency and gain versus output power of the power amplifier system. High power (HP) mode represents the case that all sub-driver-device cells and sub-power-device cells in two parallel combining paths are activated. Medium power (MP) mode represents the case that only two sub-driver-device cells and two sub-power-device cells in each parallel combining path are activated. Low power (LP) mode represents the case that only one (smallest) sub-driver-device cell and one sub-power-device cell in each combining path are activated. As shown in FIG. 6 , power back-offs of 6 dB and 12 dB were achieved by discrete power control. The efficiency increases as the number of unit sub-cells in the driver and power amplifiers gets smaller, which is effectively implementing discrete power control. In accordance with the concurrent power combining technique as an embodiment of this invention, the efficiency at low power regions were significantly improved compared to a conventional structure.
[0041] FIG. 7 illustrates measured results for the discrete power control with concurrent power combining utilizing bias control in an application of IEEE 802.11g protocol in accordance with an example embodiment of the invention. To evaluate the linearity performance of the power amplifier system, WLAN (wireless local area network)802.11g 54-Mbps 64-QAM (quadrature amplitude modulation) OFDM (orthogonal frequency division multiplexing) (EVM limit<−25 dB) signals are applied. The EVM and DC current results are presented in FIG. 7 .
[0042] Many modifications and other embodiments of the inventions set forth herein will come to mind to one skilled in the art to which these inventions pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the inventions are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.
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Systems and methods are provided for discrete resizing of power devices. The systems and methods can include a plurality of unit power amplifiers arranged in parallel, where each unit power amplifier includes at least one first input port, at least one first output port, and a plurality of sub-power-device cells configured in parallel between the at least one first input port and the at least one first output port; a switch controller, where the controller is operative to activate or deactivate at least one of the plurality of sub-power-device cells of a respective unit power amplifier; and an output matching network, where the matching network is configured to combine respective outputs from the respective plurality of unit power amplifiers to generate a system output, wherein during an operational state, all of the plurality of unit power amplifiers contribute outputs to the matching network to generate the system output.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of the U.S. patent application Ser. No. 12/827,977 filed on Jun. 30, 2010, entitled Data Center Inventory Management Using Smart Racks. While the priority date is not based thereon, this application is related to U.S. application Ser. No. 12/718,388, filed on Mar. 5, 2010, entitled “Managing a Datacenter Using Mobile Devices”, which is being incorporated herein by reference.
BACKGROUND
Data Centers
With the explosive growth in the use of computers to host business applications, Internet Websites, etc., a need to build bigger data centers to house computers and related hardware has also grown exponentially. Many data centers (also known as “server farms”) these days typically house thousands of computers and related equipments such as networking gears, etc.
A data center or a server farm is a facility to house a number of computer systems and related equipment. For example, a business organization may house all or some of their computer servers (i.e., hosts) at one physical location in order to manage these computer servers efficiently. The computer servers in a data center are typically connected to users of the computer servers via the Internet or Wide Area Network (WAN) or Local Area Network (LAN) or any other similar type of medium. These computer servers are typically used to host critical business applications. Since the business operations of these business organizations critically depend on the continuous availability of the computer servers, special attention is paid to manage data centers to prevent or minimize server down times. Inventory management of the computing resources in a data center plays a critical role in ensuring high availability of computing resources. Unfortunately, at present, data center inventory is maintained manually, typically using spreadsheets or similar manual methods. This method of tracking inventory of computing resources is highly inefficient, especially for large size data centers.
Data Center Racks
Computer systems and other related components (e.g., network switches, routers, etc.) in a data center are housed in metallic cages, typically called racks. Racks are typically designed to maximize physical space utilization in a data center room. A rack may include a number of chassis. Chassis are used to house computer systems. In some cases, a rack may house non-blade computer system directly without a use of a chassis. Chassis are typically designed to maximize physical space utilization in a rack. Computer systems and other components are typically mechanically designed to maximize space utilization in a chassis. One of these mechanical designs of computer systems is referred to as a blade. A rack typically has wire harnesses for network (and power) cables that connect each blade to the computer network. Blades are typically designed to easily slide into chassis slots. Once a blade is physically put in place in a chassis, typically, the blade automatically connects to the network and power adapters in the rack.
Radio Frequency Identification (RFID)
One of the applications of RFID technology is to track moveable objects. A typical RFID system includes a RFID tag and a RFID reader. A RFID tag is typically very small and can be produced in sizes and shapes to be easily adoptable to the objects to be tracked. A RFID tag typically includes a miniature electronic circuit and a miniature antenna. The electronic circuit generates radio frequency waves that are transmitted by the antenna. The range of such transmission is typically configurable and may vary from a few centimeters to several meters. The transmission range is configured to a particular range to fit to a particular type of object tracking application. A RFID reader is configured to receive the signals transmitted by RFID tags. One or more RFID readers are typically connected to a computer system, which is configured to read and decipher the signals transmitted by RFID tags. The signals may include some configurable information about the object to which a RFID tag is attached. The information transmitted by a RFID tag generally includes unique identification information about the RFID tag or the object being tracked.
RFID tags are typically of two types, active tags and passive tags. An active tag generally includes a built-in source of power and this type of tag may transmit signals to relatively greater distances. A passive tag, on the other hand, does not include its own built-in source of power and hence requires an external source to activate a signal transmission. Typically, a RFID reader sends signals to a passive RFID tag to activate the RFID tag.
Virtualization
The computing industry has seen many advances in recent years, and such advances have produced a multitude of products and services. Computing systems have also seen many changes, including their virtualization. Virtualization of computer resources generally connotes the abstraction of computer hardware, which essentially separates operating systems and applications from direct correlation to specific hardware. Hardware is therefore abstracted to enable multiple operating systems and applications to access parts of the hardware, defining a seamless virtual machine. The result of virtualization is that hardware is more efficiently utilized and leveraged.
The advent of virtualization has sparked a number of technologies, which allow companies to optimize the utilization of their systems. As a company's enterprise systems are usually installed at various geographic locations in different data centers, networking protocols are used to interconnect the various systems, which can then be virtualized into one or more virtual servers.
With the recent proliferation of virtual systems and servers, proper deployment and inventory management practices have become increasingly important. Even though virtual machines can be tracked using presently available tools and systems, there are no automated solutions available to track the physical locations of the physical hosts that host a particular virtual machine. Having such tracking information is important to quickly locate a malfunctioning physical server which is hosting a critical virtual machine. Manual methods of inventory control would fail to track such a physical server because virtual machines are moveable from one physical server to another and may move from one physical server to another at any time based on occurrence of some events. Some of these details are beyond the subject matter of the present disclosure, hence being omitted.
SUMMARY
In one embodiment, a user interface (UI) to depict and control a plurality of smart racks in a data center is disclosed. The depiction is at a display, such as a computer monitor. The UI includes a first graphical display to depict the plurality of smart racks in the data center. The depiction in the first graphical display mimics a physical arrangement of the plurality of smart racks in the data center. The first graphical display may include visual indicators to depict error and warning conditions in the plurality of smart racks.
The UI further includes a second graphical display to depict a plurality of blade hosts in a smart rack in the plurality of smart racks. The depiction in the second graphical display mimics a physical arrangement of the plurality of blade hosts. The second graphical display may include visual indicators to depict error and warning conditions in the plurality of blade hosts.
The UI also includes a third graphical display to display blade information about a blade host in the plurality of blade hosts. The blade information may include at least one of system information, a list of virtual machines hosted on the blade host, and physical location of the blade host in the data center. The physical location may include smart rack identification, chassis identification, and slot identification in which the blade host resides.
BRIEF DESCRIPTION OF THE DRAWINGS
So that the manner in which the above recited features of the present invention can be understood in detail, a more particular description of the invention, briefly summarized above, may be had by reference to embodiments, some of which are illustrated in the appended drawings. 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. The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which:
FIG. 1 illustrates a logical diagram of a data center management system in accordance with one or more embodiments of the present invention.
FIG. 2 illustrates a schematic diagram of a data center rack in accordance with one or more embodiments of the present invention.
FIG. 3 illustrates a schematic diagram of a data center rack chassis in accordance with one or more embodiments of the present invention.
FIG. 4 illustrates a logical diagram of a rack controller in accordance with one or more embodiments of the present invention.
FIG. 5 illustrates a logical diagram of sensors and readers interconnections with a rack controller in accordance with one or more embodiments the present invention.
FIG. 6 illustrates an exemplary graphical user interface showing racks in a data center in accordance with one or more embodiments of the present invention.
FIG. 7 illustrates a flow diagram for preparing a rack for maintenance or power shutdown in accordance with one or more embodiments of the present invention.
DETAILED DESCRIPTION
FIG. 1 illustrates a logical diagram of a data center management system 100 . Various parts of Data Center Management System 100 may be interconnected through a Local Area Network (LAN) or a Wide Area Network (WAN) or the Internet. Hence, Network 120 may be a LAN, a WAN or the Internet. The underlying connection may be either wired or wireless (e.g., WiFi or such). It should be noted that even though some of the parts of Data Center Management System 100 are shown as a box, these parts may themselves be spread across several physical or virtual systems and may include associated parts (e.g., databases, network switches, etc.). These parts are not being shown and described to avoid obscuring the present disclosure.
Data Center Management System 100 includes a Resource Management System 102 . Resource Management System 102 manages computing resources of a data center. In one example, Resource Management System 102 (e.g., VMware vSphere®) enables configuration and management of the computing infrastructure of a data center. In one or more embodiments, Resource Management System 102 may include a user interface to allow easy navigation for computing resources in a data center. Resource Management System 102 may also provide search functionality to perform lookups for virtual machines, hosts, datastores, and networks in a data center. Resource Management System 102 may also include alarms to indicate hardware failures of key components such as fans, system board and power supply. Resource Management System 102 may also provide management of data storages, including reporting storage usage, connectivity and configuration. Resource Management System 102 may also include monitoring virtual machines, resource pools and server utilization and availability.
In one or more embodiments, Resource Management System 102 may also include support for profile based configuration and management of virtualization system configurations and management. Resource Management System 102 may also be configured to provide power management functionality across the data center computer resources. Through the power management functionality, Resource Management System 102 may reduce power consumption by putting hosts in standby mode when the demand for the computing resources is lower than available online computing resources. Resource Management System 102 may also provide functionality for automatically updating or patching software on data center hosts and virtual machines.
In one or more embodiments, Resource Management System 102 may also be configured to provide physical to virtual (P2V) machine conversion functionality. For example, if a host is added to the data center that is being managed by Resource Management System 102 , the host may be automatically virtualized through automatic installation of virtualization software on the host. In one or more embodiments, Resource Management System 102 maintains preconfigured virtualization software images for different types of host hardware configurations and for different types of usages. For example, one image may include a preconfigured email server, another image may include a preconfigured Web server, etc. The pre-configurations are done to adapt to the properties of the data center and the business organization that would ultimately use the newly virtualized host. For example, the pre-configured properties may include specific server names and resource addresses.
In one or more embodiments, Resource Management System 102 may provide automatic discovery of hosts such that when a host is added to the data center, the newly added host is automatically added to the list of resources being managed by Resource Management System 102 . A data center may have one or more instances of Resource Management System 102 , all working cooperatively to provide a highly scalable system that may be capable of managing thousands of hosts and tens of thousands of virtual machines in a data center.
Resource Management System 102 , in one or more embodiments, may also provide resource management for virtual machines to allocate processor and memory resources to virtual machines running on the same physical servers and to establish minimum, maximum, and proportional resource shares for CPU, memory, disk and network bandwidth. Resource Management System 102 may also modify these allocations while virtual machines are running and may enable applications to dynamically acquire more resources to accommodate peak performance. Resource Management System 102 is also capable of effectuating moving of virtual machines from one host to another when needs arise (such as failovers, power management, etc.) or on occurrences of some pre-selected events in the data center.
Resource Management System 102 , in one or more embodiments, exposes programming and communication interfaces to enable exchange of data to and from other parts of Data Center Management System 100 (e.g., Inventory Management System 110 ).
Data Center Management System 100 includes an inventory management system 110 . Inventory Management System 100 is coupled to a data store 112 to store inventory data, including physical locations of various computing resources in a data center. Data Center Management System 100 further includes one or more smart racks 150 that are in communication with Resource Management System 102 and Inventory Management System 110 through Network 120 . Inventory Management System 110 is configured to store physical locations of Racks 150 in a data center. The physical locations of Racks 150 may be stored by isle and sequence numbers or by any other addressing mode that is capable of providing identifiable physical locations of racks in a data center. For example, reference coordinates with respect to one corner of a data center room may be used for location identification of a particular rack. In another example, a matrix addressing (row x, column y) may also be used if Racks 150 are placed in a substantial rectangular arrangement in a data center room. As it is explained later in this document, a rack is mechanically configured to receive a plurality of chassis and each chassis may have provisions to provide storage for a plurality of blades. Inventory Management System 110 also stores physical locations of each chassis and each blade slot. Hence, a particular blade slot may be addressed by the combination of a rack location identifier, a chassis number and a blade space number.
FIG. 2 illustrates a rack 150 in one embodiment. Rack 150 can be substantially rectangular in shape. However, a person skilled in the art would appreciate that other mechanical shapes are within the scope of this disclosure. Rack 150 may be made of a sturdy material, such as metal, wood, alloy or polymer plastics (or any other man made materials) so long as the material is capable of providing a sturdy cage to hold heavy payload. The dimensions of Rack 150 may depend upon the configuration of the space within a data center room in which Rack 150 would be housed. The outer physical shape of a rack typically allows stacking up a plurality of racks side by side. The space inside Rack 150 , in one embodiment, is designed to maximize natural air flow cooling. However, Rack 150 may also be configured with one or more fans to route heat out of Rack 150 effectively. Rack 150 may also include temperature, humidity and/or other types of sensors. These sensors may be configured to be in communication with Rack Controller 170 (to be described later) and data collected through one or more of these sensors may be stored in Inventory Management System 110 along with other data related to a particular rack. In another embodiment, this data may also be stored locally in Rack Controller 170 .
Rack 150 includes a plurality of RFID adapters 160 to receive sensor hubs of chassis (shown in FIG. 3 ). Each RFID adapter 160 includes a mechanical socket to easily receive a counterpart socket that is attached to a sensor hub in a chassis. Rack 150 may have guide rails to enable chassis to slide easily into a chassis slot. Guide rails, RFID adapter sockets and sensor hub sockets are so aligned that when a chassis slides in a chassis slot, the sensor hub of the chassis comes in mechanical and electrical contact with the corresponding RFID adapter in the rack.
In one embodiment, Rack 150 further includes a rack controller 170 . Wire harnesses that connect various sensors, sensor hubs and RFID adapters terminate in Rack Controller 170 . Rack Controller 170 is coupled to Inventory Management System 110 through Network Interface 180 , which is an interface to couple Rack Controller with Network 120 . Rack Controller 170 , in one embodiment, includes a programming logic to read and collect data from various sensors and store the data, at least temporarily, prior to transmitting the collected data to Inventory Management System 110 . In other embodiments, Inventory Management System 110 triggers the process of data collection. That is, at least a part of the programming logic to read and collect data from sensors resides in Inventory Management System 110 . Rack Controller 170 further includes a power interface 190 to provide power to Rack Controller 170 and various adapters and sensors in Rack 150 . In one embodiment, Power Interface 190 is also configured to provide electrical power to hosts in Rack 150 through a power wire harness. In another embodiment, a separate power harness is provided to power hosts and other computing resources in Rack 150 . In such embodiment, Rack Controller 170 may monitor the status of the power supply for reporting purposes.
In one embodiment, Rack 150 includes a Display Unit 172 to display messages from Inventory Management System 110 and/or Resource Management System 102 . Display Unit 172 may also be configured to provide a user interface to Rack Controller 170 , hence enabling a designated user (i.e., a user who is authorized to manage a data center) to interact with Rack Controller 172 for the purposes of configuring, programming, testing, or debugging Rack Controller 170 and sensors. Display Unit 172 may be a liquid crystal display (LCD) or any similar type of display that is capable of displaying textual and/or graphical data and to receive inputs from a designated user. In another embodiment, Display Unit 172 may include one or more lighting devices to provide visual messages using predefined patterns or color coding for communicating predefined sets of messages. For example, a red light signal may indicate an error condition somewhere in Rack 150 . A yellow light may indicate a warning, etc. In one example, these lights may be appropriately placed on the racks in a data center room so that when the designated user walks into the data center room, he/she may readily spot racks with error conditions. The designated user may use an admin console of Inventory Management System 110 to get more information about the error condition. Moreover, Display Unit 172 may also be used to get details of an error or warning conditions. Inventory Management System may be configured to send notifications via email, text messaging, etc. to a pre-configured group of people when error conditions arise in a rack. In another embodiment, a similar display unit may be provided at each chassis.
Referring now to FIG. 3 , which illustrates an exemplary schematic diagram of a chassis 200 . As mentioned earlier, Chassis 200 provides housing for one or more blades. As explained briefly earlier, a blade is a common term used for a special mechanical design for a computer system or any other electronic component such as a network switch. The blade design is suitable for quickly inserting or removing computing resources to or from a network and to provide optimal space utilization in a rack. The term “blade server” is well known in the art, hence a detailed description is being omitted to avoid obscuring the present disclosure. Chassis 200 includes one or more slots for sliding blades into Chassis 200 . Each slot has electro-mechanical connectors to electrically and mechanically couple an inserted blade with Network 120 and the power supply. Storage Area Storage (SAN) interfaces may also be provided in each slot on Chassis. Each slot may be provided with a RFID sensor (i.e., a RFID reader) 220 , which is capable of reading a RFID tag. Each inserted blade, if the inserted blade needs to be monitored by Rack Controller 170 , is provided with a RFID tag. Chassis 200 also includes a sensor hub 210 to aggregate input wiring from RFID Sensors 220 . Sensor Hub 210 may be a USB hub, in one embodiment. In other embodiments, Sensor Hub can be any multi conductor polarized connector. Sensor Hub 210 is configured to electrically and mechanically couple RFID sensors with the corresponding RFID Adapter 160 in Rack 150 when Chassis 200 is incorporated in Rack 150 . In one embodiment, a computing resource (e.g., a computer system) may be directly incorporated in Rack 150 without Chassis 200 . In such embodiment, the mechanical shape of the computing resource is similar to Chassis 200 . Chassis 200 may also include temperature, humidity and/or other types of sensors. These sensors may be configured to be in communication with Rack Controller 170 and data collected through one or more of these sensors may be stored in Inventory Management System 110 .
It should be noted that existing conventional racks may be retrofitted with above mentioned electro-mechanical hardware (e.g., various sensors, hubs, adapters, rack controller, etc.) to convert existing conventional racks into Rack 150 .
In one embodiment, security features may also be incorporated in Rack 150 and/or Chassis 200 . For example, a security pad may be installed on each Rack 150 . The security pad may be coupled to an electronic security system and may be used to identify and authenticate a person, who attempts to remove Chassis 200 or a blade from Chassis 200 . The security pad may have a number pad, a fingerprint scanner or a security card scanner. Mechanical locks may be provided on removable parts of Rack 150 or Chassis 200 . These mechanical locks may be released only if a person attempting to remove or insert a component properly authenticate himself/herself. In one embodiment, Display Unit 172 may also be used as a security pad for entering authentication information.
It should be noted that the mechanical placement of various sensors, hubs, adapters, rack controller, etc. may change depending upon design considerations. As such, these components may be placed at any suitable locations in Rack 150 so long as the functionality remains within the scope of the present disclosure.
It should also be noted that in some embodiments, other technologies (e.g., Bluetooth, Bar codes, Open Computer Vision, Pattern Recognition, etc.) may also be used instead of RFID by using different types of sensors and devices that are suitable for a particular type of technology. For example, if the bar code technology is used, a blade will be affixed with a unique bar code while RFID sensors are replaced by bar code readers. In one embodiment, MAC addresses of computing resources may also be used instead of RFID. In such embodiment, a MAC address to Physical location mapping may be stored in Inventory Management System 110 .
FIG. 4 illustrates a logical block diagram of Rack Controller 170 . In one embodiment, Rack Controller 170 includes a microcontroller 197 to execute programming instructions for controlling Rack 150 sensors, for collecting data from sensors, and for storing the collected data in a local database 194 . Microcontroller 197 may also be used for enabling communication between components of Rack 150 with Inventory Management System 110 and for providing display logic for Display Unit 172 . Rack Controller 170 further includes a communication port 192 to enable communication between the sensors of Rack 150 and programming modules such as Polling Module 196 and Data Collector 198 . Microcontroller 197 may also be coupled to Network Interface 180 and Power Interface 190 . Microcontroller 197 may also provide an interface to configure Rack Controller 170 through additional programming instructions. Database 194 may be a solid state memory device or it can also be a magnetic disk memory. Database 194 may also be used for storing programming instructions to or from various modules of Rack Controller 170 . Display Unit 172 may be used for adding new programming instructions or configurations to Rack Controller 170 . Alternatively, new programming instructions and/or configurations may be pushed to Rack Controller 170 from or through Inventory Management System 110 .
FIG. 5 illustrates a schematic diagram of exemplary interconnections of RFID Sensors 220 , Sensor Hubs 210 , RFID Adapters 160 and Rack Controller 170 . In one embodiment, the interconnections are through a wire harness. In other embodiments, the interconnections may be implemented through wireless communication technologies such as Bluetooth or WiFi. In another embodiment, the interconnections may be provided through the LAN wiring that can couple RFID Sensors 220 , Sensor Hubs 210 and RFID Adapters 160 to Network 120 . In one embodiment, network communication to and from computing resources in Rack 150 continues to work unaffected when one or more RFID Sensors 220 , Sensor Hubs 210 , RFID Adapters 160 , or Rack Controller 170 malfunction. To avoid introducing an extra point of failure, the system and process of collecting and managing inventory data work separate from normal computing operations of computing resources in Rack 150 . Moreover, Rack Controller 170 may be equipped with programming logic to perform routine testing of RFID Sensors 220 , Sensor Hubs 210 and RFID Adapters 160 . The programming logic in Rack Controller 170 is also configured to collect inventory data and store at least a part of collected data locally for a period of time before the collected data is transmitted to Inventory Management System 110 . The locally stored data may be transmitted to Inventory Management System 110 at pre-configured regular intervals. Alternatively, the locally stored data may be pushed to Inventory Management System 110 when Inventory Management System 110 requests such information. In another embodiment, Inventory Management System 110 may retrieve the locally stored data directly from Rack Controller 170 database. Some information, for example when a blade is removed, may be transmitted to Inventory Management System 110 immediately or as early as possible. In one or more embodiments, Polling Module 196 performs polling of sensors in Rack 150 at regular intervals. In another embodiment, any other technique for reading RFID tags may be used so long as the technique is capable of detecting events such as removal of blades, insertion of blades, etc.
Referring back to Inventory Management System 110 of FIG. 1 . In one embodiment, a user interface may be provided to enable initial data entry with respect to unique identifications (IDs) of smart racks, chassis and sensors along with physical locations of these components in a data center. When a blade with an RFID tag is inserted in any slot in any smart rack, RFID sensor of that slot sends a signal to Rack Controller 170 (or in another embodiment, Rack Controller 170 may receive this information through the polling process). The inventory data in Inventory Management System 110 is automatically updated to reflect the addition of this new blade including a host name and a unique ID number. Resource Management System 102 is also automatically updated when a new blade is detected in a smart rack. In one embodiment, Resource Management System 102 may automatically install virtualization software on the newly added host and may also perform further configurations such as setting up one or more virtual machines on the newly added host and adding these virtual machines in a particular cluster or some other type of logical group of virtual machines.
FIG. 6 illustrates an exemplary graphical user interface (GUI) 250 for viewing data center racks on a display. In one embodiment, GUI 250 shows a graphical view of a data center room in which a plurality of racks are housed. GUI 250 substantially mimics the physical arrangement of the racks in a data center room. In one embodiment, GUI 250 display may be re-arranged to match the actual arrangement of racks in a data center room. The rearrangement may be accomplished by moving displayed graphical objects on the display in a desired arrangement and saving the new arrangement. In one exemplary embodiment, Inventory Management System 110 can be configured to retrieve locations of the plurality of racks in the data center room through rack location sensors in a data center room and may automatically generate a graphical depiction of racks. In one example, the WiFi triangulation method may also be used to determine locations of racks in a data center room.
The displayed object on GUI 250 may also be configured to display error conditions. In one exemplary embodiment, a color coding method may be used to visually display various operational and/or environmental conditions for each rack. In one exemplary embodiment, when a mouse pointer is brought over (or clicked, double clicked, etc.) a particular rack object in GUI 250 , GUI 250 displays a graphical view of the internal details of the rack (as shown as “Rack View” in FIG. 6 ). The graphical objects in Rack View depict a plurality of Chassis and a plurality of blades. A color coded status may also be incorporated in each of the displayed objects to indicate operational conditions. In one exemplary embodiment, when a graphical depiction of a chassis or a blade is selected, more information about the depicted object is displayed (e.g., Blade Information 260 ). In one embodiment, Blade Information 260 may include system information, hosted virtual machines, physical location, temperature, humidity, etc. Some of the information, for example hosted virtual machines, system information, etc. is retrieved from Resource Management System 102 . Other information may be retrieved either from the corresponding Rack Controller 150 or from Inventory Management System 110 depending upon a particular configuration.
GUI 250 may also be used to configure sending out notifications to a preconfigured group of entities. For example, the system may be configured to send emails, text messages, voice calls/voice mails, etc. to a preconfigured group of people in the event of the occurrence of one or more types of error conditions.
Still further, in one exemplary embodiment, Resource Management System 102 may retrieve blade location information from Inventory Management System 110 and use the retrieved information to move critical virtual machines to relatively safe locations in the data center. For example, if flood conditions are detected, some or all virtual machines on hosts that reside in the lower parts of racks may be moved to the upper parts of racks. Furthermore, since top parts of racks would generally be hotter than the lower parts, some critical virtual machines may be moved to relatively lower parts of racks. It may be noted that Resource Management System 102 is capable of moving virtual machines from one host to another using the live migration technology (e.g., VMware VMotion™).
In one exemplary embodiment, GUI 250 may be configured to divide racks in a data center in different sections. For example, a particular section of racks may be reserved for hosting computing resources of a particular organization (in the scenarios where the same data center is being used for hosting computing resources of different business organizations). In one embodiment, if the rack reservation is based on business organization, a network fencing scheme may be adopted to provide network isolation among computing resources of distinct business organizations. In another embodiment, the partition may be done based on types of computing resources. For example, a particular rack may be reserved to host Web servers and another rack may be marked to host email servers. In one exemplary embodiment, when a new blade is inserted into the rack which is reserved for Web servers, Resource Management System 102 automatically provisions the newly added blade to be used as a Web server. In one embodiment, when a new blade is added, Resource Management System 102 queries Inventory Management System 110 for location information as well as any particular type of rack reservation. In one embodiment, rack reservation may be put in place on a live data center. In this embodiment, Inventory Management System 110 will notify Resource Management System 102 about changes in rack reservation and Resource Management System 102 will live-migrate virtual machines according to the rack reservation scheme.
In one example, Resource Management System 102 may provide automatic power saving features by consolidating virtual machines on fewer hosts when computing demand is low and then shutting down the remaining hosts. In one embodiment, Data Center Management System 100 further enhances the power save feature by consolidating virtual machines on fewer smart racks when the computing demand is low and then shutting down the remaining smart racks. Further, from time to time, smart racks may be put out of use for maintenance purposes. However, in order to do so, the hosts need be shutdown, hence causing interruptions in computing resources availability. Data Center Management System 100 , in one embodiment, is configured to automatically live migrate computing resources from a particularly identified smart rack. Further, Data Center Management System 100 may also be configured to monitor computer resource utilization for computing resources on each smart rack and if it is determined that a particular smart rack is only being used to run a number of virtual machines and if the number is below a set threshold, Data Center Management System 100 may start a process of live migrating the virtual machine from the particular smart rack to other racks. Once the virtual machines are live migrated, the particular smart rack may be put in a standby mode to save power.
Accordingly, FIG. 7 illustrates a process 300 of implementing live migration of virtual machines from a source smart rack to one or more destination smart racks. At step 302 , a list of physical hosts and a list of virtual machines running each of the physical hosts are received from Resource Management System 102 . At step 304 , Inventory Management System 102 provides the physical locations (i.e., smart racks for each of the physical hosts). At step 306 , the list of physical hosts is arranged by smart rack IDs to make a list of physical hosts on each of the smart racks in a data center. Since a list of virtual machine for each of the physical hosts is available, a list of virtual machines on each of the smart racks is created. At step 308 , virtual machines that can be live migrated are identified. In one example, if a smart rack needs to be shutdown, all virtual machines from this smart rack need to be live migrated. At step 310 , one or more destination smart racks are identified for receiving the identified virtual machines that are to be moved. At step 312 , such determination may be made based on spare computing power on one or more destination racks. For example, if a particular destination rack has hosts with a total computing capacity to run 100 virtual machines of a certain type and at present there are only 20 active virtual machines, then this destination smart rack could be candidate for receiving more virtual machines from the source smart rack. In one embodiment, a max capacity utilization factor of a destination physical host is also considered. In another embodiment, a prior capacity reservation factor of the destination physical host is taken into the consideration. At step 314 , live migration of all virtual machines from a source smart rack is commenced.
With the above embodiments in mind, it should be understood that the invention can employ various computer-implemented operations involving data stored in computer systems. These operations are those requiring physical manipulation of physical quantities. Any of the operations described herein that form part of the invention are useful machine operations. The invention also relates to a device or an apparatus for performing these operations. In one embodiment, the apparatus can be specially constructed for the required purpose (e.g. a special purpose machine), or the apparatus can be a general-purpose computer selectively activated or configured by a computer program stored in the computer. In particular, various general-purpose machines can be used with computer programs written in accordance with the teachings herein, or it may be more convenient to construct a more specialized apparatus to perform the required operations.
The embodiments of the present invention can also be defined as a machine that transforms data from one state to another state. The transformed data can be saved to storage and then manipulated by a processor. The processor thus transforms the data from one thing to another. Still further, the methods can be processed by one or more machines or processors that can be connected over a network. The machines can also be virtualized to provide physical access to storage and processing power to one or more users, servers, or clients. Thus, the virtualized system should be considered a machine that can operate as one or more general purpose machines or be configured as a special purpose machine. Each machine, or virtual representation of a machine, can transform data from one state or thing to another, and can also process data, save data to storage, display the result, or communicate the result to another machine.
The programming instructions and modules can also be embodied as computer readable code on a computer readable medium. The computer readable medium is any data storage device that can store data, which can be thereafter be read by a computer system. Examples of the computer readable medium include hard drives, network attached storage (NAS), read-only memory, random-access memory, CD-ROMs, CD-Rs, CD-RWs, magnetic tapes and other optical and non-optical data storage devices. The computer readable medium can include computer readable tangible/non-transitory medium distributed over a network-coupled computer system so that the computer readable code is stored and executed in a distributed fashion.
Although the method operations were described in a specific order, it should be understood that other housekeeping operations may be performed in between operations, or operations may be adjusted so that they occur at slightly different times, or may be distributed in a system which allows the occurrence of the processing operations at various intervals associated with the processing, as long as the processing of the overlay operations are performed in the desired way.
Although the foregoing invention has been described in some detail for purposes of clarity of understanding, it will be apparent that certain changes and modifications can be practiced within the scope of the appended claims. Accordingly, the present embodiments are to be considered as illustrative and not restrictive, and the invention is not to be limited to the details given herein, but may be modified within the scope and equivalents of the appended claims.
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A user interface (UI) is accessible on a display to depict and control a plurality of smart racks in a data center is disclosed. The UI includes first, second and third graphical displays. The first graphical display depicts smart racks in the data center so as to mimic a physical arrangement of the smart racks. The second graphical display depicts a plurality of blade hosts in a smart rack in the plurality of smart racks, so as to mimic a physical arrangement of the plurality of blade hosts. The first and second graphical display may include visual indicators to depict error and warning conditions. The third graphical display depicts blade information about a blade host in the plurality of blade hosts. The blade information includes system information, a list of virtual machines hosted on the blade host, and a physical location of the blade host in the data center.
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BACKGROUND
[0001] This application claims the benefit of the earlier filing date of provisional application of Samuel L. Forusz and Rukhsana Arastu entitled, “Fiber Formulation,” filed Jul. 28, 2000, Serial No. 60/221,629 and incorporated herein by reference.
[0002] 1. Field
[0003] The invention relates to nutritional supplements and, more particularly, to a composition and method for dietary fiber administration.
[0004] 2. Description of Related Art
[0005] The Food and Nutrition Board of the National Academy of Scientist has not set a Recommended Dietary Allowance (RDA) for dietary fiber. Nevertheless, the importance of dietary fiber is recognized by most health organizations and the federal government. The Dietary Guidelines for Americans published jointly by the United States Departments of Agriculture and Health and Human Services recommend eating foods that have adequate amounts of fiber. The National Cancer Institute recommends 20 to 30 grams of fiber per day with an upper limit of 35 grams.
[0006] Dietary fiber is plant material that is resistant to breakdown (digestion) by the human digestive system. In general, there are two major kinds of dietary fiber-insoluble (cellulose, hemicellulose, lignin) and soluble (gums, mucilages, pectins). Insoluble fiber promotes normal elimination by providing bulk for stool formation and hastening the passage of the stool through the colon. Studies indicate that soluble fibers may play a role in reducing the level of cholesterol in the blood.
[0007] What is needed are compositions and methods of administration that encourage fiber consumptions.
SUMMARY
[0008] A composition and a method of administering a composition suitable for human consumption is described. In one embodiment, the composition includes a dietary acceptable amount of a first soluble fiber comprising inulin and a dietary acceptable amount of at least a second soluble fiber. The composition is in beverage form having a viscosity on the order of 1.4 centipoise (cp) or less. A serving of the beverage may comprise a portion, including the entire portion of a daily predetermined amount of soluble fiber.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The following description relates to a composition suitable for human consumption and a method of administering a beverage composition. In one aspect, the composition serves as a dietary supplement to provide the dietary needs of fiber in men and women. By supplying fiber, particularly, soluble fiber, the composition and method promote regularity, intestinal health, and a lowering of the blood cholesterol level in men and women.
[0010] In one embodiment, the composition is a beverage formulated to contain active ingredients of a first soluble fiber including inulin and at least a second soluble fiber. The first fiber and at least a second fiber are contained at levels approaching 40 percent by weight per volume and a viscosity of 1.4 cp.
[0011] Inulin is a fructooligosaccharide derived principally from chickory root. Inulin is commercially available from Orafti of Malvern, Pa. One suitable second soluble fiber to be combined with inulin is maltodextrin derived from corn. Maltodextrin is manufactured by Archer Daniels Midland of Decatur, Ill., and is commercially available from Matsutani Chemical Industry Company, Ltd. of Decature, Ill. (Matsutani America, Inc.). Other suitable second soluble fibers include, but are not limited to, polydextrose and acacia gum, used alone or in combination with another second fiber.
[0012] In one embodiment, the composition is a fortified beverage formulated to contain active ingredients of inulin and other soluble fiber(s), and vitamin C. The beverage is non-carbonated and the delivery system may be in a ready-to-drink form or a concentrated form to be mixed with a fluid such as water or juice. A pH of the product ranges from about 4.0-4.6, and preferably about 4.1 to about 4.4. At this pH range, inulin and the other soluble fiber(s) such as maltodextrin are stable in solution and the acidic nature controls bacteria growth.
[0013] In one embodiment where the second soluble fiber is maltodextrin, the composition comprises:
[0014] about 0.26 to 6.0% (w/v) of inulin in a soluble form;
[0015] about 0.0026 to 33% (w/v) of maltodextrin;
[0016] about 0.013 to 0.26% (w/v) of ascorbic acid;
[0017] about 0.009 to 0.56% (w/v) of citric acid;
[0018] about 0.003 to 0.14% (w/v), sodium citrate, preferably granular form;
[0019] about 0.002 to 0.012% (w/v), sodium ascorbate;
[0020] different levels of sugars for different flavors used in the beverage product;
[0021] and appropriate levels of flavors which can be, but not limited to, orange, peach, cranberry, tangerine, raspberry, grapefruit, mango, black cherry, strawberry, or any combination of the above flavors. The colorants can be from natural sources or from certified F&DC colorants depending on labeling claim being sought.
[0022] In the above embodiment, the flavor choices are selected for preferred compatibility with the other ingredients, especially the active ingredients of inulin, second fiber(s), and vitamin C. Sodium ascorbate, sodium citrate and citric acid maintain a pH from about 4.1 to about 4.4. Tables 1-3 present several examples of beverage compositions with different colors and flavors.
[0023] The composition may be prepared as a single strength composition for consumption or as a concentrate to be mixed with a fluid prior to consumption. By single strength, the composition represents a predetermined periodic amount, including a predetermined daily amount or a portion of a predetermined daily amount of active ingredients (e.g., inulin, second fiber, and vitamin C).
[0024] To prepare a single strength composition, a sweetener (if utilized) is added to a volume of water equivalent to about 40 percent by weight of a final composition. To the mixed water and sweetener, inulin is added and mixed well. Next, a desired amount of soluble fiber is added and mixed until completely dissolved. Citric acid, sodium citrate dihydrate, and ascorbic acid are sequentially added and stirred until little or no particulates remain (e.g., the solution appears translucent). Optional flavors and colorants are added and mixed and the composition is adjusted with water to achieve the desired volume of, for example, 300 milliliters (mL) or 10 ounces (oz).
[0025] A concentrated composition may be prepared in the following manner. A volume of water equivalent to 20 percent by weight for volume of the final composition is combined with a sweetener (if utilized). To this composition, inulin and other fiber(s) are added and mixed, followed by, sequentially, citric acid, sodium citrate dihyrate, sodium ascorbate, and ascorbic acid. Flavors and colorants, where desired, are added to the composition, with agitation. Finally, the desired volume is achieved by adjusting with water.
[0026] The beverage can be prepared in low calorie form, substituting sweeteners such as sugar, with artificial sweeteners such as aspartame, acesulfame-K, or sucralose. The beverage can be pasteurized through tunnel pasteurization or hot fill. Cold-fill in conjunction with preservation can also be achieved by addition of preservatives such as potassium benzoate, potassium sorbate. Slight carbonation can be performed with about 2 to 2.5 volumes. The beverages can also be made in a dry-mix powder and prepared by mixing with water or juice. For example, a 18.0 g of dry-mix powder of 4.4 g inulin, 13.0 g of soluble fiber, and 0.2 g of ascorbic acid may be combined with 300 mL of water to provide a single-strength drink.
[0027] The composition described above generally relates to low viscosity soluble fiber composition. In this manner, the composition does not effect the absorption of minerals, unlike typical high viscosity fibers. In general, as viscosity is increased, the rate of absorption/diffusion of minerals is reduced. The composition described above as a beverage provides the nutrients for promoting intestinal health and lowering blood cholesterol levels. Addition of vitamin C utilizes the absorbed calcium and maintains normal calcium crystals in the bones.
[0028] None of the available beverage compositions known to the inventors include inulin and fiber in such a concentrated form and yet have such a low viscosity as described in the composition as a beverage described above. According to the inventors' best knowledge, there is no such beverage product in the market that has low viscosity with such a high concentration of fiber. The beverage lies midway between a natural medicine and a refreshing beverage to gain broader consumer acceptance. The liquid formulation is beneficial to most human subjects, particularly adult human subjects including elderly human subjects, who may have difficulties in taking solid dosage forms for regularity.
[0029] Tables 1-3 present representative examples of the composition of the invention.
TABLE 1 Formula for Peach - Pear Flavored Beverage AMOUNT, g (per serving from INGREDIENT about 8 to 10 oz) Maltodextrin 13.0 Inulin 4.4 Sugar 18.0 Citric acid 0.138 Sodium citrate, dihydrate granular 0.2 Ascorbic acid 0.2 Natural Pear flavor 0.374 Natural peach flavor 1.52 Natural fruity red colorant, liquid 0.0399 Natural caramel colorant 0.084 Sodium Ascorbate 0.035
[0030] [0030] TABLE 2 Formula for Apple Flavored Beverage AMOUNT, g (per serving from INGREDIENT about 8 to 10 oz) Maltodextrin 13.0 Inulin 4.4 Sugar 18.45 Citric acid 0.12 Sodium citrate, dihydrate granular 0.17 Ascorbic acid 0.2 Natural Apple fruit flavor 0.69 Natural caramel colorant 0.087 Sodium Ascorbate 0.035
[0031] [0031] TABLE 3 Formula for Berry Blend Flavored Beverage AMOUNT, g (per serving from INGREDIENT about 8 to 10 oz) Maltodextrin 13.0 Inulin 4.4 Sugar 18.0 Citric acid 0.144 Sodium citrate, dihydrate granular 0.17 Ascorbic acid 0.2 Natural strawberry flavor 1.32 Natural Berry flavor 0.298 Natural fruity red colorant, liquid 0.6 Sodium Ascorbate 0.035
[0032] In the preceding detailed description, the invention is described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention as set forth in the claims. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.
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The invention relates to a composition and a method of administering a composition suitable for human consumption. In one embodiment, the composition includes a dietary acceptable amount of a first fiber comprising inulin and a dietary acceptable amount of a second soluble fiber. The composition is in beverage form having a viscosity on the order of 1.4 cp or less. A serving of the beverage may comprise a portion, including the entire portion of a daily predetermined amount of soluble fiber.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of application Ser. No. 10/143,103 filed 07 May 2002, which claims the benefit of U.S. Provisional Applications No. 60/289,159 filed 07 May 2001 and No. 60/311,472 filed 10 Aug. 2001.
REFERENCE REGARDING FEDERAL SPONSORSHIP
[0002] Not Applicable
REFERENCE TO MICROFICHE APPENDIX
[0003] Not Applicable
FIELD OF THE INVENTION
[0004] The present invention relates to a device and method for monitoring the flow of liquids and, more particularly, for monitoring the flow of urine in a urinal, such as a waterless urinal, to determine when a trap cartridge needs to be changed or serviced.
DESCRIPTION OF RELATED ART AND OTHER CONSIDERATIONS
[0005] Waterless urinals, such as are disclosed in U.S. Pat. No. 6,053,197 and U.S. Pat. No. 6,425,411, typically use a water trap in which a low density sealant layer covers a small amount of wastewater remaining in the urinal trap. Such urinals conventionally do not have a flush mechanism; therefore, some amount of wastewater will remain in the trap at all times. The sealant layer prevents odors from escaping from and through the wastewater. Any slow draining of wastewater from the trap or blocking within the trap or sufficient use of the urinal to cause the supply of sealant to be significantly diminished, will result in unpleasant odors. Therefore, it is important for such urinals to be cleaned and serviced regularly, and especially when draining slowly, and a need exists for determining when the conditions for cleaning and servicing pertain.
SUMMARY OF THE INVENTION
[0006] These and other problems are successfully addressed and overcome by the present invention, along with attendant advantages. The present invention employs an electric device, including a PROM and associated algorithm, to monitor urine flow through the cartridge trap. Measuring the duration of such flow and the number of times the urinal is used will determine, in accordance with preset criteria, when servicing or replacement is needed, and alerts a janitor or repairman or other service person by a warning light or other signal. Because urine has a high mineral content, it is electrically conductive, effective to complete circuits between closely spaced metal contacts coupled to the PROM, which allows the manner and existence of the urine to be detected.
[0007] Other aims and advantages, as well as a more complete understanding of the present invention, will appear from the following explanation of an exemplary embodiment and the accompanying drawings thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] [0008]FIG. 1 is a perspective view of the present invention depicting a removable trap utilized in a urinal with a liquid flow meter installed therein;
[0009] [0009]FIG. 2 is a cross-sectional view of the present invention illustrated in FIG. 1;
[0010] [0010]FIG. 3 is a perspective view of the liquid flow meter taken from its exterior or cover;
[0011] [0011]FIGS. 4 and 5 are side views of the exterior or cover of the liquid flow meter, with one taken 90° from the other;
[0012] [0012]FIG. 6 is an electric schematic diagram of the of the liquid flow meter;
[0013] [0013]FIG. 7 is an exploded perspective view of the present invention;
[0014] [0014]FIG. 8 is a perspective view of the liquid flow meter depicted in FIG. 3 with its outer cover removed to disclose the interior components thereof;
[0015] [0015]FIG. 9 is a top view of the liquid flow meter;
[0016] [0016]FIG. 10 is a bottom, upwardly looking view of the liquid flow meter, taken 90° from that depicted in FIG. 9;
[0017] [0017]FIGS. 11 and 12 are side views of the liquid flow meter, with one view being taken 90° from the other;
[0018] [0018]FIGS. 13 and 14 are perspective views of the respective negative and positive battery clips used in the liquid flow meter illustrated in FIGS. 7-11;
[0019] [0019]FIG. 15 is a perspective view of the sensor contact clips employed in the liquid flow meter illustrated in FIGS. 8-12;
[0020] [0020]FIG. 16 is a logic flow chart depicting the algorithm utilized in operating the liquid flow meter of the present invention; and
[0021] [0021]FIG. 17 is a chart setting forth the variables for programming the computer chip used in the liquid flow meter.
DETAILED DESCRIPTION
[0022] Accordingly, as depicted in FIGS. 1 and 2, an odor trap 20 , such as disclosed in above-mentioned U.S. Pat. No. 6,053,197 and U.S. patent application Ser. No. 09/855,735, comprises a cylindrical housing 22 , a bottom portion 24 and a cover or top portion 26 , which define an interior 27 . Internally, odor trap 20 includes a vertical baffle 28 secured to and extending downwardly from cover 26 , a sloped, generally horizontal baffle 30 secured to vertical baffle 28 and an overflow riser 32 extending upwardly from bottom portion 24 . Overflow riser 32 comprises a walled section to form a discharge path from interior 27 of trap 20 through an exit 34 which is coupled to an external drain system. An entry 36 forms an opening into interior 27 .
[0023] The interior is adapted to retain a conductive liquid 38 , e.g., wastewater such as a mixture of water and urine, on which a sealant layer 40 of oily substance floats. Accordingly, the wastewater enters odor trap 20 through one or more openings 36 , flows into and passes through sealant layer 40 , and flows atop and beneath baffle 30 on its journey over overflow riser 32 and out of the odor trap through exit 34 .
[0024] Cover 26 is further provided with a centrally positioned opening 42 , surrounded by entry 36 .
[0025] As illustrated generally in FIGS. 3-5 and in greater detail in FIGS. 7-15, a liquid flow meter 50 is adapted to be secured to odor trap 20 at cover opening 42 . Specifically, meter 50 is provided with connector 52 comprising a post 54 terminating in a pair of tangs 56 with bulbous bosses 58 . Cover opening 42 and post 54 have approximately equal diameters to permit bosses 58 to pressed tangs 56 together as they pass through the cover opening and thence to snap outwardly to latch the liquid flow meter to odor trap 20 .
[0026] The electric circuit embodied in liquid flow meter 50 is shown in FIG. 6. The driving mechanism of the meter is embodied in a microcontroller 60 , such as a 12LC508A-04/SN microcontroller, which is one of a PICD12C5XX family of microcontrollers from Microchip Technology. The PICD12C5XX is defined as a family of low-cost, high performance, 8-bit, fully static, EEPROM/EPROM/ROM based CMOS microcontrollers. It employs a RISC architecture with 33 single word/single cycle instructions. All instructions are single style (1 μs) except for program branches which take two cycles. The PICD12C5XX includes 12-bit wide instructions which are highly symmetrical, resulting in 2:1 code compression.
[0027] Microcontroller 60 is provided with eight input and output pins (numbers 1-8) in which pins “6” and “7” are coupled to a pair of contact sensor probes 62 and 64 at their respective contact points 62 × and 64 ×respectively by leads 62 ′ and 64 ′. Pin “5” is coupled through a resistor 66 to a LED 68 through the intermediary of leads 67 , and pin “1” is coupled to a source of power “VCC” 70 , such as a 3.3 volt lithium battery, e.g., CR1220. The couplings to the positive side of battery 70 is through a connection device having three termini, respectively designated battery clip (positive) 70 and 70 a ′, a″, a′″ (see FIGS. 7-14). The couplings to the negative side of battery 70 are through a connection device having two termini, respectively designated battery clip (negative) 70 and 70 b ′, b″ (also see FIGS. 7-14). These termini act both as clips and as electric connections aided, for example, by soldering. LED 68 is coupled to power source 70 . Pin “8” is grounded, as designated by indicium 76 . Functioning of the microprocessor and its circuit are described below.
[0028] The various connections among the several electric components including microcontroller 60 , sensor probes 62 and 64 , resistor 66 , positive and negative battery clips 70 a and 70 b are enabled by a circuit board 78 . Where needed, insulation is provided, such as by a clip insulator 80 .
[0029] As best shown in FIGS. 2-5, sensor probes 62 and 64 are positioned in liquid flow meter 50 so that their exposed termini 63 do not extend to the bottom surface (designated by indicium 65 ) of the meter and, therefore, are spaced from cover 26 . This spacing of termini 63 avoids undesired closure between the probes, should, for example, the level of the liquids in odor trap 20 rise during use through entry 36 in cover 26 . Further, the spacing between termini 62 c and 64 b and between termini 62 b and 64 c , in particular, is limited to a minimum distance to avoid unintentional contact therebetween, for example, of droplets of wastewater that have not passed through entry 36 .
[0030] Reference is now made to FIGS. 16 and 17. FIG. 16 illustrates the flow of logic used in sensing and measuring the activities occurring in odor trap 20 . The glossary of terms used in the following is:
[0031] “Uses”—A use is when the sensor contacts detect the presence of a fluid, within a specified period of time.
[0032] “Use Counter” or “Counter #1”—Counts the total number of uses
[0033] “Use Timer” or “Timer #1”—A Use Timer determines the period of time between initial fluid contact and when the next fluid contact can be recorded.
[0034] “Blockage”—A blockage is when fluid is detected by the sensor contacts continuously for a specified amount of time.
[0035] “Blockage Timer” or “Timer #2”—Blockage Timer records records the duration of continuous fluid presence by the sensor contacts.
[0036] “Blockage Counter” or “Counter #2”—Blockage Counter records the number of blockages as determined by Blockage Timer, when the timer exceeds a specific minimum amount of time.
[0037] Further, in the following exposition of the algorithm, the term “X” indicates time which is a programmable variable, to which reference is directed to FIG. 17. Operation is assumed that meter 50 is in an inactive “turned-off” condition. Operation commences, as shown in enclosure 100 , when urine flow contacts sensors on indicator or meter to activate the system. As shown in enclosure 102 , counter #1 in microprocessor 60 records one use. Counter #1 will not record another use for “X1” amount of time or if probes 62 and 64 are submerged. If, as depicted in enclosure 104 , the urine maintains contact between the probes for a time longer than an “X3” period of time, counter #2 records one blockage. In the next step, as outlined in enclosure 106 , if blockage occurs “X4” number of times consecutively, LED 68 flashes to indicate a blockage. As shown in enclosure 108 , flashing continues until power is exhausted or reset is activated. However, as pointed out in enclosure 112 , if blockage does not occur for “X4” number of times consecutively, counter #2 resets to 0.
[0038] Alternatively, as stated in enclosure 110 , when the number of uses reaches “X5”, the end of the lifecycle of flashing LED 68 is activated for “X6” of a second and “X7” times a minute, and the program proceeds directly to the step outlined in enclosure 108 , that is, flashing continues until power is exhausted or reset is activated.
[0039] The next step proceeds to that embraced in enclosure 114 , if the reset feature is active in progress, that is, if the sensor contacts are closed “X8” number of times within 4 seconds, the indicator/meter 60 will proceed to a warning state. If the sensor contacts are closed “X8” number of times within 4 seconds again, the indicator will reset. Finally, as circumscribed in enclosure 116 , if reset is activated, all counters are reset to 0.
[0040] Optionally, as set forth in enclosure 118 , LED 68 will single flash for “X2” time per use.
[0041] Several materials may be used in the present invention. The cover shell may be made of any number of thermoplastic materials such as ABS or polypropylene plastic. The electronics are held in place in the mold by the location of the LED and the sensor contact points. Although injection molding is one method of encapsulation, other methods could be used successfully, such as potting and cold injection.
[0042] The present invention is installed by placing the split ball stem (connector 52 , post 54 , post 56 , pair of tangs 56 , bosses 58 ) located at the base of the indicator into mounting hole 42 located in the center of drain holes 36 on the top or cover of the cartridge.
[0043] The present invention operates in three states:
[0044] 1. Packaged: Preinstalled into the lid of the cartridge, the indicator is active but in a sleep mode.
[0045] 2. Installed: Indicator and cartridge is installed in a urinal and ready for first urine contact. No information is stored save for the ROM programming.
[0046] 3. Initial Fluid Detection: The high mineral content of the urine (or water, which has a lesser mineral content) will complete the circuit between the sensor probes, powering the chip and allowing information to be stored.
[0047] In one embodiment, the algorithm of the Fluid Detection state, as noted above, is as follows:
[0048] 1. Upon each detection of fluid, “Use Counter” will increment by (1), and “Use Timer” records Duration of fluid detection. The “Use Counter” will not record another use for a short, predetermined amount of time (e.g., 50 seconds) to avoid falsely recording two uses, when only one use should be recorded or as long as the fluid is still present.
[0049] 2. If number of uses (Use Counter) is greater than the predetermined number (in one embodiment, 7000), the unit activates Change Signal (continuous or flashing LED).
[0050] 3. If the Time Duration of fluid detection is greater than the predetermined value (in one embodiment, 75 seconds), Blockage Counter increments by (1).
[0051] 4. If Blockage Counter equals the predetermined number (in one embodiment, 3) and these events are consecutive, unit activates Change Signal (FLASH).
[0052] 5. If the predetermined number of Blockage Events is not consecutive then the Blockage Counter will reset to zero.
[0053] In an alternative embodiment, a reset feature is provided:
[0054] 1. If time duration of flow is less than one second, very short predetermined value (in one embodiment, 0.5 seconds), clicks the Reset Counter once, and tracks Reset Time.
[0055] 2. If the Reset Counter equals a predetermined value (in one embodiment, 10) and the Reset Time is less than or equal to a predetermined value (in one embodiment, 5 seconds), all counters are reset to zero.
[0056] 3. If Reset Time is greater than a predetermined value (in one embodiment, 5 seconds) resets Reset Counter and Reset Time to zero.
[0057] In a related alternative embodiment, a feature is provided to signal if the urinal is blocked: If time duration of flow is greater than a very long predetermined value (in one embodiment, 75 seconds, for example), the unit activates Change Signal.
[0058] In an alternative embodiment, the present invention will give a Change Signal triggered by a total time in service.
[0059] 1. Upon Initial Fluid Detection, Powers Chip and initiates Duration Clock.
[0060] 2. When Duration Clock reaches a predetermined number of days (in one embodiment, 90 days) activates Change Signal.
[0061] In another alternative embodiment, the present intention will flash an LED every time it is in use:
[0062] 1. Upon Fluid Detection, activates In-Use Flash Signal ({fraction (1/10)} second) to indicate the device is working. In-Use Flash Signal feature resets upon end of Fluid Detection.
[0063] In the another alterative embodiment, the present invention uses a second LED to provide an in-use signal, and the first LED for overfill. The two LED's may employ different colors. Further, different colors and different LED's may be used for different signals.
[0064] The device can be employed in a flush urinal, by connecting it to a solenoid valve that cuts off the flow of flush water in the event of blockage. The connection may be by hard wire or transmitter and receiver.
[0065] Although water has a lower mineral content and will work, a properly adjusted sensor is needed to determine the difference between water and urine. Thus, in an alternative embodiment, the resistance limit is set so that water, which may be used to flush out the system, is not recognized, but urine is.
[0066] Although the invention has been described with respect to a particular embodiment thereof, it should be realized that various changes and modifications may be made therein without departing from the spirit and scope of the invention.
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A liquid flow meter ( 50 ), including a microcontroller ( 60 ) and associated algorithm, monitors urine flow through a cartridge trap ( 20 ). Measuring the duration of such flow and the number of times the urinal is used will determine, in accordance with preset criteria, when servicing or replacement is needed, and alerts a service person to that effect by a warning light ( 68 ) or other signal. Because urine has a high mineral content, it is electrically conductive, effective to complete circuits between closely spaced metal contacts ( 62 a - 62 c , 64 a - 64 c ) coupled to the PROM, which allows the manner and existence of the urine to be detected. The liquid flow meter is installed in the cartridge trap by utilizing and placing a split ball stem ( 52 ) located at the base of the meter into a mounting hole ( 42 ) located in the center of the drain holes ( 36 ) on the cartridge cover ( 26 ).
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to, and is a continuation of, International Application No. PCT/NL99/00460, filed on Jul. 19, 1999, designating the United States of America, the contents of which are incorporated herein by this reference, the PCT International Patent Application itself claiming priority from European Patent Office Application Ser. No. 98202465.5 filed Jul. 22, 1998 and European Patent Office Application Ser. No. 98202467.1 filed Jul. 22, 1998.
TECHNICAL FIELD
The invention relates to Streptococcus infections in pigs, vaccines directed against those infections, tests for diagnosing Streptococcus infections and bacterial vaccines. More particularly, the invention relates to vaccines directed against Streptococcus infections.
BACKGROUND OF THE INVENTION
Streptococcus species, of which a large variety cause infections in domestic animals and man, are often grouped according to Lancefield's groups. Typing according to Lancefield occurs on the basis of serological determinants or antigens that are, among others, present in the capsule of the bacterium, and allows for only an approximate determination. Often, bacteria from different groups show cross-reactivity with each other, while other Streptococci cannot be assigned a group-determinant at all. Within groups, further differentiation is often possible on the basis of serotyping. These serotypes further contribute to the large antigenic variability of Streptococci, a fact that creates an array of difficulties within diagnosis of and vaccination against Streptococcal infections.
Lancefield group A Streptococcus species (Group A streptococci “GAS”, Streptococcus pyogenes) are common in children, causing nasopharyngeal infections and complications thereof. Among animals, cattle are especially susceptible to GAS, and the resulting mastitis.
Group A streptococci are the etiologic agents of streptococcal pharyngitis and impetigo, two of the most common bacterial infections in children, as well as a variety of less common, but potentially life-threatening, infections including soft tissue infections, bacteremia, and pneumonia. In addition, GAS are uniquely associated with the post-infectious autoimmune syndromes of acute rheumatic fever and post streptococcal glomerulonephritis.
Several recent reports suggest that the incidence of both serious infections due to GAS and acute rheumatic fever has increased during the past decade, focusing renewed interest on defining the attributes or virulence factors of the organism that may play a role in the pathogenesis of these diseases.
GAS produce several surface components and extracellular products that may be important in virulence. The major surface protein, M protein, has been studied in the most detail and has been convincingly shown to play a role in both virulence and immunity. Isolates rich in M protein are able to grow in human blood, a property thought to reflect the capacity of M protein to interfere with phagocytosis, and these isolates tend to be virulent in experimental animals.
Lancefield group B Streptococcus (“GBS”) are most often seen in cattle, causing mastitis; however, human infants are susceptible as well, often with fatal consequences. Group B streptococci (GBS) constitute a major cause of bacterial sepsis and meningitis among human neonates born in the United States and Western Europe and are emerging as significant neonatal pathogens in developing countries as well.
It is estimated that GBS strains are responsible for 10,000 to 15,000 cases of invasive infection in neonates in the United States alone. Despite advances in early diagnosis and treatment, neonatal sepsis due to GBS continues to carry a mortality rate of 15 to 20%. In addition, survivors of GBS meningitis have 30 to 50% incidence of long-term neurologic sequelae. Over the past two decades, increasing recognition of GBS as an important pathogen for human infants has generated renewed interest in defining the bacterial and host factors important in virulence of GBS and in the immune response to GBS infection.
Particular attention has focused on the capsular polysaccharide as the predominant surface antigen of the organisms. In a modification of the system originally developed by Rebecca Lancefield, GBS strains are serotyped on the basis of antigenic differences in their capsular polysaccharides and the presence or absence of serologically defined C proteins. While GBS isolated from nonhuman sources often lack a serologically detectable capsule, a large majority of strains associated with neonatal infection belong to one of four major capsular serotypes, 1 a, 1 b, II or III. The capsular polysaccharide forms the outermost layer around the exterior of the bacterial cell, superficial to the cell wall. The capsule is distinct from the cell wall-associated group B carbohydrate. It has been suggested that the presence of sialic acid, in the capsule of bacteria that causes meningitis, is important for allowing these bacteria to breach the blood-brain barrier. Indeed, in S. agalactiae, sialic acid has been shown to be critical for the virulence function of the type III capsule. The capsule of S. suis serotype is composed of glucose, galactose, N-acetylglucosamine, rhamnose and sialic acid.
The group B polysaccharide, in contrast to the type-specific capsule, is present on all GBS strains and is the basis for serogrouping the organisms into Lancefield's group B. Early studies by Lancefield and co-workers showed that antibodies raised in rabbits against whole GBS organisms protected mice against challenge with strains of homologous capsular type, demonstrating the central role of the capsular polysaccharide as a protective antigen. Studies in the 1970s by Baker and Kasper demonstrated that cord blood of human infants with type III GBS sepsis uniformly had low or undetectable levels of antibodies directed against the type III capsule, suggesting that a deficiency of anticapsular antibody was a key factor in susceptibility of human neonates to GBS disease.
Lancefield group C infections, such as those with S. equi, S. zooepidemicus, S. dysgalactiae, and others, are mainly seen in horses, cattle and pigs, but can also cross the species barrier to humans. Lancefield group D (S. bovis) infections are found in all mammals and some birds, sometimes resulting in endocarditis or septicemia.
Lancefield groups E, G, L, P, U and V (S. porcinus, S. canis, S. dysgalactiae) are found in various hosts, causing neonatal infections, nasopharyngeal infections or mastitis.
Within Lancefield groups R, S, and T (and with ungrouped types), Streptococcus suis is an important cause of meningitis, septicemia, arthritis and sudden death in young pigs (4, 46). Incidentally, it can also cause meningitis in man ( 1 ). S. suis strains are usually identified and classified by their morphological, biochemical and serological characteristics (58, 59, 46). Serological classification is based on the presence of specific antigenic polysaccharides. So far, 35 different serotypes have been described (9, 56, 14). In several European countries. S. suis serotype 2 is the most prevalent type isolated from diseased pigs, followed by serotypes 9 and 1. Serological typing of S. suis is performed using different types of agglutination tests. In these tests, isolated and biochemically characterized S. suis cells are agglutinated with a panel of 35 specific sera. These methods are very laborious and time-consuming.
Little is known about the pathogenesis of the disease caused by S. suis, let alone about its various serotypes such as type 2. Various bacterial components, such as extracellular and cell-membrane associated proteins, fimbriae, hemagglutinins, and hemolysin have been suggested as virulence factors (9, 10, 11, 15, 16, 47, 49). However, the precise role of these protein components in the pathogenesis of the disease remains unclear (37). It is well known that the polysaccharide capsule of various Streptococci and other Gram-positive bacteria plays an important role in pathogenesis ( 3 , 6 , 35 , 51 , 52 ). The capsule enables these microorganisms to resist phagocytosis and is therefore regarded as an important virulence factor. Recently, a role of the capsule of S. suis in the pathogenesis was suggested as well (5). However, the structure, organization and function of the genes responsible for capsule polysaccharide synthesis (“cps”) in S. suis is unknown. Within S. suis, serotype 1 and 2, strains can differ in virulence for pigs (41, 45, 49). Some type 1 and 2 strains are virulent, other strains are not. Because both virulent and nonvirulent strains of serotype 1 and 2 strains are fully encapsulated, it may even be that the capsule is not a relevant factor required for virulence.
Attempts to control S. suis infections or disease are still hampered by the lack of knowledge about the epidemiology of the disease and the lack of effective vaccines and sensitive diagnostics. It is well known and generally accepted that the polysaccharide capsule of various Streptococci and other gram-positive bacteria plays an important role in pathogenesis. The capsule enables these microorganisms to resist phagocytosis and is therefore regarded as an important virulence factor.
Compared to encapsulated S. suis strains, non-encapsulated S. suis strains are phagocytosed by murine polymorphonuclear leucocytes to a greater degree. Moreover, an increase in thickness of capsule was noted for in vivo grown virulent strains while no increase was observed for avirulent strains. Therefore, these data again demonstrate the role of the capsule in the pathogenesis for S. suis as well.
Ungrouped Streptoccus species, such as S. mutans, causing caries in humans, S. uberis.causing mastitis in cattle, and S. pneumonia, causing major infections in humans, and Enterococcus faecilalis and E. faecium, further contribute to the large group of Streptococci.
Streptococcus pneumoniae (the pneumococcus) is a human pathogen causing invasive diseases, such as pneumonia, bacteremia, and meningitis. Despite the availability of antibiotics, pneumococcal infections remain common and can still be fatal, especially in high-risk groups, such as young children and elderly people. Particularly in developing countries, many children under the age of five years die each year from pneumococcal pneumonia. S. pneumoniae is also the leading cause of otitis media and sinusitis. These infections are less serious, but nevertheless incur substantial medical costs, especially when leading to complications, such as permanent deafness. The normal ecological niche of the pneumococcus is the nasopharynx of man. The entire human population is colonized by the pneumococcus at one time or another, and at a given time, up to 60% of individuals may be carriers. Nasopharyngeal carriage of pneumococci by man is often accompanied by the development of protection against infection by the same serotype. Most infections do not occur after prolonged carriage but follow exposure to recently acquired strains. Many bacteria contain surface polysaccharides that act as a protective layer against the environment. Surface polysaccharides of pathogenic bacteria usually make the bacteria resistant to the defense mechanisms of the host, for example, the lytic action of serum or phagocytosis. In this respect, the serotype-specific capsular polysaccharide (“CP”) of Streptococcus pneumoniae, is an important virulence factor. Unencapsulated strains are avirulent, and antibodies directed against the CP are protective. Protection is serotype specific; each serotype has its own, specific CP structure. Ninety different capsular serotypes have been identified. Currently, CPs of 23 sero-types are included in a vaccine.
Vaccines directed against Streptococcus infections typically aim to utilize an immune response directed against the polysaccharide capsule of the various Streptococcus species. especially since the capsule is considered a primary virulence factor for these bacteria. During infection, the capsule provides resistance against phagocytosis and thus protects the bacteria from the immune system of the host, and from elimination by macrophages and neutrophils.
The capsule particularly confers the bacterium resistance to complement-mediated opsonophagocytosis. In addition, some bacteria express capsular polysaccharides (CPs) that mimic host molecules, thereby avoiding the immune system of the host. Also, even when the bacteria have been phagocytosed, intracellular killing is hampered by the presence of a capsule.
It is generally thought that the bacterium will be recognized by the immune system through the anticapsular-antibodies or serum-factors bound to its capsule, and will, through opsonization, be phagocytosed and killed only when the host has antibodies or other serum factors directed against capsule antigens.
However, these antibodies are serotype-specific, and will often only confer protection against only one of the many serotypes known within a group of Streptococci.
For example, current commercially available S. suis vaccines, which are generally based on whole-cell-bacterial preparations, or on capsule-enriched fractions of S. suis, confer only limited protection against heterologous strains. Also, the current pneumococcal vaccine, which was licensed in the United states in 1983, consists of purified CPs of 23 pneumococcal serotypes whereas at least 90 CP types exist.
The composition of this pneumococcal vaccine was based on the frequency of the occurrence of disease isolates in the US and cross-reactivity between various serotypes. Although this vaccine protects healthy adults against infections caused by serotypes included in the vaccine, it fails to raise a protective immune response in infants younger than 18 months and it is less effective in elderly people. In addition, the vaccine confers only limited protection in patients with immunodeficiencies and hematology malignancies.
Thus, improved vaccines are needed against Streptococcus infections. Much attention is directed toward producing CP vaccines by producing the relevant polysaccharides via chemical or recombinant means. However, chemical synthesis of polysaccharides is costly, and capsular polysaccharide synthesis by recombinant means necessitates knowledge about the relevant genes, which is not always available, and needs to be determined for every relevant serotype.
DISCLOSURE OF THE INVENTION
The invention provides an isolated or recombinant nucleic acid encoding a capsular (cps) gene cluster of Streptococcus suis. Biosynthesis of capsule polysaccharides has generally been studied in a number of Gram-positive and Gram-negative bacteria (32). In Gram-negative bacteria, but also in a number of Gram-positive bacteria, genes which are involved in the biosynthesis of polysaccharides are clustered at a single locus.
Streptococcus suis capsular genes, as provided by the invention, show a common genetic organization involving three distinct regions. The central region is serotype specific and encodes enzymes responsible for the synthesis and polymerization of the polysaccharides. The central region is flanked by two regions conserved in Streptococcus suis which encode proteins for common functions, such as transport of the polysaccharide across the cellular membrane. However, between species, only low homologies exist, hampering easy comparison and detection of seemingly similar genes. Knowing the nucleic acid encoding the flanking regions allows type-specific determination of nucleic acid of the central region of Streptococcus suis serotypes, as, for example, described herein.
The invention provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis or a gene or gene fragment derived thereof. Such a nucleic acid is, for example, provided by hybridizing chromosomal DNA derived from any one of the Streptococcus suis serotypes to a nucleic acid encoding a gene derived from a Streptococcus suis serotype 1, 2 or 9 capsular gene cluster, as provided by the invention (see for example, Tables 4 and 5) and cloning of (type-specific) genes as, for example, described herein. At least 14 open reading frames are identified. Most of the genes belong to a single transcriptional unit, identifying a coordinate control of these genes. The genes and the enzymes and proteins they encode, act in concert to provide the capsule with the relevant polysaccharides.
The invention provides cps genes and proteins encoded thereof involved in regulation (CpsA), chain length determination (CpsB, C), export (CpsC) and biosynthesis (CpsE, F, G, H, J, K). Although, at first glance, the overall organization seemed to be similar to that of the cps and eps gene clusters of a number of Gram-positive bacteria (19, 32, 42), overall homologies are low (see, table 3). The region involved in biosynthesis is located at the center of the gene cluster and is flanked by two regions containing genes with more common functions.
The invention provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis serotype 2, or a gene or gene fragment derived thereof, preferably as identified in FIG. 3 . Genes in this gene cluster are involved in polysaccharide biosynthesis of capsular components and antigens. For a further description of such genes see, for example, Table 2. For example, a cpsA gene is provided functionally encoding regulation of capsular polysaccharide synthesis, whereas cpsB and cpsC are functionally involved in chain-in-chain length determination. Other genes, such as cpsD, E, F, G, H, I, J, K and related genes, are involved in polysaccharide synthesis, functioning, for example, as glucosyl or glycosyltransferase. The cpsF, G, H, I, J genes encode more type-specific proteins than the flanking genes which are found more-or-less conserved throughout the species and can serve as a base for selection of primers or probes in PCR-amplification or cross-hybridization experiments for subsequent cloning.
The invention further provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis serotype 1 or a gene or gene fragment derived thereof, preferably as identified in FIG. 4 .
In addition, the invention provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis serotype 9 or a gene or gene fragment derived thereof, preferably as identified in FIG. 5 .
Furthermore, the invention provides, for example, a fragment of the cps locus or parts thereof, involved in the capsular polysaccharide biosynthesis, of S. suis, exemplified herein for serotypes 1 , 2 or 9 , and allows easy identification or detection of related fragments derived of other serotypes of S. suis.
The invention provides a nucleic acid probe or primer derived from a nucleic acid according to the invention allowing species or serotype specific serotype-specific detection of Streptococcus suis. Such a probe or primer (used interchangeably herein) is, for example, a DNA, RNA or PNA (peptide nucleic acid) probe hybridizing with capsular nucleic acid as provided by the invention. Species-specific detection is provided preferably by selecting a probe or primer sequence from a species-specific region (e.g. flanking region) whereas serotype-specific detection is provided preferably by selecting a probe or primer sequence from a type-specific region (e.g. central region) of a capsular gene cluster as provided by the invention. Such a probe or primer can be used in a further unmodified form, for example, in cross-hybridization or polymerase-chain reaction (PCR) experiments as, for example, described in the experimental part herein. The invention provides the isolation and molecular characterization of additional type-specific cps genes of S. suis types 1 and 9. In addition, we describe the genetic diversity of the cps loci of serotypes 1, 2 and 9 among the 35 S. suis serotypes known. Type-specific probes are identified. Also, a type-specific PCR, for example, for serotype 9, is provided, being a rapid, reliable and sensitive assay used directly on nasal or tonsillar swabs or other samples of infected or carrier animals.
The invention also provides a probe or primer according to the invention with at least one reporter molecule. Examples of reporter molecules are manifold and known in the art; for example, a reporter molecule can include additional nucleic acid provided with a specific sequence (e.g. oligo-dT) hybridizing to a corresponding sequence in which hybridization can easily be detected, for example, because it has been immobilized to a solid support.
Yet other reporter molecules include chromophores, e.g. fluorochromes for visual detection, for example, by light microscopy or fluorescent in situ hybridization (“FISH”) techniques, or include an enzyme such as horseradish peroxidase for enzymatic detection, for example in enzyme-linked assays (“EIA”). Yet other reporter molecules include radioactive compounds for detection in radiation-based assays.
In a preferred embodiment of the invention, at least one probe or primer according to the invention is provided (labeled) with a reporter molecule and a quencher molecule, together with an unlabeled probe or primer in a PCR-based test allowing rapid detection of specific hybridization.
The invention further provides a diagnostic test or test kit including a probe or primer as provided by the invention. Such a test or test kit is, for example, a cross-hybridization test or PCR-based test advantageously used in rapid detection and/or serotyping of Streptococcus suis.
The invention further provides a protein or fragment thereof encoded by a nucleic acid according to the invention. Examples of such a protein or fragment are proteins described in Table 2. For example, a cpsA protein is provided that functionally encodes regulation of capsular polysaccharide synthesis, whereas cpsB and cpsC are functionally involved in chain-in-chain length determination. Other proteins or functional fragments thereof, as provided by the invention, such as cpsD, E, F, G, H, I, J, K and related proteins, are involved in polysaccharide biosynthesis, functioning, for example, as glucosyl or glycosyltransferase in polysaccharide biosynthesis of Streptococcus suis capsular antigen.
The invention also provides a method of producing a Streptococcus suis capsular antigen including using a protein or functional fragment thereof as provided by the invention, and provides therewith a Streptococcus suis capsular antigen obtainable by such a method.
A comparison of the predicted amino acid sequences of the cps2 genes with sequences found in the databases allowed the assignment of functions to the open reading frames. The central region contains the type-specific glycosyltransferases and the putative polysaccharide polymerase. This region is flanked by two regions encoding for proteins with common functions, such as regulation and transport of polysaccharide across the membrane. Biosynthesis of Streptococcus capsular polysaccharide antigen using a protein or functional fragment thereof is advantageously used in chemo-enzymatic synthesis and the development of vaccines which offer protection against serotype-specific Streptococcal disease, and is also advantageously used in the synthesis and development of multivalent vaccines against Streptococcal infections. Such vaccines elicit ariticapsular antibodies which confer protection.
Furthermore, the invention provides an acapsular Streptococcus mutant for use in a vaccine, a vaccine strain derived thereof and a vaccine derived thereof. Surprisingly, and against the grain of common doctrine, the invention provides use of a Streptococcus mutant deficient in capsular expression in a vaccine.
Acapsular Streptococcus mutants have long been known in the art and can be found in nature. Griffith (J. Hyg. 27:113-159, 1928) demonstrated that pneumococci could be transformed from one type to another. If he injected live rough (acapsular or unencapsulated) type 2 pneumococci into mice, the mice would survive. If, however, he injected the same dose of live rough type 2 mixed with heat-killed smooth (encapsulated) type 1 into a mouse, the mouse would die, and, from the blood, he could isolate live smooth type 1 pneumococci. At that time, the significance of this transforming principle was not understood. However, understanding came when it was shown that DNA constituted the genetic material responsible for phenotypic changes during transformation.
Streptococcus mutants deficient in capsular expression are found in several forms. Some are fully deficient and have no capsule at all, others form a deficient capsule, characterized by a mutation in a capsular gene cluster. Deficiency can, for instance, include capsular formation wherein the organization of the capsular material has been rearranged, as, for example, demonstrable by electron microscopy. Yet others have a nearly fully developed capsule which is only deficient in a particular sugar component.
Now, after much advance of biotechnology and despite the fact that little is still known about the exact localization and sequence of genes involved in capsular synthesis in Streptococci, it is possible to create mutants of Streptococci, for example, by homologous recombination or transposon mutagenesis, which has, for example, been done for GAS (Wessels et al., PNAS 88:8317-8321, 1991), for GBS (Wessels et al., PNAS 86: 8983-8987, 1989), for S. suis (Smith, ID-DLO Annual report 1996, page 18-19; Charland et al., Microbiol. 144:325-332, 1998) and S. pneumoniae (Kolkman et al., J. Bact. 178:3736-3741, 1996). Such recombinant derived mutants, or isogenic mutants, can easily be compared with the wild-type strains from which they have been derived.
In a preferred embodiment, the invention provides use of a recombinant-derived Streptococcus mutant deficient in capsular expression in a vaccine. Recombinant techniques useful in producing such mutants are, for example, homologous recombination, transposon mutagenesis, and others, wherein deletions, insertions or (point) mutations are introduced in the genome. Advantages of using recombinant techniques include the stability of the obtained mutants (especially with homologous recombination and double crossover techniques), and the knowledge about the exact site of the deletion, mutation or insertion.
In another embodiment, the invention provides a stable mutant deficient in capsular expression obtained, for example, through homologous recombination or crossover integration events. Examples of such a mutant can be found herein, for example, mutants 1OcpsB or 10cpsEF are stable mutants as provided by the invention.
The invention also provides a Streptococcus vaccine strain and vaccine that has been derived from a Streptococcus mutant deficient in capsular expression. In general, the strain or vaccine is applicable within the whole range of Streptococcal infections, including animals or man or with zoonotic infections. It is, of course, now possible to first select a common vaccine strain and derive a Streptococcus mutant deficient in capsular expression thereof for the selection of a vaccine strain and use in a vaccine according to the invention.
In a preferred embodiment, the invention provides use of a Streptococcus mutant deficient in capsular expression in a vaccine wherein the Streptococcus mutant is selected from the group composed of Streptococcus group A, Streptococcus group B, Streptococcus suis and Streptococcus pneumoniae. Herewith the invention provides vaccine strains and vaccines for use with these notoriously heterologous Streptococci, of which a multitude of serotypes exist. With a vaccine, as provided by the invention, that is derived from a specific Streptococcus mutant that is deficient in capsular expression, the difficulties relating to lack of heterologous protection can be circumvented since these mutants do not rely on capsular antigens, per se, to induce protection.
In a preferred embodiment, the vaccine strain is selected for its ability to survive, or even replicate, in an immune-competent host or host cells and thus can persist for a certain period, varying from 1-2 days to more than one or two weeks, in a host, despite its deficient character.
Although an immunodeficient host will support replication of a wide range of bacteria that are deficient in one or more virulence factors, in general, it is considered a characteristic of pathogenicity of Streptococci that they can survive for certain periods or replicate in a normal host or host cells such as macrophages. For example, Wiliams and Blakemore (Neuropath. Appl. Neurobiol.: 16, 345-356, 1990; Neuropath. Appl. Neurobiol.: 16, 377-392, 1990; J. Infect. Dis.: 162, 474-481, 1990) show that both polymorphonuclear cells and macrophage cells are capable of phagocytosing pathogenic S. suis in pigs lacking anti-S. suis antibodies; only pathogenic bacteria could survive and multiply inside macrophages and the pig.
In a preferred embodiment, the invention, however, provides a deficient or avirulent mutant or vaccine strain which is capable of surviving at least 4-5 days, preferably at least 8-10 days in the host, thereby allowing the development of a solid immune response to subsequent Streptococcus infection.
Due to its persistent but avirulent character, a Streptococcus mutant or vaccine strain, as provided by the invention, is well suited to generate specific and/or long-lasting immune responses against Streptococcal antigens. Moreover, possible specific immune responses of the host directed against a capsule are relatively irrelevant because a vaccine strain, as provided by the invention, is typically not recognized by such antibodies.
In addition, the invention provides a Streptococcus vaccine strain according to the invention, which strain includes a mutant capable of expressing a Streptococcus virulence factor or antigenic determinant.
In a preferred embodiment, the invention provides a Streptococcus vaccine strain, according to the invention, which includes a mutant capable of expressing a Streptococcus virulence factor wherein the virulence factor or antigenic determinant is selected from a group of cellular components, such as muramidase-released protein (“MRP”), extracellular factor (“EF”) and cell-membrane associated proteins 60kDA heat shock protein, pneumococcal surface protein A (Psp A), pneumolysin, C protein, protein M, fimbriae, hemagglutinins and hemolysin or components functionally related thereto.
In a preferred embodiment, the invention provides a Streptococcus vaccine strain including a mutant capable of over-expressing the virulence factor. In this way, the invention provides a vaccine strain for incorporation in a vaccine which specifically causes a host immune response directed against antigenically important determinants of virulence (listed above), thereby providing specific protection against the determinants. Over-expression can, for example, be achieved by cloning the gene involved behind a strong promoter, which is, for example, constitutionally expressed in a multicopy system, either in a plasmid or via intergration in a genome.
In yet another embodiment, the invention provides a Streptococcus vaccine strain, according to the invention, including a mutant capable of expressing a non-Streptococcus protein. Such a vector-Streptococcus vaccine strain allows, when used in a vaccine, protection against pathogens other than Streptococcus.
Due to its persistent but avirulent character, a Streptococcus vaccine strain or mutant as provided by the invention is well suited to generate specific and long-lasting immune responses, not only against Streptococcal antigens, but also against other antigens expressed by the strain. Specifically, antigens derived from another pathogen are now expressed without the detrimental effects of the antigen or pathogen which would otherwise have harmed the host.
An example of such a vector is a Streptococcus vaccine strain or mutant wherein the antigen is derived from a pathogen, such as Actinobacillus pleuropneumonia, Mycoplasmatae, Bordetella, Pasteurella, E. coli, Salmonella, Campylobacter, Serpulina and others.
The invention also provides a vaccine including a Streptococcus vaccine strain or mutant according to the invention and a pharmaceutically acceptable carrier or adjuvant. Carriers or adjuvants are well known in the art; examples are phosphate buffered saline, physiological salt solutions, (double-) oil-in-water emulsions, aluminumhydroxide, Specol, block- or co-polymers, and others.
A vaccine according to the invention can include a vaccine strain either in a killed or live form. For example, a killed vaccine including a strain having (over) expressed a Streptococcal or heterologous antigen or virulence factor is very well suited for eliciting an immune response. In a preferred embodiment, the invention provides a vaccine wherein the strain is live, due to its persistent but avirulent character; a Streptococcus vaccine strain, as provided by the invention, is well suited to generate specific and long-lasting immune responses.
The invention also provides a method for controlling or eradicating a Streptococcal disease in a population comprising vaccinating subjects in the population with a vaccine according to the invention.
In a preferred embodiment, a method for controlling or eradicating a Streptococcal disease is provided including testing a sample, such as a blood sample, or nasal or throat swab, feces, urine, or other samples such as can be sampled at or after slaughter, collected from at least one subject, such as an infant or a pig, in a population partly or wholly vaccinated with a vaccine according to the invention for the presence of encapsulated Streptococcal strains or mutants. Since a vaccine strain or mutant according to the invention is not pathogenic, and can be distinguished from wild-type strains by capsular expression, the detection of (fully) encapsulated Streptococcal strains indicates that wild-type infections are still present. Such wild-type infected subjects can then be isolated from the remainder of the population until the infection has passed. With domestic animals, such as pigs, it is even possible to remove the infected subject from the population as a whole by culling. Detection of wild-type strains can be achieved via traditional culturing techniques, or by rapid detection techniques such as PCR detection.
In yet another embodiment, the invention provides a method for controlling or eradicating a Streptococcal disease including testing a sample collected from at least one subject in a population partly or wholly vaccinated with a vaccine according to the invention for the presence of capsule-specific antibodies directed against Streptococcal strains. Capsule specific antibodies can be detected with classical techniques known in the art, such as used for Lancefield's group typing or serotyping.
A preferred embodiment for controlling or eradicating a Streptococcal disease in a population includes vaccinating subjects in the population with a vaccine according to the invention and testing a sample collected from at least one subject in the population for the presence of encapsulated Streptococcal strains and/or for the presence of capsule-specific antibodies directed against Streptococcal strains.
For example, a method is provided wherein the Streptococcal disease is caused by Streptococcus suis.
The invention also provides a diagnostic assay for testing a sample for use in a method according to the invention including at least one means for the detection of encapsulated Streptococcal strains and/or for the detection of capsule-specific antibodies directed against Streptococcal strains.
The invention further provides a vaccine including an antigen according to the invention and a suitable carrier or adjuvant. The immunogenicity of a capsular antigen provided by the invention is, for example, increased by linking to a carrier (such as a carrier protein), allowing the recruitment of T-cell help in developing an immune response.
The invention further provides a recombinant microorganism provided with at least a part of a capsular gene cluster derived from Streptococcus suis. The invention provides, for example, a lactic acid bacterium provided with at least a part of a capsular gene cluster derived from Streptococcus suis. Various food-grade lactic acid bacteria (Lactococcus lactis, Lactobacillus casei, Lactobacillus plantarium and Streptococcus gordonii) have been used as delivery systems for mucosal immunization. It has now been shown that oral (or mucosal) administration of recombinant L. lactis, Lactobacillus, and Streptococcus gordonii can elicit local IgA and/or IgG antibody responses to an expressed antigen. The use of oral routes for immunization against infective diseases is desirable because oral vaccines are easier to administer and have higher compliance rates, and because mucosal surfaces are the portals of entry for many pathogenic microbial agents. It is within the skill of the artisan to provide such micro-organisms with (additional) genes.
The invention further provides a recombinant Streptococcus suis mutant provided with a modified capsular gene cluster. It is within the skill of the artisan to swap genes within a Species. In a preferred embodiment, an avirulent Streptococcus suis mutant is selected to be provided with at least a part of a modified capsular gene cluster according to the invention.
The invention further provides a vaccine including a microorganism or a mutant provided by the invention. An advantage of such a vaccine over currently used vaccines is that they include accurately defined microorganisms and well-characterized antigens, allowing accurate determination of immune responses against various antigens of choice.
The invention is further explained in the experimental part of this description without limiting the invention thereto.
DESCRIPTION OF THE FIGURES
FIG. 1 illustrates the organization of the cps2 gene cluster of S. suis type 2.
(A) Genetic map of the cps2 gene cluster. The shadowed arrows represent potential ORFs. Interrupted ORFs indicate the presence of stop codons or frame-shift mutations. Gene designations are indicated below the ORFs. The closed arrows indicate the position of the potential promoter sequences. I indicates the position of the potential transcription regulator sequence. III indicates the position of the 100-bp repeated sequence. (B) Physical map of the cps2 locus. Restriction sites are as follows: A: Alul; C: ClaI, E: EcoRI; H: HindIII; K: KpnI; M: MluI; N: NsiI; P: PstI; S: SnaBI; Sa: SacI; X: XbaI. (C) The DNA fragments cloned in the various plasmids.
FIG. 2 illustrates ethidium bromide stained agarose gel showing PCR products obtained with chromosomal DNA of S. suis strains belonging to the serotypes 1,2, ½, 2, 9 and 14 and cps2J, cpsII, and cps9H primer sets as described herein.
(A) cpsII primers; (B) cps2J primers and (C) cps9H primers. Lanes 1-3: serotype 1 strains; lanes 4-6: serotype 2 strains; lanes 7-9: serotype ½ strains; lanes 10-12: serotype 9 strains and lanes 13-15: serotype 14 strains. (B) Ethidium bromide stained agarose gel showing PCR products obtained with tonsillar swabs collected from pigs carrying S. suis type 2, type 1 or type 9 strains and cps2J, cpsII and cpsH primer sets as described in Materials and Methods. Bacterial DNA suitable for PCR was prepared by using the multiscreen methods as described previously (20). (C) cpsII primers. (B) cps2J primers and (C) cps9H primers. Lanes 1-3: PCR products obtained with tonsillar swabs collected from pigs carrying S. suis type 1 strains; lanes 4-6: PCR products obtained with tonsillar swabs collected from pigs carrying S. suis type 2 strains; lanes 7-9: PCR products obtained with tonsillar swabs collected from pigs carrying S. suis type 9 strains; lanes 10-12: PCR products obtained with chromosomal DNA from serotype 9, 2 and 1 strains respectively; lane 13: negative control, no DNA present.
FIG. 3 illustrates the CPS2 nucleotide sequences and corresponding amino acid sequences from the open reading frames.
FIG. 4 illustrates the CPS 1 nucleotide sequences and corresponding, amino acid sequences from the open reading frames.
FIG. 5 illustrates the CPS9 nucleotide sequences and corresponding amino acid sequences from the open reading frames.
FIG. 6 illustrates the CPS7 nucleotide sequences and corresponding amino acid sequences from the open reading frames.
FIG. 7 illustrates alignment of the N-terminal parts of Cps2J and Cps2K.
Identical amino acids are marked by bars. The amino acids shown in bold are also conserved in CPS14I Cps14J of S. pneumoniae and several other glycosyltransferases (19). The aspartate residues marked by asterisks are strongly conserved.
FIG. 8 illustrates transmission electron micrographs of thin sections of various S. suis strains.
(A) wild type strain 10;
(B) mutant strain 10cpsB;
(C) mutant strain 10cpsEF.
Bar=100 nm
FIG. 9 illustrates the kinetics of phagocytosis of wild type and mutant S. suis strains.
(A) Kinetics of phagocytosis of wild type and mutant S. suis strains by porcine alveolar macrophages. Phagocytosis was determined as described herein. The Y-axis represents the number of CFU per milliliter in the supernatant fluids as determined by plate counting, the X-axis represents time in minutes.
▭ wild type strain 10;
o mutant strain 10cpsB;
Δ mutant strain 10cpsEF.
(B) Kinetics of intracellular killing of wild type and mutant S. suis strains by porcine AM. The intracellular killing was determined as described herein. The Y-axis represents the number of CFU per ml in the supernatant fluids after lysis of the macrophages as determined by plate counting, the X-axis represents time in minutes.
▭ wild type strain 10;
o mutant strain 10cpsB;
Δ mutant strain 10cpsEF.
FIG. 10 illustrates the nucleotide sequence alignment of the highly conserved 100-bp repeated element.
(1) 100-bp repeat between cps2G and cps2H
(2) 100-bp repeat within “cps2M”
(3) 100-bp repeat between cps2O and cps2P
FIG. 11 illustrates the cps2, cps9 and cps7 gene clusters of S. suis serotypes 2, 9 and 7.
(A) Genetic organization of the cps2 gene cluster [84]. The large arrows represent potential ORFs. Gene designations are indicated below the ORFs. Identically filled arrows represent ORFs which showed homology. The small closed arrows indicate the position of the potential promoter sequences. | indicates the position of the potential transcription regulator sequence. (B) Physical map and genetic organization of the cps9 gene cluster [15]. Restriction sites are as follows: B: BamHI; P: PstI; H: HindIII; X: XbaI. The DNA fragments cloned in the various plasmids are indicated. The open arrows represent potential ORFs. (C) Physical map and genetic organization of the cps7 gene cluster. Restriction sites are as follows: C: Clal; P: PstI; Sc: ScaI. The DNA fragments cloned in the various plasmids are indicated. The open arrows represent potential ORFs.
FIG. 12 illustrates ethidium bromide stained agarose gel showing PCR products.
(A) Ethidium bromide stained agarose gel showing PCR products obtained with chromosomal DNA of S. suis strains belonging to the serotypes 1, 2, 9 and 7 and the cps7H primer set. Strain designations are indicated above the lanes. C: negative control, no DNA present. M: molecular size marker (lambda digested with EcoRI and HindIII). (B) Ethidium bromide stained agarose gel showing PCR products obtained with serotype 7 strains collected in different countries and from different organs. Bacterial DNA suitable for PCR was prepared by using the multiscreen method as described herein [89]. Strain designations are indicated above the lanes. M: molecular size marker (lambda digested with EcoRI and HindIII).
DETAILED DESCRIPTION OF THE INVENTION
Experimental part
Material and Methods
Bacterial strains and growth conditions.
The bacterial strains and plasmids used in this study are listed in Table 1. S. suis strains were grown in Todd-Hewitt broth (code CM189, Oxoid), and plated on Columbia agar blood base (code CM331, Oxoid) containing 6% (v/v) horse blood. E. coli strains were grown in Luria broth (28) and plated on Luria broth containing 1.5% (w/v) agar. If required, antibiotics were added to the plates at the following concentrations: spectinomycin: 100 μg/ml for S. suis and 50 μg/ml for E. coli and ampicillin, 50 μg/ml.
Serotyping. The S. suis Strains were serotyped by the slide agglutination test with serotype-specific antibodies (44).
DNA techniques. Routine DNA manipulations were performed as described by Sambrook et al. (36).
Alkaline phosphatase activity. To screen for PhoA fusions in E. coli, plasmid libraries were constructed. Therefore, chromosomal DNA of S. suis type 2 was digested with AluI. The 300-500-bp fragments were ligated to Smal-digested pPHOS2. Ligation mixtures were transformed to the PhoA E. coli strain CC118. Transformants were plated on LB media supplemented with 5-Bromo-4-chloro-3-indolylfosfaat (BCIP, 50 μg/ml, Boehringer, Mannheim, Germany). Blue colonies were purified on fresh LB/BCIP plates to verify the blue phenotype.
DNA sequence analysis. DNA sequences were determined on a 373A DNA Sequencing System (Applied Biosystems, Warrington, GB). Samples were prepared by using an ABI/PRISM dye terminator cycle sequencing ready reaction kit (Applied Biosystems). Sequencing data were assembled and analyzed using the MacMollyTetra program. Custom-made sequencing primers were purchased from Life Technologies. Hydrophobic stretches within proteins were predicted by the method of Klein et al. (17). The BLAST program available on Netscape Navigator™ was used to search for protein sequences related to the deduced amino acid sequences.
Construction of gene-specific knock-out mutants of S. suis. To construct the mutant strains 10cpsB and 10cpsEF, we electrotransformed the pathogenic serotype 2 strain 10 (45, 49) of S. suis with pCPS 11 and pCPS28 respectively. In these plasmids, the cpsB and cpsEF genes were disturbed by the insertion of a spectinomycin-resistance gene. To create pCPS11, the internal 400 by PstIBamHI fragment of the cpsB gene in pCPS7 was replaced by the Spc R gene. For this purpose, pCPS7 was digested with PstI and BamHI and ligated to the 1,200-bp PstI-BamHi fragment, containing the Spc R gene; from pIC-spc. To construct pCPS28, we have used pIC20R. In this plasmid we inserted the KpnI-SalI fragment from pCPS17 (resulting in pCPS25) and the XbaI-ClaI fragment from pCPS20 (resulting in pCPS27). pCPS27 was digested with PstI and XhoI and ligated to the 1,200-bp Pstl-Xhol fragment, containing the Spc R gene of pIC-spc. The electrotransformation to S. suis was carried out as described before (38).
Southern blotting and hybridization. Chromosomal DNA was isolated as described by Sambrook et al. (36). DNA fragments were separated on 0.8% agarose gels and transferred to Zeta-Probe GT membranes (Bio-Rad) as described by Sambrook et al. (36). DNA probes were labeled with [( −32 p] dCTP (3000 Ci mmol −1 ; Amersham) by use of a random primed labeling kit (Boehringer). The DNA on the blots was hybridized at 65° C. with appropriate DNA probes as recommended by the supplier of the Zeta-Probe membranes. After hybridization, the membranes were washed twice with a solution of 40 mM sodium phosphate, pH 7.2, 1 mM EDTA, 5% SDS for 30 min at 65° C. and twice with a solution of 40 mM sodium phosphate, pH 7.2, 1 mM EDTA, 1% SDS for 30 min at 65° C.
PCR. The primers used in the cps2J PCR correspond to the positions 13791-13813 and 14465-14443 in the S. suis cps2 locus. The sequences were: 5′-CAAACGCAAGGAATTACGGTATC-3′ (SEQ. ID. No. 1) and 5′-GAGTATCTAAAGAATGCCTATTG-3′ (SEQ. ID. No. 2). The primers used for the cpslI PCR correspond to the positions 4398-4417 and 4839-4821 in the S. suis cps1 sequence. The sequences were: 5′-GGCGGTCTAGCAGATGCTCG-3′ (SEQ. ID. No. 3) and 5′-GCGAACTGTTAGCAATGAC-3′ (SEQ. ID. No. 4). The primers used in the cps9H PCR correspond to the positions 4406-4126 and 4494-4475 in the S. suis cps9 sequence. The sequences were: 5′-GGCTACATATAATGGAAGCCC3′ (SEQ. ID No. 5) and 5′-CGGAAGTATCTGGGCTACTG-3′ (SEQ. ID. No. 6).
Construction of gene-specific knock-out mutants of S. suis. To construct the mutant strains 10cpsB and 10cpsEF, we electrotransformed the pathogenic serotype 2 strain 10 of S. suis with pCPS11 and pCPS28 respectively. In these plasmids, the cpsB and cpsEF genes were disturbed by the insertion of a spectinomycin-resistance gene. To create pCPS11, the internal 400 bp PstI-BamHI fragment of the cpsB gene in pCPS7 was replaced by the Spc R gene. For this purpose, pCPS7 was digested with PstI and BamHI and ligated to the 1,200-bp PstI-BamHI fragment, containing the Spc R gene, from pIC-spc. To construct pCPS28, we have used pIC20R. In this plasmid, we inserted the KpnI-SalI fragment from pCPS17 (resulting in pCPS25) and the XbaI-ClaI fragment from pCPS20 (resulting in pCPS27). pCPS27 was digested with PSI and XhoI and ligated to the 1,200-bp PstI-XhoI fragment, containing the Spc R gene of pIC-spc. The electrotransformation to S. suis was carried out as described before (38).
Phagocytosis assay. Phagocytosis assays were performed as described by Leij et al. (23). Briefly, to opsonize the cells, 10 7 S. suis cells were incubated with 6% SPF-pig serum for 30 min at 37° C. in a head-over-head rotor at 6 rpm. 10 7 AM and 10 7 opsonized S. suis cells were combined and incubated at 37° C. under continuous rotation at 6 rpm. At 0, 30, 60 and 90 min, 1- ml samples were collected and mixed with 4 ml of ice-cold EMEM to stop phagocytosis. Phagocytes were removed by centrifugation for 4 min at 110×g and 4° C. The number of colony-forming units, (“CFU”) in the supernatants was determined. Control experiments were carried out simultaneously by combining 10 7 opsonized S. suis cells with EMEM (without AM).
Killing assays. AM (10 7 /ml) and opsonized S. suis cells (10 7 /ml) were mixed 1:1 and incubated for 10 min at 37° C. under continuous rotation at 6 rpm. Ice-cold EMEM was added to stop further phagocytosis and killing. To remove extracellular S. suis cells, phagocytes were washed twice (4 min, 110×g, 4° C.) and resuspended in 5 ml EMEM containing 6% SPF serum. The tubes were incubated at 37° C. under rotation at 6 rpm. After 0, 15, 30, 60 and 90 min, samples were collected and mixed with ice-cold EMEM to stop further killing. The samples were centrifuged for 4 min at 110×g at 4° C. and the phagocytic cells were lysed in EMEM containing 1% saponine for 20 min at room temperature. The number of CFU in the suspensions was determined.
Pigs. Germfree pigs, crossbreeds of Great Yorkshire and Dutch Landrace, were obtained from sows by caesarian sections. The surgery was performed in sterile flexible film isolators. Pigs were allotted to groups, each consisting of 4 pigs, and were housed in sterile stainless steel incubators.
Experimental infections. Pigs were inoculated intranasally with S. suis type 2 as described before. To predispose the pigs for infection with S. suis, five-day old pigs were inoculated intranasally with about 10 7 CFU of Bordetella bronchiseptica strain 92932. Two days later, the pigs were inoculated intranasally with S. suis type 2 (10 6 CFU). Pigs were monitored twice daily for clinical signs of disease, such as fever, nervous signs and lameness. Blood samples were collected three times a week from each pig. White blood cells were counted with a cell counter. To monitor infection with S. suis and B. bronchiseptica and to check for absence of contaminants, we collected swabs of nasopharynx and feces daily. The swabs were plated directly onto Columbia agar containing 6% horse blood. After three weeks, the pigs were killed and examined for pathological changes. Tissue specimens from the central nervous system, serosae, and joints were examined bacteriologically and histologically as described herein (45, 49). Colonization of the serosae was scored positively when S. suis was isolated from the pericardium, thoracal pleura or the peritoneum. Colonization of the joints was scored positively when S. suis was isolated from one or more joints (12 joints per animal were scored).
Vaccination and challenge. One week old pigs were vaccinated intravenously with a dosage of 106 cfu of the S. suis strains 10cpsEF or 10cpsB. Three weeks later, the pigs were challenged intravenously with the pathogenic Serotype 2 strain 10 (107 cfu). Disease monitoring, hematological, serological and bacteriological examinations as well as post-mortum examinations were as described before under experimental infections.
Electron Microscopy. Bacteria were prepared for electron microscopy as described by Wagenaar et al. (50). Shortly, bacteria were mixed with agarose ND (Boehringer) of 37° C. to a concentration of 0.7%. The mixture was immediately cooled on ice. Upon gelifying, samples were cut into 1 to 1.5 mm slices and incubated in a fixative containing 0.8% glutaraldehyde and 0.8% osmiumtetraoxide. Subsequently, the samples were fixed and stained with uranyl acetate by microwave stimulation, dehydrated and imbedded in eponaraldite resin. Ultra-thin sections were counterstained with lead citrate and examined with a Philips CM 10 electron microscope at 80 kV ( FIG. 8 ).
Isolation of porcine alveolar macrophages (AM). Porcine AM were obtained from the lungs of specific pathogen free (“SPF”) pigs. Lung lavage samples were collected as described by van Leengoed et al. (43). Cells were suspended in EMEM containing 6% (v/v). SPF-pig serum and adjusted to 10 7 cells per ml.
RESULTS
Identification of the cps locus.
The cps locus of S. suis type 2 was identified through a strategy developed for the genetic identification of exported proteins (13, 31). In this system, we used a plasmid (pPHOS2) containing a truncated alkaline phosphatase gene (13). The gene lacked the promoter sequence, the translational start site and the signal sequence. The truncated gene is preceded by a unique Smal restriction site. Chromosomal DNA of S suis type 2, digested with AluI, was randomly cloned in this restriction site. Because translocation of PhoA across the cytoplasmic membrane of E. coli is required for enzymatic activity, the system can be used to select for S. suis fragments containing a promoter sequence, a translational start site and a functional signal sequence. Among 560 individual E. coli clones tested, 16 displayed a dark blue phenotype when plated on media containing BCIP. DNA sequence analysis of the inserts from several of these plasmids was performed (results not shown) and the deduced amino acid sequences were analyzed. The hydrophobicity profile of one of the clones (pPHOS7, results not shown) showed that the N-terminal part of the sequence resembled the characteristics of a typical signal peptide: a short hydrophilic N-terminal region is followed by a hydrophobic region of 38 amino acids. These data indicate that the phoA system was successfully used for the selection of S. suis genes encoding exported proteins. Moreover, the sequences were analyzed for similarities present in the databases. The sequence of pPHOS7 showed a high similarity (37% identity) with the protein encoded by the cps14C gene of Streptococcus pneumoniae (19). This strongly suggests that pPHOS7 contains a part of the cps operon of S. suis type 2.
Cloning of the flanking cps genes. In order to clone the flanking cps genes of S. suis type 2, the insert of pPHOS7 was used as a probe to identify chromosomal DNA fragments which contain flanking cps genes. A 6-kb HindIII fragment was identified and cloned in pKUN19. This yielded clone pCPS6 ( FIG. 1 , part C). Sequence analysis of the insert of pCPS6 revealed that pCPS6 most probably contained the 5′-end of the cps locus, but still lacked the 3′-end. Therefore, sequences of the 3′-end of pCPS6 were in turn used as a probe to identify chromosomal fragments containing cps sequences located further downstream. These fragments were also cloned in pKUN19, resulting in pCPS17. Using the same system of chromosomal walking, we subsequently generated the plasmids pCPS18, pCPS20, pCPS23 and pCPS26, containing downstream cps sequences.
Analysis of the cps operon. The complete nucleotide sequence of the cloned fragments was determined ( FIG. 4 ). Examination of the compiled sequence revealed the presence of at least 13 potential open reading frames (Orfs), which were designated as Orf 2Y, Orf2X and Cps2A-Cps2K ( FIG. 1 , part A; FIG. 11, part A). Moreover, a 14th, incomplete Orf (Orf 2Z) was located at the 5′-end of the sequence. Two potential promoter sequences were identified. One was located 313 bp (locations 1885-1865 and 1884-1889) upstream of Orf2X. The other potential promoter sequence was located 68 bp upstream of Orf2Y (locations 2241-2236 and 2216-2211). Orf2Y is expressed in opposite orientation. Between Orfs 2Y and 2Z, the sequence contained a potential stem-loop structure, which could act as a transcription terminator. Each Orf is preceded by a ribosome-binding site and the majority of the Orfs are very closely linked. The only significant intergenic gap was found between Cps2G and Cps2H (389 nucleotides). However, no obvious promoter sequences or potential stem-loop structures were found in this region. These data suggest that Orf2X and Cps2A-Cps2K are arranged as an operon.
An overview of all Orfs with their properties is shown in Table 2. The majority of the predicted gene products is related to proteins involved in polysaccharide biosynthesis. Orf2Z showed some similarity with the YitS protein of Bacillus subtilis. YitS was identified during the sequence analysis of the complete genome of B. subtilis. The function of the protein is unknown.
Orf2Y showed similarity with the YcxD protein of B. subtilis (53). Based on the similarity between YcxD and MocR of Rhizohium meliloti (33), YcxD was suggested to be a regulatory protein.
Orf2X showed similarity with the hypothetical YAAA proteins of Haemophilus influenzae and E. coli. The function of these proteins is unknown.
The gene products encoded by the cps2A, cps2B, cps2C and cps2D genes showed approximate similarity with the CpsA, CpsC, CpsD and CpsB proteins of several serotypes of Streptococcus pneumoniae (19), respectively. This suggests similar functions for these proteins. Hence, Cps2A may have a role in the regulation of the capsular polysaccharide synthesis. Cps2B and Cps2C could be involved in the chain length determination of the type 2 capsule and Cps2C can play an additional role in the export of the polysaccharide. The Cps2D protein of S. suis is related to the CpsB protein of S. pneumoniae and to proteins encoded by genes of several other Gram-positive bacteria involved in polysaccharide or exopolysaccharide synthesis, but their function is unknown (19).
The protein encoded by the cps2E gene showed similarity to several bacterial proteins with glycosyltransferase activities Cps14E and Cps19fE of S. pneumoniae serotypes 14 and 19F (18, 19, 29), CpsE of Streptococcus salvarius (X94980) and CpsD of Streptococcus agalactiae (34). Recently. Kolkman et al. (18) showed that Cps14E is a glucosyl-1-phosphate transferase that links glucose to a lipid carrier, the first step in the biosynthesis of the S. pneumoniae type 14 repeating unit. Based on these data, a similar function may be fulfilled by Cps2E of S. suis.
The protein encoded by the cps2F gene showed similarity to the protein encoded by the rfbU gene of Salmonella enteritica.(25). This similarity is most pronounced in the C-terminal regions of these proteins. The rfbU gene was shown to encode mannosyltransferase activity (25).
The cps2G gene encoded a protein that showed moderate similarity with the rfbF gene product of Campylohacter hyoilei (22), the epsF gene product of S. thermophilus (40) and the capM gene product of S. aureus (24). On the basis of similarity, the rfbF, epsF and capM genes are suggested to encode galactosyltransferase activities. Hence, a similar glycosyltransferase activity could be fulfilled by the cps2G gene product.
The cps2H gene encodes a protein that is similar to the N-terminal region of the lgtD gene product of Haemophilus influenzae (U32768). Moreover, the hydrophobicity plots of Cps2H and LgtD looked very similar in these regions (data not shown). Based on sequence similarity, the IgtD lgtD gene product was suggested to have glycosyltransferase activity (U32768).
The gene product encoded by the cps2I gene showed some similarity with a protein of Actinobacillus actinomycetemcomitans (AB002668). This protein is part of the gene cluster responsible for the serotype-b-specific antigen of A. actinomycetemcomitans. The function of the protein is unknown.
The gene products encoded by the cps2J and cps2K genes showed significant similarities to the Cps14J protein of S. pneumoniae. The cps14J gene of S. pneumoniae was shown to encode a β-1,4-galactosyltransferase activity. In S. pneumoniae, CpsJ is responsible for the addition of the fourth (i.e. last) sugar in the synthesis of the S. pneumoniae serotype 14 polysaccharide (20). Even some similarity was found between Cps2J and Cps2K ( FIG. 2 , 25.5% similarity). This similarity was most pronounced in the N-terminal regions of the proteins ( FIG. 7 ). Recently, two small conserved regions were identified in the N-terminus of Cps14J and Cps14I and their homologues (20). These regions were predicted to be important for catalytic activity. Both regions, DXS and DXDD ( FIG. 2 ), were also found in Cps2J and Cps2K.
Distribution of the cps2 genes in other S. suis serotypes. To examine the relationship between the cps2 genes and cps genes in the other S. suis serotypes, we performed crosshybridization experiments. DNA fragments of the individual cps2 genes were amplified by PCR, labeled with 32 P, and used to probe Southern blots of chromosomal DNA of the reference strains of the 35 different S. suis serotypes. Large variations in the hybridization patterns were observed (Table 4). As a positive control, we used a probe specific for 16S rRNA. The 16S rRNA probe hybridized with all serotypes tested. However, none of the other genes tested were common in all serotypes. Based on the genetic organization of the genes, we previously suggested that orfX and cpsA-cpsK genes are part of one operon and that the proteins encoded by these genes are all involved in polysaccharide biosynthesis. OrfY and OrfZ are not a part of this operon, and their role in the polysaccharide biosynthesis is unclear. Based on sequence similarity data, OrfY may be involved in regulation of the cps2 genes. OrfZ is proposed to be unrelated to polysaccharide biosynthesis. Probes specific for the orfZ, orfY, orfX, cpsA, cpsB, cpsC and cpsD genes hybridized with most other serotypes. This suggests that the proteins encoded by these genes are not type-specific, but may perform more common functions in biosynthesis of the capsular polysaccharide. This confirms previous data which showed that the cps2A-cps2D genes showed strong similarity to cps genes of several serotypes of Streptococcus pneumoniae. Based on this similarity, Cps2A is possibly a regulatory protein, whereas Cps2B and Cps2C may play a role in length determination and export of polysaccharide. The cps2E gene hybridized with DNA of Serotypes 1, 2, 14 and ½. The cps2E gene showed a strong similarity to the cps14E gene of S. pneumoniae (18). T enzyme was shown to have a glucosyl-1-phosphate activity and catalyzed the transfer of glucose to a lipid carrier (18). These data indicate that a glycosyltransferase closely related to Cps14E may be responsible for the first step in the biosynthesis of polysaccharide in the S. suis serotypes 1, 2, 14 and ½. The cps2F, cps2G, cps2H, cps2I and cps2J genes hybridized with chromosomal DNA of serotypes 2 and ½ only. The cps2G gene showed an additional weak hybridization signal with DNA of serotype 34. In agglutination tests, serotype ½ showed agglutination with sera specific for serotype 2 as well as with sera specific for serotype 1. This suggests that serotype ½ shares antigenic determinants with both types 1 and 2. The hybridization data confirmed these data. All putative glycosyltransferases present in serotype 2 are also present in serotype ½. The cps2K gene showed a hybridization pattern similar to the cps2E gene. Hybridization was observed with DNA of serotypes 1, 2, 14 and ½. Taken together, these hybridization data show that the cps2 gene cluster can be divided into three regions: a central region containing the type-specific genes is flanked by two regions containing common genes for various serotypes.
Cloning of the type-specific cps genes of serotypes 1 and 9. To clone the type-specific cps genes of S. suis serotype 1, we used the cps2E gene as a probe to identify chromosomal DNA fragments of type 1 which contain flanking cps genes. A 5 kb EcoRV fragment was identified and cloned in pKUN19. This yielded pCPS1-1 ( FIG. 1 , part B). This fragment was in turn used as a probe to identify an overlapping 2.2 kb HindIII fragment. pKUN19 containing this HindIII fragment was designated pCPS1-2. The same strategy was followed to identify and clone the type-specific cps genes of serotype 9. In this case, we used the cps2D gene as a probe. A 0.8 kb HindIII-XbaI fragment was identified and cloned, yielding pCPS9-1 ( FIG. 1 , part C). This fragment was in turn used as a probe to identify a 4 kb XbaI fragment. pKUN19 containing this 4 kb XbaI fragment was designated pCPS9-2.
Analysis of the cloned cpsl genes. The complete nucleotide sequence of the inserts of pCPS1-1 and pCPS1-2 was determined ( FIG. 5 ). Examination of the sequence revealed the presence of five complete and two incomplete Orfs ( FIG. 1 , part B). Each Orf is preceded by a ribosome-binding site. In accord with data obtained for the cps2 genes of serotype 2, the majority of the Orfs is very closely linked. The only significant gap (718 bp) was found between Cps1G and Cps1H. No obvious promoter sequences or potential stem-loop structures could be found in this region. This suggests that, as in serotype 2, the cps genes in serotype 1 are arranged in an operon.
An overview of the Orfs and their properties is shown in Table 2. As expected on the basis of the hybridization data (Table 4), the protein encoded by the cps1E gene was related to Cps2E of S. suis type 2 (identity of 86%). The fragment cloned in pCPS1-1 lacked the coding region for the first 7 amino acids of the cps1E gene.
The protein encoded by the cps1F and cps1G genes showed strong similarity to the Cps14F and Cps14G proteins of Streptococcus pneumoniae serotype 14, respectively (20). The function of the Cps14F is not completely clear, but it has been suggested that Cps14F has a role in glycosyltransferase activity. The cps14G gene of S. pneumoniae was shown to encode β-1, 4-galactosyltransferase activity. In S. pneumoniae type 14, this activity is required for the second step in the biosynthesis of the oligosaccharide subunit (20). Based on the similarity of the data, similar glyco syltransferase and enhancing activities are suggested for the cps1G and cps1F genes of S. suis type 1.
The protein encoded by the cps1H gene showed similarity to the Cps14M protein of S. pneumoniae (20). Based on sequence similarity, Cps14H was proposed to be the polysaccharide polymerase (20).
The protein encoded by the cps1I gene showed some similarity with the Cps14J protein of S. pneumoniae (19). The cps14J gene was shown to encode a β-1, 4-galactosyltransferase activity, responsible for the addition of the fourth (i.e. last) sugar in the synthesis of the S. pneumoniae serotype 14 polysaccharide.
Between Cps1G and Cps1H, a gap of 718 bp was found. This region revealed three small Orfs. The three Orfs were expressed in three different reading frames and were not preceded by potential ribosome binding sites, nor contained potential start sites. However, the three potential gene products encoded by this region showed some similarity with three successive regions of the C-terminal part of the EpsK protein of Streptococcus thermophilus (27% identity, 40). The region related to the first 82 amino acids is lacking.
Analysis of the cloned cps9 genes. We also determined the complete nucleotide sequence of the inserts of pCPS9-1 and pCPS9-2 ( FIG. 6 ). Examination of the sequence revealed the presence of three complete and two incomplete Orfs ( FIG. 1 , part C). As in serotypes 1 and 2, all Orfs are preceded by a ribosome-binding site and are very closely coupled. As suggested by the hybridization data (Table 4), the Cps2D and Cps9D proteins were highly related (Table 2). Based on sequence comparisons, pCPS9-1 lacked the first 27 amino acids of the Cps9D protein.
The protein encoded by the cps9E gene showed some similarity with the CapD protein of Staphylococcus aureus serotype 1 (24). Based on sequence similarity data, the Cap1D protein was suggested to be an epimerase or a dehydratase involved in the synthesis of N-acetylfiuctosamine or N-acetylgalactosamine (63).
Cps9F showed some similarity to the CapM proteins of S. aureus serotypes 5 and 8 (61, 64, 65). Based on sequence similarity data, Cap5M and Cap8M are proposed to be glycosyltransferases (63).
The protein encoded by the cps9G gene showed some similarity to a protein of Actinobacillus actinomycetemcomitans (AB002668 — 4). This protein is part of a gene cluster responsible for the serotype-b specific serotype b-specific antigens of Actinobacillus actinomycetemcomitans. The function of the protein is unknown.
The protein encoded by the cps 9 H gene showed some similarity to the rfbB gene of Yersinia enterolitica (68). The RfbB protein was shown to be essential for O-antigen synthesis, but the function of the protein in the synthesis of the 0:3 lipopolysaccharide is unknown.
Serotype 1 and serotype 9 specific 9-specific cps genes. To determine whether the cloned fragments in pCPS1-1, pCPS1-2, pCPS9-1 and pCPS9-2 contained the type-specific genes for serotype 1 and 9, respectively, cross-hybridization experiments were performed. DNA fragments of the individual cps1 and cps9 genes were amplified by PCR, labeled with 32 P, and used to probe Southern blots of chromosomal DNA of the reference strains of the 35 different S. suis serotypes. The results are shown in Table 5. Based on the data obtained with the cps2E probe (Table 4), the cps1E probe was expected to hybridize with chromosomal DNA of S. suis serotypes 1, 2, 14, 27 and ½. The cps1H, cps9E and cps9F probes hybridized with most other serotypes However, the cps1F and cps1G and cps1I probes hybridized with chromosomal DNA of serotypes 1 and 14 only. The cps9G and cps9H probes hybridized with serotype 9 only. These data suggest that the cps9G and cps9H probes are specific for serotype 9 and, therefore, could be useful tools for the development of rapid and sensitive diagnostic tests for S. suis type 9 infections.
Type specificType-specific PCR. So far, the probes were tested on the 35 different reference strains only. To test the diagnostic value of the type-specific cps probes further, several other S. suis serotype 1, 2, ½, 9 and 14 strains were used. Moreover, since a PCR-based method would be even more rapid and sensitive than a hybridization test, we tested, whether we could use a PCR for the serotyping of the S. suis strains. The oligonucleotide primer sets were chosen within the cps2J, cps1I and cps9H genes. Amplified fragments of 675 bp, 380 bp and 390 bp were expected, respectively. The results show that 675 bp fragments were amplified on type 2 and ½ strains using cps2J printers; 380 bp fragments were amplified on type 1 and 14 strains using cps1I primers and 390 bp fragments were amplified on type 9 strains using cps9H primers.
Construction of mutants impaired in capsule production. To evaluate the role of the capsule of S. suis type 2 in pathogenesis, we constructed two isogenic mutants in which capsule production was disturbed. To construct mutant 10cpsB, pCPS11 was used. In this plasmid, a part of the cps2B gene was replaced by the spectinomycin-resistance gene. To construct mutant strain 10cpsEF, the plasmid pCPS28 was used. In pCPS28, the 3′-end of cps2E gene, as well as the 5′-end, of cps2F gene, were replaced by the spectinomycin-resistance gene. pCPS 11 and pCPS28 were used to electrotransform strain 10 of S suis type 2 and spectinomycin-resistant colonies were selected. Southern blotting and hybridization experiments were used to select double crossover integration events (results not shown). To test whether the capsular structure of the strains 10cpsB and 10cpsEF was disturbed, we used a slide agglutination test using a suspension of the mutant strains in hyperimmune anti-S. suis type 2 serum (44). The results showed that even in the absence of serotype specific serotype-specific antisera, the bacteria agglutinated. This indicates that, in the mutant strains, the capsular structure was disturbed. To confirm this, thin sections of wild type and mutant strains were compared by electron microscopy. The results showed that, compared to the wild type ( FIG. 3 , part A), the amount of capsule produced by the mutant strains was greatly reduced ( FIG. 3 , parts B and C). Almost no capsular material could be detected on the surface of the mutant strains.
Capsular mutants are sensitive to phagocytosis and killing by porcine alveolar macrophages (“PAM”). The capsular mutants were tested for their ability to resist phagocytosis by PAM in the presence of porcine SPF serum. The wild type strain 10 seemed to be resistant to phagocytosis under these conditions ( FIGS. 9A and 9B ). In contrast, the mutant strains were efficiently ingested by macrophages ( FIGS. 9A and 9B ). After 90 min., more than 99.7% (strain 10cpsB) and 99.8% (strain 10cpsEF) of the mutant cells were ingested by the macrophages. Moreover, as shown in FIGS. 9A and 9B the ingested strains were efficiently killed by the macrophages. 90-98% of all ingested cells were killed within 90 min. No differences could be observed between wild type and mutant strains. These data indicate that the capsule of S. suis type 2 efficiently protects the organism from uptake by macrophages in vitro.
Capsular mutants are less virulent for germfree piglets. The virulence properties of the wild-type and mutant strains were tested after experimental infection of newborn germ-free pigs (45, 49). Table 1 shows that specific and nonspecific signs of disease could be observed in all pigs inoculated with the wild type strain. Moreover, all pigs inoculated with the wild type strain died during the course of the experiment or were killed because of serious illness or nervous disorders (Table 3). In contrast, the pigs inoculated with strains 10cpsB and 10cpsEF showed no specific signs of disease and all pigs survived until the end of the experiment (Table 6). The temperature of the pigs inoculated with the wild type strain increased 2 days after inoculation and remained high until day 5 (Table 3). The temperature of the pigs inoculated with the mutant strains sometimes exceeded 40° C., however, we could observe significant differences in the fever index (i.e. percent of observations in an experimental group during which pigs showed fever (>40° C.)) between pigs inoculated with wild type and mutant strains. All pigs showed increased numbers of polymorphonuclear leucocytes (PMLs) (>10×10 9 PMLs per litre) (Table 3). However, in pigs inoculated with the mutant strains, the percentage of samples with increased numbers of PMLs was considerably lower. S. suis strains and B. bronchiseptica could be isolated from the nasopharynx and feces swab samples of all pigs from 1 day post-infection until the end of the experiment (Table 3). Postmortem, the wild type strain could frequently be isolated from the central nervous system (“CNS”), kidney, heart, liver, spleen, serosae, joints and tonsils. Mutant strains could easily be recovered from the tonsils, but were never recovered from the kidney, liver or spleen. Interestingly, low numbers of the mutant strains were isolated from the CNS, the serosae, the joints, the lungs and the heart. Taken together, these data strongly indicated that mutant S. suis strains, impaired in capsule production, are not virulent for young germfree pigs.
We describe the identification and the molecular characterization of the cps locus, involved in the capsular polysaccharide biosynthesis, of S. suis. Most of the genes seemed to belong to a single transcriptional unit, suggesting a coordinate control of these genes. We assigned functions to most of the gene products. We thereby identified regions involved in regulation (Cps2A), chain length determination (Cps2B, C), export (Cps2C) and biosynthesis (Cps2E, F, G, H, J, K). The region involved in biosynthesis is located at the center of the gene cluster and is flanked by two regions containing genes with more common functions. The incomplete orf2Z gene was located at the 5′-end of the cloned fragment. Orf2Z showed some similarity with the YitS protein of B. subtilis. However, because the function of the YitS protein is unknown, this did not give us any information about the possible function of Orf2Z. Because the orf2Z gene is not a part of the cps operon, a role of this gene in polysaccharide biosynthesis is not expected. The Orf2Y protein showed some similarity with the YcxD protein of B. subtilis (53). The YcxD protein was suggested to be a regulatory protein. Similarly, Orf2Y may be involved in the regulation of polysaccharide biosynthesis. The Orf2X protein showed similarity with the YAAA proteins of H. influenzae and E. coli. The function of these proteins is unknown. In S. suis type 2, the orf2X gene seemed to be the first gene in the cps2 operon. This suggests a role of Orf2X in the polysaccharide biosynthesis. In H. influenzae and E. coli, however, these proteins are not associated with capsular gene clusters. The analysis of isogenic mutants impaired in the expression of Orf2X should give more insight in the presumed role of Orf2X in the polysaccharide biosynthesis of S. suis type 2.
The gene products encoded by the cps2E, cps2F, cps2G, cps2H, cps2J and cps2K genes showed little similarity with glycosyltransferases of several Gram-positive or Gram-negative bacteria (18, 19, 20, 22, 25). The cps2E gene product shows some similarity with the Cps14E protein of S. pneumoniae (18, 19). Cps14E is a glucosyl-1-phosphate transferase that links glucose to a lipid carrier (18). In S. pneumoniae, this is the first step in the biosynthesis of the oligosaccharide repeating unit. The structure of the S. suis serotype 2 capsule contains glucose, galactose, rhamnose, N-acetyl glucosamine and sialic acid in a ratio of 3:1:1:1:1 (7). Based on these data, we conclude that Cps2E of S. suis has glucosyltransferase activity and is involved in the linkage of the first sugar to the lipid carrier.
The C-terminal region of the cps2F gene product showed some similarity with the RfbU of Salmonella enteritica. RfbU was shown to have mannosyltransferase activity (24). Because mannosyl is not a component of the S. suis type 2 polysaccharide, a mannosyltransferase activity is not expected in this organism. Nevertheless, cps2F encodes a glycosyltransferase with another sugar specificity.
Cps2G showed moderate similarity to a family of gene products suggested to encode galactosyltransferase activities (22, 24, 40). Hence, a similar activity is shown for Cps2G.
Cps2H showed some similarity with LgtD of H. influenzae (U32768). Because LgtD was proposed to have glycosyltransferase activity, a similar activity is fulfilled by Cps2H.
Cps2J and Cps2K showed similarity to Cps14J of S. pneumoniae (20). Cps2J showed similarity with Cps14I of S. pneumoniae as well. Cps14I was shown to have N-acetyl glucosaminyltransferase activity, whereas Cps14J has a β-1,4-galactosyltransferase activity (20). In S. pneumoniae, Cps14I is responsible for the addition of the third sugar and Cps14J for the addition of the last sugar in the synthesis of the type 14 repeating unit (20). Because the capsule of S. suis type 2 contains galactose as well as N-acetyl glucosamine components, galactosyltransferase as well as N-acetyl glucoaminyltransferase activities could be envisaged for the cps2J and cps2K gene products, respectively. As was observed for Cps14I and Cps14J, the N-termini of Cps2J and Cps2K showed a significant degree of sequence similarity. Within the N-terminal domains of Cps14I and Cps14J, two small regions were identified, which were also conserved in several other glycosyltransferases (22). Within these two regions, two Asp residues were proposed to be important for catalytic activity. The two conserved regions, DXS and DXDD, were also found in Cps2J and Cps2K.
The function of Cps2I remains unclear. Cps2I showed some similarity with a protein of A. actinomycetemcomitans. Although this protein part is of the gene cluster responsible for the serotype-B-specific antigens, the function of the protein is unknown.
We further describe the identification and characterization of the cps genes specific for S. suis serotypes 1, 2 and 9. After the entire cps2 locus of S. suis serotype 2 was cloned and characterized, functions for most of the cps2 gene products could be assigned by sequence homologies. Based on these data, the glycosyltransferase activities, required for type specificity, could be located in the center of the operon. Cross-hybridization experiments, using the individual cps2 genes as probes on chromosomal DNAs of the 35 different serotypes, confirmed this idea. The regions containing the type-specific genes of serotypes 1 and 9 could be cloned and characterized, showing that an identical genetic organization of the CpS operons of other S. suis serotypes exists. The cps1E, cps1F, cps1G, cps1H, and cps1I genes revealed a striking similarity with cps14E, cps14F, cps14G, cps14H and cps14J genes of S. pneumoniae. Interestingly, S. pneumoniae serotype 14 is the serotype most commonly associated with pneumococcal infections in young children (54), whereas S. suis serotype 1 strains are most commonly isolated from piglets younger than 8 weeks (46). In S. pneumoniae, the cps14E, cps14G, cps14I and cps14J encode the glycosyltransferases required for the synthesis of the type 14 tetrameric repeating unit, showing that the cps1E, cps1G and cps1I genes encoded glycosyltransferases. The precise functions of these genes as well as the substrate specificities of the enzymes can be established. In S. pneumoniae, the cps14E gene was shown to encode a glucosyl-1-phosphate transferase catalyzing the transfer of glucose to a lipid carrier. Moreover, cpsE-like genes were found in S. pneumoniae serotypes 9N, 13, 14, 15B, 15C, 18F, 18A and 19F (60). CpsE mutants were constructed in the serotypes 9N, 13, 14 and 15B. All mutant strains lacked glucosyltransferase activity (60). Moreover, in all these S. pneumoniae serotypes, the cpsE gene seemed to be responsible for the addition of glucose to the lipid carrier. Based on these data, we suggest that in S. suis type 1, the cps1E gene may fulfil a similar function. The structure of the S. suis type 1 capsule is unknown, but it is composed of glucose, galactose, N-acetyl glucosamine, N-acetyl galactosamine and sialic acid in a ratio of 1:2.4:1:1:1.4 (5). Therefore, a role of a cpsE-like glucosyltransferase activity can easily be envisaged. CpsE-like sequences were also found in serotypes 2, ½ and 14.
For polysaccharide biosynthesis in S. pneumoniae type 14, transfer of the second sugar of the repeating unit to the first lipid-linked sugar is performed by the gene products of cps14F and cps14G (20). Similar to Cps14F and Cps14G, the S. suis type 1 prot Cps1G may act as one glycosyltransferase performing the same reaction. Cps14F and Cps14G of S. pneumoniae showed similarity to the N-terminal half and C-terminal half of the SpsK protein of Sphingomonas (20, 67), respectively. This suggests a combined function for both proteins. Moreover, cps14F- and cps14G-like sequences were found in several serotypes of S. pneumoniae and these genes always seemed to exist together (60). The same was observed for S. suis type 1. The cps1F and cps1G probes hybridized with type 1 and type 14 strains.
According to the similarity found between the cps1H gene and the cps14H gene of S. pneumoniae (20), cps1H is expected to encode a polysaccharide polymerase.
The protein encoded by the cps1I gene showed some similarity with the Cps14J protein of S. pneumoniae (19). The cps14J gene was shown to encode a β-1, 4-galactosyltransferase activity, responsible for the addition of the fourth (i.e. last) sugar in the synthesis of the S. pneumoniae serotype 14 polysaccharide. In S. suis type 2, the proteins encoded by the cps2J and cps2K genes showed similarity to the Cps14J protein. However, no significant homologies were found between Cps2J, Cps2K and Cps1I. In the N-terminal regions of Cps14J and Cps14I, two small conserved regions, DXS and DXDD, were identified (19). These regions seemed to be important for catalytic activity (13). At the same positions in the sequence, Cps2I contained the regions DXS and DXED.
In the region between Cps1G and Cps1H, three small Orfs were identified. Since the Orfs were expressed in three different reading frames, and did not contain potential start sites, expression is not expected. However, the three potential gene products encoded by this region showed some similarity with three successive regions of the C-terminal part of the EpsK protein of Streptococcus thermophilus (27% identity, 40). The region related to the first 82 amino acids is lacking. The EpsK protein was suggested to play a role in the export of the exopolysaccharide by rendering the polymerized exopolysaccharide more hydrophobic through a lipid modification. These data could suggest that the sequences in the region between Cps1G and Cps1H originated from epsK-like sequence. Hybridization experiments showed that this epsK-like region is also present in other serotype 1 strains as well as in serotype 14 strains (results not shown).
The function of most of the cloned serotype 9 genes can be established. Based on sequence similarity data, the cps9E and cps9F genes could be glycosyltransferases (61, 24, 63, 64, 65). Moreover, the cps9G and cps9H genes showed similarity to genes located in regions involved in polysaccharide biosynthesis, but the function of these genes is unknown (68).
Cross-hybridization experiments using the individual cps2, cps1 and cps9 genes as probes showed that the cps9G and cps9H probes specifically hybridized with serotype 9 strains.
Therefore, these are useful as tools for the identification of S. suis type 9 strains both for diagnostic purposes as well as in epidemiological and transmission studies. We previously developed a PCR method which can be used to detect S. suis strains in nasal and tonsil swabs of pigs (62). The method was used to identify pathogenic (EF-positive) strains of S. suis serotype 2. Besides S. suis type 2 strains, serotype 9 strains are frequently isolated from organs of diseased pigs. However, until now, a rapid and sensitive diagnostic test was not available for type 9 strains. Therefore, the type 9 specific probes 9-specific probes or the type 9 specific 9-specific PCR is of great diagnostic value. The cps1F, cps1G and cps1I probes hybridized with serotype 1 as well as with serotype 14 strains. In coagglutination tests, type 1 strains react with the anti-type 1 as well as with the anti-type 14 antisera (56). This suggests the presence of common epitopes between these serotypes. On the other hand, type 1 strains agglutinated only with anti-type 1 serum (56, 57), indicating that it is possible to detect differences between those serotypes.
The cps2F, cps2G, cps2H, cps2JI and cps2J probes hybridized with serotypes 2 and ½ only. Serotype 34 showed a weak hybridizing signal with the cps2G probe. As shown in agglutination tests, type ½ strains react with sera directed against type 1 as well as with sera directed against type 2 strains (46). Therefore, type ½ shared antigens with both types 1 and 2. Based on the hybridization patterns of serotype ½ strains with the cps1 and cps2 specific cps1- and cps2-specific genes, serotype ½ seemed to be more closely related to type 2 strains than to type 1 strains. In our current studies, we identify type-specific genes, primers or probes which are used for the discrimination of serotypes 1, 14 and 2 and ½ and others of the 35 serotypes yet known. Furthermore, type-specific genes, primers or probes can now easily be developed for yet unknown serotypes, once they become isolated.
Cloning and characterization of a further part of the cps2 locus.
Based on the established sequence, 11 genes, designated cps2L to cps2T, orf2U and orf2V, were identified. A gene homologous to genes involved in the polymerization of the repeating oligosaccharide unit (cps2O) as well as genes involved in the synthesis of sialic acid (cps2P to cps2T) were identified. Moreover, hybridization experiments showed that the genes involved in the sialic acid synthesis are present in S. suis serotypes 1, 2, 14, 27 and ½. The “cps2M” and “cps2N” regions showed similarity to proteins involved in the polysaccharide biosynthesis of other Gram-positive bacteria. However, these regions seemed to be truncated or were nonfunctional as the result of frame-shift or point mutations. At its 3′-end, the cps2 locus contained two insertional elements (“orf2U” and “orf2V”), both of which seemed to be non-functional.
To clone the remaining part of the cps2 locus, sequences of the 3′-end of pCPS26 ( FIG. 1 , part C) were used to identify a chromosomal fragment containing cps2 sequences located further downstream. This fragment was cloned in pKUN19, resulting in pCPS29. Using a similar approach, we subsequently isolated the plasmids pCPS30 and pCPS34 containing downstream cps2 sequences ( FIG. 1 , part C).
Analysis of the cps2 operon.
The complete nucleotide sequence of the cloned fragments was determined. Examination of the compiled sequence revealed the presence of: a sequence encoding the C-terminal part of Cps2K, six apparently functional genes (designated cps2O-cps2T) and the remnants of 5 different ancestral genes (designated “cps2L” “cps2M”, “cps2N”, “orf2U” and “orf2V”). The latter genes seemed to be truncated or incomplete as the result of the presence of stop codons or frame-shift mutations ( FIG. 1 , part A). Neither potential promoter sequences nor potential stem-loop structures could be identified within the sequenced region. A ribosome-binding site precedes each ORF and the majority of the ORFs are very closely linked. Three intergenic gaps were found: one between “cps2M” and “cps2N” (176 nucleotides), one between cps2O and cps2P (525 nucleotides), and one between cps2T and “orf2U” (200 nucleotides). These and our above data show that Orf2X and Cps2A-Orf2T are part of a single operon.
A list of all loci and their properties is shown in Table 4. The “cps2L” region contained three potential ORFs of 103, 79 and 152 amino acids, respectively, which were only separated from each other by stop codons. Only the first ORF is preceded by a potential ribosomal binding site and contained a methionine start codon. This suggests that “cps2L” originates from an ancestral cps2L gene, which coded for a protein of 339 amino acids. The function of this hypothetical Cps2L protein remains unclear so far: no significant homologies were found between Cps2L and proteins present in the data libraries. It is not clear whether the first ORF of the “cps2L” region is expressed into a protein of 103 amino acids. The “cps2M” region showed homology to the N-terminal 134 amino acids of the NeuA proteins of Streptococcus agalactiae and Escherichia coli (AB017355, 32). However, although the “cps2 M” region contained a potential ribosome binding site, a methionine start codon was absent. Compared with the S. agalactiae sequence, the ATG start codon was replaced by a lysin encoding AAG codon. Moreover, the region homologous to the first 58 amino acids of the S. agalactiae NeuA (identity 77%) was separated from the region homologous to amino acids 59-134 of NeuA by a repeated DNA sequence of 100-bp (see, herein). In addition, the region homologous to amino acids 59 to 95 of NeuA (identity 32%) and the region homologous to the amino acids 96 to 134 of NeuA (identity 50%) were present in different reading frames. Therefore, the partial and truncated NeuA homologue is probably nonfunctional in S. suis. The “cps2N” region showed homology to CpsJ of S. agalactiae (accession no. AB017355). However, sequences homologous to the first 88 amino acids of CpsJ were lacking in S. suis. Moreover, the homologous region was present in two different reading frames. The protein encoded by the cps2O gene showed homology to proteins of several streptococci involved in the transport of the oligosaccharide repeating unit (accession no. AB017355), suggesting a similar function for Cps2O. The proteins encoded by the cps2P, cps2S and cps2T genes showed homology to the NeuB, NeuD and NeuA proteins of S. agalactiae and E. coli (accession no. AB017355). Because the “cps2M” region also showed homology to NeuA of E. coli, the S. suis cps2 locus contains a functional neuA gene (cps2T) as well as a nonfunctional (“cps2M”) gene. The mutual homology between these two regions showed an identity of 77% at the amino acid level over amino acids 1-58 and 49% over the amino acids 59-134. Cps2Q and Cps2R showed homology to the N-terminal and C-terminal parts of the NeuC protein of S. agalactiae and E. coli, respectively. This suggests that the function of the S. agalactiae NeuC protein in S. suis is likely fulfilled by two different proteins. In E. coli, the neu genes are known to be involved in the synthesis of sialic acid. NeuNAc is synthesized from N-acetylmannosamine and phosphoenolpyruvate by NeuNAc synthetase. Subsequently, NeuNAc is converted to CMP-NeuNAc by the enzyme CMP-NeuNAc synthetase. CMP-NeuNAc is the substrate for the synthesis of polysaccharide. In E. coli, K1 NeuB is the NeuNAc synthetase, and NeuA is the CMP-NeuNAc synthetase. NeuC has been implicated in the NeuNAc synthesis, but its precise role is not known. The precise role of NeuD is not known. A role of the Cps2P-Cps2T proteins in the synthesis of sialic acid can easily be envisaged, since the capsule of S. suis serotype 2 is rich in sialic acid. In S. agalactiae, sialic acid has been shown to be critical to the virulence function of the type III capsule. Moreover, it has been suggested that the presence of sialic acid in the capsule of bacteria which can cause meningitis may be important for these bacteria to breach the blood-brain barrier. So far, however, the requirement of the sialic acid for virulence of S. suis remains unclear.
“Orf2U” and “Orf2V” showed homology to proteins located on two different insertional elements. “Orf2U” is homologous to IS1194 of Streptococcus thermophilus, whereas “Orf2V” showed homology to a putative transposase of Streptococcus pneumoniae. This putative transposase was recently found to be associated with the type 2 capsular locus of S. pneunioniae. Compared with the original insertional elements in S. thermophilus and S. pneumoniae, both “Orf2U” and “Orf2V” are likely to be nonfunctional due to frame shift mutations within their coding regions.
A striking observation was the presence of a sequence of 100 bp ( FIG. 10 ) which was repeated three times within the cps2 operon. The sequence is highly conserved (between 94% and 98%) and was found in the intergenic regions between cps2G and cps2H, within “cps2M” and between cps2O and cps2P. No significant homologies were found between this 100-bp direct repeat sequence and sequences present in the data libraries, suggesting that the sequence is unique for S. suis.
Distribution of the cps2 sequences among the 35 S. suis serotypes.
To examine the presence of sialic acid encoding genes in other S. suis serotypes, we performed cross-hybridization experiments. DNA fragments of the individual cps2 genes were amplified by PCR, radiolabeled with 32P and hybridized to chromosomal DNA of the reference strains of the 35 different S. suis serotypes. As a positive control, we used a probe specific for S. suis 16S rRNA. The 16S rRNA probe hybridized with almost equal intensities to all serotypes tested (Table 4). The “cps2L” sequence hybridized with DNA of serotypes 1, 2, 14 and ½. The “cps2M”, cps2O, cps2P, cps2Q, cps2R, cps2S and cps2T genes hybridized with DNA of serotypes 1, 2, 14, 27 and ½. Because the cps2P-cps2T genes are most likely involved in the synthesis of sialic acid, these results suggest that sialic acid is also a part of the capsule in the S. suis serotypes 1, 2, 14, 27 and ½. This is in agreement with the finding that the serotypes 1, 2 and ½ possess a capsule that is rich in sialic acid. Although the chemical compositions of the capsules of serotypes 14 and 27 are unknown, recent agglutination studies using sialic acid-binding lectins suggested the presence of sialic acid in S. suis serotype 14, but not in serotype 27. In these studies, sialic acid was also detected in serotypes 15 and 16. Since the latter observation is not in agreement with our hybridization studies, it might be that other genes, not homologous to the cps2P-cps2T genes, are responsible for the sialic acid synthesis in serotypes 15 and 16.
A probe based on “cps2N” sequences hybridized with DNA from serotypes 1, 2, 14 and ½. A probe specific for “orf2U” hybridized with serotypes 1, 2, 7, 14, 24, 27, 32, 34, and ½, whereas a probe specific for “orf2V” hybridized with many different serotypes. In addition, we prepared a probe specific for the 100-bp direct repeat sequence. This probe hybridized with the serotypes 1, 2, 13, 14, 22, 24, 27, 29, 32, 34 and ½ (Table 4). To analyze the number of copies of the direct repeat sequence within the S. suis serotype 2 chromosome, a Southern blot hybridization and analysis was performed. Therefore, chromosomal DNA of S. suis serotype 2 was digested with NcoI and hybridized with a 32P-labeled direct repeat sequence. Only one hybridizing fragment, containing the three direct repeats present on the cps2 locus, was found (results not shown). This indicates that the 100-bp direct repeat sequence is only associated with the cps2 locus. In S. pneumoniae, a 115-bp long repeated sequence was found to be associated with the capsular genes of serotypes 1, 3, 14 and 19F. In S. pneumoniae, this 115-bp sequence was also found in the vicinity of other genes involved in pneumococcal virulence (hyaluronidase and neuraminidase genes). A regulatory role of the 115-bp sequence in coordinate control of these virulence-related genes was suggested.
To study the role of the capsule in resistance to phagocytosis and in virulence, we constructed two isogenic mutants in which capsule synthesis was disturbed. In 10cpsB, the cps2B gene was disturbed by the insertion of an antibiotic-resistance gene, whereas in 10cpsEF, parts of the cps2E and cps2F genes were replaced. Both mutant strains seemed to be completely unencapsulated. Because the cps2 genes seemed to be part of an operon, polar effects cannot be excluded. Therefore, these data did not give any information about the role of Cps2B, Cps2E or Cps2F in the polysaccharide biosynthesis. However, the results clearly show that the capsular polysaccharide of S. suis type 2 is a surface component with antiphagocytic activity. In vitro wild type encapsulated bacteria are ingested by phagocytes at a very low frequency, whereas the mutant unencapsulated bacteria are efficiently ingested by porcine macrophages. Within 2 hours, over 99.6% of mutant bacteria were ingested and over 92% of the ingested bacteria were killed. Intracellularly, wild type as well as mutant strains seemed to be killed with the same efficiency. This suggests that the loss of capsular material is associated with loss of capacity to resist uptake by macrophages. This loss of resistance to in vitro phagocytosis was associated with a substantial attenuation of the virulence in germfree pigs. All pigs inoculated with the mutant strains survived the experiment and did not show any specific clinical signs of disease. Only some aspecific clinical signs of disease could be observed. Moreover, mutant bacteria could be reisolated from the pigs. This supports the idea that, as in other pathogenic Streptococci, the capsule of S. suis acts as an important virulence factor. Transposon mutants prepared by Charland impaired in the capsule production showed a reduced virulence in pigs and mice. To construct these mutants, the type 2 reference strain S735 was used. We previously showed that this strain is only weakly virulent for young pigs. Moreover, the insertion site of the transposon is unsolved so far.
As a further example herein, a rapid PCT test for Streptococcus suis type 7 is described.
Recent epidemiological studies on Streptococcus suis infections in pigs indicated that, besides serotypes 1, 2 and 9, serotype 7 is also frequently associated with diseased animals. For the latter serotype, however, no rapid and sensitive diagnostic methods are available. This hampers prevention and control programs. Here we describe the development of a type-specific PCR test for the rapid and sensitive detection of S. suis serotype 7. The test is based on DNA sequences of capsular (cps) genes specific for serotype 7. These sequences could be identified by cross-hybridization of several individual cps genes with the chromosomal DNAs of 35 different S. suis serotypes.
Streptococcus suis is an important cause of meningitis, septicemia, arthritis and sudden death in young pigs (69, 70). It can however, also cause meningitis in man (71). Attempts to control the disease are still hampered by the lack of sufficient knowledge about the epidemiology of the disease and the lack of effective vaccines and sensitive diagnostics.
S. suis strains can be identified and classified by their morphological, biochemical and serological characteristics (70, 73, 74). Serological classification is based on the presence of specific antigenic determinants. Isolated and biochemically characterized S. suis cells are agglutinated with a panel of specific sera. These typing methods are very laborious and time-consuming and can only be performed on isolated colonies. Moreover, it has been reported that non-specific cross-reactions may occur among different types of S. suis (75, 76).
So far, 35 different serotypes have been described (7, 78, 79). S. suis serotype 2 is the most prevalent type isolated from diseased pigs, followed by serotypes 9 and 1. However, recently, serotype 7 strains were also frequently isolated from diseased pigs (80, 81, 82). This suggests that infections with S. suis serotype 7 strains seem to be an increasing problem. Moreover, the virulence of S. suis serotype 7 strains was confirmed by experimental infection of young pigs (83).
Recently, rapid and sensitive PCR assays specific for serotypes 2 (and ½), 1 (and 14) and 9 were developed (84). These assays were based on the cps loci of S. suis serotypes 2, 1 and 9 (84, 85). However, until now, no rapid and sensitive diagnostic test was available for S. suis serotype 7. Herein we describe the development of a PCR test for the rapid and sensitive detection of S. suis serotype 7 strains. The test is based on DNA sequences which form a part of the cps locus of S. suis serotype 7. Compared with the serological serotyping methods, the PCR assay was a rapid, reliable and sensitive assay. Therefore, this test, in combination with the PCR tests which we previously developed for serotypes 1, 2 and 9, will undoubtedly contribute to a more rapid and reliable diagnosis of S. suis and may facilitate control and eradication programs.
Materials and Methods
Bacterial strains, growth conditions and serotyping.
The bacterial strains and plasmids used in this study are listed in Table 7. The S. suis reference strains were obtained from M. Gottschalk, Canada. S. suis strains were grown in Todd-Hewitt broth (code CM189, Oxoid), and plated on Columbia agar blood base (code CM331, Oxoid) containing 6% (v/v) horse blood. E. Coli strains were grown in Luria broth (86) and plated on Luria broth containing 1.5% (w/v) agar. If required, ampicillin was added to the plates. The S. suis strains were serotyped by the slide agglutination test with serotype-specific antibodies (70).
DNA techniques.
Routine DNA manipulations and PCR reactions were performed as described by Sambrook et al. (88). Blotting and hybridization were performed as described previously (84, 86).
DNA sequence analysis.
DNA sequences were determined on a 373A DNA Sequencing System (Applied Biosystems, Warrington, GB). Samples were prepared by use of an ABI/PRISM dye terminator hcycle sequencing ready reaction kit (Applied Biosystems). Custom-made sequencing primers were purchased from Life Teclmologies. Sequencing data were assembled and analyzed using the McMollyTetra program. The BLAST program was used to search for protein sequences homologous to the deduced amino acid sequences.
PCR.
The primers used for the cps7H PCR correspond to the positions 3334-3354 and 3585-3565 in the S. suis cps7 locus.
The sequences were:
5′-AGCTCTAACACGAAATAAGGC-3′ (SEQ. ID. No. 7) and 5′-GTCAAACACCCTGGATAGCCG3′ (SEQ. ID. No. 8).
The reaction mixtures contained 10 mM Tris-HCl, pH 8.3; 1.5 mnM
MgCl2; 50 mM KCl; 0.2 mM of each of the four deoxynucleotide triphosphates; 1 microM of each of the primers and 1U of AmpliTaq Gold DNA polymerase (Perkin Elmer Applied Biosystems, N.J.). DNA amplification was carried out in a Perkin Elmer 9600 thermal cycler and the program consisted of an incubation for 10 min at 95° C. and 30 cycles of 1 min at 95° C., 2 min at 56° C. and 2 min at 72° C.
Results and discussion
Cloning of the seroytpe 7-specific cps genes.
To isolate the type-specific cps genes of S. suis serotype 7, we used the cps9E gene of serotype 9 as a probe to identify chromosomal DNA fragments of type 7 containing homologous DNA sequences (84). A 1.6-kb PstI fragment was identified and cloned in pKUN19. This yielded pCPS7-1 ( FIG. 11 , part C). In turn, this fragment was used as a probe to identify an overlapping 2.7 kb ScaI-ClaI fragment. pGEM7 containing the latter fragment was designated pCPS7-2 ( FIG. 11 , part C).
Analysis of the cloned cps7 genes.
The complete nucleotide sequences of the inserts of pCPS7-1, pCPS7-2 were determined. Examination of the cps7 sequence revealed the presence of two complete and two incomplete open reading frames (ORFs) ( FIG. 11 , part C). All ORFs are preceded by a ribosome-binding Site. In accord with the data obtained for the cps1, cps2 and cps9 genes of serotypes 1, 2 and 9, respectively, the type 7 ORFs are very closely linked to each other. The only significant intergenic gap was that found between cps7E and cps7F (443 nucleotides). No obvious promoter sequences or potential stem-loop structures were found in this region. This suggests that, as in serotypes 1, 2 and 9, the cps genes in serotype 7 form part of an operon.
An overview of the ORFs and their properties is shown in Table 8. As expected on the basis of the hybridization data (84), the Cps9E and Cps7E proteins showed a high similarity (identity 99%. Table 8). Based on sequence comparisons between Cps9E and Cps7E, the PstI fragment of pCPS7-1 lacks the region encoding the first 371 codons of Cps7E. The C-terminal part of the protein encoded by the cps7F gene showed some similarity with the Bp1G protein of Bordetella pertussis (88), as well as with the C-terminal part of S. suis Cps2E (85). Both Bp1G and Cps2E were suggested to have glycosyltransferase activity and are probably involved in the linkage of the first sugar to the lipid carrier (85, 88). The protein encoded by the cps7G gene showed similarity with the Bp1F protein of Bordetella pertussis (88). B1pF is likely to be involved in the biosynthesis of an amino sugar, suggesting a similar function for Cps7G. The protein encoded by the cps7H gene showed similarity with the WbdN protein of E. coli (89) as well as with the N-terminal part of the Cps2K protein of S. suis (81). Both WbdN and Cps2K were suggested to have glycosyltransferase activity (85, 89).
Serotype 7 specific 7-specific cps genes.
To determine whether the cloned fragments in pCPS7-1 and pCPS7-2 contained serotype 7-specific DNA sequences, cross-hybridization experiments were performed. DNA fragments of the individual cps7 genes were amplified by PCR, labeled with 32P, and used to probe spot blots of chromosomal DNA of the reference strains of 35 different S. suis serotypes. The results are summarized in Table 9. As expected, based on the data obtained with the cps9E probe (84), the cps7E probe hybridized with chromosomal DNA of many different S. suis serotypes. The cps7F and cps7G probes showed hybridization with chromosomal DNA of S. suis serotypes 4, 5, 7, 17, and 23. However, the cps7H probe hybridized with chromosomal DNA of serotype 7 only, indicating that this gene is specific for serotype 7.
Type specificType-specific PCR.
We tested whether we could use PCR instead of hybridization for the typing of the S. suis serotype 7 strains. For that purpose, we selected an oligonucleotide primer set within the cps7H gene with which an amplified fragment of 251-bp was expected. In addition, we included in our analysis several S. suis serotype 7 strains, other than the reference strain. These strains were obtained from different countries and were isolated from different organs (Table 7). The results show that indeed a fragment of about 250-bp was amplified with all type 7 strains used ( FIG. 12 , part B), whereas no PCR products were obtained with serotype 1, 2 and 9 strains ( FIG. 12 , part A). This suggests that the PCR test, as described here, is a rapid diagnostic tool for the identification of S. suis serotype 7 strains. Until now, such a diagnostic test was not available for serotype 7 Strains strains. Together with the recently developed PCR assays for serotypes 1, 2, ½, 14 and 9, this assay may be an important diagnostic tool to detect pigs carrying serotype 2, ½, 1, 14, 9 and 7 strains and may facilitate control and eradication programs.
TABLE 1
Bacterial strains and plasmids
relevant
strain/plasmid
characteristics
source/reference
Strain
E coli
CC118
PhoA
(28)
XL2 blue
Stratagene
E. coli
XL2 blue
Stratagene
S. suis
10
virulent serotype 2 strain
(49)
3
serotype 2
(63)
17
serotype 2
(63)
735
reference strain serotype 2
(63)
T15
serotype 2
(63)
6555
reference strain serotype 1
(63)
6388
serotype 1
(63)
6290
serotype 1
(63)
5637
serotype 1
(63)
5673
serotype 1/2
(63)
5679
serotype 1/2
(63)
5928
serotype 1/2
(63)
5934
serotype 1/2
(63)
5209
reference strains serotype 1/2
(63)
5218
reference strain, serotype 9
(63)
5973
serotype 9
(63)
6437
serotype 9
(63)
6207
serotype 9
(63)
reference strains
serotypes 1-34
(9, 56, 14)
S. suis
10
virulent serotype 2 strain
(51)
10cpsB
isogenic cpsB mutant of strain 10
this work
10cpsEF
isogenic cpsEF mutant of strain 10
this work
Plasmid
pKUN19
replication functions pUC, Amp R
(23)
pGEM7Zf(+)
replication functions pUC, Amp R
Promega Corp.
pIC19R
replication functions pUC, Amp R
(29)
pIC20R
replication functions pUC, Amp R
(29)
pIC-spc
pIC19R containing spc R gene
labcollection
of pDL282
pDL282
replication functions of pBR322
(43)
and pVT736-1, Amp R , Spc R
pPHOS2
pIC-spc containing the truncated
this work
phoA gene of pPHO7 as a
PstI-BamHI fragment
pPHO7
contains truncated phoA gene
(15)
pPHOS7
pPHOS2 containing chromosomal
this work
S. suis DNA
pCPS6
pKUN19 containing 6 kb HindIII
this work (FIG. 1)
fragment of cps operon
pCPS7
pKUN19 containing 3,5 kb EcoRI-
this work (FIG. 1)
HindIII fragment of cps operon
pcPS11
pCPS7 in which 0.4 kb PstI-
this work (FIG. 1)
BamHI fragment of cpsB gene is
replaced by Spc R gene of pIC-spc
pCPS17
pKUN19 containing 3.1 kb KpnI
this work (FIG. 1)
fragment of cps operon
pCPS18
pKUN19 containing 1.8 kb SnaBI
this work. (FIG. 1)
fragment of cps operon
pCPS20
pKUN19 containing 3.3 kb XbaI-
this work (FIG. 1)
HindIII fragment of cps operon
pCPS23
pGEM7Zf(+) containing 1.5 kb
this work (FIG. 1)
Mini fragment of cps operon
pCPS25
pIC20R containing 2.5 kb
this work (FIG. 1)
KpnI-SalI fragment of pCPS17
pCPS26
pKUN19 containing 3.0 kb HindIII
this work (FIG. 1)
fragment of cps operon
pCPS27
pCPS25 containing 2.3 kb XbaI
this work (FIG. 1)
(blunt)-ClaI fragment of pCPS20
pCPS28
pCPS27 containing the 1.2 kb
this work (FIG. 1)
PstI-XhoI Spc R gene of pIC-spc
pCPS29
pKUN19 containing 2.2 kb SacI-
this work (FIG. 1)
PstI fragment of cps operon
pCPS1-1
pKUN19 containing 5 kb EcoRV
this work (FIG. 1)
fragment of cps operon of type I
pCPS1-2
pKUN19 containing 2.2 kb HindIII
this work (FIG. 1)
fragment of cps operon of type I
pCPS9-1
pKUN19 containing 1 kb HindIII-
this work (FIG. 1)
XbaI fragment of cps operon of
serotype 9
pCPS9-2
pKUN19 containing 4.0 kb
this work (FIG. 1)
XbaI-XbaI fragment of cps operon
of serotype 9
Amp R : ampicillin resistant
Spc R : spectinomycin resistant
cps: capsular polysaccharide
TABLE 2
Properties of Orfs in the cps locus of S. suis serotype 2 and similarities to gene product other bacteria
nucleotide
number
position in
of amino
GC
proposed function
similar gene product
ORF
sequence
acids
%
of gene product 1
(% identity)
Orf2Z
1-719
240
44
Unknown
B. subtilis YitS (26%)
Orf2Y
2079-822
419
38
Transcription
B. subtilis YcxD (39%)
regulation
Orf2X
2202-2934
244
39
Unknown
H. influenzae YAAA (24%)
Cps2A
3041-4484
481
39
Regulation
S. pneumoniae Cps19fA (58%)
Cps2B
4504-5191
229
40
Chain length
S. pneumoniae type 3 Orfl (58%)
determination
Cps2C
5203-5878
225
40
Chain length
S. pneumoniae Cps23fD (63%)
determination/Export
Cps2D
5919-6648
243
38
Unknown
S. pneumoniae CpsB (62%)
Cps2E
6675-8052
459
33
Glycosyltransferase
S. pneumoniae Cps14E (56%)
Cps2F
8089-9256
389
32
Glycosyltransferase
S. pneumoniae Cps23fT
Cps2G
9262-10417
385
36
Glycosyltransferase
S. thermophilus EpsF (25%)
Cps2H
10808-12176
457
31
Glycosyltransferase
S. mutans RGPEC, N (29%)
Cps2I
12213-13443
410
29
CP polymerase
S. pneumoniae Cps23f1 (48%)
Cps2J
13583-14579
332
29
Glycosyltransferase
S. pneumoniae Cps14J (31%)
Cps2K
14574-15576
334
37
Glycosyltransferase
S. pneumoniae Cps14J (40%)
“Cps2L”
15618-16635
103
37
Unknown
—
“Cps2M”
16811-17322
—
38
—
S. agalactiae CpsF N (77%)
E. coli NeuA, N (47%)
“Cps2N”
17559-18342
—
39
—
S. agalactiae CpsJ (43%)
Cps2O
18401-19802
476
40
Repeat unit
S. agalactiae CpsK (41%)
transporter
Cps2P
20327-21341
338
39
Sialic acid synthesis
S. agalactiae NeuB (80%)
E. coli NeuB (59%)
Cps2Q
21355-21865
170
42
Sialic acid synthesis
S. agalactiae NeuC N (61%)
E. coli NeuC N (54%)
Cps2R
21933-22483
184
40
Sialic acid synthesis
S. agalactiae NeuC c (55%)
E. coli NeuC c (40%)
Cps2S
22501-23125
208
42
Sialic acid synthesis
E. coli NeuD (32%)
Cps2T
23136-24366
395
40
CMP-NeuNAc
S. agalactiae CpsF (49%)
synthetase
E. coli NeuA (34%)
“Orf2U”
24566-25488
168
42
Transposase
S. thermophilus IS1194 (51%)
“Orf2V”
25691-26281
116
37
Transposase
S. pneumoniae orfl (85%)
1 Predicted by sequence similarity
N Similarity refers to the amino-terminal part of the gene product
c Similanty refers to the carboxy-terminal part of the gene product
ORFs between “ ” are truncated or non-functional as the result of frame-shift or point mutations
TABLE 3
Properties of Orfs in the cps genes of S. suis serotypes 1 and 9 and similarities to gene products of other bacteria
nucleotide
number
(kDa)
position in
of amino
predicted
predicted
proposed function
similar gene product
reference/
ORF
sequence
G + C%
acids
mol. mass
pI
of gene product 1
(% identity)
accession nr.
Cps1E 2
1-1363
34%
454
52.2
8.0
Glucosyltransferase
Streptococcus suis Cps2E
(26)
(86%)
Streptococcus pneumoniae Cps14E
(12)
(48%)
Cps1F
1374-1821
33%
149
17.3
8.2
Unknown
Streptococcus pneumoniae Cps14F
(14)
(83%)
Cps1G
1823-2315
25%
164
19.5
7.5
Glycosyltransferase
Streptococcus pneumoniae Cps14G
(14)
(50%)
Cps1H
3035-4202
24%
389
45.5
8.4
CP polymerase
Streptococcus pneumoniae Cps14H
(14)
(30%)
Cps1I
4197-
Glycosyltransferase
Streptococcus pneumoniae Cps14J
(13)
(38%)
Lactococus lactis EpsG
(29)
(31%)
Streptococcus thermophilus EpsI
(28)
(33%)
Cps1J
Glycosyltransferase
Streptococcus pneumoinae Cps14J
(13)
( )
Cps1K 3
37%
278
32.5
7.8
Glycosyltransferase
Streptococcus pneumoniae Cps14J
(13)
(44%)
Cps9D 2
1-646
37%
215
24.9
8.1
Unknown
Streptococcus suis Cps2D
(26)
(89%)
Cps9E
680-
Glycosyltransferase
Staphylococcus aureus Cap1D
(18)
(27%)
Cps9F
36%
200
22.3
8.2
Glycosyltransferase
Staphylococcus aureus Cap5M
(17)
(52%)
Cps9G
35%
269
31.5
8.0
Unknown
Actinobacillus acunomycetemcomitans
(A8002668_4)
(43%)
Haemophilus influenzae Lsg
(005081)
(43%)
Cps9H 3
30%
143
16.5
7.2
Unknown
Yersinia enterolitica RfbB
(33)
(28%)
1 Predicted by sequence similarity
2 N-terminal part of protein is lacking
3 C-terminal part of protein is lacking
TABLE 4
Hybridization of serotype 2 cps genes and neighboring sequences with chromosomal DNA of other serotypes
DNA
serotypes
probes
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
orf2Z
+
+
+
+
+
+
+
+
+
+
+
+
±
+
+
+
+
+
orf2Y
+
+
+
+
+
+
+
+
+
+
+
+
±
+
+
+
+
+
orf2X
+
+
+
+
+
+
+
+
+
+
+
+
±
+
+
+
+
+
cps2A
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
cps2B
+
+
+
+
+
+
+
+
+
+
−
−
±
+
−
−
±
±
cps2C
+
+
+
+
+
+
+
+
+
+
+
−
±
+
−
±
−
−
cps2D
+
+
+
+
+
+
+
+
+
+
+
±
±
+
−
±
+
+
cps2E
+
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2F
−
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2G
−
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2H
−
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2I
−
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2J
−
+
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
cps2K
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
“cps2L”
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
“cps2M”
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
“cps2N”
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2O
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2P
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2Q
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2R
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2S
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
cps2T
+
+
−
−
−
−
−
−
−
−
−
−
−
+
−
−
−
−
“orf2U”
+
+
−
−
−
−
+
−
−
−
−
−
−
+
−
−
−
−
“orf2V”
+
+
±
±
±
−
±
−
−
−
−
−
−
+
+
−
+
+
100-bp repeat
+
+
−
−
−
−
−
−
−
−
−
−
+
+
−
−
−
−
16SrRNA
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
serotypes
DNA probes
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
½
orf2Z
+
−
+
−
+
+
+
−
+
+
+
+
+
−
−
−
+
orf2Y
+
±
+
±
+
+
+
+
+
+
+
+
+
−
−
−
+
orf2X
+
−
+
−
+
+
+
−
+
+
+
+
+
−
−
−
+
cps2A
+
−
+
−
+
+
+
−
+
+
+
+
+
−
−
−
+
cps2B
±
−
±
−
+
+
+
−
−
−
+
±
+
−
±
−
+
cps2C
−
−
−
−
+
+
+
−
+
±
−
−
+
−
±
−
+
cps2D
+
−
±
−
+
+
+
−
+
+
+
±
+
−
−
−
+
cps2E
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2F
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
cps2G
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
±
+
cps2H
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
cps2I
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
cps2J
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
cps2K
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
“cps2L”
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
“cps2M”
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
“cps2N”
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
+
cps2O
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2P
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2Q
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2R
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2S
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
cps2T
−
−
−
−
−
−
−
−
+
−
−
−
−
−
−
−
+
“orf2U”
−
−
−
−
−
+
−
−
+
−
−
−
−
+
−
+
+
“orf2V”
±
−
−
±
+
−
−
+
−
−
−
−
+
+
−
±
+
100-bp repeat
−
−
−
+
−
+
−
−
+
−
−
−
−
+
−
+
+
16SrRNA
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
TABLE 5
Hybridization of serotypes 1 and 9 cps genes
with chromosomal DNA of other S. suis serotypes
DNA probes
Serotype
cps1E
cps1F
cps1G
cps1H
cps1I
cps9E
cps9F
cps9G
cps9H
16rRNA
1
+
+
+
+
+
−
−
−
−
+
2
+
−
−
−
−
−
−
−
−
+
3
−
−
−
+
−
+
−
−
−
+
4
−
−
−
+
−
+
−
−
−
+
5
−
−
−
+
−
+
−
−
−
+
6
−
−
−
−
−
−
−
−
−
+
7
−
−
−
+
−
+
−
−
−
+
8
−
−
−
−
−
−
−
−
−
+
9
−
−
−
+
−
+
+
+
+
+
10
−
−
−
+
−
+
+
−
−
+
11
−
−
−
+
−
+
±
−
−
+
12
−
−
−
±
−
+
±
−
−
+
13
−
−
−
+
−
+
−
−
−
+
14
−
−
−
+
+
−
−
−
−
+
15
−
−
−
−
−
−
−
−
−
+
16
−
−
−
−
−
−
−
−
−
+
17
−
−
−
+
−
+
−
−
−
+
18
−
−
−
+
−
+
−
−
−
+
19
−
−
−
+
−
+
−
−
−
+
20
−
−
−
−
−
−
−
−
−
+
21
−
−
−
+
−
+
±
−
−
+
22
−
−
−
−
−
−
−
−
−
+
23
−
−
−
+
−
+
−
−
−
+
24
−
−
−
+
−
+
+
−
−
+
25
−
−
−
−
−
−
−
−
−
+
26
−
−
−
−
−
−
±
−
−
+
27
+
−
−
−
−
−
−
−
−
+
28
−
−
−
+
−
+
±
−
−
+
29
−
−
−
+
−
+
−
−
−
+
30
−
−
−
+
−
+
±
−
−
+
31
−
−
−
+
−
+
−
−
−
+
32
−
−
−
−
−
−
−
−
−
+
33
−
−
−
−
−
−
±
−
−
+
34
−
−
−
−
−
−
−
−
−
+
½
+
−
−
−
−
−
−
−
−
+
TABLE 6
Virulence of wild type and capsular mutant S. suis strains, in germfree pigs
clinical index of
isolation of
pigs/
the group
leuco-
S suis in pigs
S. suis
group
mortality 2
morbidity 3
spec
non-spec.
fever
cyte
[n] per group in
strains 1
[n]
[%]
[%]
symptoms 5
symptoms 6
index 7
index 8
CNS
serosae
joints
10
4
100
100
11
88
43
44
2
3
4
10cpsB
4
0
0
0
10
1
3
1
3
2
10cpsEF
4
0
0
0
0
1
0
1
3
2
1 strain10 in the wild type strain, strains 10cpsB and 10cpsEF are isogenic capsular mutant strains
2 piglets which died spontaneously or had to be killed for animal welfare reasons
3 only considering pigs with specific symptoms
4 clinical index: % of observations which matched the described criteria
5 specific symptoms: ataxia, lameness on at least one joint, stiffness
6 non-specific symptoms: inappetance, depression
7 % of observations in the experimental group with a body temperature > 40° C.
8 % of blood samples in the group in which nunber of granulocytes > 10 10 /1
TABLE 7
Bacterial strains and plasmids
strain/plasmid
relevant characteristics
Strain
E. coli
XL2 blue
S. suis
reference strains
serotypes 1-34
5667
serotype 7, tonsil (1993)
7037
serotype 7, organs (1994)
7044
serotype 7, brains (1994)
7068
serotype -7 (1994)
7646
serotype 7 (1994)
7744
serotype 7, lungs (1996)
7759
serotype 7, joints (1996)
8169
serotype 7 (1997)
15913
serotype 7, meninges (1998)
Plasmid
pKUN19replication
functions pUC, Amp R
pGEM7Zf(+)
replication functions MIC, Amp R
pCPS9-1
pKUN19 containing 1 kb HindIII-XbaI
fragment of cps operon of serotype 9
pCPS9-2
pKUN19 containing 4.0 kb XbaI-XbaI
fragment of cps operon of serotype 9
pCPS7-1
pKUN19 containing 1.6-kb PstI fragment
of cps operon of type 7
pCPS7-2
pGEM7 containing 2.7-kh ScaI-C1aI fragment
of cps operon of type 7
Amp R : ampicillin resistant
cps: capsular polysaccharide
TABLE 8
Properties of Orfs in the cps genes of S. suis serotype 7 and
similarities to gene products of other bacteria
nucleotide
position in
proposed function
similar gene product
Orf
sequence
of gene product
(% identity)
Cps7E
1-719
Glycosyltransferase
Streptococcus suis
Cps9E (99%)
Cps7F
1164-1863
Glycosyltransferase
Bordetella pertussis
Bp1G 1 (43%)
Streptococcus suis
Cps2E 1 - (33%)
Cps7G
1872-3086
Biosynthesis amino sugar
Bordetella pertussis
Bp1F (48%)
Cps7H
3104-3737
Glycosyltransferase
Escherichia coli
WbdN (35%)
Streptococcus suis
Cps2K 2 (31%)
1 similarity refers to the Cdenninal part of the gene product
2 similarity refers to the N-terminal part of the gene product
TABLE 9
Hybridization of serotype 7 cps probes with chromosomal DNA of S. suis serotypes
serotypes
DNA probes
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
cps7E
−
−
+
+
+
−
+
−
+
+
+
+
+
−
−
−
+
+
cps7F
−
−
−
+
+
−
+
−
−
−
−
−
−
−
−
−
+
−
cps7G
−
−
−
+
+
−
+
−
−
−
−
−
−
−
−
−
+
−
cps7H
−
−
−
−
−
−
+
−
−
−
−
−
−
−
−
−
−
−
16SrRNA
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
serotypes
DNA probes
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
½
cps7E
+
−
+
−
+
+
−
−
−
−
+
+
+
−
−
−
−
cps7F
−
−
−
−
+
−
−
−
−
−
−
−
−
−
−
−
−
cps7G
−
−
−
−
+
−
−
−
−
−
−
−
−
−
−
−
−
cps7H
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
16SrRNA
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
REFERENCES
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2. Arrecubieta, C., E. Garcia, and R. Lopez. 1995. Sequence and transcriptional analysis of a DNA region involved in the production of capsular polysaccharide in Streptococcus pneumoniae type 3. Gene 167: 1-7
3. Arrecubieta, C., R. Lopez, and E. Garcia. 1994. Molecular characterization of cap3A, a gene from the operon required for the synthesis of the capsule of Streptococcus pneumoniae type 3: sequencing of mutations responsible for the unencapsulated phenotype and localization of the capsular cluster on the pneumococcal chromosome. J. Bacteriol. 176: 6375-6383.
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The invention relates to Streptococcus suis infection in pigs, vaccines directed against those infections and tests for diagnosing Streptococcus suis infections. The invention provides an isolated or recombinant nucleic acid encoding a capsular gene cluster of Streptococcus suis or a gene or gene fragment derivated thereof. The invention further provides a nucleic acid probe or primer allowing species or serotype-specific detection of Streptococcus suis. The invention also provides a Streptococcus suis antigen and vaccine derived thereof.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is related to the following patent applications filed simultaneously herewith which are incorporated herein by reference: "Plated Electrical Connectors", to Victor Zaderej et al., Ser. No. 484,579, now abandoned; "Three Dimensional Plating Or Etching Process And Masks Therefor", to John Mettler et al., Ser. No. 484,387 now U.S. Pat. No. 4,985,116; "Plated D-Shell Connector", to Victor Zaderej et al., Ser. No. 484,391; and "Audio Jack Connector", to Victor Zaderej et al., Ser. No. 484,229, now abandoned.
BACKGROUND
1. Field of the Invention
This invention relates generally to the field of electrical connectors. More particularly, this invention relates to a circuit board edge connector fabricated by molding and plating or etching metalization patterns on the plastic.
2. Background of the Invention
Circuit card edge connectors are widely used throughout the electronics industry to mate various circuit cards together for various reasons. For example, such connectors are frequently wired together in large card cages in communications equipment such as telephone office equipment. They are similarly used in computer equipment in large and small racks. In personal computers and other devices, such connectors are used to mate together mother and daughter boards. For example, in personal computers such connectors may be used to couple modems, memory cards, disk drive controllers and the like to the main computer mother board.
Currently available circuit card edge connectors are somewhat costly devices which contain relatively large numbers of metal and plastic parts and which are soldered to a circuit board. The present invention provides an integral circuit card edge connector which may be fabricated as a part of a printed wiring board (PWB) eliminating secondary operations required for installation.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved molded circuit board edge connector.
It is another object of the present invention to provide such a circuit board edge connector which may be fabricated as a portion of a printed wiring board using three dimensional plating or etching techniques.
It is an advantage of the invention that fewer components must be inserted and soldered into a circuit board to enable mating with a circuit card edge.
It is another advantage that circuit card edge connectors of any configuration and number of contacts may be fabricated using the present invention without significant cost penalties.
These and other objects and advantages of the invention will become apparent to those skilled in the art upon consideration of the following description of the invention.
A molded circuit card edge connector according to the present invention includes an electrically insulative substrate. A first row of contact arms is molded as an integral part of the insulative substrate and extend upward from the substrate. The contact arms include a base adjacent the insulative substrate and a first contact surface. A second row of contact arms are molded as an integral part of the insulative substrate and extend upward from the substrate, the contact arms include a base adjacent the insulative substrate and a second contact surface. An electrically conductive material is plated to the first and second contact surfaces of the first and second contact arms, to conductively connect the contact surface to the insulative substrate. The first and second rows of contact arms are spaced apart by a predetermined distance with the contact surfaces facing opposite directions, to accept a circuit card between the first and second rows of contact arms in a manner such that the contact surfaces contact the circuit card.
A molded circuit card edge connector according to the preferred embodiment includes an insulative substrate forming a part of a printed wiring board. A first row of contact arms are molded as an integral part of the insulative substrate and extend upward at an angle approximately seven degrees from perpendicular with the substrate. The contact arms include a base adjacent the insulative substrate a first contact surface. A second row of contact arms is also molded as an integral part of the insulative substrate and extend upward at an angle approximately seven degrees from perpendicular with the substrate These contact arms also include a base adjacent the insulative substrate and a second contact surface. Each row of contact arms includes two ends and further includes a guide situated at each end for guiding the circuit card into position between the rows of contact arms. The guide includes a column having an approximately U-shaped channel for accepting the circuit card. An electrical conductor is plated to the first and second contact surfaces of the first and second contact arms, and lead to the insulative substrate. The first and second rows of contact arms are spaced apart by a predetermined distance which is less than a thickness of a circuit card, with the contact surfaces facing opposite directions, to accept the circuit card between the first and second rows of contact arms in a manner such that the contact surfaces contact the circuit card and cause the contact arms to flex away from each other and to hold the circuit card. The contact surfaces taper toward each other so that the circuit card encounters a tapered space between the first and second rows when inserted between the rows. A stop prevents the circuit card from traveling too far when inserted between the rows of contact arms.
The present invention generally relates to a molded plastic circuit card edge connector. The connector of the preferred embodiment includes two opposing rows of cantilever contact arms. The rows of contact arms are spaced apart adequately to allow insertion of a circuit board between the arms. The contact arms flex outward to provide spring pressure toward the circuit board. The contact arms include a main contact area which is dimensioned to produce a tapered entrance for receiving a circuit board. A plurality of stop ribs prevent the circuit board from going in too far while a pair of U-shaped guides serve to properly register the circuit board and guide it into place. The connector may be molded as an integral part of a printed wiring board.
The features of the invention believed to be novel are set forth with particularity in the appended claims. The invention itself, however, both as to organization and method of operation, together with further objects and advantages thereof, may be best understood by reference to the following description taken in conjunction with the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a perspective view of the circuit card edge connector of the preferred embodiment.
FIG. 2 shows a top view of the edge connector of the present invention.
FIG. 3 shows a side view of the edge connector of the present invention.
FIG. 4 shows a sectional view of the connector of the present invention with the cross section taken along lines A--A of FIG. 2 showing a daughter board partially inserted in the connector.
DETAILED DESCRIPTION OF THE INVENTION
Turning now to the several figures of the drawing in which like reference numerals designate corresponding parts throughout the several figures thereof, and in particular to FIG. 1, a circuit card edge connector according to the present invention is shown. This connector 10 is fabricated as a part of a printed wiring board (PWB) 12. The connector 10 includes eight cantilevered contact arms or contacts 14 fabricated as two rows of four such contacts. Of course, this is not to be limiting since any desired number of such contacts may be provided, with fifty or eighty such contacts being commonly used in conventional edge connectors. Each contact arm 14 acts as a spring using the resilient spring properties of the plastic material from which the connector 10 and PWB 12 are molded. In the preferred embodiment, the material used to mold the connector is General Electric Ultem 2312 Polyetherimide, but other materials may also be suitable.
In the preferred embodiment, each row of contacts 14 contains the same number of contacts 14 with each such contact 14 being situated in diametric opposition with another contact on the opposite row. Of course, this is not to be limiting since each connector 10 may be custom designed to fit the individual needs of the particular environment of use. In general, if the connector 10 is fabricated as shown as a part of a printed wiring board 12. Since PWB's 12 must, in general, be custom designed anyway, making custom connector configurations adds little if any additional cost to the overall structure. Accordingly, staggered contact configurations, missing or irregularly spaced contact arms 14 and other variations may be readily accommodated as needed or desired without the cost associated with manufacturing separate custom connectors.
The circuit card edge connector 10 also includes a pair of guides 18 situated at each end of the two rows of contacts 14. These guides 18 serve to align a mating daughter board 16 or other circuit card between the two rows of contacts 14 so that the contacts 14 each contact an appropriate pad 17 on the daughter board. In the preferred embodiment, these guides have an approximately U-shaped cross section so that the mating daughter board 16 is registered within a U-shaped channel formed by the U-shape of the guides 18. At the upper end of the U-shaped channel, the inside corners may be chamfered or otherwise tapered as shown in FIG. 2 and FIG. 3. This facilitates insertion of the daughter board 16 by guiding the daughter board into proper registration with the space formed between the two rows of contact arms.
The channel is preferably slightly wider than the maximum thickness of the daughter board 16 to ensure it will always properly receive the daughter board. Of course, this is not to be limiting, but has the advantage of assisting in guiding the daughter board 16 into proper place and helps prevent transfer of undue stress to the contacts 14 in the event the daughter board 16 is bent or pulled in one direction or the other. Guides 18 are preferably a bit taller than the contacts 14. In the preferred embodiment, they are approximately 0.50 inches tall.
The circuit card edge connector 10 also preferably includes a bottom stop 22 which may be fabricated in any number of configurations including a solid strip. In the preferred embodiment, it is fabricated as a plurality of individual plastic rungs or ribs 22 disposed between each of the contacts 14 in a ladder like arrangement joining each side of the circuit card 12 from which the connector 10 is molded. The bottom stop 22 serves several purposes. First, it allows the daughter board 16 to fully seat in the connector 10. Also, the stop permits connections to be made between contacts 14 on opposite sides of the daughter board or to facilitate transportation of PWB metal traces from one side of connector 10 to the other for whatever reason required by the circuit layout. Furthermore, such a rib configuration or similar serves to stiffen the circuit board 12 to help prevent it from flexing in the region of the connector 10 thus inhibiting intermittent connections.
The contacts 14 are plated with any of a plurality of conductive metals using a plating or etching process such as that disclosed in the above incorporated John Mettler et al. patent application in order to provide for maximum metal to metal contact compatibility. The plating may substantially cover the entire contact 14 from its base at the circuit board 12 to the top and completely encircling it. At the base of the contacts 14, each contact should be isolated from adjacent contacts 14 by a spacing in the plating as shown unless it is desired that adjacent contacts 14 should be electrically connected. The contacts may then be interconnected with various electrical components using plated PWB traces such as 24 as shown in FIG. 2. Such traces 24 are omitted from the other views for clarity.
A flexible or rigid mask may be used in plating the contact arms 14 and may allow plating to substantially cover the entire arm. Only the substrate area adjacent the bases of the contact arms need to be masked to produce electrical isolation between adjacent contact arms 14 as required. Due to the shape of the contact arms 14, a mask cannot tightly register over each arm at the lower inner surface. This is of no particular consequence since the entire arm 14 may be plated.
Turning now to FIG. 4, a sectional view along lines A--A of FIG. 2 is shown. In the preferred embodiment, the plastic spring formed by the contact arms 14 is designed to provide approximately 150 to 500 grams of normal contact force. Of course, this force is dependent upon the exact dimensions, tolerance and materials of the contacts 14 and may be accordingly designed for a wide range of forces. In the preferred embodiment, the contacts 14 are approximately 0.40 inches in total vertical height above the top surface of board 10. Each contact 14 includes a main contact area 26 which physically contacts the daughter board. This main contact area 26 is centered approximately 0.30 inches above the top surface of the board 10 and extends outward from the contact arm 14.
The main contact area 26 is tapered from the center of the main contact area 26 to the top of the contact 14 to provide a tapered entrance to the connector which facilitates guiding the daughter board into proper registration with the connector 10. The main contact areas 26 are also tapered downward for approximately 0.10 inches to the nominal dimension of the contact arm 14. Of course, this contact configuration may be varied substantially without departing from the present invention. The main contact area 26 may be rounded, flat, triangular, trapezoidal, etc. with similar results. The contact arm 14 itself may also be varied in angle, taper, length, width, thickness, etc. to achieve various forces and effects.
The contact arms are approximately 0.08 inches wide near the base adjacent the substrate (in the dimension shown in FIG. 4) and about 0.050 inches thick (in the dimension shown in FIG. 3). The spacing between adjacent contacts in the same row can be approximately 0.050 inches. The main contact area 26 is dimensioned to provide a nominal spacing between corresponding contacts of approximately 0.060 inches (without daughter board inserted) in order to accommodate daughter boards of nominal thickness of 0.062 inches. The contact arms 14 extend upward from the circuit board 10 at an angle of approximately seven degrees from perpendicular. All dimensions are within plus or minus approximately 0.005 inches in linear tolerance unless specified otherwise.
While the dimensions disclosed herein, are not intended to be limiting, they provide for a good mate with standard commercially available circuit cards having nominal thickness of 0.062. The dimensions disclosed are for the unplated plastic part and assume that a plating thickness of approximately 0.0015 inches will be deposited on the part as shown and / or described. The contact arms 14 are dimensioned so that the displacement of the contact arms 14 in use are limited to a deflection which will prevent significant stress on the preferred plastic material.
Of course, the embodiment shown is intended only to be illustrative. Many variations can be devised without departing from the present invention. In particular, although an eight contact connector is shown and described, the greatest utility of the present invention is probably with much larger connectors or connectors of custom configuration. Similarly, only a small PWB 12 is shown, but it will be understood by those skilled in the art that much larger PWB's which possibly include other three dimensional features and possibly multiple connectors are contemplated. In this manner, a mother board, such as those commonly used for personal computers, may be fabricated with integral expansion slots fabricated as a portion of the mother board. Similarly, backplane cards for circuit card cages can be fabricated without requiring separate edge connector part installation.
Thus it is apparent that in accordance with the present invention, an improved apparatus and method that fully satisfies the objectives, aims and advantages is set forth above. While the invention has been described in conjunction with specific embodiments, it is evident that many alternatives, variations, modifications and permutations will become apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended that the present invention embrace all such alternatives, variations, modifications and permutations as fall within the spirit and broad scope of the appended claims.
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A molded plastic circuit card edge connector. The connector includes two opposing rows of cantilever contact arms. The rows of contact arms are spaced apart adequately to allow insertion of a circuit board between the arms. The contact arms flex outward to provide spring pressure toward the circuit board. The contact arms include a main contact area which is dimensioned to produce a tapered entrance for receiving a circuit board. A plurality of stop ribs prevent the circuit board from going in too far while a pair of U-shaped guides serve to properly register the circuit board and guide it into place. The connector may be molded as an integral part of a printed wiring board.
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FIELD OF THE INVENTION
The present invention concerns a electromagnetic valve, in particular a cartridge electromagnetic valve, and the relative assembly method.
BACKGROUND OF THE INVENTION
Various types of electromagnetic valves are available, usually comprising a casing, a coil, a fixed nucleus coaxial to the coil and a mobile nucleus subject to the action of the magnetic field generated by the coil; in particular, the mobile nucleus is influenced by an axial force of attraction exchanged with the fixed nucleus and moves between two separate working positions in which it interfaces with pneumatic connections, such as, for example, a powering position and a discharging position.
The solutions available present several disadvantages. For example, the mobile nucleus tends to stick inside the coil during its working stroke; moreover, the electromagnetic valves available are complex to assemble and the assembly operations do not always guarantee the necessary precision, with particular reference to the working stroke of the mobile nucleus.
SUMMARY OF THE INVENTION
The problem of the present invention is to create a electromagnetic valve which solves the problems mentioned with reference to currently used techniques.
These problems and restrictions are solved by a electromagnetic valve as described below.
As can be seen from the description below, the valve according to the invention makes it possible to overcome the problems of the currently used technique.
In particular, the flow lines of the magnetic field generated by the coil cross the nucleus axially, the polar expansion radially, then the casing in an axial direction and then a radial direction until they reach the shoulder in order to exercise an action of attraction on the plate of the mobile nucleus. Therefore, the flow lines are not subject to any interruption; in this way the dispersion of the field is limited as is the consumption of the valve.
Advantageously, the mobile nucleus crosses the whole coil in order to prevent the nucleus from sticking. Moreover, the force of friction between the mobile nucleus and the coil is constant and does not depend on the position of the nucleus inside the coil.
Advantageously, the grooves on the mobile nucleus link up the openings in the casing; moreover, the passage of air through the ribs favours the dispersion of the heat produced by the electric winding. Moreover, improved cooling of the nucleus prevents the risk of it sticking due to thermal dilatation for example.
The use of a flat spring guarantees the exercise of purely axial force, in order to perfectly guide the mobile nucleus, reducing friction inside the coil.
Thanks to the radial rigidity of the disc spring, the mobile nucleus guided by it is prevented from coming into contact with the polar expansion, creating points of contact between said two elements of the magnetic circuit which could cause gluing phenomena during the activation of the valve.
The spring, being made of ferromagnetic material, reduces the value of total reluctance of the magnetic circuit, directly linking the casing and mobile nucleus; in this way the flow lines can cross the spring and avoid running across the radial air gap between the polar expansion and the mobile nucleus. The guide means, such as the collar, being made of ferromagnetic material, also help reduce the total reluctance of the magnetic circuit.
The conical shape of the polar expansion creates a compartment in which the spring is free to deform and supply, together with the powering body, the necessary preload.
The electromagnetic valve according to the present invention also presents numerous advantages in terms of assembly.
In particular, the configuration of the valve with the mobile nucleus passing through makes it possible, at the end of the first manual assembly phase (with the assembly of the flat spring), to obtain a stable assembly, where the action of the spring, contrasted by the plate at the far end of the passing nucleus, prevents the nucleus from slipping out and guarantees the stability of the whole assembly.
Consequently there are further advantage, such as easy storage of goods in progress and the possibility to create, for example, a store, and therefore a production detachment between the first, entirely manual phase and the subsequent phases involving extensive automation. Therefore, the restriction of continuity in the production process and one-piece flow production cease to exist.
Moreover, the stability of the semi-assembly enables the performance of intermediate checks in order to identify non-conformant products even before assembly is complete (for example, assuming the rejection of the assemblies for which the stroke cannot be corrected by subsequent calibrated plantings).
The electromagnetic valves currently available require the planting of the valve body before carrying out the checks, carrying out all the tests at the end of the assembly process.
Moreover, the valves currently available are extremely unstable due to the action of the springs which tend to oust the nucleus and complicate the powering body planting phase, requiring the supervision and intervention of the operator.
The configuration of the valve according to the present inventions enables the clear separation in the assembly process between a first entirely annual phase and a subsequent extensively/totally automated phase (where the use of automation is determined by the criticality of the plantings due to the tolerances applied.
The clear separation of the two phases makes it possible to minimise the need for staff, reduce labour costs and, therefore, the cost of manufacturing the cartridge: the intervention of the operator in the phases characterised by extensive automation—e.g.: for the position of components—involves the supervision of dedicated staff or staff who operate in accordance with machine times.
The stability of the assembly constructed at the end of the first manual phase however enables quick and almost completely independent automation, in the subsequent assembly and automatic test phases.
The electromagnetic valve according to the present invention presents a limited number of components.
The configuration of the electromagnetic valve enables the control and correction of the nominal stroke according to the geometric and dynamic characteristics of the components through the automatic planting of the powering and discharging bodies.
A technician in the sector, in order to meet contingent and specific requirements, may make numerous changes and variations to the electromagnetic valves described above, all of which are contained within the context of the invention as defined by the following claims.
BRIEF DESCRIPTION OF THE DRAWINGS
Other embodiments of the electromagnetic valve according to the invention are described in the subsequent claims.
Further characteristics and advantages of the present invention shall become clearer in the description of preferable but non-restrictive embodiments, in which:
FIG. 1 represents a prospective view in separate parts of a electromagnetic valve in accordance with an embodiment of the present invention;
FIG. 2 represents a sectioned view in separate parts of the electromagnetic valve in FIG. 1 ;
FIG. 3 a represents a sectioned view in a configuration of assembly of the electromagnetic valve in FIG. 2 ;
FIG. 3 b represents a sectioned view of an example of assembly of electromagnetic valves in accordance with the present invention;
FIG. 4 represents a prospective view of pert IV of FIG. 3 a;
FIG. 5 represents a prospective view of part V of FIG. 3 a;
FIG. 6 represents a frontal view of part VI of FIG. 3 a , according to possible variants of embodiment in accordance with the present invention;
FIG. 7 represents a prospective view in separate parts of a electromagnetic valve in accordance with a further embodiment of the present invention;
FIGS. 8 and 9 represent sectioned views in configuration of assembly of the electromagnetic valve in FIG. 7 ;
FIGS. 10-17 represent sectioned views of subsequent phases of assembly of a electromagnetic valve in accordance with the present invention:
FIG. 18 represents a diagram relating to the progress of the planting force of a spring of the electromagnetic valve depending on the movement during the spring assembly phase.
The elements or parts of elements in common between the embodiments described hereinafter shall be indicated with the same numeric references.
DETAILED DESCRIPTION OF THE INVENTION
With reference to said figures, 4 is used to globally indicate a electromagnetic valve.
The electromagnetic valve 4 comprises a casing 8 , with a mainly X-X axial extension, suitable for building a supporting structure for the electromagnetic valve 4 . For example, the casing 8 has a tubular structure which identifies a cavity 9 and extends from one powering end 10 to one discharging end 12 ; said ends 10 , 12 are preferably axially open. The term axial direction means a direction parallel to said mainly X-X extension.
The casing 8 comprises a shoulder 16 which reduces the passage section of the cavity 9 ; the shoulder 16 preferably divides the cavity into a first and second housing compartment 18 ′, 18 ″ which communicate through a connection hole 20 . The shoulder 16 preferably has a pair of electrical connection holes 22 , 23 passing through the shoulder 16 and arranged, according to one embodiment, in decentralised positions compared with the connection hole 20 ; the electrical connection holes 22 , 23 are preferably arranged in positions which are diametrically opposed to the connection hole 20 .
The casing 8 , on the side of the shoulder 16 , comprises means of contrast 24 , such as a circular border 25 positioned inside the casing ( FIG. 4 ).
Advantageously, the casing 8 is made of ferromagnetic material, thus forming an integrated part of the magnetic circuit of the electromagnetic valve.
According to a possible embodiment, the casing 8 comprises several pneumatic connections 26 , for example, for pneumatic uses of the electromagnetic valve or to construct a powering and/or discharging body for the electromagnetic valve. Said pneumatic connections 26 can be, for example, in the form of openings in the lateral wall of the casing 8 so that pneumatic uses of the electromagnetic valve can be achieved.
According to one embodiment, said pneumatic connections 26 are suitable for creating a powering and discharging body for the electromagnetic valve 4 .
For example, said pneumatic connections 26 comprise at least one powering hole 28 for the electromagnetic valve and/or one discharging hole 34 for the electromagnetic valve.
According to one embodiment, the electromagnetic valve 4 comprises a powering body provided with a powering hole 28 with relative powering nozzle 29 , suitable for sending a flow of power to the electromagnetic valve 4 .
For example, the powering body 27 is introduced into the cavity 9 of the casing and in particular in the first housing compartment 18 ′, from the powering end 10 ; the powering body 27 is preferably coupled for interference inside the casing 8 .
According to one embodiment, the electromagnetic valve 4 comprises a discharging body 32 provided with a discharging hole 34 with relative discharging nozzle 35 . The discharging body 32 is preferably introduced into the cavity 9 of the casing 8 and in particular in the second housing compartment 18 ″, from the discharging end 12 ; in particular, the discharging nozzle is introduced into the connection hole 20 of the shoulder; to guarantee the seal, an O-ring can be used between the discharging body 32 and the second housing compartment 18 ″.
According to possible embodiments of the electromagnetic valve according to the invention, at least either said powering body 27 and/or discharging body 32 is one-piece with the casing 8 .
The electromagnetic valve 4 comprises a coil 44 to generate a magnetic field, which has a central seat 48 coaxial to the same coil and to the X-X axial extension. The coil 44 comprises a reel 46 , which has to support the electric winding, and electrical connections 52 , of the ‘pin’ type for example, to power the same coil. The reel is preferably made of non-friction material.
Preferably following the introductions of the coil 44 into the casing 8 , the electrical connections 52 pass through the electrical connection holes 22 , 23 of the shoulder 16 and come out of the discharging end 12 of the casing 8 . After introduction into the casing 8 , the coil 44 is placed with a radial gap in the first housing compartment 18 ′ and brought to rest against the means of contrast 24 , 25 of the casing 8 . The term radial gap means a gap compared with a direction perpendicular to the X-X axial extension and incident with the latter.
The electromagnetic valve 4 comprises a mobile nucleus 60 , arranged coaxially to the coil 44 , made of ferromagnetic material to be influenced by the magnetic field and mobile between two working position in which it interfaces with the powering hole 28 and the discharging hole 34 respectively.
Advantageously the mobile nucleus 60 passes through the whole axial extension of the coil 44 in order to selectively open and close the powering hole 28 and the discharging hole 34 , sliding axially within the seat 48 of the coil 44 .
In particular, the mobile nucleus 60 in correspondence with opposite axial ends directly facing the powering and discharging holes 28 , 34 preferably has a pair of rubber inserts 64 , which guarantee the hermetic closure of said holes 28 , 34 . It is possible to create axial seats on the ends of the mobile nucleus and introduce the rubber inserts 64 into them, or to envisage a co-moulding phase of the mobile nucleus 60 with the rubber inserts 84 , perhaps following by the rectification of the contrast surfaces of the rubber inserts on the holes 28 , 34 .
According to one embodiment, the mobile nucleus 60 is at least partially counter-shaped in comparison to the seat 48 of the coil 44 so that it is guided axially by the coil 44 in the translational movement thereof inside the seat, between a position in which it comes to rest against the powering nozzle 29 and a position in which it comes to rest against the discharging nozzle 35 . Preferably, the mobile nucleus has a substantially cylindrical shape and is coupled, with a gap, inside the cylindrical seat 48 .
Preferably, the mobile nucleus 60 is provided with at least one groove 68 on its lateral wall 70 directly facing the seat 48 in order to identify an opening between the coil 44 and the mobile nucleus 60 which forms a duct to allow the passage of air.
According to one embodiment, the groove 68 is substantially parallel to the X-X axial direction.
Preferably, the groove 68 extends along the lateral wall 70 of the mobile nucleus 60 in order to create fluidic communication between the powering end 10 and the discharging end 12 ; in particular the axial extension of said grooves 68 is preferably greater than or equal to the axial extension of the coil 44 .
Preferably, the mobile nucleus 60 comprises a plurality of grooves 68 arranged angularly at a pitch according to an axialsymmetric configuration compared with the X-X axial direction, along the lateral wall 70 .
Advantageously, the mobile nucleus 60 comprises a plate 74 suitable for exchanging a force of attraction with the shoulder 16 of the casing 8 .
In particular, the plate 74 , in one configuration of assembly, axially faces the shoulder 16 and is positioned externally compared with the seat 48 , between the coil 44 and the shoulder 16 , inside the first housing compartment 18 ′.
Therefore, the plate 74 is positioned in correspondence with an axial end of the mobile nucleus 60 directly facing the shoulder 16 of the casing 8 in order to exchange an axial force between the casing 8 and the nucleus 60 .
The plate 74 has a radial size greater than the radial size of the seat 48 of the nucleus so that it cannot pass through the seat 48 .
Moreover, the plate 74 has a radial size smaller than the first housing compartment 18 ′ of the casing 8 so that it does not interfere radially with the casing and can slide freely inside it along the axial direction X-X.
Preferably, the plate 74 comprises at least one notch 76 to allow the passage of electrical connections 52 of the coil 44 . Preferably the notches 76 are radially aligned with the electrical connection holes 22 , 23 in the casing 8 .
The mobile nucleus 60 comprises a recess 78 to allow an axial block for elastic means 82 suitable of elastically influencing the stroke of the mobile nucleus 60 .
Preferably, said recess 78 is set in a position axially opposite the plate 74 .
The elastic means 82 comprise, for example, a disc spring 84 suitable of exercising a purely axial force on the mobile nucleus 60 . Advantageously, the elastic means 82 , and particularly the disc spring 84 , is made of ferromagnetic material.
Advantageously, the disc spring 84 comprises a plurality of through openings 86 , suitable for allowing the fluidic connection between the powering end 10 and the discharging end 12 .
Preferably the disc spring 84 is radially restricted by a lateral wall inside the casing 8 .
Advantageously, the elastic means 82 , and particularly the spring 84 , radially support the mobile nucleus 60 in order to restrict rubbing between the mobile nucleus 60 and the coil 44 as much as possible. In other words, the spring 84 also has to radially support the mobile nucleus 60 in order to guarantee the coaxial relationship with the coil 44 and prevent possible rubbing against the cavity of the coil 44 . According to a further embodiment of the present invention, the electromagnetic valve comprises radial guide means, suitable of radially guiding the mobile nucleus 60 in order to guarantee the coaxial relationship between the mobile nucleus 60 and the coil 44 .
For example, said guide means comprise a collar 87 suitable for being fitted over the mobile nucleus, preferably in a position axially opposed to the elastic means 82 , and for radially restricting the mobile nucleus 60 . In other words, the mobile nucleus 60 is radially guided in correspondence with its axially opposed ends.
According to a further embodiment, said guide means comprise a further spring, preferably of the disc type, suitable of exercising a radial guide action as well as an axial action on the mobile nucleus 60 . Preferably, said further spring is provided with a lower preload than the disc spring 84 positioned at the opposite axial end of the mobile nucleus 60 . Preferably, the guide means comprise openings 86 to allow the fluid link between the powering and discharging ends 10 , 12 . For example, the guide means are fastened to the mobile nucleus according to a coupling of shape.
Preferably, the guide means are made of ferromagnetic material.
Advantageously, the electromagnetic valve 4 comprises a polar expansion 90 coaxial to the coil 44 and positioned in correspondence with one end of the coil 44 , preferably facing the powering body 27 .
The polar expansion 90 is made of ferromagnetic material in order to form a guide means for the dissemination of the magnetic field flow lines.
For example, the polar expansion 90 has a ring configuration and is counter-shaped compared with the lateral wall inside the casing. The polar expansion comprising an opening 92 to allow the passage of the opposite end of the mobile nucleus 60 compared with the plate 74 . Advantageously, the diameter of the opening 92 of the polar expansion 90 is bigger than the diameter of the central seat 48 of the coil 44 ; this prevents the risk of possible contacts between the mobile nucleus 60 and the polar expansion 90 which could cause sticking.
In particular, the polar expansion 90 is directly in contact with the casing in order to guarantee continuity of the flow lines of the magnetic field between the mobile nucleus 80 and the casing 8 .
Preferably, the polar expansion is slid with interference into the casing, in order to form an axial block for the coil 44 which, after the introduction of the polar expansion, is axially blocked between the polar expansion 90 and the means of contrast 24 , 25 of the casing 8 .
Advantageously, the polar expansion 90 is positioned axially between the coil 44 and the disc spring 84 .
The polar expansion 90 , on the opposite side to the coil 44 , comprises a flaring 94 , axially facing the spring 84 and suitable for creating a seat to contain said spring 84 in its axial deformation.
Advantageously, the disc spring 84 is fastened in contact with the polar expansion 90 , for example in correspondence with the outer diameter of the spring and of the polar expansion, in order to create continuity for the flow lines from the nucleus to the casing.
As can be seen, the electromagnetic valve shown in the figures attached is a cartridge type electromagnetic valve and presents three ways and two positions. Obviously it is possible to envisage a different number of ways, or pneumatic connections, depending on the type of component to which the electromagnetic valve is applied. In other words, the number of ways, positions and pneumatic connections of the electromagnetic valve can be varied to suit the requirements and uses of the component.
The method used to assemble a valve according to the invention will now be described.
In particular, before assembling the various components of the valve 4 , the rubber seal inserts 64 are fitted in the mobile nucleus 60 for example being planted with a press and subsequently adjusted; according to a possible alternative embodiment it is possible to co-mould the rubber inserts 64 directly in their position on the mobile nucleus 60 . The term planting means forced insertion with interference.
After axially aligning the casing 8 , the coil 44 and the mobile nucleus 60 ( FIG. 10 ), the mobile nucleus 60 must be introduced, manually for example. Into the coil ( FIG. 11 ) and these components must then be introduced into the casing ( FIGS. 12-13 ).
To facilitate these operations, a piece holder 110 can be used.
The procedure continues with the assembly of the polar expansion 90 into the casing 8 by planting with interference, preferably with an automatic press; in this way the pieces assembled so far are locked in place; in other words, the polar expansion 90 closes the components in a pack inside the casing 8 , with the coil blocked axially between the polar expansion 90 and the means of contrast 24 , 25 of the casing 8 .
Advantageously, the mobile nucleus 60 can slide inside the coil 44 but cannot come out of the semi-assembly, thanks to the fact that the plate 74 of the mobile nucleus 60 acts as a lock to prevent the extraction of the mobile nucleus 60 from the coil 44 .
The flat spring 84 is then fitted to the mobile nucleus 60 , preferably through planting with an automatic electric press ( FIG. 14 ).
The shape of the end of the mobile nucleus 60 enables easy planting of the spring 84 elastically deforming it and locking it permanently in the recess 78 on the mobile nucleus 60 .
Planting takes place with force control; in other words, when the spring 84 enters the recess 78 there will be a drop in force indicating the end of planting.
For example, FIG. 18 shows the progress of the force of introduction of the press compared with the insertion stroke. The force undergoes a sudden change n gradient in correspondence with the introduction of the spring 84 into the appropriate recess 78 , highlighted in FIG. 18 with the reference ‘E’.
The powering body 27 is then assembled in the casing 8 through planting with an automatic press and calibration ( FIG. 15 ).
A feeler pushes on the mobile nucleus 60 and takes the plate 74 of the mobile nucleus 60 to rest against the shoulder 16 of the casing 8 and, as it ascends, measures the stroke travelled.
The value of this stroke is transferred to a PC and relative software determines the planting stroke of the powering body 27 on the basis of the nominal stroke and the measurement of the height of the powering nozzle 29 positioned on the powering body 27 .
The electric press plants the powering body 27 in the casing 8 , checking that the movement made is equal to the measurement calculated.
Advantageously, with these operations it is possible to guarantee the preload of the spring 84 , the stroke of the mobile nucleus 60 and therefore the pulling force and capacity values.
The discharging body 32 is then assembled ( FIG. 16 ) onto the casing through planting with an automatic electric press.
In this case too, the discharging body 32 and its seat in the casing 8 must be measured in order to calculate the planting stroke.
The planting operation of the discharging body 32 can be carried out as a second calibration (or a fine tuning of the first calibration). Finally, it is possible to proceed with the application of resin to the electrical connections 52 (of the ‘pin’ type for example) and to the discharging body 32 in order to guarantee the pneumatic seal of the valve 4 .
To speed up the polymerisation of the resin applied. UV-sensitive adhesive (not shown) and a special lamp 62 are used ( FIG. 17 ).
Preferably, the assembly operations are followed by an electrical pneumatic test of the electromagnetic valve 4 .
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An electromagnetic valve comprising casing, a coil and a mobile nucleus, sliding axially across the entire extension of the coil, between two operative positions wherein there is an interface with a powering body and a discharging body. The configuration of the electromagnetic valve guarantees a precise guide of the mobile nucleus free from sticking and enables speed and precision in the assembly of the electromagnetic valve.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The disclosure is generally related to haptic systems employing force feedback.
2. Description of the Related Art
Touch, or haptic interaction is a fundamental way in which people perceive and effect change in the world around them. Our very understanding of the physics and geometry of the world begins by touching and physically interacting with objects in our environment. The human hand is a versatile organ that is able to press, grasp, squeeze or stroke objects; it can explore object properties such as surface texture, shape and softness; and it can manipulate tools such as a pen or wrench. Moreover, touch interaction differs fundamentally from all other sensory modalities in that it is intrinsically bilateral. We exchange energy between the physical world and ourselves as we push on it and it pushes back. Our ability to paint, sculpt and play musical instruments, among other things depends on physically performing the task and learning from the interactions.
Haptics is a recent enhancement to virtual environments allowing users to “touch” and feel the simulated objects with which they interact. Haptics is the science of touch. The word derives from the Greek haptikos meaning “being able to come into contact with”. The study of haptics emerged from advances in virtual reality. Virtual reality is a form of human-computer interaction (as opposed to keyboard, mouse and monitor) providing a virtual environment that one can explore through direct interaction with our senses. To be able to interact with an environment, there must be feedback. For example, the user should be able to touch a virtual object and feel a response from it. This type of feedback is called haptic feedback.
In human-computer interaction, haptic feedback refers both to tactile and force feedback. Tactile, or touch feedback is the term applied to sensations felt by the skin. Tactile feedback allows users to feel things such as the texture of virtual surfaces, temperature and vibration. Force feedback reproduces directional forces that can result from solid boundaries, the weight of grasped virtual objects, mechanical compliance of an object and inertia.
Tactile feedback, as a component of virtual reality simulations, was pioneered at MIT. In 1990 Patrick used voice coils to provide vibrations at the fingertips of a user wearing a Dextrous Hand Master Exoskeleton. Minsky and her colleagues developed the “Sandpaper” tactile joystick that mapped image texels to vibrations (1990). Commercial tactile feedback interfaces followed, namely the “Touch Master” in 1993, the CyberTouch® glove in 1995, and more recently, the “FEELit Mouse” in 1997.
Scientists have been conducting research on haptics for decades. Goertz at Argonne National Laboratories first used force feedback in a robotic tele-operation system for nuclear environments in 1954. Subsequently the group led by Brooks at the University of North Carolina at Chapel Hill adapted the same electromechanical arm to provide force feedback during virtual molecular docking (1990). Burdea and colleagues at Rutgers University developed a light and portable force feedback glove called the “Rutgers Master” in 1992. Commercial force feedback devices have subsequently appeared, such as the PHANTOM™ arm in 1993, the Impulse Engine in 1995 and the CyberGrasp® glove in 1998.
Haptic devices (or haptic interfaces) are mechanical devices that mediate communication between the user and the computer. Haptic devices allow users to touch, feel and manipulate three-dimensional objects in virtual environments and tele-operated systems. Most common computer interface devices, such as basic mice and joysticks, are input-only devices, meaning that they track a user's physical manipulations but provide no manual feedback. As a result, information flows in only one direction, from the peripheral to the computer. Haptic devices are input-output devices, meaning that they track a user's physical manipulations (input) and provide realistic touch sensations coordinated with on-screen events (output). Examples of haptic devices include consumer peripheral devices equipped with special motors and sensors (e.g., force feedback joysticks and steering wheels) and more sophisticated devices designed for industrial, medical or scientific applications (e.g., PHANTOM™ device).
Haptic interfaces are relatively sophisticated devices. As a user manipulates the end effecter, grip or handle on a haptic device, encoder output is transmitted to an interface controller at very high rates. Here the information is processed to determine the position of the end effecter. The position is then sent to the host computer running a supporting software application. If the supporting software determines that a reaction force is required, the host computer sends feedback forces to the device. Actuators (motors within the device) apply these forces based on mathematical models that simulate the desired sensations. For example, when simulating the feel of a rigid wall with a force feedback joystick, motors within the joystick apply forces that simulate the feel of encountering the wall. As the user moves the joystick to penetrate the wall, the motors apply a force that resists the penetration. The farther the user penetrates the wall, the harder the motors push back to force the joystick back to the wall surface. The end result is a sensation that feels like a physical encounter with an obstacle.
The human sensorial characteristics impose much faster refresh rates for haptic feedback than for visual feedback. Computer graphics has for many years contented itself with low scene refresh rates of 20 to 30 frames/sec. In contrast, tactile sensors in the skin respond best to vibrations that are more than an order-of-magnitude higher than visual rates. This order-of-magnitude difference between haptics and vision bandwidths often requires that the haptic interface incorporate a dedicated controller. Because it is computationally expensive to convert encoder data to end effecter position and translate motor torques into directional forces, a haptic device will often have its own dedicated processor. This removes computation costs associated with haptics and the host computer can dedicate its processing power to application requirements, such as rendering high-level graphics.
General-purpose commercial haptic interfaces used today can be classified as either ground-based devices (force reflecting joysticks and linkage-based devices) or body-based devices (gloves, suits, exoskeletal devices). The most popular design on the market is a linkage-based system, which consists of a robotic arm attached to a grip (usually a pen). A large variety of linkage based haptic devices have been patented (examples include U.S. Pat. Nos. 5,389,865; 5,576,727; 5,577,981; 5,587,937; 5,709,219; 5,828,813; 6,281,651; 6,413,229; 6,417,638). The arm tracks the position of the grip and is capable of exerting a force on the tip of this grip. To meet the haptic demands required to fool one's sense of touch, sophisticated hardware and software are required to determine the proper joint angles and torques necessary to exert a single point of force on the tip of the pen. Not only is it difficult to control force output because of the update demand, the mass of a robotic arm introduces inertial forces that must be accounted for.
An alternative to a linkage-based device is one that is tension-based. Instead of applying force through links, cables are connected a point on a “grip” in order to exert a vector force on that grip. Encoders can be used to determine the lengths of the connecting cables, which in turn can be used to establish position of the cable connection point on the grip. Motors are used to create tension in the cables, which results in an applied force at the grip. There is only one commercial tension based device available, through a Japanese company called Cyverse.
The SPIDAR-G is a 7 degree of freedom haptic device that allows translational, rotational and grip force. This design resulted from Dr. Seahak Kim's PhD work (Dr. Seahak Kim is currently an employee of Mimic Technologies, Inc.). References for much of Dr. Seahak Kim's work on the SPIDAR-G have been listed above.
Predating Dr. Seahak Kim's work on the SPIDAR-G, Japanese Patent No. 2771010 and U.S. Pat. No. 5,305,429 were filed that describe a “3D input device” as titled in the patent. This system consists of a support means, display means and control means. The support means is a cubic frame. Attached to the frame are 4 encoders and magnetic switches capable of preventing string movement over a set of pulleys. The pulleys connect the tip of each encoder to strings that are wound through the pulleys. Each string continues out of the pulley to connect with a weight that generates passive tension in the string. The ON/OFF magnetic switches allow the strings to be clamped on command from the host computer. The strings connect to the user's fingertip, which are connected to the weights through the pulleys. The user moves his or her fingertip to manipulate an “instruction point” in a virtual environment, which is displayed through a monitor. As the user moves his or her fingertip, the length of the four strings change, and a computer calculates a three-dimensional position based on the number of pulses from the encoder, which indicate the change of string length between the pulleys and the user's finger. If the three-dimensional position of the fingertip is found to collide with a virtual object as determined by a controlling host computer, then the ON/OFF magnetic switch is signaled to grasp some or all of the strings so that movement is resisted. Forces are not rendered in a specific direction, but resistance to movement in some or all directions indicates that a user has contacted a virtual object. When the fingertip is moved outside the boundary of a virtual object, the magnetic switch is turned off to release the strings. The user is then able to move his or her finger freely.
The “3 dimensional input device” introduced in U.S. Pat. No. 5,305,429 is not capable of controlling or rendering directional forces. It is therefore not possible to render three-dimensional forces in the manner typically associated with a haptic device. In other words, this device is not capable of simulating haptic effects such as the feel or contact with a virtual three-dimensional surface.
The “3 dimensional input device” cannot render controlled vector forces because of the following reasons, (i) it is impossible to display exact directional force, because the device can only apply drag, or resistance to movement to each string by ON/OFF magnetic switches and cannot impose an exact tension in each string; (ii) there is no accounting for the changing force applied by the weights attached to each string which provide a variable tension as the velocity of the moving weight changes the tension; (iii) there is no accounting for extraneous forces resulting from friction between the frame, pulleys, ON/OFF magnetic switches and the strings; and (iv) there is no initialization sequence described which is required for determining initial string lengths as need for determining string orientations and finger position so that forces can be reflected accurately. In summary this is not a true force feedback device, but instead is only a tracking mechanism with a single force effect (direction nonspecific drag). As an input device, the system also lacks a robust measurement method for determining the length of the strings, which results in substantial fingertip position measurement errors. There is also no means for measuring orientation of the finger (roll, pitch and yaw).
A system that combines virtual reality with exercise is described in U.S. Pat. No. 5,577,981. This system uses sets of three cables with retracting pulleys and encoders to determine the position of points on a head mounted display. Using the lengths of the three cables, the position of the point in space is found. Tracking three points on the helmet (9 cables) allows head tracking of 6 degrees of freedom. Three cables attached to motor and encoders are also used to control the movement of a boom that rotates in one dimension through a vertical slit in a wall. The boom also has a servomotor at its end, about which the boom rotates. It is claimed that the force and direction of force applied by the boom can be controlled via the cables, servo motor and computer software, but no details are provided for how this is accomplished.
Applications have been filed for patents in Japan and the US to support the SPIDAR-G (as discussed earlier). This apparatus was titled “three-dimensional input apparatus” and was filed under patent No. 2001-282448 in Japan, and a U.S. patent application has also been submitted: No. 20010038376. This device also consists of a support means, display means and control means similar to that described in U.S. Pat. No. 5,305,429. However, this device uses “at least seven strings” to accommodate “at least six degrees of freedom” (actually the patent application only explains 7 degrees of freedom with 8 strings, but a claim is made for 6 degrees of freedom with seven strings). The mentioned support means includes a cubic frame, where a motor and encoder are attached to at least seven locations on the frame. The tip of each encoder is connected to a spool on a motor, and this spool winds the string. The encoder and motor are rotated simultaneously. The motors are meant to create tension in the strings in place of the weights used in the earlier patent. Instead of the string attaching to the users finger, the strings attach to a sphere shaped grip.
This grip has a mechanical structure that consists of two poles that are rotated based on the grasp force between the thumb and other fingers of the user. Two strings are connected to each of the four extremities of the two poles. If the user moves the tool to manipulate a virtual object in a virtual environment, as displayed through a monitor, each string length is changed, and the computer is used to calculate a three dimensional position (translation, rotation and grasp information) based on the number of pulses from the encoder, which is an indication of a change in string length. If contact is made with a virtual object, the controlling computer is used to calculate the tensions in the strings that are necessary to render force and torque at the grip.
The system described in Japanese patent 2001-282448 can therefore actively display translation, rotation, and grasp force. As a result, the user is able to “touch” virtual objects through the display of force. However, the above-mentioned “3 Dimensional interface device” requires at least seven strings to determine position and render force, even if rotation and grip forces are not being applied, and, while the design described above is adequate for displaying seven degrees of force feedback, there are severe limitations imposed if less than seven degrees of force feedback are required.
BRIEF SUMMARY OF THE INVENTION
In one aspect of the invention, an input/output haptic interface is provided, to input the position of a tool(s) held by the user to a computer by directly determining position and orientation of the tool in a three-dimensional space. Tracking may be accomplished over as many as six degrees of freedom.
In another aspect, a method is provided, for determining a tool position through cable lengths with minimal error. Position of the tool may also be established with alternative tracking mechanisms such as through infrared, electromagnetic, gyro or acceleration sensors.
In another aspect, an input/output haptic interface is provided, to render forces to a point on a tool held by a user over two or three dimensions as signaled from software running on a host computer. Multiple sets of cables render vector forces to multiple points on a tool. Alternatively, multiple sets of cables render vector forces to points on multiple tools used in the same workspace.
In yet another aspect, a new calibration system is provided, for maintaining tool position accuracy with minimal user intervention, even after powering down and reactivation of the apparatus over multiple iterations.
In a further aspect, an input/output haptic interface provides a user with the “touch” sensation generated as a result of interaction with virtual environments, which could include force effects such as contact force resulting from tool collision with rigid or deformable virtual surfaces, the pull, push, weight or vibration of a virtual object contacting a tool(s), and/or viscous resistance and inertia experienced as a tool moves through virtual fluid.
In still a further aspect, an interface relays position and forces data to and from a robot (or similar system). Control of the robot (or similar system) through the invention can be used to establish telepresence.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)
In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn, are not intended to convey any information regarding the actual shape of the particular elements, and have been solely selected for ease of recognition in the drawings.
FIG. 1 is a block diagram that describes the components of the invention and how they relate to each other.
FIG. 2 is a perspective view of one possible configuration of the interface device which includes tool translation effecter components, cables and a supporting frame.
FIG. 3 is a perspective view of one possible configuration of a tool translation effecter device.
FIG. 4 is a perspective view of another possible configuration of a tool translation effecter device that uses an eyelet rather than a pulley and associated parts.
FIG. 5 is a top view of the tool translation effecter device shown in FIG. 3 .
FIG. 6 is a side view of the tool translation effecter device shown in FIG. 3 .
FIG. 7 shows the grooves on the second pulley of the tool translation effecter device that help evenly guide a winding cable.
FIG. 8 is a perspective view of another possible configuration of the interface device, which includes tool translation effecter components, cables, a supporting frame, a port and a minimally invasive othoscope.
FIG. 9 shows a typical cycle of information/action flow as position of a tool is detected and force is displayed at the tool.
FIG. 10 shows a generalized schematic for rendering force and tracking a tool over two dimensions.
FIG. 11 shows a configuration of the invention that will allow forces to be applied and controlled on a port, or trocar, over two dimensions in a system that might be used for minimally invasive surgery simulation. The system also allows for tracking the position of the point on the port where the cables connect.
DETAILED DESCRIPTION OF THE INVENTION
While the system described in Japanese patent 2001-282448, and outlined in the background section of this document, provides significant advantages over the previous art, there are still some problems that remain unaddressed. For example, when calculating the length of each string, error is introduced because a changing spool diameter resulting from string wrapped over itself on the spool is not accounted for; the device calculates rotation based on the length change in eight strings, where a minor error in length variation of one string can substantially affect accuracy (calculation algorithm is not robust about rotation); there is no initialization sequence provided, which is necessary for determining initial string length as required for determining position, orientation and grip, and minimizing associated error; the grip is connected with eight strings, so workspace is limited if the user wishes to avoid tangling the strings; and there is no accounting for extraneous forces resulting from friction between the frame, pulleys, motors and strings.
In the following description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the invention. However, one skilled in the art will understand that the invention may be practiced without these details. In other instances, well-known structures associated with motors, motor controllers, computers, microprocessors, memories and the like have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments of the invention.
Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is as “including, but not limited to.”
The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.
FIG. 1 shows a tension based force feedback system 10 using cables, includes a number of devices or modules, such as: an interface module 100 to detect translational and rotational signals concerning the tracking of a tool manipulated by the user; a control module 200 to convert analog and pulse signals generated from the interface device 100 to digital signals and to relay force signals to the mentioned interface device 100 ; a calculation module 300 to control force feedback, to calculate the position of a tool based on translation and rotational manipulation by the user, and to mathematically represent objects and/or environments that might interact with the tool; a display module 400 for the user to perceive visual and/or audible information about the tool 160 and objects and/or environments which are modeled in the calculation device 300 ; and a robotic module 500 , which in those embodiments of the invention that are so configured, receives control instructions from, and provides feedback signals to, the calculation module 300 .
FIG. 2 shows one possible configuration of the interface device 100 . This configuration of the interface device includes a frame 110 , four cable control units or tool translation effecter devices 120 , 130 , 140 , and 150 , a tool 160 , and a sensor array, or tool rotation detection device 170 .
Reference to the tool 160 may also be construed to refer to a connection point to which the cables 11 , 12 , 13 , and 14 are attached. According to some embodiments of the invention, a separate tool, device, handle, or other implement is coupled to the tool 160 .
The frame 110 in FIG. 2 represents one possible structure for supporting the tool translation effecter devices 120 , 130 , 140 , and 150 and the other components that are located within a three dimensional space. The frame 110 can be constructed from a variety of materials, such as sheet metal, trusses or rigid plastic, and can take the form of a wide variety of geometries that partially enclose a three dimensional volume. The main requirement of the frame is to provide rigid support of elements such as the detection devices 120 , 130 , 140 , and 150 . At the same time the frame geometry should allow the user to freely manipulate the tool 160 within a prescribed workspace, without excessive collision of the tool 160 , or the user's hands, with the frame 110 . In the embodiment illustrated in FIG. 2 , the prescribed workspace is approximately cubic with the volume partially enclosed by sides 111 - 119 .
Each tool translation effecter device 120 , 130 , 140 and 150 is positioned in three-dimensional space, and coupled at a corresponding anchor point to the frame 110 . In the embodiment of FIG. 2 , the tool translation effecter device 120 is positioned at the end of the upper right arm on the frame side 111 , the tool translation effecter device 130 is positioned at the end of the upper left arm on the frame side 112 , the tool translation effecter device 140 is positioned at the lower front of the frame in the center of side 115 , and the tool translation effecter device 150 is positioned at the lower back of the frame in the center of side 116 . Tool translation effecter devices 120 and 130 are centered in-between the tool translation effecter devices 140 and 150 when viewed along the X-axis. Tool translation effecter devices 140 and 150 are centered in-between the tool translation effecter device 120 and 130 when viewed along the Y-axis. The tool translation effecter devices 120 , 130 , 140 and 150 can be positioned in a variety of configurations, and are not limited to that illustrated by FIG. 2 . The main objective when placing the tool translation effecter devices 120 , 130 , 140 and 150 is to maximize the volume enclosed by the devices 120 , 130 , 140 , 150 given the geometry of the frame 110 .
FIG. 3 , 5 and 6 show detailed views of an illustrative one of the tool translation effecter devices 120 , 130 , 140 , 150 . While translation effecter device 120 is described for the purpose of illustration, it will be understood that, according to one embodiment of the invention, translation effecter devices 130 , 140 , and 150 are substantially identical in structure and operation.
The illustrated tool translation effecter 120 includes a mounting system 121 , a pulley 122 , a first bearing 123 , a motor 124 , an encoder 125 , a spool 126 , a cable 11 , a second bearing 128 , and a motor brake 129 .
The four tool translation effecter devices 120 , 130 , 140 and 150 of FIG. 2 are oriented so that spools 126 generally guide the cables 11 , 12 , 13 and 14 toward the tool 160 with the objective of minimizing friction in the cable run (i.e., path) to the tool 160 .
The mounting system 121 of each tool translation effecter 120 , 130 , 140 , 150 provides a path that guides the cable 11 from the spool 126 to the pulley 122 , while providing stability for the spool 126 and the pulley 122 , so that the center of the axis of each stays fixed in position when tension is applied to the cable 11 . The mounting system 121 also provides a structure to couple the respective tool translation effecter device 120 , 130 , 140 , 150 to the frame 110 . The mounting system 121 also positions the pulley 122 away from both the frame 110 and the spool 126 in a manner that enables ideal use of tool workspace. The mounting system 121 may vary in size or geometry depending on workspace requirements.
The mounting system 121 includes a link 121 a that is fixed to a bracket 121 c . A rotary fulcrum 121 b is attached to link 121 a through a secondary bearing 128 . The rotary fulcrum 121 b can rotate about an axis that is perpendicular to the adjacent face of link 121 a . The secondary bearing between link 121 a and rotary fulcrum 121 b allows smooth rotation around an axis defined by hole 121 e of FIG. 5 as illustrated by arrow 121 f (see FIG. 6 ). The hole 121 e runs through the center of the rotary fulcrum 121 b , and the cable 11 passes through the hole 121 e . The cable 11 is guided to the pulley 122 from the spool 126 through the hole 121 e . The pulley 122 is mounted to the rotary fulcrum through bracket 121 d . The pulley 122 rotates around bearing 123 as illustrated by arrow 121 g ( FIG. 6 ), which lies between bracket 121 d and the pulley 122 . In addition to its attachment to link 121 a , bracket 121 c is attached to the motor 124 , the brake 129 , and also to the frame 110 .
Each motor 124 is typically a DC motor that displays minimal back drive friction. The shaft of each motor 124 is drivingly coupled to a spool 126 , which is in turn coupled to a cable 11 . When the motor 124 turns the respective pulley 126 , the cable 11 wraps or unwraps around the pulley 126 . Tension occurs in each cable 11 , 12 , 13 and 14 because the cables 11 , 12 , 13 and 14 pull at the tool 160 in opposing directions. The tension applied to each cable 11 , 12 , 13 and 14 is based on the torque applied by the motors 124 to the spool 126 as governed by the control device 200 . In order to reduce backlash, a gear is not used, however some embodiments may include a gear where suitable.
An encoder 125 is coupled to each motor 124 and converts the user's manipulation as represented by rotation of the motor shaft into electrical pulses that are sent to the control device 200 . Typically, an optical encoder is used with a resolution of 1024 pulses per rotation of the motor shaft. However, a variety of optical encoders can be used that have a wide range of resolutions. An encoder is therefore chosen based on application requirements and price constraints. Determining translational movement of the tool 160 can be calculated from the length of each cable 11 , 12 , 13 and 14 , which is determined from encoder 124 pulse signals. There is a mathematical relationship between cable length change, diameter of the spool 126 , and the pulses per rotation. The spool 126 can be made of a variety of materials, such as aluminum, steel, rigid plastic or any other stiff material. The spool 126 may be grooved as shown in FIG. 7 , allowing the cable to wrap evenly about spool 126 , although such is not required.
FIG. 4 shows, according to an alternative embodiment, a cable control unit 135 , wherein the pulley 122 , the first bearing 123 , the second bearing 128 , and parts 121 a , 121 b and 121 d (shown in FIG. 3 ) are omitted. In the place of these components is a low friction eyelet 122 that guides the cable 11 from the spool 126 through the mounting system 121 . The cable control unit 135 has fewer moving parts than the cable control unit 120 described with reference to FIGS. 3 , 5 , and 6 , but may, in some applications, introduce more drag to the associated cable 11 .
The cables 11 , 12 , 13 and 14 connect between the spools 126 of the tool translation effecters to the tool 160 . The cables 11 , 12 , 13 and 14 are ideally made of a material that is substantially inelastic under tension, such as Dacron fishing line, but any string, wire or other cable that is flexible, durable and exhibits minimal stretch under tension can be used. The cables 11 , 12 , 13 and 14 connect to a point, or series of points in close proximity, on the tool 160 or tool holder. The tool 160 might be a stylus, pen, pliers, wrench, forceps, needle holder, scalpel, endoscope, arthroscope, minimally invasive surgical tool or other mechanical or medical tool. The tool could be free floating as illustrated in FIG. 2 , or might move through a pivot point, such as the port 172 as illustrated in FIG. 8 , or the port 174 of FIG. 11 . Any object that can be connected to the cables 11 , 12 , 13 and 14 , such that the cables 11 , 12 , 13 and 14 can apply vector forces to a point, or series of points in close proximity, on the object through cable tension, may be considered the tool 160 as used herein. The cables 11 , 12 , 13 , 14 , apply a vector force to the tool 160 .
According to an embodiment of the invention, the tool 160 also carries a sensor array 170 having one or more sensors, such as gyro sensors, acceleration sensors, infrared or electromagnetic sensors that can relay signals to the control module 200 . The purpose of these sensors is to relay information that can be used to determine tool orientation (roll, pitch and yaw) at the control module 200 . Such sensors can also be used to relay information about the tool translation in the x, y and/or z directions in three dimensional space instead of, or in addition to, the encoders 124 to determine the cable 11 , 12 , 13 , and 14 lengths. Such sensors are commercially available from a wide variety of vendors and take a wide variety of shapes and configurations, so the details of these sensors have not been illustrated in the figures. The wires and/or wireless transmitters/receivers for to transferring sensor signals from the sensor array 170 to the control module 200 are also not shown in the figures, although in at least one embodiment the cables 11 , 12 , 13 , 14 may carry such signals.
As has been previously explained, according to some embodiments of the invention the tool 160 comprises a connection point to which the cables 11 , 12 , 13 , and 14 are attached. A separate tool or device may then be coupled to the tool 160 . Accordingly, the sensor array 170 may be configured to detect rotation of the separate tool, as it moves or rotates in one or more axes within the tool 160 .
According to another embodiment, the tool 160 includes a vibrating element attached, whose frequency and magnitude of vibration are regulated by the control module 200 . The vibration element may be used to create tactile effects. Vibration can also be used to simulate different materials. For example, a dissipating vibration signal at a high frequency might be used when simulating contact with steel as compared to a dissipating vibration signal at a lower frequency, which could be used when simulating contact with wood. Suitable vibrating elements are generally known, such as those employed in paging devices and cellular phones, so will not be discussed in detail in the interest of brevity.
The control module 200 sends control signals to the motors 124 and receives signals from the encoders 125 of each tool translation effecter device 120 , 130 , 140 , 150 . The control module 200 includes three primary components; a motor controller 210 , which controls tension in each cable 11 , 12 , 13 and 14 via the motors 124 as directed by the calculation module 300 ; an encoder counter 220 that receives and counts pulse signals from the encoders 125 and provides these counts to the calculation module 300 ; and an A/D converter 230 that converts analog signals transmitted from each tool translation effecter device 120 , 130 , 140 , 150 to digital signals that are relayed between the calculation module 300 and the control module 200 .
The calculation module 300 consists of a local processor, memory storage and associated components on a printed circuit board for implementing local software control. The calculation module 300 may also include a remote computer, such as a conventional Pentium processor type or workstation with conventional memory and storage means. The remote computer may transfer data to the local processor through connections such as USB, serial, parallel, Ethernet, Firewire, SCSI, or any other means of transferring data at a high rate. The calculation module 300 processes information via software control. The functions of the calculation module 300 may be classified into five parts or functions: an object/environment representation function 310 , a position calculation function 320 , a collision detection function 330 , a force control function 340 , and an application recording function 350 .
According to an embodiment of the invention, some or all of the processing tasks, including those described with reference to the control device 200 and the calculation device 300 , may be performed by a conventional system or workstation.
The object/environment representation function 310 manages and controls modeling information about virtual (or real) objects, the three dimensional environment, the tool 160 , and determines the proper interaction between the objects, environment and the tool 160 . The object/environment representation function 310 might also include information about a robotic module 500 , information sent from the robotic module 500 , and/or how movement of the tool 160 effects navigation of the robotic module 500 . The visual representation of these objects is relayed from the object/environment representation function 310 to the display module 400 . The position calculation function 320 determines the position of the tool 160 by processing signals from the control module 200 about translation and rotational movement of the tool 160 . The collision detection function 330 determines whether a collision has occurred between modeled objects and the tool 160 . This might also include the indication of existing environmental effects such as viscous resistance and inertia experienced as a tool 160 moves through virtual fluid. When the system 10 is used to control a robot associated with the robotic module 500 , collisions may be collected from the robot as it collides with real objects. The force control function 340 is used to calculate tension of each cable 11 that is appropriate for rendering reaction forces that take place at the tool 160 . The summation of vector forces in the cables 11 , 12 , 13 and 14 will equal the reaction force at the tool 160 . Such forces might be the result of reaction forces collected by a robot as it interacts with real objects. The application record function 350 manages all other software interaction that takes place in an application that utilizes the system 10 .
The display module 400 displays manufactured virtual objects modeled through the calculation module 300 . The display module 400 might also be used to convey visual information about real objects, such as in the case of using the system 10 to control the robotic system 500 as it interacts with real objects. The display module 400 is typically understood to be a conventional video monitor type and may be, for example, NTSC, PAL, VGA, or SVGA. The display module may also consist of a head mounted display or a video projection system. The display module 400 may relay a 2D representation or a stereoscopic representation for 3D projection. The display module 400 might be used, for example, to collocate stereoscopic representations into the workspace of the system 10 . This could be accomplished by placing the face of a monitor between sides 116 and 117 or the images could be projected through mirrors located at the back, bottom or top of the frame 110 . Stereoscopic images may also be relayed through a head mounted display. The display module 400 may relay virtual environments where the entire environment can be classified as a rendered graphical image. The display module 400 may also transmit augmented environments where graphical rendering is overlaid onto video feeds or “see through” displays of real environments. The display module 400 could also transmit pure video of real environments, such as might be the case when the system 10 is used to control a robot operating in a real environment.
In one embodiment the system 10 performs a variety of processes. A process to establish the initial length of each cable 11 , 12 , 13 , and 14 is achieved through processing transmitted signals between the calculation device 300 and each encoder counter device 220 and by utilizing a history of encoder pulse counts from each tool translation effecter 120 , 130 , 140 and 150 as stored in the calculation device 300 . The system 10 performs the process of relaying position and orientation (roll, pitch and yaw) information about the tool 160 to the calculation device 300 through optical encoders and/or sensors such as gyro sensors, acceleration sensors, infrared or electromagnetic tracking mechanisms located in and/or around the tool 160 . The system 10 performs the process of establishing the position and orientation (roll, pitch and yaw) of the tool 160 in three dimensional space at the calculation device 300 . The system 10 performs the process of determining the position and orientation of the tool 160 with the calculation device 300 from the signals sent by the control device 200 and/or the tool 160 to the calculation device 300 .
The system 10 further performs the process of establishing in the calculation device 300 a force response that is appropriate at the tool 160 based on position and orientation of the tool 160 as it relates to virtual or real objects defined at the calculation device 300 . The system 10 carries out the process of determining tension values in each cable 11 , 12 , 13 , and 14 that will deliver a force response to the tool 160 as determined at the calculation device 300 , and controlling tension in each cable 11 , 12 , 13 , and 14 , by driving the motor 124 of each tool translation effecter devices 120 , 130 , 140 , 150 based on the tension values determined in the calculation device 300 . Finally, the system 10 performs the process of relaying visual and audible information to the display device 400 from the calculation device 300 about the location and orientation of the tool 160 and virtual or real objects that the tool 160 may be interacting with.
As used in the claims, the term active tension refers to a force applied in a longitudinal direction to a cable that, if it were not resisted, would result in lengthwise movement of the cable. For example, the driving motor 124 of each of the tool translation effecters 120 applies active tension to the cable, in that the motor applies a force in the form of torque to the associated spool to retract the associated cable, thereby transferring the force longitudinally along the cable. If the force is resisted, tension on the cable will be exerted, proportionate to the force applied by the motor; if the force is not fully resisted, the cable will rewind, i.e., the active tension will result in movement of the cable. If active tension applied to each of the cables of a haptic system is equal, the system will be balanced and no movement will result. By selectively varying the force applied to individual cables, a force response, as described above, will be applied, which, if not resisted by the operator, will result in movement of the tool or attachment point according to a net value of the longitudinal forces applied. Calculation of values to produce a given force response will be described in more detail later.
This is in contrast to systems such as that described in the background of this disclosure with reference, for example, to U.S. Pat. No. 5,305,429, in which a static weight applies a constant and equal tension to each of the lines, and in which the system can resist movement of the “instruction point” by application of drag, but cannot vary the longitudinal force applied by the weights so as to result in movement of the instruction point independent of force applied by the operator.
A typical cycle of information/action flow is shown in FIG. 9 , however, there would likely be more acts or steps in the case of representing a very complex environment. The steps of FIG. 9 utilize the processes outlined above.
A process for establishing the initial length of each cable 11 , 12 , 13 , and 14 is described below. According to one embodiment of the invention, these lengths are determined before the position of the tool 160 is calculated. Calibrating these lengths can include the following acts:
1) The point on the tool 160 where the cable 11 is attached is moved to the pulley 122 of the tool translation effecter 120 located on the upper right arm of the frame side on side 111 . At this calibration point (P 1 ), the length of cable 11 extending from the pulley 122 to the tool 160 is considered to be 0 cm. The counter value of the encoder 125 of the tool translation effecter 120 is then set to 0 by the calculation device 300 while the tool 160 is in this position. The encoder counts of each tool translation effecter 120 , 130 , 140 and 150 are recorded at this position. 2) The point on the tool 160 where the cable 12 is attached is moved to the pulley 122 of the tool translation effecter 130 located on the upper left arm of the frame on side 112 . At this calibration point (P 2 ), the length of cable 12 extending from the pulley 122 to the tool 160 is considered to be 0 cm. The counter value of the encoder 125 of the tool translation effecter 130 is then set to 0 by the calculation device 300 while the tool 160 is in this position. The encoder counts of each tool translation effecter 120 , 130 , 140 and 150 are recorded at this position. 3) The point on the tool 160 where the cable 13 is attached is moved to the pulley 122 of the tool translation effecter 140 located on the lower front portion of the frame on side 115 . At this calibration point (P 3 ), the length of cable 13 extending from the pulley 122 to the tool 160 is considered to be 0 cm. The counter value of the encoder 125 of the tool translation effecter 140 is then set to 0 by the calculation device 300 while the tool 160 is in this position. The encoder counts of each tool translation effecter 120 , 130 , 140 and 150 are recorded at this position. 4) The point on the tool 160 where the cable 14 is attached is moved to the pulley 122 of the tool translation effecter 150 located on the lower back portion of the frame on side 116 . At this calibration point (P 4 ), the length of cable 14 extending from the pulley 122 to the tool 160 is considered to be 0 cm. The counter value of the encoder 125 of the tool translation effecter 150 is then set to 0 by the calculation device 300 while the tool 160 is in this position. The encoder counts of each tool translation effecter 120 , 130 , 140 and 150 are recorded at this position. 5) There is now a relationship between the number of encoder pulses and the change in distance between the tool 160 and the pulleys 122 attached to the tool translation effecters 120 , 130 , 140 and 150 . The method for determining cable length and the position of the tool will be described later in this document. At this point, the recorded encoder counts are adjusted to account for the fact that some pulse counts were recorded before the counter value was set to zero. Values counted before the encoder was set to zero are offset by the appropriate amount. Steps 1 through 5 can be repeated to calibrate the device if it is believed that tracking inaccuracies exist, but normally, steps 1 though 5 are only required when powering up the system 10 for the first time with a new computer. 6) When powering down the system 10 , the calculation device 300 first signals for the current to be removed from each spring actuated brake 129 attached to the motor spool 126 of the tool translation effecters 120 , 130 , 140 and 150 . This prevents the motors 124 from spinning their respective spools 126 . This also keeps the encoders 125 locked in position. The calculation device 300 can then store the current pulse count from all the encoders 125 before completely powering down the system. 7) The next time the system 10 is powered up, the encoder pulse count values are then restored to each encoder 125 based on the values stored by the calculation device 300 . Current to the brakes 129 is then re-established by the calculation device 300 , which releases the hold on the motor spools 126 . The tracking of the lengths of cables 11 , 12 , 13 , and 14 can then resume as it did before the system 10 was last powered down.
The process to relay position, orientation and rotational information of the tool 160 to the calculation device 300 through optical encoders and/or sensors such as gyro sensors, acceleration sensors, infrared or electromagnetic tracking mechanisms located in and/or around the tool 160 will now be discussed. The optical encoders 125 of the tool translation effecter devices 120 , 130 , 140 , 150 output analog signals that are transferred to an A/D converter 230 . These signals are then converted to digital signals that are relayed to the calculation device 300 as encoder pulse counts. The digital signals are transferred to the position calculation part 320 of the calculation device 300 by way of the encoder counter part 220 . The encoder pulse counts are used to determine the lengths of the cables 11 , 12 , 13 , and 14 .
The system 10 may employ a sensor array 170 having, for example, three gyro sensors or acceleration sensors to detect rotational movement of the tool 160 . The sensor array 170 outputs analog signals depending on rotational acceleration or rotational degree of movement of the tool 160 . The analog signals reflect rotation over three degrees of freedom (roll, pitch and yaw). These signals are transferred to A/D converter 230 , which converts the signals to digital signals. The digital signals are then transferred to the position calculation part 320 of the calculation device 300 by way of the encoder counter part 220 . The orientation (roll, pitch and yaw) of the tool 160 is determined based on the digital information received according to means specified by the manufacturer of the gyro sensors or acceleration sensors. Such sensors can also be used to transfer translation information about the tool 160 in a similar manner to that described above. Other sensors such as infrared or electromagnetic tracking mechanisms could likewise be used.
The process for finding tool position and orientation based on the digital information sent from the control device 200 to the calculation device 300 can be accomplished by a variety of means. In particular, there are various approaches to finding the tool position based on cable length. Some of these options are discussed in the following.
One simple approach for finding the position of the tool 160 is based on solving four equations that define cable length. These equations contain only three unknown variables, which are the tool's rectangular coordinates, x, y, and z. Equations 1 through 4 define the length l n of each cable 11 , 12 , 13 , 14 (where n=11, 12, 13, 14), where x i , y i and z i define the positions of the calibration points P i (where i=1,2,3,4) and x, y and z is the point where the cable 11 , 12 , 13 and 14 attach to the tool 160 .
l 11 =√{square root over (( x−x 1 ) 2 +( y−y 1 ) 2 +( z−z 1 ) 2 )}{square root over (( x−x 1 ) 2 +( y−y 1 ) 2 +( z−z 1 ) 2 )}{square root over (( x−x 1 ) 2 +( y−y 1 ) 2 +( z−z 1 ) 2 )} (Eq. 1)
l 12 =√{square root over (( x−x 2 ) 2 +( y−y 2 ) 2 +( z−z 2 ) 2 )}{square root over (( x−x 2 ) 2 +( y−y 2 ) 2 +( z−z 2 ) 2 )}{square root over (( x−x 2 ) 2 +( y−y 2 ) 2 +( z−z 2 ) 2 )} (Eq. 2)
l 13 =√{square root over (( x−x 3 ) 2 +( y−y 3 ) 2 +( z−z 3 ) 2 )}{square root over (( x−x 3 ) 2 +( y−y 3 ) 2 +( z−z 3 ) 2 )}{square root over (( x−x 3 ) 2 +( y−y 3 ) 2 +( z−z 3 ) 2 )} (Eq. 3)
l 14 =√{square root over (( x−x 4 ) 2 +( y−y 4 ) 2 +( z−z 4 ) 2 )}{square root over (( x−x 4 ) 2 +( y−y 4 ) 2 +( z−z 4 ) 2 )}{square root over (( x−x 4 ) 2 +( y−y 4 ) 2 +( z−z 4 ) 2 )} (Eq. 4)
Consider the origin of the coordinate system to be in the center of the frame 110 shown in FIG. 2 . Consider sides 115 , 116 and 117 to be of length 2a. Consider sides 111 and 112 to be of length b and sides 113 and 114 to be 2b. Also consider sides 118 and 119 to be of length 2c.
Equations 1 through 4 can be combined to determine a solution for the tool position (as defined by coordinates x, y and z) in terms of the lengths a, b and c.
x
=
l
12
2
-
l
11
2
4
a
(
Eq
.
5
)
y
=
l
14
2
-
l
13
2
4
b
(
Eq
.
6
)
z
=
l
14
2
+
l
13
2
-
l
12
2
-
l
11
2
+
2
a
2
-
2
b
2
8
c
(
Eq
.
7
)
Equation 5 can be found by squaring both sides of equations 1 and 2, subtracting equation 1 from equation 2, and then by isolating the variable x. Equation 6 can be found by squaring both sides of equations 3 and 4, subtracting equation 3 from equation 4, and then by isolating the variable y. Equation 7 can be found by squaring both sides of equations 1-4, adding equations 3 and 4 and from this subtract equations 1 and 2, and then by isolating the variable z. It should be noted that only three of equations 1-4 are necessary to solve for x, y, and z, but using all four equations is a simpler approach. There are a variety of algebraic mathematical methods for solving for x, y and z given equations 1, 2, 3 and 4 and the invention is not limited to the solving method described above.
To briefly summarize another method for determining the lengths of cable 11 , 12 , 13 and 14 , the calibrations points P 1 , P 2 , P 3 , P 4 discussed earlier form a tetrahedral volume, V. The position of the tool 160 where the cables 11 , 12 , 13 and 14 are attached can be used to divide this tetrahedron volume into four smaller tetrahedrons. If P is the cable connection point to the tool 160 , consider V 1 the volume formed by P, P 2 , P 3 and P 4 , V 2 the volume formed by P, P 1 , P 3 and P 4 , V 3 the volume formed by P, P 1 , P 2 and P 4 , and V 4 the volume formed by P, P 1 , P 2 and P 3 . Since we know the side lengths of all of these tetrahedrons, we can determine these volumes from the side lengths (for example using Piero della Francesca's formula or Heron's formula) where the distance between the calibration points and the tool 160 (in other words, the cable lengths) form the sides. It is then possible to use volume coordinates and shape functions to find the tool position (Zienkiewicz) as shown below.
x
=
V
1
V
x
1
+
V
2
V
x
2
+
V
3
V
x
3
+
V
4
V
x
4
(
Eq
.
8
)
y
=
V
1
V
y
1
+
V
2
V
y
2
+
V
3
V
y
3
+
V
4
V
y
4
(
Eq
.
9
)
z
=
V
1
V
z
1
+
V
2
V
z
2
+
V
3
V
z
3
+
V
4
V
z
4
(
Eq
.
10
)
The cable lengths described in equations 1-7 are determined through the number of encoder pulses that result from spinning the spool 126 of the tool translation effecter devices 120 , 130 , 140 , 150 . Assume an encoder count of c pulses, where C represents the number counts per one complete motor shaft revolution (also known as encoder resolution). Also assume the spool 126 has a radius of r and that the groove separation 126 a is d. The calibration process described earlier insures that the pulse count is zero when the cable length is zero. The pulse number increases as the cable unwraps from spool 126 of a tool translation effecter 120 . Therefore, the length of each cable can be determined from the number of pulses based on equation 11, where the subscript i refers to the different tool translation effecter devices 120 , 130 , 140 , 150 and their associated cables 11 , 12 , 13 and 14 .
l
i
=
c
i
C
(
2
Π
r
)
2
+
d
2
(
Eq
.
11
)
The difficulty with relying completely on equation 11 is that it is possible for a cable 11 to become miss wrapped so that it does not perfectly follow the grooves 126 a of the spool 126 . The cable 11 might also end up wrapping on top of previously wrapped cable if the spool 126 width and/or radius are not great enough. This can change variables r and d of equation 11, which will introduce error if not accounted for. To address this source of error, the method described below can be employed.
L ij =m ij p ij +n ij (Eq. 12)
Equation 12 relates cable length at the calibration positions P 1 , P 2 , P 3 and P 4 to the recorded encoder pulses obtained during the calibration process. The cable length, L ij is known at every calibration position P j , where i refers to each of the four cables and j refers to the different calibration positions (where i=1 . . . 4, j=1 . . . 4 and i≠j). The number of encoder counts recorded at these lengths for the cables, p ij , was recorded during the calibration process for calibration positions P 1 , P 2 , P 3 and P 4 . Given the known lengths, L ij , of the cables at each calibration position and recorded pulse counts, p ij , the linear curve of equation 12 can be fit to the data and variables m ij and n ij can be solved. Methods, such as the least mean squared method, could be used to fit this curve. n ij will be close to zero so long as the encoder counters are set to zero at the calibration positions and the relationship between pulse count and length is truly linear. Otherwise, a spline or non-linear curve fit might be more appropriate for defining the relationship between cable length and pulse count.
The process defined above for finding a linear relationship between encoder counts and cable length could be adapted to include more (or less) calibration positions as described for the calibration process. The user simply moves the point on the tool 160 where the cables 11 , 12 , 13 and 14 are attached to a specified calibration point. So long as the lengths of all the cables 11 , 12 , 13 and 14 are known at this point and the encoder counts are recorded at this position, then this data can be used to find a curve fit. The more calibration points the more accurate the curve fit will be.
It is also possible to use cable lengths as determined from alternative tool tracking mechanisms, such as infrared, electromagnetic, gyro or acceleration sensors. These sensors may or may not be fast enough to record tool positions at haptic compatible rates. If such a tracking mechanism is considered accurate, but provides too slow of an update for haptics, the tracking mechanisms might be used to continuously calibrate a tracking system based on the encoders 126 of the tool translation effecter devices 120 , 130 , 140 , 150 . The alternative tool tracking mechanisms would yield tool positions, which in turn can be used to determine cable lengths. These lengths can be associated with encoder counter values. A sample of such data can be used to fit a curve, such as that defined by equations 12, to find an updated relationship between cable length and encoder pulses at any given time. This method would therefore not require the user to move to any specific calibration positions. Note that n ij of equation 12 does not have to be zero in this case, if the encoder counters are not set to zero at the calibration positions.
The process to establish in the calculation device 300 a force response that is appropriate at the tool 160 is normally determined according to the software application utilizing the system 10 under discussion. Typically, an application uses the tool 160 position and orientation information to determine if a collision has occurred with virtual objects. The force response can be rendered to simulate a wide range of effects. For example, a force response might simulate a collision of the tool 160 with a rigid or deformable virtual surface, the pull, push, weight or vibration of a virtual object contacting the tool 160 , and/or viscous resistance and inertia experienced as a tool 160 moves through virtual fluid. Forces could also be derived from a robot touching real objects where the robot measures the reaction forces upon collision. The only limitation is that the force response determined at the calculation device 300 must be representable as a single vector force in the x, y and z direction at the point(s) where the cables 11 , 12 , 13 , 14 connect with the tool 160 . It is this vector force that the user will feel at the tool 160 . This vector force can be updated at a rate that is appropriate for the application.
The process for determining tension values in each cable 11 , 12 , 13 , and 14 that will deliver a force vector response to the tool 160 as determined by the calculation device 300 will now be discussed. The force control part 340 calculates tension using the following equation.
J =( A τ−ƒ)+α[τ] 2
for
min[ J] 2 0 (Eq. 13)
In equation 13, τ is the tension where τ=[τ 1 , τ 2 , τ 3 , τ 4 ] in the cables 11 , 12 , 13 and 14 , α is a coefficient that displays stability of force, J is the target function. Consider w i (i=11,12,13,14) (R ε3×1 ) a set of unit force vectors (in 3D) that are displayed along the direction of tension for each cable 11 , 12 , 13 and 14 . A={w 11 , w 12 , w 13 , w 14 ) (R ε3×4 ) is a force matrix filled with the unit vector forces. ƒ=(ƒ x , ƒ y , ƒ z ) is the force vector that is to be displayed at the tool 160 . The force control 340 calculates positive tension values, which minimizes the target function, J (in other words, J should end up close to zero). A good value to use for α is 0.1, but the teachings herein are not limited to the use of this value. A variety of standard mathematical methods can be used to minimize the target function J and thus determine τ.
The process to control tension in each cable 11 , 12 , 13 , and 14 is accomplished by driving each motor 124 , 134 , 144 and 154 based on tension values determined in the calculation device 300 . The force control part 340 of the control device 300 regulates motor torque by controlling the current sent to the motors 124 . Each motor 124 applies torque to the attached spool 126 . The torque that accomplishes the appropriate tension in each cable 11 is dependent on the radius of the spool 126 , which is accounted for by the force control part 340 of the control device 300 .
A wide variety of structures can be used to control the process that relays visual and audible information to the display device 400 from the calculation device 300 . Typically, the location and orientation of the tool 160 and virtual or real objects that the tool 160 may be interacting with are displayed graphically. This allows the user to see how he or she is effecting a virtual environment or a robot as the user moves the tool 160 . This information is displayed according to the software application utilizing the system 10 under discussion and could constitute a vast range of possible formats. Audio output can also be utilized to display information resulting from tool 160 interaction with virtual objects or real objects encountered through a robot.
There are a variety of configurations that the system 10 can employ that rely on the same concepts outlined above. According to one embodiment of the invention, The system 10 includes a tool shaft 180 that passes through a port 172 , and is coupled at one end to the tool or attachment point 160 . The cables 11 , 12 , 13 and 14 are attached to the point 160 , which is coupled to the tool shaft 180 , which in turn passes through the port 172 of interface device 20 , as shown in FIG. 8 . While the system 10 applies translation forces in the x, y and z direction through cable 11 tensions to the point 160 , or a set of points 160 in close proximity, on the tool shaft 180 , the user will feel an insertion force (along with pitch and yaw). In FIG. 8 , the insertion force is along the direction of the tool shaft 180 as confined by the port 172 . Pitch and yaw are felt at the tool shaft handle with the pivot point at the port 172 . Such a configuration is ideal to apply three degrees of freedom force feedback to minimally invasive instruments used when simulating a surgical procedure.
More degrees of force feedback, such as rotation around the tool shaft 180 and grip force at a handle of the tool shaft, can be added through additional motors independent of the cable system. For example, a motor in the tool shaft 180 , or attached to the port 172 , allows twisting force feedback, and a motor in the handle of the tool shaft 180 adds a squeezing grip force. Such uses of motors to apply simple force feedback over 1 degree of freedom may be used to augment the system 10 .
It is common when working through a port 172 to define forces in terms of moment around the port rather than vector forces as applied to the end of the tool attachment point 160 . In this case, equation 15 should be adjusted to accommodate moment about the port 172 which can be defined as M x and M y , and an insertion force f l which is a vector force in the direction of the shaft of the tool 180 .
J
=
(
TA
τ
-
M
)
+
α
[
τ
]
2
for
min
[
J
]
2
⇒
0
and
T
=
[
0
L
z
L
y
L
z
0
L
x
v
x
v
y
v
z
]
(
Eq
.
14
)
In equation 14, consider the port 172 to be located at coordinate (N x , N y , N z ) and L x =x−N x , L y =y−N y and L z =z−N z where x, y and z can be found using equations 5, 6 and 7. v={v x , v y , v z } is a unit vector that points from the port 172 axis origin (or the port pivot point) toward the point on the tool 160 where the cables 11 , 12 , 13 , 14 are connected. M={M x , M y , f l } are the moment and insertion force values prescribed by the user.
Embodiments of the invention are not limited to three degrees of force feedback freedom. In general, n degrees of force feedback can be accomplished with n+1 cables or feedback devices. FIG. 10 shows the schematic of a simple two-degree of freedom force feedback system 30 , according to another embodiment of the invention. The system 30 requires three cables 11 , 12 , 13 and three tool translation effecter devices 120 , 130 and 140 . Equations 1, 2 and 3 define the length of the three cables 11 , 12 and 13 . Assume that tool translation effecter device 120 lies at coordinate (0, b, 0), tool translation effecter device 130 lies at coordinate (−a, −b, 0) and tool translation effecter device 140 lies at coordinate (a, −b, 0). Equations 1, 2 and 3 can be combined to isolate the x and y position values of the tool 160 .
x
=
l
12
2
-
l
13
2
4
a
(
Eq
.
17
)
y
=
l
12
2
+
l
13
2
8
b
-
l
11
2
+
a
2
4
b
(
Eq
.
18
)
Equation 13 can be used, with two dimensional coefficient representations, to find two degrees of freedom force feedback in the x and y direction for the configuration shown in FIG. 10 . τ is the tension where τ=[τ 11 , τ 12 , τ 13 ] in the cables 11 , 12 and 13 . Consider w i (i=11,12,13) (R ε2×1 ) a set of unit force vectors (in 2D) that are displayed along the direction of tension in each cable 11 , 12 and 13 in the x-y plane. A={w 11 , w 12 , w 13 ) (R ε2×3 ) is a force matrix filled with the unit vector forces that correspond to the cables 11 , 12 and 13 . ƒ=(ƒ x , ƒ y ) is the 2D force vector that is to be displayed at the tool 160 . It should be noted that a force along the z axis will be present if the tool 160 is moved outside of the x-y plane. This force will always pull the tool 160 back toward the x-y plane.
FIG. 11 shows an interface device 40 , according to another embodiment of the invention. The port 174 is elongated, with an upper end fixed to a pivot point 171 , while the point defined in other embodiments as the tool or attachment point 160 is defined in this embodiment as the lower end 165 of the port 174 , which is free to move, within the constraints imposed by the device 40 . In this configuration, the cables are attached to the lower end 165 of the port 174 rather than the tool 160 . The port 174 rotates freely around the port axis origin 171 (or port pivot point) while the tool 190 itself slides freely through the port 174 .
When finding the cable tensions that will result in moment about the port 174 , which can be defined as M x and M y , a reduced version of equation 14 can be used. This is because insertion of the tool 190 is not being constrained, so the insertion force is essentially zero. T and M of equation 14 are simply redefined to reflect the two degrees of force feedback problem, as shown below:
T
=
[
0
L
z
L
y
L
z
0
L
x
]
and
M
=
{
M
x
,
M
y
}
In equation 14, τ is the tension where τ=[τ 1 ,τ 2 ,τ 3 ] in the cables 11 , 12 and 13 , respectively. Consider w i (i=11,12,13)(R ε3×1 ) a set of unit force vectors (in 3D) that are displayed along the direction of tension in each cable 11 , 12 and 13 . A={w 11 ,w 12 ,w 13 )(R ε3×3 ) is a force matrix filled with the unit vector forces that correspond to the cables 11 , 12 and 13 .
It may be seen that when the port 174 is rotated on the pivot point 171 , the cable connection point 165 of the port 174 moves out of the x-y plane, as shown in dotted lines in FIG. 11 . Because f z does exist when the point 165 is moved out of the x-y plane, it is not straight forward to convert from moments about a port 174 to cable tensions using equation 16. By accounting for the forces that result in the z direction as the cable connection point 165 on the port 174 moves out of the x-y plane when the port 174 is rotated, accurate moments (M={M x , M y }), can be achieved.
While the x, y and z position on the port 174 , where the cables 11 , 12 , 13 attach, can be solved using only equations 1, 2 and 3, it is also convenient to consider the constant length of the port shaft 15 as l 14 . Under this assumption, equations 5, 6 and 7 can be used to determine position. This is only one example of how to determine position for the configuration of FIG. 11 . Methods similar to those discussed earlier also apply.
Rotational feedback and gripping force feedback may also be provided for the tool 190 of FIG. 10 , as has been described in more detail with reference to the tool shaft 180 of FIG. 8 .
Although not shown in any figure, a set of cables may be applied to multiple points on a tool so that different vector forces can be rendered at each point. A single calculation device can be used to control all the cable sets, or different calculation devices, for example on separate circuit boards, may be used. The effect of applying separate force vectors to different points on a single tool yields the effect of rotational forces as felt by the user, or may serve to control the movement of a jointed tool. Multiple sets of cables can also be used to apply force vectors to multiple tools that exist in the same workspace.
Although specific embodiments of and examples for the haptic system and method are described herein for illustrative purposes, various equivalent modifications can be made without departing from the spirit and scope of the invention, as will be recognized by those skilled in the relevant art. The teachings provided herein of the invention can be applied to other haptic systems, not necessarily the exemplary haptic system 10 generally described above.
The various embodiments described above can be combined to provide further embodiments. All of the above U.S. patents, patent applications and publications referred to in this specification are incorporated by reference. Aspects of the invention can be modified, if necessary, to employ systems, circuits and concepts of the various patents, applications and publications to provide yet further embodiments of the invention.
These and other changes can be made to the invention in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the invention to the specific embodiments disclosed in the specification and the claims, but should be construed to include all haptic systems that operate in accordance with the claims. Accordingly, the invention is not limited by the disclosure, but instead its scope is to be determined entirely by the following claims.
All of the above U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, including but not limited to U.S. Pat. No. 5,305,429; Seahak Kim, Masahiro Ishii, Yasuharu Koike, Makoto Sato, “Development of Tension Based Haptic Interface with 7 DOF:SPIDAR-G,” ICAT2000, 25-27, Oct., 2000, National Taiwan University, Taiwan; Seahak Kim, Masahiro Ishii, Yasuharu Koike, Makato Sato, “Design of a Tension Based Haptic Interface with 6 DOF,” 4th World Multiconference on Systemics, Cybernetics and Informatics (SCI2000) and the 6th International Conference on Information Systems Analysis and Synthesis (ISAS2000), Orlando, USA, in Jul. 23-26, 2000; Seahak Kim, Masahiro Ishii, Yasuharu Koike, Makoto Sato, “Development of SPIDAR-G and Possibility of its Application to Virtual Reality,” VRST2000, 22-25, Oct., 2000, Seoul, Korea; Seahak Kim, Masahiro Ishii, Yasuharu Koike, Makoto Sato, “Design of tension based haptic interface: SPIDAR-G,” IMECE2000 (joint with ASME2000), 5-10, Nov., 2000, Orlando, USA; Seahak Kim, Masahiro Ishii, Yasuharu Koike, Makoto Sato, “Cutting edge Haptic interface device: SPIDAR-G,” Proceedings of the 32nd ISR (International Symposium on Robotics), 19-21, Apr., 2001, Seoul, Korea; Seahak Kim, Shoichi Hasegawa, Yasuharu Koike, Makoto Sato, “Tension Based 7 DOFs Force Feedback Device: SPIDAR-G” by the IEEE Computer Society Press in the proceedings of the IEEE Virtual Reality Conference 2002, 24-28 Mar. 2002 in Orlando, Florida; Seahak Kim, Shouichi Hasegawa, Yasuharu Koike, Makoto Sato, “Tension based 7 DOF Force Feedback Device,” Trans. On ICASE, Vol. 4, No. 1, pp. 8-16, 2002; Seahak Kim, Jeffrey J. Berkley, and Makoto Sato, “A Novel Seven Degree of Freedom Haptic Device for Engineering Design,” Journal of virtual reality, Springer UK (accepted), are incorporated herein by reference, in their entirety.
From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.
|
A haptic device for human/computer interface includes a user interface tool coupled via cables to first, second, third, and fourth cable control units, each positioned at a vertex of a tetrahedron. Each of the cable control units includes a spool and an encoder configured to provide a signal corresponding to rotation of the respective spool. The cables are wound onto the spool of a respective one of the cable control units. The encoders provide signals corresponding to rotation of the respective spools to track the length of each cable. As the cables wind onto the spools, variations in spool diameter are compensated for. The absolute length of each cable is determined during initialization by retracting each cable In turn to a zero length position. A sensor array coupled to the tool detects rotation around one or more axes.
| 0
|
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of copending International Application No. PCT/EP99/09220, filed Nov. 26, 1999, which designated the United States.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention lies in the field of household appliances. The invention relates to a laundry treatment machine with an electronic control device for the automatic implementation of laundry treatment programs.
[0004] A laundry treatment machine may include, in particular, a washing machine, a laundry drying machine, or a combined washing and drying machine. Such machines are generally in the prior art.
[0005] Furthermore, depending on the material of the items of laundry, the items can be subjected to different degrees of mechanical loading, can be heated only up to a certain temperature, and/or must not be treated with certain chemical substances. Depending on the degree to which the items are soiled or the type of their soiling, items of laundry should be treated differently. On one hand, the items of laundry should be treated as gently as possible, while, on the other hand, their soiling should be removed as completely as possible. Another important parameter is the energy required for the treatment of the laundry. As little energy as possible should be required for such treatment. A further criterion is the time period for the treatment of the laundry, which should be as short as possible. The prior art washing machines include a large number of washing programs and other laundry treatment programs, for example, drying programs, from which an operator can choose a program that, in the user's own judgement, is the most suitable for the laundry to be treated. To make such a determination, the operator requires considerable knowledge and experience for judging what material is relevant to the items of laundry to be treated and which type of soiling of the items of laundry is at issue. If an item of laundry has no label indicating its material and the type of permissible laundry treatment, it is often not possible for an operator to identify the type of material of the item of laundry and to determine the permissible treatment process or washing process. Also, in the case of stains, an operator often cannot identify which type of soiling is present.
[0006] In the days before washing machines and laundry dryers, and before there were so many different types of fabric and types of detergent for laundry, the operator was directly involved with the laundry. The person was able to “test” the laundry. He or she also knew exactly which item of laundry could be subjected to greater or lesser degrees of mechanical loading, for example, when wringing out the laundry after the laundering operation. The wringing out of the laundry corresponds today to the spinning in a washing machine or in a drier.
[0007] Today, the operator is separated from the laundry by the washing machine. He or she can only set a certain program. According to the program set, the entire laundry treatment takes place either completely correctly or completely incorrectly or partly correctly.
SUMMARY OF THE INVENTION
[0008] It is accordingly an object of the invention to provide a laundry treatment machine that overcomes the hereinafore-mentioned disadvantages of the heretofore-known devices of this general type and that treats items of laundry more gently, with less energy, and in an optimized time without the operator needing to have special knowledge concerning the type of the items of laundry.
[0009] With the foregoing and other objects in view, there is provided, in accordance with the invention, a laundry treatment machine, including an electronic control device for automatic implementation of laundry treatment programs having a decision-making means for identifying a type of each laundry item placed into the laundry treatment machine and making a decision concerning an optimized laundry treatment program of a plurality of laundry treatment programs to be used for treating a combination of the identified laundry items placed into the laundry treatment machine, information output means for presenting to a user the optimized laundry treatment program as a proposal, the information output means connected to the decision-making means, and input means connected to the electronic control device, the input means to be actuated by a user for confirming the laundry treatment program determined by the decision-making means.
[0010] According to the invention, a possible way of identification and communication is to be created between the operator, the laundry treatment machine, and the items of laundry to be treated, thus assisting the operator in making a decision concerning good laundry treatment by the laundry treatment machine.
[0011] Within the scope of the invention, “type of items of laundry” can be understood as meaning not only the type of material, type of fiber, and type of dyes of the items of laundry to be treated, but also the type and degree of their soiling, depending on how the control device of the laundry treatment machine is constructed.
[0012] For example, within the scope of the invention, the control device or the decision-making device of the laundry treatment machine may have stored the following parameters of the items of laundry, which it takes into consideration when determining a laundry treatment program: types of fabric, types of soil, permissible temperatures, treatment duration, the amount and type of treatment water, detergent, rinsing agent. etc.
[0013] The decision-making device is combined with the electronic control device. It may be disposed separately from the latter, or be formed partly or completely by the electronic control device, or be integrated in the latter. The decision-making device identifies the type of the items of laundry and calculates for the identified items of laundry an optimum laundry treatment program (washing program and/or drying program and/or other laundry treatment operations).
[0014] As a result, laundry is treated with a program optimized for the laundry even if the operator has no detailed knowledge concerning the type of fabric and/or the type of soiling of the items of laundry.
[0015] The operator need only present the items of laundry to a detecting device or a measuring head of the decision-making means and then load them into the laundry treatment machine. Then, after all the desired items of laundry have been loaded, the operator closes the laundry treatment compartment of the machine and gives it a starting command. The control device is preferably configured to start the laundry treatment program only when the laundry treatment compartment is closed, for example, in the case of a washing machine, the door of the washing drum is closed.
[0016] In accordance with another feature of the invention, a communication system is provided, by which the decision-making device can communicate with a person. Depending on the embodiment, information output of the decision-making device may be optical and/or acoustic, for example, a voice output. The information to be conveyed by a person can be entered in the communication system manually and/or by speech, depending on its embodiment.
[0017] In accordance with a further feature of the invention, decision-making device not only permits a “YES” or “NO” decision to be possible, by confirming or canceling a laundry treatment program proposed by the machine, but the possibility of a person modifying the laundry treatment program proposed by the decision-making device and starting it in a modified form is also provided.
[0018] In accordance with an added feature of the invention, the input means includes a selection device modifying the optimized laundry treatment program and executing the modified laundry treatment program.
[0019] The decision-making device may be configured to propose one of the laundry treatment programs that are stored in the electronic control device, or to generate an individual laundry treatment program based on the type of the items of laundry identified. Such an individually generated laundry program may include parts of the stored laundry treatment programs.
[0020] In accordance with an additional feature of the invention, the decision-making means selectively sets a stored laundry treatment program and generates a custom laundry treatment program individually adapted to at least one identified laundry item and proposes the custom laundry treatment program to the user.
[0021] In accordance with yet another feature of the invention, the decision-making device forms clusters concerning the frequency with which identified items of laundry that correspond to predetermined parameters occur. These parameters are stored in the control device or the decision-making device and are, for example, types of fabric or types of fiber and/or types of soil that may be present in the laundry items. The decision-making device checks, for each identified item of laundry, which of the parameters also apply to the item of laundry.
[0022] In accordance with yet a further feature of the invention, the decision-making device calculates from the clusters the laundry treatment program suitable for the items of laundry identified.
[0023] In accordance with yet an added feature of the invention, the decision-making device is preferably configured to calculate from the clusters based on fuzzy logic the decision as to which laundry treatment program can be used for treating the items of laundry identified.
[0024] In accordance with yet an additional feature of the invention, the decision-making device preferably includes a spectrometer for identifying the type of the items of laundry.
[0025] In accordance with again another feature of the invention, to identify the items of laundry, they can be placed manually one after the other in front of a measuring head or sensor of the decision-making device. The measuring head may be fixedly disposed on the laundry treatment machine or be a hand-held device. Depending on the technical configuration, the measuring head can pick up information from the item of laundry in question concerning the type of the item of laundry, for example, its type of fiber, and concerning the type of its soiling, either by contact or without contact. The measuring head may be connected to the electronic control device or its decision-making device by a cable or by radio link.
[0026] In accordance with again a further feature of the invention, the decision-making device preferably has a display device to optically display the type of the item of laundry identified. Such display allows an operator to “learn” the type of fabric or fibers of the item of laundry identified.
[0027] In accordance with again an added feature of the invention, the display device is configured to indicate separately for each type of laundry item the number of these items of laundry per type. Such indication has several advantages. Items of laundry can be washed or dried at a different maximum temperature, according to their fabric type. The mechanical strength of the items of laundry is likewise dependent on their type of fabric. Thus, for example, higher or lower rotational speeds or more frequent changes in the direction of rotation or pauses in rotation of a laundry treatment drum, for example, of a laundry drum, a spin drier, or a laundry drier, are permissible, based upon the type of fabric of the item of laundry. When a number of items of laundry are being treated at the same time, the temperature and the mechanical treatment of the items of laundry are governed by the item of laundry that has the lowest temperature tolerance and lowest mechanical stress tolerance. Taking these parameters into consideration, the time duration of a suitable laundry program can also be lengthened or shortened. An optical or acoustic or written or other indication to the operator as to the type of the items of laundry and the number of items of laundry per type by the laundry treatment machine gives the operator the possibility of taking back again one or more identified items of laundry and having a new laundry treatment program proposed by the control device or its decision-making device. Preferably, other parameters, for example, chemical laundry treatment agents, fabric softeners, spinning speed, etc., can also be influenced by an operator.
[0028] In accordance with again an additional feature of the invention, the decision-making device has a switchable sensor or switchable measuring head or an additional sensor or additional measuring head with a respective evaluation device. The evaluation device subtracts from the identified items of laundry those items of laundry presented to it once again by the operator. As a result, it is no longer necessary for an operator to have all the items of laundry newly identified if he or she takes one or more items of laundry away from the items of laundry identified, such that a new laundry treatment program is calculated by the decision-making device. A measuring head or sensor that adds or subtracts the items of laundry to or from the decision-making process according to the direction of movement of an item of laundry in relation to it can also be used.
[0029] In accordance with a concomitant feature of the invention, the laundry treatment machine is a washing machine, a drying machine, or a combination washing and drying machine.
[0030] Other features that are considered as characteristic for the invention are set forth in the appended claims.
[0031] Although the invention is illustrated and described herein as embodied in a laundry treatment machine, it is, nevertheless, not intended to be limited to the details shown because various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims.
[0032] The construction and method of operation of the invention, however, 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
[0033] [0033]FIG. 1 is a diagrammatic front view of a laundry treatment machine according to the invention;
[0034] [0034]FIG. 2 is a diagrammatic illustration of a display device of the laundry treatment machine according to FIG. 1 with display zones for indicating the type of fabric of identified items of laundry and, for each type, the number of items of laundry identified;
[0035] [0035]FIG. 3 is a diagram showing clusters indicating a frequency of different types of items of laundry presented to the laundry treatment machine for identification and items that have been identified;
[0036] [0036]FIG. 4 is a diagrammatic illustration of a display device of the laundry treatment machine according to FIG. 1 with the display zone proposing to an operator a decision on implementing a program; and
[0037] [0037]FIG. 5 is a diagrammatic illustration of a display device of the laundry treatment machine according to FIG. 1 with the display zone indicating the currently running program step of the laundry treatment program.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0038] In all the figures of the drawing, sub-features and integral parts that correspond to one another bear the same reference symbol in each case.
[0039] For the following description, it is assumed that the laundry treatment machine is a washing machine. However, it could also be a laundry drier or a combined washing and drying machine.
[0040] Referring now to the figures of the drawings in detail and first, particularly to FIG. 1 thereof, there is shown a washing machine 2 including on the front side a door 4 for closing a rotatable laundry drum. Also on the front side is a display device 6 with a plurality of display zones or display areas for the optical display of machine functions, in particular, washing programs, and information on the current program status and the type of identified items of laundry. Furthermore, an operator control device 7 with a large number of manual operator control elements (buttons, switches) for operating the washing machine 2 is disposed on the front side. In the washing machine, there is an electronic control device 8 with an electronic decision-making means or electronic decision-maker 10 . The control device 8 and its decision-maker 10 may have permanently integrated or variable laundry treatment programs and a storage device or means for storing a large number of parameters. The parameters are, in particular, data for detecting and identifying types of fabric of items of laundry and types and degrees of soiling of the items of laundry and data on how many different types of items of laundry and different types of soiling can be treated by a washing program and/or a drying program. Such parameters also include data on permissible treatment temperatures, treatment time periods, and data on chemical, inorganic, or organic agents for treating the items of laundry and their soiling.
[0041] The decision-maker 10 is connected by a flexible cable 12 to a sensor or to a measuring head 14 , with which items of laundry that are manually presented to the measuring head 14 by an operator can be scanned without contact or by contact, depending on a technical configuration. The decision-maker 10 identifies the items of laundry detected by the measuring head 14 and calculates, from the measured data and the stated parameters, which washing program the identified items of laundry can be washed and/or dried together at the same time.
[0042] According to a preferred embodiment, the display device 6 displays the values of the items of laundry measured by the measuring head 14 . According to FIG. 2, the display device 6 contains a display zone 16 . The display zone 16 is divided into a large number of display areas 17 , 18 , 19 , 20 , 21 , and 22 . Each display area 17 to 22 shows items of laundry of a different type of fabric. The embodiment may be such that the number of items of laundry identified by the measuring head 14 for a laundry treatment process is displayed in each display area 17 to 22 for a different type of items of laundry. For example: in display area 20 , items of laundry made of synthetic fibers are displayed; in display area 21 , items of laundry made of cotton are displayed; in display area 22 , items of laundry made of multicolored textiles are displayed; in display area 17 , items of white, un-dyed laundry are displayed; etc. According to one particular embodiment, only the type of the material of the identified items of laundry is displayed, but not the number per type of material.
[0043] Clusters 25 , 27 , 28 , 29 , 30 are formed by the control device 8 and its decision-maker 10 , preferably a spectrometer. The formation involves the control device 8 performing a frequency calculation as to how frequently a certain type of laundry was identified, for example, how many items of laundry can be washed at 30° C., how many items of laundry can be washed at 40° C., how many items of laundry can be washed at 60° C., how many items of laundry can be washed at 90° C., and how many can be dry cleaned. An example of a spectrum of these clusters is schematically represented in FIG. 3.
[0044] As the next method step after the cluster formation, the control device 8 calculates with its decision-maker 10 a laundry treatment program suitable for the identified items of laundry, for example, a combined washing and drying program. The program is optically displayed for an operator in a display zone 32 of the display device 6 , as is represented in FIG. 4 for example. Preferably, a selection or separation from the clusters is carried out based on fuzzy logic principles in the calculation of the laundry treatment program.
[0045] For example, the display zone 32 in FIG. 4 indicates the following program proposal: “wash gently at 30° C. for 1½ hours and then dry, okay?”
[0046] Thus, the laundry treatment machine makes a proposal to the operator. The operator can acknowledge the program proposal at an operator control element with a “YES” or “NO” response. The operator control element may be provided at the display zone 32 or be contained in the operator control device 7 .
[0047] If the operator acknowledges the program proposed by the machine with “YES”, the proposed program can start automatically or be started manually by actuating an operator control element of the operator control device 7 , depending on the embodiment of the control device 8 .
[0048] For safety reasons, a locking circuit is, of course, provided, allowing a program to be started only when the door 4 of the washing drum is closed. The laundry treatment program then runs.
[0049] According to one particular embodiment of the machine, a further display zone 36 may be provided, respectively indicating to an operator the current state of the laundry treatment program, for example “laundry is being dried, ready at 21:12”.
[0050] The invention offers the operator a cleaning assistant, which assists, if a cleaning process is selected, the laundry treatment program, in particular, a washing program, some other cleaning program, a detergent, a drying program, or the like. The assistant also gives information on the type of the material, in particular, the fibers of the items of laundry. The assistant then makes a proposal for a suitable laundry treatment process.
[0051] According to a preferred embodiment, the control device 8 or its decision-maker 10 includes a spectrometer, by which types of material, in particular, textiles, fibers, type of soiling, and amount of soiling of items of laundry are analyzed. From these parameters, the required type of detergent and amount of detergent, and the laundry treatment program to be recommended are then calculated and displayed on the display device 6 .
[0052] According to one particular embodiment, an optical display of may be replaced by a voice output or be combined with such a voice output. The laundry treatment program proposed by the machine can start once the operator has confirmed the program, either by one or more words spoken by the operator or by a manual acknowledgement at an operator control element, depending on the embodiment of the laundry treatment machine.
[0053] According to the preferred embodiment of the invention, active intervention by an operator in the choice of laundry treatment programs also continues to be possible. Such intervention may include, for example, in deliberate acknowledgement by an operator of the program proposed by the machine, in a new selection, or in a manual entry of the degree of soiling of the items of laundry, a changing of the program time, etc.
[0054] By having the operator use the measuring head 14 of the spectrometer for consciously ascertaining the type of the items of laundry, the operator is introduced into the area of laundry care in a very easy way. Information concerning the type of materials of the items of laundry gives the operator the possibility, when desired, of increasing his or her knowledge in the area of laundry care. According to a preferred embodiment, the laundry treatment machine may alternatively also be used in a conventional way without activation of the decision-maker 10 .
[0055] The invention consequently provides an operator-friendly and user-friendly means for a laundry treatment machine that can be integrated in an existing laundry treatment machine or be additionally connected. The invention is a significant step toward a new human-laundry-machine communication and information level.
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A laundry treatment machine, in particular, a washing machine and/or drier, includes an electronic controller, an information output device, and an input device. The electronic controller automatically implements laundry programs and has a decision-maker identifying each laundry item placed therein. The decision-maker makes decisions to create an optimized treatment program for treating the combination of identified laundry items placed into the machine. An information output device presents to a user the optimized program as a proposal. An input device is connected to the electronic controller and is to be actuated by a user for confirming the laundry treatment program determined by the decision-maker.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a software product for and a method of laying-out (designing) a semiconductor device. More particularly, the present invention relates to a software product for and a method of laying-out a semiconductor device by using a hierarchical design method.
[0003] 2. Description of the Related Art In recent years, in the field of a semiconductor device such as a system LSI and an ASIC, the increase in required functions and performances makes the circuit configuration more complex. A hierarchical design method is often employed to design a semiconductor device. According to the hierarchical design method, a semiconductor device is treated as a set of function blocks (modules), and each of the function blocks is treated as a set of small-scale modules. Thus, a hierarchy structure is established. In the top hierarchy according to the hierarchical design, mega macros (large-scale function blocks) such as a CPU core and a DSP core are arranged, and then interconnections which connect between the arranged mega macros are provided. Interconnections and components within the mega macros correspond to the second hierarchy. A “macro” may be referred to as a “hierarchy macro” hereinafter.
[0004] FIGS. 1A and 1B are schematic diagrams showing a layout in the top hierarchy. As shown in FIG. 1A , three hierarchy macros 201 , 202 and 203 and an interconnection 210 are arranged in the top hierarchy. The interconnection 210 is provided to connect between the hierarchy macro 201 and the hierarchy macro 203 . In the layout of the top hierarchy, the interconnection 210 is allowed to pass over the hierarchy macro 202 located between the macros 201 and 203 in order to optimize the interconnection path. In some cases, a timing-adjustment component such as a repeater may be inserted into an interconnection of the top hierarchy for adjusting a signal timing. Such a timing-adjustment component is also allowed to be located on a hierarchy macro.
[0005] In the case that an interconnection which is not connected with a certain macro passes over the certain macro as mentioned above, an “incorporating (embedding) process” is carried out in which an overlapping section of the interconnection is incorporated (embedded) into the certain macro. More specifically, an information regarding the overlapping section is added to a netlist which describes the connectivity between components within the certain macro. Such an information does not exist originally in the netlist of the macro at the step of logic design.
[0006] For example, the above-mentioned interconnection 210 can be divided into an interconnection 211 , an interconnection 212 and an interconnection 213 as shown in FIG. 1B . The interconnection 211 is located between the macro 201 and the macro 202 , and the interconnection 213 is located between the macro 202 and the macro 203 . The interconnection 212 corresponds to the overlapping section of the interconnection 210 and is referred to as an “overpassing interconnection”. The overpassing interconnection 212 is dropped from the top hierarchy to a lower hierarchy, and is incorporated into the hierarchy macro 202 .
[0007] Japanese Laid Open Patent Application (JP-P2000-100949A) and Japanese Laid Open Patent Application (JP-P2000-156414A) disclose such a conventional incorporating process in which an overpassing interconnection in the top hierarchy is dropped to the lower hierarchy.
[0008] Also, FIG. 2A shows another layout in the top hierarchy. As shown in FIG. 2A , hierarchy macros 204 a, 204 b, 204 c and 204 d and interconnections are arranged in the top hierarchy. In this example, the hierarchy macros 204 a to 204 d are the same macro and have the same functions. Here, the orientations of the hierarchy macros 204 a to 204 d are different from each other. A hierarchy macro stored in a macro library is copied and arranged in the top hierarchy after inverted and rotated. In the example shown in FIG. 2A , the orientation of the hierarchy macro 204 a is defined as an N-orientation. In this case, the hierarchy macro 204 b is inverted left-to-right with respect to the N-orientation. The hierarchy macro 204 c is inverted top-to-bottom with respect to the N-orientation. The hierarchy macro 204 d is inverted left-to-right and top-to-bottom with respect to the N-orientation.
[0009] Also, as shown in FIG. 2A , timing-adjustment components such as repeaters are inserted to predetermined positions of the interconnections in the top hierarchy in order to adjust a signal timing. An overlapping section is defined as a section of the interconnections and repeaters which overlaps with any of the macros 204 a to 204 d. When the interconnections and the repeaters are arranged in the top hierarchy as shown in FIG. 2A , positions of the overlapping sections to be incorporated into respective of the macros 204 a to 204 d are different from each other, although the hierarchy macros 204 a to 204 d have the same functions. Therefore, at the time of the incorporating process and laying-out of the second hierarchy (interior of each macro), the hierarchy macros 204 a to 204 d mentioned above are recognized as different hierarchy macros 204 to 207 , respectively, as shown in FIG. 2B . The layouts of the second hierarchy are carried out independently for respective of the hierarchy macros 204 to 207 .
[0010] According to the conventional layout method as described above, the hierarchy macros 204 to 207 are treated as four different macros at the time of the incorporating process, even though they are the same hierarchy macros having the same function. In this case, although only one kind of hierarchy macro in the macro library is used, four kinds of hierarchy macros must be processed in laying-out the semiconductor device. Thus, the number of steps for designing increases as the number of hierarchy macros used increases. Also, the operation and the layout of the designed semiconductor device are checked (verified) after the layout process. Such a verification should be also carried out for each of the four kinds of the hierarchy macros. As a result, the TAT (Turn Around Time) in the design process of the semiconductor device increases.
SUMMARY OF THE INVENTION
[0011] It is therefore an object of the present invention to provide a software product and a method for laying-out a semiconductor device which can reduce the time necessary for the layout process.
[0012] Another object of the present invention is to provide a software product and a method for laying-out a semiconductor device which can reduce the TAT (Turn Around Time) in the layout process.
[0013] In an aspect of the present invention, a software product for laying-out a semiconductor device by using a hierarchical design method is stored in a recording medium and is executed by a computer. The software product includes the functions of: (A) locating a plurality of macros belonging to a first hierarchy, the plurality of macros including a plurality of first macros having the same function; (B) arranging a connection structure connecting between the plurality of macros; (C) extracting from the connection structure a plurality of overlapping sections which overlap with the plurality of first macros, respectively; (D) incorporating respective of the plurality of overlapping sections into the plurality of first macros, interiors of the plurality of first macros being associated with a second hierarchy lower than the first hierarchy; (E) calculating a forbidden area associated with any of the plurality of overlapping sections by superposing the plurality of overlapping sections with reference to orientations of respective of the plurality of first macros; and (F) arranging interconnections and components belonging to the second hierarchy within each of the plurality of first macros such that the interconnections and the components are not provided in the forbidden area.
[0014] The connection structure mentioned above includes a group of interconnections connecting between the plurality of macros. The connection structure can further includes a component for adjusting a signal timing which is inserted into the group of interconnections.
[0015] According to the software product, the forbidden area is calculated after the orientations are aligned with each other in the above-mentioned (E) calculating.
[0016] The software product further includes the function of (G) generating a layout data by integrating the plurality of macros belonging to the first hierarchy, a non-overlapping section of the connection structure which does not overlap with the plurality of first macros, the plurality of overlapping sections and the interconnections and the components belonging to the second hierarchy.
[0017] In another aspect of the present invention, a method of laying-out a semiconductor device by using a computer includes (a) locating a plurality of macros belonging to a first hierarchy, the plurality of macros including a plurality of first macros having the same function; (b) arranging a connection structure connecting between the plurality of macros; (c) extracting from the connection structure a plurality of overlapping sections which overlap with the plurality of first macros, respectively; (d) incorporating respective of the plurality of overlapping sections into the plurality of first macros, interiors of the plurality of first macros being associated with a second hierarchy lower than the first hierarchy; (e) calculating a forbidden area associated with any of the plurality of overlapping sections by superposing the plurality of overlapping sections with reference to orientations of respective of the plurality of first macros; (f) arranging interconnections and components belonging to the second hierarchy within each of the plurality of first macros such that the interconnections and the components are not provided in the forbidden area; and (g) generating a layout data by integrating the plurality of macros belonging to the first hierarchy, a non-overlapping section of the connection structure which does not overlap with the plurality of first macros, the plurality of overlapping sections and the interconnections and the components belonging to the second hierarchy, and storing the layout data in a storage unit.
[0018] The connection structure includes a group of interconnections connecting between the plurality of macros. The connection structure further includes a component for adjusting a signal timing which is inserted into the group of interconnections.
[0019] According to the method, the forbidden area is calculated after the orientations are aligned with each other in the above-mentioned (e) calculating.
[0020] According to a software product and a method for designing a semiconductor device of the present invention, the overlapping sections of the connection structures (interconnections, timing-adjustment components) to be incorporated to the macros in the lower hierarchy are superposed (merged) for each kind of macro. Then, the layout in each of the macros (the second hierarchy) is carried out. Thus, it is enough to execute the layout only one time for the macros of the same kind. Therefore, it is possible to reduce the number of steps for laying-out (designing) a semiconductor device, and hence to reduce the time necessary for the layout process and the TAT in the layout process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1A is a schematic diagram showing a layout in the top hierarchy according to the conventional technique;
[0022] FIG. 1B is a schematic diagram showing an incorporating process according to the conventional technique;
[0023] FIG. 2A is a schematic diagram showing another layout in the top hierarchy according to the conventional technique;
[0024] FIG. 2B is a schematic diagram showing an incorporating process according to the conventional technique;
[0025] FIG. 3 is a flowchart showing a procedure of a method of laying-out a semiconductor device according to the present invention;
[0026] FIG. 4 is a schematic diagram showing a layout in the top hierarchy according to the present invention;
[0027] FIG. 5 is a schematic diagram showing a top hierarchy floor plan data after incorporating process according to the present invention;
[0028] FIG. 6 is a schematic diagram showing overlapping sections (overpassing interconnections) incorporated into macros 101 a to 101 d according to the present invention;
[0029] FIG. 7 is a schematic diagram showing a forbidden area according to the present invention; and
[0030] FIG. 8 is a schematic diagram showing a generation of an intra-macro final layout data according to the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0031] Embodiments of the present invention will be described below with reference to the attached drawings.
[0032] According to the present invention, laying-out (designing) of a semiconductor device is carried out by using a computer system, i.e., a CAD (Computer Aided Design) system. The computer system has a storage unit, a processing unit accessible to the storage unit, and a computer program (software product) executed by the processing unit. The software product can be stored in a recording medium. To implement a method of laying-out according to the present, the software product has computer readable codes configured to cause the computer (processing unit) to operate as described below. In other words, the software product has functions as described below.
[0033] FIG. 3 is a flowchart showing a procedure of a method of laying-out a semiconductor device according to the present invention. First, a layout hierarchy is determined, and a netlist is divided based on the hierarchy structure. Next, a floor plan in each hierarchy is created (Step S 1 ). For example, a plurality of hierarchy macros belonging to the top hierarchy are located. More specifically, a shape, a size, a position and an orientation of each macro (hierarchy macro) in each hierarchy are determined. As a result, for example, a top hierarchy floor plan data 11 and intra-macro floor plan data 12 are generated as shown in FIG. 3 . The top hierarchy floor plan data 11 includes a floor plan of the top hierarchy (first hierarchy). Each of the intra-macro floor plan data 12 includes a floor plan within each hierarchy macro (second hierarchy). The second hierarchy is lower than the first hierarchy.
[0034] The top hierarchy floor plan data 11 and the intra-macro floor plan data 12 which are generated at the Step S 1 are stored in the storage unit. When there are N (N is a natural number) kinds of hierarchy macros to be arranged on the top hierarchy, N kinds of intra-macro floor plan data 12 are generated in the Step S 1 , as shown in FIG. 3 . A plurality of hierarchy macros of the same kind, in other words, a plurality of hierarchy macros having the same function may be arranged on the top hierarchy. The plurality of hierarchy macros of the same kind may be arranged with different orientations due to inversion and rotation.
[0035] FIG. 4 is a schematic diagram showing an example of the layout in the top hierarchy according to the present invention. As shown in FIG. 4 , hierarchy macros 101 a to 101 d belonging to the top hierarchy are located. The hierarchy macros 101 a to 101 d (first macros) are hierarchy macros of the same kind and have the same function. In the example shown in FIG. 4 , the orientation of the first macro 101 a is defined as an N-orientation. In this case, the first macro 101 b is inverted left-to-right with respect to the N-orientation. The first macro 101 c is inverted top-to-bottom with respect to the N-orientation. The first macro 101 d is inverted left-to-right and top-to-bottom with respect to the N-orientation.
[0036] After the top hierarchy floor plan data 11 is generated, “connection structures” which connect between the plurality of hierarchy macros are arranged in the top hierarchy (Step S 2 ). The connection structures includes a group of interconnections and timing-adjustment components such as repeaters. The interconnections connect between the plurality of hierarchy macros. The timing-adjustment components are provided in order to adjust a signal timing and are inserted into desirable positions of the interconnections. In FIG. 4 , for example, interconnections Net 1 to Net 9 and repeaters (components) C 1 to C 7 are arranged on the top hierarchy.
[0037] In the layout of the top hierarchy, the interconnections are allowed to pass over a hierarchy macro in order to optimize the interconnection path. The repeaters are also allowed to be located over a hierarchy macro. For example, the interconnection Net 2 overlaps with the first macros 101 a and 101 b as shown in FIG. 4 . Similarly, the interconnection Net 3 overlaps with the first macro 101 b, the interconnection Net 6 overlaps with the first macro 101 c, and the interconnection Net 7 overlaps with the first macros 101 c and 101 d. Also, the repeaters C 2 and C 5 are formed over the first macros 101 b and 101 c, respectively. An “overlapping section” is defined as a section of the connection structure (interconnections and repeaters) which overlaps with any of the first macros 101 a to 101 d.
[0038] As shown in FIG. 5 , the interconnection Net 2 can be divided into sections Net 2 ( 0 ), Net 2 ( 1 ), Net 2 ( 2 ) and Net 2 ( 3 ). The interconnection Net 3 can be divided into sections Net 3 ( 0 ) and Net 3 ( 1 ). The interconnection Net 6 can be divided into sections Net 6 ( 0 ) and Net 6 ( 1 ). The interconnection Net 7 can be divided into sections Net 7 ( 0 ), Net 7 ( 1 ), Net 7 ( 2 ), Net 7 ( 3 ) and Net 7 ( 4 ). Each of the sections Net 2 ( 1 ), Net 2 ( 3 ), Net 3 ( 0 ), Net 6 ( 1 ), Net 7 ( 0 ) and Net 7 ( 2 ) corresponds to the “overlapping section”. Also, each of the repeaters C 2 and C 5 corresponds to the “overlapping section”.
[0039] After the above-mentioned interconnection process in the top hierarchy (Step S 2 ), the computer extracts a plurality of overlapping sections from the connection structure. Then, the computer carries out an “incorporating (embedding) process” in which each of the plurality of overlapping sections is incorporated (embedded) into corresponding one of the hierarchy macro (Step S 3 ). It should be noted that the interior of each hierarchy macro is associated with the second hierarchy. Due to the incorporating process, a post-incorporating top hierarchy floor plan data 13 and a post-incorporating intra-macro floor plan data 14 are generated and stored in the storage unit. The positions of the overlapping sections in the hierarchy macros are different from each other. Thus, when the numbers of respective of the N kinds of hierarchy macros arranged on the top hierarchy are M 1 , M 2 to M N , (M 1 +M 2 +. . . M N ) kinds of post-incorporating intra-macro floor plan data 14 are generated in the Step S 3 .
[0040] In the post-incorporating top hierarchy floor plan data 13 , as shown in FIG. 5 , the overlapping sections which include the interconnections Net 2 ( 1 ), Net 2 ( 3 ), Net 3 ( 0 ), Net 6 ( 1 ), Net 7 ( 0 ), and Net 7 ( 2 ), and the repeaters C 2 and C 5 over the first macros 101 a to 101 d are removed. After the incorporating process, the interconnections Net 1 , Net 4 , Net 5 , Net 8 , Net 9 , Net 2 ( 0 ), Net 2 ( 2 ), Net 3 ( 1 ), Net 6 ( 0 ), Net 7 ( 1 ), Net 7 ( 3 ) and Net 7 ( 4 ), and the repeaters C 1 , C 3 , C 4 , C 6 and C 7 remain on the top hierarchy.
[0041] Also, FIG. 6 schematically shows the overlapping sections incorporated into the macros 101 a to 101 d. In FIG. 6 , the orientations of the respective first macros 101 a to 101 d are aligned to the same direction (the N-orientation) with each other, although the first macros 101 b to 101 d are shown inverted or rotated with respect to the N-orientation in FIG. 4 . As shown in FIG. 6 , the positions of the incorporated (embedded) overlapping sections in the first macros 101 a to 101 d are different from each other. Thus, due to the incorporating process, four different post-incorporating intra-macro floor plan data 14 are generated from a same intra-macro floor plan data 12 .
[0042] Next, the computer reads the post-incorporating intra-macro floor plan data 14 from the storage unit, and extracts information with regard to the positions of the overlapping sections in all the hierarchy macros. Then, the plurality of overlapping sections are superposed (merged) for each of the N kinds of the hierarchy macros (Step S 4 ). For example, in the case of the first macros 101 a to 101 d, the positions of the incorporated overlapping sections Net 2 ( 1 ), Net 2 ( 3 ), Net 3 ( 0 ), Net 6 ( 1 ), Net 7 ( 0 ), Net 7 ( 2 ), C 2 and C 5 are superposed. The four post-incorporating intra-macro floor plan data 14 are merged to generate one merged data. Here, the superposing process (merging process) is carried out by referring to the orientations of respective of the plurality of first macros 101 a to 101 d. More specifically, the positions of the incorporated overlapping sections are superposed after the orientations of the respective first macros 101 a to 101 d are aligned with each other as shown in FIG. 6 . As a result, a merged area is calculated and obtained as shown in FIG. 7 .
[0043] The merged area is referred to as a “forbidden area”. The forbidden area shown in FIG. 7 is associated with any of the overlapping sections. The forbidden area is an area in which arrangement of interconnections and components belonging to the second hierarchy, which will be described later, is prohibited. More specifically, for example, the area corresponding to the incorporated interconnections is converted into an interconnection inhibition region, and the areas corresponding to the incorporated repeaters are converted into FILL cells which are arranged such that no other components are arranged therein. The computer calculates the forbidden area, and stores data indicative of the forbidden area in the storage unit.
[0044] Next, an interconnection (layout) process is carried out by the computer for each of the interiors of the hierarchy macros (Step S 5 ). For example, interconnections and components belonging to the second hierarchy are arranged within each of the plurality of first macros. Here, the interconnection process is carried out such that the interconnections and the components within each first macro are not provided in the above-mentioned forbidden area. The interconnection process is carried out for each of the N kinds of hierarchy macros. As a result, N kinds of intra-macro layout data 15 are generated in the Step S 5 . Each of the intra-macro layout data 15 indicates a layout within the corresponding hierarchy macro, and is stored in the storage unit.
[0045] An operation verification is performed on each hierarchy macro on the basis of the intra-macro layout data 15 generated at the step S 5 . The operation verification includes, for example, a verification for checking whether or not a circuit operates at an expected timing based on a simulation or a static timing analysis, a verification for checking that a netlist after the layout process is consistent with a netlist prior to the layout process by using a style verification tool, a verification of an electric power consumption and the like. If the operation verification results in “Fail”, the layout process at the Step S 5 is repeatedly performed until the fail is removed the result of the verification.
[0046] After the operation verification, a layout verification is performed for each hierarchy macro. At the time of the layout verification, a model of the hierarchy macro used for the operation verification of the top hierarchy is prepared. After the completion of the layout verification of the hierarchy macro, an operation verification of the top hierarchy is carried out by using the prepared model of the hierarchy macro. When it is confirmed that there is no fail in the result of the operation verification of the top hierarchy, the computer removes the information regarding the forbidden area from the intra-macro layout data 15 . Then, the computer merges (integrates) the intra-macro layout data 15 from which the information regarding the forbidden area is removed and incorporated data regarding the incorporated overlapping sections (overpassing interconnections and repeaters) indicated by the post-incorporating intra-macro floor plan data 14 . As a result, (M 1 +M 2 +. . . +M N ) kinds of intra-macro final data 16 are generated from the N kinds of the intra-macro layout data 15 (Step S 6 ). The generated intra-macro final data 16 are stored in the storage unit.
[0047] FIG. 8 is a schematic diagram showing a generation of the intra-macro final layout data 16 . The intra-macro layout data 15 from which the information regarding the forbidden area is removed is given as shown in FIG. 8 . For example, the intra-macro layout data 15 shown in FIG. 8 corresponds to the first macros 101 a to 101 d of the same kind. Also, the above-mentioned four post-incorporating intra-macro floor plan data 14 (see FIG. 6 ) associated with the first macros 101 a to 101 d are given. The intra-macro layout data 15 is merged with each of the four post-incorporating intra-macro floor plan data 14 . As a result, four intra-macro final layout data 16 a to 16 d corresponding to respective of the hierarchy macros 101 a to 101 d are obtained.
[0048] Then, the computer merges the post-incorporating top hierarchy floor plan data 13 generated at the step S 2 and the intra-macro final data 16 , and planarizes the hierarchical structure. Accordingly, a desired chip data is generated (Step S 7 ). At this time, each hierarchy macro in the intra-macro final data 16 is merged after inverted or rotated so as to coincide with the orientation in the top hierarchy. For example, the intra-macro final data 16 a corresponding to the first macro 101 a in FIG. 4 is moved in parallel and then merged with the post-incorporating top hierarchy floor plan data 13 . The intra-macro final data 16 b corresponding to the first macro 101 b in FIG. 4 is inverted left-to-right and then merged with the post-incorporating top hierarchy floor plan data 13 . As a result, a chip data having the connectivity shown in FIG. 4 is obtained.
[0049] According to the conventional designing method, when a plurality of hierarchy macros of the same kind are arranged on the top hierarchy and the positions of the overlapping sections to be incorporated into the respective hierarchy macros are different from each other, the laying-out of the second hierarchy needs to be performed on each of the hierarchy macros. Thus, the number of hierarchy macros requiring the laying-out process is larger than the kinds of the hierarchy macros arranged on the top hierarchy. The operation verification and the layout verification are necessary for each of the hierarchy macros on which the laying-out process is performed. This causes the increase in TAT.
[0050] According to the present invention, the positions of the overlapping sections with respect to the hierarchy macros of the same kind are superposed after the orientations of the hierarchy macros are aligned to the same direction, to acquire the forbidden area. Then, the laying-out of the second hierarchy is carried out for each kind of the hierarchy macro with reference to the forbidden area. Therefore, even when a plurality of hierarchy macros of the same kind are arranged on the top hierarchy and the positions of the overlapping sections to be incorporated into the respective hierarchy macros are different from each other, it is enough to execute the laying-out within the macros only one time as for the macros of the same kind. Thus, it is possible to reduce the number of steps for laying-out (designing) a semiconductor device, and hence to reduce the time necessary for the layout process and the TAT in the layout process.
[0051] Moreover, according to the present invention, after the layout process in the hierarchy macros, the operation verification and the layout verification are executed for each of the intra-macro layout data 15 . The interconnections and components in the verified intra-macro layout data 15 are merged with the incorporated overlapping sections provided from the upper hierarchy, to generate the intra-macro final layout data 16 . Thus, it is not necessary to verify each of the intra-macro final layout data 16 . Therefore, the TAT in the layout process can be reduced.
[0052] According to the present invention, when the N kinds of the hierarchy macros are arranged on the top hierarchy, it is enough to execute the layout design for the N kinds of the hierarchy macros. Thus, the number of the hierarchy macros requiring the layout design and verification is reduced as compared with the conventional technique. Therefore, the TAT can be reduced.
[0053] It will be obvious to one skilled in the art that the present invention may be practiced in other embodiments that depart from the above-described specific details. The scope of the present invention, therefore, should be determined by the following claims.
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A software product for laying-out a semiconductor device includes the functions of: (A) locating a plurality of macros including a plurality of first macros of the same kind belonging to a first hierarchy; (B) arranging interconnections connecting between the plurality of macros; (C) extracting from the interconnections a plurality of overlapping sections which overlap with the plurality of first macros, respectively; (D) incorporating respective of the overlapping sections into the first macros; (E) calculating a forbidden area associated with any overlapping section by superposing the plurality of overlapping sections with reference to orientations of the first macros; and (F) arranging interconnections/components belonging to a lower hierarchy within each first macro such that the interconnections/components are not provided in the forbidden area.
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FIELD OF THE INVENTION
The present invention relates to the field of lighting systems and more particularly to recessed lighting systems and provides a structure for facilitating a completely flush recessed lighting arrangement for an enhanced and finely customizable recessed lighting installation.
BACKGROUND OF THE INVENTION
Conventional recessed lighting systems offer a rivet-type installation in which structural and visually hidden portions of the light fixture are provided above and partially within a wall or ceiling barrier, and in which an engaging fixture is attached to the opposite side of the wall or ceiling with or without further rigid attachment to the portions of the light fixture on the other side. The engaging fixture, in order to hide the imperfections in the aperture extending through the wall or ceiling material, typically includes a generously proportioned cover flange. In the case of a ceiling, for example, the flange extends through the aperture, downward to a point at least below the ceiling level and then radially outward. The radial extent of the flange hides imperfections which occurred in the making of the through-hole, such as a tear in the dry wall sandwiching paper, deviations from circularity in the hole, etc.
Typically the radial extent is not flat, and curves downwardly more at the inner radial edge and usually tapers in the direction of its radial outermost extent. The taper provides more clearance space at the radial innermost extent to accommodate foreign objects, such as those formed by gauges in the dry wall, chips of torn paper at the rim, and the like. The shape of the radial extent can vary, and may include an abbreviated taper at the outermost extent for example. The object is to accommodate imperfections without further treatment and provide an outer sealing with respect to the wall or ceiling.
However, the radial design becomes a defacto part of the wall's finish. Moreover, the fixture is typically painted at the factory in a stock color such as white or eggshell and typically in a gloss or enamel finish. Most wall coverings are non-reflective and have a light dispersive finish. The fixture finish virtually never matches the wall color. In highly stylized surroundings, such as art galleries, and custom homes where great care and attention is given to the space, and objects within the space to be illuminated, adding the hodge podge of finishing collar designs to raw need for lighting is undesirable.
Lighting systems have other requirements which continue to demand to be met, including accessibility for cleaning, light bulb and reflector changes and preferably some ability to re-direct the position of the light source. An elimination of the intrusive shape and color of a flange collar can only be reasonably accomplished while leaving these other requirements in tact.
What is therefore needed is a system which meets all of the necessary requirements for lighting system operation and servicablity, but which facilitates a more custom installation. The needed system should be as structurally secure as a conventional system and facilitate a customized installation flush with the surrounding wall or ceiling.
SUMMARY OF THE INVENTION
A flush lighting system includes a support ring for attachment, typically to the underside surface, of a lighting fixture containment space, and a finishing ring which can lockably engage the support ring, either directly using threaded members, or by the use of raised dimples on the support ring which interfits with a groove on the finishing ring. The finishing ring preferably contains apertures and radius grooves for accommodating plaster or dry wall compound. A raised abbreviated radial width inner surface transition lies at the inner most portion of the face of the finishing ring. Inside the raised transition and extending axially is an engagement structure for mating with the support ring, through either a groove or apertures for threaded attachment against a radially outwardly existing axial surface of the support ring. The aforementioned system works well with an additional fixture engagement structure which typically lies within the lighting fixture and for which an additional holding structure provides some engagement to the lighting fixture, and particularly a structure which contemplates a fixture which mounts flush with the surrounding ceiling or wall and the finishing ring.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention, its configuration, construction, and operation will be best further described in the following detailed description, taken in conjunction with the accompanying drawings in which:
FIG. 1 is a perspective lower view of a lighting fixture accommodation box to which a support ring of the invention is attached, typically with four screws and overlying a ceiling board, finishing ring and also shown with a light fixture which fits within and through the finishing ring, ceiling board, support ring and through and protruding into the accommodation box;
FIG. 2 is an isolated view of the support ring and finishing ring where the support ring contains dimple projections radially toward the center of the support ring, and where the finishing ring includes an outwardly disposed groove into which the dimple projections interfit and engage the finishing ring;
FIG. 3 is an isolated view of the support ring and finishing ring where the finishing ring carries apertures and where the support ring may contain a series of different axial height apertures for different thicknesses of wall or ceiling board or no apertures to facilitate the drilling of apertures to exactly match the axial displacement of the support ring with respect to the finishing ring;
FIG. 4 is a perspective view of the finishing ring showing an expanded view of the apertures and grooves which facilitate the retention of wall joint compound;
FIG. 5 is an assembled view of the flush fixture system seen in exploded perspective in FIG. 1 before the addition of wall joint compound;
FIG. 6 is a sectional view taken along line 6 of FIG. 5 and illustrating the addition of wall joint compound over the structures on the planar outer radial surface of the finishing ring and shown with the access afforded with the fixture removed;
FIG. 7 is a sectional view as seen in FIG. 6, but with the fixture in place and illustrating the final, flush appearance of the flush fixture system of the invention;
FIG. 8 is a variation on the system of the invention shown in FIG. 2, but where the support ring has a threaded axial portion and where the finishing ring simply threads onto the axial portion of the support ring, with any excess length of the axial portion acting as a rim to limit the innermost extent of the dry wall compound; and
FIG. 9 is the simplest variation of the invention as a free standing ring having a rim for limiting the joint compound radially inner extension and which would be held in solely by dry wall screws or by nails.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The description and operation of the invention will be best initiated with reference to FIG. 1 and which illustrates a perspective view from below and looking upward at a flush trim collar lighting system 11 . At the uppermost section is a light accommodation box 13 which is usually provided to more than adequately house the wiring and light support, and is typically made oversize in order to aid in heat dissipation. Accommodation box 13 has a light fixture accommodation aperture 14 at its lower side. A larger metal accommodation box 13 will result in a lower temperature and increased thermal dissipation.
Just inside the metal accommodation box 13 two friction clips 15 are noted which will make frictional contact with a removable fixture 17 having a light aperture 18 , seen at the bottom of FIG. 1 . The bottom of the removable fixture 17 is seen as having a lip or outermost radial structure which will be shown to engage a complementary structure to limit its extent of travel in the direction of box 13 . Other shapes of light fixture 17 may be used and in conjunction with other limiting structures to limited the extent of travel toward box 13 . In some cases the clips 15 will be mounted to other structures which may cooperate with any of the structures shown and described in system 11 .
Just below the box 13 , a support ring 19 includes a radially planar portion 21 which will ideally fit directly against the bottom of the box 13 , and an axial portion 23 which, in the preferred embodiment, provides both strength and further structural support. A set of four screws 25 are used to extend through apertures 27 at the outer periphery of the support ring 19 to attach the support ring 19 to the box 13 . This is typically done before the installation takes place, and the combination of the box 13 and support ring 19 may be available commercially as a pre-assembled unit. Manufacturing advantages may be had by using rivets, where a pre-assembled box 19 section is attached to the support ring 19 before the box 13 formation is complete.
The support ring 19 is shown just above a section of wall or ceiling board 31 having a central aperture 33 through which the axial portion 23 may partially extend. Ceiling board 31 may be plaster or dry wall. In most applications the ceiling board 31 will be already installed and the central aperture 33 will be cut with the dimensional clearances and attachment of box 13 taken to account.
Below the ceiling board 13 is a finishing ring 41 . Finishing ring 41 has a radially extending flange 43 which is generally flat but may be tapered in the direction of the outermost periphery. Radially extending flange 41 may also be thin and may generally range from one eighth of an inch to about one sixteenth of an inch. The finishing ring 41 has a plurality of apertures 45 which may have a diameter of about one quarter of an inch to about an eighth of an inch. The apertures 45 help hold wall joint compound so that the wall finish can be brought over the radially extending flange 43 and up to a rim 47 seen as a prominent surface disposed on the same side of the radially extended flange 43 which will receive joint compound to finish the custom installation. In addition, the apertures 45 can also be used with nails having thin heads where the nails are driven into the apertures 45 , but not left so high that the heads would extend above the natural application level of wall joint compound, sometimes referred to as spackle. Where nails are used, the upper nail structure, although displacing part of an aperture 45 , helps to provide additional surface for the wall joint compound to take hold. Rim 47 demarks a radial limit at which the finishing compound approach toward the radial center of the finishing ring 41 will extend. As will be seen, the radially extending flange 43 also includes a plurality of radiused grooves which help to hold the wall joint compound in place over the radially extending flange 43 .
The system 11 is generally seen as having an axis which extends through the accommodation box 13 opening, through the support ring 19 , through the finishing ring 41 and fixture 17 . The general axis of this system is a main axis through which the orientation of the other members may be described.
On the inside of the finishing ring 41 is a radially extending portion which includes an outwardly disposed groove, the rear of which is labeled as 49 which continues axially with an upper wall 51 . Into the upper wall 51 are a series of cutouts 53 . The cutouts 53 give access into the outwardly disposed slot and is generally the best way to open an upper portion of the slot to entry from projections, which will be shown, into the slot. In the alternative, small vertical grooves, leading into the radially outwardly disposed slot, may be provided. However, cutouts 53 are relatively easy to form and where the material of the finishing ring 41 is very thin, this is the preferred method.
Rim 47 is made wide enough in FIG. 1 to be observable, but in actual use it may be radially narrower or wider. The main function of the rim 47 is to provide a transition structure which separates the wall joint compound and the clearance for the ingress and egress of the fixture 17 . The radial width of the rim 47 can be nearly razor thin. Another reason to have a wider rim is to provide sufficient structure against which scraping and sanding can occur. Where hand finishing is performed, the rim 47 can be quite thin, but where a mechanical sander is used, a wider rim, for a given material thickness, can withstand the rubbing away of material without loss of structural integrity. In addition, the rubbing away of material makes the surface of the rim 47 more amenable to holding paint and causes the transition between wall joint compound and metal surface of the rim 47 to be more nearly seamless.
Referring to FIG. 2, a view above the separated supporting ring 19 and finishing ring 41 exposes the radially outwardly disposed groove 61 , and more clearly indicates how the series of cutouts 51 provide access from above. The axial portion 23 of the supporting ring 19 is seen as having a series of inwardly protruding engagement structures 63 which align with the cutouts 51 and which can ride in the slot 61 and enable the supporting ring 19 to engage and support the finishing ring 41 . Any number of engagement structures 63 can be used so long as a matching series of cutouts 53 are properly aligned to accommodate them. In the system 11 with the cutouts 53 and inwardly protruding engagement structures 63 , the finishing ring 61 need only have its cutouts 53 aligned with the projections 63 , followed by a raising of the finishing ring 41 to bring the protruding engagement structures 63 into alignment with the groove 61 and then turn the finishing ring 41 either clockwise or counter clock wise to position the protruding engagement structures 63 in the slot 61 between two adjacent cut outs 53 . In this position, the finishing ring 41 is secured with respect to the support ring 19 , and in an installation with the ceiling board 31 sandwiched in between.
In another embodiment, seen in FIG. 3, a variation is shown in which the support ring 19 carries a series of apertures 65 which may be threaded, and engageable with a series of screws 67 . The screws 67 engage the apertures 65 of the support ring 19 through apertures 69 of the finishing ring 41 . This provides a direct attachment method, and can be used to make custom installations. For example, where the thickness of the ceiling board 31 is thinner or thicker, the holes 65 can be drilled to match for a custom fit, or a series of apertures 65 can be provided which are radially shifted and axially varied. An example is seen as aperture 71 to one side of aperture 65 which is higher up and as an aperture 73 to the other side of aperture 65 which is lower down. If the axial heights are still unacceptable, the apertures 69 can be positioned over a portion of the upper wall 51 having no apertures 65 , 71 , or 73 , and a matching hole drilled. As such, the attachment structure seen in FIG. 4 works well with odd thickness size wall board 31 .
FIG. 4 is a perspective view of the finishing ring 41 showing an expanded view of the apertures and grooves 77 which facilitate the retention of wall joint compound.
FIG. 5 is an assembled view of the flush fixture system 11 seen in exploded perspective in FIG. 1 with the finishing ring 41 seen before the addition of wall joint compound and possibly held in place with the addition of a fastening structure 78 which may be a nail or a dry wall screw. FIG. 5 illustrates the assembled structure as seen with respect to beams 79 . The underside of the fixture 17 is seen. In the fully finished configuration, only the fixture 17 and possibly the rim 47 , assuming that it is not otherwise finished and painted, will be seen. Where the rim 47 is sanded along with the joint compound, only the ceiling's painted surface (not shown) and the bottom surface of the fixture 11 will be seen. The section lines and orientation facilitate further explanation in the following Figures.
FIG. 6 is a sectional view taken along line 6 — 6 , along a main axial extent of the system, and seen in FIG. 5 and illustrating the addition of wall joint compound 81 leading up to and over the structures on the planar surface of the outer radial portion 43 of the finishing ring 41 . As can be seen, the finishing ring 41 radially extending flange 43 extends downward from the lower surface of the ceiling board 31 . Where a more customized finish is desired, a chamfer can be formed in the lower portion of the wall or ceiling board 31 by simply scribing a radius of a lower paper layer 82 equivalent to or greater than the radius of the finishing ring 41 and peeling it away. If further depth of chamfer is desired, some of the wall or ceiling board material 31 can be scraped away. Over chamfering will not be harmful and will help to further seat the finishing ring 41 , although chamfering will probably not be necessary due to the thinness of the radially extending flange 43 .
The fixture 17 is seen enclosing a light support 83 shown in phantom. Typically the light support 83 will support a lamp and enable positional aiming adjustment through the light aperture 18 seen in FIG. 5 . The box 13 is seen has having a lower wall 85 supporting clips 87 which are positioned to frictionally engage a side wall 89 of the fixture 17 . The box 85 may include either as an integral part or as a bracket upholding the clips 87 , a downwardly extending axial wall 91 . Clips 87 will typically be radially dispersed to exert equal opposing force on the fixture 17 . The wall 91 is distinguishable from the wall 23 of the of the support ring 19 . Also seen is the wall or ceiling board 31 now seen sandwiched between the support ring radial planar portion 21 and the finishing ring 21 radially extending flange 43 . Also clearly seen are the of inwardly protruding engagement structures 63 which are engaging the slot 61 , and enable the supporting ring 19 to engage and support the finishing ring 41 .
FIG. 7 is a sectional view as seen in FIG. 6, but with the fixture 17 in place and illustrating the final, flush appearance of the flush fixture system 11 of the invention.
The installation of the system 11 is quite simple. First, a larger metal accommodation box 13 is typically fitted already with a support ring 19 . Into the wall or ceiling board 31 is formed a central aperture 33 just beneath where the box 13 is to be mounted. Next the box 13 is secured, typically with respect to beams rafters or other structural members of a building, in a position where the support ring 19 may partially fit through the central aperture 33 . Next, the finishing ring 41 upper wall 51 , which is a cylindrical shape, is moved upwardly and into the axial portion 23 of the support ring 19 such that the inwardly protruding engagement structures 63 fit within the radially outwardly disposed groove. A short turn of the finishing ring secures it into place and such the radially extending flange 43 should lie closely adjacent to the surrounding wall or ceiling board 31 and flatly against it. Next, the joint compound is applied to the wall or ceiling board 31 around the finishing ring 41 and onto the finishing ring 41 up to the rim 47 . Typically smoothing will be performed by a wide blade tool. Once the joint compound dries, the whole area is sanded and the addition of joint compound possibly repeated. The surrounding surfaces, joint compound and possibly the rim 47 are now ready for painting.
A further variation on the connectability of a support ring 101 is seen in FIG. 8 by providing threads 103 on an outer surface of an axial portion 105 of the support ring 101 . A finishing ring 107 has an internal thread 109 or has an internal surface suitable for interactably engaging a threaded surface. The excess of the axial portion 105 which goes past the finishing ring 107 forms a stop or rim similar to rim 47 to limit the concentric inner extent of drywall compound.
Another variation is seen in FIG. 9 where a finishing ring 121 is provided which is not intended to link up with a support ring. The finishing ring 121 contains the rim 47 and radially extending flange 43 seen in FIG. 2, but requires other methods and structures to attach, such as the dry wall screw, nail or like structure 78 of FIG. 5, as well as glue or other holding structures.
While the present invention has been described in terms of an flush trim collar lighting system, the principles contained therein are applicable to other types of custom finishing systems.
Although the invention has been derived with reference to particular illustrative embodiments thereof, many changes and modifications of the invention may become apparent to those skilled in the art without departing from the spirit and scope of the invention. Therefore, included within the patent warranted hereon are all such changes and modifications as may reasonably and properly be included within the scope of this contribution to the art.
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A flush lighting system includes a support ring for attachment, typically to the underside surface, of a lighting fixture containment space, and a finishing ring which can lockably engage the support ring, either directly using threaded members, or by the use of raised dimples on the support ring which interfits with a groove on the finishing ring. The finishing ring preferably contains apertures and radius grooves for accommodating plaster or dry wall compound. A raised abbreviated radial width inner surface transition lies at the inner most portion of the face of the finishing ring. Inside the raised transition and extending axially is an engagement structure for mating with the support ring, through either a groove or apertures for threaded attachment against a radially outwardly existing axial surface of the support ring. The aforementioned system works well with an additional fixture engagement structure which typically lies within the lighting fixture and for which an additional holding structure provides some engagement to the lighting fixture, and particularly a structure which contemplates a fixture which mounts flush with the surrounding ceiling or wall and the finishing ring.
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SUMMARY OF THE INVENTION
This invention relates to an improved convertible seat-bed assembly, and will have special application to a power driven convertible seat which includes storage provisions beneath the assembly seat support.
The seat-bed assembly embodied in this invention is principally adapted for use in a vehicle such as a camper or van. Heretofore, seat-bed assemblies were manually convertible from a seating position to a bed position. Such as prior construction is shown in U.S. Pat. No. 4,321,716, which is incorporated herein by reference.
The seat-bed assembly of this invention utilizes a gear mechanism connected to a power motor which upon activation urges the assembly into a selected one of its seat or bed positions. Also, the seat frame support may be lifted when the assembly is in the seat position to allow article storage beneath the seat support within the assembly.
Accordingly, it is an object of this invention to provide for a motorized convertible seat-bed assembly.
Another object of this invention is to provide a motorized seat-bed assembly which includes storage provisions beneath the assembly seat support.
Another object of this invention is to provide for a motorized seat-bed assembly which can be rapidly and easily converted from a seat to a twin sized bed.
Still another object of this invention is to provide for a motorized seat-bed assembly which is lightweight, durable and economical.
Other objects of this invention will become apparent upon a reading of the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
A preferred embodiment of the invention has been chosen for purposes of illustration wherein:
FIG. 1 is a perspective view of the seat-bed assembly in its seat position.
FIG. 2 is a perspective view of the seat-bed assembly in its bed position.
FIG. 3 is a side elevational view of the assembly in its bed position.
FIG. 4 is a side elevational view of the assembly in an intermediate position.
FIG. 5 is a side elevational view of the assembly in its seat position.
FIG. 6 is a side elevational view of the assembly in its seat position with the seat frame support lifted to expose the storage area beneath the seat support.
FIG. 7 is a fragmentary cross-sectional view of the drive mechanism of the seat-bed assembly.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The preferred embodiment herein described is not intended to be exhaustive or to limit the invention to the precise form disclosed. It is chosen and described to explain the principles of the invention and its application and practical use to thereby enable others skilled in the art to utilize the invention.
The seat-bed assembly 10 shown in the drawings includes a base frame 12 formed of spaced U-shaped end members 14. End members 14 are connected by longitudinal cross members 15 which extend the length of assembly 10. Each end member 14 includes vertical legs 16 between which a support 18 extends. Guide channels 20 and 22, as shown in FIGS. 3-6, are positioned on each support 18. The connecting linkage for the seat and back frame supports extending from each end member 14 is the same and thus only one complete end member is shown and will be described. It is understood that the other end member 14 and its connecting linkage rest specifically described works and is constructed in similar fashion.
Seat support 26 includes a fixed link 24 which is slidably retained at its lower end 28 for movement along guide channel 20 by a roller 30 located within the guide channel. A bench type spring frame and seat cushion 32 is attached to support 26. A link 34 is pivotally connected at one end 36 to seat support 26 and is slidably retained for movement along guide channel 22 at its other end 38 by a roller (not shown) located within the guide channel.
A lazy tong-like linkage controls movement of a back frame support 40 and includes links 42, 44 and 46. A spring frame and back cushion 48 is attached to back support 40. One end 50 of link 42 is pivotally connected to end 38 of link 34 and is slidably retained for movement along guide channel 22 by being connected at its other end to link 34. Link 44 is pivotally connected at one end 52 to rear vertical leg 16 of end member 14 and is pivotally connected at its other end 54 to back support 40. Link 44 is also pivotally connected at 56 to link 42. Link 46 is pivotally connected at one end 58 to link 42 and is pivotally connected at the other end 60 to back support 40. The assembly as thus far described is similar to the seat-bed assembly disclosed in U.S. Pat. No. 4,321,716.
Assembly 10 includes a mechanized device attached to one end member 14 and its connecting linkage for shifting the assembly between the seat position of FIG. 3 to the bed position of FIG. 5. A bracket 62 is joined to seat support 26 in front of link 34. A threaded sleeve 63 is pivotally connected to bracket 62. A gear box 66 is attached to support leg 16 and supports a worm gear 68 which extends through sleeve 63. A battery operated motor 70 is connected through reduction gears within gear box 66 to worm gear 68. A spring biased switch 72 is associated with motor 70 to allow for motor actuation and the resulting rotation of gear 68. Switch 72 is located at one side of cushion 32 for ease of accessibility.
Assembly 10 is operated as follows. With assembly 10 in its seat position of FIG. 5, switch 72 is moved in one direction and held to activate motor 70. Upon activation of motor 70, gear 68 rotates within sleeve 63, causing movement of bracket 62 towards gear box 66. This pulls seat cushion 32 forward and back cushion 48 downward as shown in FIG. 4 until the bed position of FIG. 3 is reached and further movement is prevented. At this time motor switch 72 is released. To restore assembly 10 to the seat position, switch 72 is moved in the opposite direction and held to reverse motor 70 and gear 68 which pushes seat cushion 32 rearwardly until the assembly 10 is in its seat position of FIG. 5 where switch 72 is released to stop the motor.
Also, due to the pivotal action of sleeve 63 and links 24 and 34, seat support 26 may be movably raised as shown in FIG. 6, allowing items to be stored beneath the seat support.
It is to be understood that the scope of the invention is not limited to the above description, but may be modified within the scope of the appended claims.
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An improved seat-bed assembly which includes seat and back supports associated with a linkage and a motor to convert the assembly from seat form to a bed. The seat support may be raised when in the seat position to allow articles to be stored beneath the seat support.
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BACKGR0UND OF THE INVENTION
This invention relates generally to a dental device, and more particularly to an intra-oral dental device.
Still more specifically, the invention relates to an intra-oral aligning assembly for tooth prostheses, occlusion diagnostic and/or occlusion therapy in general, and more particularly to such an assembly which includes rigid upper jaw and lower jaw components of which one is provided with a through-going tapped bore into which a supporting pin is threaded, the tip of which is insertable into an opening in the area of that surface of the other jaw plate which faces the jaw plate having the tapped bore.
Aligning assemblies of this type are known, for example from U.S. Pat. Nos. 3,068,570 and 3,564,717. When assemblies of this type are used, the two plates are inserted into and fixed in the upper and lower jaw, respectively. Thereafter, the patient is requested to cause his lower jaw to perform sliding movements in anterior-posterior as well as lateral direction, and during these movements the tip of the supporting pin traces on preferably colored surface of the other jaw plate a figure having essentially an arrow-shaped configuration and which is called a Gothic Arch. Thereafter, the dentist places a thin apertured plate onto the other jaw plate in such a manner that the middle of the opening of the apertured plate coincides with the tip of the arrow. In this position the apertured plate is fixed with respect to the other of the jaw plate and thereafter the other jaw plate is again inserted into the mouth of the patient who is then instructed to close his jaws with slight pressure, the purpose being to have the tip of the supporting pin enter into the opening of the apertured plate. The dentist then places dental molding material or the like between the two bite plates in order to fix them in this position relative to one another. After the material hardens the bite plates can be taken out of the patient's mouth as a unit, i.e. in a state in which they are fixed relative to one another.
In the devices known from the prior art the tip of the supporting pin is formed by a sphere which is turnably journalled in an appropriate journal of the tip of the pin shaft. In this manner the pin is constructed somewhat analogously to a ball-point pen, so as to assure that during tracing of the Gothic Arch rolling of the sphere produces ready movement of the tip of the pin with respect to the other bite plate. Of course, the sphere or ball must be so mounted that during the use of the assembly it does not fall out of its support, which means that it must enter the socket holding it to a depth which is greater than its radius.
The opening and closing movement of the lower jaw takes place over a range of approximately the first two centimeters (adjacent the closed position) in a circular path about a center formed by the condyles. The position of the condyles is defined by the concept of the retrograde contact position, which is the starting point of each functional analysis and prosthetic treatment. Therefore, it must not be allowed to change in the determination of the bite height, because it determines the vertical position of the lower jaw with reference to the upper jaw.
Since the opening and closing movement of the lower jaw with the condyle position in retrograde contact position takes place in a circular path, this circular path must be taken into account during the point-like fixation of the selected bite height. Any lack of accuracy in the vertical direction results in an improper bite height, whereas any lack of accuracy in the horizontal direction produces a false condyle position.
With respect to the known assemblies of the type here in question, the accuracy is limited. During the terminal bite position the tip of the supporting pin will meet the arrowhead traced on the other bite plate in cooperation with the opening of the apertured plate in an exact manner only, if the bite plates and the axial directions of the supporting pin tip and the apertured plate opening approach one another in exact parallelism at the end of the jaw movement. Such an exactly parallel approach of the bite plates, the supporting pin tip and the opening in the apertured plate in the terminal phase of the circular movement of the lower jaw cannot be assured in actual practice. It is obtained only in certain fortunate exceptional conditions. In the vast majority of cases the tip of the supporting pin will engage the edge or the inner wall of the opening in the apertured plate prematurely, due to tilting of the pin with reference to the axis of the opening. This results in a wedging effect and a maladjustment of the supporting pin tip and the arrowhead tip. The result is improper registration during the fixation both in the vertical direction (bite height) and in the horizontal direction (condyle position). This results in a condyle shift which is undesirable.
One of the objects of the invention is to eliminate these problems and to produce a device of the type in question which is simple to use and which excludes registration errors to the maximum extent possible, which result from the fact that in the terminal phase of the bite movement deviations with respect to parallelism of the bite plates occur and the circular movement of the lower jaw during the closing movement has a forwardly directed component.
Another disadvantage of the known devices is that the bite plates can be only insufficiently fixed in the upper and lower jaws, because the bite plates are constructed either as narrow strips, or triangular or of hour-glass shape. This means that they have few supporting areas which are closely adjacent to one another, so that there is a substantial danger that the bite plates may tilt during the tracing of the Gothic arch and during the final bite.
The determination of the joint-related position of the lower jaw with reference to the upper jaw, during which heads of the jaw joint are centered at the highest points of the cavities of the jaw points, is effected according to the static principle of the three-point support and requires that the supporting pin is centrally arranged. If the supporting pin deviates from the central arrangement in the saggital or transversal direction, a tilting of the lower jaw results which causes a shifting of the heads of the jaw joint in their sockets. This clinical experience is used in the treatment of patients who have the symptoms of myoarthropaty and for whom the heads of the jaw joint are to be therapeutically displaced in the sockets until a reduction of pain or freedom of pain during the final bite has been achieved. In the known devices the supporting pin is adjustable with reference to the bite plate carrying it, only in the direction of the supporting pin axis, which is normal to the bite plate plane. If a change in the supporting pin position is desired in the saggital or transversal directions, the bite plate must be removed from the supporting substrate and subsequently be connected again thereto. This is time consuming and inaccurate, because there is no appropriate reference system.
In German published application No. 2,645,852 it has been proposed to provide an aligning assembly with a three-dimensionally displaceable supporting pin. A threaded sleeve receiving the supporting pin is movable in longitudinal direction of an elongated slot of an intermediate plate and can be fixed with reference to the intermediate plate by means of a set screw. The intermediate plate itself is adjustable in a direction normal to the elongation of the elongated slot, by means of a guide which is inserted in the respective bite plate. To fix the intermediate plate two clamping screws and bars are provided at opposite sides of the intermediate plate which serve to press the bars against the intermediate plate and are threaded into the bite plate. This solution, however, is rather expensive and, in addition, requires a very significant amount of space.
When taking a bite using intra-oral aligning assemblies, it is desired that the retrograde contact position of the condyles in the sockets are fixed under the same pressure loads on the gums and the teeth, as they occur if a definitive tooth replacement is provided. Loading of the gums and of the teeth during the taking of the bite is to correspond to the later loading by the prostheses. This requires readily workable types of bite plates which can reach any desired point of the dental arc and be there positioned. The known devices are too small and too narrow for this purpose and as a consequence disadvantageous tilting moments can arise during the registration and fixation.
For this reason another object of the invention is to provide an intra-oral assembly device of the type in question the bite plate of which can be mounted particularly safely in the upper and lower jaws. Furthermore, the device is to have a three-dimensional adjustability of the supporting pin in a simple manner. The device is to permit a prostheses-simultaneous mounting and to require little room.
SUMMARY OF THE INVENTION
Pursuant to the above objects, and to others which will become apparent hereafter, one aspect of the invention resides in a device of the type in question having a supporting pin the tip of which is a segment of a sphere which is rigidly coupled with the shaft of the pin, and the free part-spherical surface of which reaches from the front end of the pin located on the longitudinal axis of the shaft in all directions rearwardly over an angle of at least 100°, in such a manner that even during the largest relative tilting to be expected of the bite plates the edge of the opening facing towards one of the bite plates engages along its entire circumference with the spherical surface.
Because of the turnable journalling of the balls in the prior-art devices of this type, the exposed spherical surface can extend up from the very tip (located on the longitudinal axis of the pin) of the pin rearwardly only over an angle of 90°. By contrast, the surface of the spherical segment used in the contact pin of the device according to the present invention extends rearwardly beyond the plane of the major circle which extends normal to the pin axis. Only this assures that the tip of the spherical segment will always contact one and the same point on the surface of the other bite plate respectively of a plane assumed to be parallel to and spaced from this surface by a predetermined distance, namely the point corresponding to the traced arrowhead respectively a point at the junction between the aforementioned imaginary plane and a straight line intersecting this plane and the tip of the arrowhead. Moreover, this will be independent of whether the axis of the supporting pin is tilted with reference to the vertical towards the other bite plate or not. Possible deviations in the respective parallel arrangement of the bite plates therefore cannot disadvantageously influence the registration in the vertical (bite height) or in the horizontal (condyle position). Accuracy of registration and fixation on the order of 1/100 millimeter are possible without any difficulties. The error sources of known devices of this type during fixing of the two bite plates after the final bite has been taken, are thus eliminated in a simple and highly effective manner.
Preferably, the spherical surface will extend symmetrically from the forward tip or end of the pin over an angle of 220°-320°, and preferably between 250°-320°. Angles of at least 220° and preferably at least 250° permit even substantial tilting of the bite plates relative to one another during the final bite, without thereby disadvantageously influencing the accuracy of registration and fixation. The aforementioned angles are delimited upwardly only by consideration of strength and simple manufacture. Angles over 320° may cause the material cross-section, over which the spherical segment is in contact with the shaft of the supporting pin, to be too small to be reliable.
It is currently preferred if the spherical segment is seated on its side where it is connected with the shaft of the supporting pin, on a frustonical portion the wider end of which is connected with the shaft of the pin whereas the narrower end of which is connected with the spherical segment and has a smaller diameter than the diameter of the spherical segment itself. This eliminates the danger that during the final bite the edge of the opening might undesirably engage the frustoconical portion. The frustoconical portion or the part of the pin shaft adjacent the spherical segment may be provided with flats which can be engaged by a wrench-like tool to permit adjustment of the supporting pin even when the bite plate is already inserted into the mouth cavity.
The opening which is engageable with the spherical surface of the spherical segment is advantageously formed in known manner in an apertured plate that can be mounted on the other bite plate. According to a variation this opening may, however, also be formed by a bore in the other bite plate itself, the diameter of which is smaller than the diameter of the spherical segment by a predetermined amount. If this construction is chosen, then a suitable tool can be used to produce in the other bite plate at the tip of the arrowhead traced on it during the Gothic arch tracing movement, a hole having a diameter which is smaller than the diameter of the spherical segment by a predetermined figure. During the final bite the spherical segment then enters into this bore to a depth which is fixedly predetermined by the relative relation of spherical segment diameter and bore diameter, and which therefore can be easily taken into account in advance.
To be certain to effect error-free fixing when using an apertured plate, even in the event of more substantial relative tilting of the bite plates, the length of the opening in the apertured plate in the direction of the opening axis should be at most equal to the radius of the spherical segment at the tip of the supporting pin. Also, the length and the diameter of the opening in the apertured plate and the diameter of the spherical segment at the tip of the supporting pin should be so coordinated with one another that when the tip of the supporting pin engages the other bite plate the upper edge of the opening in the apertured plate engages the spherical surface practically without freedom of play. To obtain good retention the thickness of the apertured plate should be equal to the radius of the spherical segment or only slightly smaller than the same.
The apertured plate itself may be constructed as a circular plate which may be self-adhesive, i.e. a member which is provided on one of its major surfaces with a self-adhesive coating preferably covered, until the time of use, by a release paper. The apertured plate may advantageously be of a foil material.
It is particularly advantageous if the bite plates have the form of a planar surface surrounded by the arch of the teeth, the alveolar ridge or the residual rib of an upper respectively lower jaw. This assures a large-area and reliable fixation of the bite plate in the upper and lower jaw during the tracing of the Gothic arch and the final bite, and which is largely immune to tilting moments.
The bite plates, as known from German Gebrausmuster No. 7,709,769, are preferably of a stiff synthetic plastic material. Bite plates of synthetic plastic material are not only substantially less expensive than metallic bite plates, but also greatly facilitate the use of the aligning assembly irrespective of whether in a particular application a toothless jaw is involved, a jaw having some teeth, a jaw having all teeth, a jaw having ground-down teeth or a jaw having a partial or a total prostheses. The bite plates can be trimmed by the dentist very simply in accordance with the particular requirements, for example cutouts can be made to allow them to fit about existing teeth. In this manner the aligning assembly can be universally employed. It is, of course, possible to use different sized bite plates for differently sized jaws, and to keep them in stock. If, however, the bite plates are so dimensioned that they exceed the surface surrounded by the tooth arch of a large upper or lower jaw, by about one centimeter everywhere, then a single aligning assembly size can be used wherein the bite plates are merely trimmed to the desired shape and size when the assembly is to be used.
To obtain the necessary rigidity for synthetic plastic bite plates, which is needed for exact registration, the bite plates may advantageously be reinforced with glass fibers, carbon fibers or metal. In addition, or in lieu thereof, the bite plates may be provided with reinforcing ribs or the like. In particular, it may be advantageous to increase the thickness of the center area of the bite plates. The facing surfaces of the two bite plates are preferably either matte or roughened. This assures a reliable bonding of small quantities of quick-hardening synthetic plastic which may be used to advantage for fixing the bite plates with reference to one another. In addition, it assures good adhesion of the color coating which may be used to help in marking the Gothic arch.
To facilitate the trimming of the bite plates to the desired shape and size, they are either opaque, translucent or transparent in at least their marginal regions.
It has been found to be advantageous if the exterior thread of the supporting pin has a diameter which is slightly (fractions of a millimeter) larger than that of the tapped bore into which the pin is to be threaded. This assures that the pin does not turn too easily and, in turn, prevents the pin from becoming inadvertently repositioned after the Gothic arch has been traced, because this would throw off the results.
For static reasons the tapped bore into which the pin is to be threaded is preferably provided at a part of the one bite plate which is essentially in registry with the center of gravity of the lower jaw. This automatically assures proper centering of the condyles in the sockets.
The tapped bore may be formed in one of the bite plates itself. A more stable mounting of the supporting pin is, however, achieved if the bite plate carrying the supporting pin is provided with a threaded sleeve receiving the supporting pin and which projects from that side of the bite plate facing away from the other bite plate.
If a three-dimensional adjustability of the supporting pin is desired, then it is advantageous to use such a threaded sleeve and mount it in a recess of the one bite plate so that it can be adjusted in two directions of the bite plate plane extending normal to the axis of the supporting pin, and which can be fixed via a clamping portion projecting radially outwardly from the threaded sleeve and a nut that is threaded onto the threaded sleeve itself, with both the clamping portions and the nut having parts extending into the recess of the one bite plate in each desired relative positioning of the threaded sleeve and bite plate, which parts engage for fixing the threaded sleeve with the opposite lateral sides of the one bite plate. Contrary to the construction known from German allowed application No. 2,645,852 this eliminates both the intermediate plate and the clamping members as well as the clamping screws associated with the same. The bite plate itself requires no threaded bore under this arrangement.
The parts overlapping the recess of the one bite plate may be ring flanges or any other projecting portions. A particularly simple use is assured if the threaded sleeve and/or the nut are provided with wing-shaped radial projections which permit a reliable engagement of the threaded sleeve and the nut and thus facilitate their handling. It has been found particularly advantageous to provide the threaded sleeve and/or the nut each with four radial projections spaced about the sleeve or nut at 90 degree angles of offset.
The radial projections of the threaded sleeve may advantageously cooperate in the manner of pointers with two graduations extending at right angles to one another and which are engraved or otherwise formed in the lateral side of the one bite plate facing towards the radial projections. Advantageously the sides of the radial projections facing the graduations have a surface profile which is complementary (e.g. edged) to the graduation. This permits a simple snap-type adjustment of the supporting pin in the bite plate plane. The radial projections together with the graduations serve to prevent undesired turning of the threaded sleeve when the nut is to be turned in order to release the clamping connection between the one bite plate and the unit composed of supporting pin, threaded sleeve and nut, or when the connection is to be tightened.
The novel features which are considered as characteristic for the 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, showing in exploded condition the upper bite plate, the lower bite plate and an apertured plate of a device according to the present invention;
FIG. 2 is an enlarged-scale view, in section, of the assembly of FIG. 1 wherein the tip of the supporting pin engages into the apertured plate;
FIG. 3 is a view analogous to FIG. 2 but showing a different embodiment;
FIG. 4 is a top-plan view of the arrangement of FIG. 3;
FIG. 5 is a cross-section through a further embodiment of a bite plate according to the present invention, taken in a section on line V--V of FIG. 6 and having a three-dimensionally adjustable supporting pin;
FIG. 6 is a bottom-plan view of the bite plate of FIG. 5;
FIG. 7 is a top-plan view of the bite plate in FIG. 5; and
FIG. 8 is a fragmentary section of FIG. 5, on an enlarged scale, taken on line VIII--VIII of FIG. 5.
DESCRIPTION OF PREFERRED EMBODIMENTS
Referring firstly to FIGS. 1 and 2 it will be seen that the upper bite plate is identified with reference numeral 1. It is preferably of glass fiber reinforced synthetic plastic material and may have a thickness up to 3 millimeters, or perhaps more. At the side which is facing upwardly in FIG. 2 the plate 1 is provided with a threaded sleeve 7 which is of one piece with it. The threaded sleeve 7 and the adjacent part of the bite plate 1 are provided with a threaded or tapped bore 2 into which a supporting pin 3 is threaded. The pin 3 is provided in the area of its cylindrical shaft 9 with an external thread 4 which permits the user to adjust the spacing of the tip 5 of the supporting pin from the underside of the bite plate 1. The cylindrical shaft 9 merges into a downwardly tapering frustoconical intermediate portion 6 the narrower end of which carries the tip 5 of the pin in form of a spherical segment. The segment 5 has a diameter which is larger than the diameter of the narrow end of the frustoconical portion 6. The exposed spherical surface of the spherical segment 6 extends from the forward tip of the pin, i.e., the tip located on the longitudinal axis 14, on all sides through an angle of at least 100° and preferably at least 125°, so that the rigid connection between the spherical segment 5 and the frustoconical intermediate portion 6 is located on that side of a large circle of the spherical segment 5 normal to the axis 14, which faces away from the tip of the pin. In the region of the portion 6 flaps 39 are provided which permit turning of the pin 3 by means of a not-illustrated tool, e.g. a wrench-like tool.
The lower-jaw bite plate 8 is preferably also made of fiber-reinforced synthetic plastic material and preferably has approximately the same thickness as the bite plate 1. In its upper surface facing the bite plate 1 it may be provided with a coating (not shown) of color serving to facilitate tracing of the Gothic Arch. The bite plates 1 and 8 have a size corresponding to that area surrounded by the dental arch, the alveolar ridge or the residual ridge of an upper jaw, respectively lower jaw, with a dorsal limitation in the tuber and retromolar area. If desired, the bite plates may be produced in indifferent sizes and kept in stock for use with different-sized jaws, except that this is not necessary as explained before. The external thread 4 of the pin 3 has a diameter which is slightly (on the order of fractions of millimeters) larger than the internal diameter of the threads in the tapped bore 2.
The apertured plate may simply be a circular plate or washer 10 provided with a circular center opening 11. The thickness of the plate 10 is smaller than the radius of the spherical segment 5 and the thickness of the plate 10, the diameter of the opening 11 and the diameter of the spherical segment 5 are so coordinated with one another that the upper edge 13 of the opening 11 will engage the spherical surface of the segment 5 without any freedom of play when the tip of the supporting pin rests on the upper side of the bite plate 8. For example, the spherical segment 5 may have a diameter of 1.61 millimeters, in which case the diameter of the opening 11 may be 1.4 millimeters and the thickness of the plate 10 may be 0.4 millimeters. When the lower jaw is closed the segment 5 then enters into the opening 11 to a depth of 0.4 millimeters and, in so doing, engages the upper side of the bite plate 8 at the center of the opening 11. It will be appreciated that other dimensions can also be used and that these given herein are exemplary and not limiting, provided only that it is assured that the exposed spherical surface of the spherical segment 5 projects from the forward tip of the pin 3 (i.e. the tip located on the axis 14) rearwardly to such an extent that even during the largest relative tilting of bite plates 1 and 8 which can be expected, the edge 13 of the opening 11 will still engage the spherical surface of the segment 5 along the entire circumference of the edge 13.
To use the device according to the present invention the bite plates 1 and 8 are mounted in the upper and lower jaws of the patient. If the jaws are without teeth the mounting can be effected by first inserting into the jaw an appropriately shaped base plate of synthetic plastic material which bolts to the jaw by suction. The respective bite plate is then secured to the base plate by means of dental wax or synthetic plastic material. If jaws are to be treated which have some teeth in them the bite plate is cut out to make allowance for the residual teeth, and may be secured by a wax or synthetic plastic wall by means of synthetic plastic material. If the teeth have an advantageous position, then the bite plate can be connected to the teeth directly by means of suitable synthetic plastic material known to those skilled in the dental art. Generally speaking, the bite plate (each of the bite plates) is so mounted as required for the later mounting of the definitive tooth prostheses, i.e. gingival, dental or mixed gingival dental.
When the patient, after the plates have been so mounted, moves his lower jaw as described earlier, then the tip 5 will form on the bite plate 8, respectively in the coating of color provided thereon, the arrow 12 indicated in FIG. 1.
After this is done, a protractor or the like can be used to form a circle of e.g. 2 centimeter diameters about the tip of the arrow, the tip serving as the center of the circle. The plate 10, the diameter of which in this particular example is also advantageously 2 centimeters, is now placed into this circle so as to register with the same and secured to the bite plate 8 with wax or a suitable synthetic plastic. However, the plate 10 could also be of foil material and provided with a self-adhesive coating on one surface. In any case, by securing the plate 10 in this manner the longitudinal central axis of the opening 11 becomes centered on the tip of the arrow 12.
For the final bite the bite plates 1 and 8 are again inserted into the mouth of the patient, and the patient thereupon closes his jaws with slight pressure, causing the tip 5 of the pin to enter into the opening 11 in the manner illustrated in FIG. 2. Two or three drops of synthetic plastic material of the quick-hardening type which have first been placed upon the lower bite plate 8, now connect the bite plates 1 and 8 in the position which has been registered in this manner.
It is essential that the respectively lowermost point of the spherical segment 5 which is rigid with the shaft 9 will always form a tangent to the upper side of the bite plate 8 at the identical point which is predetermined by the opening 11. This point of contact is located on the longitudinal center axis of the opening 11, independently of whether the longitudinal axis 14 of the pin 3 is aligned with the longitudinal axis of the opening 11 as shown in FIG. 2, or assumes an inclined position as for example suggested at 14'. In other words, independently of whether the bite plates 1, 8 are arranged in parallelism with one another or not, and independently of the circular closing movement of the lower jaw, the tip of the pin 3 will always contact the tip of the arrowhead 12 without contacting the apertured plate 10 in a manner capable of flowing off the registration, causing the pin to become inclined and to dislocate the condyles. The space required between the bite plates is only very small.
In the embodiment according to FIGS. 3 and 4 the apertured plate is omitted. In this embodiment the upper bite plate 16 is provided in the region of the supporting pin 3 with a reinforcement 17 and the pin 3 is mounted by means of a tapped bore 18 in the center of the reinforcement. The marking of the arrowhead is effected in the same manner as described with respect to FIGS. 1 and 2. However, instead of putting an apertured plate in place, concentric to the tip of the arrowhead as described with respect to FIGS. 1 and 2, in FIGS. 3 and 4 a hole is drilled at the registered tip of the arrowhead into the lower bite plate 8. A conventional dental drill used for such purposes can be employed to drill this hole. The diameter of the bore 19, analogously to the diameter of the opening in the apertured plate 10 of FIGS. 1 and 2, is smaller by a predetermined amount than the diameter of the tip 5. During the final bite the spherical segment 5 therefore enters into the bore 19 to an imaginary plane 20 which has a predetermined spacing from that upper side of the bite plate 8 which faces the bite plate 16.
In order to compensate from the depth of penetration of the tip 5 and to assure that the spacing of the bite plates 8 and 16 relative to one another during the tracing of the arrowhead and during the final bite is always the same, the supporting pin 3 is threaded out or forward subsequent to the tracing of the arrowhead and prior to taking the final bite, by a distance which corresponds to the depth of penetration of the tip 5. Preferably, the relation of the diameters of the tip 5 and of the bore hole 19 which determines the depth of penetration of the tip 5 into the bore hole, as well as the turns of the threads of the supporting pin 3, are so coordinated with one another that a trimming of the pin 3 through an angle of e.g. 180° or 360° corresponds to a forward advancement of the pin 3 by an amount equal to the depth of penetration. This readjustment of the pin 3 prior to the patient's taking the final bite is particularly simple if markings are provided at the upper side of the bite plate 16 and possibly also on the supporting pin 3, as indicated with reference numeral 21 in FIG. 4.
A further embodiment of the invention is illustrated in FIGS. 5-8, wherein the upper-jaw bite plate 24 is provided with a quadratic recess 25 through which the supporting pin 3 extends vertically down to the bite plate plane. The pin 3 is threaded into a tapped sleeve 26 and projects with its tip 5 beyond the lower end (FIG. 5) of the tapped sleeve 26. As is shown in the drawing, particularly in FIG. 6, the tapped sleeve 26 is provided with four radial projections 28 which are offset from one another through 90 degree angles and which have sufficient length to extend over the recess 25 in any desired relative position of threaded sleeve 26 and bite plate 24. The end of the tapped sleeve 26 which projects in FIG. 5 beyond the bite plate 24 and is provided with an external thread, has a nut 29 threaded onto it which, in the illustrated embodiment, has radial projections 30 similar to the radial projections 28 of the tapped sleeve 26.
FIGS. 5, 6 and 7 show that in any desired relative position of supporting pin 3 and bite plate 24 the radial projections 28, 30 engage the two broad sides of the bite plate 24. By tightening the nut 29 the position of the axis of the pin 3 can be fixed with respect to the bite plate plane. After releasing the nut 29 the unit composed of pin 3, threaded sleeve 26 and nut 29 can readily be adjusted with reference to the bite plate 24. By threading the pin 3 to a greater or lesser extent out of the tapped sleeve 26, an adjustment of the pin 3 can be effected in a third direction. To facilitate the adjustment of pin 3 and nut 29 these may be provided with transverse flaps 32 and 33, respectively. In order to make it possible to readily adjust the nut 29 even after the bite plate 24 has been inserted into the mouth of the patient, recesses 40 are provided into which complementary projections of a not-illustrated tool can be placed which then serves to turn the nut 29.
The bite plate 24 is provided at the underside cooperating with the radial projections 28 of the threaded sleeve 26, with two graduations 35, 36 which are engraved or otherwise provided and extend at right angles to one another. These each extend to the respective edge of the recess 25. FIG. 8 shows that the radial projections opposite the graduations 35 and 36 have a surface profile 37 which is complementary to the graduation and may, e.g. be blade-like. This means that after the nut 29 is released the pin 3 can be adjusted stepwise in longitudinal and transverse direction of the bite plate 24, with the steps corresponding to the subdivisions of the graduations 35 and 36. It is clear, of course, that the subdivision of the graduations is not limited to the number of steps which are diagrammatically illustrated in FIGS. 6 and 8 for exemplary purposes only. For example, if the recess 25 has an edge length of 15 millimeters, graduations may be provided with fifteen steps in order to permit an adjustment of the pin 3 in the plane of the bite plate 24 by distances each having the length of a millimeter. The graduations 35 and 36, together with the radial projections 28, constitute anti-turning means which prevent a turning of the threaded sleeve 26 during loosening and tightening of the nut 29.
While the invention has been illustrated and described as embodied in an intra-oral aligning assembly, 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.
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An aligning assembly for prosthodontic applications has an upper jaw plate, a lower jaw plate, and a pin on one of these plates. The pin has a free end shaped as a spherical segment whose surface is curved rearwardly from the tip through at least 100° of arc towards the shaft of the pin. The other jaw plate has an opening and, due to the shape of the spherical-segment surface, the surface will always be in full circumferential contact with the edge of the opening when the plates are brought together, even though skewing of the plates relative to one another should occur.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application claims priority from U.S. Provisional Application No. 61/167,817, filed on Apr. 8, 2009, which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
The present invention relates to the field of enhancement mode gallium nitride (GaN) transistors. More particularly, the invention relates to an enhancement mode GaN transistor with a diffusion barrier.
BACKGROUND OF THE INVENTION
Gallium nitride (GaN) semiconductor devices are increasingly desirable for power semiconductor devices because of their ability to carry large current and support high voltages. Development of these devices has generally been aimed at high power/high frequency applications. Devices fabricated for these types of applications are based on general device structures that exhibit high electron mobility and are referred to variously as heterojunction field effect transistors (HFET), high electron mobility transistors (HEMT), or modulation doped field effect transistors (MODFET). These types of devices can typically withstand high voltages, e.g., 100 Volts, while operating at high frequencies, e.g., 100 kHz-10 GHz.
A GaN HEMT device includes a nitride semiconductor with at least two nitride layers. Different materials formed on the semiconductor or on a buffer layer causes the layers to have different band gaps. The different material in the adjacent nitride layers also causes polarization, which contributes to a conductive two dimensional electron gas (2DEG) region near the junction of the two layers, specifically in the layer with the narrower band gap.
The nitride layers that cause polarization typically include a barrier layer of AlGaN adjacent to a layer of GaN to include the 2DEG, which allows charge to flow through the device. This barrier layer may be doped or undoped. Because the 2DEG region exists under the gate at zero gate bias, most nitride devices are normally on, or depletion mode devices. If the 2DEG region is depleted, i.e. removed, below the gate at zero applied gate bias, the device can be an enhancement mode device. Enhancement mode devices are normally off and are desirable because of the added safety they provide and because they are easier to control with simple, low cost drive circuits. An enhancement mode device requires a positive bias applied at the gate in order to conduct current.
FIG. 1 illustrates a conventional enhancement mode GaN transistor device 100 without a diffusion barrier. Device 100 includes substrate 101 that can be composed of silicon (Si), silicon carbide (SiC), sapphire, or other material, transition layers 102 typically composed of AlN and AlGaN that is about 0.1 to about 1.0 μm in thickness, buffer material 103 typically composed of GaN that is about 0.5 to about 10 μm in thickness, barrier material 104 typically composed of AlGaN where the Al to Ga ratio is about 0.1 to about 0.5 with thickness from about 0.005 to about 0.03 μm, p-type AlGaN 105 , heavily doped p-type GaN 106 , isolation region 107 , passivation region 108 , ohmic contact metals 109 and 110 for the source and drain, typically composed of Ti and Al with a capping metal such as Ni and Au, and gate metal 111 typically composed of a nickel (Ni) and gold (Au) metal contact over a p-type GaN gate.
There are several disadvantages of the conventional enhancement mode GaN transistors shown in FIG. 1 . During growth of the p-type AlGaN 105 (in FIG. 1 , for example) over the undoped GaN 103 or AlGaN 104 , Mg atoms will diffuse back down the crystal into the active region of the device, leading to unintentional doping of layers 104 and 103 . These Mg atoms act as acceptors, taking electrons, and become negatively charged. The negatively charged Mg repels electrons from the 2-dimensional electron gas. This leads to higher threshold voltage under the gate and lower conductivity in the region between the gate and the ohmic contacts. In addition, the charging and discharging of these Mg atoms can lead to time dependent changes in the threshold and conductivity of the device. A second disadvantage of the conventional GaN transistor is the high gate leakage when the transistor is turned on by applying positive voltage to the gate contact. During growth of layer 106 (in FIG. 1 , for example), Mg atoms diffuse to the growth surface. When growth is terminated, a heavily doped layer exists at the surface. When positive bias is applied to the gate contact, a large current is generated due to the high doping at the top of this layer.
It would therefore be desirable to provide a GaN transistor with a diffusion suppression structure which avoids the above-mentioned disadvantages of the prior art.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a cross-sectional view of a conventional enhancement mode GaN transistor device.
FIG. 2 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a first embodiment of the present invention.
FIG. 3 is a schematic representation comparing the aluminum content in conventional GaN transistors and the device of FIG. 2 .
FIG. 4 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a second embodiment of the present invention.
FIG. 5 is a schematic representation comparing the aluminum content in conventional GaN transistors and the device of FIG. 4 .
FIG. 6 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a third embodiment of the present invention.
FIG. 7 is a schematic representation comparing the aluminum content in conventional GaN transistors and the device of FIG. 6 .
FIG. 8 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a fourth embodiment of the present invention.
FIG. 9 is a schematic representation comparing the magnesium content in conventional GaN transistors and the device of FIG. 8 .
FIG. 10 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a fifth embodiment of the present invention.
FIG. 11 is a schematic representation comparing the magnesium content in conventional GaN transistors and the device of FIG. 10 .
FIG. 12 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a sixth embodiment of the present invention.
FIG. 13 is a schematic representation comparing the magnesium content in conventional GaN transistors and the device of FIG. 12 .
FIG. 14 illustrates a cross-sectional view of an enhancement mode GaN transistor device formed according to a seventh embodiment of the present invention.
FIGS. 15A-15D illustrate a method of forming an enhancement mode GaN transistor device according to an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In the following detailed description, reference is made to certain embodiments. These embodiments are described with sufficient detail to enable those skilled in the art to practice them. It is to be understood that other embodiments may be employed and that various structural, logical, and electrical changes may be made.
Embodiments of the invention described herein relate to an enhancement mode GaN transistor with a diffusion barrier that prevents Mg atoms from diffusing through the crystal into the active regions of the device. The embodiments are based on the addition of a diffusion barrier and/or a graded doping profile to reduce or eliminate the diffusion of dopant atoms (e.g., Mg). In one embodiment of the current invention, a thin AlN, or high Al content AlGaN layer is deposited above the primary channel layer to block the back diffusion of Mg into this region. In another embodiment of the invention, a thin AlN or high Al AlGaN layer is deposited within or above the barrier layer. In another embodiment, the Mg doping profile is controlled to reduce the quantity of Mg diffused into or through the barrier layer by adding an undoped region between the p-GaN layer and barrier layer. In yet another embodiment, a doping modification near the gate contact is used either to facilitate ohmic or Schottky contact formation.
Referring to FIG. 2 , a first embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 2 illustrates a cross-sectional view of the device 200 . Device 200 includes substrate 21 composed of Si, SiC, sapphire, or other material, transition layers 22 typically composed of AlN and AlGaN from about 0.1 to about 1.0 μm in thickness, buffer layer 23 typically composed of GaN from about 0.5 to about 10 μm in thickness, channel layer 20 typically composed of GaN or InGaN with a thickness from about 0.01 to about 0.3 μm, barrier layer 27 typically composed of AlGaN where the Al fraction is about 0.1 to about 0.5 with a thickness between about 0.005 and about 0.03 μm, gate structure 26 typically composed of p-type GaN with a refractory metal contact such as Ta, Ti, TiN, W, or WSi 2 . The p-type GaN and refractory metal contact are each between about 0.01 and about 1.0 μm in thickness. Ohmic contact metals 24 , 25 are composed of Ti and Al with a capping metal such as Ni and Au or Ti and TiN. Diffusion barrier 28 is typically composed of AlGaN, where the Al fraction is between about 0.2 and about 1 with a thickness between about 0.001 and about 0.003 μm. The Al fraction is the content of Al such that Al fraction plus Ga fraction equals 1. Buffer layer 23 , barrier layer 27 , and diffusion barrier 28 are made of a III Nitride material. A III Nitride material can be composed of In x Al y Ga 1-x-y N where x+y≦1.
In accordance with the above-described embodiment, a double layer of different Al contents is formed. The structure in FIG. 2 has higher Al content close to the channel layer, and lower Al content near the gate layer. A comparison of Al content between the channel layer and gate layer in a conventional GaN transistor and the structure of FIG. 2 is shown in FIG. 3 . In the structure shown in FIG. 2 , the diffusion barrier layer 28 above the channel layer is high in Al, while the barrier layer 27 is of lower Al content. Although FIG. 3 shows 2 distinct layers of constant Al content, the combination of layer 28 and 27 into a graded Al content layer can also be employed, such that the Al content is graded from high near the channel layer to low near the gate structure. This grading can be done in many fashions, such as linear, multiple steps down, alternating between high and low Al content while gradually decreasing the average Al content, or alternating between high and low Al content while changing the thickness of the high and low Al layers from thicker high Al near the channel to thinner high Al near the gate. The high Al content material blocks diffusion of Mg and confines it to regions above the channel layer. The high Al content layer also leads to high electron mobility. In the structure shown in FIG. 2 , however, diffusion still proceeds into the top barrier layer.
Referring to FIG. 4 , a second embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 4 illustrates a cross-sectional view of the device 300 . FIG. 4 is similar to FIG. 2 , but differs in that diffusion barrier 38 and barrier layer 37 are inverted from their positions in FIG. 2 , thus providing diffusion barrier 38 next to the gate structure 36 . The dimensions and compositions of the various layers are similar to that of the first embodiment.
In accordance with the above-described embodiment, a double layer of different Al contents is provided, with similar advantages as the first embodiment. A comparison of Al content between the channel layer and gate layer in a conventional GaN transistor and the structure of FIG. 4 is shown in FIG. 5 . In the structure shown in FIG. 4 , the barrier layer 37 above the channel layer is low in Al, while the diffusion barrier layer 38 is of higher Al content. The high Al content material blocks diffusion of Mg and confines it to regions above the barrier layers. In the structure shown in FIG. 4 , however, the lower Al content layer does not have the advantage of higher electron mobility possessed by the first embodiment.
Referring to FIG. 6 , a third embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 6 illustrates a cross-sectional view of the device 400 . The third embodiment is essentially a combination of the first and second embodiments described above, and includes two diffusion barrier layers 48 , 49 , one of either side of the barrier layer 47 . The dimensions and compositions of the various layers are similar to that of the first and second embodiments.
This embodiment has the advantages of both the first and second embodiments described above. The structure of FIG. 6 has a triple layer of different Al contents with higher Al content close to the gate layer and higher Al content near the channel layer. A comparison of Al content between the buffer layer and gate layer in a conventional GaN transistor and the structure of FIG. 6 is shown in FIG. 7 . In the structure shown in FIG. 6 , the diffusion layer 49 above the channel layer is high in Al, while the barrier layer 47 is of lower Al content, and the other diffusion layer 48 is again of high Al content. The high Al content material of layer 48 blocks diffusion of Mg, and confines it to regions above the barrier layers. The high Al content material of layer 49 leads to higher electron mobility.
Referring to FIG. 8 , a fourth embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 8 illustrates a cross-sectional view of the device 500 . This embodiment is similar to the first and second embodiments described above, but has a p-type GaN gate with a Mg doping profile and does not have diffusion barrier layers. The gate layer 57 in this embodiment has lower Mg concentration near the barrier layer 54 and higher Mg concentration near the gate contact 58 . Typical values for Mg concentration in gate layer 57 are about 10 16 atoms per cm 3 near the barrier layer, increasing to about 5×10 19 atoms per cm 3 at the gate contact.
In accordance with the above-described embodiment, the Mg doping level of the gate layer 57 is low near the barrier layer 54 , and higher near the gate contact 58 . This is shown in FIG. 9 with comparison to a conventional GaN transistor. The structure in FIG. 8 has higher Mg content close to the gate layer. The Mg concentration level can begin at zero or a low level, e.g., about 10 16 atoms per cm 3 , and then increase towards the gate contact. The shape of the Mg concentration through the p-type GaN gate layer 57 can vary in a number of ways, some of which are shown in FIG. 9 (e.g., a linear graded Mg concentration or a spiked Mg concentration near the gate contact). Included in these are versions in which there is a spacer layer above the barrier that does not contain Mg. Associated with this low Mg region is a doping offset thickness. The structure of FIG. 8 has various advantages. The low Mg concentration near the barrier layer reduces the back diffusion into the barrier layer. Combined with a doping offset, very low unintentional doping of the barrier layers and the buffer layers can be achieved. The high Mg concentration near the gate contact helps create an ohmic contact between the gate contact and p-type GaN that leads to improved device turn on characteristics.
Referring to FIG. 10 , a fifth embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 10 illustrates a cross-sectional view of the device 600 . This embodiment is similar to the fourth embodiment, except that the Mg doping profile of the p-type GaN gate layer 67 is different. The gate layer 67 in this embodiment has a lower Mg concentration near the barrier layer 64 and near the gate contact 68 , with an increased concentration in the middle. Typical values for Mg concentration are about 10 16 atoms per cm 3 near the barrier layer, increasing to about 5×10 19 atoms per cm 3 near the center of the p-GaN gate, and decreasing to about 10 16 atoms per cm 3 near the gate contact.
In accordance with the above-described embodiment, the Mg doping level is low near the barrier layer and higher near the center of the gate. This is shown in FIG. 11 with comparison to a conventional GaN transistor. The shape of the Mg concentration through the p-type GaN layer can vary in a number of ways, some of which are shown in FIG. 11 (e.g., a peaked Mg concentration or a flat topped Mg profile). The structure of FIG. 10 has higher Mg content in the center of the gate layer. The low Mg concentration near the barrier layer reduces the back diffusion into the barrier layer. Combined with a doping offset, very low unintentional doping of barrier, channel, and buffer layers can be achieved. The low Mg concentration near the gate contact allows formation of a Schottky contact between the gate contact and p-type GaN that leads to improved device gate leakage.
A sixth embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 12 illustrates a cross-sectional view of the device 700 . This embodiment is similar to the fifth embodiment, except that n-type doping is provided through addition of Si in gate layer 77 near the gate contact. Typical values for Mg concentration are similar to the fifth embodiment. Si concentration near the gate contact can rage from about 10 15 to about 10 19 atoms per cm 3 .
In accordance with the above-described embodiment, the Mg doping level is low near the barrier layer and higher near the center of the gate. Si atoms are added near the gate contact. This is shown in FIG. 13 with comparison to a conventional GaN transistor. The low Mg concentration near the barrier layer reduces the back diffusion into the barrier layer. Combined with a doping offset, very low unintentional doping of barrier, channel, and buffer layers can be achieved. The low Mg concentration near the gate contact results in a low hole density. The hole density is further reduced by the addition of Si atoms. Part A of FIG. 13 illustrates the addition of Si atoms to reduce the density of holes. The density of Si atoms is less than or equal to the density of Mg atoms. This very low hole density improves the formation of a Schottky contact. Further increasing the Si content beyond the level of Mg, results in a p-n junction. Part B of FIG. 13 illustrates the addition of Si atoms far beyond the density of Mg atoms near the gate contact. This results in a p-n junction within the gate structure and can lead to further reduction in gate leakage.
A seventh embodiment is now described with reference to the formation of an enhancement mode GaN transistor. FIG. 14 illustrates a cross-sectional view of the device 800 . This embodiment is similar to the fifth and sixth embodiments, except that region 89 , composed of a portion of the spacer layer, remains above the barrier layer in the region outside the gate region. Typical values of layer 89 thickness are about 0% to about 80% of the spacer layer thickness.
An additional advantage of the low doped or undoped layer is a reduction in damage from manufacturing, and an improvement in manufacturing tolerances. Referring to FIGS. 15A-15D , the steps in fabrication consist of: (a) deposition of AlN and AlGaN transition layers 82 on substrate 81 , GaN buffer layer 83 , channel layer 80 , barrier layer 84 , p-GaN layer 87 , and gate contact material 88 ; (b) etching of the gate contact and most of the p-GaN layer 87 leaving a small amount of material 89 ; (c) passivation of the surface through deposition of an insulating material such as SiN 90 ; and (d) etching open contact area and depositing ohmic contact material to form source 86 and drain 85 . The advantage is achieved in step (b). During the etch of p-GaN, the etching is stopped before reaching the barrier layer. This is done to avoid causing damage to this sensitive material that can result in high resistivity in the channel layer, and trapping of charge at the SiN interface. Without use of the low doped spacer layer, layer 89 is composed of p-GaN. This leads to negative charge in layer 89 that repels electrons from the channel layer and increases resistance to current flow when the device is on. The use of an undoped spacer layer allows the etching of step (b) to terminate above the barrier layer, thus avoiding damage, without leaving highly doped material that is detrimental to resistance of the channel layer. The spacer layer may be grown at a very high temperature (around 1000° C. to around 1100° C.), grown at around 900° C. with high ammonia, and/or grown very slowly.
The above description and drawings are only to be considered illustrative of specific embodiments, which achieve the features and advantages described herein. Modifications and substitutions to specific process conditions can be made. Accordingly, the embodiments of the invention are not considered as being limited by the foregoing description and drawings.
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An enhancement-mode GaN transistor, the transistor having a substrate, transition layers, a buffer layer comprised of a III Nitride material, a barrier layer comprised of a III Nitride material, drain and source contacts, a gate containing acceptor type dopant elements, and a diffusion barrier comprised of a III Nitride material between the gate and the buffer layer.
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FIELD OF THE INVENTION
The present invention relates generally to the field of exterior building surfaces. More particularly, the present invention relates to a system for custom fitting siding panels which uses individual trim bands to conceal siding edges or terminations while still allowing the system and siding panels to float on the house.
DESCRIPTION OF THE PRIOR ART
The use of aluminum, vinyl, and steel siding panels on the exterior surface of buildings has become more commonplace due to the increased economy of such panels resulting from increased durability and decreased maintenance. Several starter strips, support strips, and cover strips which are designed for use with siding panels are known in the prior art. For example, U.S. Pat. No. 3,139,703 to Hilt discloses a sheet metal cover for window and door frames to be used in connection with the installation of siding. The cover comprises a metal band which is bent to form a channel for holding and concealing the edges of siding which surround the perimeter of a door or window frame on a house. Although the Hilt cover piece may be used in the present inventive system, the inventive system is an improvement over the Hilt cover piece in that it provides for a complete custom trim system for the edges of all existing siding panels which are attached to a house.
U.S. Pat. No. 4,292,781 to Chalmers et al. describes a siding system with support strips that are nailed to the house which function to support the siding panels. The support strips include both retainer strips and starter strips. The retainer strip comprises a horizontally extending mounting leg and a horizontally extending hook which depends from the leg and forms an inwardly and upwardly opening channel for engaging and holding edge portions of siding panels. The starter strip comprises a horizontally extending longitudinally upwardly opening channel flange that extends from a horizontally extending longitudinal upwardly projecting leg. A plurality of nail holes are spaced along an upper length of the retainer strip hook and the starter strip leg for attaching the strips to a building.
Another piece designed for use with mounting siding panels is disclosed in U.S. Pat. No. 4,947,609 to Champagne. The Champagne patent describes a clip for installing the top out panel of vinyl siding. The clip comprises a continuous strip of metal having seven contiguous portions which define two vertically spaced downwardly opening gripping channels. The gripping channels engage the overlying top edge of a bottom siding panel and the bottom edge of a top out siding panel, respectively.
The Port-O-Bender Operations Manual produced by Tapco Products Co., Inc. discloses a machine for bending sheet metal into desired trim shapes and designs. Several common trim shapes are disclosed which can be custom made on the job site with built in "J" channels or hemmed edges.
U.S. Pat. No. 2,309,453 to Hasenburger et al. discloses a prefabricated building wall which includes a bottom support sill and panel locking clips that ride in vertical frames. The bottom support sill includes longitudinally extending sections and lower strip portions which extend from the sections. The lower strip portion positioned on the outer side of the sill comprises an upwardly extending rib which functions as an attachment means for a siding panel.
Strip configurations for starting and retaining roof and wall tiles are also disclosed in the prior art. U.S. Pat. No. 4,418,505 to Thompson describes a starter strip for laying tile roofs. The starter strip includes a base portion which is supported by the roof structure, a cover portion which extends downwardly from a front edge of the base portion to overlie an exposed portion of the roof, and a riser portion which extends upwardly from the front end of the base portion.
U.S. Pat. No. 2,245,785 to Jentzer et al. discloses a wall covering system which includes metal stamped wall tiles and a series of retaining strips to secure the tiles in place. The tile retaining strips are bent from sheet metal and constitute a base plate, a web extending from the base plate, and oppositely disposed rails which extend from the web and hook into the tiles.
Another U.S. patent to Epstein et al., U.S. Pat. No. 4,015,391, discloses a simulated cedar shake construction which includes bottom starter strips, top or gable strips, corners, and ridge caps. The bottom starter strip contains a nailing strip and a U-shaped channel. The bottom edges of the lower most shakes are fitted into the U-shaped channel. The gable strip comprises a U-shaped channel wherein one leg of the "U" contains an inward bend directed toward the other leg of the "U", and a nailing tab which extends from the bent leg.
In summary, there are a number of strip members which are designed to start, retain, support, and cover the siding panels which are used in siding a building or home. However, no complete system is disclosed for custom fitting siding panels such that the siding panel edges on an entire surface of a home or building structure are internally concealed without the use of "J" type channels and underlying support structures. Furthermore, no trim components are disclosed without standard "J" type channels which function as base bands, frieze bands, mid bands, or inside corners on a structure.
Accordingly, there is a need for an improved system and associated trim bands which function to accentuate the length, height, bulk, weight, and overall aesthetic effect of a building by providing a channel free siding system. There is also a need for an improved trim system containing trim bands for siding panels which is capable of being custom fit to any type of building.
SUMMARY OF THE INVENTION
It is a principal object of the present invention to provide trim bands and a trim band system for custom fitting siding panels on a building or home.
It is a further object of the present invention to provide trim bands which simulate the length, height, bulk and weight of painted trim boards, and a trim band system for custom fitting siding which enhances the overall aesthetic effect of a building or home.
It is a still further object of the present invention to provide a system for custom fitting siding that includes trim bands having furrows which internally conceal the edges of the siding thereby eliminating the cluttered look of using standard "J" type channels.
It is yet a further object of the present invention to provide trim bands and a trim band system for custom fitting siding which accommodates the moving or shifting of a structure over time by floating the trim band system and siding on the surface of the structure.
It is still a further object of the present invention to provide trim bands and a trim band system which do not require an underlying support structure.
The inventive trim bands contained in the trim band system of the present invention include a base band, a frieze band, a mid band, and an inside corner band. The base band is a generally a one-piece member having five continuous horizontally elongated planar portions which include a first vertical portion, a first horizontal portion extending from the first vertical portion to form a ledge, a second vertical portion extending downwardly from the ledge, a second horizontal portion extending from the back of the second vertical portion, and a third vertical portion extending upwardly from the second horizontal portion.
The frieze band of the present invention is generally a one-piece member having six continuous horizontally elongated planar portions which include a first vertical portion, a first horizontal portion extending outwardly from the front surface of the first vertical portion, a second vertical portion extending downwardly from the first horizontal portion, a third vertical portion extending upwardly from and back against the second vertical planar portion, a second horizontal portion extending back and outwardly from the third vertical portion, and a fourth vertical portion extending downwardly from the second horizontal portion.
The mid band of the present invention generally defines a one-piece member having seven continuous horizontally elongated planar portions including a first vertical portion, a first horizontal portion extending outwardly from the front surface of the first vertical portion, a second vertical portion extending upwardly from the first horizontal portion, a third vertical portion extending downwardly from and back against the front surface of the second vertical portion, a fourth vertical portion extending upwardly from and back against the back surface of the third vertical portion, a second horizontal portion extending outwardly from the back surface of the fourth vertical portion, and a fifth vertical portion extending downwardly from the second horizontal portion.
The inside corner band of the present invention is generally a one-piece member having eight continuous vertically elongated vertical planar portions including a first portion, a second portion extending outwardly at a right angle from the front surface of the first portion, a third portion extending outwardly at a right angle from the front surface of the second portion, a fourth portion extending back against and adjacent to the front surface of the third portion, a fifth portion extending outwardly at a right angle from the front surface of the fourth portion, a sixth portion extending back against and adjacent to the back surface of the fifth portion, a seventh portion extending outwardly at a right angle from the back surface of the sixth portion, and an eighth portion extending outwardly at a right angle from the front surface of the seventh portion.
The trim band system of the present invention for custom fitting siding panels includes the steps of fastening a plurality of trim bands to the exterior surface of a building and securing a plurality of siding panels to the exterior building surface so that all of the exposed edges of the siding panels are concealed within the trim bands.
The objects and advantages of the invention will appear more fully from the following more detailed description of the preferred embodiments of the invention made in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the base band which comprises one of the trim bands of the present invention.
FIG. 2 is a side elevational view of the base band of the present invention.
FIG. 2A is a side elevational view showing the attachment of the base band to an external building surface and the placement of the siding panels in conjunction with the base band.
FIG. 3 is a perspective view of the frieze band which comprises one of the trim bands of the present invention.
FIG. 4 is a side elevational view of the frieze band of the present invention.
FIG. 5 is a perspective view of the mid band which comprises one of the trim bands of the present invention.
FIG. 6 is a side elevational view of the mid band of the present invention.
FIG. 7 is a perspective view of the inside corner band which comprises one of the trim bands of the present invention.
FIG. 8 is a top elevational view of the inside corner band of the present invention.
FIG. 9 is a perspective view of part of the trim band system of the present invention showing the fitting of siding panels within the frieze band, base band, and inside corner band of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides unique trim bands and a trim band system for custom fitting siding panels to the exterior surface of a building to produce what appears to be a channelless siding system. Referring now to the figures, where numerals represent various elements of the present invention, the unique trim bands of the present invention are shown in FIGS. 1-8.
FIG. 1 illustrates a perspective view of the base band 10 of the present invention. The base band 10 generally comprises a one-piece member having at least five continuous portions which include a first horizontally elongated vertical planar portion 12, a first horizontally elongated horizontal planar portion 14, a second horizontally elongated vertical planar portion 16, a second horizontally elongated horizontal planar portion 18, and a third horizontally elongated vertical planar portion 20. A horizontally elongated lip member 22 may also be provided between the first horizontal portion 14 and the second vertical portion 16.
The relationship of the continuous portions can be seen more clearly in FIG. 2 which depicts a side elevational view of the base band 10. The first vertical portion 12 comprises a first front surface 24 and a second back surface 26. The first horizontal portion 14 extends outwardly from the first front surface 24 of the first vertical portion 12 to form a ledge. The ledge may further comprise the lip member 22 which constitutes another continuous horizontally extending vertical planar member having a first front surface 28 and a second back surface 30.
The second vertical portion 16 also comprises a first front surface 32 and a second back surface 34. The second vertical portion 16 extends from the lip member 22 such that the second back surface 34 of the second vertical portion 16 is folded back against and lies adjacent to the first front surface 28 of the lip member 22. If no lip member 22 is present, then the second vertical portion 16 extends downwardly from the first horizontal portion 14.
The second horizontal portion 18 extends from the second back surface 34 of the second vertical portion 16 while the third vertical portion 20 extends upwardly from the second horizontal portion 18 to form a channel 35. The third vertical portion 20 comprises a first front surface 36 and a second back surface 38.
The base band 10 is shown mounted to an exterior surface of a building 40 with a lower most siding panel 42 in FIG. 2A. A starter clip 44 is attached to the exterior building surface 48 by nails 46, screws, or other similar attachment means. The base band 10 is secured to the exterior building surface 48 by attaching the first vertical portion 12 of the base band 10 to the exterior building surface 40 by nails 46 or other similar attachment means, and then hooking the channel 35 formed at the bottom of the base band 10 around the starter clip 44.
Once the base band 10 is secured to the exterior building surface 40, the lower most siding panel 42 is positioned over the first vertical portion 12 of the base band 10 just above the first horizontal portion 14 of the base band 10. The lower most siding panel is then attached to the exterior building surface 48 near its top end 48 so that the next siding panel 49 can be positioned over the attachment point of the lower most siding panel 42.
Turning now to FIG. 3, there is shown a perspective view of the frieze band 50 of the present invention. The frieze band 50 generally comprises a one piece member having at least six horizontally elongated continuous planar portions which include a first vertical portion 52, a first horizontal portion 54, a second vertical portion 56, a third vertical portion 58, a second horizontal portion 60, and a fourth vertical portion 62. The frieze band 50 may also include a horizontally elongated third horizontal planar portion 64 having a first upper surface 66 and a second lower surface 68 where the third horizontal member 64 extends from the first vertical portion 52 of the frieze band 50.
The contiguous connection of the various portions comprising the frieze band 50 is illustrated in the side elevational view of the frieze band 50 shown in FIG. 4. The first vertical portion 52 extends from the second lower surface 68 of the optional horizontally elongated third horizontal planar portion 64. The first vertical portion 52 comprises a first front surface 70 and a second back surface 72. The first horizontal portion 54 extends from the first front surface 70 of the first vertical portion 52 to form a channel 74 for receiving a soffit.
The second vertical portion 56 extends downwardly from the first horizontal portion 54 and comprises a first front surface 76 and a second back surface 78. The third vertical portion 58 also has a first front surface 80 and a second back surface 82. The second back surface 82 of the third vertical portion 58 is folded back against and lies adjacent to the second back surface 78 of the second vertical portion 56.
The second horizontal portion 60 extends from the first front surface 80 of the third vertical portion 58 and the fourth vertical portion 62 extends downwardly from the second horizontal portion 60 thereby forming a second channel 84. The fourth vertical portion 62 comprises a first front surface 86 and a second back surface 88. During actual use, a top portion of an upper most siding panel is positioned within the second channel 84 and adjacent to the first front surface 86 of the fourth vertical portion 62 of the frieze band 50.
A perspective view of the mid band 90 of the present invention is shown in FIG. 5. The mid band 90 generally comprises a continuous one piece member having at least seven horizontally elongated contiguous planar portions which include a first vertical portion 92, a first horizontal portion 94, a second vertical portion 96, a third vertical portion 98, a fourth vertical portion 100, a second horizontal portion 102, and a fifth vertical portion 104.
FIG. 6 illustrates the contiguous connection of the portions which comprise the continuous one piece mid band 90. The first vertical portion comprises a first front surface 106 and a second back surface 108. The first horizontal portion 94 extends outwardly from the first front surface 106 of the first vertical portion 92 and the second vertical portion 96 extends upwardly from the first horizontal portion 94 to form a first channel 110.
The second vertical portion 96 comprises a first front surface 112 and a second back surface 114 and the third vertical portion 98 comprises a first front surface 116 and a second back surface 118. The first front surface 112 of the second vertical portion 96 is folded back against and adjacent to the second back surface 118 of the third vertical portion 98. The fourth vertical portion 100 also comprises a first front surface 120 and a second back surface 122 with the second back surface 122 being folded against and positioned adjacent to the second back surface 118 of the third vertical portion 98.
The second horizontal portion 102 extends outwardly from the first front surface 120 of the fourth vertical portion 100 and the fifth vertical portion 104 extends downwardly from the fourth vertical portion 100 to form a second channel 124. During use, the mid band 90 is placed on a mid portion of the exterior surface of a building and siding panels are positioned within the first and second channels 110, 124 such that a bottom portion of a siding panel is placed within the first channel 110 and a top portion of a siding panel is placed in the second channel 124. Once the siding panels are positioned and secured, the first and second channels 110, 124 are not visible.
FIG. 7 shows a perspective view of the inside corner band 126 of the present invention. The inside corner band 126 generally comprises a one piece member having at least eight vertically elongated continuous planar portions which include a first portion 128 having a first front surface 130 and a second back surface 132, a second portion 134 having a first front surface 136 and a second back surface 138, a third portion 140 having a first front surface 142 and a second back surface 144, a fourth portion 146 having a first front surface 148 and a second back surface 150, a fifth portion 152 having a first front surface 154 and a second back surface 156, a sixth portion 158 having a first front surface 160 and a second back surface 162, a seventh portion 164 having a first front surface 166 and a second back surface 168, and an eighth portion 170 having a first front surface 172 and a second back surface 174.
As illustrated in FIG. 5, which shows a top elevational view of the inside corner band 126, the second portion 134 extends from the first front surface 130 of the first portion 130 at a right angle to the first portion 130. The third portion 140 extends at a right angle form the first front surface 136 of the second portion 134 to form a first channel 176 for retaining the side edges of siding panels (See FIG. 9).
The second back surface 150 of the fourth portion 146 is bent back against and positioned adjacent to the first front surface 142 of the third portion 140. The fifth portion 152 extends outwardly at a right angle from the first front surface 148 of the fourth portion 146, and the first front surface 160 of the sixth portion 158 is bent back against and positioned adjacent to the second back surface 156 of the fifth portion 152.
The seventh portion 164 extends outwardly at a right angle from the second back surface 162 of the sixth portion 158 and the eighth portion 170 extends outwardly at a right angle to the first front surface 166 of the seventh portion 164 to form a second channel 178. The second channel 178 functions to retain the side edges of siding panels in the same way as the first channel 176.
FIG. 9 shows a perspective view of a portion of the trim band system in use. As previously described, siding panels 180 are positioned within the base band 10, frieze band 50, and inside corner band 126 to provide a trim and siding system which appear to be channelless.
The trim bands of the present invention are preferably comprised of bent sheet metal, extruded plastic, or extruded vinyl.
While preferred embodiments of the invention have been shown and described, it will be apparent to those skilled in this art that various modifications may be made in these embodiments without departing from the spirit of the present invention. Therefore, all suitable modifications and equivalents fall within the scope of the invention.
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Trim bands and a trim band system for custom fitting siding is presented. The trim bands include a base band, a frieze band, a mid band, and an inside corner band which function to retain the rough edges of siding panels without exposing channels thereby providing a custom fit and enhanced aesthetic appearance. The trim bands are one piece continuous members which comprise varying numbers of portions which depend on the structural area of the building for which the trim bands are designed. The trim band system includes securing a plurality of trim bands to the exterior surface of a building followed by the placement and attachment of siding panels in conjunction with the trim bands to conceal all exposed edges of the siding panels without exposing channels or troughs formed within the trim bands.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 11/186,587 filed on Jul. 21, 2005, which is a continuation of U.S. application Ser. No. 10/205,513, now U.S. Pat. No. 6,951,536, which claims benefit of Japanese Applications Nos. 2001-229952 filed on Jul. 30, 2001 and 2001-333125 filed on Oct. 30, 2001, the contents of each of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a capsule-type medical device and medical system for conducting, for example, examinations in somatic cavities with a capsule body incorporating an image pickup device.
[0004] 2. Description of the Related Art
[0005] Capsule-type endoscopes, which are used to conduct, for example, examinations by inserting a capsule body shaped as a capsule into somatic cavities and lumens of human being or animals have recently been suggested.
[0006] For example, the endoscope disclosed in Japanese Patent Application Laid-open No. H7-111985 comprises a spherical capsule whose shape was split in two.
[0007] However, within the framework of such conventional technology, the two capsules were almost of the same size. Therefore, ability of advancing and easiness of swallowing were not sufficiently improved.
[0008] Further, endoscopes have recently come into wide use in medical and industrial fields. For example, in case of endoscopic examinations in somatic cavity, an insertion member has to be inserted and the patient's pain is increased. A conventional example of a capsule-type endoscope shaped as a capsule to resolve this problem was disclosed in Japanese Patent Application Laid-open No. 2001-95755.
[0009] However, because capsule-type endoscopes capture images while executing unidirectional movement in lumen portions in the body by utilizing peristalsis inside the body, in the conventional example, the images of the entire inner wall of lumen are difficult to be captured without a miss.
[0010] On the other hand, Japanese Patent Application Laid-open No. 2000-342526 discloses an endoscope in which illumination and observations means are provided on the front and back ends of a long cylindrical member.
[0011] In this case, observations can be conducted with two observation means with different observation directions. Therefore, the drawbacks of the above-described conventional examples can be overcome or eliminated. However, the problem is that because of a long cylindrical shape, the endoscope is difficult to move smoothly through curved portions and the significant patient's pain is increased.
SUMMARY OF THE INVENTION
[0012] Accordingly, a capsule-type medical device, which is advanced through a digestive tract of a human being or animal for conducting an examination, therapy, or treatment is provided. The capsule-type medical device comprising: a plurality of capsule bodies; a soft linking unit which links the plurality of capsule bodies and has an outer diameter less than that of any of the capsule bodies; and a joining member which joins two or more of the plurality of capsule bodies in a prescribed position.
[0013] Also provided is a method for examination, therapy, or treatment of the digestive tract of a human being by using a capsule-type medical device comprising a plurality of capsule bodies. The method comprising: swallowing the capsule-type medical device in a linear shape; advancing the capsule-type medical device entirely through the narrow lumen portion of the digestive tract; and joining at least two of the plurality of capsule bodies in the prescribed position at a predetermined portion of the digestive tract.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 illustrates the capsule-type endoscopic system of the first embodiment of the present invention;
[0015] FIG. 2 is a sectional view illustrating the structure of the capsule-type endoscope of the first embodiment;
[0016] FIG. 3 illustrates the capsule-type endoscope of the first embodiment, which moves from the stomach into the duodenum;
[0017] FIG. 4 illustrates the structure and functions of the illumination device and observation device component of the first embodiment;
[0018] FIG. 5 illustrates a part of the structure shown in FIG. 4 ;
[0019] FIG. 6 is a sectional view illustrating the structure of a part of the capsule-type endoscope which is a modification example of the first embodiment;
[0020] FIG. 7 is a sectional view illustrating the structure of the capsule-type endoscope of the second embodiment of the present invention;
[0021] FIG. 8 illustrates the state of examining the inside of a somatic cavity with the capsule-type endoscope of the second embodiment;
[0022] FIG. 9 illustrates the state of recovering the endoscope with a recovery tool when the endoscope is blocked in an isthmus;
[0023] FIG. 10 is a sectional view illustrating the first capsule portion in the modification example of the second embodiment;
[0024] FIG. 11 is a perspective view, with a partial cut-out, of the structure of the capsule-type medical device of the third embodiment of the present invention;
[0025] FIG. 12 is a sectional view illustrating the configuration of the main components of the capsule-type medical device of the first modification example of the third embodiment of the present invention;
[0026] FIG. 13 illustrates the configuration of the main components of the capsule-type medical device of the second modification example of the third embodiment of the present invention;
[0027] FIG. 14 illustrates the external appearance of the capsule-type endoscope of the fourth embodiment of the present invention;
[0028] FIG. 15 illustrates the internal structure of one capsule body of the fourth embodiment of the present invention;
[0029] FIG. 16A and FIG. 16B explain the operation in the usage state of the capsule-type endoscope of the fourth embodiment;
[0030] FIGS. 17A to 17 D illustrate the sequence of operations in conducting the endoscopic examination according to the fourth embodiment;
[0031] FIG. 18 is a block-diagram illustrating the configuration of the electric system of the external unit and display system of the fourth embodiment;
[0032] FIG. 19 is a block-diagram illustrating a modification example of the configuration of the external unit of the fourth embodiment;
[0033] FIGS. 20A to 20 F are timing charts of illumination and image capturing conducted when the external unit shown in FIG. 19 was used;
[0034] FIG. 21 illustrates a modification example of the antenna configuration of the fourth embodiment;
[0035] FIG. 22 is a perspective view illustrating a part of the capsule-type endoscope of the first modification example of the fourth embodiment;
[0036] FIG. 23 illustrates the state in which the cover of capsule-type endoscope shown in FIG. 22 was removed and the capsule body is installed in a rewriting device;
[0037] FIG. 24 illustrates the internal structure of the capsule body shown in FIG. 22 ;
[0038] FIG. 25 illustrates the internal structure of the capsule body in the second modification example of the fourth embodiment;
[0039] FIG. 26 schematically illustrates the capsule-type endoscope of the fifth embodiment of the present invention;
[0040] FIG. 27 schematically illustrates the capsule-type endoscope of the first modification example of the fifth embodiment of the present invention;
[0041] FIG. 28 schematically illustrates the capsule-type endoscope of the second modification example of the fifth embodiment of the present invention;
[0042] FIG. 29 illustrates a part of internal configuration of the capsule-type endoscope of the sixth embodiment of the present invention;
[0043] FIG. 30A and FIG. 30B are timing charts for explaining the operation of controlling the intensity of light emission by an external signal, according to the sixth embodiment of the present invention;
[0044] FIG. 31 explains a part of configuration of the capsule-type endoscope of the seventh embodiment of the present invention;
[0045] FIG. 32 illustrates a part of configuration of the capsule-type endoscope of the modification example of the seventh embodiment of the present invention;
[0046] FIG. 33 illustrates the structure of the antenna of the external unit of the eighth embodiment of the present invention;
[0047] FIG. 34 illustrates the structure of the antenna of the first modification of the eighth embodiment of the present invention;
[0048] FIG. 35 illustrates the structure of the antenna of the second modification of the eighth embodiment of the present invention;
[0049] FIG. 36A and FIG. 36B explain the structure of the capsule-type endoscopic system of the ninth embodiment of the present invention;
[0050] FIG. 37 illustrates the structure of the capsule-type endoscope of the tenth embodiment of the present invention;
[0051] FIG. 38 explains endoscopic examination of the tenth embodiment of the present invention;
[0052] FIG. 39A and FIG. 39B explain the structure of the capsule-type endoscope of the first modification of the tenth embodiment of the present invention;
[0053] FIG. 40A and FIG. 40B explain the structure of the capsule-type endoscope of the second modification of the tenth embodiment of the present invention;
[0054] FIG. 41 illustrates the structure of the capsule-type endoscope of the third modification of the tenth embodiment of the present invention; and
[0055] FIG. 42 explains the operation in a state in which two capsule bodies of the capsule-type endoscope of the third modification of the tenth embodiment of the present invention are combined.
[0056] The above and other objects, features and advantages of the invention will become more clearly understood from the following description referring to the accompanying drawings.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0057] The embodiments of the present invention will be explained hereinbelow with reference to the accompanying drawings.
First Embodiment
[0058] FIGS. 1 to 6 illustrate the first embodiment of the present invention. FIG. 1 illustrates the structure of the capsule-type endoscopic system of the first embodiment. FIG. 2 illustrates the internal structure of the capsule-type endoscope of the first embodiment. FIG. 3 illustrate an example of utilization relating to the movement from the stomach to the duodenum. FIG. 4 illustrates the structure and functions of the illumination device and observation device components. FIG. 5 illustrates a part of the structure shown in FIG. 4 . FIG. 6 illustrates the structure of a part of the capsule-type endoscope which is a modification example.
[0059] As shown in FIG. 1 , a capsule-type endoscopic system 1 of the first embodiment of the capsule-type medical device of the present invention is composed of a capsule-type endoscope 3 of the first embodiment, which is swallowed by a patient 2 and used for examination inside the somatic cavities, an external unit 5 disposed outside the body of patient 2 and equipped with an antenna 4 for wireless reception of image information picked up by the capsule-type endoscope 3 , and a personal computer (abbreviated as PC hereinbelow) 7 capable of taking in the images accumulated in the external unit 5 and displaying them on a monitor 6 by virtue of detachable connection of the external unit 5 . The PC 7 is composed by connecting a keyboard 9 for data input and the monitor 6 to a PC body 8 and is detachably connected to the external unit 5 with an USB cable 10 or the like.
[0060] FIG. 2 illustrates the internal structure of the capsule-type endoscope 3 of the first embodiment.
[0061] The capsule-type endoscope 3 comprises a first capsule 11 a and a second capsule 11 b as two capsule-like hard units of different diameters and a soft flexible tube 12 connecting the capsules and having a diameter less than the diameter of the two capsules 11 a , 11 b , and has a structure in which the two capsules 11 a , 11 b are connected by the tube.
[0062] In the first capsule 11 a , the cylindrical peripheral portion of a hard capsule frame 13 is water-tight sealed with a dome-like hard transparent cover 15 via a seal member 14 , this cover also covering the opening of capsule frame 13 . An image pickup device and an illumination device are housed inside the first capsule.
[0063] An objective lens 16 constituting the image pickup device (observation device) is mounted on a light-shielding lens frame 17 and disposed opposite the transparent cover 15 in the central portion of the internal space covered with the dome-like transparent cover 15 . An image pickup element, for example, a CMOS image pickup device 18 is disposed in the image forming position of the objective lens.
[0064] Furthermore, for example, white LEDs 19 are disposed as illumination devices in a plurality of places around the lens frame 17 , and the light emitted by the white LEDs 19 passes through the transparent cover 15 and illuminates the space outside thereof. Moreover, a drive circuit 20 for driving and inducing the emission of light by the white LEDs 19 and for driving the CMOS image pickup device 18 , and a controller 21 for controlling this drive circuit 20 and provided with a function of conducting signal processing with respect to the output signals of CMOS image pickup device 18 are disposed on the rear surface side of CMOS image pickup device 18 . The drive circuit and the controller are secured to the capsule frame 13 .
[0065] Further, a connection socket 22 for connecting and securing one end of tube 12 is provided in the center of the end surface (back end surface) of capsule frame 13 on the side thereof opposite the transparent cover 15 . One end of tube 12 is water-tightly connected and secured to the connection socket.
[0066] Moreover, one end of an electric cable 23 which is an electric connection member advanced the inside of the tube 12 is connected to the controller 21 , and the other end thereof is connected to the second capsule 11 b . The tube 12 is formed from a flexible tube made from polyurethane, poly(vinyl chloride), silicone, and the like.
[0067] The length of tube 12 linking the first capsule 11 a and the second capsule 11 b is almost equal to, or greater than the length of the smaller first capsule 11 a.
[0068] The electric cable 23 is curled, laid in a zigzag manner, or spirally wound inside the tube 12 so that practically no tension is applied to the electric cable 23 even when the shape of tube 12 is changed.
[0069] In the second capsule 11 b which is larger in size than the first capsule 11 a , the open end side of capsule frame 24 , which is a battery housing provided with a function of battery housing means, is detachably covered with a battery housing lid 26 , for example, via a seal member 25 inserted in the cylindrical surface part thereof. The external part of the battery housing lid 26 is covered with an elastic resin cover 28 , which serves as a protective cover, to a proximity of a connection socket 27 of tube 12 in the capsule frame 24 . The elastic resin cover 28 can be put on or taken off by using an elastic force thereof.
[0070] A battery 29 , for example, a button-type battery, a transmission-receiving, circuit 30 , and an antenna 31 are enclosed in the capsule frame 24 . The transmission-receiving circuit 30 is electrically connected to the controller 21 , generates the signals which are to be transmitted, and demodulates the received signals. The antenna 31 is connected to the transmission-receiving circuit 30 and sends the image information picked up by the CMOS image pickup device 18 to the external unit 5 or receives control signals radio transmitted from the external unit 5 .
[0071] The battery 29 serving as a power supply is connected so as to supply a drive power to the transmission-receiving circuit 29 , controller 21 , and drive circuit 20 .
[0072] An external thread 32 is provided on the cylindrical side surface portion of the second capsule 11 b , and an internal thread for engaging with the external thread 32 is provided on the inner peripheral surface of battery housing lid 26 . Furthermore, a circular groove is provided on the cylindrical side surface portion of the second capsule 11 b , and a seal member 25 for waterproofing, for example, such as an O-ring, is housed therein, thereby water-tightly sealing the inside of the capsule between the seal member and the battery housing lid 26 which is brought in contact therewith under pressure.
[0073] Furthermore, the other end of tube 12 is water-tightly secured, for example, with an adhesive to the connection socket 27 located in the central portion of capsule frame 24 on the side opposite the battery housing lid 26 .
[0074] Moreover, the external unit 5 receives signals from the capsule-type endoscope 3 with the antenna 4 , and the image demodulated by an internal signal processing circuit (not shown in the figure) is displayed on a liquid-crystal monitor 5 a provided in the external unit 5 and also compressed and stored in the internal nonvolatile memory or a small hard disk or the like.
[0075] A control member 5 b is provided in the external unit 5 . By operating the control member 5 b , it is possible to send a control signal in the form of electromagnetic wave from the antenna 4 , and if the capsule-type endoscope 3 receives this control signal, the controller 21 can vary the illumination interval of illumination device and the image capturing period of the image pickup device.
[0076] For example, the capsule-type endoscope 3 usually conducts one cycle of illumination and image pickup within 2 seconds, but if control signals are once received with a short interval, one cycle of illumination and image pickup is conducted within 1 second. If the control signals with a short interval are received twice in a row, two cycles of illumination and image pickup are conducted within 1 second. Furthermore, if a cancel control signal is sent, the capsule-type endoscope 3 returns to the usual illumination and image pickup period.
[0077] Furthermore, connecting the external unit 5 to PC 7 upon completion of endoscopic examination with the capsule-type endoscope 3 makes it possible to load the image data accumulated by the external unit 5 into the PC 7 and to display them with the monitor 6 .
[0078] In the capsule-type endoscope 3 of such a configuration, the two capsules 11 a , 11 b one of which is smaller than the other are linked by a flexible tube 12 , and the image pickup device and illumination device are housed in the first capsule 11 a . Furthermore, the battery 29 serving as a power supply and the antenna 31 are housed in the larger second capsule 11 b , electric power is supplied to the image pickup device and illumination device via the electric cable 23 is passed through the inside of the tube 12 , and the image signals picked up by the image pickup device are transmitted to the outside from the antenna 31 .
[0079] In this case, making one of the capsules 11 a , 11 b smaller than the other facilitates swallowing and makes advancing easier. Furthermore, housing the illumination device and image pickup device on the front end side, namely on the end side opposite to the one connected with the tube 12 , of the smaller first capsule 11 a and illuminating zones ahead in the movement direction of capsule-type endoscope 3 allows to pick up images of the illuminated somatic cavities.
[0080] Furthermore, the rear side of the smaller first capsule 11 a is corner cut and a chamfer 34 is provided so as to obtain an inclined or spherical surface. Thus, the periphery of the surface connected to the tube 12 which is a soft part linking the hard units is chamfered to obtain a spherical or inclined shape.
[0081] The outer periphery of the front portion of the larger second capsule 11 b , which is connected by the tube 12 , is also provided with a chamfer 35 to obtain an inclined or spherical shape improving the advancing ability. The chamfer 35 is made larger than the chamfer 34 on the back end side of the first capsule 11 a to permit unobstructed passage.
[0082] Further, the electric cable 23 is made longer than the tube 12 to follow the deformation of flexible tube 12 .
[0083] The length of tube 12 is equal to or greater than the length of the smaller first capsule 11 a . Thus, providing a length exceeding the fixed value makes it easier to swallow the endoscope. When the length of tube 12 is within a range from the length almost equal to that of the smaller first capsule 11 a to the length twice that, twisting or knotting of the soft linking unit is prevented.
[0084] In case of endoscopic examination of patient 2 who swallows the capsule-type endoscope 3 of the above-described embodiment, as shown in FIG. 1 , making the two capsules 11 a , 11 b different in size allows them to be smoothly and easily swallowed, when the endoscope is swallowed with the smaller end forward, and also permits the movement direction to be controlled, as shown in FIG. 3 .
[0085] As shown in FIG. 3 , when the capsule-type endoscope 3 advances from a stomach 36 , through a pylorus 37 , to a duodenum 38 , the smaller first capsule 11 a easily enters first, thereby allowing the movement direction and observation direction to be matched.
[0086] The dome-like transparent cover 15 is provided on the front side of the smaller first capsule 11 a so as to cover the front surface of this capsule, and this transparent cover 15 encloses the image pickup device and illumination device. The objective lens 16 constituting the image pickup device is fit into the light-shielding lens frame 17 for shielding the unnecessary light reflected from the inner side of the transparent cover 15 and protrudes forward beyond the illumination device. Thus, the light-shielding lens frame is provided around the observation device and the front surface of the light-shielding lens frame projects beyond the front surface of illumination device.
[0087] Because of its shape, the capsule-type endoscope 3 conducts illumination and observation (image pickup) through the dome-like window. In this case, the reflection and back reflection of the illuminated light on the inner surface of the dome-like transparent cover 15 provided on the front surface of illumination device and observation device can occur with a high probability and the observed image can contain a ghost component or flare. For this reason, the function of the light-shielding lens frame 17 is of major importance.
[0088] In the present embodiment, as shown in FIG. 4 , when the height of lens frame 17 is represented by h and the distance between objective lens 16 and illuminating device is represented by s, the positional relationship of lens frame 17 and illumination device is set such as to prevent the light emitted from the illumination device and then reflected from the inner surface of transparent cover 15 , as completely as possible, from entering the objective lens 16 . In other words, the outer diameter and height of the light-shielding lens frame and the distance between the illumination device and observation device are set such as to substantially prevent the incidence of the unnecessary light such as the light emitted from the illumination device and then reflected from the inner surface of the dome-like observation window onto the observation device. For example, a part of the light emitted, as shown by the arrow, from one white LED 19 constituting the illumination device shown in FIG. 4 is reflected by the inner surface of transparent cover 15 , but practically all the reflected light is prevented from entering the objective lens 16 located on the inner side of lens frame 17 , thereby ensuring the field of view created by the objective lens 16 .
[0089] Furthermore, the light that passed through the inner surface of transparent cover 15 and was reflected by the outer surface thereof is also prevented as completely as possible from entering the objective lens 16 . As a result, random penetration of reflected light is substantially eliminated and observation performance is improved.
[0090] FIG. 5 is an expanded view of the main part of the structure shown in FIG. 4 , which illustrates the effective illumination of the view field range.
[0091] As shown in FIG. 5 , the range of field of view with respect to the observation object 39 , which is defined by the objective lens 16 installed in the lens frame 17 disposed in the center, can be illuminated with white LEDs 19 serving as illumination devices and disposed on both sides of the range of field of view. Here, for the sake of simplicity, the objective optical system is represented by a combination of objective lens 16 and lens frame 17 .
[0000] In the figure:
[0092] x: distance from the front surface of the objective optical system to the observation object 39 ,
[0093] h: height of objective optical system (from the end surface of the white LED 19 ),
[0094] d: diameter of the objective optical system,
[0095] θ: view angle of the objective optical system,
[0096] s: distance between the objective optical system and white LED 19 ,
[0097] a: radius of field of view,
[0098] b: illumination range.
[0099] As shown in FIG. 5 , a and b are set such that a≦b. As a result, the range of field of view can be effectively illuminated, without shielding the illumination light with the objective optical system.
[0100] Here,
a=d/ 2 +x tan θ
b =( x/h )·( s−d/s )− d/ 2.
[0101] The operation of the present embodiment will be described below.
[0102] When somatic cavities of the patient 2 are examined with the capsule-type endoscope 3 , the battery 29 has to be housed as shown in FIG. 2 . In this case, the portion where the battery 29 is housed can be detached by unscrewing. If the elastic resin cover 28 is removed and the battery housing lid 26 is removed by unscrewing, then a new battery 29 can be housed in an easy manner.
[0103] When the capsule-type endoscope 3 is to be used, the patient 2 or doctor installs the battery 29 and screws the battery housing lid 26 into the capsule frame 24 , which is one part of the split battery housing unit, that is, assembles the battery housing unit, thereby turning the power supply ON and initiating the capturing of images or transmission and receiving of signals. The power supply can be thus turned ON in an easy manner, and no special switch is required. Conversely, when the capsule-type medical device is discarded, the battery can be easily removed, which is beneficial for the environment.
[0104] Further, in the present embodiment, the battery 29 is placed in the second capsule 11 b . Therefore, if it is broken, problems can be associated with electric discharge or leakage. To prevent the breakage, the capsule is protected with the elastic resin cover 28 . Further, water-tight sealing with the seal member 25 such as an O-ring is implemented to prevent water and other body fluids from penetrating into the space where the battery 29 is housed.
[0105] As shown in FIG. 1 , the patient 2 can smoothly swallow the medical capsule 3 by inserting it into the mouth the first capsule 11 a side first, this first capsule having a small outer diameter.
[0106] The capsule-type endoscope 3 conducts illumination and image pickup with a constant cycle, and the picked-up image information is wireless transmitted from the antenna 31 . The image information is received by the external unit 5 and displayed on the liquid-crystal monitor 5 a or stored.
[0107] Therefore, the endoscopic examination crew can monitor the information with the liquid-crystal monitor 5 a . Further, since the outer diameter of the first capsule 11 a is less than that of the second capsule 11 b and the first capsule 11 a advances easier than the second capsule 11 b , the first capsule 11 a readily becomes ahead in the movement direction. In other words, when the endoscope advances from the stomach 36 , through the pylorus 37 , to the duodenum 38 , as shown in FIG. 3 , it easily advances to the deep zones smaller first capsule 11 a first.
[0108] Furthermore, in this case since the illumination and image pickup devices are provided on the distal end of the first capsule 11 a , the image of somatic cavities in the movement direction can be picked up and images, which can be easily diagnosed in the same manner as diagnostic images obtained with the usual endoscope, can be also obtained.
[0109] In another modification example, the below-described image pickup device may be used instead of the CMOS image pickup device.
[0110] The image pickup device used herein employs a threshold voltage modulation image sensor (VMIS), which is the next-generation image sensor, possessing the merits of both the above-described CMOS image pickup device and the CCD (charge coupled device). The structure of this sensor is entirely different from that of the conventional CMOS sensor in which the light receiving unit is composed of 3-5 transistors and photodiodes. Thus, the VMIS has a structure employing a technology of modulating the threshold value of a MOS transistor with a charge generated by the received light and outputting the changes of the threshold value as the image signals.
[0111] Such an image sensor features a combination of high quality of CCD and a high degree of integration and low power consumption of CMOS sensor.
[0112] For this reason, it was employed in the disposable capsule-type endoscopes. Using such a feature makes it possible to realize a disposable endoscope (soft or hard) or a low-price endoscope. The voltage modulation image sensor (VMIS) can be used not only in such endoscopes, but also in usual videoscopes. In addition, such voltage modulation image sensor (VMIS) has the below-described excellent features.
[0113] The structure is simple, with one transistor per one image sensor.
[0114] The VMIS has excellent photoelectric characteristic such as high sensitivity and high dynamic range.
[0115] Since the sensor can be fabricated by a CMOS process, a high degree of integration and low cost can be realized.
[0116] There are sensors of a variety of types, such as QCIF (QSIF) size, CIF (SIF) size, VGA type, SVGA type, XGA type, and the like. In the capsule-type endoscope with wireless communication of the present invention, small sensors of “QCIF (QSIF) size” and “CIF (SIF) size” are especially preferred from the standpoint of wireless transmission speed, power consumption, and because they are easy to swallow.
[0117] FIG. 6 illustrates a modification example of the first embodiment and shows part of the first capsule 11 a of this modification example.
[0118] In this modification example, a water-tight seal 40 is additionally implemented in white LEDs 19 , objective lens 16 , and lens frame 17 located inside the transparent cover 15 in the first capsule 11 a shown in FIG. 2 . In other words, a structure is employed in which the illumination device and observation device ensure water tightness for the hard unit with no dome-like observation window attached. Thus, the transparent cover 15 has a water-tight structure inside thereof on the front side, but even when cracks appear in the transparent cover 15 and it loses the waterproofing function thereof, using the water-tight seal 40 provides a water-tight structure for the entire surface facing the transparent cover 15 inside the transparent cover 15 so as to ensure electric insulation preventing the permeation of water into the electric system, such as the internal drive circuit 20 . The side surface portion is sealed with the seal member 14 in the same manner as shown in FIG. 2 .
[0119] With such a structure no water permeates into the electric system located inside the transparent cover 15 and electric insulation properties can be maintained even when cracks appear in the cover and it loses the waterproofing function thereof.
[0120] The present embodiment has the following effects.
[0121] Swallowing is facilitated by splitting one capsule in two to decrease the size thereof and making one of the resulting capsules less than the other. In other words, easiness of swallowing can be improved. Furthermore, changing the size of the capsules readily matches the movement direction with the observation direction. In other words, the observation ability can be improved.
[0122] Further, adjusting the arrangement of the objective optical system and also the illumination and transparent cover 15 reduces random penetration of reflected light. In other words, the observation ability can be improved.
[0123] Moreover, the power supply ON/OFF and battery replacement can be conducted in an easy manner. The endoscope is easy to handle and environment-friendly.
[0124] Since waterproofing of inner circuits is maintained even when cracks appear in the transparent cover, accidents are prevented.
[0125] In another modification example of the present embodiment, the front surface of the objective lens 16 of the lens frame 17 may be brought in contact with the inner surface of the transparent cover 15 . In this case, the transparent cover 15 has high resistance to deformation even when a large external force is applied thereto.
[0126] In other words, since the objective lens 16 or lens frame 17 is arranged so as to be in contact with the transparent cover 15 , the transparent cover 15 is not deformable nor rupturable and, therefore, the strength can be increased.
Second Embodiment
[0127] The second embodiment of the present invention will be described hereinbelow with reference to FIGS. 7 to 10 .
[0128] FIG. 7 is a sectional view illustrating a capsule-type endoscope 2 B of the second embodiment of the present invention. This capsule-type endoscope 2 B comprises three capsules 41 a , 41 b , 41 c and flexible tubes 42 a and 42 b linking the adjacent capsules 41 a , 41 b and the adjacent capsules 41 b , 41 c.
[0129] In this case, the first capsule 41 a and third capsule 41 c disposed on both ends have almost the same outer diameter, whereas the second capsule 41 b disposed in the center with respect thereto has a larger outer diameter.
[0130] Furthermore, the first capsule 41 a and third capsule 41 c have a structure similar to that of the first capsule 11 a of the first embodiment, and the second capsule 41 b has a structure similar to that of the second capsule 11 b.
[0131] In the first capsule 41 a , a cylindrical permanent magnet 43 a is provided to surround the cylindrical peripheral portion of a capsule frame 13 a and the opening of capsule frame 13 a is covered with a dome-like transparent cover 15 a . The circumferential part of this opening is water-tightly fixed with a waterproofing adhesive 44 a , and an image pickup device and an illumination device are housed inside thereof. A ferroelectric substance producing a strong magnetic force may be used instead of the permanent magnet 43 a.
[0132] An objective lens 16 a constituting the image pickup device (observation device) is mounted on a light-shielding lens frame 17 a and disposed opposite the transparent cover 15 a in the central portion of the internal space covered with the dome-like transparent cover 15 a . An image pickup element, for example, a CMOS image pickup device 18 a is disposed in the image forming position of the objective lens. For example, the objective lens 16 a is disposed so that the outer surface thereof is in contact with the inner surface of transparent cover 15 a.
[0133] Furthermore, for example, white LEDs 19 a are disposed as illumination devices in a plurality of places around the lens frame 17 a , and the light emitted by the white LED 19 a passes through the transparent cover 15 a and illuminates the space outside thereof.
[0134] Moreover, a drive circuit 20 a for driving and inducing the emission of light by the white LEDs 19 a and for driving the CMOS image pickup device 18 a , and a controller 21 a for controlling this drive circuit 20 a and provided with a function of conducting signal processing with respect to the output signals of CMOS image pickup device 18 a are disposed on the rear surface side of CMOS image pickup device 18 a . The drive circuit and the controller are secured to the capsule frame 13 a.
[0135] As shown in FIG. 6 , a water-tight seal 40 a is implemented on the inner side of the transparent cover 15 a , and the electric system such as the drive circuit 20 a and the like can be maintained in an electrically insulated state by the water-tight seal 40 a even when cracks appear in the transparent cover 15 a and water tightness provided by the portions covered with the transparent cover 15 a is lost.
[0136] Further, a connection socket 22 a for connecting and securing one end of a tube 42 a is provided in the center of the end surface of capsule frame 13 a on the side thereof opposite the transparent cover 15 a . One end of the tube 42 a is water-tightly connected and secured to the connection socket.
[0137] Moreover, one end of an electric cable 23 a which is passed through the inside of the tube 42 a via the opening of a disk-like latch 45 a is connected to the controller 21 a , and the other end thereof is connected to the second capsule 41 b.
[0138] The latch 45 a is connected to a latch 47 a of the second capsule 41 b via a linking metallic wire 46 a inserted into the tube 42 a and provides free bendability for the flexible tube 42 a , so as to prevent disrupting the linkage between capsules 41 a and 41 b.
[0139] An electric cable 23 a is, for example, wound around the linking metallic wire 46 a and inserted into the tube 42 a . A chamfer 34 a is formed on the rear peripheral portion of the first capsule 41 a by cutting it at an angle or corner cutting so as to obtain a spherical shape.
[0140] The third capsule 41 c has a similar structure. The components assigned with the reference symbol (a) that were explained in describing the first capsule 41 a are now assigned with the reference symbol (c) and the explanation thereof is omitted.
[0141] In the second capsule 41 b which is larger in size than the first and third capsules 41 a , 41 c , a seal member 25 is inserted, for example, into the cylindrical side surface of a capsule frame 24 serving as battery housing means and the end side thereof which is opened toward the third capsule 41 c is detachably covered with a battery housing lid 48 .
[0142] Connection sockets 27 a , 27 c for connecting and securing the tubes 42 a , 42 b are provided in the center of respective end surfaces of the capsule frame 24 and the battery housing lid 48 , and the tubes 42 a , 42 b are water-tightly connected and fixed, for example, with a waterproofing adhesive.
[0143] Further, the outer peripheral portions of the batteries housing the lid 48 and the capsule frame 24 are covered with an elastic resin cover 49 up to the vicinity of connection sockets 27 a , 27 c.
[0144] The capsule frame 24 encloses, for example, a button-type battery 29 , a transmission-receiving circuit 30 , and an antenna 31 . The transmission-receiving circuit 30 is electrically connected to controllers 21 a , 21 c , generates signals to be transmitted, and demodulates the received signals. The antenna 31 is connected to the transmission-receiving circuit 30 and sends the image information captured by the CMOS image pickup devices 18 a , 18 c to the external unit (not shown in the figure) or receives control signals wireless transmitted from the external unit.
[0145] The battery 29 is connected so as to supply drive electric power to the transmission-receiving circuit 30 , controllers 21 a , 21 c , and drive circuits 20 a , 20 c.
[0146] An external thread 32 is provided on the cylindrical side surface of the second capsule 41 b , and an internal thread, which is to be engaged with the external thread 32 , is provided on the inner peripheral surface of the battery housing lid 48 . Further, a circumferential groove is provided on the cylindrical side surface of the second capsule 41 b and a seal member 25 such as an O-ring is housed therein, thereby water-tightly sealing the inside of the capsule between the seal member and the battery housing lid 48 which is brought in contact therewith under pressure.
[0147] In the capsule-type endoscope 2 B of such a structure, three capsules 41 a , 41 b , 41 c obtained by splitting into three portions are linked by the flexible tubes 42 a , 42 b . In this case, both end capsules 41 a , 41 c are of almost the same size, and the central capsule 41 b is larger than the two end capsules 41 a , 41 c.
[0148] The two end capsules 41 a , 41 c are provided with an illumination device, image pickup device, drive circuits used for illumination and image pickup devices, and a processing circuit for the image pickup device. The central capsule 41 b is provided with the battery 29 , transmission-receiving circuit 30 , and antenna 31 , and various functions of the two end capsules 41 a , 41 c commonly use the battery 29 and transmission-receiving circuit 30 of the central capsule.
[0149] Further, exchange of electric power and signals between the three capsules 41 a , 41 b , 41 c is conducted by electric cables 23 a , 23 c located inside the flexible tubes 42 a , 42 b . Linking metal wires 46 a , 46 b are passed through the inside of the tubes 42 a , 42 b so that the tubes 42 a , 42 b can be freely bent without disrupting the connection of capsules 41 a , 41 b and 41 b , 41 c.
[0150] Further, chamfers 35 a , 35 b larger than the above-described chamfers 34 a , 34 c are formed in the elastic resin cover 49 , which serves as a protective cover, in the corner portion facing the first capsule 41 a and the corner portion facing the third capsule 41 c , respectively.
[0151] The operation of this embodiment will be described below.
[0152] Since the size of the two end capsules 41 a , 41 c is smaller than that of the central capsule 41 b , any of the two end capsules moves first in a somatic cavity 50 , as shown in FIG. 8 . Therefore, zones ahead and behind in the movement direction can be observed with the two end capsules 41 a , 41 c , each being provided with the illumination and image pickup devices. When the endoscope moves leftward, as shown in FIG. 8 , the capsule 41 a illuminates the zone ahead and picks up the images therefrom, and the capsule 41 c illuminates the zone behind and picks up the images therefrom. The reverse is the case when the endoscope moves rightward.
[0153] In the present embodiment, cylindrical permanent magnets 43 a , 43 c or magnetic substance is provided in both end capsules 41 a , 41 c . As shown in FIG. 9 , the permanent magnets 43 a , 43 c or magnetic substance makes it possible to recover the endoscope easily with a recovery tool 55 provided with a permanent magnet 54 at a front end of a cord-like member 53 when the capsule-type endoscope 2 B is stuck and cannot advance through an isthmus 51 in the somatic cavity 50 and has to be recovered.
[0154] In other words, when the front end of the recovery tool 55 is brought close to the capsule-type endoscope 2 B, the permanent magnet 54 is attracted to the permanent magnet 43 a or 43 c due to a magnetic force acting between the permanent magnet 54 at the front end of recovery tool 55 and the permanent magnet 43 a or 43 c at the capsule-type endoscope 2 B. The capsule-type endoscope 2 B can be then easily pulled out, that is, recovered by pulling out the recovery tool 55 .
[0155] The above explanation is related to the recovery operation, but the permanent magnets 43 a , 43 c or magnetic substance can be also used for remotely controlling the position or orientation of the capsule-type endoscope 2 B inside a somatic cavity by an external magnetic field.
[0156] The effect of the present embodiment will be described below.
[0157] Of the three above-described hard units, the outer diameter or length of the two end hard units is smaller than that of the hard unit other than the two end units. In particular, splitting a capsule in three decreases the size of capsule body and makes it easy to swallow the capsule. Thus, easiness of swallowing can be improved. In this case, swallowing can be made even more easier by decreasing the size of the capsules 41 a , 41 c located on both sides of central capsule 41 b . The outer diameters or lengths of the two end hard units are almost the same.
[0158] Since the illumination devices and image pickup devices are provided in capsules 41 a , 41 c at the both sides, the observation direction can be the same as the movement direction and zones ahead and behind in the movement direction can be observed at the same time. Therefore, observation performance is improved. Further, since the size of capsules 41 a , 41 c located on both sides of the central capsule 41 b is decreased, movement is facilitated.
[0159] Further, since the power supply function and signal transmission and receiving function are made common for a plurality of illumination devices and image pickup devices, the number of components can be decreased, which is beneficial for size reduction. In other words, size can be reduced and easiness of swallowing can be improved. The function of control unit may be also made common.
[0160] Further, providing the cylindrical permanent bodies 43 a , 43 c or magnetic substance allows the recovery or magnetic guidance. The recovery is facilitated and operability is improved.
[0161] FIG. 10 illustrates a part of the first capsule 41 a as a modification example of the present embodiment.
[0162] One end of a linking metal wire 46 a located inside the tube 42 a connecting the capsules 41 a , 41 b , on the side of capsule 41 a , as shown in FIG. 10 , has a slidable latch structure.
[0163] Thus, a latch 45 a located inside the capsule 41 a is disposed so that it is free to slide forward and backward inside a tubular body (ring) 56 a disposed between the rear surface of controller 21 a and the inner surface of capsule frame 13 a.
[0164] Further, in the present embodiment, a lens frame 17 a is abutted with the inner surface of the transparent cover 15 a.
[0165] The resulting effect is that the transparent cover 15 a is reinforced and the resistance thereof to external forces is improved.
[0166] Further, in the present embodiment, the linking metal wires 46 a , 46 c located inside the tubes 42 a , 42 c connecting the three capsules were separate from electric cables 23 a , 23 c , but in a structure of yet another modification example, the electric cables 23 a , 23 c may also serve as the linking metal wires 46 a , 46 c.
[0167] The resulting effect is that the structure can be simplified.
[0168] A structure may be also used in which one end of the linking metal wire is made slidable, as shown in FIG. 10 , and the electric cables 23 a , 23 c also serve as the linking metal wires 46 a , 46 c . In this case, a sliding latch 45 a may be provided with an electric contact and electrically connected to the controller 21 a via the tubular body 56 a.
[0169] In yet another modification example, a VMIS may be used instated of the CMOS image pickup device.
Third Embodiment
[0170] The third embodiment of the present invention will be described below with reference to FIGS. 11 to 13 . FIG. 11 illustrates a capsule-type medical device 2 C which is the third embodiment of the present invention. Structural components identical to those of the first embodiment are assigned with the same reference symbols and the explanation thereof is omitted.
[0171] The capsule-type medical device 2 C has a structure in which a variety of sensor means 61 such as a pH sensor, optical sensor, temperature sensor, pressure sensor, blood sensor (hemoglobin sensor), and the like are provided, for example, as in the first capsule 11 a , for example, in the capsule-type endoscope 2 of the first embodiment.
[0172] Various sensor means 61 are secured to the outer member of the capsule, such as the transparent cover 15 , so that sensing zone of sensor means 61 is exposed to the outside and the inside of the capsule is maintained in a water-tight state. Otherwise, the structure is the same as in the first embodiment.
[0173] Data such as chemical parameters (pH value) of body fluids, brightness inside a somatic cavity, temperature of various organs, pressure applied by the inner surface of somatic cavities to the outer surface of the capsule when the capsule advances therethrough, amount of hemoglobin in various organs (presence of hemorrhage) are obtained from the sensing zones. The data obtained are temporarily accumulated in a memory (not shown in the figures) located inside the capsule and then transmitted by the transmission-receiving circuit 30 and antenna 31 to a receiver such as the external unit 5 located outside the body. By comparing the data obtained by the receiver with the standard values, the medical crew, such a doctor or nurse, can externally establish the presence of abnormalities, such as disease or hemorrhage, and to determine the capsule advancing position or state.
[0174] In particular, diagnostics of gastroenterological diseases or physiological analysis can be conducted with high efficiency by painlessly establishing the pH value of hemoglobin level in digestive organs of the living body with the capsule-type medical device 2 C. Highly efficient examination can be conducted by providing a plurality of sensors according to the object of examination.
[0175] FIG. 12 illustrates a part of the capsule-type medical device 2 D which is a modification example of the third embodiment. In the present embodiment, an ultrasound probe 71 is additionally provided in the second capsule 11 b of the first embodiment. In this case, for example, a battery housing lid 26 is formed with a material transmitting ultrasound waves, a sealed space is formed in the battery housing lid 26 , a rotary-type ultrasound oscillator 72 is housed inside this space, and the area around the oscillator is filled with a transfer medium 73 .
[0176] The ultrasound oscillator 72 is rotated by a motor 74 . The elastic resin cover 28 of the external surface of the capsule around the ultrasound oscillator 72 functions as an acoustic lens of ultrasound oscillator 72 . The battery housing lid 26 is detachably secured to a capsule frame 24 with a screw 76 .
[0177] The ultrasound oscillator 72 makes possible the ultrasound tomography inside the somatic cavities, driving and signal processing being conducted by the control circuit 75 . Data obtained are transmitted to the external receiver in the same manner as described above. As a result, diagnostics of the presence of abnormalities in the depth direction of deep portions of somatic cavities such as a small intestine can be conducted. If a structure is used with observation devices on both sides, then diagnostics of both the surface and deep portions in somatic cavities can be conducted. An ultrasound probe with an electronic scanning system rather than mechanical scanning system may be also used.
[0178] FIG. 13 illustrates a capsule-type medical device 2 E of the second modification example. This capsule-type medical device 2 E is provided with treatment-therapy means.
[0179] In the capsule-type medical device 2 E, a medicine compartment 81 and a body fluid compartment 82 are provided, for example, in the elastic resin cover 28 in the second capsule 11 b , for example, in the capsule-type endoscope 2 of the first embodiment.
[0180] The medicine compartment 81 and body fluid compartment 82 have openings that are open on the outer surface of the capsule, and the openings are covered with soluble membranes 83 , 84 composed of fatty acid membranes or the like that are digested by the liquid present in intestines or of gelatin consumed by gastric juice. A medicine 85 for treatment is enclosed in the medicine compartment 81 . Once the capsule-type medical device 2 E has arrived to the target location, the soluble membrane 83 is dissolved, the opening is opened, and the medicine 85 is directly administered. At the same time, body fluid can be sucked into the body fluid compartment 82 .
[0181] Further, a linear actuator 88 for driving a syringe 87 so that it can be protruded is provided, for example, inside a part of transparent cover 15 in the first capsule 11 a , this syringe having a compartment 86 accommodating a hemostatic drug.
[0182] Thus, once a hemorrhaging zone has been established by a blood sensor or observation device, usually a procedure can be employed by which the syringe 87 for injecting the hemostatic drug accommodated inside the capsule is projected in response to a signal from the external unit 5 located outside the body and a powdered drug or ethanol which is the hemostatic drug located inside the compartment 86 is sprayed over the hemorrhaging zone to stop bleeding.
[0183] Embodiments composed by partially combining the above-described embodiments are also covered by the present invention.
[0184] As described above, in accordance with the present invention, a capsule-type medical device which is advanced the inside of the somatic cavities and lumens of human being or animals for conducting examination, therapy, or treatment comprises at least two hard units and a soft linking unit which links the aforesaid plurality of the hard units and has a diameter less than that of any of the hard units, wherein one of the plurality of hard units is different in size from other hard units. Therefore, when the smaller hard unit is swallowed first, the medical device can be easily swallowed and the smaller unit can easily be advanced the inside of the lumens.
Fourth Embodiment
[0185] FIGS. 14 to 21 illustrate the first embodiment of the present invention. FIG. 14 shows the external appearance of the capsule-type endoscope of the fourth embodiment. FIG. 15 shows the internal structure of one of the capsule bodies. FIGS. 16A and 16B explain the operation in a state of usage. FIGS. 17A, 17B , 17 C, and 17 D illustrate the endoscopic examination procedure. FIG. 18 is a block-diagram illustrating the structure of electric systems of the external unit and display system. FIG. 19 is a block-diagram illustrating the structure of the external unit, which is a modification example of the fourth embodiment. FIGS. 20A to 20 F are timing charts illustrating timing diagrams of illumination and image pickup in the embodiment employing the external unit shown in FIG. 19 . FIG. 21 illustrates an example of antenna structure in another modification example of the fourth embodiment.
[0186] As shown in FIG. 14 , a capsule-type endoscope 101 of the fourth embodiment of the present invention is composed of a capsule-shaped first capsule body 102 A and a second capsule body 102 B, each containing an image pickup device, and a soft thin strap 103 connecting back end sides of the two capsule bodies 102 A, 102 B.
[0187] In the present embodiment, the first capsule 102 A and the second capsule 102 B have the same structure. As an example, FIG. 15 shows the inner structure of the second capsule 102 B.
[0188] In the second capsule 102 B the front surface side of the body that has an almost cylindrical shape and is semi-spherically closed on the back end side thereof is covered with a semi-spherical transparent cover 105 b.
[0189] An objective lens 106 b is mounted in the center of the front surface portion of a body 104 b inside the transparent cover 105 b , and a CMOS image pickup device 107 b serving as a solid-state image pickup element is disposed in the image forming position of the lens.
[0190] A plurality of LEDs 108 b generating, for example, a white light are disposed around the objective lens 106 b . LEDs 108 b are driven by a LED drive circuit 109 b provided inside the body 104 b.
[0191] The image of the examinee located inside a somatic cavity and illuminated by the LEDs 108 b is formed by the objective lens 106 b on the CMOS image pickup device 107 b serving as an image pickup element and disposed in the image forming position of the lens. This image is photoelectrically converted by the CMOS image pickup device 107 b . The CMOS image pickup device 107 b is driven by the drive signals from a driving and processing circuit 111 b , conducts signal processing by extraction and compression of image signal components with respect to photoelectrically converter output signals, and sends the signals to a transmission circuit 112 b.
[0192] The transmission circuit 112 b conducts high-frequency modulation of the input image signals, converts them into high-frequency signals, for example, with a frequency of 2.4 GHz, and emits electromagnetic waves from an antenna 113 b to the outside. Power necessary for an operation of the transmission circuit 112 b , driving and processing circuit 111 b , and LED drive circuit 109 b is supplied from a battery 114 b.
[0193] Structural components of capsule body 102 A corresponding to structural components of capsule body 102 B explained with reference to FIG. 15 will be explained below by using reference symbols (a) instead of reference symbols (b). Furthermore, structural components identical to those explained in FIG. 15 are shown, for example, in FIG. 24 .
[0194] In the present modification, transmission from a transmission circuit 112 a of capsule body 102 A and transmission circuit 112 b of capsule body 102 B is conducted by slightly changing the transmission frequency. The signals are received by an external unit 116 (see FIG. 17A ) disposed outside.
[0195] In other words, electromagnetic waves transmitted by antennas 113 a and 113 b connected to the transmission circuit 112 a of the capsule body 102 A and transmission circuit 112 b of the capsule body 102 B, respectively, are received by the external unit 116 shown in FIG. 17A .
[0196] FIG. 17A shows how a patient 117 swallows the capsule 101 when the endoscopic examination is begun. In this case, since the picked-up image signals are transmitted by the capsule-type endoscope 101 as electromagnetic waves, those electromagnetic waves are received by the external unit 116 mounted, for example, with a belt of the patient 117 at a waist line of the patient 117 and stored in the memory located inside the external unit 116 .
[0197] When the endoscopic examination with the capsule-type endoscope 101 is completed, the external unit 116 is installed in a data capture unit 119 provided in a display system 118 shown in FIG. 17B , and the image data accumulated in the external unit 116 can be imported in the display system 118 via the data capture unit 119 .
[0198] FIG. 18 shows the configuration of the electric systems of the external unit 116 and display system 118 .
[0199] The external unit 116 serving as a receiver comprises two antennas 121 a , 121 b receiving with good efficiency the electromagnetic waves of the frequency transmitted by the antennas 113 a , 113 b of the capsule bodies 102 A and 102 B, and the high-frequency signals induced in the antennas 121 a , 121 b are input in respective receiving circuits 122 a , 122 b.
[0200] The receiving circuits 122 a , 122 b are controlled by respective control circuits 123 a , 123 b , and the control circuits 123 a , 123 b demodulate the high-frequency signals received by the receiving circuits 122 a , 122 b and conduct control so that those signals are successively stored in a memory 124 .
[0201] The memory 124 is composed of a hard disk (abbreviated as HDD in the figure). The memory 124 is connected to a connector 125 . When the external unit 116 is installed in the data capture unit 119 shown in FIG. 17B , a connector 125 is connected to a connector 126 of data capture unit 119 , as shown in FIG. 18 .
[0202] The connector 126 is connected to a memory 130 of display system 118 . The memory 130 is controlled by a control circuit 131 . The image data of observed images that are accumulated in the memory 124 of external unit 116 are developed and processed by an image processing circuit 132 via the memory 130 and stored, that is, recorded in a memory 133 which is a recording unit.
[0203] The memory 133 is, for example, composed of a hard disk. The memory 133 is connected to a display circuit 134 conducting display processing, and image signals sent to the display circuit 134 are displayed by a display unit 136 conducting display of images as captured images via a comparison circuit 135 conducting comparison. The comparison circuit 135 is connected to a disease image database (abbreviated as DB) 137 , compares the images from the disease image database 137 with the captured image, retrieves a similar past disease image, and simultaneously displays it on the display unit 136 as the DB image.
[0204] Furthermore, the control circuit 131 is connected to a console 138 such as a keyboard, and the command to capture images, to input patient data, to input diagnostic results, and the like are conducted from the console 138 .
[0205] A specific feature of this embodiment, as shown in FIG. 14 , is that the back ends of the two capsule bodies 102 A, 102 B, which are opposite to the front ends covered with transparent covers 105 a , 105 b are connected with a flexible strap 103 that has a width sufficiently less than that of the outer diameter of those capsule bodies 102 A, 102 B and such a structure allows for illumination and image pickup in mutually opposite directions.
[0206] The operation relating to this embodiment will be described below.
[0207] When endoscopic examination is conducted, the external unit 116 is attached to the waste of the patient 117 , for example, as shown in FIG. 17A , and the patient 117 is asked to swallow the capsule-type endoscope 101 .
[0208] The capsule-type endoscope 101 , for example, after the preset time, conducts illumination and image pickup, the picked-up image signals are transmitted from the antenna 113 a , 113 b , and the external unit 116 receives the transmitted image signals and stores them in the memory 124 .
[0209] FIGS. 16A and 16B show how the images of the inside, for example, of a large intestine 140 are picked up with the capsule-type endoscope 101 .
[0210] In the present embodiment, the two capsule bodies 102 A, 102 B are connected by the thin flexible strap 103 . Therefore, even when examination is conducted inside a lumen, for example, a right colon curve, as shown in FIG. 16A , the endoscope can be freely bent in strap 103 . Therefore, the endoscope can smoothly advance the inside of the lumen, similarly to a single-capsule-type endoscope. Therefore, examination can be conducted without causing paint or discomfort to the patient 117 .
[0211] Furthermore, in the present embodiment, the capsule bodies 102 A, 102 B have a structure such that the sides opposite to the back ends linked by the strap 103 serve as illumination and image pickup sides. Therefore, for example, as shown in FIG. 16A , there may be instances when a portion 140 shown by dotting becomes a dead zone whose image cannot be picked up by the capsule body 102 B, which is located in the zone ahead in the movement direction, due to half-moon folds. However, following this state, as shown in FIG. 16B , illumination and image pickup with the illumination and image pickup devices of the other capsule 102 A is conducted from the direction opposite to that of the preceding capsule 102 B, and the image of the zone that was a dead zone for the preceding capsule can be picked up with the succeeding capsule 102 A.
[0212] Thus, with the present embodiment, the occurrence of portions becoming the dead zones is prevented to a greater degree than with a single capsule body and effective images can be obtained.
[0213] Image signals obtained from two capsule bodies 102 A, 102 B are accumulated in the memory 124 of the external unit 116 , and after the capsule-type endoscope 101 is discharged to the outside of body, the external unit 116 is installed in the data capture unit 119 shown in FIG. 17B and the command signal of image capture is input from the console 138 of the display system 118 .
[0214] In such a case, the image data accumulated in the memory 124 of the external unit 116 are transferred into the image processing circuit 132 via the memory 130 functioning as a buffer, subjected to processing such as development, and accumulated one by one as image data in memory 133 .
[0215] The image data stored in the memory 133 can be successively displayed on the display device 136 if a display command is input from the console 138 by an operator.
[0216] Furthermore, when a command input was made to pick up the image similar to the disease image that was accumulated in the disease database 137 with respect to the captured image, the image that was captured by the capsule-type endoscope 101 is displayed together with the disease image from the disease database 137 on the display surface of display device 136 , as shown in FIG. 17C . In this state, the control circuit 131 shown in FIG. 18 conducts a comparative processing such as pattern matching of the captured image and the disease image read out from the disease database 137 with the comparison circuit 135 and makes a decision as to whether there is a similarity exceeding the preset ratio. If a decision is made that there is a similarity exceeding the preset ratio, this image together with several adjacent images are linked to the data of disease database 137 and stored in the memory 133 .
[0217] Then, only the images that can be related to a disease are extracted from all of the captured images and stored, for example, in an image extraction folder of the memory 133 .
[0218] As shown in FIG. 17D , the operator then conducts command input from the console 138 so as to display the extracted image on the display device 136 . As a result, the images stored in the image extraction folder are displayed successively and the operator can conduct final diagnostics with good efficiency. Thus, using the database to assist the diagnostics allows the diagnostics to be half automated and makes possible a significant reduction of time spent by the doctor on examination.
[0219] With the present embodiment, the illumination devices and image pickup devices are provided in both capsules. Therefore, the observation direction can be the same as the movement direction and observations can be simultaneously conducted ahead and behind in the movement direction. As a result, the endoscope can be moved more smoothly inside curved lumens in a body than in the conventional examples and images can be picked up without causing strong pain in the patient, and from different directions, more specifically, from the movement direction and the direction opposite thereto. Therefore, high-quality images can be obtained and the number of occurring dead zones is small. Furthermore, a set of images captured inside the body can be obtained and, thus, the operator saves such a time of picking up images while inserting the endoscope.
[0220] FIG. 19 illustrates the structure of a modification example of the external unit 116 .
[0221] The external unit 116 shown in FIG. 18 comprised the two antennas 121 a , 121 b , receiving circuits 122 a , 122 b , and control circuits 123 a , 123 b . In the present modification example, the external unit comprises single antenna 121 , a receiving circuit 122 , and a control circuit 123 .
[0222] Further, in the present modification example, as shown in FIGS. 20A to 20 F, the timings at which the transmission circuits 112 a , 112 b transmit the images obtained by illumination and image pickup by two capsule bodies 102 A, 102 B are shifted by half a period (T/2) with respect to each other to avoid overlapping thereof.
[0223] In other words, when the power supply of the two capsule bodies 102 A, 102 B is turned ON and they are set into the operation state, for example, a LED 108 a of the capsule body 102 A is ignited for a short time (for example, 1/30 sec) and an image is picked up by the CMOS image pickup device 107 a and transmitted by the transmission circuit 112 a (almost within half a period, T/2).
[0224] Once the transmission by the transmission circuit 112 a has been completed, the LED 108 b of the other capsule body 102 B is ignited for a short timer an image is picked up by the CMOS image pickup device 107 b and transmitted by the transmission circuit 112 b . Once the transmission by the transmission circuit 112 b has been completed, the LED 108 a of the first capsule body 102 A is again ignited.
[0225] With such an operation, the image signals transmitted by the transmission circuits 112 a , 112 b are received by one antenna 121 , received by the receiving circuit 122 , and stored in the memory 124 .
[0226] In this case, when the transmission frequencies of the transmission circuits 112 a and 112 b are slightly different, they can be received with a sufficiently good efficiency by the same antenna 121 . Furthermore, based on the transmission frequency, the external unit 124 can decide which of the image pickup elements has picked up the image.
[0227] Further, when the transmission circuits 112 a and 112 b transmit at the same frequency, transmission may be conducted as shown in FIGS. 20A to 20 F. In this case, the transmission may be conducted by adding an identification code, for example, to the header of the image which is to be transmitted.
[0228] In this case, the identification code may be recognized by the external unit 116 and separated from the image data, followed by storage in the memory 124 , or the image data may be stored in the memory 124 , with the identification code attached thereto, and the identification code may be recognized and separated from the image data in the display system 118 .
[0229] FIG. 21 shows an antenna of the modification example of external unit 116 . In the present modification example, the external unit 116 installed in a belt is connected with a connection cable 142 to a necktie-type antenna row 144 located on a shirt 143 that is worn by the patient 117 . This necktie-type antenna row 144 is detachably secured to the shirt 143 with a button 145 .
[0230] The necktie-type antenna row 144 thus hangs down from the neck of the patient 117 , and the antenna of the most intensive electromagnetic wave received among a plurality of antennas 144 a constituting the antenna row 144 is used.
[0231] With the present modification example, the installation can be conducted in an easy manner, without intensifying the pressure on the patient 117 . Further, a plurality of antennas 144 a are arranged in the vertical direction and located in the vicinity of the center in the width direction of the body of patient 117 . Therefore, as the capsule-type endoscope 101 descends by peristalsis, since a plurality of antennas 144 a are present along this direction, signals can be effectively received by the closest antenna 144 a.
[0232] The first modification example of the present embodiment will be described below with reference to FIG. 22 .
[0233] In the capsule-type endoscope 101 B of modification example shown in FIG. 22 , the external portion of the capsule body 102 A shown in FIG. 14 can be removed as a cover 146 . An electrode 148 of a communication port 147 is exposed in the back end of a capsule body 102 A′ from which the cover 146 has been removed.
[0234] As shown in FIG. 23 , the back end of the capsule body 102 A′ from which the cover 146 has been removed is installed in a connector socket 149 a of a rewriting unit 149 , and the operation program located inside the capsule body 102 A′ can be changed by manipulating the input keys 150 of the rewriting unit 149 .
[0235] FIG. 24 illustrates the rewriting unit 149 and the internal structure of the capsule body 102 A′ in this case, that is, when the cover 146 has been removed. In the fourth embodiment, the capsule body 102 A′ additionally comprises a timing control circuit for conducting timing control or a timing (abbreviated as TG in FIG. 22 and elsewhere) generator 151 and the above-mentioned communication port 147 connected to the timing generator 151 .
[0236] A CPU 152 conducting control operation and a memory 153 such as a flash memory having written therein a program determining the control operation of the CPU 152 are provided inside the timing generator 151 , and the contents of programs thereof can be rewritten by connecting to the rewriting unit 149 . The other capsule body 102 B has the same structure.
[0237] The operation is described below.
[0238] Prior to using the endoscope for endoscopic examination, the cover 146 is removed and the capsule body 102 A′ is set into the rewriting unit 149 , as shown in FIG. 23 . Then, input keys 150 are manipulated and the rewriting unit 149 sends data such as driving timing of illumination and image pickup or illumination period to the timing generator 151 of capsule body 102 A′ via the communication port 147 .
[0239] The CPU 152 of timing generator 151 rewrites the data in memory 153 with the transmitted data. Thus, the CPU 152 serving as a setting unit can randomly set from the outside the settings required for the realization of functions in at least one of the illumination device, observation device, wireless transmission unit, and control unit.
[0240] The capsule body 102 A′ is thereafter disconnected from the rewriting unit 149 , and the cover 146 is attached. Further, the same operation is conducted with respect to the other capsule body 102 B′. The patient 117 is then asked to swallow the capsule-type endoscope 101 B.
[0241] Illumination and image pickup are then conducted at the illumination and device timing set by manipulating the input keys 150 .
[0242] As a specific example of data that are written, for example, when mainly the large intestine of the patient 117 is examined, the settings are made such that one frame image is picked up in 2 seconds within 6 hours after the capsule-type endoscope 101 B was swallowed and two frame images are picked up in 1 second after the 6 hours have elapsed.
[0243] In such a modification example, a frame rate can be increased to conduct detail observation, for example, in the zone where the patient's symptoms are suspicious, so as to obtain a large number of images in the zone which requires careful examination based on the patient's symptoms. In other words, the operator can freely set the image pickup conditions according to the zone which is to be examined, thus, effective picked-up images can be obtained, and the consumption of battery energy can be reduced.
[0244] FIG. 25 shows a capsule body 102 A″ of the second modification example. In the structure of this capsule body 102 A″, a drive and processing circuit 111 a shown in FIG. 24 is connected to a memory 154 a and the memory 154 a is connected to a communication port 147 a.
[0245] Data on the patient which is to be examined can be input into the memory 154 a by the rewriting unit 149 prior to endoscopic examination.
[0246] Furthermore, image data picked up by the driving and processing circuit 111 a are accumulated in the memory 154 a during endoscopic examination. Once the endoscope capsule has been recovered, the image data accumulated in the memory 154 a are read out together with the patient's data by a display system provided with a communication port connectable to the communication port 147 a . As a result, the image data can be managed in a state in which the relationship thereof with the patient's data is maintained.
[0247] In the first modification example shown in FIG. 24 , a memory storing the patients data may be also provided, and when the image data are transmitted, the patient's data stored in the memory may be initially transmitted as header information of the image data.
Fifth Embodiment
[0248] The fifth embodiment of the present invention will be described below with reference to FIGS. 26 to 28 . FIG. 26 shows a capsule-type endoscope 101 C of the fifth embodiment. In the capsule-type endoscope 101 C, for example, the objective lenses 106 a , 106 b of capsule bodies 102 A, 102 B of the fourth embodiment are replaced with an objective lens 107 a ′ with a standard angle of view and an objective lens 107 b ′ with a wide angle of view. For sake of simplicity, only the objective lens 107 a ′ and objective lens 107 b ′ are shown in FIG. 26 . The same is true for FIG. 27 described hereinbelow.
[0249] In this case, an angle of view providing for an observation field of view from 120° to 140° is set as a standard angle of view, and an angle of view providing for an observation field of view from 160° to 180° is set as the wide angle of view.
[0250] Further, the movement direction in case of endoscopic examination with the capsule-type endoscope 101 C is such that the images are first picked up with the objective lens 107 a ′ with the standard angle of view. Otherwise the structure is identical to that of the fourth embodiment. The observation devices of each hard unit have objective optical systems with mutually different angles of field of view.
[0251] With the present embodiment, overlooking can be reduced by conducting far-point observations with the objective lens 107 a ′ with a standard angle of view in the capsule body 102 A located ahead zone in the movement direction and conducting near-point observations with the objective lens 107 b ′ with a wide angle of view in the rear capsule body 102 B.
[0252] FIG. 27 shows a capsule-type endoscope 101 D of the first modification example. In this capsule-type endoscope 101 D, the devices conducting illumination and image pickup in the direct-viewing direction of capsule bodies 102 A, 102 B in the fourth embodiment are modified so as to conduct illumination and image pickup in the directions inclined to the movement direction of capsule-type endoscope 101 D.
[0253] In case of the structure shown in FIG. 27 , the fields of view of objective lenses 107 a ″, 107 b ″ are defined by directions inclined in the mutually opposite directions with respect to the movement direction of capsule-type endoscope 101 D. For example, if the field of view of objective lens 107 a ″ is inclined downward, then the field of view of the other objective lens 107 b ″ is inclined upward.
[0254] With the present modification example, since the inclined viewing directions are different ahead and behind the endoscope, the lumens can be observed within a wider range by combining the images obtained with both lenses.
[0255] FIG. 28 shows a capsule-type endoscope 101 E of the second modification example. This capsule-type endoscope 101 E has a structure in which three capsule bodies 156 A, 156 B, and 156 C are linked by a thin flexible strap 57 . Further, the capsule 156 A has an objective lens 158 a with a field of view in the direct-viewing direction, the capsule body 156 B has an objective lens 158 b with a field of view in the downward side-viewing direction, and the capsule 156 C has an objective lens 158 c with a field of view in the upward side-viewing direction.
[0256] With this modification example, the inside of lumens can be observed within even wider range by combining the images obtained with all of the capsule bodies.
Sixth Embodiment
[0257] The sixth embodiment of the present invention will be described hereinbelow with reference to FIG. 29 , FIG. 30A , and FIG. 30B . FIG. 29 shows a capsule-type endoscope 101 F of the sixth embodiment. In the capsule-type endoscope 101 F, a toggle switch 161 and a charge accumulation circuit 162 are provided as the LED drive circuit 109 a in the capsule-type endoscopes 102 A′ and 102 B′, for example, in the capsule-type endoscope 101 B shown in FIG. 22 . Only one capsule body 102 A is shown in FIG. 29 .
[0258] Further, a transmission-receiving circuit 112 a ′ is employed instead of the transmission circuit 112 a . If a switch operation signal Sk is sent from the outside, it is received by the antenna 113 a , demodulated by the transmission-receiving circuit 112 a ′, and sent to a CPU 152 a of timing generator 151 a . The CPU 152 a conducts control operation according to the switch operation signal Sk.
[0259] More specifically, the LED 108 a , as shown in FIG. 30A and FIG. 30B , intermittently emits light under the effect of electric power of battery 114 a . However, if the switch operation signal Sk is received, the CPU 152 a of timing generator 151 a switches the toggle switch 161 a so that it is connected to the charge accumulation circuit 162 a . As a result, the electric power accumulated in the charge accumulation circuit 162 a is supplied to the LED 108 a and a large quantity of light is emitted.
[0260] With the present embodiment, for example, when the capsule-type endoscope 101 F reaches the position which apparently requires careful examination, transmitting the switch operation signal Sk from the outside makes it possible to cause the emission of a large quantity of light by the LED 108 a and to obtain a bright image with a good S/N ratio.
[0261] More specifically, even when the LED 108 a is caused by the battery 114 a to emit light inside the esophagus or small intestine, a sufficiently bright image can be obtained. However, inside the stomach or large intestine, the illumination light is not fully received and dark images are sometimes obtained.
[0262] If a switch operation signal Sk is sent from the outside with respect to the zones for which dark images are obtained, for example, zones that are apparently the affected areas, then the entire electric power that was charged into the charge accumulation circuit 162 within the sufficient period of time is supplied via the toggle switch 161 as a large electric current into the LED 108 a , and a large quantity of light is emitted instantaneously. As a result, a bright image, even if still image, with a good S/N ratio can be obtained in the desired zones inside the stomach and large intestines.
[0263] Further, since the LED 108 a generates heat, illumination in usual observations is conducted at an electric current of no higher than a standard value. However, the LED 108 a practically does not degrade even if a large electric current such as reaching the standard value is passed instantaneously therethrough.
[0264] In the present embodiment, the amount of illumination light was switched by the switch operation signal Sk. However, a configuration may be also used in which the illumination and image pickup periods can be changed by the switch operation signal, that is, the operation periods of a plurality of illumination devices and observation devices can be changed by the switch operation signal from the outside.
Seventh Embodiment
[0265] The seventh embodiment of the present invention will be described below with reference to FIG. 31 and FIG. 32 . FIG. 31 shows a capsule-type endoscope 101 G of the seventh embodiment. In this capsule-type endoscope 101 G, a dip switch 164 a is provided instead of the communication port 147 a shown in FIG. 22 and the transmission frequency of the internal transmission circuit can be variably set by the dip switch 164 a.
[0266] With this embodiment, even if a plurality of capsule-type endoscopes 101 G are swallowed, setting different frequencies for the transmission of image signals by each endoscope makes it possible to recognize and manage the signals during receiving.
[0267] FIG. 32 shows a capsule-type endoscope 101 H of the modification example of the seventh embodiment. In this capsule-type endoscope 101 H, an infrared radiation (IR) port 167 a is provided on the inner side of a transparent cover glass 166 a provided on the external surface in the capsule body 102 A, for example, shown in FIG. 29 .
[0268] The communication is conducted with infrared radiation and the IR port 168 provided in the rewriting unit 149 . Further, in this modification example, the cover 146 is not separated. With this modification example, setting of illumination and image pickup timing can be conducted even without connecting to the rewriting device 149 . Thus, the CPU conducts those settings by using remote communication such as infrared radiation communication and the like. Otherwise, the effect obtained is almost identical to that explained with reference to FIG. 29 .
Eighth Embodiment
[0269] The eighth embodiment of the present invention will be described hereinbelow with reference to FIGS. 33 to 35 . FIG. 33 shows a structure relating to the antenna of external unit 116 . In this embodiment, a stripe-like antenna row 172 is attached to the front button 171 portion of a shirt 143 of the patient 117 . A plurality of antennas 172 a constituting the antenna row 172 are connected to the external unit 116 with a connection cable 142 .
[0270] The operation and effect of this embodiment are almost identical to those explained with reference to FIG. 21 .
[0271] FIG. 34 shows the first modification example of the eighth embodiment. In FIG. 34 , a shirt 174 incorporates the antenna row. Buttons 175 also function as antennas.
[0272] FIG. 35 shows the second modification example of the eighth embodiment. In FIG. 35 , an apron-like antenna row 176 is in the form of an apron put on the shirt 143 . A plurality of antennas 176 a are provided in the apron-like antenna row 176 . The operation and effect of this embodiment are almost identical to those explained with reference to FIG. 33 .
Ninth Embodiment
[0273] The ninth embodiment of the present invention will be described hereinbelow with reference to FIGS. 36A and 36B . FIGS. 36A and 36B illustrate a state of endoscopic examination of the ninth embodiment. FIG. 36A relates to the initial stage of examination. FIG. 36B illustrates how the images obtained in the course of the examination are transmitted from the patient's home to the hospital.
[0274] In this embodiment, the data capture unit 119 , for example, installed in the external unit 116 is connected to a connection unit 183 of a telephone line 182 connected to a telephone 181 , and further connected to the display system 118 disposed in a hospital 184 via the telephone line 182 .
[0275] Otherwise, the configuration is identical to that of the fourth embodiment.
[0276] As for the operation of this embodiment, when endoscopic examination is conducted, as shown in FIG. 36A , the patient 117 swallows the capsule-type endoscope 101 .
[0277] Image data obtained with capsule-type endoscope 101 are accumulated in the external unit 116 . Upon completion of the endoscopic examination, the external unit 116 is connected to the data capture unit 119 connected to the telephone line 182 and the image data are automatically transferred to the hospital or other remote site via the telephone line 182 .
[0278] In the hospital, the image data are received and automatically imported. The final diagnostics is conducted by the doctor.
[0279] In this embodiment, diagnostics is possible even when the patient is in a remote location far from a hospital. Furthermore, since the examination of the patient can be conducted not only in a hospital, the degree of freedom of patient 117 is increased.
[0280] Further, the transmission of image data is not limited to that via the telephone line and wireless transmission may be also conducted. Moreover, the transmission may be conducted with other communications means such as cellular phones, internet, and the like.
Tenth Embodiment
[0281] The tenth embodiment of the present invention will be described hereinbelow with reference to FIGS. 37 to 42 . In this embodiment, illumination and image-pickup functions are separated between a plurality of capsule bodies, and illumination and image pickup are conducted by combining the operations of the capsule bodies. In a capsule-type endoscope 185 of the tenth embodiment shown in FIG. 37 , a capsule body 186 A and capsule body 186 B are connected with a strap 187 .
[0282] Further, a LED 188 emitting white light, a LED drive circuit 189 , and a battery 190 are enclosed in the capsule body 186 A. An objective lens 191 , a CMOS image pickup device 192 , a drive and processing circuit 193 , a transmission circuit 194 , and an antenna (not shown in the figure) are enclosed in the other capsule body 186 B. The capsule bodies 186 A, 186 B are connected with a signal line 195 .
[0283] Magnets 196 a , 196 b are provided inside the capsule bodies 186 A, 186 B, respectively. As shown in FIG. 38 , the capsule bodies can be easily attracted to each other by magnetic forces of magnets 196 a , 196 b serving as joining components. Therefore, the two capsules are joined in the prescribed position.
[0284] FIG. 38 illustrates the operation of the present embodiment. When endoscopic examination of the patient 117 is conducted, the patient is asked to swallow the capsule-type endoscope 185 straightened out into a line.
[0285] When the endoscope passes through a narrow lumen portion of an esophagus 197 , the endoscope advances to a deeper region, while maintaining the linear shape. If it then reaches a wide zone, such as a stomach 198 , the two capsule bodies 186 R, 186 B are drawn close to each other by the magnetic forces of the magnets 196 a , 196 b.
[0286] Illumination and image pickup (including the function of transmitting the image signals) are then conducted in such a state. At least one of the capsule bodies is provided with a magnetic sensor, such as a Hall element, for detecting the state in which the capsule bodies are combined by magnetic forces of the magnets 196 a , 196 b , and the control initiating the illumination and image pickup based on the detection output of the sensor is conducted by a control unit (not shown in the figures). Alternatively, as shown in FIG. 24 , illumination and image pickup may be conducted after the prescribed time has elapsed, or as shown in FIG. 29 , the operation control may be conducted based on the external signals.
[0287] With the present embodiment, image signals can be can be obtained by improving the illumination and image pickup functions executed by the capsule bodies. For example, high-resolution images with good S/N ratio can be obtained by increasing the quantity of illumination light or increasing the number of pixels in the image pickup element.
[0288] FIGS. 39A and 39B show a capsule-type endoscope 185 ′ of the first modification example. The magnets 196 a , 196 b are not used in the capsule-type endoscope 185 ′ and a strap 187 ′ formed from a shape memory material is employed as the strap 187 serving as a joining member.
[0289] In this case, the strap 187 ′ formed from a shape memory material was subjected to shape memory processing such that it has a linear shape at room temperature, as shown in FIG. 39A , but is bent, as shown in FIG. 39B , if the temperature becomes no less than the body temperature, thereby combining the two capsule bodies 186 A, 186 B. In this case, too, the operation and effect are almost identical to those explained with reference to FIG. 37 .
[0290] FIGS. 40A and 40B show a capsule-type endoscope 185 ″ of the second modification example. In the capsule-type endoscope 185 ″, a strap 187 ″ is formed from a spring material processed (impelled) so as to be bent and to combine the two capsule bodies 186 A, 186 B, as shown in FIG. 40A . When the endoscope is swallowed, the strap is straightened out, as shown in FIG. 40B . In this case, too, the operation and effect are almost identical to those explained with reference to FIG. 37 .
[0291] FIG. 41 shows a capsule-type endoscope 201 of the third modification example. In this modification example, combining the capsules improves the illumination and image pickup function, more specifically, the image pickup range, over those obtained when the capsules are not combined.
[0292] In the capsule-type endoscope 201 , three capsule bodies 202 A, 202 B, 202 C are linked with a thin soft strap 203 . The capsule body 202 A and other capsule bodies are hard and have a hard length shown in the figure.
[0293] The objective lenses 204 a , 204 c with a field of image view inclined upward are enclosed in transparent covers in the respective capsule bodies 202 A, 202 C on both end sides, and image pickup elements 205 a , 205 c are disposed in image forming positions of respective lenses. The image pickup elements 205 a , 205 c are driven and signals therefrom are processed by the image element drive and processing circuits 206 a , 206 c.
[0294] Further, LEDs 207 a , 207 c for illumination are disposed around the objective lenses 204 a , 204 c , respectively. The LEDs 207 a , 207 c are driven by an LED drive circuit 208 provided in the central capsule body 202 B.
[0295] Further, signals that were processed by the image element drive and the processing circuits 206 a , 206 c are sent to a transmission circuit 209 provided in the central capsule body 202 B and are transmitted to the outside from an antenna (not shown in the figure). A battery 210 is also enclosed in the capsule body 202 B. Energy such as electric current is supplied to the observation devices such as the image pickup elements 205 a , 205 c enclosed in the capsule bodies 202 A and 202 C by the battery 210 .
[0296] Magnets 211 a , 211 c are provided inside the capsule bodies 202 A, 202 C on both end sides.
[0297] Therefore, similarly to the case explained with reference to FIG. 38 , if the capsule-type endoscope 201 reaches a wide portion such as a stomach, the capsule bodies 202 A, 202 C located on both end sides are attracted and combined by the magnets 211 a , 211 c , as shown in FIG. 42 . Therefore, the two capsules are joined in the prescribed position.
[0298] In such a state, image pickup is possible within a wide range because of respective inclined fields of view. The operation and effect in this case are similar to those explained with reference to FIG. 37 .
[0299] The present invention also covers embodiments composed, for example, by partial combinations of the above-described embodiments.
[0300] Having described the preferred embodiments of the invention referring to the accompanying drawings, it should be understood that the present invention is not limited to those precise embodiments and various changes and modifications thereof could be made by one skilled in the art without departing from the spirit or scope of the invention as defined in the appended claims.
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A method of transmitting images in a subject to an outside of the subject using a wireless signal is provided. The method including: (a) transmitting to the outside of the subject a first signal corresponding to a first image obtained using a first imaging device; (b) transmitting to the outside of the subject a second signal corresponding to a second image obtained using a second imaging device; and (c) repeating (a) and (b), where at least initiation of the transmitting the first signal and initiation of the transmitting the second signals is alternately performed
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FUNDED RESEARCH
This work is supported in part by the following grant from the National Institute of Health: R01DC005762-03. The Government may have certain rights in this invention.
RELATED APPLICATIONS
The present application is related to U.S. Pat. No. 6,788,796 for DIFFERENTIAL MICROPHONE, issued Sep. 7, 2004; and copending U.S. patent application Ser. No. 10/689,189 for ROBUST DIAPHRAGM FOR AN ACOUSTIC DEVICE, filed Oct. 20, 2003, and Ser. No. 11/198,370 for COMB SENSE MICROPHONE, filed Aug. 5, 2005, all of which are incorporated herein by reference.
FIELD OF THE INVENTION
The present invention pertains to differential microphones and, more particularly, to a micromachined, differential microphone absent a backside air pressure relief orifice, fabricatable using surface micromachining techniques.
BACKGROUND OF THE INVENTION
In typical micromachined microphones of the prior art, it is generally necessary to maintain a significant volume of air behind the microphone diaphragm in order to prevent the back volume air from impeding the motion of the diaphragm. The air behind the diaphragm acts as a linear spring whose stiffness is inversely proportional to the nominal volume of the air. In order to make this air volume as great as possible, and hence reduce the effective stiffness, a through-hole is normally cut from the backside of the silicon chip. The requirement of this backside hole adds significant complexity and expense to such prior art micromachined microphones. This present invention enables creation of a microphone that does not require a backside hole. Consequently, the inventive microphone may be fabricated using only surface micromachining techniques.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided a differential microphone having a perimeter slit formed around the microphone diaphragm. Because the motion of the diaphragm in response to sound does not result in a net compression of the air in the space behind the diaphragm, the use of a very small backing cavity is possible, thereby obviating the need for creating a backside hole. The backside holes of prior art microphones typically require that a secondary machining operation be performed on the silicon chip during fabrication. This secondary operation adds complexity and cost to, and results in lower yields of the microphones so fabricated. Consequently, the microphone of the present invention requires surface machining from only a single side of the silicon chip.
BRIEF DESCRIPTION OF THE DRAWINGS
A complete understanding of the present invention may be obtained by reference to the accompanying drawings, when considered in conjunction with the subsequent, detailed description, in which:
FIG. 1 is a top view of a micromachined microphone diaphragm in accordance with the invention;
FIG. 2 is a side, sectional, schematic view of a differential microphone of the invention;
FIGS. 3 and 4 are, respectively, schematic representations of the differential microphone of FIG. 2 as a series of diaphragms without and with an indication of the motion thereof;
FIG. 5 is a diagram showing the orientation of an incident sound wave on the diaphragm of FIG. 1 ;
FIGS. 6 a - 6 d are schematic representations of the stages of fabrication of the inventive, surface micromachined microphone of the invention;
FIG. 7 is a side, sectional, schematic view of a differential microphone formed by removing a portion of a sacrificial layer of FIG. 6 d ; and
FIG. 8 is a side, sectional, schematic view of an alternate embodiment of the microphone of FIG. 2 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention relates to a micromachined differential microphone formed by surface micromachining a single surface of a silicon chip.
The motion of a typical microphone diaphragm results in a fluctuation in the net volume of air in the region behind the diaphragm (i.e., the back volume). The present invention provides a microphone diaphragm designed to rock due to acoustic pressure, and hence does not significantly compress the back volume air.
An analytical model for the acoustic response of the microphone diaphragm including the effects of a slit around the perimeter and the air in the back volume behind the diaphragm has been developed. If the diaphragm is designed to rock about a central pivot, then the back volume and the slit has a negligible effect on the sound-induced response thereof.
Referring first to FIGS. 1 and 2 , there are shown, respectively, a top view of a micromachined microphone diaphragm, including a slit around the perimeter of the diaphragm, and a side, sectional, schematic view of a differential microphone in accordance with the invention, generally at reference number 100 . A rigid diaphragm 102 is supported by hinges 104 that form a pivot point 106 around which diaphragm 102 may “rock” (i.e., reciprocally rotate). A back volume of air 108 is formed in a cavity 110 formed in the chip substrate 112 . A slit 114 is formed between the perimeter 103 of diaphragm 102 and the chip substrate 112 .
Diaphragm 102 rotates about the pivot point 106 due to a net moment that results from the difference in the acoustic pressure that is incident on the top surface portions 116 , 118 that are separated by the central pivot point 106 .
In order to more readily examine the effects of the back volume 108 and the slit 114 around the diaphragm 102 , several assumptions are made. It is assumed that the pivot point 106 is centrally located and that diaphragm 102 is designed such that the rocking, or out-of-phase motion of diaphragm 102 is the result of the pressure difference on the two portions 116 , 118 of the exterior surface thereof. Because diaphragm 102 is normally designed to respond to the difference in pressure on its two portions 116 , 118 , microphone 100 is referred to it as a differential microphone. However, in addition to motion induced by pressure differences, it is also possible that diaphragm 102 will be deflected due to the average pressure on its exterior surface. Such pressure causes diaphragm 102 motion in which both portions 116 , 118 of the diaphragm 102 separated by the pivot point 106 respond in-phase.
The air 108 a in the slit 114 around the diaphragm 102 on each portion 116 , 118 is assumed to have a mass ma. Consequently, diaphragm 102 responds like an oscillator. Hence, the two portions 116 , 118 of the differential microphone 100 , along with the two masses of air 108 , 108 a can be represented by a system of diaphragms 120 , 122 , 124 , 126 as shown in FIG. 3 . Each of the diaphragms is identified as air 108 (reference number 120 ), microphone portion 116 (reference number 122 ), microphone portion 118 (reference number 124 ), and air 108 a (reference number 126 ). The response of each diaphragm is governed by the following equation:
m i {umlaut over (X)} i +k i X i =F i (1)
where: F i is the net force acting on each diaphragm 120 , 122 , 124 , 126 and X 4 , X 1 , X 2 , and X 3 , represent the motion of each respective diaphragm 120 , 122 , 124 , 126 . As may be seen in FIG. 4 , X 1 and X 2 represent the average motion of each portion 116 , 118 of the diaphragm and X 3 and X 4 represent the motion of the air 108 a in the slit 114 .
A differential microphone without the slit 114 (i.e., a differential microphone of the prior art) can be represented by a two degree of freedom system with rotational response θ and translational response x:
m{umlaut over (x)}+kx=F (2a)
I{umlaut over (θ)}+k t θ=M (2b)
where: F is the net applied force, and M is the resulting moment about the pivot point. k and k t represent the effective transverse mechanical stiffness and the torsional stiffness respectively, of the diaphragm and pivot 102 , and 106 .
If d is the distance between the centers of each portion 116 , 118 of the diaphragm 102 , then X 1 and X 2 may be expressed in terms of the generalized co-ordinates x and θ:
X
1
=
x
+
d
2
θ
and
X
2
=
x
-
d
2
θ
⇒
x
=
X
1
+
X
2
2
and
θ
=
X
1
-
X
2
2
(
3
)
These relations may also be written in matrix form:
(
X
1
X
2
X
3
X
4
)
=
[
d
/
2
1
0
0
-
d
/
2
1
0
0
0
0
1
0
0
0
0
1
]
(
θ
x
X
3
X
4
)
=
[
T
]
(
θ
x
X
3
X
4
)
(
4
)
If the dimensions of the air cavity 110 ( FIG. 2 ) behind the diaphragm 102 are much smaller than the wavelength of sound, it may be assumed that the air pressure in the back volume 108 is spatially uniform within the air cavity. The air 108 in this back volume (i.e., cavity 110 ) then acts as a linear spring. It is necessary to relate the pressure in the back volume air 108 to the displacement of the diaphragm 102 to estimate the stiffness of this spring. If the mass of the air in back volume 108 is assumed to be constant, then the motion of the diaphragm 102 results in a change in the density of the air 108 in cavity 110 . The relation between the acoustic, or fluctuating density, ρ a and the acoustic pressure, p, is the equation of state:
p=c 2 ρ a (5)
where: c is the speed of sound.
The total density of air is the mass divided by the volume, ρ=M/V. If the volume fluctuates by an amount ΔV due to the motion of diaphragm 102 , then the density becomes ρ=M/(V+ΔV)=M/V(1+ΔV/V. For small changes in the volume, this can be expanded in a Taylor's series ρ≈(M/V)(1−ΔV/V). The acoustic fluctuating density is then ρ a =−ρ 0 ΔV/V, where the nominal density is ρ 0 =M/V. The fluctuating pressure in the volume V due to the fluctuation ΔV, resulting from an outward motion, x, of the diaphragm 102 is then given by:
P d =−ρ 0 c 2 ΔV/V=−ρ 0 c 2 AX/V (6)
where: A is half the area of the diaphragm.
This pressure in the back volume 108 exerts a force on the diaphragm 102 given by:
F d =P d A=−ρ 0 c 2 A 2 x/V=−K d x (7)
where: K d =ρ 0 c 2 A 2 /V is the equivalent spring constant of the air 108 with units of N/m.
The force due to the back volume of air 108 adds to the restoring force from the mechanical stiffness of the diaphragm 102 . Including the air in the back volume 108 , Equation (2) becomes:
m{umlaut over (x)}+kx+k d x=−PA (8)
The negative sign on the right hand side of Equation (8) is attributed to the convention that a positive pressure on the diaphragm's exterior causes a force in the negative direction. From Equation (8), the mechanical sensitivity at frequencies well below the resonant frequency is given by S m =A/(k+K d ) m/Pa.
The air 108 a in the slit or vent 114 is forced to move due to the fluctuating pressures both within the space 110 behind the diaphragm 102 and in the external sound field, not shown. Again, it may be assumed that the dimensions of the volume of moving air in the slit 114 to be much smaller than the wavelength of sound and hence it may be approximately represented as a lumped mass ma. An outward displacement, X a , of the air 108 a in the slit 114 causes a change in the volume of air in the back volume 108 . A corresponding pressure similar to Equation (6) is given by:
P aa =−ρ 0 c 2 A a x a /V (9)
where: A a is the area of the slit 114 on which the pressure acts.
Again, the pressure due to motion of air 108 a in the slit 114 applies a restoring force on the mass thereof given by:
F aa =P aa A a =−ρ 0 c 2 A a 2 x a /V=−K aa x a (10)
Since the pressure in the back volume 108 is nearly independent of position within the back volume, a change in the pressure due to motion of the air 108 a in the slit 114 exerts a force on the diaphragm 102 given by:
F ad =P aa A=−ρ 0 c 2 A a Ax a /V=−K ad x a (11)
Similarly, the motion of the diaphragm causes a force on the mass of air 108 given by:
F da =P d A a =−ρ 0 c 2 AA a x/V=−K da x (12)
From Equations (6), (10), (11) and (12), it may be seen that the forces add to the restoring forces due to mechanical stiffness in the system of Equation (1). Hence the volume change due to motion of each co-ordinate is given by ΔV i =A i X i and F i =PA i . Now, the total pressure due to the motion of all co-ordinates is given by:
P
tot
=
-
ρ
0
c
2
V
(
A
1
X
1
+
A
2
X
2
+
A
3
X
3
+
A
4
X
4
)
=
-
ρ
0
c
2
V
∑
i
A
i
X
i
(
13
)
The force due to this pressure on the jth coordinate in this model (indicating the motions of 120 , 122 , 124 , and 126 in FIG. 3 ) is then given by:
F j = P tot A j = ( - ρ 0 c 2 V ∑ i A i X i ) A j = - ∑ i K ij X i ( 14 )
where:
K
ij
=
-
ρ
0
c
2
V
A
i
A
j
.
Equation (14) may be written as:
(
F
1
F
2
F
3
F
4
)
=
-
[
K
11
K
12
K
13
K
14
K
21
K
22
K
23
K
24
K
31
K
32
K
33
K
34
K
41
K
42
K
43
K
44
]
(
X
1
X
2
X
3
X
4
)
(
15
)
Combining Equations (4) and (15), in terms of the coordinates θ and x of the differential microphone, the force is represented as:
(
F
1
F
2
F
3
F
4
)
=
-
[
K
11
K
12
K
13
K
14
K
21
K
22
K
23
K
24
K
31
K
32
K
33
K
34
K
41
K
42
K
43
K
44
]
[
T
]
(
θ
x
X
3
X
4
)
(
16
)
Equation (16) may be rewritten in terms of the average force acting on the differential microphone 100 and the net moment acting on the pivot point 106 . This is given by:
F
=
F
1
+
F
2
2
and
M
(
F
1
-
F
2
)
d
2
⇒
F
1
=
F
+
M
d
and
F
2
=
F
-
M
d
What follows therefrom is:
(
M
F
F
3
F
4
)
=
[
d
/
2
-
d
/
2
0
0
1
/
2
1
/
2
0
0
0
0
1
0
0
0
0
1
]
(
F
1
F
2
F
3
F
4
)
⇒
(
M
F
F
3
F
4
)
=
-
[
d
/
2
-
d
/
2
0
0
1
/
2
1
/
2
0
0
0
0
1
0
0
0
0
1
]
[
K
11
K
12
K
13
K
14
K
21
K
22
K
23
K
24
K
31
K
32
K
33
K
34
K
41
K
42
K
43
K
44
]
[
T
]
(
θ
x
X
3
X
4
)
⇒
(
M
F
F
3
F
4
)
=
-
[
K
′
]
(
θ
x
X
3
X
4
)
(
17
)
Hence, the system of equations:
[
I
0
0
0
0
m
0
0
0
0
m
a
0
0
0
0
m
a
]
(
θ
¨
x
¨
X
¨
3
X
¨
4
)
+
[
k
t
0
0
0
0
k
0
0
0
0
0
0
0
0
0
0
]
(
θ
x
X
3
X
4
)
=
(
M
F
F
3
F
4
)
-
[
K
′
]
(
θ
x
X
3
X
4
)
⇒
[
I
0
0
0
0
m
0
0
0
0
m
a
0
0
0
0
m
a
]
(
θ
¨
x
¨
X
¨
3
X
¨
4
)
+
{
[
k
t
0
0
0
0
k
0
0
0
0
0
0
0
0
0
0
]
+
[
K
′
]
}
(
θ
x
X
3
X
4
)
=
(
M
F
F
3
F
4
)
(
18
)
It is important to note that the coupling between the coordinates in Equation (18) is due to the matrix [K′]. Evaluating the elements of [K′] from equations (4) and (17), the governing equation for the rotation, θ, of the diaphragm is:
I θ ¨ + ( k t + ( d 2 ) 2 ( k 11 - k 12 - k 21 + k 22 ) ) θ + ( d 2 ) ( k 11 + k 12 - k 21 - k 22 ) x + ( d 2 ) ( k 13 - k 33 ) X 3 + ( d 2 ) ( k 14 - k 24 ) X 4 = M ( 19 )
where:
K
ij
=
-
ρ
0
c
2
V
A
i
A
j
.
Note that if the diaphragm is symmetric, A 1 =A 2 , and A 3 =A 4 . As a result, the coefficients of x, X 3 , and X 4 in equation (19) become zero. This causes the governing equation for rotation to be independent of the other coordinates as well as independent of the volume, V (i.e., I{umlaut over (θ)}+k t θ=M). The rotation is also independent of the area of the slits 114 , because of the assumption that the pressure created within the back volume 108 is spatially uniform and therefore does not create any net moment on the diaphragm 102 .
In the foregoing analysis, it has been assumed that the microphone diaphragm 102 is symmetric about the central pivot point 106 . As mentioned above, in this case, the diaphragm 102 behaves like a differential microphone diaphragm and has a first-order directional response. If, however, the diaphragm 102 is designed to be asymmetrical with respect to pivot point 106 , then the directionality departs from that of a differential microphone and tends toward that of a nondirectional microphone. The effect of the back volume 108 on the rotation of the diaphragm 102 can be determined by extending the foregoing analysis to this non-symmetric case.
In the following, expressions are derived for the forces and moment that are applied to the microphone diaphragm 102 due to an acoustic plane wave. For plane waves, the pressure acting on the diaphragm 102 is assumed to be of the form p=Pe îωt e (−îk x x−îk y y) , where
k x = ω c sin ϕ sin θ , k y = ω c sin ϕ cos θ and k z = ω c cos ϕ ,
where the angles are defined in FIG. 5 . The net moment due to the incident sound is given by
M = ∫ - L x / 2 L x / 2 ∫ - L y / 2 L y / 2 P ⅇ ⅈ ^ ω t ⅇ ( - ⅈ ^ k x x - ⅈ ^ k y y ) x ⅆ x ⅆ y
where L x and L y are the lengths in the x and y directions, respectively.
The expression for the moment can be integrated separately over the x and y directions to give
⇒ M = P ⅇ ⅈ ^ ω t ∫ - L x / 2 L x / 2 ⅇ - ⅈ ^ k x x x ⅆ x ∫ - L y / 2 L y / 2 ⅇ - ⅈ ^ k y y ⅆ y .
Integrating over the y coordinate becomes
⇒
M
=
P
ⅇ
ⅈ
^
ω
t
(
ⅇ
ⅈ
^
k
y
L
y
/
2
-
ⅇ
ⅈ
^
k
y
L
y
/
2
-
i
k
y
∫
-
L
x
/
2
L
x
/
2
ⅇ
-
ⅈ
^
k
x
x
x
ⅆ
x
⇒
M
=
P
ⅇ
ⅈ
^
ω
t
2
sin
(
k
y
L
y
2
∫
-
L
x
/
2
L
x
/
2
ⅇ
-
ⅈ
^
k
x
x
x
ⅆ
x
.
Integrating by parts for the x-component gives:
⇒
M
=
P
ⅇ
ⅈ
^
ω
t
2
sin
(
k
y
L
y
2
)
k
y
[
L
x
2
(
ⅇ
-
ⅈ
^
k
x
L
x
/
2
+
ⅇ
ⅈ
^
k
x
L
x
/
2
)
-
i
k
x
+
1
k
x
2
(
ⅇ
ⅈ
^
k
x
L
x
/
2
-
ⅇ
-
ⅈ
^
k
x
L
x
/
2
)
]
.
Simplifying the above gives:
⇒
M
=
P
ⅇ
ⅈ
^
ω
t
[
2
sin
(
k
y
L
y
2
)
k
y
]
[
-
L
x
i
^
k
x
cos
(
k
x
L
x
2
)
-
2
i
^
k
x
2
sin
(
k
x
L
x
2
)
]
(
20
)
Because the dimensions of the diaphragm are very small relative to the wavelength of sound, the arguments of the sin and cosine functions are very small, which results in
sin ( k y L y 2 ) ≈ k y L y 2 .
The second term in brackets in Equation (20) is expanded to second order using Taylor's series. Using
cos θ ≈ 1 - θ 2 2 and sin θ ≈ θ - θ 3 6 ,
in Equation (16),
M
≈
P
ⅇ
ⅈ
^
ω
t
[
2
(
L
y
2
)
]
[
-
L
x
i
^
k
x
(
1
-
k
x
2
L
x
2
8
)
-
2
i
^
k
x
2
(
k
x
L
x
2
-
k
x
3
L
x
3
48
)
]
.
Simplifying gives:
M
≈
P
ⅇ
ⅈ
^
ω
t
L
y
k
x
L
x
2
12
i
^
(
21
)
The net force is given by a surface integral of the acoustic pressure,
F = - ∫ - L x / 2 L x / 2 ∫ - L y / 2 L y / 2 P ⅇ ⅈ ^ ω t ⅇ - ⅈ ^ k x x -- ⅈ ^ k y y ⅆ x ⅆ y .
Carrying out the integration gives:
F
--
P
ⅇ
ⅈ
^
ω
t
2
sin
(
k
x
L
x
2
)
k
x
2
sin
(
k
y
L
y
2
)
k
y
.
Again, for small angles this becomes
F=−Pe îωt ( L x L y ) (22)
Using Equations (15), (18) and (19):
[
I
0
0
0
0
m
0
0
0
0
m
a
0
0
0
0
m
a
]
(
θ
¨
x
¨
X
¨
3
X
¨
4
)
+
{
[
k
t
0
0
0
0
k
0
0
0
0
0
0
0
0
0
0
]
+
[
K
′
]
}
(
θ
x
X
3
X
4
)
=
(
P
ⅇ
ⅈ
^
ω
t
L
y
k
x
L
x
3
12
i
^
-
P
ⅇ
ⅈ
^
ω
t
(
L
x
L
y
)
-
PA
a
-
PA
a
)
Let
K eq = { [ k i 0 0 0 0 k 0 0 0 0 0 0 0 0 0 0 ] + [ K ′ ] } and
assume θ=Θe îωt ,x=Xe îωt ,X 3 =X 3 e îωt and X 4 =X 4 e îΩt
[
K
eq
(
1
,
1
)
-
I
ω
2
K
eq
(
1
,
2
)
K
eq
(
1
,
3
)
K
eq
(
1
,
4
)
K
eq
(
2
,
1
)
K
eq
(
2
,
2
)
-
m
ω
2
K
eq
(
2
,
3
)
K
eq
(
2
,
4
)
K
eq
(
3
,
1
)
K
eq
(
3
,
2
)
K
eq
(
3
,
3
)
-
m
a
ω
2
K
eq
(
3
,
4
)
K
eq
(
4
,
1
)
K
eq
(
4
,
2
)
K
eq
(
4
,
3
)
K
eq
(
4
,
4
)
-
m
a
ω
2
]
(
Θ
/
P
X
/
P
X
3
/
P
X
4
/
P
)
=
(
L
y
k
x
L
x
3
12
i
^
-
(
L
x
L
y
)
-
A
a
-
A
a
)
(
23
)
Using Equation (23), the displacement and rotation relative to the amplitude of the pressure, X/P and θ/P, as a function of the excitation frequency, ω may be computed.
Based on the foregoing analysis, it may be observed that if the air in the back volume 108 is considered to be in viscid, the performance of the differential microphone diaphragm 102 is not degraded if the depth of the backing cavity 110 is reduced significantly. Thus the microphone 100 can be fabricated without the need for a backside hole behind the diaphragm 102 . The fabrication process for the surface micromachined microphone diaphragm is shown in FIGS. 6 a - 6 d.
Referring now to FIG. 6 a , there is shown a bare silicon wafer 200 before fabrication is begun. Such silicon wafers are known to those skilled in the art and are not further described herein.
As may be seen in FIG. 6 b , a sacrificial layer (e.g., silicon dioxide) 202 is deposited on an upper surface of wafer 200 . While silicon dioxide has been found suitable for forming sacrificial layer 202 , many other suitable material are know to those of skill in the art. For example, low temperature oxide (LTO), phosphosilicate glass (PSG), aluminum are known to be suitable. Likewise, photoresist material may be used. In still other embodiments, polymeric materials may be used to form sacrificial layer 202 . It will be recognized that other suitable material may exist. The choice and use of such material is considered to be known to those of skill in the art and is not further described herein. Consequently, the invention is not considered limited to a specific sacrificial layer material. Rather, the invention covers any suitable material used to form a sacrificial layer in accordance with the inventive method.
Over sacrificial layer 202 , a layer of structural material (for example polysilicon) is also deposited. While polysilicon has been found suitable for the formation of layer 204 , it will be recognized that layer 204 may be formed from other materials. For example, silicon nitride, gold, aluminum, copper or other material having similar characteristic may be used. Consequently, the invention is not limited to the specific material chosen for purposes of disclosure but covers any and all similar, suitable material. Layer 204 will ultimately form diaphragm 102 ( FIG. 2 ).
As is shown in FIG. 6 c , the diaphragm material, layer 204 is next patterned and etched to form the diaphragm 102 , leaving slits 114 .
Finally, as may be seen in FIG. 6 d , the sacrificial layer 202 under diaphragm 102 is removed leaving cavity 110 . After the removal of the sacrificial layer, the microphone diaphragm 102 has a back volume 108 with a depth equal to the thickness of the sacrificial layer 202 . The microphone is shown schematically in FIG. 7 .
To convert motion of diaphragm 102 into an electronic signal, comb fingers incorporated at 208 ( FIG. 7 ) may be integrated with the diaphragm. Such comb or interdigitated fingers are described in detail in copending U.S. patent application Ser. No. 11/198,370 for COMB SENSE MICROPHONE, filed Aug. 5, 2005.
As an alternative sensing scheme, the fundamental microphone structure of FIG. 7 may be modified slightly to include two conductive layers 206 disposed between silicon chip 200 and additional conductive layer 204 to form back plates forming fixed electrodes of capacitors. These back plates are electrically separated from each other in order to allow differential capacitive sensing of the diaphragm motion.
It should be noted that one could employ both the comb fingers 208 and the back plate 206 to perform capacitive sensing. In this case, in addition to serving as an element of a capacitive sensing arrangement, a voltage applied to comb sense fingers 208 may be used to stabilize diaphragm 102 . The voltage applied between the comb fingers and the diaphragm can be used to reduce the effect of the collapse voltage, which is a common design issue in conventional back plate-based capacitive sensing schemes.
It will be recognized that many other sensing arrangements may be used to convert motion of diaphragm 102 to an electrical signal. Consequently, the invention is not limited to any particular diaphragm motion sensing arrangement.
Since other modifications and changes varied to fit particular operating requirements and environments will be apparent to those skilled in the art, the invention is not considered limited to the example chosen for purposes of disclosure, and covers all changes and modifications which do not constitute departures from the true spirit and scope of this invention.
Having thus described the invention, what is desired to be protected by Letters Patent is presented in the subsequently appended claims.
|
A differential microphone having a perimeter slit formed around the microphone diaphragm that replaces the backside hole previously required in conventional silicon, micromachined microphones. The differential microphone is formed using silicon fabrication techniques applied only to a single, front face of a silicon wafer. The backside holes of prior art microphones typically require that a secondary machining operation be performed on the rear surface of the silicon wafer during fabrication. This secondary operation adds complexity and cost to the micromachined microphones so fabricated. Comb fingers forming a portion of a capacitive arrangement may be fabricated as part of the differential microphone diaphragm.
| 7
|
SUMMARY OF THE INVENTION
Combination plumbing fixtures are frequently used in nursing homes, hospitals, and the like. The combination fixture has a fixed toilet bowl with a swinging lavatory which swings over the toilet when it is desired to use the lavatory.
Such fixtures are very efficient since they occupy much less space than an individual lavatory and toilet.
Further, they are esthetically pleasing since the ordinarily unattractive toilet bowl is concealed except when it is in actual use. Thus, the fixture can be installed along one wall of an ordinary hospital or nursing home room so that it is not necessary to provide a separate bathroom.
One difficulty with such fixtures is that the spout for the washbasin must extend out over the washbasin when the washbasin is in use and, when the washbasin is swung away to permit use of the toilet, the spout extends over the toilet.
It is undesirable to have the spout over the toilet for the reason that upon arising, the patient can easily strike his head on the spout which can result in severe injury. The problem is particularly aggravated by the fact that such fixtures are frequently used by elderly patients who are less adept at avoiding hazards than ordinary people.
In accordance with the present invention, a safety spout is provided wherein the spout automatically swings out of the way when the washbasin is swung to the inoperative position revealing the toilet.
Thus, when the toilet is in use, the spout is swung out of the way, obviating any possibility of contact between the spout and the patient's head.
The objects of the present invention are achieved in a very simple and economical manner which adds little to the expense of the fixture and does not detract from the utility of the fixture in any manner.
Various other features and objects of the invention will be brought out in the balance of the specifications.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a combination plumbing fixture embodying the present invention showing the lavatory swung out of the way so that the toilet can be used.
FIG. 2 is a partial perspective view of the fixture showing the position of the parts when the lavatory can be used.
FIG. 3 is a section on the line 3--3 of FIG. 2.
FIG. 4 is a section on the line 4--4 of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings by reference characters, there is shown a combination fixture which includes a cabinet 6, suitable for mounting on a wall which has a toilet bowl 8 attached thereto. A lavatory bowl 10 is mounted in the frame 12 which is mounted on hinges 14 so that it can be swung outward to a position as is shown in FIG. 1, wherein the toilet 8 can be used or to a position against the cabinet, as is shown in FIG. 2, in which position the lavatory bowl 10 can be used.
Also mounted on the cabinet are the usual valve handles 14 and 16 for controlling the flow of water to a spout 18. Spout 18 is of the gooseneck variety and has a terminal end 20 which normally extends out over the lavatory bowl 10, as is shown in FIG. 2, so that one can use the lavatory in the usual manner with water discharged from the spout 18 flowing into the bowl 10.
It is apparent that if the spout 18 has terminal end 20 extending over the toilet bowl when the lavatory is swung outward, that a patient rising from toilet 8 might hit his head on the end 20 of the spout.
In accordance with the present invention, the spout 18 is mounted on a swivel connection 22 mounted between the spout 18 and the inlet supply pipe 24 so that it can rotate. In the embodiment illustrated, the supply pipe 24 leads to a shut-off valve 26 having a push button actuator 28 so that water to the spout 18 is shut off when the lavatory is in the outer position, as is shown in FIG. 1, preventing the patient from getting splashed should one of the faucets be accidentally opened while the lavatory is in the out position. However, this valve 26 forms no part of the present invention, and the supply pipe 24 leading to the swivel 22 could extend directly to the water supply valves operated by handles 14 and 16. Spout 18 is provided with an arm 30 which is normally biased by spring 32, to the right (clockwise) as is shown in FIG. 3 so the terminal end 20 of the spout 18 is in the operative position, i.e. over the basin 10, as is shown in FIG. 2. A flexible cord 34 is attached to arm 30 and this passes over pulleys 36, 38, and 40 and is attached at point 42 of the frame 12.
The operation of the device will be obvious. When the washbasin is in use, as is shown in FIG. 2, the spring 32 will bias spout 18 in a clockwise direction so that one can use the lavatory in the normal manner. Now, if one wishes to use the toilet, the lavatory is swung out, putting tension on the cord 34, rotating lever arm 30 in a counterclockwise direction which will swing the spout so that the terminal end 20 is now over the frame 6 and does not extend over the toilet. In this position, the spout is completely out of the way so that there is no possibility of a patient injuring himself when rising from the toilet.
Although a specific mechanical system is shown for swinging the spout, it will be obvious to those skilled in the art that other mechanical motions, such as levers, could be used instead of the spring and cord arrangement illustrated.
|
In a combination toilet fixture having a fixed toilet bowl and a swing-out lavatory, a swivel device is provided on the spout so that the spout automatically swings out of the way when the toilet is in use, preventing possible injury to the user.
| 4
|
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of application Ser. No. 103,148, filed Dec. 13, 1979, now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to novel semisynthetic antifungal compounds which are prepared by the acylation of the cyclic peptide nucleus produced by the enzymatic deacylation of antibiotic S31794/F-1.
Antibiotic S31794/F-1 is an antifungal cyclic peptide having the formula: ##STR9## wherein R is the myristoyl group. Throughout this application, the cyclic peptide formulas, such as formula I, assume that the amino acids represented are in the L-configuration.
Antibiotic S31794/F-1, which is disclosed in German Offenlegungschrift 2,628,965 and U.S. Pat. No. 4,173,629, is produced by Acrophialophora limonispora nov. spec. Dreyfuss et Muller NRRL 8095. S31794/F-1 has the following characteristics: m.p. 178°-180° C. (dec.) (amorphous) or 181°-183° C. (dec.) (crystalline); [α] D 20 -24° (c 0.5, CH 3 OH) or +37° (c 0.5, pyridine) (crystalline); UV absorption maxima in methanol at 194 nm (E 1cm 1% =807), 225 nm (shoulder) E 1cm 1% =132), 276 nm (E 1cm 1% =12.8), 284 nm (shoulder) E 1cm 1% =10.5); 13 C-NMR spectrum in deuteromethanol (190 mg in 1.5 ml deuteromethanol, tetramethylsilane as internal standard) with the following characteristics (crystalline):
______________________________________PPM PPM PPM______________________________________176.2 75.5 51.2175.0 74.0 39.7173.7 71.0 38.8172.6 70.5 36.6172.0 69.7 34.8171.8 68.0 32.8171.7 62.2 30.6168.6 58.3 26.7157.7 57.0 23.5132.5 56.2 19.7129.0 55.4 14.3115.9 52.9 11.1 76.6______________________________________
an approximate elemental analysis (after drying crystalline material for two hours in a high vacuum at 100° C.) as follows: 55.5-56.5 percent carbon, 7.5-7.7 percent hydrogen, 10.5-10.8 percent nitrogen and 25.5-26.0 percent oxygen; is readily soluble in methanol, ethanol, pyridine, dimethyl sulfoxide and poorly soluble in water, chloroform, ethyl acetate, diethyl ether, benzene and hexane; and has antifungal activity, especially against Candida albicans.
Antibiotic S31794/F-1 is prepared by submerged aerobic cultivation of Acrophialophora limonispora NRRL 8095 as described in Examples 4 and 5. This microorganism is a part of the permanent culture collection of the Northern Regional Research Center, U.S. Department of Agriculture, Agricultural Research Culture Collection, North Central Region, Peoria, Ill. 61604, from which it is available to the public under the designated NRRL number.
Antibiotic S31794/F-1 has antifungal activity, particularly against Candida strains such as Candida albicans. Thus, production and isolation of the antibiotic can be monitored by bioautography using a Candida species such as Candida albicans.
In the antibiotic S31794/F-1 molecule (Formula I), the myristoyl side chain (R) is attached at the cyclic peptide nucleus at the α-amino group of the dihydroxyornithine residue. Surprisingly, it has been found that the myristoyl side chain can be cleaved from the nucleus by an enzyme without affecting the chemical intregity of the nucleus. The enzyme employed to effect the deacylation reaction is produced by a microorganism of the family Actinoplanaceae, preferably the microorganism Actinoplanes utahensis NRRL 12052, or a variant thereof. To accomplish deacylation, antibiotic S31794/F-1 is added to a culture of the microorganism and the culture is allowed to incubate with the substrate until the deacylation is substantially complete. The cyclic nucleus thereby obtained is separated from the fermentation broth by methods known in the art. Unlike antibiotic S31794/F-1, the cyclic nucleus (lacking the linoleoyl side chain) is substantially devoid of antifungal activity.
The cyclic nucleus afforded by the aforedescribed enzymatic deacylation of antibiotic S31794/F-1 is depicted in Formula II. ##STR10##
S31794/F-1 nucleus has an empirical formula of C 35 H 52 N 8 O 16 and a molecular weight of 840.87.
Removal of the side chain group affords a free primary α-amino group in the dihydroxyornithine residue of the cyclic peptide. For convenience, the compound having the structure given in Formula II will be referred to herein as "S31794/F-1 nucleus." As will be apparent to those skilled in the art, S31794/F-1 nucleus can be obtained either in the form of the free amine or of the acid addition salt. Although any suitable acid addition salt may be employed, those which are non-toxic and pharmaceutically acceptable are preferred.
The method of preparing S31794/F-1 nucleus from antibiotic S31794/F-1 by means of fermentation using Actinoplanes utahensis NRRL 12052 is described in the co-pending application of Bernard J. Abbott and David S. Fukuda, entitled "S 31794/F-1 NUCLEUS", Ser. No. 103,313 which was filed Dec. 13, 1979. A continuation-in-part application of this application, with corresponding Ser. No. 181,036, is being filed herewith this even date, the full disclosure of which is incorporated herein by reference. Example 3 herein, illustrates the preparation of S31794/F-1 nucleus by fermentation using antibiotic S31974/F-1 as the substrate and Actinoplanes utahensis NRRL 12052 as the microorganism.
The enzyme produced by Actinoplanes utahensis NRRL 12052 may be the same enzyme which has been used to deacylate penicillins (see Walter J. Kleinschmidt, Walter E. Wright, Frederick W. Kavanagh, and William M. Stark, U.S. Pat. No. 3,150,059, issued Sept. 22, 1964).
Cultures of representative species of Actinoplanaceae are available to the public from the Northern Regional Research Laboratory under the following accession numbers:
______________________________________Actinoplanes utahensis NRRL 12052Actinoplanes missouriensis NRRL 12053Actinoplanes sp. NRRL 8122Actinoplanes sp. NRRL 12065Streptosporangium roseumvar. hollandesis NRRL 12064______________________________________
The effectiveness of any given strain of microorganism within the family Actinoplanaceae for carrying out the deacylation of this invention is determined by the following procedure. A suitable growth medium is inoculated with the microorganism. The culture is incubated at about 28° C. for two or three days on a rotary shaker. One of the substrate antibiotics is then added to the culture. The pH of the fermentation medium is maintained at about pH 6.5. The culture is monitored for activity using a Candida albicans assay. Loss of antibiotic activity is an indication that the microorganism produces the requisite enzyme for deacylation. This must be verified, however, using one of the following methods: (1) analysis by HPLC for presence of the intact nucleus; or (2) re-acylation with an appropriate side chain (e.g. linoleoyl, stearoyl, or palmitoyl) to restore activity.
SUMMARY OF THE INVENTION
The invention sought to be patented comprehends novel compounds derived by acylating S31794/F-1 nucleus (Formula II). The compounds of the present invention have the chemical structure depicted in Formula III: ##STR11## wherein R 1 is an N-alkanoyl amino acyl group of the formula ##STR12## wherein:
W is a divalent aminoacyl radical of the formula: ##STR13## wherein A is C 1 -C 10 alkylene or C 5 -C 6 cycloalkylene; ##STR14## wherein R 3 is hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indolemethyl, benzyl, or substituted phenyl or substituted benzyl in which the benzene ring thereof is substituted with chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR15## wherein X is hydrogen, chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkoxy, mercapto, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR16## wherein X 1 is chloro, bromo, or iodo; ##STR17## wherein B is a divalent radical of the formula: --(CH 2 ) n --, wherein n is an integer from 1 to 3; --CH═CH--; --CH═CH--CH 2 --; or ##STR18## and
R 2 is C 1 -C 17 alkyl or C 2 -C 17 alkenyl.
As employed herein the terms "alkylene", "alkyl", "alkoxy", "alkylthio", and "alkenyl" comprehend both straight and branched hydrocarbon chains. "Alkyl" means a univalent saturated hydrocarbon radical. "Alkenyl" means a univalent unsaturated hydrocarbon radical containing one, two, or three double bonds, which may be oriented in the cis or trans configuration. "Alkylene" means a divalent saturated hydrocarbon radical. "Cycloalkylene" means a divalent cyclic saturated hydrocarbon radical.
Illustrative C 1 -C 10 alkylene radicals, which are preferred for purposes of this invention are: --CH 2 --; ##STR19## in which R 5 is C 1 -C 4 alkyl (i.e., methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, or l-methylpropyl); --(CH 2 ) m --in which m is an integer from 2 to 10; and CH 3 --(CH 2 ) q --CH--(CH 2 ) p --, in which p is an integer from 1 to 8 and q is an integer from 0 to 7, provided that n+m must be no greater than 8.
Illustrative C 1 -C 17 alkyl groups which are preferred for the purposes of this invention are:
(a) CH 3 --;
(b) --(CH 2 ) n CH 3 wherein n is an integer from 1 to 16; and
(c) ##STR20## wherein r and s are independently, an integer from 0 to 14 provided that r+s can be no greater than 14.
Illustrative C 2 -C 17 alkenyl radicals, which are preferred for the purpose of this invention, are
(a) --(CH 2 ) t --CH═CH--(CH 2 ) u --CH 3 wherein t and u are independently, an integer from 0 to 14 provided that t+u can be no greater than 14.
(b) --(CH 2 ) v --CH═CH--(CH 2 ) y --CH═CH--(CH 2 ) z --CH 3 wherein v and z are independently, an integer from 0 to 11 and y is an integer from 1 to 12 provided that v+y+z can be no greater than 11.
In particular, the following embodiments of the C 1 -C 17 alkyl groups are preferred:
CH 3 --
CH 3 (CH 2 ) 5 --
CH 3 (CH 2 ) 6 --
CH 3 (CH 2 ) 8 --
CH 3 (CH 2 ) 10 --
CH 3 (CH 2 ) 12 --
CH 3 (CH 2 ) 14 --
CH 3 (CH 2 ) 16 --
In particular, the following embodiments of the C 2 -C 17 alkenyl groups are preferred:
cis-CH 3 (CH 2 ) 5 CH═CH(CH 2 ) 7 --
trans-CH 3 (CH 2 ) 5 CH═CH(CH 2 ) 7 --
cis-CH 3 (CH 2 ) 10 CH═CH(CH 2 ) 4 --
trans-CH 3 (CH 2 ) 10 CH═CH(CH 2 ) 4 --
cis-CH 3 (CH 2 ) 7 CH═CH(CH 2 ) 7 --
trans-CH 3 (CH 2 ) 7 CH═CH(CH 2 ) 7 --
cis-CH 3 (CH 2 ) 5 CH═CH(CH 2 ) 9 --
trans-CH 3 (CH 2 ) 5 CH═CH(CH 2 ) 9 --
cis, cis-CH 3 (CH 2 ) 4 CH═CHCH 2 CH═CH(CH 2 ) 7 --
trans, trans-CH 3 (CH 2 ) 4 CH═CHCH 2 CH═CH(CH 2 ) 7 --
cis,cis,cis-CH 3 CH 2 CH═CHCH 2 CH═CHCH 2 CH═CH--(CH 2 ) 7 --.
When "W" is a divalent radical of the formula ##STR21## it will be recognized by those skilled in the art that the ##STR22## function and the --NH-- function may be oriented on the benzene ring in the ortho, meta, or para configuration relative to each other. The substituent represented by X may be substituted at any available position of the benzene ring. Preferred embodiments are those in which X is hydrogen and the ##STR23## and --NH-- functions are oriented in the para configuration.
The terms "substituted phenyl" and "substituted benzyl", as defined by R 3 in Formula III, contemplate substitution of a group at any of the available positions in the benzene ring--i.e. the substituent may be in the ortho, meta, or para configuration. The term "C 1 -C 3 alkyl" as defined by R 3 or X in Formula III includes the methyl, ethyl, n-propyl, or i-propyl groups.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of Formula III inhibit the growth of pathogenic fungi, and are useful, therefore, for controlling the growth of fungi on environmental surfaces (as an antiseptic) or in treating infections caused by fungi. In particular, the compounds are active against Candida albicans and are, thus especially useful for treating candidosis. The activity of the compounds can be assessed in standard microbiological test procedures, such as in vitro in agar plate disc diffusion tests or in agar tube dilution tests, or in vivo in tests in mice infected in C. albicans. The compounds are also active against Trichophyton mentagrophytes (a dermatophytic organism), Saccharomyces pastorianus, and Neurospora crassa.
The compounds of Formula III are prepared by acylating S31794/F-1 nucleus at the α-amino group of dihydroxyornithine with the appropriate N-alkanoyl aminoacyl or N-alkenoyl amino acyl side chain using methods conventional in the art for forming an amide bond. The acylation is accomplished, in general, by reacting the nucleus with an activated derivative of the acid (Formula IV) corresponding to the desired acyl side chain group. ##STR24## (W and R 2 have the meaning described herein supra).
By the term "activated derivative" is meant a derivative which renders the carboxyl function of the acylating agent reactive to coupling with the primary amino group to form the amide bond which links the acyl side chain to the nucleus. Suitable activated derivatives, their methods of preparation, and their methods of use as acylating agents for a primary amine will be recognized by those skilled in the art. Preferred activated derivatives are: (a) an acid halide (e.g. acid choride), (b) an acid anhydride (e.g. an alkoxyformic acid anhydride or aryloxyformic acid anhydride) or (c) an activated ester (e.g. a 2,4,5-trichlorophenyl ester, a N-hydroxybenztriazole ester, or an N-hydroxysuccinimide ester). Other methods for activating the carboxyl function include reaction of the carboxylic acid with a carbonyldiimide (e.g. N,N-dicyclohexylcarbodiimide or N,N'-diisopropylcarbodiimide) to give a reactive intermediate which, because of instability, is not isolated, the reaction with the primary amine being carried out in situ.
A preferred method for preparing the compounds of Formula III is by the active ester method. The use of the 2,4,5-trichlorophenyl ester of the desired N-alkanoylamino acid or N-alkenoylamio acid (Formula IV) as the acylating agent is most preferred. In this method, an excess amount of the active ester is reacted with the nucleus at room temperature in a nonreactive organic solvent such as dimethyl formamide (DMF). The reaction time is not critical, although a time of about 15 to about 18 hours is preferred. At the conclusion of the reaction, the solvent is removed, and the residue is purified such as by column chromatography using silica gel as the stationary phase and a mixture of ethyl acetate/methanol (3:2, v/v) as the solvent system.
The 2,4,5-trichlorophenyl esters of the N-alkanoylamino acids or N-alkanoylamino acids can be prepared conveniently by treating the desired amino acid (Formula IV) with 2,4,5-trichlorophenol in the presence of a coupling agent, such as N,N'-dicyclohexylcarbodiimide. Other methods suitable for preparing amino acid esters will be apparent to those skilled in the art.
The N-alkanoylamino acids or N-alkenoylamino acids are either known compounds or they can be made by acylating the appropriate amino acid with the appropriate alkanoyl or alkenoyl group using conventional methods, such as those described herein supra. A preferred way of preparing the N-alkanoylamino acids is by treating the appropriate amino acid with an alkanoic acid chloride in pyridine. The alkanoic acids, the activated derivatives thereof, and the amino acids employed in the preparation of the products of this invention are either known compounds or they can be made by known methods or by modification of known methods which will be apparent to those skilled in the art.
If a particular amino acid contains an acylable functional group other than the amino group, it will be understood by those skilled in the art that such a group must be protected prior to reaction of the amino acid with the reagent employed to attach the alkanoyl or alkenoyl group. Suitable protecting groups can be any group known in the art to be useful for the protection of a side chain functional group in peptide synthesis. Such groups are well known, and the selection of a particular protecting group and its method of use will be readily known to one skilled in the art [see, for example, "Protective Groups In Organic Chemistry", M. McOmie, Editor, Plenum Press, N.Y., 1973].
It will be recognized that certain amino acids employed in the synthesis of the products of this invention may exist in optically active forms, and both the natural configuration (L-configuration) and unnatural configuration (D-configuration) may be employed as starting materials and will give products which are within the contemplation of this invention.
When employed systemically, the dosage of the compounds of Formula III will vary according to the particular compound being employed, the severity and nature of the infection, and the physical condition of the subject being treated. Therapy should be initiated at low dosages, the dosage being increased until the desired antifungal effect is obtained. The compounds can be administered intravenously or intramuscularly by injection in the form of a sterile aqueous solution or suspension to which may be added, if desired, various conventional pharmaceutically acceptable preserving, buffering, solubilizing, or suspending agents. Other additives, such as saline or glucose may be added to make the solutions isotonic. The proportions and nature of such additives will be apparent to those skilled in the art.
When employed to treated vaginal candida infections, the compounds of Formula III can be administered in combination with pharmaceutically acceptable conventional excipients suitable for intravaginal use. Formulations adapted for intravaginal administration will be known to those skilled in the art.
One of the methods of making and using the compounds of the present invention is illustrated in the following examples:
EXAMPLE 1
The following procedure, which give the preparation of the compound of Formula III wherein R 1 is N-(n-dodecanoyl)-p-aminobenzoyl, illustrates a method of preparation of the compounds of Formula III.
A. Preparation of N-(n-dodecanoyl)-p-aminobenzoic acid
n-Dodecanoyl chloride (8.74 g.; 40 mmoles) is added dropwise to a solution of p-aminobenzoic acid (40 mmoles) dissolved in pyridine (100 ml.). The mixture is stirred for 3 hours and poured into water (3 l.). The precipitate which forms is filtered and dried in vacuo to give N-(n-dodecanoyl)-p-aminobenzoic acid (11.01 g.).
B. Preparation of the 2,4,5-trichlorophenyl ester of N-dodecanoyl-p-aminobenzoic acid
N-(n-Dodecanoyl)-p-aminobenzoic acid (11.01 g.; 34.5 mmoles), 2,4,5-trichlorophenol (7.5 g.; 38 mmoles), and dicyclohexylcarbodiimide (6.94 g.; 34.5 mmoles) are dissolved in methylene chloride (250 ml). The mixture is stirred at room temperature for 3.5 hours and then filtered. The filtrate is evaporated in vacuo to give a residue which is crystallized from acetonitrile/water to afford the 2,4,5-trichlorophenyl ester of N-(n-dodecanoyl)-p-aminobenzoic acid (12.84 g.).
C. Acylation of S31794/F-1 nucleus
S317941F-1 nucleus (10.2 mmoles) and the 2,4,5-trichlorophenyl ester of N-(n-dodecanoyl)-p-aminobenzoic acid (10.2 mmoles) are dissolved in dimethylformamide (100 ml.). The solution is stirred at room temperature for 15 hours. Solvent is removed in vacuo to give a residue which is washed twice with diethylether. The washes are discarded. The washed residue is dissolved in methanol (50 ml.) and is purified by reversed phase HPLC by means of a "Prep LC/System 500" unit (Waters Associates, Inc., Milford, Mass.) using a Prep Pak-500/C18 column (Water Associates, Inc.) as the stationary phase. The column is eluted isocratically with H 2 O/CH 3 OH/CH 3 CN (25:65:10 v/v) at 500 psi. The fractions are analyzed by TLC using silica gel plates and H 2 O/CH 3 OH/CH 3 CN (25:65:10 v/v) as the solvent system. Fractions containing the desired products are combined and lyophilized to give the N-(n-dodecanoyl)-p-aminobenzoyl derivative of S31794/F-1 nucleus.
EXAMPLE 2
The method described in Example 1, with minor changes, can be used to synthesize additional derivatives of the S31794/F-1 nucleus. The substitution of the appropriate acyl chloride and amino acid in Step A, the substitution of the appropriate N-alkanoyl amino acid, (plus the use of tetrahydrofuran as the solvent for N-alkanoyl monochloro-substituted aminobenzoic acids), in Step B, and the substitution of the appropriate 2,4,5 trichlorophenyl ester in Step C of Example 1 can yield the derivatives of the S31794/F-1 nucleus shown below:
______________________________________N-Alkanoylamino Acid Derivatives of S31794/F-1 Nucleus ##STR25## IIIR.sup.1______________________________________CH.sub.3 (CH.sub.2).sub.10 CONHCH(CH.sub.2 C.sub.6 H.sub.5)COCH.sub.3 (CH.sub.2).sub.10 CONH(CH.sub.2).sub.4CO(CH.sub.3 (CH.sub.2).sub.10 CONH(CH.sub.2).sub.10CO ##STR26## ##STR27## ##STR28## ##STR29## ##STR30## ##STR31## ##STR32## ##STR33## ##STR34## ##STR35## ##STR36##CH.sub.3 (CH.sub.2).sub.5 CONH(CH.sub.2).sub.10CO ##STR37## ##STR38## ##STR39## ##STR40## ##STR41## ##STR42## ##STR43## ##STR44## ##STR45## ##STR46## ##STR47## ##STR48## ##STR49## ##STR50##
EXAMPLE 3
Preparation of S31794/F-1 Nucleus
A. Fermentation of Actinoplanes utahensis NRRL 12052
A stock culture of Actinoplanes utahensis NRRL 12052 is prepared and maintained on an agar slant. The medium used to prepare the slant is selected from one of the following:
______________________________________MEDIUM A______________________________________Ingredient Amount______________________________________Baby oatmeal 60.0 gYeast 2.5 gK.sub.2 HPO.sub.4 1.0 gCzapek's mineral stock* 5.0 mlAgar 25.0 gDeionized water q.s. to 1 liter______________________________________ pH before autoclaving is about 5.9; adjust to pH 7.2 by addition of NaOH; after autoclaving, pH is about 6.7. *Czapek's mineral stock has the following composition:
Ingredient AmountFeSO.sub.4 . 7H.sub.2 O (dissolved in2 ml conc HCl) 2 gKCl 100 gMgSO.sub.4 . 7H.sub.2 O 100 gDeionized water q.s. to 1 liter
______________________________________MEDIUM BIngredient Amount______________________________________Potato dextrin 5.0 gYeast extract 0.5 gEnzymatic hydrolysate of casein* 3.0 gBeef extract 0.5 gDextrose 12.5 gCorn starch 5.0 gMeat peptone 5.0 gBlackstrap molasses 2.5 gMgSO.sub.4 . 7H.sub.2 O 0.25 gCaCO.sub.3 1.0 gCzapek's mineral stock 2.0 mlAgar 20.0 gDeionized water q.s. to 1 liter______________________________________
The slant is inoculated with Actinoplanes utahensis NRRL 12052, and the inoculated slant is incubated at 30° C. for about 8 to 10 days. About 1/2 of the slant growth is used to inoculate 50 ml of a vegetative medium having the following composition:
______________________________________Ingredient Amount______________________________________Baby oatmeal 20.0 gSucrose 20.0 gYeast 2.5 gDistiller's Dried Grain* 5.0 gK.sub.2 HPO.sub.4 1.0 gCzapek's mineral stock 5.0 mlDeionized water q.s. to 1 liter______________________________________ adjust to pH 7.4 with NaOH; after autoclaving, pH is about 6.8. *National Distillers Products Co., 99 Park Ave., New York, N.Y.
The inoculated vegetative medium is incubated in a 250-ml wide-mouth Erlenmeyer flask at 30° C. for about 72 hours on a shaker rotating through an arc two inches in diameter at 250 RPM.
This incubated vegetative medium may be used directly to inoculate a second-stage vegetative medium. Alternatively and preferably, it can be stored for later use by maintaining the culture in the vapor phase of liquid nitrogen. The culture is prepared for such storage in multiple small vials as follows: In each vial is placed 2 ml of incubated vegetative medium and 2 ml of a glycerol-lactose solution [see W. A. Dailey and C. E. Higgens, "Preservation and Storage of Microorganisms in the Gas Phase of Liquid Nitrogen, Cryobiol 10, 364-367 (1973) for details]. The prepared suspensions are stored in the vapor phase of liquid nitrogen.
A stored suspension (1 ml) thus prepared is used to inoculate 50 ml of a first-stage vegetative medium (having the composition earlier described). The inoculated first-stage vegetative medium is incubated as above-described.
In order to provide a larger volume of inoculum, 10 ml of the incubated first-stage vegetative medium is used to inoculate 400 ml of a second-stage vegetative medium having the same composition as the first-stage vegetative medium. The second-stage medium is incubated in a two-liter wide-mouth Erlenmeyer flask at 30° C. for about 48 hours on a shaker rotating through an arc two inches in diameter at 250 RPM.
Incubated second-stage vegetative medium (800 ml), prepared as above-described, is used to inoculate 100 liters of sterile production medium selected from one of the following:
______________________________________MEDIUM IIngredient Amount (g/L)______________________________________Peanut meal 10.0Soluble meat peptone 5.0Sucrose 20.0KH.sub.2 PO.sub.4 0.5K.sub.2 HPO.sub.4 1.2MgSO.sub.4 . 7H.sub.2 O 0.25Tap water q.s. to 1 liter______________________________________
The pH of the medium is about 6.9 after sterilization by autoclaving at 121° C. for 45 minutes at about 16-18 psi.
______________________________________MEDIUM IIIngredient Amount (g/L)______________________________________Sucrose 30.0Peptone 5.0K.sub.2 HPO.sub.4 1.0KCl 0.5MgSO.sub.4 . 7H.sub.2 O 0.5FeSO.sub.4 . 7H.sub.2 O 0.002Deionized water q.s. to 1 liter______________________________________ Adjust to pH 7.0 with HCl; after autoclaving, pH is about 7.0.
______________________________________MEDIUM IIIIngredient Amount (g/L)______________________________________Glucose 20.0NH.sub.4 Cl 3.0Na.sub.2 SO.sub.4 2.0ZnCl.sub.2 0.019MgCl.sub.2 . 6H.sub.2 O 0.304FeCl.sub.3 . 6H.sub.2 O 0.062MnCl.sub.2 . 4H.sub.2 O 0.035CuCl.sub.2 . 2H.sub.2 O 0.005CaCO.sub.3 6.0KH.sub.2 PO.sub.4 * 0.67Tap water q.s. to 1 liter______________________________________ *Sterilized separately and added aseptically Final pH about 6.6.
The inoculated production medium is allowed to ferment in a 165-liter fermentation tank at a temperature of about 30° C. for about 42 hours. The fermentation medium is stirred with conventional agitators at about 200 RPM and aerated with sterile air to maintain the dissolved oxygen level above 30% of air saturation at atmospheric pressure.
B. Deacylation of Antibiotic S31794/F-I
A fermentation of A. utahensis is carried out as described in Sect. A, using production medium I. After the culture is incubated for about 48 hours, antibiotic S31794F-1, dissolved in a small amount of methanol, is added to the fermentation medium.
Deacylation of S31794/F-1 is monitored by paper-disc assay against Candida albicans. The fermentation is allowed to continue until deacylation is complete as indicated by disappearance of activity.
C. Isolation of S31794/F-1 Nucleus
Whole fermentation broth, obtained as described in Sect. B is filtered. The mycelial cake is discarded. The clear filtrate thus obtained is passed through a column containing HP-20 resin (DIAION High Porous Polymer, HP-Series, Mitsubishi Chemical Industries Limited, Tokyo, Japan). The effluent thus obtained is discarded. The column is then washed with up to eight column volumes of deionized water at pH 6.5-7.5 to remove residual filtered broth. This wash water is discarded. The column is then eluted with a water:methanol (7:3) solution. Elution is monitored using the following procedure: Two aliquots are taken from each eluted fraction. One of the aliquots is concentrated to a small volume and is treated with an acid chloride such as myristoyl chloride. This product and the other (untreated) aliquot are assayed for activity against Candida albicans. If the untreated aliquot does not have activity and the acylated aliquot does have activity, the fraction contains S31794/F-1 nucleus. The eluate containing S31794/F-1 nucleus is concentrated under vacuum to a small volume and lyophilized to give crude nucleus.
D. Purification of S31794F-1 Nucleus by Reversed-Phase Liquid Chromatography
Crude S31794/F-1 nucleus, obtained as described in Section C, is dissolved in water:acetonitrile:acetic acid:pyridine (96:2:1:1). This solution is chromatographed on a column filled with Lichroprep RP-18, particle size 25-40 microns (MC/B Manufacturing Chemists, Inc. E/M, Cincinnati, OH). The column is part of a Chromatospac Prep 100 unit (Jobin Yvon, 16-18 Rue du Canal 91160 Longjumeau, France). The column is operated at a pressure of 90-100 psi, giving a flow rate of about 60 ml/minute, using the same solvent. Separation is monitored at 280 nm using a UV monitor (ISCO Absorption Monitor Model UA-5, Instrumentation Specialties Co., 4700 Superior Ave., Lincoln, Nebraska 68504) with an optical unit (ISCO Type 6).
On the basis of absorption at 280 nm, fractions containing S31794/F-1 nucleus are combined, evaporated under vacuum and lyophilized to give purified S31794/F-1 nucleus.
EXAMPLE 4
Preparation of Antibiotic S31794/F-1
Antibiotic S31794/F-1 is produced by submerged culture of Acrophialophora limonispora NRRL 8095 with stirring, shaking, and/or aeration at pH 3-8, preferably pH 5-7, and at 15°-30° C., preferably at 18°-27° C., for from 48 to 360 hours, preferably from 120 to 288 hours.
Antibiotic S31794/F-1 is isolated by treating the culture broth (90 L) with ethyl acetate:isopropanol (4:1, 90 L) and homogenizing for 30 minutes at room temperature. The organic phase is separated and evaporated under vacuum at about 40° C. The residue thus obtained is chromatographed on a 10-fold amount of silica gel, using CHCl 3 :CH 3 OH (95:5 to 60:40). Fractions which have antifungal activity are combined and chromatographed on a 100-fold amount of "Sephadex LH-20" with methanol. Fractions from the Sephadex column which have antifungal activity are combined and rechromatographed on a 100-fold amount of silica gel (0.05-0.2 mm) with a CHCl 3 :CH 3 OH:H 2 O (71:25:4) solvent system. The fractions eluted which have antifungal activity are combined and evaporated under vacuum to give crude antibiotic S31794/F-1. This product is dissolved in small amounts of methanol and precipitated with diethyl ether to give S31794/F-1 as a white amorphous powder, mp 178°-180° C. (dec.) after drying in high vacuum at 25°-30° C. Crystallization from a 10-fold amount of ethyl acetate:methanol:water (80:12:8) gives crystalline S31794/F-1, mp 181°-183° C. (dec) after drying in high vaccuum at 20° C.
EXAMPLE 5
Isolation of Antibiotic S31794/F-1
Crude antibiotic S31794/F-1, obtained as described in Example 4 after chromatography over Sephadex, is introduced onto a silica-gel column (Michel-Miller Column) through a loop with the aid of a valve system. The column is packed with LP-1/C 18 silica-gel reversed-phase resin (10-20 microns), prepared as described in Example 6, in chloroform:methanol:water (71:25:4) through a loop with the aid of a valve system. The slurry packing procedure described in Example 7 is used. The solvent is moved through the column using an F.M.I. pump with valveless piston design. Elution of the antibiotic is monitored using a UV monitor at 280 nm as in Example 3. Fractions having antifungal activity are combined and concentrated under vacuum to give antibiotic S31794/F-1.
S31794/F-1 has R f values as follow on silica-gel thin-layer chromatography (Merck, 0.25 mm):
______________________________________Solvent System R.sub.f Value______________________________________Chloroform:methanol:water (71:25:4) 0.17Chloroform:methanol:conc. acetic acid(70:29:1) 0.19Chloroform:methanol (2:1) 0.27______________________________________
S31794/F-1 can also be detected by iodine vapor.
EXAMPLE 6
Preparation of Silica Gel/C 18 Reversed Phase Resin
Step 1: Hydrolysis
LP-1 silica gel (1000 g from Quantum Corp., now Whatman) is added to a mixture of concentrated sulfuric acid (1650 ml) and concentrated nitric acid (1650 ml) is a 5-L round-bottom flask and shaken for proper suspension. The mixture is heated on a steam bath overnight (16 hours) with a water-jacketed condenser attached to the flask.
The mixture is cooled in an ice bath and carefully filtered using a sintered-glass funnel. The silica gel is washed with deionized water until the pH is neutral. The silica gel is then washed with acetone (4 L) and dried under vacuum at 100° C. for 2 days.
Step 2: First Silylation
The dry silica gel from Step 1 is transferred to a round-bottom flask and suspended in toluene (3.5 L). The flask is heated on a steam bath for 2 hours to azeotrope off some residual water. Octadecyltrichlorosilane (321 ml, Aldrich Chemical Company) is added, and the reaction mixture is refluxed overnight (16 hours) with slow mechanical stirring at about 60° C. Care is taken so that the stirrer does not reach near the bottom of the flask. This is to prevent grinding the silica gel particles.
The mixture is allowed to cool. The silanized silica gel is collected, washed with toluene (3 L) and acetone (3 L), and then air-dried overnight (16-20 hours). The dried silica gel is suspended in 3.5 L of acetonitrile:water (1:1) in a 5-L flask, stirred carefully at room temperature for 2 hours, filtered, washed with acetone (3 L) and air-dried overnight.
Step 3: Second Silylation
The procedure from the first silylation is repeated using 200 ml of octadecyltrichlorosilane. The suspension is refluxed at 60° C. for 2 hours while stirring carefully. The final product is recovered by filtration, washed with toluene (3 L) and methanol (6 L), and then dried under vacuum at 50° C. overnight (16-20 hours).
EXAMPLE 7
Slurry Packing Procedure for Michel-Miller Columns
General Information
This procedure is employed for packing silica gel C 18 reversed phase resin such as that prepared by the method of Example 6. Generally, a pressure of less than 200 psi and flow rates between 5-40 ml/minute are required for this slurry packing technique; this is dependent on column volume and size. Packing pressure should exceed the pressure used during actual separation by 30-50 psi; this will assure no further compression of the adsorbent during separation runs.
A sudden decrease in pressure may cause cracks or channels to form in the packing material, which would greatly reduce column efficiency. Therefore, it is important to let the pressure drop slowly to zero whenever the pump is turned off.
The approximate volume of columns (Ace Glass Cat. No., unpacked) are No. 5795-04, 12 ml; No. 5795-10, 110 ml; No. 5795-16, 300 ml; No. 5795-24, 635 ml; and No. 5796-34, 34 ml.
The time required to pack a glass column will vary from minutes to several hours depending on column size and the experience of the scientist.
Example:
1. Connect glass column to a reservoir column via coupling (volume of reservoir column should be twice that of the column). Place both columns in vertical positions (reservoir column above).
2. Weigh out packing material (ca. 100 g for 200 ml column).
3. Add ca. five volumes of solvent to packing material; use a mixture of 70-80% methanol and 20-30% water.
4. Shake well until all particles are wetted, let stand overnight or longer to assure complete soaking of particles by solvent. Decant supernatant liquid.
5. Slurry the resin with sufficient solvent to fill reservoir column. Pour swiftly into reservoir. The column must be pre-filled with the same solvent and the reservoir column should be partly filled with solvent before slurry is poured. The use of larger slurry volumes may also provide good results; however, this will require (a) larger reservoir or (b) multiple reservoir fillings during the packing procedure.
6. Close reservoir with the Teflon plug beneath the column (see FIG. 1 of U.S. Pat. No. 4,131,547, plug No. 3); connect to pump; and immediately start pumping solvent through system at maximum flow rate if Ace Cat. No. 13265-25 Pump or similar solvent-delivery system is used (ca. 20 ml/minute).
7. Continue until column is completely filled with adsorbent. Pressure should not exceed maximum tolerance of column during this operation (ca. 200 psi for large columns and 300 psi for analytical columns). In most cases, pressures less than 200 psi will be sufficient.
8. Should pressure exceed maximum values, reduce flow-rate; pressure will drop.
9. After column has been filled with adsorbent, turn off pump; let pressure drop to zero; disconnect reservoir; replace reservoir with a pre-column; fill pre-column with solvent and small amount of adsorbent; and pump at maximum pressure until column is completely packed. For additional information, see general procedure. Always allow pressure to decrease slowly after turning off pump--this will prevent formation of any cracks or channels in the packing material.
10. Relieve pressure and disconnect pre-column carefully. With small spatula remove a few mm (2-4) of packing from top of column; place 1 or 2 filter(s) in top of column; gently depress to top of packing material, and place Teflon plug on top of column until seal is confirmed. Connect column to pump, put pressure on (usually less than 200 psi) and observe through glass wall on top of column if resin is packing any further. If packing material should continue to settle (this may be the case with larger columns), some dead space or channelling will appear and step 9 should be repeated.
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Compounds of the formula ##STR1## wherein R 1 is an N-alkanoyl amino acyl group of the formula ##STR2## wherein: W is a divalent aminoacyl radical of the formula: ##STR3## wherein A is C 1 -C 10 alkylene or C 5 -C 6 cycloalkylene; ##STR4## wherein R 3 is hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indolemethyl, phenyl, benzyl, or substituted phenyl or substituted benzyl in which the benzene ring thereof is substituted with chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR5## wherein X is hydrogen, chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkoxy, mercapto, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR6## wherein X 1 is chloro, bromo, or iodo; ##STR7## wherein B is a divalent radical of the formula: --(CH 2 ) n --, wherein n is an integer from 1 to 3; --CH═CH--; --CH═CH--CH 2 --; or ##STR8## and R 2 is C 1 -C 17 alkyl or C 2 --C 17 alkenyl; have antifungal activity.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional patent application No. 62/057,113, entitled “Quality Users Information Employed For Improved User Experience Including Ratings And Recommendations,” which was filed on Sep. 29, 2014 and is incorporated by reference in its entirety.
BACKGROUND
[0002] Any service or item that is used or sold may be related to its user or potential user by a variety of criteria, where each item of criteria relates to the user's use of the item or the context of that use. One example of relating product criteria to a user occurs in the area of ratings. Customers or users apply their personal rating to all types of products and services such as software, dining, movies, consumer products, etc. Most rating systems rely on user comments and only a few metrics to illustrate why the user liked or didn't like a product or service. For example, a typical restaurant rating service may show noise level, food quality and service as separate ratable criteria, but to truly understand the user's experience, a reader must closely review comments provided by the rating user (e.g. a user that has purchased the product or service and provided a rating). In order to understand the usefulness of any particular rating, the reading user (e.g. a user considering the purchase of a product or service and reading the ratings provided by other users) may typically try to understand how well she relates to the perspective of the rating user. In other words, the reading user should try to use the rating user as a reference and determine whether the reference may be relied upon to indicate whether the reading user would share the opinion of the rating user. The more that is known about the reading user and the rating user, the more rich and therefore valuable ratings information can be. This is because a system can automatically correlate reading users with rating users to determine their compatibility.
[0003] Matching information about product and service users/buyers with potential user/buyers has applications far beyond just ratings. For example, similar information can be used to make recommendations to shoppers or to change or optimize product features as well as sales and marketing strategies and tactics. In addition, matching and analyzing information about buyers and users of a product or service can reveal very useful information for product improvement and customer satisfaction improvement.
[0004] One issue with exploiting user data for ratings, recommendations, and other customer oriented issues is that manufacturers and sellers are incented to game the system by providing contrived reviews, ratings, and other feedback information to the services that inform consumers. There are many ways to contrive ratings and other feedback information. For example, farms of paid users may be employed by a manufacturer or developer or the developer may unfairly influence real users to artificially inflate ratings. If a service relies on the contrived information, the output of the service will be skewed, for example, resulting in artificially high ratings, inappropriate recommendations, or sub-optimal marketing, sales, and customer service tactics and strategies.
SUMMARY
[0005] A “quality user” or “user quality” profile represents a set of metrics derived from a variety of data regarding a user's (or potentially a device's) use of a particular product or service (e.g. an application program) and the context of that use. At a high level, in certain embodiments, one metric for a quality user profile is a rating for the user (and/or the host device) that indicates how much the user's behaviors should be considered in rating or recommending the product to others. For example, assuming a scale from zero to 10 is applied to each metric of a “quality user” profile, the zero side of the scale correlates with a user whose feedback and use-related information should be totally disregarded. A zero rating might apply to a user that is paid by the application developer to use and rate the application in order to artificially increase ratings and recommendations, and thereby actually increase sales. Alternatively, a 10 rating (on the zero-10 scale) may apply to a genuine user, where the particular product represents a significant amount of the user's time using one or more devices. Of course, the exact behaviors or contextual facts that correlate with a zero or 10 (or any other) rating may vary between products based upon the details of that product and its users. For example, in the area of gaming software, the most representative enthusiastic users of one game may spend many hours using the game, while for a second game, the total use time may be less important than number of game openings/accesses or the amount of in-game purchases.
[0006] With respect to an overall quality user profile, the importance of any particular contextual or behavioral use metric may be determined in any of several ways: by software algorithm; by the developer/manufacturer/service provider; by the developer in cooperation with one or more resellers; by the proprietor of a particular source or store; by independent third parties; or by any combination of the foregoing. In addition, with respect to software, in determining the importance of use metrics for a particular software product, analytics may be employed on prior use of either the software or the host devices. For example, in evaluating use behaviors, data may be acquired regarding an identified user or an identified device or both. In some instances one or another will be available and when both are available, certain embodiments may exploit either or both.
[0007] In addition, the importance of any particular contextual or behavioral metric may change over time as either: past use data yields more insight; or external data (e.g. consumer surveys or identity of paid users) is obtained regarding identified users or devices that sheds light on previously collected behavioral and contextual data. For example, if a software store proprietor develops an algorithm for determining whether a user is genuine or contrived, that algorithm will be based upon the varying importance of certain specific use and contextual metrics. However, as more data is gathered or external data is obtained, it may be desirable to alter the algorithm based upon newer data analytics.
[0008] For some embodiments, the quality user profile will have different common characteristics or patterns that associate with a software application's desirability either generally or for a certain demographic of users. For example, the quality user profile may have a certain characteristic pattern for a good game; a different characteristic patter for a medium game; yet a different pattern for a bad game; and even another pattern for a suspicious use associated with a developer trying to cheat the rating or recommendation system. In general, the quality user profile can be employed to emphasize the metrics for a particular user or device so that ratings and recommendations can rely more on users that genuinely like or do not like an application for its intended use. Similarly, the quality user profile allows ratings and recommendations to rely less on users that are contrived, sampling, surfing, or merely experimenting without experiencing the application enough to become a reliable reference for ratings and recommendations.
[0009] Quality user profiles may also be used to improve monetization and profitability for application developers and sellers. For example, the profiles may be analyzed to determine the correlation of different use and contextual metrics with the amount of in-application purchases. The developer can make changes to the application or the in-application purchase strategy to take advantage of the correlations. This may result in higher profits and revenue as well as more satisfied application users (presumably users pay for what they enjoy or view most important). As another example, a developer may notice that they have too many low quality users or that they have many high quality users, but those high quality users are not correlating with more revenue and profit. The developer or seller of an application can use the quality user profiles to increase revenue, profit and customer satisfaction by incenting usage patterns that correlate with revenue and converting low quality users to high quality users (presumably those with higher revenue usage patterns)
[0010] Ratings and recommendations can be further refined by matching quality user profile patterns of a shopper with a previous buyer. For example, a user that is shopping for applications may gain more information if the ratings and recommendations provided during the shopping experience are biased to overweight users that have profile patterns that are either similar to the shopper or that correlate with the shopper. The bias can be implemented either automatically by the system providing ratings and recommendations or the shopper can be given the ability to bias the ratings herself (e.g. by separately rating products based upon raters having certain profile patterns or by asking the system to mathematically bias the results toward certain profile patterns). In addition, quality user profile patterns may vary by geography, culture, habits, interests or any user characteristics or context derived on or off a host system or application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 shows a representative hardware environment.
[0012] FIG. 2 shows a representative network environment.
[0013] FIG. 3 shows representative software architecture.
[0014] FIG. 4 shows a conceptual organization of hardware, software and function for some embodiments of the invention.
[0015] FIG. 5 shows a generic quality user profile associated with some embodiments of the invention.
[0016] FIG. 6 shows an illustrative quality user profile associated with some embodiments of the invention.
[0017] FIG. 7 illustrates ratings user interfaces associated with some embodiments of the invention.
[0018] FIG. 8 illustrates an exemplary recommendations interface.
[0019] FIG. 9 shows an illustrative process associated with embodiments of the invention.
DETAILED DESCRIPTION
[0020] The inventive embodiments described herein may have implication and use in and with respect to all types of devices, including single and multi-processor computing systems and vertical devices (e.g. cameras or appliances) that incorporate single or multi-processing computing systems. The discussion herein references a common computing configuration having a CPU resource including one or more microprocessors. The discussion is only for illustration and not intended to confine the application of the invention to the disclosed hardware. Other systems having other known or common hardware configurations (now or in the future) are fully contemplated and expected. With that caveat, a typical hardware and software operating environment is discussed below. The hardware configuration may be found, for example, in a server, a laptop, a tablet, a desktop computer, a phone, or any computing device, whether mobile or stationary.
[0021] Referring to FIG. 1 , a simplified functional block diagram of illustrative electronic device 100 is shown according to one embodiment. Electronic device 100 could be, for example, a mobile telephone, personal media device, portable camera, or a tablet, notebook or desktop computer system or even a server. As shown, electronic device 100 may include processor 105 , display 110 , user interface 115 , graphics hardware 120 , device sensors 125 (e.g., GPS, proximity sensor, ambient light sensor, accelerometer and/or gyroscope), microphone 130 , audio codec(s) 135 , speaker(s) 140 , communications circuitry 145 , image capture circuitry 150 (e.g. camera), video codec(s) 155 , memory 160 , storage 165 (e.g. hard drive(s), flash memory, optical memory, etc.) and communications bus 170 . Communications circuitry 145 may include one or more chips or chip sets for enabling cell based communications (e.g., LTE, CDMA, GSM, HSDPA, etc.) or other communications (WiFi, Bluetooth, USB, Thunderbolt, Firewire, etc.). Electronic device 100 may be, for example, a personal digital assistant (PDA), personal music player, a mobile telephone, or a notebook, laptop, tablet computer system, or any desirable combination of the foregoing.
[0022] Processor 105 may execute instructions necessary to carry out or control the operation of many functions performed by device 100 (e.g., such to run applications like games and agent or operating system software to observe and record user behaviors and the context of those behaviors). In general, many of the functions described herein are based upon a microprocessor acting upon software (instructions) embodying the function. Processor 105 may, for instance, drive display 110 and receive user input from user interface 115 . User interface 115 can take a variety of forms, such as a button, keypad, dial, a click wheel, keyboard, display screen and/or a touch screen, or even a microphone or camera (video and/or still) to capture and interpret input sound/voice or images including video. The user interface 115 may capture user input for any purpose including for use as application ratings information or search information or a response to recommendations.
[0023] Processor 105 may be a system-on-chip such as those found in mobile devices and include a dedicated graphics processing unit (GPU). Processor 105 may be based on reduced instruction-set computer (RISC) or complex instruction-set computer (CISC) architectures or any other suitable architecture and may include one or more processing cores. Graphics hardware 120 may be special purpose computational hardware for processing graphics and/or assisting processor 105 to process graphics information. In one embodiment, graphics hardware 120 may include one or more programmable graphics processing units (GPU).
[0024] Sensors 125 and camera circuitry 150 may capture contextual and/or environmental phenomenon such as location information, the status of the device with respect to light, gravity and the magnetic north, and even still and video images. All captured contextual and environmental phenomenon may be used to contribute to descriptions (e.g. metrics) of users' behaviors and the context of those behaviors with respect to a device or any particular application program that may be running on a device. Output from the sensors 125 or camera circuitry 150 may be processed, at least in part, by video codec(s) 155 and/or processor 105 and/or graphics hardware 120 , and/or a dedicated image processing unit incorporated within circuitry 150 . Information so captured may be stored in memory 160 and/or storage 165 and/or in any storage accessible on an attached network. Memory 160 may include one or more different types of media used by processor 105 , graphics hardware 120 , and image capture circuitry 150 to perform device functions. For example, memory 160 may include memory cache, electrically erasable memory (e.g., flash), read-only memory (ROM), and/or random access memory (RAM). Storage 165 may store data such as media (e.g., audio, image and video files), computer program instructions, or other software including database applications, preference information, device profile information, and any other suitable data. Storage 165 may include one more non-transitory storage mediums including, for example, magnetic disks (fixed, floppy, and removable) and tape, optical media such as CD-ROMs and digital video disks (DVDs), and semiconductor memory devices such as Electrically Programmable Read-Only Memory (EPROM), and Electrically Erasable Programmable Read-Only Memory (EEPROM). Memory 160 and storage 165 may be used to retain computer program instructions or code organized into one or more modules in either compiled form or written in any desired computer programming language. When executed by, for example, processor 105 , such computer program code may implement one or more of the acts or functions described herein.
[0025] Referring now to FIG. 2 , illustrative network architecture 200 , within which the disclosed techniques may be implemented, includes a plurality of networks 205 , (i.e., 205 A, 205 B and 205 C), each of which may take any form including, but not limited to, a local area network (LAN) or a wide area network (WAN) such as the Internet. Further, networks 205 may use any desired technology (wired, wireless, or a combination thereof) and protocol (e.g., transmission control protocol, TCP). Coupled to networks 205 are data server computers 210 (i.e., 210 A and 210 B) that are capable of operating server applications such as databases and also capable of communicating over networks 205 . One embodiment using server computers may involve the operation of one or more central systems to collect, process, and distribute user behavior, contextual information, or other information to and from other servers as well as mobile computing devices, such as smart phones or network connected tablets.
[0026] Also coupled to networks 205 , and/or data server computers 210 , are client computers 215 (i.e., 215 A, 215 B and 215 C), which may take the form of any computer, set top box, entertainment device, communications device, or intelligent machine, including embedded systems. In some embodiments, users will employ client computers in the form of smart phones or tablets. Also, in some embodiments, network architecture 210 may also include network printers such as printer 220 and storage systems such as 225 , which may be used to store multi-media items (e.g., images) that are referenced herein. To facilitate communication between different network devices (e.g., data servers 210 , end-user computers 215 , network printer 220 , and storage system 225 ), at least one gateway or router 230 may be optionally coupled there between. Furthermore, in order to facilitate such communication, each device employing the network may comprise a network adapter. For example, if an Ethernet network is desired for communication, each participating device must have an Ethernet adapter or embedded Ethernet capable ICs. Further, the devices may carry network adapters for any network in which they will participate.
[0027] As noted above, embodiments of the inventions disclosed herein include software. As such, a general description of common computing software architecture is provided as expressed in layer diagrams of FIG. 3 . Like the hardware examples, the software architecture discussed here is not intended to be exclusive in any way but rather illustrative. This is especially true for layer-type diagrams, which software developers tend to express in somewhat differing ways. In this case, the description begins with layers starting with the O/S kernel, so lower level software and firmware has been omitted from the illustration but not from the intended embodiments. The notation employed here is generally intended to imply that software elements shown in a layer use resources from the layers below and provide services to layers above. However, in practice, all components of a particular software element may not behave entirely in that manner.
[0028] With those caveats regarding software, referring to FIG. 3 , layer 31 is the O/S kernel, which provides core O/S functions in a protected environment. Above the O/S kernel is layer 32 O/S core services, which extends functional services to the layers above, such as disk and communications access. Layer 33 is inserted to show the general relative positioning of the Open GL library and similar application and framework resources. Layer 34 is an amalgamation of functions typically expressed as multiple layers: applications frameworks and application services. For purposes of our discussion, these layers provide high-level and often functional support for application programs which reside in the highest layer shown here as item 35 . Item C 100 is intended to show the general relative positioning of the agent software, including any client side agent software described for some of the embodiments of the current invention. In particular, in some embodiments, agent software (or other software) that observes user behaviors (including context) and the behavior of applications such as games may reside below the application layer and above the operating system. In addition, some user behaviors may be expressed directly by the user through a user interface (e.g. the response to a question regarding application rating or feature preference). Since the observation of these behaviors may require a user interface, software may be required in the application layer. Further, some user behaviors are monitored by the operating system, and embodiments of the invention herein contemplate enhancements to an operating system to observe and track more user behaviors; such embodiments may use the operating system layers to observe and track user behaviors. While the ingenuity of any particular software developer might place the functions of the software described at any place in the software stack, the software hereinafter described is generally envisioned as all of: (i) user facing, for example, to receive ratings or provide recommendations; (ii) as a utility, or set of functions or utilities, beneath the application layer, for tracking and recording user behaviors and the context of those behaviors; and (iii) as one or more server applications for organizing, analyzing, and distributing user behavior information and analytics that may depend on that information including ratings and recommendations. Furthermore, on the server side, certain embodiments described herein may be implemented using a combination of server application level software, database software, with either possibly including frameworks and a variety of resource modules.
[0029] No limitation is intended by these hardware and software descriptions and the varying embodiments of the inventions herein may include any manner of computing device such as Macs, PCs, PDAs, phones, servers, or even embedded systems.
[0030] Some embodiments of the invention employ a concept of user quality or a “quality user.” Generally, a user may be considered to be high quality if her use of an item (application, genre of applications, device, etc.) is considered representative of other users. The other users may be typical users or a category of users defined by use behaviors and context, demographics or some other sorting mechanism. Also generally, a user may be considered low quality if her use of an item (application, genre of applications, device, etc.) is contrived or more arbitrary when compared to a group of other users. For example, the user's behavior is contrived if the user is paid by a developer to perform use scenarios. Similarly, a user's behavior is arbitrary when the user's behaviors do not correlate well with the behavior of other legitimate users, and perhaps even similarly situated other legitimate users. As used in this disclosure, the concept of a “quality user” or user quality simply represents a set of data (including a single or many aspects) indicating how well one or more users represents the behavior of other users for a given purpose; the purpose being potentially very broad (e.g. use of mobile devices) or more narrow (e.g. use of a particular game on a particular type of device), or anywhere in-between.
[0031] FIG. 4 is a very high-level diagram describing how some embodiments of the invention collect, assemble, and employ user behavior and context information that may contribute to a user quality profile. With reference to FIG. 4 , device 401 is a client device that is pictured as a mobile device but may represent any type of device that a user may employ to run software, such as game software. Device 401 may include any of the hardware forms discussed above and run any of the software. However, device 401 is illustrated in FIG. 4 to include at least a subject application 410 , other applications 415 , and other software 420 . The subject application 410 represents a particular application program run on device 401 by real user 405 . Some embodiments of the invention may employ a set of user behavior and context data that represents the user quality of real user 405 with respect to subject application 410 . For example, if subject application 410 is a driving game, the user quality of real user 405 with respect to the driving game might be represented by data showing how often the game is used, for how long and at what time of day.
[0032] In some embodiments, other applications 415 represents the other applications present on device 401 or the other applications on device 401 that are or have been used by real user 405 . Real user 405 's behavioral data with respect to the other applications may be employed as user quality data with respect to subject application 410 , any one or more of other applications 415 , or anything else relating to the user's behavior on device 401 or elsewhere. For example, the use of subject application 410 may be viewed in light of comparatively: how often one or more of other applications 415 are used; the genres of other applications 415 ; the sources of any of the applications, etc. In addition, some embodiments employ other software 420 to represent system software such as an operating system or specialty software such as agent software, either of which may be employed to observe and/or track user behaviors and context with respect to device 401 , subject application 410 or other applications 415 .
[0033] Referring again to FIG. 4 , real user 405 represents use of application software on device 401 . While real user 405 is illustrated as a specific person, the concept is intended to represent whatever level of use data is available or desired with respect to the user identity. For example, real user 405 may represent a specific user that is identified on device 401 through a personal authentication (e.g. such as when using an operating system offering multiple user accounts and profiles). However, real user 405 may also represent: the overall usage of the device 401 (e.g. where the real user 405 is synonymous with the device); a user of a particular application such as subject application 410 ; a user of a group of applications such as a genre; a presumed user as distinguished by user behaviors from one or more other presumed users of device 401 ; or any logical division of the operation of device 405 . Further, in some embodiments of the invention, behavioral information regarding real user 405 may be augmented by information concerning real user 405 's use of other devices or a marketing, financial, or personal profile available from sources outside device 401 . As we discuss below, most embodiments of the invention seek to protect the privacy of a user by anonymizing the identity of a user prior to assembling and/or using behavioral and contextual information on a server or elsewhere that could compromise the user's privacy. However, in the user's own set of devices (e.g. phone, tablet, laptop, desktop, etc.) and accounts (e.g. Internet based accounts such as gmail, Facebook, Twitter, etc.), the personal identity of the user may be known so that information may be aggregated from multiple sources prior to being anonymized to protect the user's privacy.
[0034] Referring again to FIG. 4 , user behavioral and contextual information may be transmitted from Device 401 over a network 430 , such as the Internet, to servers 435 . The behavioral information may be transmitted in any suitable way at any convenient interval. For example, information may be transmitted as it is collected, or it may be held for a time or until a quantum is obtained prior to transmission. In addition, information may be held to await an available network or a desirable networks status (e.g. desirable speed, low cost, desirable security).
[0035] As illustrated above with respect to the representative hardware discussion, servers 435 may be one or more computers cooperating together. Individual computers that make up server 435 may be co-located or geographically dispersed.
[0036] In most embodiments, the user's real or actual identification will be cleansed from the data in order to protect the privacy of the real user's 405 identity. Other embodiments may allow for maintaining real or actual identity of the user with consent. The behavioral data may be cleansed of identifying information either before the data is transmitted from device 401 or after the data is received at server 435 . By moving the data to the server before cleansing identity, there may be more opportunity to aggregate with other data relating to a specific user. For example, online vendors typically retain purchase history, address, and financial information of customers. In one embodiment, a user account or registration on the server 435 may be used as an aggregation point for data regarding the user. The data may, for example, include user behaviors and context with respect to multiple devices (e.g. phone, tablet, laptop, etc.) and multiple data sources (e.g. online store data, or other Internet activity of the user). This aggregated data may be securely retained subject to a published privacy policy. The aggregated data may also be cleansed of user-identifying information by using an anonymous proxy for a user indication. The cleansed data may be pooled with data from other users and employed for ratings, recommendations, quality control, marketing, product research, etc.
[0037] Once at the server, user behavioral and contextual data may be organized by metrics and used to assemble user quality profiles and/or to perform analytics. As discussed above, there may be a variety of user quality measures because each user may have a quality profile with respect to several references, e.g. user quality profile for an application, user quality profile for a genre of applications, user quality profile with respect to the user's device, etc. Finally, as shown in FIG. 4 , in addition to deriving user quality profiles, analytics on the user behavioral and contextual data may be employed in: ratings for items such as application software or devices; recommendations of software, devices or other products for users; determining techniques and strategies to improve customer satisfaction; and determining techniques and strategies to improve profits and revenue. Of course, the uses of the analytics are not limited to the examples shown in FIG. 4 and can relate to any operational concern of a business.
[0038] Referring now to FIG. 5 , there is shown an illustrative quality user profile or measure for a particular user (whether anonymous or identified). The example embodiment shows consideration of seventeen metrics. Each metric in the illustration is scored with respect to scale 530 . The scores vary between zero and 10 to indicate whether the metric strongly applies to the user (e.g. 10) or does not apply at all (e.g. 0). Of course, the profile may include any number of metrics and any scale or scoring system. In addition, rather than a scale or scoring system, some metrics may be represented by actual behavioral data. For example, for metrics like the following, actual data may be most useful: average minutes of application use per day/week/month; total minutes application use per day/week; month; ratio of time using a particular application versus all application on a specific device or for a particular user. Of course, the profile may include other metrics that are most suited for a scaled score, e.g. the likelihood the user is genuine, the proclivity of the user to make in-app purchases, or the presumed user preference for a certain genre of application. Generally, if a metric can be measured objectively, the use of real data may be appropriate rather than a scaled score. Alternatively, metrics that are derived from real data using an algorithm or subjective analysis may be more appropriate for a scaled score. None of this illustration, however, is intended to confine the invention to employing a certain type of scale or using actual data for any particular metric.
[0039] With reference to FIG. 5 , the illustrated quality user profile is merely populated with generic metrics labeled as metric one 501 , metric two 502 and so on to metric seventeen 517 . Actual metrics used for any particular user quality measurement or profile may depend upon the reference for the user quality profile and may include significant contextual information such as the user's use of hardware and/or software as well as demographic and personal preference information about a user. There are many more specific types of user behavior and other metrics contemplated for varying embodiments of the invention.
[0040] One category of metrics contemplated by certain embodiments of the invention relates to a subject application or any application under consideration for data collection. For example if device 401 has or acquires a specific application, there are several metrics that may be observed and recorded with respect to that application program and associated with the user:
a. The identity of the application under consideration and its feature set, including multi-user support, GameCenter or similar support for a cooperative networked environment, controller, or accessory support, etc. b. The amount paid for the application (including $0, to effectively answer the question of whether the application was purchased or free). c. Whether the user had a payment method on file with the application source (e.g. a credit card or PayPal account on file at the App store). d. Ratings for the subject application provided by the user for the subject application and other applications, and when the ratings were provided. e. The location, time and/or date of each time the application is opened, which may also effectively reveal several other metrics:
i. The number of times the application is opened during any particular time interval, e.g. day, week, month, year, ever. ii. The recency of opening the program, potentially including: the amount of time elapsed since the last time the application was opened or since the application was acquired, installed, updated or published; the amount of time elapsed since each time the program was opened; and the average time elapsed since the prior program openings during a defined interval, such as the prior week or month. iii. How many times the user opened the program. iv. The distribution of program opening times with respect to a day, circadian rhythm, normal work hours, normal sleep hours, week, work week, month, or other intervals (e.g. opened mostly on weekdays between 7 and 11 PM, with only sparse openings at other times) v. The motion of the host device each time the application was opened (e.g. the approximate speed of motion of the host device in motion when the program was opened). vi. The average number of times the application was opened each hour, day, month or other designated time interval. The average may be taken over the entire life of the application on a device or over a time period such as a recent time period (the prior day, week, month, etc.). vii. The rate of change of program openings over a time interval (e.g. during the prior month the number of daily openings increased).
f. Session lengths (e.g. each time the application is opened, how long is it used, in the device's foreground, or actively used), which may also effectively reveal several other metrics:
i. The average session time during any particular time interval, e.g. day, week, month, year, ever. ii. The recency of sessions, potentially including: the amount of time elapsed since the last session of a certain length (e.g. above 10 minutes); and, the average time elapsed between sessions of a certain length (e.g. over 10 minutes) iii. Overall session time. iv. The average session time over a time interval (e.g. during the last day, week, month, etc.) v. The distribution of session lengths with respect to a day, normal work hours, circadian rhythm, normal sleep hours, week, work week, month, or other intervals (e.g. longer sessions (e.g. over 20 minutes) mostly on weekdays between 7 and 11 PM, with only very short session (e.g. under 5 minutes) at other times) vi. The motion of the host device during each session (e.g. the approximate distance covered or geography traversed during each session). vii. The average session time each day, month or other designated time interval. The average may be taken over the entire life of the application on a device or over a time period such as a recent time period (the prior day, week, month, etc.). viii. The rate of change of session times over a time interval (e.g. during the prior month the session times are increasing or the average daily session time is increasing, etc.).
g. How extensively the features of the application are exercised (e.g. each time the application used, which features of the application are used), which may also effectively reveal several other metrics:
i. The total number or identity of features or most common features used during any particular time interval, e.g. day, week, month, year, ever. ii. The recency of each feature used potentially including the amount of time elapsed since each feature or selection of features has been accessed. iii. The average feature set or number of features used over a time interval (e.g. during the last day, week, month, etc.) iv. The distribution of features used with respect to a day, circadian rhythm, normal work hours, normal sleep hours, week, work week, month, or other intervals (e.g. some features used in the morning but never at night). v. The motion of the host device during the use of each feature (e.g. the approximate distance covered or geography traversed while a particular feature is in use). vi. The average number of features or set of features used each day, month or other designated time interval. The average may be taken over the entire life of the application on a device or over a time period such as a recent time period (the prior day, week, month, etc.). vii. The rate of change of feature use over a time interval (e.g. during the prior month the user increased their feature use or the average daily number of features used is increasing, etc.).
h. In-application purchase information (e.g. each time the application is opened, the amount of money spent on in-application purchases, and exactly what is purchased), which may also effectively reveal several other metrics:
i. The average spent on in-application purchases during any particular time interval, e.g. day, week, month, year, ever. ii. The recency of in application purchases, potentially including: the amount of time elapsed since the last in-application purchase or since an in-application purchase exceeded a threshold; and, the average time elapsed between in-application purchases or in application purchases over a threshold. iii. Overall total of in-application purchases. iv. The amount of refunds of in-application purchases and whether there has been a request for a refund. v. The average amount of in-application purchases over a time interval (e.g. during the last day, week, month, etc.) vi. The distribution of in-application purchases with respect to a day, circadian rhythm, normal work hours, normal sleep hours, week, work week, month, or other intervals (e.g. in-application purchases or those over a threshold mostly occur on weekdays between 7 and 11 PM). vii. The average amount of in-application purchases each day, month or other designated time interval. The average may be taken over the entire life of the application on a device or over a time period such as a recent time period (the prior day, week, month, etc.). viii. The rate of change of in-application purchases or the currency amount of those purchases over a time interval (e.g. during the prior month the session times are increasing or the average daily session time is increasing, etc.).
i. The use of the subject application program relative to the other use or uses of the host device (e.g. 5% of device usage time is spent using the application, of game play (genre) time on the device is spent using the subject application program), which may also effectively reveal several other metrics:
i. The average percentage of device usage time employed for the subject application during any particular time interval, e.g. day, week, month, year, ever. ii. The recency of a time interval where the application usage time exceeded a threshold of device usage time (e.g. the last time the subject application was over 10% of a day's device usage), potentially including: the amount of time elapsed since the last time application usage percentage exceeded a threshold; and, the average time elapsed between time intervals (e.g. days) where application usage percentage exceeded a threshold. iii. Overall percentage of device usage time employed for the subject application. iv. The average percentage of device usage time employed for the subject application over a time interval (e.g. during the last day, week, month, etc.). The average may be taken over the entire life of the application on a device or over a time period such as a recent time period (the prior day, week, month, etc.). v. The rate of change of application usage percentage over a time interval (e.g. during the prior month the percent application usage times are increasing or the average daily percent application usage time is increasing, etc.).
j. The geographic location of a device during any of the other observed behaviors. k. The identity of the host device (e.g. model and brand, including software versions such as operating system version). l. Companion applications on the device including metrics such as:
i. The identity, genre, or other information about applications other than the subject application that are installed on the host device. Other information may include any of the information discussed regarding the subject application. ii. The identity, genre, or other information about applications other than the subject application that open on the host device while the subject application is in use.
[0090] Useful metrics may also include observations regarding behaviors that are less directly tied to a subject application. For example the following user and/or device behaviors may be of use in constructing a quality user profile:
a. The identity of sources for all of the software or media held by the host device (e.g. App. Stores, book stores, Audible, Amazon, Internet download, etc.). b. The overall use pattern of the device, including for example, the local time of each device feature or software use and any pattern of use over time. c. The user's purchase history with any particular network-accessible storefront. d. The user's use of multiple devices (either linearly in time or contemporaneously) to access any particular network-accessible account. e. The personal demographics of the user, such as race, religion, address, income class, etc.
[0096] Referring now to FIG. 6 , a user quality profile is shown employing specific metrics 601 to 617 . Some of the metrics are represented by actual data, for example, metric 601 , “the amount paid for the application.” Other metrics can be yes/no data, such as metric 602 , “user payment method on file.” The quality user profile shown in FIG. 6 illustrates that some related metrics may be individually scored with data or otherwise, such as metrics 603 to 605 relating to the number of times the application has been opened. In the same profile, sets of related metrics may carry only a cumulatively scaled score determined by an algorithm or other process, such as metric 606 , “session length scaled score.” As FIG. 6 exemplifies, metrics can be employed in a quality user profile in any desirable way—individually and discretely or with scoring that encompasses a category of behaviors.
[0097] After collecting or assembling quality user profiles on a variety of users (whether or not anonymized), the profiles may be correlated to assist in efforts relating to ratings, recommendations, sales and marketing, and customer satisfaction. The data for various users may be correlated employing any mathematical techniques, which are commonly known now or in the future.
[0098] Many embodiments may employ profile data to eliminate or de-rate information from users that is contrived or otherwise not representative of legitimate natural users. For example, user profiles may be eliminated or have their affects de-rated if session time data or application opening data reveals that the subject applications were too briefly used to receive a meaningful rating from the user or to consider the user's behavioral information very informative toward recommendations, customer service or other efforts. Similarly, it may be desirable to de-rate or exclude certain user's profile information if data regarding the location of use combined with session time data shows that many uses of the program were contrived, e.g. performed in collective environments in regions of the world with low labor cost and unlikely abilities to use the subject application in its native language. Alternatively, certain quality user profiles may be de-rated or eliminated on a statistical or mathematical basis. For example, certain user profiles may not fall within designated boundaries of any common profile pattern determined by analytics. In addition, mathematical concepts such as Benford's law may also be applied.
[0099] In some embodiments, the overall user profile data (or a large amount of the data) is correlated for a large number of users, and patterns are identified for which many users correlate. For example, in correlating 10,000 profiles, we may find that 200 geographically close users provided ratings for a game application within a few days of the game release, with high ratings and very little session time. These users might then be de-rated or excluded as contrived and their overall profile information can be used to identify other contrived users through correlation of other metrics (location, time, device identity, etc.). In the same manner, correlation patterns can be used to find power users of an application, or other types of users and then the other metrics from the identified group can be employed to correlate related users.
[0100] By using correlation techniques as discussed above or otherwise, application rating systems may be improved. By way of illustration, FIG. 7 shows an exemplary application store page 700 from the Apple App store or an analogous store. This illustrated store page shows advertising information 705 for each of a variety of game genre applications. Each application's advertising information contains a user rating section 710 . The quality user information discussed herein as well as the correlation analysis of many user profiles can be used to enhance the quality and usefulness of this rating information. For example, in some embodiments, for any particular application program, the application's rating score may only be affected by ratings provided by users that are determined: to not be contrived; to be casual, moderate, or power users of the application. By way of illustration, the rating 719 shown in advertising information 715 may only contemplate the input of users whose quality user profile information does not correlate with contrived users. In other embodiments, if a user viewing ratings is determined to be a power user according to her quality profile, then the ratings visible to that user may rely only on other power users or may be weighted to power users. Also by way of illustration, assuming a user viewing the rating has a profile indicating that she is a power user, game information 720 shows a rating line featuring only ratings from power users. The same concept could be adopted to any type of user or application-related item, e.g. casual user, game controller user, child under 10, senior citizen, etc. Similarly, in some embodiments, for example, application information 725 , the rating score interface presented to the user may show ratings information for multiple user bases (a rating by power users, another by casual users and so on). Alternatively, as illustrated in application information 730 , the UI may allow the user to select the user base that provides basis for the visible recommendation. In the illustration of application information 730 , a dropdown menu is shown 734 to allow the user to select the desired information base for ratings. The number of options for dividing the user base in order to give more specific ratings results are only limited by the extent of the quality user profile data. The more data that exists in each profile, the more control and specificity that may be provided to a user.
[0101] Similar to ratings, the quality user profiles and correlations of that data may be used to improve or enhance recommendations. By way of illustration, FIG. 8 shows an exemplary recommendation page 800 from an Apple App store displaying application information 805 for each of four applications that are recommended to the user based upon analysis of information the App Store knows about the user. The quality of these recommendations may be improved by using quality user information as described along with correlations of the quality user profiles. For example, recommendations to a subject (e.g. reading) user may be presented with recommendations that prioritize applications used by other users with profiles or partial profiles that correlate with the subject user. This technique might be enhanced by basing the recommendations for a particular application on other users that are both high quality users with respect to that application and have profile similarities to the reading user. A sample user interface for these concepts is illustrated as item 830 and expressly states that the recommendation emphasizes the opinions of similar users. Of course, the express qualification relating to “similar users” is optional and may be placed in the user interface so as to apply to multiple recommended applications (e.g. together in a box, in a line, on a page, etc.).
[0102] Other examples are as follows: a subject user may be presented with recommendations that only show applications used by other users with profiles or partial profiles that correlate with the subject user (optional user interface shown at 815 ); recommendations that present the subject user with recommendations that exclude applications used by other users with profiles that do not sufficiently correlate with the subject user (optional user interface shown at 820 ); recommendations that present the user with recommendations that are derived as selected by the user through the user interface (e.g. by using a checklist, dropdown or other technique as shown at 825 ); or, any combination of the foregoing or other use of the quality user profile data metrics that can correlate similar and dissimilar users. Furthermore, any of the options for displaying ratings on an interface may be combined with any of the options for displaying recommendations.
[0103] With reference to FIG. 9 , a general process is shown that reflects many embodiments of the invention. The process is intended to be illustrative so that many of the concepts herein may be embodied in the diagramed process or portions of the process. According to the illustrative process, at 905 a user and/or device is identified either explicitly (e.g. by user or software registration) or implicitly (e.g. by noting activity). Either the user or the device or a combination of both may be employed as a reference for a user quality profile so that data relating to the user/device/both is associated with the reference. At 910 the process involves collecting behavioral and contextual information regarding the user/device reference. As discussed above, this data may relate to the use of an application, the device, a group of applications, or any desirable area for which it is desirable to correlate users. Moving to 915 , collected data may be optionally aggregated with other information regarding the user/device. For example, account information, social media information, financial information, or other data obtained from sources outside the device(s) being monitored may be combined to form a more rich data collection. At 920 , steps may be taken to protect the privacy concerns of the user. For example, consent may be obtained, or identifying information may be removed and exchanged for an anonymous indicator. Of course, any known technique for privacy protection may be employed.
[0104] At 925 , a quality user profile is assembled, if it is not already implicit in the data. For example, a quality user profile may be represented by a collection of metrics regarding behavioral and contextual information about the user's/device's interaction with a program, device, group of programs, etc. Examples of quality user profiles are shown in FIGS. 5 and 6 . At 930 , a plurality of quality user profiles are analyzed to find correlations and patterns of user/device metrics. For example, the analysis may reveal a group of users/devices that frequently (e.g. several times each week) employ a subject application program, such as a game, for long sessions (e.g. greater than 30 minutes). Similarly, the analysis may find a group of users that provide explicit ratings for programs with very little use of those programs.
[0105] At 935 , the process calls for employing user profile information in accordance with the correlation results. For example, the profiles that are frequent users of a game for long sessions may be more heavily weighted for ratings and recommendations. Alternatively, the profiles that provide ratings with little or no application use may be de-rated or ignored for ratings and recommendations. Finally, at 940 , a GUI is created and/or displayed to reflect the correlation results. For example, ratings and recommendations may be collected or displayed as discussed above, at least with respect to FIGS. 7 and 8 .
[0106] It is to be understood that the above description is intended to be illustrative, and not restrictive. The material has been presented to enable any person skilled in the art to make and use the invention as claimed and is provided in the context of particular embodiments, variations of which will be readily apparent to those skilled in the art (e.g., many of the disclosed embodiments may be used in combination with each other). In addition, it will be understood that some of the operations identified herein may be performed in different orders. The scope of the invention therefore should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.”
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An apparatus, method, and computer readable medium related to monitoring computer users to acquire information regarding use of application programs and device features as well as the context of such use. Computer users are monitored and data is collected to indicate the computer users' activities including the use of any particular application program. Profiles of each computer user may be created where the profiles are an aggregate of the collected information or a portion thereof. The Profiles may correlated to determine relationships between user behaviors. Various analytics regarding the relationship information may be employed to improve customer-oriented information such as ratings, recommendations, customer support, marketing, communications, and product features design.
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[0001] This application is a divisional of co-pending U.S. patent application Ser. No. 11/319,912, filed Dec. 27, 2005 (Attorney Docket No. OPP-GZ-2005-0006-US-00), which claims the benefit of Korean Application No. P2004-118276, filed on Dec. 31, 2004, each of which is hereby incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a memory device, and more particularly, to a Split Gate (Flash) Electrically Erasable Programmable Read Only Memory (EEPROM) and a method for manufacturing the same.
[0004] 2. Discussion of the Related Art
[0005] A typical example of a nonvolatile memory device, which has electric program and erase functions, is a (flash) EEPROM (Electrically Erasable Programmable Read Only Memory) cell. Such (flash) EEPROM cells may be classified into a stack structure and a split gate structure.
[0006] FIG. 1 shows a cross sectional view of a stack type EEPROM cell according to the related art. FIG. 2 shows a cross sectional view of a split gate type EEPROM cell according to the related art.
[0007] As shown in FIG. 1 , the stack type EEPROM cell according to the related art includes a p-type semiconductor substrate 1 , a tunneling oxide layer 2 , a floating gate 3 , an inter-poly oxide layer 4 , and a control gate 5 formed in sequence. Also, source and drain regions 6 and 7 are formed at opposed sides of the floating gate 3 and the control gate 5 in the p-type semiconductor substrate 1 by implantation of, e.g., n-type impurity ions.
[0008] In case of the stack type EEPROM cell, the floating gate 3 and the control gate 5 are stacked on the p-type semiconductor substrate 1 . In this case, even though an area of the cell is relatively small, it may have a problem in that the erase function of the cell can be excessive. In such an excessive erase problem, the cell threshold may be shifted after many repeated write/erase cycles. In order to overcome the problem of the excessive erase function, the split gate type EEPROM cell has been proposed.
[0009] As shown in FIG. 2 , a split gate type EEPROM cell according to the related art, a tunneling oxide layer 2 may be formed on a p-type semiconductor substrate 1 , and a floating gate 3 is generally formed on a predetermined portion of the tunneling oxide layer 2 . Then, an inter-poly oxide layer 4 is generally formed on the floating gate 3 , and a select gate oxide layer 8 is formed at one side of the floating gate 3 on the p-type semiconductor substrate 1 . After that, a control gate 5 may be formed on the inter-poly oxide layer 4 and the select gate oxide layer 8 , where the inter-poly oxide layer 4 may be formed as one body (e.g., may be unitary) with the select gate oxide layer 8 . Then, source and drain regions 6 and 7 are generally formed at opposed sides of the floating gate 3 and the control gate 5 in the (p-type) semiconductor substrate 1 by implantation of a high concentration or doping level of n-type impurity ions.
[0010] Accordingly, the split gate design makes it possible to solve the problem of the excessive erase function of the cell. However, the control gate 5 is formed not only on the floating gate 3 but also over the p-type semiconductor substrate 1 , so that it can be difficult to decrease the area of the cell (or make it about the same size as the stacked gate structure). As a result, it may be difficult to satisfy the trend toward high integration in semiconductor devices containing EEPROM cells, particularly flash EEPROM cells.
[0011] In the related art split gate type (flash) EEPROM cell, a channel length of the control gate is generally formed or determined by an overlay control of photolithography. As a result, a threshold voltage and/or a cell current may be changed during operation of the cell. Also, since the control gate is formed along the surface of a wafer, it is highly desirable to consider overlay margins during scaling.
SUMMARY OF THE INVENTION
[0012] Accordingly, the present invention is directed to a split gate flash EEPROM cell and a method for manufacturing the same that substantially obviates one or more problems due to limitations and disadvantages of the related art.
[0013] An object of the present invention is to provide a split gate (flash) EEPROM cell and a method for manufacturing the same, in which a control gate and a floating gate have a vertical structure (e.g., a height greater than the width), to minimize the cell size and/or to obtain a high coupling ratio, thereby lowering a programming voltage.
[0014] Additional advantages, objects, and features of the invention will be set forth at least in part in the description which follows and in part will become apparent to those skilled in the art upon examination of the following or may be learned from practice of the invention. The objectives and other advantages of the invention may be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
[0015] To achieve these objects and other advantages and in accordance with the purpose of the invention, as embodied and broadly described herein, a memory device may include a semiconductor substrate having a trench; a tunneling oxide layer at sidewalls of the trench; a floating gate, a dielectric layer and a control gate, in order, on the tunneling oxide layer at sidewalls of the trench; a buffer dielectric layer at sidewalls of the floating gate and the control gate; a source junction on the semiconductor substrate of the bottom surface of the trench; a source electrode in the trench between the buffer dielectric layers, electrically connected to the source junction; and a drain junction on the surface of the semiconductor substrate outside the trench.
[0016] The upper surface of the floating gate may have a hollow part or indentation (generally, a topography with a lower portion, but generally referred to herein as an indentation), and the lower surface of the control gate may have a complementary protrusion, generally corresponding to the floating gate indentation. Also, the source and drain junctions may contain different impurity ions having the same conductivity type. Furthermore, the floating gate and the control gate may overlap each other along their sides (e.g., the vertical axis). Also, in an exemplary embodiment, the present split gate EEPROM cell is capable of storing two bits of data per cell.
[0017] In another aspect, a method for manufacturing a memory device may include steps of depositing an insulating layer on a semiconductor substrate; forming a first trench by etching the insulating layer and the semiconductor substrate to a predetermined depth; forming a tunneling oxide layer in the first trench; forming a floating gate layer on the tunneling oxide layer inside the first trench; forming a dielectric layer on the floating gate layer; forming a control gate layer in the first trench of the dielectric layer; forming an oxide layer on the surface of the control gate layer; forming a second trench by removing central portions of the oxide layer, the control gate layer, the dielectric layer, the floating gate layer and the tunneling oxide layer in the trench; forming a buffer dielectric layer on a sidewall of the second trench; forming a source junction by implanting impurity ions into the semiconductor substrate below the second trench; forming a source electrode in the second trench, electrically connected to the source junction; and forming a drain junction by implanting impurity ions into areas of the semiconductor substrate from which the insulating layer is removed (more generally, exposed areas of the semiconductor substrate).
[0018] The source and drain junctions may be formed by implanting different impurity ions having the same conductivity type (i.e., forming source junctions may comprise implanting a first impurity ion of a first conductivity type, and forming drain junctions may comprise implanting a second impurity ion of the first conductivity type, but different from the first impurity ion).
[0019] In another aspect, a method for manufacturing a memory device may include depositing an insulating layer on a semiconductor substrate; forming a first trench by etching the insulating layer and the semiconductor substrate to a predetermined depth; forming a tunneling oxide layer in the trench; forming a floating gate layer on the tunneling oxide layer in the first trench; forming a hollow part, indentation or depression (more generally, “indentation”) by etching a central portion of the floating gate layer to a predetermined depth; forming a dielectric layer on the floating gate layer; forming a control gate layer in the first trench on the dielectric layer; forming an oxide layer on the control gate layer; forming a second trench by removing central portions of the oxide layer, the control gate layer, the dielectric layer, the floating gate layer, and the tunneling oxide layer in the first trench; forming a buffer dielectric layer at a sidewall of the second trench; forming a source junction by implanting impurity ions into the semiconductor substrate below the second trench; forming a source electrode in the second trench, electrically connected to the source junction; and forming a drain junction by removing the insulating layer and implanting impurity ions into exposed areas of the semiconductor substrate, from which the insulating layer is removed (e.g., using the insulating layer as a mask).
[0020] The control gate layer may be formed in (e.g., complementary to) the indentation in the floating gate layer, so that the floating gate layer overlaps with the control gate layer at a side part thereof (e.g., along a vertical axis of the cell).
[0021] It is to be understood that both the foregoing general description and the following detailed description of the present invention are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principle of the invention. In the drawings:
[0023] FIG. 1 is a cross-sectional view of a stack type flash EEPROM cell according to the related art;
[0024] FIG. 2 is a cross-sectional view of a split gate flash EEPROM cell according to the related art;
[0025] FIG. 3A to FIG. 3G are cross-sectional views of an exemplary process for manufacturing a split gate (flash) EEPROM cell according to a first embodiment of the present invention; and
[0026] FIG. 4A to FIG. 4H are cross-sectional views of an exemplary process for manufacturing a split gate (flash) EEPROM cell according to a second embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0027] Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
[0028] Hereinafter, a memory device and a method for manufacturing the same according to the present invention will be described with reference to the accompanying drawings.
[0029] FIG. 3A to FIG. 3G are cross sectional views of the process for manufacturing a split gate flash EEPROM cell according to the first embodiment of the present invention.
[0030] As shown in FIG. 3A , a semiconductor substrate 200 may have therein an active area and a field area, defined at least in part by a device isolation layer (not shown). Then, a buffer oxide (e.g., silicon dioxide) layer 201 and an insulating layer 202 are sequentially deposited on the semiconductor substrate 200 . After that, a first photoresist 215 is coated on the insulating layer 202 , and then the first photoresist 215 is patterned on the insulating layer 202 by a conventional photolithography (e.g., exposure and development) process. At this time, the insulating layer 202 may comprise a nitride layer (e.g., silicon nitride).
[0031] As shown in FIG. 3B , the insulating layer 202 , the buffer oxide layer 201 and the semiconductor substrate 200 are etched to a predetermined depth (e.g., a trench depth) using the patterned first photoresist 215 as a mask, thereby forming a trench T 1 in a cell region. Then, the semiconductor substrate 200 may be etched and/or cleaned by a clean active pit reactive ion etching method. After that, a tunneling oxide layer 203 is formed in a trench T 1 of the semiconductor substrate 200 , and then the first photoresist 215 is removed.
[0032] The tunneling oxide layer 203 may be formed by a chemical vapor deposition (CVD) process (such as plasma enhanced [PE]-CVD or high density plasma [HDP]-CVD, from silicon sources such as TEOS or silane [SiH 4 ], and oxygen sources such as ozone [O 3 ] or oxygen [O 2 ], as is known in the art) or a thermal oxidation process (which may be wet or dry). In the case of the CVD process, the tunneling oxide layer 203 is formed on an entire surface of the semiconductor substrate 200 , including the insulating layer 202 . On the other hand, in the case of the thermal oxidation process, the tunneling oxide layer 203 is formed generally only on the semiconductor substrate 200 in the trench T 1 . In FIG. 3B , the tunneling oxide layer 203 is formed by thermal oxidation.
[0033] Referring to FIG. 3C , a conductive layer (e.g., comprising amorphous silicon, which may be later converted to polysilicon) is deposited on the entire surface of the semiconductor substrate 200 including the trench T 1 . Then, the conductive layer is conventionally etched back so that it remains in a predetermined (e.g., lower) portion of the trench, thereby forming a floating gate layer 204 on the tunneling oxide layer 203 . At this time, after the etch-back process, the trench T 1 has a sufficient space for a control gate.
[0034] As shown in FIG. 3D , a dielectric layer 205 is formed on an upper surface of the floating gate layer 204 . The dielectric layer 205 comprises an oxide layer (e.g., silicon dioxide) and may be formed by a CVD process or a thermal oxidation process. As shown in FIG. 3D , dielectric layer 205 is formed by thermal oxidation. Then, a conductive layer is deposited on the entire surface of the semiconductor substrate 200 . The conductive layer is etched back so that it remains in the trench, whereby a control gate layer 206 is formed on the dielectric layer 205 . Control gate layer 206 generally comprises polysilicon (which may be further doped with one or more conventional silicon dopants and/or which may further contain a conventional metal silicide). After that, an upper surface of the control gate layer 206 may be conventionally oxidized to form an oxide layer 207 .
[0035] As shown in FIG. 3E , a second photoresist layer 216 is formed on the entire surface of the semiconductor substrate 200 including the oxide layer 207 , and then the second photoresist 216 is patterned to expose a central portion of the trench T 1 by a conventional photolithography (e.g., exposure and development) process. Generally, the patterned second photoresist 216 covers a sufficient width and/or length of an outer or peripheral portion of the underlying oxide layer 207 to enable subsequent formation of an electrode or contact to the control gate layer 206 (e.g., after formation of the cell is substantially complete and/or during formation of an electrode or contact to the drain junctions).
[0036] Referring to FIG. 3F , the oxide layer 207 , the control gate layer 206 , the dielectric layer 205 , the floating gate layer 204 and the tunneling oxide layer 203 (corresponding to the central portion of the trench T 1 ) are etched using the patterned second photoresist 216 as a mask, thereby forming a second trench T 2 . The bottom surface of second trench T 2 is substantially coplanar with the bottom surface of first trench T 1 . Then, the semiconductor substrate 200 may be conventionally cleaned. Subsequently, a buffer dielectric layer 208 (generally comprising or consisting essentially of silicon dioxide) is formed on inner surfaces of the cleaned second trench T 2 (generally by CVD or conventional oxidation), and then a predetermined portion of the buffer dielectric layer 208 , corresponding to the bottom surface of the second trench T 2 , is removed by the etch-back process (e.g., anisotropic etching). When formed by oxidation, the buffer dielectric layer 208 is generally on only the control gate layer 206 and the floating gate layer 204 , but when formed by CVD, the buffer dielectric layer 208 may be on (or laterally adjacent to) the control gate layer 206 , the dielectric layer 205 , and the floating gate layer 204 (and in most cases the tunneling oxide layer 203 ).
[0037] Then, impurity ions are implanted into the semiconductor substrate 200 below the second trench T 2 (e.g., by straight and/or angled implantation) and conventionally diffused (e.g., by annealing), thereby forming a source junction 209 . Then, the second photoresist 216 is removed. Alternatively, the second photoresist 216 may be removed before forming the source junction 209 . In a preferred embodiment, at least two different impurity ions (generally having the same conductivity type) may be implanted for formation of the source junction 209 . For example, phosphorous (P + ) and arsenic (As + ) impurity ions may be implanted at dosages of 10 14 atoms/cm 2 to 10 15 atoms/cm 2 , and then the implanted impurity ions are diffused by a thermal process (e.g., annealing). Accordingly, phosphorous impurity ions may be relatively widely diffused (e.g., for effective overlap with floating gates 204 ), and arsenic impurity ions may be relatively narrowly diffused (e.g., to decrease a contact resistance of a subsequently formed source contact/electrode).
[0038] As shown in FIG. 3G , a conductive layer (e.g., comprising polysilicon [which may be further doped with one or more conventional silicon dopants] and/or a conventional metal silicide) is deposited in an amount or to a thickness sufficient to fill the second trench T 2 , and then the conductive layer is selectively removed (e.g., by conventional photolithography or chemical mechanical polishing), thereby forming a source electrode layer 210 . In FIG. 3G , portions of the conductive layer have been selectively removed by photolithography. Then, the surface of the source electrode layer 210 is thermally oxidized, thereby forming an oxide layer 211 . Alternatively, other conductors, such as conventional tungsten contacts (generally formed by CVD) or sputtered aluminum (generally following conventional formation of an adhesive and/or barrier liner [e.g., comprising a conventional Ti/TiN bilayer]), may also be suitable for the source electrode layer 210 , but in such cases, formation of oxide layer 211 may not necessary take place. After removing the insulating layer 202 , impurity ions are implanted into the semiconductor substrate 200 (e.g., in areas or regions from which the insulating layer 202 has been removed), and then the implanted impurity ions are diffused, thereby forming drain junctions 212 . The drain junction 212 may be formed in the same process as that of the source junction 209 . Although not shown, following a process of forming a drain electrode layer to the drain junction 212 (e.g., by conventional CMOS processes for forming contacts to source/drain terminals), the memory device is substantially complete.
[0039] Accordingly, the control gate and the floating gate of the split gate flash EEPROM cell are formed in a vertical structure, and two EEPROM cells may be formed in one trench, whereby it is possible to reduce or minimize the size of the cell.
[0040] However, in the first embodiment of the present invention, the control gate 206 and the floating gate layer 204 have a relatively minimal overlap in a channel region between the source junction 209 and the drain junction 212 . As a result, the erase characteristics of the cell may be less than optimal. Accordingly, a second embodiment of the present invention for improving the erase characteristics of the cell will be described as follows.
[0041] FIG. 4A to FIG. 4G are cross-sectional views of an exemplary process for fabricating a split gate (flash) EEPROM cell according to a second embodiment of the present invention.
[0042] As shown in FIG. 4A , a semiconductor substrate 300 generally contains an active area and a field area, defined at least in part by a device isolation layer (not shown). In this state, a buffer oxide layer 301 and an insulating layer 302 are sequentially deposited on the semiconductor substrate 300 . Then, a first photoresist 315 is coated on the insulating layer 302 , and the first photoresist 315 is patterned by a conventional photolithography (e.g., exposure and development) process. As for insulating layer 202 (e.g., FIG. 3A ), the insulating layer 302 may comprise a nitride layer.
[0043] Referring to FIG. 4B , the insulating layer 302 , the buffer oxide layer 301 and the semiconductor substrate 300 are etched to a predetermined depth by using the patterned first photoresist 315 as a mask, thereby forming a trench T 1 in a cell region. Then, the semiconductor substrate 300 may be etched and/or cleaned by a clean active pit reactive ion etching method. After that, a tunneling oxide layer 303 is formed in the trench T 1 of the semiconductor substrate 300 in a manner similar to tunneling oxide layer 203 (e.g., FIG. 3B ), and the first photoresist 315 is removed.
[0044] Thus, the tunneling oxide layer 303 may be formed by a CVD process or a thermal oxidation process. In the case of the CVD process, the tunneling oxide layer 302 is generally formed on an entire surface of the semiconductor substrate 300 , including the insulating layer 302 . In the case of thermal oxidation, the tunneling oxide layer 302 is formed generally only on the semiconductor substrate 300 inside the trench T 1 . In FIG. 4B , the tunneling oxide layer 303 is formed by thermal oxidation.
[0045] As shown in FIG. 4C , a conductive layer is deposited on the entire surface of the semiconductor substrate 300 , including in the trench T 1 . Then, the conductive layer is etched back to remain in a predetermined (e.g., lower) portion of the trench T 1 , thereby forming a floating gate layer 304 on the tunneling oxide layer 303 . At this time, after the etch-back process, the trench T 1 has a sufficient space for a control gate.
[0046] As shown in FIG. 4D , a second photoresist 316 is deposited on the entire surface of the semiconductor substrate 300 , including the floating gate layer 304 . Then, the second photoresist 316 is patterned to expose a central portion of the floating gate layer 304 by an exposure and development process. Then, the floating gate layer 304 is partially etched to a predetermined depth (e.g., a vertical overlap depth) using the patterned second photoresist 316 as a mask, and the second photoresist 316 is removed. Given a known etch rate for the material of the floating gate layer 304 under known etch conditions, the predetermined depth of etching the floating gate layer 304 may be determined and/or controlled by a timed etch (e.g., etching for a predetermined period of time).
[0047] Referring to FIG. 4E , a dielectric layer 305 is formed on an upper surface of the floating gate layer 304 . The dielectric layer 305 generally comprises an oxide layer formed by a CVD process or a thermal oxidation process. Then, a conductive layer similar to the conductive layer 206 ( FIG. 3D ) is deposited on the entire surface of the semiconductor substrate 300 . The conductive layer is also etched back so that it remains in the trench, whereby a control gate layer 306 is formed on the dielectric layer 305 . After that, an upper surface of the control gate layer 306 is oxidized to form an oxide layer 307 .
[0048] As shown in FIG. 4F , a third photoresist 317 is formed on the entire surface of the semiconductor substrate 300 including the oxide layer 307 , and then the third photoresist 316 is patterned to expose a central portion of the trench T 1 by an exposure and development process. Generally, the patterned third photoresist 317 has dimensions substantially similar or equivalent to those of patterned second photoresist 216 ( FIG. 3E ), but exposing a smaller portion of oxide layer 307 along its length and/or width than the central portion of the floating gate layer 304 exposed by the second photoresist 316 ( FIG. 4D ). FIG. 4F shows an opening in the patterned third photoresist 317 having a width less than that of a corresponding opening in the second photoresist 316 .
[0049] Referring to FIG. 4G , portions of the oxide layer 307 , the control gate layer 306 , the dielectric layer 305 , the floating gate layer 304 and the tunneling oxide layer 303 corresponding to the central portion of the trench T 1 are etched by using the patterned third photoresist 317 as a mask, thereby forming a second trench T 2 . Then, the semiconductor substrate 300 may be cleaned. Subsequently, a buffer dielectric layer 308 is formed in the cleaned second trench T 2 , and a predetermined portion of the buffer dielectric layer 308 , corresponding to the bottom surface of the second trench T 2 , is removed by an etch-back (e.g., anisotropic etching) process.
[0050] Then, impurity ions are implanted into and diffused in the semiconductor substrate 300 below the second trench T 2 similar to the process for source junction 209 ( FIG. 3F ), thereby forming a source junction 309 . The third photoresist 317 may be removed, either before or (preferably) after ion implantation to form the source junction 309 . For formation of the source junction 309 , in one embodiment, at least two impurity ions are implanted. As for source junction 209 , phosphorous and arsenic impurity ions may be implanted at dosages of from 10 14 atoms/cm 2 to 10 15 atoms/cm 2 , and then the implanted impurity ions may be diffused by a thermal process. Accordingly, phosphorous impurity ions may be widely diffused, and arsenic impurity ions may decrease a contact resistance.
[0051] As shown in FIG. 4H , a conductive layer is deposited sufficiently to fill the second trench T 2 , and then the conductive layer is selectively removed by photolithography or CMP (preferably, photolithography), thereby forming a source electrode layer 310 . Then, the surface of the source electrode layer 310 may be thermally oxidized, thereby forming an oxide layer 311 . After removing the insulating layer 302 , impurity ions are implanted into the semiconductor substrate 300 (e.g., in areas from which the insulating layer 302 is removed), and then the implanted impurity ions are diffused, thereby forming a drain junction 312 . The drain junction 312 may be formed in the same process as that of the source junction 309 . Although not shown, following the process of forming a drain electrode layer to the drain junction 312 , the memory device is substantially complete.
[0052] In the memory device according to the second embodiment of the present invention, as shown in FIG. 4H , the control gate layer 306 and the floating gate layer 304 overlap vertically and horizontally in a channel region between the source junction 309 and the drain junction 312 , thereby improving the erase characteristics of the cell.
[0053] As mentioned above, the memory device and the method for manufacturing the same have the following advantages.
[0054] First, the control gate and the floating gate of the split gate cell are formed in a vertical structure, whereby it is possible to reduce or minimize the cell size, and to improve device integration. Also, it is possible to obtain a high coupling ratio, thereby lowering the programming voltage.
[0055] In addition, the control gate and the floating gate of the split gate cell may overlap vertically and horizontally in the channel region between the source junction and the drain junction, thereby improving the cell erase characteristics.
[0056] It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention. Thus, it is intended that the present invention covers the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.
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A split gate (flash) EEPROM cell and a method for manufacturing the same is disclosed, in which a control gate and a floating gate are formed in a vertical structure, to minimize a size of the cell, to obtain a high coupling ratio, and to lower a programming voltage. The split gate EEPROM cell includes a semiconductor substrate having a trench; a tunneling oxide layer at sidewalls of the trench; a floating gate, a dielectric layer and a control gate in sequence on the tunneling oxide layer; a buffer dielectric layer at sidewalls of the floating gate and the control gate; a source junction in the semiconductor substrate at the bottom surface of the trench; a source electrode in the trench between opposing buffer dielectric layers, electrically connected to the source junction; and a drain junction on the surface of the semiconductor substrate outside the trench.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related to applicant's co-pending U.S. patent application Ser. No. 09/107,546 filed Jun. 30, 1998 entitled METHOD AND DEVICE FOR IMPROVING DFE PERFORMANCE IN A TRELLIS-CODED SYSTEM, the whole contents and disclosure of which is incorporated by reference as if fully set forth herein.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention generally relates to digital communication systems, and more specifically, to an enhanced system and method for performing feedback equalization and complementary code key (CCK) decoding using a trellis structure.
[0004] 2. Prior Art
[0005] In many digital communication scenarios (e.g. telephone transmission, broadcast TV transmission, cable etc.). The transmitted signal arrives at the receiver through more than one path in addition to the direct path. This condition is called “multipath” and leads to intersymbol interference (“ISI”) in the digital symbol stream. This ISI is compensated for in the receiver through an equalizer which in many cases is a DFE as shown in FIG. 1. U.S. Pat. No. 5,572,262 shows one method of combating these multipaths.
[0006] A DFE 10 (FIG. 1) has two filter sections, a forward filter 12 and a feedback filter 16 . The input to the forward filter 12 is the received data which includes the transmitted symbol sequence a k , noise n k and multipath h i . The input to the feedback filter is the quantized equalizer output â k . The output of both the sections are summed 18 to form the final equalizer output ã k 19 which is also the input to the next stage in a trellis-coded system, the trellis decoder. While a DFE performs better than a linear equalizer in severe ISI, the performance is limited by error propagation through the feedback filter 16 of the DFE 10 . Error propagation occurs in the feedback filter 16 when the quantized equalizer output â k is not the same as the transmitted symbol a k . If an error is made in determining the symbol â k at the output of the slicer 14 , this incorrect symbol is fed back to the input of the feedback filter 16 and propagates. As known, the slicer 14 quantizes the filtered signal, providing an estimate of the symbol received. In many systems which employ error correction codes like trellis codes and/or Reed-Solomon codes to obtain very low error rates at moderate SNRs, the “raw” symbol error rate (SER) at the equalizer output can be extremely high. For example, in a Vestigal Sideband (VSB) system, at threshold in white noise the SER at the equalizer output is about 0.2. The increased error propagation due to these high SERs can cause the DFE to lose a couple of db in performance as compared to the case of no error propagation. Additionally, the error propagation causes the error sequence at the equalizer output to be correlated, since it depends on past incorrect symbol decisions. This correlation has an adverse effect on the subsequent trellis decoder which is usually designed for a white noise sequence.
[0007] According to the IEEE 802.11b high-rate wireless communications standard implementing direct sequence spread spectra techniques, bit stream data may be encoded using a standard known as Complementary Code Keying (CCK). This CCK encoding scheme is used to achieve 5.5 Mbps or 11 Mbps in wireless LANs. Rather than using the Barker code, which is the standard 11-bit chipping sequence used to encode data bits, CCK requires that data be encoded using a series of codes called Complementary Sequences. Because there are 256 unique code words that can be used to encode the signal, up to 8 bits can be represented by any one particular code word (assuming an 11 Mps bit stream).
[0008] It is the case that, for most symbol modulation schemes, the Decision Feedback Equalizer adequately performs notwithstanding the difficulty of providing symbol estimates â k . This is because the estimation is done on a symbol-by-symbol basis.
[0009] It would be highly desirable to provide a DFE that exploits the fact that when a symbol is received, there is a relationship between the other symbols before and after it, e.g., if it is in the middle of a CCK code word.
[0010] Past efforts have relied upon providing equalization first and, then perform the CCK decoding. However, it would be highly desirable to provide both CCK modulation decoding and equalization at the same time.
SUMMARY OF THE INVENTION
[0011] An object of this invention is to provide an improved system and method for decoding CCK-encoded digital data streams implementing a trellis-decoding technique.
[0012] Another object of the present invention is to provide an improved receiver device for use in digital communication systems implementing the IEEE 802.11b high rate digital communications standard that implements a novel, computationally efficient trellis decoding technique for decoding CCK encoded symbols.
[0013] These and other objectives are attained with a method and system for performing joint equalization and decoding of Complementary Code Key (CCK) encoded symbols. The system comprises: a decision feedback equalizer (DFE) structure for simulating an inverse communications channel response and providing an output comprising an estimation of the received symbols, the DFE structure including a forward equalizer path and a feedback equalizer path including a feedback filter; and, a CCK decoder embedded in the feedback path and operating in conjunction with a feedback filter therein for decoding the chips based on intermediate DFE outputs including those chips corresponding to past decoded CCK symbols. Decisions on a symbol chip at a particular time are not made until an entire CCK codeword that the chip belongs to is decoded, thereby reducing errors propagated when decoding the symbols.
[0014] Advantageously, the trellis decoding method is implemented as a computationally efficient 64-state trellis.
[0015] Further benefits and advantages of the invention will become apparent from a consideration of the following detailed description, given with reference to the accompanying drawings, which specify and show preferred embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] [0016]FIG. 1 illustrates generally a DFE equalizer structure according to the prior art;
[0017] [0017]FIG. 2 depicts the joint DFE and CCK decoding technique according to a first embodiment of the invention;
[0018] [0018]FIG. 3 depicts the joint DFE and CCK decoding technique according to a preferred embodiment of the invention; and,
[0019] [0019]FIG. 4 depicts the generated trellis structure underlying the joint DFE and CCK decoding technique of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] The present invention is directed to a digital communications system and a computationally efficient decoding structure for decoding data received in the form of symbols modulated according to Complementary Code Keying (CCK) technique. The system of the invention will be described herein for the case of an 11 Mbps digital data stream in accordance with the IEEE 802.11b standard, however, it is understood that skilled artisans may readily apply the principles described herein to other bit stream data rates in accordance with the standard, e.g., 5.5 Mps.
[0021] In a first embodiment of the invention, as shown in FIG. 2, the system includes a receiver device comprising, in part, a Decision Feedback Equalizer (“DFE”) 20 such as the equalizer used in a 802.11b communications receiver. The DFE 20 may be a fractionally spaced decision-feedback equalizer (DFE) having a forward filter 12 ′ with taps that are fractionally (T/2) spaced. This forward filter 12 ′ will perform both matched filtering and equalization. The equalizer 20 further includes a feedback filter 16 ′ that may be sample spaced, i.e., T spaced, where “T” denotes the sample rate, which is also the chip rate, e.g., 11 MHz. The input to the equalizer 20 is assumed to be T/2 spaced, i.e., sampled at 22 MHz. The DFE 20 may be used for all the possible 802.11b communications modes, i.e., 1, 2, 5.5 and 11 Mbps. In the first embodiment, as shown in FIG. 2, the input to the feedback filter section 16 comprises the output of the slicer 14 ′, which provides an estimate of the true transmitted chips and may include either a BPSK or QPSK slicer, depending on the transmitted mode. Equation (1) describes this structure as follows:
c ~ k = ∑ i = 0 L f - 1 f i r 2 k + d f - i + ∑ i = 1 L b b i c ^ k - i ( 1 )
[0022] where, f i are the forward equalizer taps, b i are the feedback equalizer taps, r k is the received input stream at T/2 rate, {tilde over (c)} k is the DFE equalizer output at T rate, L f is the length of the forward filter, d f is the delay through the forward filter, L b is the length of the feedback filter, and ĉ k is the slicer output which is an estimate of the true transmitted chip c k . As shown in FIG. 2, there is provided a CCK decoder 25 for providing the decoding of the received chips. It should be understood that in other embodiments, the decode element 25 may comprises a typical Barker despreader, for the low-rate modes. The input to the CCK decoder 25 is {tilde over (c)} k . It is readily seen that, in this embodiment, equalization and CCK decoding/Barker dispreading are completely separated and, as such, may be subject to propagation errors due to errors made by the slicer.
[0023] For improved performance, in a preferred embodiment, the DFE structure 20 ′ illustrated in FIG. 3 is implemented. In accordance with the configuration illustrated in FIG. 3, the CCK decoder/Barker despreader device 25 ′ is embedded into a DFE feedback loop 30 including the feedback filter. Decoding and equalization is done on a block of eight chips for the CCK modes and on eleven chips for DSSS modes. Equation 2) describes the structure for the CCK mode as follows:
c ~ k + j = ∑ i = 0 L f - 1 f i r 2 ( k + j ) + d f - i + ∑ i = 1 L b b i c ~ k + j - i , j = 0 , 1 , … 7 = ∑ i = 0 L f - 1 f i r 2 ( k + j ) + d f - i + ∑ i = j + 1 L b b i c ^ k + j - i + ∑ i = 1 j b i c k + j - i = s k + j + ∑ i = 1 j b i c k + j - i ( 2 )
[0024] where s k+j
s k + j = ∑ i = 0 L f - 1 f i r 2 ( k + j ) + d f - i + ∑ i = j + 1 L b b i c ^ k + j - i j = 0 , … 7
[0025] represents the intermediate DFE equalizer outputs that include, in the feedback filter, only those chips corresponding to past decoded CCK symbols and the
∑ i = 1 j b i c k + j - i
[0026] component represents the chips comprising the present transmitted symbol. According to the invention, the CCK decoder 20 ′ then chooses, from the set of 256 possible codewords, that codeword [c 0 ,c 1 , . . . , c 7 ] that minimizes the metric set forth in equation 3) as follows:
∑ j = 0 7 s k + j + ∑ i = 1 j b i c j - i - c j 2 ( 3 )
[0027] It is understood that similar equations may be written for the DSSS modes except that blocks of 11 chips at a time would be considered and that there are only 2, or 4 possible 11-chip words.
[0028] The configuration in accordance with the preferred embodiment greatly reduces error propagation, as decisions on the chip at time k are not made until the entire CCK codeword that the chip belongs to is decoded. The complexity of this solution is greater than the configuration in accordance with the first embodiment (FIG. 2), however, according to the preferred embodiment of the invention, a computationally efficient decoding method employing a trellis structure is provided, as will be described.
[0029] According to this method, the variable c =[c 0 , c 1 . . . , c 7 ] represents the 8-symbol CCK codeword. The symbols in the codeword “ c ” are expressed in terms of the four QPSK phases ø 1 , ø 2 , ø 3 and ø 4 used to create the CCK codes according to equation 4) as follows:
c _ = [ j ( φ 1 + φ 2 + φ 3 + φ 4 ) , j ( φ 1 + φ 3 + φ 4 ) , j ( φ 1 + φ 2 + φ 4 ) , - j ( φ 1 + φ 4 ) , j ( φ 1 + φ 2 + φ 3 ) , j ( φ 1 + φ 3 ) , - j ( φ1 + φ2 ) , - j ( φ 1 ) ] ( 4 )
[0030] As the phase ø 1 is common to all the symbols in a codeword, the following definitions for values α 1 , α 2 and α 3 are provided according to equation 5) as follows:
α 1 =ø 2 +ø 3 +ø 4
α 2 =ø 3 +ø 4
α 3 =ø 2 +ø 4 (5)
[0031] Thus, the CCK codeword C may be re-written in terms of the variables α i and ø 1 according to equation 6) as follows:
c _ = j φ 1 [ j α 1 , j α 2 , j α 3 , - j ( α 2 + α 3 - α 1 ) , j ( 2 α 1 - α 2 - α 3 ) , j ( α 1 - α 3 ) , - j ( α 1 - α 2 ) , 1 ] ( 6 )
[0032] In other words, the codeword c may be expressed as: c =e jφ1 d , where d is a function of α 1 , α 2 and α 3 as shown in equation 6). Each of the α i may take on one of 4 values [0, π/2, π, 3π/2] and hence d belongs to a set of 64 possible vectors, whereas c can have 256 possible values. Utilizing a brute force methodology, the embedded CCK decoder may be programmed to choose from the set of 256 possible code words (a number 8 symbols long), that minimizes the metric, and use the corresponding c 0 , c 1 , . . . , c 7 values. For this brute force minimization, this value would be computed 256 times (for each of the 256 possible combinations that could be transmitted) with the combination that minimizes this metric distance being picked.
[0033] According to the preferred embodiment, however, rather than a brute force methodology, a trellis structure may be used because of the memory effect of the feedback filter in the DFE feedback loop 30 (FIG. 3). That is, the eight intermediate outputs s k+j , j=0, 1, . . . , 7, are processed by the trellis to determine the transmitted codeword at time k. Advantageously, as will be described, the dimensionality of a trellis search may be reduced from 256 to 64. That is, as shown in FIG. 4, a trellis structure 100 is generated which represents basically as a state diagram having an initial state 102 j=0 , whereby, in the case of a multi-path channel and considering only the contribution in the feedback filter from symbols in the present CCK code word, the maximum number of states 102 in a corresponding set 102 j=0 , . . . , 102 j=7 at each corresponding level 103 j=0 , . . . , 103 j=7 (equal to eight (8) levels), grows up to a maximum of sixty-four (64). Preferably, the trellis structure is embodied as an algorithm executing in hardware provided in the combined CCK decoder/equalizer feedback filter structure (FIG. 3), however, it could easily be executed in software.
[0034] In the description of how the programmed trellis structure and algorithm of FIG. 4 operates to process the block of eight symbols s k+j , reference is had to equation 3, which sets forth the metric to be minimized and which may be re-written in terms of variables d and ø 1 according to equations 7) and 8) as follows:
∑ j = 0 7 s k + j + ∑ i = 0 j b i c j - i 2 ( 7 )
[0035] where b 0 =−1; and, using the relation c i =e jφ1 d i , the following equation 8) is obtained:
∑ j = 0 7 s k + j + j φ 1 ∑ 1 = 0 j b i d j - i 2 = ∑ j = 0 7 [ s k + j 2 + ∑ i = 0 j b i d j - i 2 + 2 Re ( s k + j * j φ 1 ∑ i = 0 j b 1 d j - i ) ] ( 8 )
[0036] where Re denotes a real part and * denotes complex conjugate. Minimizing the above equation is equivalent to minimizing the metric according to equation 9) as follows:
∑ j = 0 7 ∑ i = 0 j b i d j - i 2 + 2 Re [ j φ i ∑ j = 0 7 s k + j * ∑ i = 0 j b i d j - i ] ( 9 )
[0037] Defining now the term
χ j = ∑ i = 0 j b i d j - i .
[0038] then, the metric to be minimized may be set forth according to equation 10) as follows:
∑ j = 0 7 χ j 2 + 2 Re [ j φ 1 ∑ j = 0 7 s k + j * χ j ] ( 10 )
[0039] Returning to FIG. 4, a state in the trellis 100 is defined by the vector [α 1 , α 2 , α 3 ] and a block of eight (8) symbols s k+j , j=0, 1, . . . , 7, are processed by the trellis as follows: At each time, j, the following quantities are calculated for each state 102 in the set 102 j=0 , . . . , 102 j=7 as follows: χ j , a real-valued m 1 (j)=|χ j | 2 and a complex-valued m 2 (j)=s*k+jχ j . Substituting these values into equation 10), the metric to be minimized may now be set forth according to equation 11) as follows:
∑ j = 0 7 m 1 ( j ) + 2 Re [ j φ 1 ∑ j = 0 7 m 2 ( j ) ] ( 11 )
[0040] Thus, for every branch in a trellis path, two (2) quantities need to be computed: a real-valued m 1 (j)=|χ j | 2 and a complex-valued m 2 (j)=s*k+jχ j . These quantities are then added to the corresponding quantities of the state from which the branch originated. Unlike the trellis decoding in a convolutional code, here there is only one branch coming into any state and hence there is no “survivor path”. At 102 j=0 there are 4 possible paths corresponding to the 4 possible values of α 1 , at 102 j=1 there are 16 possible paths corresponding to the 16 possible combinations of [α 1 , α 2 ], at 102 j=2 there are 64 possible paths corresponding to the 64 possible combinations of [α 1 , α 2 , α 3 ] and after that the trellis size does not grow since all succeeding values of d j are functions of the same three phases, as shown in equation (6). After the entire codeword has been received, i.e., at the end of the trellis 100 when 102 j=7 at level 103 j=7 , for each of the 64 states the metric set forth in equation 11) is calculated for each of the 4 possible values of ø 1 for a total of 256 values. Then, the state and ø 1 value is chosen that corresponds to the minimum metric. The vector [α 1 , α 2 , α 3 ] corresponding to the state with the minimum metric along with the ø 1 value is then used to calculate the transmitted codeword c.
[0041] It should be understood that the extra quantity m 1 (j) has to be computed in the equation 11), because, in general, this term will be a function of the codeword and the filter taps. In the absence of multipath, i.e., b 0 =−1 and b j =0 elsewhere, it is easy to see that m 1 (j)=1 always, and hence does not contribute towards the final metric.
[0042] As shown in FIG. 4, at each state, the trellis structure moves to four (4) other values, depending upon what the so value was because that goes into b 0 (equation 3). Then from each value, the trellis may branch into four other values. It is readily seen that, if at every state 102 a , . . . , 102 n in the trellis there may be four possible inputs corresponding to four different values, then the structure would grow exponentially and basically end up with a number of combinations (states) equal to 4 8 . However, according to the CCK structure, this trellis structure only moves to 64 states (i.e., 102 c , . . . , 102 n ) and then saturates. This is because all of the eight symbols may be expressed in terms of just three (phase) values α 1 , α 2 and α 3 , i.e., each of these three phases can take one of four values so there is 4 3 =64 possible combinations which makes the trellis structure extremely manageable.
[0043] While it is apparent that the invention herein disclosed is well calculated to fulfill the objects stated above, it will be appreciated that numerous modifications and embodiment may be devised by those skilled in the art, and it is intended that the appended claims cover all such modifications and embodiments as fall within the true spirit and scope of the present invention.
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A method and system for performing joint equalization and decoding of Complementary Code Key (CCK) encoded symbols. The system comprises: a decision feedback equalizer (DFE) structure for simulating an inverse communications channel response and providing an output comprising an estimation of the received symbols, the DFE structure including a forward equalizer path and a feedback equalizer path including a feedback filter; and, a CCK decoder embedded in the feedback path and operating in conjunction with a feedback filter therein for decoding the chips based on intermediate DFE outputs including those chips corresponding to past decoded CCK symbols. Decisions on a symbol chip at a particular time are not made until an entire CCK codeword that the chip belongs to is decoded, thereby reducing errors propagated when decoding the symbols. Advantageously, the trellis decoding method is implemented as a computationally efficient 64-state trellis.
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PRIORITY CLAIM
[0001] This is a Divisional application of U.S. application. Ser. No. 13/712,739 entitled “A SOLID-STATE DRIVE HOUSING, A SOLID-STATE DISK USING THE SAME AND AN ASSEMBLING PROCESS THEREOF,” filed Dec. 12, 2012, which is incorporated herein by reference
FIELD OF THE INVENTION
[0002] This invention relates to a solid-state drive housing, a solid-state disk using the same and an assembling process thereof. More particularly, the present invention related to a solid-state drive housing assembling process which is capable of preventing the disassembly of the solid-state drive housing by the consumer.
BACKGROUND
[0003] A solid-state drive (SSD) is a data storage device that uses integrated circuit assemblies as memory to store data persistently. SSD technology uses electronic interfaces compatible with traditional block input/output (I/O) hard disk drives. SSDs do not employ any moving mechanical components, which distinguishes them from traditional magnetic disks such as hard disk drives (HDDs) or floppy disks, which are electromechanical devices containing spinning disks and movable read/write heads. Compared with electromechanical disks, SSDs are typically less susceptible to physical shock, are silent, and have lower access time and latency, however, the high manufacturing cost thereof prevents the widespread of the SSD.
[0004] Usually, the SSD is mainly composed of three main components, such as housing, PCB having chips sealed thereon and the connecting port. Please refer to the U.S. Pat. No. 8,213,182 (hereinafter called as '182), it discloses a housing case having an electronic circuit board, which includes: a lower case portion which internally houses a circuit board for mounting electronic components; and an upper case portion which is externally fitted to the lower case portion to form a box-like member. More specifically, the '182 discloses a screw free SSD housing that can be easily assembled and disassembled.
[0005] However, apart from the screw free SSD housing design, a need exists that some of the manufacturer may wants to prevent the consumer to disassemble the housing without the authorization thereof. Accordingly, a need of a low cost, simple design hosing capable of prevent the unauthorized disassembly of the consumer exists.
SUMMARY OF THE INVENTION
[0006] One object of the present invention is to provide a solid-state drive housing and an assembling process thereof so as to solve the problem of the prior art. According to an embodiment of the invention, the solid-state drive housing of the present invention is capable of preventing the consumer to disassemble the housing without the authorization of the manufacturer. The solid-state drive housing comprises a first member and a second member. The first member has a plurality of first hollows formed on the surface thereof and the second member, having a second base and a plurality of fastening structures one pieced formed therewith, part of the end of the fastening structures are plastically bent and disposed in the corresponding first hollows so as to secure the second member therewith.
[0007] While in practice, the fastening structures may, or may not, be hook shaped. Furthermore, the first member may further has a first base and a sidewall, the first base having a first inner base surface and a corresponding first outer base surface having the plurality of first hollows formed thereon, the sidewall extending outward from the first inner base surface so as to surround and form an spacing therein.
[0008] Furthermore, the sidewall has an inner sidewall surface and a corresponding outer sidewall surface, the fastening structures of the second member extends outward from the second inner base surface toward the first base along the outer sidewall surface. Furthermore, the fastening structures may have a body portion and an end portion, each of the end portions of the fastening structures disposes in the corresponding first hollows and connects with the second base via the body portion. Moreover, the outer sidewall surface may has a plurality of second hollows formed thereon and part of the body portion of the fastening structures is plastically bent and disposed therein. Furthermore, the bottom surface of the second hollow has a groove liked structure extending along the outer sidewall surface.
[0009] Moreover, the extending direction of the body portion is approximately inverse or horizontal to the extending direction of the top end of the end portion after the assembly. Furthermore, the second member may further has at least one interval formed between the plurality of fastening structures so as to expose part of the sidewall therethrough.
[0010] Another object of the present invention is to provide a novel solid-state drive having a PCB fasten in the SSD housing previously described so as to solve the problem in the prior art.
[0011] Moreover, another object of the present invention is to provide a novel solid-state drive assembling process for solving the problem in the prior art. The process comprises the steps of preparing a first member, preparing a second member, and securing the said members. It should be noticed that, since the specific design of the first member and second member are described as previously shown, therefore, the detail description thereof shall be herein omitted.
[0012] Then, after the preparation of the first member and the second member, the assembler may connects the sidewall of the first member with the second inner base surface of the second member so as to cover the spacing. Then, the user may presses and plastically deforms the top end of the end portion of the fastening structure into the corresponding hollow portion, meanwhile, the extending direction of the body portion may be approximately inverse to the extending direction of the top end of the end portion so as to secure the first member with the second member so as to secure the second member with the first member.
[0013] Furthermore, in the actual practice, the inner sidewall surface of the first member may optionally has a plurality of second hollows formed thereon, so as to allowing the body portion of the fastening structures to be plastically deformed and be accommodated therein. It worth a mention that, an adhesive layer is disposed on the contact area between the first member and the second member, the adhesive layer is formed on the surface of the second member. Moreover, part of the end of the fastening structures and the corresponding surface of the first hollows are both plastically deformed and the amount of deformation are approximately the same.
[0014] By the said design, the consumer shall not able to disassemble the SSD easily without damaging the housing solving the long lasted problem exists in the art. On the advantages and the spirit of the invention, it can be understood further by the following invention descriptions and attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIGS. 1A and 1B illustrates the assembled solid-state drive according to an embodiment of the present invention in various viewing angles.
[0016] FIG. 2A and FIG. 2B are schematic drawings illustrating the first member of the embodiment of FIG. 1A in various viewing angles.
[0017] FIG. 3A and FIG. 3B are schematic drawings illustrating the second member of the embodiment of FIG. 1A in various viewing angles.
[0018] FIG. 4A and FIG. 4B are the cross-section diagrams along the Z-Z of FIG. 1 before and after the fastening structures are plastically bent.
[0019] FIG. 5 illustrates the schematic figure of the second member after the said second crimping process according to an embodiment of the present invention.
DETAILED DESCRIPTION
[0020] The present invention discloses a solid-state drive housing (hereinafter called as the housing), a solid-state disk (hereinafter called as SSD) using the same and an assembling process thereof.
[0021] Please refer to FIG. 1A and FIG. 1B . FIGS. 1A and 1B illustrates the assembled solid-state drive 1 according to an embodiment of the present invention in various viewing angles. As shown in FIG. 1A and FIG. 1B , the solid-state drive D (hereinafter called as SSD) of the present invention mainly includes a SSD housing 1 with a printed circuit board 2 (hereinafter called as PCB) secured therein. The PCB 2 may, but not limited to, be a circuit board having a plurality of NAND chips sealed thereon. Moreover, the SSD housing 1 is essentially composed of, but not limited to, a first member 10 and a second member 20 .
[0022] As shown in the FIG. 1A and FIG. 1B , the first member 10 is, but not limited to, the lower casing of the SSD housing 1 and has a plurality of first hollows 13 formed thereon. The second member 20 is, but not limited to, the upper cover of the SSD housing and has a plurality of fastening structures 22 . By simply pressing the edge material of the second member 20 , the edge material thereof shall be plastically deformed into the first hollows 13 of the first member 10 so as to secure the first member 10 with the second member 20 with no screw liked fasteners required. It should be noticed that, the edge material of the second member 20 may be optionally dug into the surface of the first member 10 for better fixity.
[0023] The details of the assembling process of the SSD housing 1 shall be herein described. First, a first member 10 and a second member 20 have to be prepared. Please refer to FIG. 2A and FIG. 2B , FIG. 2A and FIG. 2B are schematic drawings illustrating the first member of the embodiment of FIG. 1A in various viewing angles. By the FIG. 2A and FIG. 2B , it is clearly shown that the first member 10 has a first base 11 and a sidewall 12 . The first base 11 has a first inner base surface 11 B and a corresponding first outer base surface 11 A with a plurality of first hollows 13 formed thereon. In this embodiment, the first hollows 13 may, or may not, extends along the edge of the first base 11 and be groove shaped. Moreover, the first hollows 13 are not penetrated through the second member 20 so as to maintain the tightness thereof. Furthermore, the width WD of the first hollows 13 are larger than the depth DP thereof so as to allow the end of the end portion 222 of the fastening structure 22 to be pressed and plastically deformed therein.
[0024] The sidewall 12 has an outer sidewall surface 12 A and a corresponding inner sidewall surface 12 B, the sidewall 12 extends outward vertically from the first inner base surface 11 B and forms along the circumference of the first base 11 so as to surround and define a spacing S therein, allowing the PCB 3 or other essential electronic member to be disposed therein. Furthermore, apart from the first hollows 13 , the first member may, or may not, further has a second hollows 16 formed on the outer sidewall surface 12 A as shown in the figures.
[0025] Furthermore, the first member 10 may further has a platform 15 formed on the inner sidewall surface 12 B, horizontally extended inwardly from the inner sidewall surface 12 B, for supporting the PCB 2 thereon. It should be noticed that the sum of the height of the platform 15 and the thickness of the PCB 2 is preferred to smaller than the total height of the sidewall 12 in order to spare a reasonable size of space for the PCB 2 . Moreover, the sidewall 12 may further has a plurality of tenon 14 formed on the inner sidewall surface 12 B. The tenons 14 horizontally extend inwardly from the inner sidewall surface 12 B and have approximately the same height as the sidewall 12 . The plurality of tenons 14 may be utilized to position the PCB 2 by the mortises of the PCB 2 . Furthermore, in order to secure the PCB 2 with the first member 10 , a plurality of thin layers of dielectric adhesive material (grey colored) may be disposed among the interface of the first member 10 and the PCB 2 . In the present embodiment, the first member 10 may, but not limited to, be formed of a metal or polymer material by die casting process and the first base thereof may only has an average thickness of 0.035 inches. More specifically, the first member depicts in the FIG. 2A and FIG. 2B has the length, width and the height of approximately 2.75 inches, 3.95 inches and 0.22 inches.
[0026] Please refer to FIG. 3A and FIG. 3B , FIG. 3A and FIG. 3B are schematic drawings illustrating the second member of the embodiment of FIG. 1A in various viewing angles. By the FIG. 3A and FIG. 3B , it is clearly shown that the second member 20 has a second base 21 and a plurality of fastening structures 22 extended therefrom. The second base 21 has a second outer base surface 21 A and a corresponding second inner base surface 21 B. Each of the plurality of fastening structures 22 has a corresponding inner surface 22 A and outer surface 22 B respectively. The plurality of fastening structures 22 extend outward vertically from the second inner base surface 21 B which the fastening structure 22 may, but not limited to, be one piece formed with the second base 21 . More specifically, a flat state second member 20 may firstly be formed by blanking process from a plate shaped material. Then, the fastening structures 22 may be folded so as to form the second base 21 and fastening structure 22 as depicted in FIG. 3A . More specifically, the second member 20 is preferred to be formed of a metal or polymer material.
[0027] Moreover, in actual practice, the entire, or at least part of the, internal surface of the second member 20 may optionally has an adhesive AD applied thereon for subsequent use. More specifically, in the embodiment, the entire internal surface of the second member 20 , including the inner surface 22 A of the fastening structures 22 and the second inner base surface 21 B, may has an adhesive AD applied thereon before the initial folding process.
[0028] More specifically, in the embodiment, each of the fastening structure 22 may comprises a body portion 221 and end portion 222 , the end portion 222 is formed on the top end of the fastening structures 22 and be connected to the second inner base surface 21 B via the body portion 221 . Before the assembly, the extending direction of the body portion 221 is approximately the same as the extending direction of the top end of the end portion 222 . However, after the assembly, the extending direction of the body portion 221 may either vertical or inverse to the extending direction of the top end of the end portion 222 so as to secure the first member 10 with the second member 20 . Moreover, at least one interval 23 is formed between the plurality of fastening structures 22 so as to allow the internal contents to be exposed therethrough. In the present embodiment depicted in the FIG. 3A and FIG. 3B , the second base of the second member 20 may only has an average thickness of 0.01 inches and the length and the width is approximately 2.75 inches and 4 inches.
[0029] Please refer to FIG. 4A , FIG. 4B and FIG. 4C , FIG. 4A , FIG. 4B and FIG. 4C depicts the assembling process of the present invention. The FIG. 4A to 4C are corresponding to the cross-section diagrams along the Z-Z of FIG. 1 . Once the first member 10 , the second member 20 and the PCB 2 are ready, then the assembler may begin the assembling process by disposing the PCB 2 onto the platform 15 and matching the tenon 14 of the PCB with the mortise 31 of the PCB. Then, the assembler may connects the sidewall 12 of the first member 10 with the second inner base surface 21 B so as to cover the spacing S thereby. Meanwhile, the body portion 221 of the fastening structures 22 covers part of the outer sidewall surface 12 A, and at least part of the end portion 222 excess the first outer base surface 11 A.
[0030] Then, the user may utilizes pressing tool, such as arbor press, or any other mechanical means to plastically deform the top end of the end portion 222 and force the top end thereof to be disposed into the corresponding first hollow 13 as shown in the FIG. 4B . It should be noticed that the top end of the end portion 222 is preferred, but not essentially, to be stamped, dug or embedded into the surface of the first hollow 13 by mechanically deforming the surface of the first hollow 13 with huge amount of force applied via the fastening structure 22 . More specifically, the top end of the fastening structures are dug into the surface of the corresponding first hollows with approximately no interval formed between the embedded portion of fastening structures and the surface of the first hollow 13 . Furthermore, the said crimpling process may be done by repeatedly applying various forces from various angles thereto so to as to create teeth like effect from the second member 20 to create grips so as to fix the first member 10 with the second member 20 . Therefore, the amount of deformation of each of the surface of the first hollow 13 and the top end of the end portion 222 is approximately the same.
[0031] After the pressing process, the end portion 222 of the fastening structure 22 buckles with the first base 11 so as to secure the first member 10 with the second member 20 mutually. In the embodiment, the fastening structure 22 is now an U shaped hook liked structure. More specifically, while the first member 10 and the second member 20 are mutually secured, the extending direction of the body portion 221 may approximately inverse to the extending direction of the top end of the end portion 222 . However, the shape thereof is not limited to a U shaped hook, the end portions 222 of the fastening structures 22 may also be V shaped, L shaped, C shaped or any other shape that are capable of fixing the relatively positions of the first member 10 and the second member 20 .
[0032] Then, the assembler may, but not essentially, crimping the body portion 221 of the fastening structure 22 and plastically deforming the body portion 221 into the second hollows 16 by roll crimp process so as to provide more fixing capability. Meanwhile, the first member 10 or second member 20 may be heated so as to activate the dielectric adhesive material to provide further stability. Meanwhile, please refer to the FIG. 5 , FIG. 5 illustrates the schematic figure of the second member after the said second crimping process.
[0033] As described above, the SSD housing can easily be assembled by simply pressing and plastically deforming the fastening structure of the second member 20 into the first hollow 13 so as to fix the relative position therebetween. By the said process, the screw liked fasteners and the screwing process thereof can be omitted and the unauthorized disassembly of the consumer can also be prevented since the disassembly thereof shall lead to the destruction of the housing 1 . However, in the product maintaining process or malfunction eliminating process, the disassembly of the SSD housing can still be completed by pulling the end portion 222 of the fastening structure 22 toward the V cut portion 17 (or called as groove liked structure), the groove liked structure 17 extending along the outer sidewall surface as depicted as the enlarged figure shown in the FIG. 2B . Meanwhile, the second member is destroyed but PCB is safe. Accordingly, only the manufacturer itself may process the disassembly process since the consumer has no relative machine or raw member to replace the broken member previously described.
[0034] Compared to the prior art, the solid-state drive housing, the solid-state disk using the same and the assembling process thereof in the present invention is provided with fewer components and easy assembly, so as to reduce the assembly cost of the solid-state drive significantly. Furthermore, the present invention may also capable of preventing the unauthorized disassembly of the consumer.
[0035] Reference will now be made in detail to embodiments, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout. In this regard, the present embodiments may have different forms and should not be construed as being limited to the descriptions set forth herein. Accordingly, the embodiments are merely described below, by referring to the figures, to explain aspects of the present description. Furthermore, it should be noticed that the members depicted in the figures are approximately proportionate to the real scale of the objective products, therefore the scale or the relative position of the components depicted therein should be considered as part of the contents of present specification.
[0036] It will be understood that when an element is referred to as being “connect” or “on” another element, it can be directly on the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being “contact” or “directly on” another element, there are no intervening elements present.
[0037] It will be understood that, although the terms “first,” or “second,” may be used herein to describe various elements or components, these elements or components should not be limited by these terms. These terms are only used to distinguish one element, component or region from another element or component. Thus, “a first member,” or “component,” discussed below could be termed a second element or component without departing from the teachings herein.
[0038] Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation illustrated in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. The device may be otherwise oriented and the spatially relative descriptors used herein interpreted accordingly.
[0039] Finally, although the present invention has been illustrated and described with reference to the embodiment thereof, it should be understood that it is in no way limited to the details of such embodiment but is capable of numerous modifications within the scope of the appended claims.
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This invention relates to a solid-state drive housing, a solid-state disk using the same and an assembling process thereof. The present invention is capable of preventing the unauthorized disassembly of the consumer. The solid-state drive housing comprising a upper cover and a basement, where the lower casing has a plurality of first hollows, the upper cover has a second base and a plurality of fastening structures one pieced formed therewith, part of the end of the fastening structures are bent and disposed in the corresponding first hollows so as to secure the second member with the first member. By the novelty assembling process provided by the present invention, the user may secures the upper cover and the lower casing without the screw liked fasteners and completes the assembly in only a few quick steps, meanwhile, the present invention is also capable of preventing the unauthorized disassembly of the consumer.
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BACKGROUND
The present invention is directed to portable changing rooms that can be used in remote locations.
The inventor of the present invention conceived the present invention because of her need for privacy as a youngster. She played high school soccer and realized that during many weekend tournaments she would find herself on fields that where quite a distance away from changing rooms, and that when she had uniform malfunctions, it became very awkward to fix the uniform or to change her uniform.
When watching professional sports, she also noticed that professional players, during the heat of games were sometimes forced to have uniform malfunctions fixed before full stadiums. Usually, they accomplished this by having teammates surround the player while an equipment manager fixed the uniform malfunction or the player changed his/her uniform.
She also found herself having the same issue of needing a changing room when she went to the beach. On more than one occasion, she was forced to go home in a wet bathing suit because of the lack of changing rooms.
Portable changing rooms have been described in the prior art, yet they have not shown themselves to be practical or affordable. Some prior art changing rooms proved themselves difficult to assemble or were too expensive to be marketable. U.S. Pat. No. 5,592,961 describes a portable changing room that unwinds into a changing room. The patent appears to unfold quite nicely into a changing room, yet it appears that it would take some effort to house the changing room after use. Other patents describe portable changing rooms, yet they appear to have parts that could easily be lost after a few uses.
The inventor does not know of any prior art that discloses a portable changing room that has an inflatable skeleton that has a removable cover that is slid over the inflatable skeleton after inflation.
Accordingly, there is a need for an inexpensive, durable, light weight, and easily transportable portable changing room that is inflatable which can be assembled and disassembled in a timely manner.
SUMMARY
The present invention is directed to an portable changing room that is inflatable that is inexpensive, durable, light weight, and easily transportable. The present invention comprises of an inflatable skeleton, a cover that slides over the inflatable skeleton after the inflatable skeleton is filled with air, and a valve that is attached to the inflatable skeleton. A pump is used to fill the inflatable skeleton.
The inflatable skeleton comprises of a seven sided flexible weighted mat base, wherein one side of the flexible mat base is approximately two times the size of the remaining sides of the flexible mat base, a base inflatable air channel connected to the flexible mat base around the mat base's periphery and, seven vertical air channels connected to the base inflatable air channel at positions that line up with each corner of the flexible mat base, each vertical air channel measures at least six feet in height and each vertical channel has a diameter of at least three inches, six webbing panels fixedly attached between all of the vertical air channels having the same separating distance between them and at a position of at least one third of the height of the vertical air channels from the flexible mat base, and an inflatable domed ceiling attached to the seven vertical air channels. The dome comprising of a first dome air channel that has the same dimensions as the base inflatable air channel and that aligns with the base inflatable air channel, seven dome air channels connectors connected to the first dome air channel so that each of the seven dome air channel connectors flow from positions aligned from each of the vertical air channels, a shorter dome air channel connector that is attached to the first dome air channel at a position between the largest side of the first dome air channel, and lastly a second circular dome air channel that attaches to all of the air channel connectors, all of the inflatable skeleton air channels are connected so that air can flow undisrupted through them. Lastly, a valve, the valve attaches to one of the inflatable skeleton's air channels near the flexible mat base.
The inflatable skeleton might be inflated with a portable foot air pump or with a powered air pump.
The cover is a heptagonal enclosure that has dimensions that allow it to be slid over the inflatable skeleton from the dome section of the inflatable skeleton toward the base, the cover is be made to have a slightly larger diameter than the inflatable skeleton, thereby allowing the cover to be easily slid over the inflatable skeleton. The cover would have a foldable opening on the side of the cover that fits over the largest side of the mat base. The foldable opening might be secured by a zipper, hook and loop materials, or magnets. The cover might be made of nylon or of any other materials known in the art to promote privacy and that is light weight and durable.
The portable inflatable changing room of the present invention is used by first placing the flexible mat on a surface, then finding the valve of the portable inflatable changing room, then attaching an air pump to the valve, then inflating the inflatable skeleton of the portable changing room so that the inflatable skeleton is rigid, next sliding that cover over the inflatable skeleton, and lastly, securing the portable changing room to the surface.
An object of the present invention is to allow a user to have an inflatable portable changing room that can be easily assembled and disassembled in most locations.
DRAWINGS
These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, appended claims, and drawings where:
FIG. 1 is a perspective view of the inflatable skeleton of the present invention; and
FIG. 2 is a perspective of the present invention, wherein a cover is over the inflatable skeleton.
DESCRIPTION
The following discussion describes in detail one embodiment of the invention and several variations of that embodiment. This discussion should not be construed as limiting the invention to that particular embodiment or to those particular variations. Practitioners skilled in the art will recognize numerous other embodiments and variations, as well. For a definition of a complete scope of the invention, the reader is directed to the appended claims.
An portable changing room that is inflatable 500 according to the present invention comprises an inflatable skeleton 100 , a valve 50 , and a removable cover 200 .
The inflatable skeleton 100 comprises of a seven sided flexible weighted mat base 10 , wherein one side 12 of the flexible weighted mat base 10 is approximately two times the size of the remaining sides 14 of the flexible mat base 10 , a base inflatable air channel 20 connected to the flexible weighted mat base 10 around the flexible weighted mat base's periphery 10 . 1 and, seven vertical air channels 30 connected to the base inflatable air channel 20 at positions that line up with each corner 10 . 2 of the flexible weighted mat base 10 , each vertical air channel 30 measures at least six feet in height and each vertical air channel 30 has a diameter of at least three inches, six webbing panels 32 fixedly attached between all of the vertical air channels 30 and having the same separating distance between each vertical air channel 30 and at a position that is at least one third of the height of each vertical air channel 30 from the flexible weighted mat base 10 , and an inflatable domed ceiling 40 attached to the seven vertical air channels 30 . The dome ceiling 40 comprising of a first dome air channel 42 that has the same dimensions as the base inflatable air channel 20 and that aligns with the base inflatable air channel 20 , seven dome air channels connectors 44 connected to the first dome air channel 42 so that each of the seven dome air channel connectors 44 flow from positions aligned from each of the vertical air channels 30 , a shorter dome air channel connector 45 that is attached to the first dome air channel 42 at a position between the largest side 46 of the first dome air channel 42 , and lastly a second circular dome air channel 48 that attaches to all of the air channel connectors 44 / 45 , all of the inflatable skeleton air channels 20 / 30 / 42 / 44 / 45 / 48 are connected so that air can flow undisrupted through them. Lastly, a valve 50 , the valve attaches to one of the inflatable skeleton's air channels 20 / 30 near the flexible mat base 10 .
The inflatable skeleton might be inflated with a portable foot air pump 60 or with a powered air pump 60 .
The removable cover 200 is a heptagonal enclosure 200 that has dimensions that allow it to be slid over the inflatable skeleton 100 from the dome section 40 of the inflatable skeleton 100 toward the flexible weighted mat base 10 , the cover 200 is made to have a slightly larger diameter than the inflatable skeleton 100 , thereby allowing the cover 200 to be easily slid over the inflatable skeleton 100 . The cover 200 has a foldable opening 210 on the side of the cover 212 that fits over the largest side 12 of the flexible weighted mat base 10 . The foldable opening might be secured by a zipper 214 , or magnets 216 . The cover 200 might be made of nylon or of any other materials known in the art to promote privacy and that is light weight and durable. The cover 200 might further comprise of a first set of grommets 86 attached to each corner of the heptagonal enclosure 200 at a location of the heptagonal enclosure 200 that would rest over the mat base 10 . Each grommet 86 is secured to a surface by a pin 76 .
In a further embodiment of the present invention, the webbing panels 32 would define an aperture 32 a centrally located within each webbing panel 32 . The embodiment would further comprise of an I hook 70 , the I hook 70 having two ends, the first end of the I hook 70 inserts within the aperture 32 a , a second set of grommet attachments 74 , each grommet attachment 74 having one top grommet attachment, two securing means flowing from each grommet attachment and a ground grommet attachment attached to each securing means, each grommet attachment 74 attaches to the second end of each I hook 72 and a pin 76 secures each ground grommet attachment to the surface.
The portable changing room that is inflatable 500 of the present invention is used by first placing the flexible weighted mat base 10 on a surface, then finding the valve 50 of the inflatable skeleton 100 , then attaching an air pump 60 to the valve 50 , then inflating the inflatable skeleton 100 of the portable changing room so that the inflatable skeleton 100 is rigid, next sliding the cover 200 over the inflatable skeleton 100 , and lastly, securing the portable changing room 500 to the surface.
An advantage of the present invention is that it allows a user to use a portable changing room that is inflatable which is easily assembled and disassembled.
Although the present invention has been described in considerable detail in reference to preferred versions, other versions are possible. Therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained herein.
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A portable changing room that is inflatable. The portable changing room includes an inflatable skeleton, a valve, and a removable cover. A pump is used to inflate the inflatable skeleton. The changing room is used for privacy in outdoor environments.
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BACKGROUND OF THE INVENTION
[0001] 1. Technical Field
[0002] The present invention relates to reinforced resin-derived carbon foams useful for high temperature and/or high strength applications, such as composite tooling; electrodes; thermal insulation; core material used in sandwich structures; impact and sound absorption; and high-temperature furnace insulation and construction. More particularly, the present invention relates to carbon fiber reinforced carbon foams exhibiting superior graphitic strength, weight and density characteristics. The invention also includes methods for the production of such carbon foams.
[0003] 2. Background Art
[0004] Carbon foams have attracted considerable recent activity because of their properties of low density, coupled with either very high or low thermal conductivity. Conventionally, carbon foams are prepared via two general routes. Highly graphitizable foams have been produced by thermal treatment of mesophase pitches under high pressure. These foams tend to have high thermal and electrical conductivities. For example, in Klett, U.S. Pat. No. 6,033,506, mesophase pitch is heated while subjected to a pressure of 1000 psi to produce an open-cell foam containing interconnected cells with a size range of 90-200 microns. According to Klett, after heat treatment to 2800° C., the solid portion of the foam develops into a highly crystalline graphitic structure with an interlayer spacing of 0.366 nm. The foam is asserted to have compressive strengths greater than previous foams (3.4 MPa or 500 psi for a density of 0.53 g/cm 3 ).
[0005] In Hardcastle et al. (U.S. Pat. No. 6,776,936), carbon foams with densities ranging from 0.68-1.5 g/cm 3 are produced by heating a pitch in a mold at pressures up to 800 psi. The foam is alleged to be highly graphitizable and provide high thermal conductivity (250 W/m° K).
[0006] According to H. J. Anderson et al. in Proceedings of the 43rd International SAMPE Meeting, p. 756 (1998), carbon foam is produced from mesophase pitch followed by oxidative thermosetting and carbonization to 900° C. The foam has an open-cell structure of interconnected cells with varying shapes and with cell sizes ranging from 39 to greater than 480 microns.
[0007] Rogers et al., in Proceedings of the 45 th SAMPE Conference, p. 293 (2000), describe the preparation of carbon foams from coal-based precursors by heat treatment under high pressure to produce materials with densities of 0.35-0.45 g/cm 3 with compressive strengths of 2000-3000 psi (thus a strength/density ratio of about 6000 psi/(g/cm 3 )). These foams have an open-cell structure of interconnected cells with cell sizes up to 1000 microns. Unlike the mesophase pitch foams described above, the coal-based foams are not highly graphitizable. In a recent publication, the properties of this type of foam are described (High Performance Composites, September 2004, p. 25). The foam has a compressive strength of 800 psi at a density of 0.27 g/cm 3 or a strength-to-density ratio of 3000 psi/(g/cm 3 ).
[0008] Stiller et al. (U.S. Pat. No. 5,888,469) describe production of carbon foam by pressure heat treatment of a hydrotreated coal extract. These materials are claimed to have high compressive strengths of 600 psi for densities of 0.2-0.4 g/cm 3 (strength/density ratio of 1500-3000 psi/(g/cm 3 )). It is suggested that these foams are stronger than those having a glassy carbon or vitreous nature that are not graphitizable.
[0009] Carbon foams can also be produced by direct carbonization of polymers or polymer precursor blends. Mitchell, in U.S. Pat. No. 3,302,999, discusses preparing carbon foams by heating a polyurethane foam at 200-255° C. in air followed by carbonization in an inert atmosphere at 900° C. These foams have densities of 0.085-0.387 g/cm 3 and compressive strengths of 130 to 2040 psi (ratio of strength/density of 1529-5271 psi/(g/cm 3 )).
[0010] In U.S. Pat. No. 5,945,084, Droege describes the preparation of open-celled carbon foams by heat treating organic gels derived from hydroxylated benzenes and aldehydes (phenolic resin precursors). The foams have densities of 0.3-0.9 g/cm 3 and are composed of small mesopores with a size range of 2 to 50 nm.
[0011] Mercuri et al. (Proceedings of the 9 th Carbon Conference, p. 206 (1969)) prepare carbon foams by pyrolysis of phenolic resins. For foams with a density range of 0.1-0.4 gm/cm 3 , the compressive strength-to-density ratios are from 2380-6611 psi/(g/cm 3 ). The cells are ellipsoidal in shape with cell sizes of 25-75 microns for a carbon foam with a density of 0.25 g/cm 3 .
[0012] Stankiewicz (U.S. Pat. No. 6,103,149) prepares carbon foams with a controlled aspect ratio range of 0.6-1.2. The patentee points out that users often require a completely isotropic foam for superior properties with an aspect ratio of 1.0 being ideal. An open-cell carbon foam is produced by impregnation of a polyurethane foam with a carbonizable resin followed by thermal curing and carbonization. The cell aspect ratio of the original polyurethane foam is thus changed from 1.3-1.4 to 0.6-1.2.
[0013] Unfortunately, carbon foams produced by the prior art processes are not effective certain applications where high thermal and electrical conductivities as well as a high compressive strength are required to maintain the structural integrity of the carbon foam. Generally, the most economical and convenient method of producing carbon foam is to directly carbonize a precursor foam derived from either phenolic or polyurethane resin. These resins are known to produce a non-graphitizable, glassy carbon, which have much lower thermal and electrical conductivities. Thus, these carbon foam structures are suitable for applications such as thermal insulation and composite tooling but not for commercial applications where higher conductivities and compressive strength are desirable.
[0014] What is desired, therefore, is a reinforced resin-derived carbon foam which is monolithic and has a controllable cell structure, where the cell structure, strength and strength-to-density ratio make the foam suitable for use in composite tooling, heat and electrical conductors, batteries and fuel cell components, aerospace components, satellite structures, cores used in sandwich structures, and also in high-temperature insulation and construction as well as in other high temperature and/or high strength applications. Indeed, a combination of characteristics, including improved conductivities and strength-to-density ratios higher than those contemplated in the prior art, have been found to be necessary for use of a carbon foam in high temperature and strength applications. Also desired is a process for preparing such foams.
SUMMARY OF THE INVENTION
[0015] The present invention provides a carbon foam which exhibits improved conductivities, thermal and electrical conductivity, density, compressive strength and compressive strength-to-density ratio to provide a combination of strength, conductivity and relatively light weight characteristics not heretofore seen. In addition, the monolithic nature and bimodal cell structure of the foam, with a combination of larger and smaller cells, which are relatively spherical, provide a carbon foam which can be produced in a desired block size and configuration and which can be readily machined.
[0016] More particularly, the inventive carbon foam has a density of about 0.03 to about 0.6 gram per cubic centimeter (g/cm 3 ), with a compressive strength of at least about 2000 pounds per square inch (psi) (measured by, for instance, the ASTM C695 method). An important characteristic for the foam when intended for use in a high temperature application is the ratio of strength to density. For such applications, a ratio of compressive strength to density of at least about 7000 psi/(g/cm 3 ) is required, more preferably at least about 8000 psi/(g/cm 3 ).
[0017] The inventive carbon foam should have a relatively uniform distribution of cells in order to provide the required high compressive strength. In addition, the cells should be relatively isotropic, by which is meant that the cells are relatively spherical, meaning that the cells have, on average, an aspect ratio of between about 1.0 (which represents a perfect spherical geometry) and about 1.5. The aspect ratio is determined by dividing the longer dimension of any cell with its shorter dimension.
[0018] The foam should have a total porosity of about 50% to about 95%, more preferably about 60% to about 95%. In addition, it has been found highly advantageous to have a bimodal cell size distribution, that is, a combination of two average cell sizes, with the primary fraction being the larger size cells and a minor fraction of smaller size cells. Preferably, of the cells, at least about 90% of the cell volume, more preferably at least about 95% of the cell volume should be the larger size fraction, and at least about 1% of the cell volume, more preferably from about 2% to about 10% of the cell volume, should be the smaller size fraction.
[0019] The larger cell fraction of the bimodal cell size distribution in the inventive carbon foam should be about 10 to about 150 microns in diameter, more preferably about 15 to about 95 microns in diameter, most preferably about 25 to about 95 microns in diameter. The smaller fraction of cells should comprise cells that have a diameter of about 0.8 to about 3.5 microns, more preferably about 1 to about 2 microns. The bimodal cell-structure nature of the inventive foams provide an intermediate structure between open-cell foams and closed-cell foams, thus limiting the fluid permeability of the foam while maintaining a foam structure. Indeed, advantageously, the inventive carbon foams should exhibit a nitrogen gas permeability of no greater than about 3.0 darcys, more preferably no greater than about 2.0 darcys (as measured, for instance, by the ASTM C577 method).
[0020] Advantageously, to produce the inventive foams, a polymeric foam block, particularly a phenolic foam block, is carbonized in an inert or air-excluded atmosphere, at temperatures which can range from about 500° C., more preferably at least about 800° C., up to about 3200° C. to prepare carbon foams useful in high temperature applications.
[0021] An object of the invention is to provide a reinforced carbon foam having improved conductivities and strength characteristics which enable it to be employed for commercial applications where a higher thermal conductivity and electrical conductivity are desired as well as a greater compressive strength.
[0022] Another object of the invention, therefore, is a monolithic carbon foam having characteristics which enable it to be employed in high temperature applications such as composite tooling, core materials for sandwich panels and high-temperature furnace construction.
[0023] Yet another object of the invention is a carbon foam having improved graphitizability, density, compressive strength and ratio of compressive strength to density sufficient for high temperature applications.
[0024] Still another object of the invention is a carbon foam having a porosity and cell structure and size distribution to provide utility in applications where highly connected porosity is undesirable.
[0025] Yet another object of the invention is a carbon foam which can be produced in a desired block size and configuration, and which can be readily machined or joined to provide larger carbon foam structures.
[0026] Another object of the invention is to provide a method of producing the inventive carbon foam.
[0027] These aspects and others that will become apparent to the artisan upon review of the following description can be accomplished by providing a carbon foam article produced using a resin-derived foam, such as a phenolic resol, formed by polymerization in the presence of carbon fibers, single and multi-walled and phenolic micro-balloons, selected to improve the conductivity and/or the strength of the finished carbon foam. The precursor polymeric foam can also include graphitization promoting additives to increase the thermal and electrical conductivities of the final carbon foam product as well as oxidation-protective additives to reduce the foam's rate of oxidation.
[0028] The inventive carbon foam has a ratio of compressive strength to density of at least about 7000 psi/(g/cm 3 ), especially a ratio of compressive strength to density of at least about 8000 psi/(g/cm 3 ). The inventive foam product advantageously has a density of from about 0.03 to about 0.6 g/cm 3 and a compressive strength of at least about 2000 psi, and a porosity of between about 50% and about 95%. The cells of the carbon foam have, on average, an aspect ratio of between about 1.0 and about 1.5.
[0029] Preferably, at least about 90% of the cell volume is composed of the cells having a diameter of between about 10 and about 150 microns; indeed, most preferably, at least about 95% of the cell volume is composed of the cells having a diameter of between about 25 and about 95 microns. Advantageously, at least about 1% of the cell volume is composed of the cells having a diameter of between about 0.8 and about 3.5 microns, more preferably, from about 2% to about 10% of the cell volume is composed of the cells having a diameter of about 1 to about 2 microns.
[0030] The inventive foam can be produced by carbonizing a polymeric foam article, especially a phenolic foam, in an inert or air-excluded atmosphere. The phenolic foam should preferably have a compressive strength of at least about 100 psi.
[0031] It is to be understood that both the foregoing general description and the following detailed description provide embodiments of the invention and are intended to provide an overview or framework of understanding to nature and character of the invention as it is claimed.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0032] Carbon foams in accordance with the present invention are prepared from polymeric foams, such as polyurethane foams or phenolic foams, with phenolic foams being preferred. Phenolic resins are a large family of polymers and oligomers, composed of a wide variety of structures based on the reaction products of phenols with aldehydes. Phenolic resins are prepared by the reaction of phenol or substituted phenol with an aldehyde, especially formaldehyde, in the presence of an acidic or basic catalyst. Phenolic resin foam is a cured system composed of open and closed cells. The resins are generally aqueous resol catalyzed by sodium hydroxide at a formaldehyde-to-phenol ratio which can vary, but is preferably about 2:1. Free phenol and formaldehyde contents should be low, although urea may be used as a formaldehyde scavenger.
[0033] The foam is prepared by adjusting the water content of the resin and by adding a surfactant (e.g., an ethoxylated nonionic), a blowing agent (e.g., pentane, methylene chloride, or chlorofluorocarbon), and a catalyst (e.g., toluenesulfonic acid or phenolsulfonic acid). The sulfonic acid catalyzes the reaction, while the exotherm causes the blowing agent, emulsified in the resin, to evaporate and hence expand the foam. The surfactant controls the cell size as well as the ratio of open-to-closed cell units. Both batch and continuous processes are employed. In the continuous process, the machinery is similar to that used for continuous polyurethane foam. The properties of the foam depend mainly on density and the cell structure.
[0034] The preferred phenol is resorcinol; however, other phenols of similar kind that are able to form condensation products with aldehydes can also be used. Such phenols include monohydric and polyhydric phenols, pyrocatechol, hydroquinone, alkyl-substituted phenols, such as, for example, cresols or xylenols, polynuclear monohydric or polyhydric phenols, such as, for example, naphthols, p.p′-dihydroxydiphenyl dimethyl methane or hydroxyanthracenes.
[0035] The phenols used to make the foam starting material can also be used in admixture with non-phenolic precursors that are able to react with aldehydes in the same way as phenol.
[0036] The preferred aldehyde for use in the solution is formaldehyde. Other suitable aldehydes include those that will react with phenols in the same manner. These include, for example, acetaldehyde and benzaldehyde.
[0037] In general, the phenols and aldehydes that can be used in the process of the invention are those described in U.S. Pat. Nos. 3,960,761 and 5,047,225, the disclosures of which are incorporated herein by reference.
[0038] In order to create a reinforced resin-derived carbon foam with improved strength and/or graphitic properties, the carbon foam should be prepared with carbon fibers, carbon nanotubes and carbonized phenolic micro-balloons, incorporated throughout the foam's structure. The particular type of carbon fibers determines the resulting improvement of the carbon foam as carbon fibers derived from PAN, isotropic pitch, and mesophase pitch improve the strength characteristics of the carbon foam while fibers derived solely from mesophase pitch increase the foam's electrical and thermal conductivities. When carbon nanotubes are the selected type of carbon fiber for incorporation into the foam, both the strength and conductive properties of the foam are improved. Additionally, the graphitic properties of reinforced carbon foam are increased because of the physical incorporation of the carbon fibers. The individual carbon fiber filaments physically enhance the graphitizability of the precursor phenolic resins through stress-induced graphitization resulting in a more graphitic carbon foam end product.
[0039] The preferred method for creating reinforced phenolic-derived carbon foam is by incorporating carbon fibers into the initial liquid resol resin. Optimally, the liquid resol resin will have a water content of about 10% to about 30% by weight and the carbon fibers will have a length of about 0.1 inch to about 1.0 inch. Typically, the carbon fibers are added to the liquid resol resin in carbon fiber bundles under room temperature conditions. Each bundle consists of approximately 2,000 to 30,000 individual carbon fiber filaments held together in the tow form with a polymer resin or a sizing agent. The carbon fiber filaments are typically, either mesophase pitch carbon fibers, isotropic pitch carbon fibers, carbonized rayon fibers, cotton fibers, polyacrylonitrile (PAN) carbon fibers, cellulose fibers, carbon nanofibers, carbon nanotubes, or a combination of the aforementioned fibers. Phenolic microballoons either in the natural or carbonized state can also be employed as a reinforcing additive. For the most effective reinforcement and the greatest uniformity in properties of the carbon foam, the carbon fiber bundles need to be separated into individual filaments and dispersed throughout the carbon foam's structure. Optimally, the resin used in holding the carbon fiber bundles is water soluble and will readily dissolve upon addition to the liquid resol resin, allowing for the dispersion of individual carbon fiber filaments.
[0040] The carbon fiber bundles adhered with a water-soluble resin, can be added from about 0.5% to about 10% by weight to the liquid resol phenolic resin. This percentage range will optimally increase the strength and graphitic properties of the foam while not substantially reducing the inherent desirable properties of phenolic resin-derived carbon foam. Upon addition of the carbon fiber bundles to the liquid resol resin, the individual carbon fiber filaments will disperse throughout the resin and provide an ideal carbon fiber-resin mixture for the subsequent foaming process. Through foaming the phenolic resin, the carbon fiber will become uniformly dispersed and fixed in a specific spatial orientation within the phenolic foam product. During the carbonization of the phenolic foam, the carbon fiber filaments will aid in the stress orientation of the carbon foam ligaments, leading to an improved graphitizability and ultimately higher thermal and electrical conductivities. Also, the carbon fiber filaments will act as reinforcing agents to the solid carbon fraction of the foam and act as a conductive filler within the carbon foam.
[0041] In another embodiment, various additives can be added with the carbon fiber bundles to the initial liquid resol resin to achieve supplementary improvements. Additional additives for improving electrical and thermal conductivities include natural graphite flakes, graphitized powders and metal powders. Furthermore, oxidation-protective additives can also be added along with the carbon fiber bundles into the initial resol resin. The oxidation-protective additives include both polycarbosilane and silicon-nitrogen-containing polymers that will decompose at elevated temperatures into silicon carbide and silicon nitride. The above additives impart oxidation resistance to carbon foam, improving the performance of the carbon foam while minimally affecting the carbon foam's desired characteristics.
[0042] The polymeric foam precursor prepared as described above, that is used as the starting material in the production of the inventive carbon foam, should have an initial density that mirrors the desired final density for the carbon foam to be formed. In other words, the polymeric foam should have a density of about 0.03 to about 0.8 g/cm 3 , more preferably about 0.03 to about 0.6 g/cm 3 . The cell structure of the polymeric foam should be closed with a porosity of between about 50% and about 95% and a relatively high compressive strength, i.e., on the order of at least about 100 psi, and as high as about 300 psi or higher.
[0043] In order to convert the polymeric foam to carbon foam, the foam is carbonized by heating to a temperature of from about 500° C., more preferably at least about 800° C., up to about 3200° C., in an inert or air-excluded atmosphere, such as in the presence of nitrogen. The heating rate should be controlled such that the polymeric foam is brought to the desired temperature over a period of several days, since the polymeric foam can shrink by as much as about 50% or more during carbonization. Care should be taken to ensure uniform heating of the polymeric foam piece for effective carbonization.
[0044] By the use of a polymeric foam heated in an inert or air-excluded environment, a non-graphitizable carbon foam is obtained, which has the approximate density of the starting polymeric foam, but a compressive strength of at least about 2000 psi and, significantly, a ratio of strength to density of at least about 7000 psi/(g/cm 3 ), more preferably at least about 8000 psi/(g/cm 3 ). The carbon foam has a relatively uniform distribution of isotropic cells having, on average, an aspect ratio of between about 1.0 and about 1.5.
[0045] The resulting carbon foam has a total porosity of about 50% to about 95%, more preferably about 60% to about 95% with a bimodal cell size distribution; at least about 90%, more preferably at least about 95%, of the cell volume is composed of the cells of about 10 to about 150 microns in diameter, more preferably about 15 to about 95 microns in diameter, most preferably about 25 to about 95 microns in diameter, while at least about 1%, more preferably about 2% to about 10%, of the cell volume is composed of the cells of about 0.8 to about 3.5 microns, more preferably about 1 to about 2 microns, in diameter. The bimodal cell-structure nature of the inventive foam provides an intermediate structure between open-cell foams and closed-cell foams, limiting the fluid permeability of the foam while maintaining a foam structure. Nitrogen gas permeabilities less than 3.0 darcys, even less than 2.0 darcys, are preferred.
[0046] Typically, characteristics such as porosity and individual cell size and shape are measured optically, such as by the use of an optical microscopy using bright field illumination, and are determined using commercially available software, such as Image-Pro Software available from MediaCybernetic of Silver Springs, Md.
[0047] The cell structure of the foam is unique as compared to other foams in that it is intermediate to a closed cell and open cell configuration. The large cells appear to be only weakly connected to each other and connected by the fine porosity so that the foam exhibits permeability in the presence of water but does not readily absorb more viscous liquids.
[0048] Accordingly, by the practice of the present invention, carbon foams having heretofore unrecognized characteristics are prepared. These foams exhibit graphitizability as well as high compressive strength to density ratios and have a distinctive bimodal cell structure, making them uniquely effective at applications, such as composite tooling applications, core materials for sandwich panels and high-temperature furnace construction.
[0049] The disclosures of all cited patents and publications referred to in this application are incorporated herein by reference.
[0050] The above description is intended to enable the person skilled in the art to practice the invention. It is not intended to detail all of the possible variations and modifications that will become apparent to the skilled worker upon reading the description. It is intended, however, that all such modifications and variations be included within the scope of the invention that is defined by the following claims. The claims are intended to cover the indicated elements and steps in any arrangement or sequence that is effective to meet the objectives intended for the invention, unless the context specifically indicates the contrary.
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A reinforced carbon foam material is formed from carbon fibers incorporated within a carbon foam's structure. First, carbon fiber bundles are combined with a liquid resol resin. The carbon fiber bundles separate into individual carbon fiber filaments and disperse throughout the liquid resol resin. Second, the carbon fiber resin mixture is foamed thus fixing the carbon fibers in a permanent spatial arrangement within the phenolic foam. The foam is then carbonized to create a carbon fiber reinforced foam with improved graphitic characteristics as well as increased strength. Optionally, various additives can be introduced simultaneously with the addition of the carbon fiber bundles into the liquid resol, which can improve the graphitic nature of the final carbon foam material and/or increase the foam's resistance to oxidation.
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RELATED APPLICATION DATA
[0001] This application is based on and claims the benefit of U.S. Provisional Patent Application No. 60/505,935 filed on Sep. 24, 2003, the disclosure of which is incorporated herein in its entirety by this reference.
[0002] Financial assistance for this invention was provided by the United States Government, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Department of Health and Human Services Outstanding Investigator Grant Numbers CA44344-05-12; R01-CA90441-01; and R01 CA090441-03-041; the Arizona Disease Control Research Commission contract Number 9815; and private contributions. Thus, the United States Government has certain rights in this invention.
FIELD OF THE INVENTION
[0003] This invention relates to novel compounds having utility in the treatment of cancer and/or as antimicrobials.
BACKGROUND OF THE INVENTION
[0004] Pharmaceutical agents to treat cancer and/or tumors are widely sought. Antiangiogenesis agents are being pursued as a promising antitumor therapeutic agents. Combretastatin A-4 is one such antiangiogenesis agent. Studies have demonstrated that combretastatin A-4 disrupts the microtubules of human umbilical vein endothelial cells (HUVEC) in culture. It has also been shown that the tubulin-binding properties shown in cell-free systems are retained when the compound enters cells, and that tubulin binding is a significant component of biological acitivity.
[0005] The African Bush Willow Combretum caffrum has proved to be a very important source of cancer cell growth inhibitory constituents named combretastatins. The most potent of these constituents is combretastatin A-4 (1a, “CA-4”), and its sodium phosphate derivative (1b, “CA-4P”) was advanced to Phase I human cancer clinical trials in 1998. (Remick, S. C., et al., (1999) Phase I Pharmacokinetics Study of Single Dose Intravenous (IV) Combretastatin A-4 Prodrug (CA4P) in Patients (pts) with Advanced Cancer, Molecular Targets and Cancer Therapeutics Discovery Discovery, Development, and Clinical Validation, Proceedings of the AACR-NCI-EORTC International Congress, Washington, D.C., #16, p. 4.) Overall results continue to be promising, and human cancer Phase II and combination Ib trials are currently underway.
[0006] Antivascular, antiangiogenesis and general antimetastatic activities of CA4P as well as its synergistic utility in combination with other anticancer drugs, radioimmunotherapy and hyperthermia are all areas of active research interest. (see Griggs, J., et al., Combretastatin A-4 Disrupts Neovascular Development in Non-Neoplastic Tissue, British J. of Cancer 2001, 84, 832-835; Folkman, J., Angiogenesis-Dependent Diseases, Seminars in Oncology 2001, 28, 536-542; Kruger, E. A. et al., Approaches to Preclinical Screening of Antiangiogenic Agents, Seminars in Oncology 2001, 28, 570-576; Jin, X., et al., Evaluation of Endostatin Antiangiogenesis Gene Therapy in vitro and in vivo, Cancer Gene Therapy 2001, 8, 982-989; Vacca, A., et al., Bone Marrow Angiogenesis in Patients with Active Multiple Myeloma, Seminars in Oncology 2001, 28, 543-550; Rajkumar, S. V., et al., Angiogenesis in Multiple Myeloma, Seminars in Oncology 2001, 28, 560-564; Griggs, J., et al., Potent Anti-metastatic Activity of Combretastatin A-4, Int. J. Oncol. 2001, 821-825; Pedley, R. B. et al., Eradication of Colorectal Xenografts by Combined Radioimmunotherapy and Combretastatin A-4 3-O-Phosphate, Cancer Research 2001, 61, 4716-4722; Eikesdal, H. P., et al., Tumor Vasculature is Targeted by the Combination of Combretastatin A-4 and Hyperthermia, Radiotherapy and Oncology 2001, 61, 313-320.)
[0007] Several of the compounds of the present invention are particularly concerned with treatment of thyroid gland cancer. By 2002, some 20,000 people in the United States were diagnosed with carcinoma of the thyroid gland; of these the distribution was about 80% papillary and 14% follicular differentiated carcinomas derived from follicular epithelial cells producing thyroid hormone. Of the remaining thyroid malignancies, about 4% were medullary carcinoma (neuroendocrine) and 2% of the exceptionally aggressive anaplastic carcinoma (median survival 4-5 months and a near 100% lethal outcome). Significantly, the incidence of both follicular and anaplastic carcinomas are elevated in geographic areas of iodine deficiency. Radiation exposure represents the most general risk factor for thyroid cancer. In addition, excess production of the pituitary hormone thyroid-stimulating hormone (THS), which is very important in regulating thyroid gland growth and function, may be important in the etiology of thyroid cancer. Previously used clinical treatments for thyroid cancer include surgery, suppression of THS, 131 -radiotherapy, and anticancer drugs. But in 2002, another 1,300 victims of thyroid cancer in the U.S. died, emphasizing the great need for more routinely effective anticancer drugs.
SUMMARY OF THE INVENTION
[0008] The present invention relates to novel compounds constituting modifications of combretastatin A-3 (3a) and its phosphate prodrug (3b), wherein the 3-hydroxy group or the 3-hydroxy and 5-hydroxy groups are replaced with a halide. Representative halides are fluorine, chlorine, bromine and iodine. Salts of the novel compounds are also disclosed herein. Also described herein are phosphate ester derivatives of the 3-fluoro, 3-chloro, 3-bromo and 3-iodo-stilbenes.
[0009] Compounds of the invention comprise:
[0010] Wherein X is F, Cl, Br or I
[0011] Wherein X is F, Cl, Br or I, and R is a metal cation such as Na, Li, K, Cs, Rb, Ca, Mg or is morpholine, piperidine, glycine-OCH 3 , tryptophan-OCH 3 or NH(CH 2 OH) 3 .
[0012] Wherein X is F, Cl, Br or I, and Z is a metal cation such as Na, Li, K, Cs, Rb, Ca, Mg or is morpholine, piperidine, glycine-OCH 3 , tryptophan-OCH 3 or NH(CH 2 OH) 3 .
[0013] Several of the compounds of the invention exhibit greatly enhanced (>10-100×) cancer cell growth inhibition, as compared to prior art combretastatin compounds such as CA-4 and CA-3, against a panel of human cancer cell lines and the murine P388 leukemia. The iodo compounds appear to show particular promise in the treatment of thyroid cancers. The compounds of the present invention exhibit inhibiting of tubulin polymerization and binding of colchicine to tubulin. In addition, several of the compounds exhibit antimicrobial properties.
DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 shows the structural formulas of several prior art compounds.
[0015] FIG. 2 shows the reaction scheme for synthesizing some of the compounds of the present invention, including structural formulas for the compounds of the invention.
[0016] FIG. 3 shows a continuation of the reaction scheme of FIG. 2 .
[0017] FIG. 4 shows the reaction scheme for synthesizing some of the compounds of the present invention, including structural formulas for the compounds of the invention.
[0018] FIG. 5 shows photographs of results of the cord formation assay.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The concept of antiangiogenesis as a therapeutic approach for the treatment of cancer, particularly tumors, is being actively pursued as a promising strategy. The compound combretastatin A-4 has previously been demonstrated to disrupt the microtubules of human umbilical vein endothelial cells (HUVEC) in culture. Those studies confirmed that the tubulin-binding properties shown in cell-free systems are retained when the compound enters cells, and that tubulin binding is a significant component of the biological activity.
[0020] Thus, an object of the present invention is to provide new compounds that may be useful as tubulin binding agents.
[0021] A further object of the invention is to provide compounds that possess antiangiogenesis properties.
[0022] Yet another object of the invention is to provide compounds for use as therapeutic agents for the treatment of mammals, including humans, afflicted with cancer, particularly tumors.
[0023] Still a further object of the invention is to provide compounds for use as antimicrobials.
[0024] Results and Discussion
[0025] Preparation of the stilbenes of the present invention was accomplished as described in detail herein. The reaction sequence was initiated by protection of isovanillin as the tert-butyldiphenylsilyl ether 4. Benzaldehyde 4 was reduced using sodium borohydride to benzyl alcohol 5, followed by conversion to phosphonium bromide 6. Condensation of Wittig intermediate 6 with the respective halo-aldehyde using n-butyllithium in THF led to silyl group protected stilbenes 7-10. Subsequent deprotection (Scheme 2) with tetrabutylammonium fluoride afforded 3-halo-stilbenes 11-14. The Z isomers 11a, 13a and 14a were phosphorylated using dibenzylphosphite, diisopropylethyl-amine, N,N-dimethylamino-pyridine and carbon tetrachloride in acetonitrile to provide bisbenzyl phosphates 15-17. Debenzylation of phosphate esters 15-17 was achieved using trimethylsilybromide followed by the corresponding base to produce phosphates 18-20. (See Pettit, G. R., et al., Antineoplastic Agents 440. Asymmetric Synthesis and Evaluation of the Combretastatin A-1 SAR Probes (1S,2S) and (1R,2R)-1-2-Dihydroxy-1-(2′,3′-dihydroxy-4′-methoxyphenyl)-2-(3″,4″,5″-trimethoxyphenyl)-ethane, J. Nat. Prod. 2000, 63, 969-974; Pettit, G. R., et al., Antineoplastic Agents 460. Synthesis of Combretastatin A-2 Prodrugs, Anticancer Drug Design 2001, 16, 185-194; Pettit, G. R., et al. Antineoplastic Agents 463. Synthesis of Combretastatin A-3 Diphosphates, Anticancer Drug Design 2000, 15, 397-404.; Ladd, D. L., et al.; A New Synthesis of 3-Fluoroveratrole and Z-Fluoro-3,4 Dimethoxy Benzaldahyde, Synth. Commun. 1985, 15, 61.)
[0026] Compared to the related combretastatins, the new halo-stilbenes or halocombstatins shown in Table I as compounds 11a through 20a, all exhibited very strong inhibition of cancer cell growth. The three stilbenes (11a, 13a, 14a) converted to phosphate salts all retained strong activity and demonstrated markedly better aqueous solubility than their 3-halo-stilbene precursors. The E geometrical isomers evaluated appeared in vitro to be much less effective as inhibitors of cancer cell growth.
[0027] Because of their potent cytotoxicity, the four halocombstatins (11a, 12a, 13a, and 14a) were compared to combretastain A-4 (1a) for inhibitory effects on tubulin polymerization and on the binding of [ 3 H]colchicine to tubulin. The results of this comparison are shown in Table II. These experiments demonstrate that the five compounds are essentially identical in their apparent interactions with tubulin. The four halocombretastatins inhibited the polymerization reaction with IC 50 values of 1.5-1.6 μM:M, versus an IC 50 value of 1.8 μM:M for CA4 (1a). The minor differences between the compounds were within experimental error as indicated by the standard deviations.
[0028] Similarly, all four cis-stilbenes were highly potent inhibitors of the colchicine binding assay. When present at a concentration one fifth of that of [ 3 H]colchicine but equimolar to the tubulin concentration, binding of the radio labeled ligand was inhibited by 75-89% (note that the lowest and highest inhibitory effects were observed with stilbenes 11a and 13a, which were the two compounds that displayed the greatest inhibitory effects in the polymerization assay). In an earlier study, combretastatin A-3 (3a), with a hydroxyl substituent instead of the methoxy group or a halogen at position C-3 in the A ring, was found to be about half as active as CA4 (1a) as an inhibitor of tubulin assembly, about one fifth as active as an inhibitor of colchicine binding to tubulin, and about one seventh as active as an inhibitor of cell growth. (See Lin, C. M., et al, Interactions of Tubulin with Potent Natural and Synthetic Analogs of the Antimitotic Agent Combretastatin: A Structure-activity Study, Mol. Pharmacol., 1988, 34, 200-208). A related finding is that elimination of the C-3 substituent entirely, by replacing it with a hydrogen atom, results in about a 7-fold reduction in inhibitory effect on polymerization and complete loss of cytotoxic activity. (See Cushman, M., et al., Synthesis and Evaluation of (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane as Potential Cytotoxic and Antimitotic Agents, J. Med. Chem. 1992, 35, 2293-2306.)
[0029] Thus, while not intending to be bound by this theory, it appears the optimal activity observed with CA4 (1a) and the novel halocombstatins of the present invention requires a C-3 substituent of some size, where the fluorine atom may represent a minimum. Therefore, it seems unlikely that the predominant effect of the substituent results from direct enhancement of the interaction of ligand with protein. The A-ring substituents most likely cause the active cis-stilbenes to assume with greater probability a conformation that favors the drug-tubulin interaction. (See Hamel, E.; Evaluation of Antimitotic Agents by Quantitative Comparisons of Their Effects on the Polymerization of Purified Tubulin, Cell Biochem. Biophys., In Press.)
[0030] Tubulin polymerization was evaluated by turbidimetry at 350 nm using Beckman DU7400/7500 spectrophotometers as described in detail elsewhere. (See National Committee for Clinical Laboratory Standards. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard M27-A. Wayne, Pa.: NCCLS, 1997.) Varying concentrations of drug were preincubated with 10 μM:M (10 mg/mL) purified tubulin (See Hamel, E., et al., Separation of Active Tubulin and Microtubule-associated Proteins by Ultracentrifugation and Isolation of a Component Causing the Formation of Microtubule Bundles, Biochemistry 1984, 23, 4173-4184). Samples were chilled on ice, GTP (0.4 mM) was added, and polymerization was followed at 30° C. The parameter measured was extent of the reaction after 20 minutes. Colchicine binding was measured as described in detail previously. Reaction mixtures contained 1.0 μM:M tubulin, 5.0:M [ 3 H]colchicine (from Dupont), and inhibitor at 1.0 μM:M. Incubation was for 10 minutes at 37° C.
[0031] The inventors have also demonstrated the ability of halocombstatins 11a and 12a to disrupt microtubules in human umbilical vein endothelial cells (HUVEC). HUVECs were isolated according to methods know to one of skill in the art (see Jaffe, E. A. et al., Culture of Human Endothelial Cells Derived From Umbilical Veins. Identification by Morphologic and Immunologic Criteria, J. Clin. Invest. 1973, 52, 2754-2756.)
[0032] In a further detailed series of experiments, compound 11a (flurocombstatin) was further evaluated against HUVECs in vitro. These cells showed significant sensitivity to the fluorocombstatin (11a): ED 50 0.00025 μg/mL. Cords length as well as junction numbers were markedly reduced at both 0.01 and 0.001 μg/mL compared to untreated controls. Such activity against endothelial cells is significant, as endothelial cells are known to play a central role in the angiogenic process.
[0033] The halocombstatins of the present invention appear to also have antimicrobial properties. More specifically, they appear to have antifungal and/or antibacterial properties. Antimicrobial evaluation of the halocombstatins involved susceptibility testing performed by the reference broth microdilution assay. The antimicrobial activities of the halocombstatins were very similar, targeting Gram-positive bacteria and the pathogenic fungi Cryptococcus neoformans, and results are shown in Table III. The sodium phosphate dervative (16a) of fluorocombstatin (11a) did not retain significant antimicrobial activity.
[0034] Similarly, the inventors have previously shown that combretastatin A-3 but not its sodium phosphate prodrug inhibited growth of the pathogenic fungus Cryptococcus neoformans. (See Pettit, G. R., et al., Antineoplastic Agents 463. Synthesis of Combretastatin A-3 Diphosphates, Anticancer Drug Design 2000, 15, 397-404.) To determine the antimicrobial activity of the present compounds, susceptibility testing was performed by the reference broth microdilution assay. (See National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard M7-A5. Wayne, Pa.: NCCLS, 2000. National Committee for Clinical Laboratory Standards. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Aproved Standard M27-A. Wayne, Pa.: NCCLS, 1997.) The antimicrobial activities of the halocombretastatins of the present invention were very similar, targeting Gram-positive bacteria and Cryptococcus neoformans. This is illustrated in further detail in Table III. Thus, several of the novel compounds of the present invention appear to have potential as antimicrobial agents, such as antifungals and antibacterials.
[0035] Experimental Section
[0036] Materials and Methods. All solvents (ether refers to diethyl ether) and reagents were obtained from commercial sources (Acros Organics, Sigma-Aldrich Co., Alfa Aesar, City Chemicals or Lancaster Synthesis, Inc.). The 3-iodo-4,5-dimethoxybenzaldehyde was purchased from Lancaster Synthesis. Solvents were redistilled. Solvent extracts of aqueous solutions were dried over anhydrous magnesium sulfate. Gravity column chromatography was performed using silica gel from VWR Scientific 70-230 mesh) or from Merck (230-400 mesh). Analtech silica gel GHLF plates were employed for TLC.
[0037] All melting points were determined with an electrochemical digital melting point apparatus, Model 9100 or IA-9200, and are uncorrected. NMR spectra were recorded employing Varian Gemini 300 or Varian Unity 400 instruments. Chemical shifts are reported in ppm downfield from tramethylsilane as an internal standard in CDCl 3 or where noted in D 2 O. High resolution mass spectra were obtained with a Kratos Ms-50 instrument (Midwest Center for Mass Spectroscopy, University of Nebraska-Lincoln) or in the Cancer Research Institute at Arizona State University with a Jeol LCmate instrument. Elemental analyses were determined by Galbraith Laboratories, Inc., Knoxville, Tenn.
[0038] General Procedure for Synthesis of Dimethoxyhalobenzaldehydes.
[0039] 3-Fluoro-4,5-dimethoxybenzaldehyde. To a stirred solution prepared from 100 mL of DMF and 5-fluorovanillin (lit 1.0 g, 5.88 mmol). After 15 minutes, iodomethane was added, and stirring at room temperature continued for 16 hours. The reaction was terminated by the addition of water, the mixture was extracted with hexane (3×100 ML), and solvents were removed in vacuo. Purification by flash chromatography on a column of silica gel using hexane-ethyl acetate (4:1) as eluent afforded a colorless solid (1 g, 93% yield); mp 51-53° C. (Lit 17 mp 52-53° C.) 1 H-NMR (300 MHz, CDCl 3 ) δ 3.94 (s, 3H), 4.05 (s, 3H), 7.24 (s, 1H), 7.26 (s, 1H), 9.82 (s, 1H).
[0040] 3-Chloro-4,5-dimethoxybenzaldehyde. The preceding reaction was repeated with 5-chlorovanillin (10 g, 54 mmol) to give this compound, which was isolated as set forth in the preceding experiment to afford a colorless solid (10.4 g, 97% yield); mp 88-90° C. (Lit 17 mp 87-89° C.); 1 H-NMR (300 MHz, CDCl 3 ) δ 3.95 (s, 3H), 3.96 (s, 3H), 7.36 (d, J=1.5 Hz, 1H), 7.50 (d, J=1.5 Hz, 1H), 9.85 (s, 1H).
[0041] 3-Bromo-4,5-dimethoxybenzaldehyde. The experiment was repeated with 5-bromovanillin (10 g, 43.3 mmol) as described for the preceding aldehydes to give compound (6) which was separated by flash chromatography on a column of silica gel using hexane-ethyl acetate (9:1) as eluent to afford a colorless solid (8 g, 75% yield); mp 64-65° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.94 (s, 3H), 3.95 (s, 3H), 7.40 (d, 1H, J=1.8 Hz), 7.65 (d, 1H, J=1.8 Hz), 9.85 (s, 1H).
[0042] 3,5-diiodo-4-methoxybenzaldehyde
[0043] 3-Iodo-4,5-dimethoxybenzaldehyde was obtained from Sigma-Aldrich Chemical Company.
[0044] 3-O-tert-Butlydiphenylsiloxy-4-methoxybenzyltriphenylphosphonium bromide (6). To 400 mL of dry dichloromethane was added benzyl alcohol 5 (84 g, 214 mmol) (Pettit, G. et al., Antineoplastic Agents 463, Synthesis of Combretastatin A-3 Diphosphates. Anticancer Drug Design 2000, 15, 397-404) and phosphorous tribromide (10 mL, 106 mmol, 0.5 eq). The reaction mixture was allowed to stir for 16 hours, and was terminated by the addition of 10% NaHCO 3 , and the product was extracted with dichloromethane. The solvent was removed (in vacuo), the resulting benzyl bromide was dissolved in 500 mL of toluene, and triphenylphosphine (62 g, 236 mmol, 1.1 eq) was added. The mixture was heated at reflux for 1 hour and stirred at RT for 15 hours. The precipitate was collected and triturated with ether to afford 132 g of phosphonium salt, in 86% yield; 1 H-NMR (300 MHz CD 3 OD) δ 1.00 (s,9H), 3.51 (s,3H), 4.69 (d, 2H, J=17.4 Hz), 6.34 (dt, 1H, J=2.4, 8.1 Hz), 6.59 34 (d, 1H, J=8.1 Hz), 6.65 34 (t, 1H, J=2.4 Hz); and 13 C NMR (75 MHz CD 3 OD) δ 20.47, 27.07, 55.60, 102.20, 113.15, 118.48, 119.60, 123.43, 126.56, 126.85, 128.17, 128.74, 131.07, 131.12, 133.91, 135.10, 135.23, 136.17, 136.55, 146.55, 152.76.
[0045] General Procedure for the Stilbene Syntheses.
[0046] 3-Fluoro-4,4′,5-trimethoxy-3′-O-tert-butyldiphenylsilyl-Z-stilbene (7a). To a mixture of phosphonium salt 6 (4.7 g, 6.5 mmol) and tetrahydrofuran (25 ml, cooled to −78° C.) was added n-BuLi (2.6 mL, 2.5 M, 6.5 mmol, over 5 minutes), followed by stirring for one hour. Next, 3-fluoro-4,5-dimethoxybenzaldehyde (1g, 5.4 mmol) in tetrahydrofuran (10 ml) was added (dropwise) over 30 minutes. The mixture was allowed to warm to room temperature, and stirring continued for 16 hours. The reaction was terminated by the addition of water (50 mL), the product was extracted with ethyl acetate, solvents were removed in vacuo, and the residue (1:1 E/Z, 75% yield) obtained was subjected to flash chromatography on silica gel using hexane-ethyl acetate (9:1) as eluent to afford Z-stilbene 7a (1 g, 34%) as a clear oil; 1 H-NMR (300 MHz, CDCl 3 ) δ 1.07 (s, 9H), 3.46 (s, 3H), 3.65 (s, 3H), 3.90 (s, 3H), 6.24 (d, 1H, J=12 Hz), 6.33 (d, 1H, J=12 Hz), 6.56 (m, 2H), 6.72 (m, 3H), 7.35 (m, 6H), 7.70 (m, 4H); and 13 C NMR (75 MHz, CDCl 3 ) δ 19.75, 26.65, 55.07, 55.99, 61.43, 108.26, 108.28, 109.40, 109.55, 111.74, 120.83, 122.42, 127.36, 127.46, 127.48, 127.70, 129.37, 129.50, 129.63, 130.32, 132.59, 132.66, 133.57, 134.77, 135.27, 135.83, 135.95, 144.74, 149.88, 152.91, 152.95, 154.59, 156.53; HRMS (calcd for C 33 H 36 FO 4 Si) [M+H] + 543.2368, found 543.2372.
[0047] Further elution gave the E-isomer 7b (1.2 g, 41% yield): 1 H-NMR (300 MHz, CDCl 3 ) δ 1.19 (s, 9H), 3.58 (s, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 6.48 (d, 1H, J=15.9 Hz), 6.76 (d, 1H, J=8.7 Hz), 6.77 (d, 1H, J=16.5 Hz), 6.8 (d, 1H, J=1.5 Hz), 6.92 (d, 1H, J=2.1 Hz), 6.97 (dd, 1H, J=1.8, 8.4 Hz), 7.42 (m, 6H), 7.78 (m, 4H). 13 C NMR (75 MHz, CDCl 3 ) δ 19.76, 26.62, 55.20, 56.13, 61.39, 105.40, 106.45, 106.75 112.62, 117.62, 120.57, 125.26, 127.48, 128.52, 129.58, 139.68, 133.15, 133.28, 133.59, 135.35, 145.14, 150.52, 153.52. HRMS calcd for. C 33 H 36 FO 4 Si [M+H] + 543.2368, found 543.2392.
[0048] 3-Chloro-4,4′,5-trimethoxy-3′-O-tert-butyl-diphenylsilyl-Z-stilbene (8a). The experimental procedure noted above for 7a was repeated with 3-Chloro-4,5-dimethoxybenzaldehyde (2.8 g, 14 mmol) to yield the Z-isomer 8a (1.6 g, 21%) as a clear oil: 1 H-NMR (300 MHz, CDCl 3 ) δ 1.07 (s, 9H), 3.46 (s, 3H), 3.60 (s, 3H), 3.84 (s, 3H), 6.24 (d, 1H, J=12 Hz), 6.34 (d, 1H, J=12 Hz), 6.59 (s, 1H, J=7.5 Hz), 6.66 (s, 1H), 6.73 (s, 1H), 6.73 (d, 1H, J=9 Hz) 6.81 (s, 1H), 7.33 (m, 6H), 7.65 (dd, 4H, J=6.67, 1.2 Hz), and 13 C NMR (125 MHz, CDCl 3 ) δ 19.76, 26.66, 55.11, 55.82, 60.71, 111.35, 111.75, 120.86, 122.40, 122.46, 127.13, 127.38, 127.85, 129.32, 129.51, 130.27, 133.60, 133.81, 135.27, 144.22, 144.75, 149.91, 153.12; HRMS calcd for C 33 H 36 ClO 4 SiCl 561.2042 [M+H] + , found 561.2449, Cl 559.2071 [M+H] + ; found 559.1996.
[0049] Continued elution of the chromatographic column led to the isolation of E-stilbene 8b (4.9 g, 62% yield) as a clear oil; 1 H-NMR (300 MHz, CDCl 3 ) δ 1.14 (s, 9H), 3.56 (s, 3H), 3.86 (s, 3H), 3.90 (s, 3H), 6.44 (d, 1H, J=16.5 Hz), 6.74 (d, 1H, J=16.5 Hz), 6.74 (s, 1H), 6.82 (d, 1H, J=1.5 Hz), 6.87 (d, 1H, J=1.8 Hz), 6.94 (dd, 1H, J=8.1, 2.1 Hz), 6.99 (d, 1H, J=1.5 Hz), 7.40 (m, 6H), 7.75 (m, 4H); and 13 C NMR (75 MHz, CDCl 3 ) δ 19.82, 26.67, 55.30, 55.09, 60.78, 108.43, 112.13, 117.71, 119.78, 120.59, 124.97, 127.53, 128.78, 129.61, 129.73, 133.65, 134.31, 135.41, 144.55, 150.61, 153.74.
[0050] 3-Bromo-4,4′,5-trimethoxy-3′-O-tert-butyl-diphenylsilyl-Z-stilbene (9a). To 100 mL of THF was added phosphonium salt 6 (25.7 g, 36 mmol) and the solution cooled to −78° C. Once the temperature reached −78° C., n-BuLi (14.4 mL, 2.5 M, 36 mmol) was added over 5 minutes followed by stirring for one hour. Then the bromo-benzaldehyde (8 g, 33 mmol, in 100 mL THF) was added dropwise over 30 minutes. The mixture was allowed to warm to room temperature and stirring continued for 16 hours. The reaction was then terminated by the addition of water (50 mL), product was extracted with ethyl acetate, solvents were removed in vacuo, and the residue was separated by column chromatography to yield 4.2 g 9a (Z-stilbene), 2:1, E:Z (65% overall yield); HRMS (M+Na)+625.1364, (M+Na)+2 627.1338; IR 2962, 1730, 1510, 1267, 908, 735, 650 cm −1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 1.07 (s, 9H), 3.45 (s, 3H), 3.58 (s, 3H), 3.82 (s, 3H), 6.97 (d, 1H, J=1.5 Hz), 6.23 (d, 1H, J=12 Hz), 6.32 (d, 1H, J=12 Hz), 6.52 (d, 1H, J=8.1 Hz), 6.71 (dd, 1H, J=1.5 Hz, J=8.1 Hz), 7.57 (d, 1H, J=1.5 Hz), 7.32 (m, 6H), 7.65 (dd, 4H); 13 C NMR (100 MHz, CDCl 3 ) δ 152.87, 149.79, 145.16, 144.66, 135.17, 134.37, 133.52, 130.40, 129.43, 129.24, 127.30, 126.90, 125.16, 122.40, 120.79, 117.18, 112.01, 111.71, 94.38, 60.61, 55.81, 55.15, 21.10.
[0051] Further elution of the chromatogram led to isolation of 8.1 g of the E-isomer 9b: IR 2934, 2859, 1710, 1510, 1275, 908, 732, 650 cm −1 ; 1 H-NMR (300 MHz, CDCl 3 ) δ 1.14 (s, 9H), 3.54 (s, 3H), 3.84 (s, 3H), 3.88 (s, 3H),), 6.46 (d, 1H, J=12 Hz), 6.76 (d, 1H, J=12 Hz), 6.71 (d, 1H, J=8.1 Hz), 6.85 (d, 1H, J=2.1 Hz), 6.87 (d, 1H, J=2.1), 6.94 (dd, 1H, J=8.4 Hz, J=2.4 Hz), 7.15 (d, 1H, J=2.4) 7.38 (m, 6H), 7.74 (dd, 4H); and 13 C-NMR (75 MHz, CDCl 3 ) δ 19.76, 26.65, 55.25, 56.03, 60.59, 109.18, 109.85, 112.13, 117.70, 120.57, 122.59, 124.79, 127.48, 128.80, 129.58, 133.64, 134.91, 135.35, 145.16, 150.57, 153.58.
[0052] 3-Iodo-4,4′,5-trimethoxy-3′O-tert-butyl-diphenyl-Z-stilbene (10a). A gradient column chromatogram from 0-3% ethyl acetate in hexane afforded Z-stilbene 10a (1.4 g) in 21% yield mp 122-124° C.: HRMS, found: [M+H] + 651.1474. C 33 H 36 O 4 Si requires M+H, 651.1427; 1 H-NMR (300 MHz, CDCl 3 ) δ 1.07 (s, 9H), 3.45 (s, 3H), 3.55 (s, 3H), 3.79 (s, 3H), 6.21 (d, 1H, J=12 Hz), 6.31 (d, 1H, J=12 Hz), 6.59 (d, 1H, J=7.8 Hz), 6.72 (s, 2H), 6.77 (dd, 1H, J=7.8, 1.5 Hz), 7.19 (d, 1H, J=1.8 Hz), 7.32 (m, 6H), 7.64 (d, 4H, J=7.5 Hz); and 13 C NMR (75 MHz, CDCl 3 ) δ 19.68, 26.62, 55.05, 55.56, 60.33, 91.94, 111.72, 113.09, 120.78, 122.43, 126.73, 127.33, 129.32, 130.28, 130.93, 133.54, 135.17, 144.70, 149.82, 151.82.
[0053] General Procedure for Cleavage of the Silyl Ether Protecting Group.
[0054] 3-Fluoro-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene (11a, Fluorcombstatin). A solution prepared from Z-isomer 7a (2.4 g, 4.4 mmol), tetrahydrofuran (50 ml) and 1M tetrabutylammonium fluoride (4.5 ml, 4.5 mmol) was stirred fro 3 hours. The reaction was terminated by the addition of water (50 ml), the mixture was extracted with ethyl acetate and the solvents were removed in vacuo. Separation by flash chromatography using: 1:4 ethyl acetate-hexane as eluent provided Z-stilbene (11a) (1.12 g, 83%) as a colorless solid, which was recrystallized from ethyl acetate-hexane: mp 93-94° C.; (300 MHz, CDCl 3 ) δ 3.67 (s, 3H), 3.87 (s, 3H), 3.90 (s, 3H), 5.30 (bs, 1H), 6.35 (d, J=12 Hz, 1H), 6.48 (d, J=12 Hz, 1H), 6.61 (d, J=2.4 Hz, 1H), 6.64 (d, J=1.8 Hz, 1H), 6.72 (d, J=8.4 Hz, 1H), 6.75 (dd, J=1.5, 8.4 Hz, 2H), 6.86 (d, J=1.5 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 55.87, 56.01, 61.39, 108.24, 109.37, 109.57, 110.32, 114.83, 120.88, 127.72, 130.03, 130.14, 132.38, 132.48, 135.81, 135.95, 145.15, 145.78, 152.85, 152.88, 154.22, 156.65; and 19 F NMR (CDCl 3 ) δ −11.32 (d, J=12.8 Hz, 1F). HRMS calcd for C 17 H 18 FO 4 305.1189 [M+H] + .
[0055] 3-Fluoro-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene (11b). Cleavage of silyl ester 7b (150 mg, 0.27 mmol) was performed as described for the synthesis of 11a. Separation by flash chromatography on silica using ethyl acetate-hexane (3:7) afforded a colorless solid 11b (75 mg, 88% yield): mp 86-87° C.; 1 H NMR (300 MHz, CDCl 3 ) δ 3.87 (s, 3H), 3.90 (s, 3H), 3.93 (s, 3H), 5.75 (bs, 1H), 6.77-6.86 (m, 5H), 6.93 (m, 1H), 6.86 (d, J=1.8 Hz, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 55.87, 56.18, 61.39, 100.64, 105.68, 106.51, 106.79, 107.55, 110.63, 111.76, 119.30, 125.80, 127.61, 128.62, 129.53, 130.56, 133.13, 133.23, 134.73, 136.41, 145.78, 146.59, 153.57, 154.40, 157.64.
[0056] 3-Chloro-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene (12a). Deprotection of silyl ester 8a (1.5 g, 2.7 mmol) was conducted as summarized for the synthesis of 11a. Separation by flash chromatography on silica using ethyl acetate-hexane (3:7) gave compound 12a (754 mg, 89%). Recrystallization from hexane gave a white solid; mp 105-106° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.65 (s, 3H), 3.86 (s, 3H), 3.88 (s, 3H), 5.52 (s, 1H), 6.36 (d, 1H, J=12.3 Hz), 6.49 (d, 1H, J=12 Hz), 6.75 (m, 3H), 6.88 (m, 2H); 13 C NMR (75 MHz, CDCl 3 ) δ 55.86, 55.94, 60.76, 110.37, 111.40, 114.86, 114.94, 121.05, 122.51, 127.60, 127.92, 130.15, 130.43, 133.74, 144.36, 145.31, 145.92, 153.21.
[0057] 3-Chloro-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene 5 (12b). Column chromatography (elution with 7:3 hexane-ethyl acetate) afforded a colorless solid, E-isomer 12b, mp 138-140° C., in 79% yield: 1 H-NMR (300 MHz, CDCl 3 ) δ 3.87 (s, 3H), 3.88 (s, 3H), 3.90 (s, 3H), 5.69 (bs, 1H), 6.79 (d, 1H, J=15.9 Hz), 6.81 (d, 1H, J=8.4 Hz), 6.90 (d, 1H, J=1.5 Hz), 6.90 (d, 1H, J=15.9 Hz), 6.94 (dd, 1H, J=8.1, 1.5 Hz), 7.08 (dd, 1H, J=1.8 Hz), 7.11 (d, 1H, J=2.1 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 55.93, 56.06, 60.74, 100.66, 108.66, 110.65, 111.77, 119.38, 119.79, 125.49, 128.41, 128.85, 130.59, 134.24, 144.65, 145.79, 146.61, 153.78. HRMS calcd for C 17 H 17 ClO 4 321.0894 [M+H] + , found 321.0893. Anal. Calcd for C 17 H 17 ClO 4 C, H.
[0058] 3-Bromo-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene (13a). The silyl ester cleavage reaction for 9a (4 g, 6.6 mmol) was completed as described for the synthesis of phenol 11a. Isolation by flash chromatography on silica gel using ethyl acetate-hexane (1:4) gave compound 13a (2.22 g of 92%). Recrystallization from hexane afforded a colorless solid: mp 108-109° C.; HRMS calcd for C 17 H 17 BrO 4 364.0303, found [M +2 ] 366.0287; 1 H NMR (300 MHz, CDCl 3 ) δ 3.63 (s, 3H) 3.84 (s, 3H), 3.86 (s, 3H), 6.34 (d, 1H, J=12 Hz), 6.49 (d, 1H, J=12 Hz), 6.73 (d, 1H, J=8.4 Hz), 6.77 (dd, 1H, J=8.7, 1.8 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.86 (d, 1H, J=1.5 Hz), 7.04 (d, 1H, J=1.5 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 55.77, 55.88, 60.56, 110.45, 112.13, 114.98, 117.18, 121.01, 125.28, 127.33, 130.07, 130.43, 134.37, 145.32, 146.02, 153.03. IR 3539, 3441, 3011, 2939, 2839, 1554, 1510, 1273, 1047, 908, 732 cm −1 . HRMS calcd for C 17 H 17 O 4 81 Br. 366.0287.
[0059] 3-Bromo-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene (13b). By the same procedure used to obtain phenol 13a, silyl ester 9b was converted to E phenol 13b, and isolated by flash chromatography on silica gel with ethyl acetate-hexane (3:7) to give E-isomer 13b (0.14 g, 81%). Recrystallization from hexane gave colorless solid. mp 152-154° C.; 1 H NMR (300 MHz, CDCl 3 ) δ 3.86 (s, 3H), 3.89 (s, 3H), 3.90 (s, 3H), 6.80 (d, 1H, J=15.9 Hz), 7.38(d, 1H, J=15.9 Hz), 6.82 (d, 1H, J=8.4 Hz), 6.96 (dd, 1H, J=8.4, 2.4 Hz), 6.88 (s, 1H), 7.11 (d, 1H, J=1.8 Hz), 7.25 (d, 1H, J=1.5 Hz); and 13 C NMR (75 MHz, CDCl 3 ) δ 56.00, 56.11, 60.58, 94.36, 109.32, 110.60, 11.72, 117.81, 119.32, 122.58, 125.29, 128.82, 130.53, 134.81, 145.60, 145.70, 146.50, 153.53.
[0060] 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene (14a). The silyl ester cleavage reaction for 10a was completed as described for the phenol 11a. The crude product was separated by column chromatography using 1:4 ethyl acetate-hexane as eluent to give 1.38 g of Z-isomer 14a in 81% yield: mp 92-94° C.: HRMS calc for C 17 H 18 O 4 Si found (M+H) + 413.0250. 1 H NMR (300 MHz, CDCl 3 ) δ 3.61 (s, 3H), 3.81 (s, 3H), 3.84 (s, 3H), 6.32 (d, 1H, J=12 Hz), 6.34 (s, 1H), 6.56 (d, 1H, J=12 Hz), 6.75 (s, 1H), 6.83 (d, 1H, J=1.8 Hz), 6.85 (s, 3H), 7.25 (d, 1H, J=1.5 Hz); and 13 C NMR (75 MHz, CDCl 3 ) δ 55.56, 55.82, 60.33, 91.78, 110.50, 113.11, 115.00, 120.91, 126.96, 129.94, 130.28, 135.93 145.29, 146.10, 147.67, 151.79. IR 3543, 3011, 2937, 2841, 1510, 1273, 1001, 908, 732 cm −1 .
[0061] 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene (14b). Separation by column chromatography (30% ethyl acetate-hexane as eluent) gave 0.29 g of E-isomer 14b in 98% yield: mp 111-113° C.; 1 H NMR (300 MHz, CDCl 3 ) δ 3.84 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 5.85 (bs, 1H), 6.77 (d, 1H, J=16.5 Hz), 6.89 (d, 1H, J=16.5 Hz), 6.82 (s, 1H), 6.96 (s, 1H), 6.93 (d, 1H, J=2.4 Hz), 7.11 (d, 1H, J=1.5 Hz), 7.46 (d, 1H, J=1.5 Hz); and 13 C NMR (75 MHz, CDCl 3 ) δ 55.85, 60.41, 92.56, 110.40, 110.63, 111.77, 119.28, 124.97, 128.36, 128.70, 130.15, 135.71, 145.71, 146.56, 148.11, 152.44.
[0062] Dibenzyl (Z)-3-fluoro-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (15). Z-stilbene 11a (1.1 g, 3.6 mmol) in 20 mL of acetonitrile (20 mL) and 3.5 mL (36 mmol) of carbon tetrachloride was cooled to −10° C., and stirred for 10 minutes. Then DIPEA (1.3 mL, 7.4 mmol), immediately followed by DMAP (44 mg, 0.36 mmol), were added. After 1 minute dibenzyl phosphite (1.2 mL, 5.4 mmol) was added over 5 minutes, and the mixture was stirred for an additional 3 hours at −10° C. The reaction was terminated by the addition of 0.5 M KH 2 PO 4 , the mixture was extracted with ethyl acetate, solvents were removed in vacuo, and the product was isolated by column chromatography (1:1 elution with ethyl acetate-hexane) to yield 1.5 g of phosphate in 74% yield: b.p. dec. 280° C. (0.01 mmHg); 1 H-NMR (500 MHz, CDCl 3 ) δ 3.65 (s, 3H), 3.77 (s, 3H), 3.87 (s, 3H), 5.12 (s, 2H), 5.14 (s, 2H), 6.38 (d, 1H, J=12 Hz), 6.43 (d, 1H, J=12Hz), 6.57 (s, 1H) 6.62 (dd, 1H, J=1.5, 11.5 Hz), 6.78 (d, 1H, J=8.5 Hz), 7.03 (d, 1H, J=8.5 Hz), 7.12 (s, 1H), 7.82 (m, 10H); 13 C NMR (125 MHz, CDCl 3 ) δ; and 31 P NMR (162 MHz CDCl 3 ) δ −7.84 (s).
[0063] Dibenzyl (3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (16). The preceding reaction (see Compound 15) was repeated with Z-stilbene 13a (1 g, 2.7 mmol) to afford 1.6 g of phosphate 16 in 94% yield: b.p. dec. 271° C. (0.01 mmHg); 1 H-NMR (300 MHz, CDCl 3 ) δ 3.59 (s, 3H), 3.76 (s, 3H), 3.79 (s, 3H), 5.11 (s, 2H), 5.13 (s, 2H), 6.37 (d, 1H, J=12.4 Hz), 6.43 (d, 1H, J=12 Hz), 6.72 (d, 1H, J=1.5 Hz), 6.78 (d, 1H, J=8.4 Hz), 7.02 (d, 1H, J=8.2 Hz), 7.03 (d, 1H, J=2.4 Hz), 7.10 (d, 1H, J=1.8 Hz), 7.28 (m, 10H); 13 C NMR (75 MHz, CDCl 3 ) δ 55.77, 55.88, 60.51, 65.59, 69.67, 69.73, 111.83, 112.22, 117.23, 121.96, 121.99, 125.04, 126.32, 126.75, 127.30, 127.69, 127.77, 127.88, 128.31, 128.35, 129.46, 129.47, 133.93, 135.44, 135.51, 139.30, 139.38, 145.30, 149.77, 149.82, 152.99; and 31 P NMR (162 MHz CDCl 3 ) δ −7.84 (s).
[0064] Dibenzyl 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (17). The phosphorylation reaction used to obtain phosphate 15 was repeated with Z-stilbene 14a (2.39 g, 0.95 mmol) to obtain 0.55 g of Z-stilbene 17 in 86% yield as a colorless oil: b.p. dec. 274° C. (0.01 mmHg); HRMS calc for C 31 H 31 PO 7 (M+H) 673.0852; found [M+H] + , 673.0808. 1 H-NMR (300 MHz, CDCl 3 ) δ 3.51 (s, 3H), 3.65 (s, 3H), 3.72 (s, 3H), 5.04 (s, 2H), 5.06 (s, 2H), 6.36 (d, 1H, J=9Hz), 6.42 (d, 1H, J=9Hz), 6.77 (d, 1H, J=1.2 Hz), 6.89 (d, 1H, J=6 Hz), 7.02 (d, 1H, J=6 Hz), 7.01 (s, 1H), 7.19 (d, 1H, J=1.2 Hz), 7.28 (m, 10H); and 13 C-NMR (75 MHz, CDCl 3 ) δ 56.20, 56.50, 60.73, 71.18, 71.24, 92.73, 113.72, 114.23, 122.58, 122.61, 128.10, 128.93, 129.50, 129.56, 130.18, 130.85, 130.86, 131.87, 136.26, 136.66, 136.73, 140.32, 140.39, 149.12, 151.21, 151.25, 153.26.
[0065] General Procedure for Synthesis of Phosphate Cation Derivatives
[0066] Method A. Each of the metal cation containing salts were obtained by the procedure outlined below for preparing sodium salt 19a. The metal counter ions were introduced by treatment of the phosphoric acid with either the corresponding hydroxide (e.g., potassium, lithium) or acetate (e.g. magnesium).
[0067] Sodium 3-bromo-4,4′,-5-trimethoxy-Z-stilbene 3′-O-phosphate (19a). To a solution of dibenzyl phosphate 16 (0.28 g, 0.45 mmol) in dry dichloromethane (10 mL) was added trimethylsilylbromide (125 μL, 0.95 mmol). The reaction mixture was stirred for 30 minutes under argon, and the reaction was terminated by the addition of methanol (20 mL). Following removal of solvents (in vacuo), the free phosphoric acid was dissolved in ethanol (10 mL) and sodium methoxide (49 mg, 0.9 mmol) were added to the residue. After the reaction mixture was stirred for 30 minutes, the precipitate was collected and washed with ether to provide sodium salt 19a (0.17 g) as a colorless solid: m.p. 196-197° C.; 1 H-NMR (300 MHz, D 2 O) δ 3.53 (s, 3H), 3.68 (s, 3H), 3.70 (s, 3H), 6.52 (d, 1H, J=12 Hz), 6.72 (d, 1H, J=12 Hz), 6.75 (s, 1H), 6.77 (s, 1H), 6.79 (s, 1H), 7.01 (s, 1H), 7.15 (s, 1H).
[0068] Sodium 3-fluoro-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (18a). m.p. 200-202° C.; 1 H-NMR (300 MHz, D 2 O) δ 3.52 (s, 3H), 3.67 (s, 3H), 3.68 (s, 3H), 6.52 (d, 1H, J=12 Hz), 6.71 (d, 1H, J=12 Hz), 6.72 (s, 1H), 6.78 (s, 1H), 6.79 (s, 1H), 7.03 (s, 1H), 7.16 (s, 1H).
[0069] Lithium 3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (19b). m.p. 265-268° C. (dec); 1 H NMR (300 MHz, D 2 O) δ 3.53 (s, 3H), 3.66 (s, 3H), 3.69 (s, 3H), 6.35 (d, 1H, J=12 Hz), 6.52 (d, 1H, J=12 Hz), 6.70 (s, 2H), 6.81 (d, 1H, J=1.5 Hz), 7.01 (d, 1H, J=1.5 Hz), 7.23 (s, 1H).
[0070] Potassium 3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (19c). m.p. 230-233° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.53 (s, 3H), 3.66 (s, 3H), 3.69 (s, 3H), 6.35 (d, 1H, J=12 Hz), 6.52 (d, 1H, J=12 Hz), 6.70 (s, 2H), 6.81 (d, 1H, J=1.5 Hz), 7.01 (d, 1H, J=1.5 Hz), 7.23 (s, 1H).
[0071] Cesium 3-bromo-4,4′,5-trimethoxy-phenyl-Z-stilbene 3′-O-phosphate (19d). m.p. 233-235° C.; 1 H-NMR (300 MHz, DMSO) δ 3.51 (s, 3H), 3.62 (s, 3H), 3.65 (s, 3H), 6.38 (d, 1H, J=12 Hz), 6.50 (d, 1H, J=12 Hz), 6.71 (s, 1H), 6.83 (d, 1H, J=1.5 Hz), 7.03 (d, 2H, J=1.5 Hz), 7.23 (s, 1H).
[0072] Rubidium 3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (19e). m.p. 204-206° C.; 1 H-NMR (300 MHz, DMSO) δ 3.50 (s, 3H), 3.64 (s, 3H), 3.66 (s, 3H), 6.35 (d, 1H, J=12 Hz), 6.52 (d, 1H, J=12 Hz), 6.68 (s, 2H), 6.80 (d, 2H, J=1.5 Hz), 7.00 (d, 2H, J=1.5 Hz), 7.25 (s, 1H).
[0073] Calcium 3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (19f). m.p. 245-248° C. (dec); 1 H-NMR (300 MHz, DMSO) δ 3.53 (s, 3H), 3.69 (s, 3H), 3.70 (s, 3H), 6.33 (d, 1H, J=12 Hz), 6.50 (d, 1H, J=12 Hz), 6.71 (s, 2H), 6.81 (d, 2H, J=1.5 Hz), 7.99 (d, 2H, J=1.5 Hz), 7.23 (s, 1H).
[0074] Magnesium 3-bromo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (19g). m.p. 280-285° C. (dec); 1 H-NMR (300 MHz, DMSO) δ 3.50 (s, 3H) 3.60 (s, 3H), 3.65 (s, 3H), 6.33 (d, 1H, J=12 Hz), 6.50 (d, 1H, J=12 Hz), 6.68 (s, 2H), 6.79 (d, 2H, J=1.5 Hz), 7.00 (d, 2H, J=1.5 Hz), 7.21 (s, 1H).
[0075] Sodium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (20a). m.p. 194-195° C., 1 H-NMR (300 MHz, D 2 O) δ 3.50 (s, 3H), 3.67 (s, 3H), 3.68 (s, 3H), 6.50 (d, 1H, J=12 Hz), 6.70 (d, 1H, J=12 Hz), 6.72 (s, 1H), 6.77 (s, 1H), 6.79 (s, 1H), 7.01 (s, 1H), 7.13 (s, 1H).
[0076] Method B The potassium salt 18c (approximately 30 mg) was dissolved in de-ionized water (1 mL) and applied to a Dowex-50w (HCR-W2) resin column (amine or amino acid) and developed by water. The eluent was concentrated by freeze drying to give the required compound.
[0077] 3-Iodo-4,4′,5-trimethoxy-3′-O-tert-butyldiphenylsilyl-Z-stilbene (10a) and 3-Iodo-4,4′,5-trimethoxy-3′-O-tert-butyldiphenylsilyl-E-stilbene (10b).
[0078] Method A. Phosphonium bromide 6 (3.67 g, 5.13 mmol) was dissolved in DCM at 0° C. Sodium hydride (60% dispersion in mineral oil, 0.41 g, 10.2 mmol) was added and the mixture turned orange. Next, 3-iodo-4,5-dimethoxybenzaldehyde (1 g, 3.42 mmol) was added and stirring was continued for 21 hrs. The reaction was terminated by adding water (50 mL) and extracted with DCM (3×50 mL), which was dried, filtered and concentrated. The oil obtained was subjected to flash chromatography on silica gel with the eluent 0-3% ethyl acetate in hexane to afford Z-stilbene 10a (0.86 g, 39%) which crystallized as a colorless solid from hexane: mp 122-124° C.: 1 H-NMR (300 MHz, CDCl 3 ) δ 1.07 (s, 9 H), 3.45 (s, 3 H), 3.55 (s, 3 H), 3.79 (s, 3 H), 6.21 (d, 1 H, J=12 Hz), 6.31 (d, 1 H, J=12 Hz), 6.59 (d, 1 H, J=7.8 Hz), 6.72 (s, 2 H), 6.77 (dd, 1 H, J=7.8, 1.5 Hz), 7.19 (d, 1 H, J=1.8 Hz), 7.40-7.20 (m, 6 H), 7.64 (d, 4H, J=7.5 Hz); 13 C-NMR (75 MHz, CDCl 3 ) δ 19.68, 26.62, 55.05, 55.56, 60.33, 91.94, 111.72, 113.09, 120.78, 122.43, 126.73, 127.33, 129.32, 130.28, 130.93, 133.54, 135.17, 144.70, 149.82, 151.82; HRMS calcd for C 33 H 36 IO 4 Si 651.1428 [M+H] + , found 651.1474; Anal. calcd for C 33 H 35 I0 4 Si C, 60.92; H, 5.45. Found, C, 60.79; H, 5.67%.
[0079] Further elution gave E-stilbene 10b (0.96 g, 43%) that crystallized from hexane as a colorless solid; mp 98-99° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 1.14 (s, 9H), 3.55 (s, 3H), 3.82 (s, 3H), 3.82 (s, 3H), 3.89 (s, 3H), 6.43 (d, 1H, J=15.9 Hz), 6.71-6.76 (m, 2H), 6.86-6.95 (m, 3H), 7.33-7.42 (m, 6H); 13 C-NMR (100 MHz, CDCl 3 ) δ 19.81, 26.67, 55.28, 60.50, 92.65, 110.22, 112.11, 117.70, 120.56, 124.58, 127.52, 128.45; 128.68, 129.60, 129.77, 133.64, 135.38, 135.82, 145.18, 148.13, 150.56, 152.49; HRMS calcd for C 33 H 36 IO 4 Si 651.1428 [M+H] + , found 651.1400; Anal. calcd for C 33 H 35 I0 4 Si, C, 60.92; H, 5.42, found C, 60.88; H, 5.63%.
[0080] Method B. Butyllithium (4.5 mL, 11.3 mmol) was added to a stirred and cooled (−70° C.) suspension of phosphonium bromide 6 in dry THF (100 mL). The solution was stirred for 30 min at −70° C. then 6 hours at room temperature. Water (50 mL) was added and the reaction mixture was extracted with EtOAc (3×100 mL), the extract dried, filtered and concentrated. The oil obtained was subjected to flash chromatography on silica eluent 0-3% ethyl acetate in hexane to afford Z-stilbene 10a (1.4 g, 21%) as a colorless solid: mp 122-124° C.
[0081] 3,5-diiodo-4,4′-dimethoxy-3′-O-tert-butyl-diphenylsilyl-Z-stilbene and 3,5-diiodo-4,4′-dimethoxy-3′-O-tert-butyl-diphenylsilyl-E-stilbene
[0082] Method A. Phosphonium bromide 6 (2.77 g, 3.87 mmol) (8) was dissolved in DCM at 0° C. When sodium hydride (60% dispersion in mineral oil, 0.31 g, 7.7 mmol) was added, the mixture turned orange. Aldehyde (1.0 g, 2.57 mmol) was added and stirring was continued for 7.5 hrs. The reaction was terminated by adding water (50 mL) and extracted with DCM (3×50 mL). The organic extract was dried, filtered and concentrated. The oily residue was subjected to flash chromatography on silica gel using hexane as eluent to give an isomeric mixture of the title compounds (71% yield, 1.35 g). Further elution gave E-isomer (0.10 g, 5%) as a colorless oil in pure form: 1 H-NMR (300 MHz, CDCl 3 ) δ 1.14 (s, 9H), 3.56 (s, 3H), 3.84 (s, 3H), 6.33(d, 1 H, J 15.9 Hz), 6.72 (d, 1 H, J 8.4 Hz), 6.73 (d, 1 H, J 15.9 Hz), 6.72 (d, 1 H, J 8.4 Hz, ArH), 6.85 (d, 1H, J 2.1 Hz), 6.92 (dd, 1H, J 1.8 Hz and J 8.4 Hz), 7.34-7.46 (m, 6H) and 7.72-7.75 (m, 6H); 13 C-NMR (100 MHz, CDCl 3 ) δ 19.82, 26.69, 55.30, 60.77, 90.59, 112.09, 117.73, 120.83, 122.47, 127.55, 129.38, 129.65, 129.99, 133.58, 135.40, 137.15, 137.73, 145.22, 150.84 and 157.55; and HRMS calcd for C 32 H 33 I 2 O 3 Si 747.0289 [M+H] + , found 747.0442.
[0083] Method B. Butyllithium (0.6 mL, 1.47 mmol) was added to a stirred and cooled (−10° C.) suspension of phosphonium bromide 6 (1.01 g, 1.4 mmol) in dry THF (80 mL). The orange-red solution was stirred for 10 minutes at room temperature. Aldehyde (0.50 g, 1.33 mmol) was added and the reaction mixture color changed from red to yellow. Stirring was continued at room temperature for 10 minutes, ice water (100 mL) was added and the mixture extracted with EtOAc (3×100 mL). The extract was washed with water (100 mL), dried, filtered and concentrated. The resulting oil was partially separated by flash chromatography on silica gel using hexane-EtOAc (100:1) as eluent to give an isomeric mixture in a ratio approximately 1:1.9, (cis:trans, 0.90 g, 90%).
[0084] 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene (14a). To a solution of silyl ether 7a (1.30 g, 1.99 mmol) in THF was added tetrabutylammonium flouride (2.2 mL, 2.2 mmol). The mixture was stirred under Ar in the dark for 10 min. and the reaction was terminated by the addition of water (5 mL), the product was extracted with EtOAc (3×15 mL), and the extract dried, filtered and concentrated. The crude product was separated by silica gel column chromatography using 1:4 ethyl acetate-hexane as eluent to give stilbene 14a (0.70 g, 85%) as colorless solid: mp 92-94° C.; IR 3543, 3011, 2937, 2841, 1510, 1273, 1001, 908, 732 cm −1 ; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.61 (s, 3 H), 3.81 (s, 3 H), 3.84 (s, 3 H), 6.32 (d, 1 H, J=12 Hz), 6.34 (s, 1 H), 6.56 (d, 1 H, J=12 Hz), 6.75 (s, 1 H), 6.83 (d, 1 H, J=1.8 Hz), 6.85 (s, 3 H), 7.25 (d, 1 H, J=1.5 Hz); 13 C-NMR (75 MHz, CDCl 3 ) δ 55.56, 55.82, 60.33, 91.78, 110.50, 113.11, 115.00, 120.91, 126.96, 129.94, 130.28, 135.93 145.29, 146.10, 147.67, 151.79; HRMS calcd for C 17 H 18 IO 4 413.0259 [M+H] + , found 413.0250. Anal. calcd for C 17 H 17 IO 4 C, 49.53; H, 4.16. Found C, 49.38; H, 4.24%.
[0085] 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene (9b). The trans isomer 14b (0.29 g, 98%) was obtained from silyl ether 10b (0.46 g, 0.7 mmol) as described above for the synthesis of the cis isomer 14a. Separation by column chromatography (7:3 hexane-ethyl acetate as eluent) gave E-isomer 14b (0.29 g, 98%) as colorless solid: mp 111-113° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.84 (s, 3 H), 3.87 (s, 3 H), 3.88 (s, 3 H), 5.85 (bs, 1 H), 6.77 (d, 1 H, J=16.5 Hz), 6.89 (d, 1 H, J=16.5 Hz), 6.82 (s, 1 H), 6.96 (s, 1 H), 6.93 (d, 1 H, J=2.4 Hz), 7.11 (d, 1 H, J=1.5 Hz), 7.46 (d, 1 H, J=1.5 Hz); 13 C-NMR (75 MHz, CDCl 3 ) δ 55.85, 60.41, 92.56, 110.40, 110.63, 111.77, 119.28, 124.97, 128.36, 128.70, 130.15, 135.71, 145.71, 146.56, 148.11, 152.44; HRMS calcd for C 17 H 18 IO 4 413.0257 [M+H] + , found 413.0250. Anal. calcd for C 17 H 17 IO 4 C, 49.53; H, 4.16. Found, C, 49.38; H, 4.24%.
[0086] 3,5-diiodo-4,4′-dimethoxy-3′-hydroxy-Z-stilbene 22a and 3,5-diiodo-4,4′-dimethoxy-3′-hydroxy-E-stilbene 22b
[0087] These stilbenes were obtained from the Z and E silyl ether mixture 21ab (1.35 g, 1.81 mmol) as described above for the synthesis of cis-isomer 14a. The oily mixture was separated by column chromatography with 2:1 hexane-EtOAc as eluent to provide cis-isomer 22a as an oil (0.45 g, 49%): 1 H-NMR (300 MHz, CDCl 3 ) δ 3.85 (s, 3 H), 3.89 (s, 3 H), 5.54 (s, 1 H), 6.26 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.74 (s, 2H), 6.82 (s, 1 H) and 7.67 (s, 2 H); 13 C-NMR (125 MHz, CDCl 3 ) δ 55.98, 60.73, 89.98, 110.46, 114.87, 120.98, 125.08, 29.47, 131.57, 137.37, 139.96, 145.42, 146.21, 157.50. HRMS calcd for C 16 H 15 I 2 O 3 508.9113 [M+H] + , found 508.9111. Anal. calcd for C 16 H 14 I 2 O 3 C, 37.82; H, 2.78. Found, C, 37.80; H, 2.83.
[0088] Further elution led to the E-stilbene 22b (0.46 g, 50% yield) as a colorless solid which was crystallized from hexane: mp 127-129° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.86 (s, 3 H), 3.91 (s, 3 H), 5.62 (s, 1 H), 6.71 (d, 1 H, J=16.5 Hz), 6.83 (d, 1 H, J=8.1 Hz), 6.90 (d, 1 H, J=17.1 Hz), 6.95 (d, 1 H, J=8.4 Hz), 7.10 (d, 1 H, J=2.4 Hz) and 7.85 (s, 2 H, H-2); 13 C-NMR (75 MHz, CDCl 3 ) δ 55.51, 60.30, 90.17, 100.17, 100.21, 110.18, 111.35, 119.17, 122.56, 129.63, 129.81, 136.82, 137.19, 146.34 and 157.25; HRMS calcd for C 16 H 15 I 2 O 3 508.9113 [M+H] + , found 508.9119. Anal. calcd for C 16 H 14 I 2 O 3 C, 37.82; H, 2.78. Found, C, 38.01; H, 2.91.
[0089] 3,5-diiodo-4,4′-dimethoxy-3′-acetyl-Z-stilbene (22c)
[0090] An appropriate phenol 22a (0.45 g) was dissolved in pyridine (3 mL)-acetic anhydride (170 μL) and stirred for 2 hrs. The mixture was concentrated under reduced pressure from toluene (3×10 mL). The residue was diluted with EtOAc (30 mL), washed successively with water (10 mL), NaHCO 3 (10% aq. sol., 10 mL), dried, and the solution filtered and concentrated. The acetate was further purified by flash chromatography on silica using 1:24 hexane-EtOAc:hexane as eluent to afford acetate 22c (0.20 g, 41%) as a colorless solid:recrystallized from hexane mp 121-122° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 2.29 (s, 3 H), 3.83 (s, 3 H), 3.85 (s, 3 H), 6.29 (d, 1 H, J=12 Hz), 6.48 (d, 1 H, J=12 Hz), 6.85 (d, 1 H, J=8.7 Hz), 6.93 (d, 1 H, J=2.43), 7.06 (d, 1 H, J=1.5), 7.09 (d, 1 H, J=2.4 Hz) and 7.67 (s, 2 H); 13 C-NMR (125 MHz, CDCl 3 ) δ 20.66, 55.94, 60.72, 90.11, 112.16, 123.25, 125.41, 127.47, 128.85, 130.64, 137.10, 139.54, 139.89, 150.69, 157.67 and 168.79; HRMS calcd for C 19 H20I 2 O 5 582.9479 [M+CH 3 OH] + , found 582.9482; Anal. calcd for C 18 H 16 I 2 O 4 C, 39.30; H, 2.93. Found C, 39.30; H, 3.13%.
[0091] 3-iodo-4,4′,5-trimethoxy-3′-acetyl-Z-stilbene
[0092] An appropriate phenol (0.1 g, 0.24 mmol) was dissolved in 3 mL anhydrous pyridine. Acetic anhydride (50 μL, 0.51 mmol) was added with cat DMAP. The mixture was stirred for 90 minutes. The reaction was terminated by the addition of 5 mL CH 3 OH. The mixture was diluted with toluene and concentrated under reduced pressure. It was purified on flash chromatography on silica gel using EtOAc:hexane (1:9) as eluent to give a white solid (0.1 mg, 91%). The solid was crystallized from hexane: mp 103-104° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 2.27 (s, 3H), 3.61 (s, 3H), 3.81 (s, 6H), 6.38 (d, 1H, J=12 Hz), 6.48 (d, 1H, J=12 Hz), 6.77 (d, 1H, J=1.8 Hz), 6.83 (d, 1H, J=8.4 Hz), 6.96 (d, 1H, J=1.5 Hz), 7.09 (dd, 1H, J=8.4 Hz, J=2.4 Hz), and 7.26 (s, 1H); 13 C-NMR (125 MHz, CDCl 3 ) δ 20.61, 55.67, 55.93, 60.44, 92.07, 112.07, 112.92, 123.17, 127.63, 127.74, 129.39, 129.65, 103.97, 134.96, 139.49, 147.99, 150.39, 152.05 and 168.81; HRMS calcd for C 19 H 20 IO 5 455.0355 [M+H] + , found 455.0356. Anal. calcd for C 19 H 19 IO 5 C, 50.24; H, 4.22. Found, C, 49.67; H, 4.18 %.
[0093] Dibenzyl 3,5-diiodo-4,4′-dimethoxy-Z-stilbene 3′-O-phosphate (23)
[0094] An appropriate dibenzyl phosphate (0.38 g, 55% yield) was obtained (0.46 g, 0.91 mmol) as described above for the synthesis of iodide 10a. Colorless oil: bp dec 220° C.; 1 H-NMR (300 MHz, CDCl 3 ) δ 3.78 (s, 3 H), 3.81 (s, 6 H), 5.13 (s, 2 H), 5.16 (s, 2 H), 6.28 (d, 1 H, J=12 Hz), 6.42 (d, 1 H, J 12 Hz), 6.78 (d, 1 H, J 9 Hz), 7.00 (d, 1 H, J 8.7 Hz), 7.07 (s, 1 H), 7.33 (s, 10 H) and 7.64 (s, 2 H); 13 C-NMR (100 MHz, CDCl 3 ) δ 55.96, 60.71, 69.83, 69.89, 90.15, 112.40, 122.23, 122.26, 125.60, 126.20, 126.21, 127.93, 128.49, 128.55, 130.66, 137.12, 139.92 and 157.68; HRMS calcd for C 30 H 28 I 2 O 6 P 768.9713 [M+H] + , found 768.9699; 31 P-NMR (162 MHz, CDCl 3 ) δ −5.51.
[0095] General Procedures for Syntheses of the Phosphoric Acids and Derivatives.
[0096] Method A. Each of the metal cation phosphate salts was obtained by the procedure outlined herein for preparing the potassium salt 20c, except for the metal counterions introduced by treatment of the phosphoric acid using either lithium hydroxide or sodium methoxide.
[0097] Method B. Dowex-50W (2 g) (HCR-W2) was placed in a column and washed successively with CH 3 OH (50 mL), 1 N HCl (until pH 1), water (until pH 7), base/amine/amino acid (until pH 7-14) and water (until pH 7). The column was recycled. The potassium salt or its corresponding diiodo phosphate salt (about 25 mg) was dissolved in de-ionized water (1 mL) and applied to a Dowex-50W (HCR-W2) resin column (bearing the appropriate amine or amino acid methyl ester) and developed with approximately 40 mL of water. The eluent was concentrated by freeze drying to give the required cation derivative.
[0098] Method C. Amino Acid Methyl Esters. The amino acid methyl ester hydrochloride was neutralized in CH 3 OH solution by adding potassium carbonate. Ether was added to precipitate the potassium chloride and the solution was filtered and concentrated. The amino acid methyl ester residue was then applied to the Dowex-50W (HCR-W2) resin column as described in Method B.
[0099] Potassium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (20c).
[0100] Trimethylbromosilane (277 μL, 1.8 mmol) was added to a cooled (0° C.) solution of phosphate 9a in DCM (40 mL). After stirring for 90 minutes, sodium thiosulfate (10% aq., 10 mL) was added and the mixture was stirred for an additional 1 minute. The phases were separated and the aqueous phase extracted with DCM (20 mL), followed by EtOAc (2×20 mL). The combined organic extracts were dried, filtered and concentrated to afford the phosphoric acid intermediate as a clear oil. After drying (high vacuum) for 1 hour, the oil was dissolved in CH 3 OH (10 mL), cooled to 0° C., and KOH (1.8 mL, 1 M sol. in CH 3 OH) was added. The mixture was stirred for 20 minutes, the precipitate was collected and triturated with ether to afford the potassium salt as a colorless solid: mp 197-198° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.51 (s, 3 H), 3.64 (s, 3 H), 3.71 (s, 3 H), 6.33 (d, 1 H, J=12 Hz), 6.51 (d, 1 H, J=12 Hz), 6.70 (s, 2 H), 6.84 (s, 1 H) and 7.22 (s, 2 H); and 31 P-NMR (162 MHz, D 2 O) δ 0.94.
[0101] Sodium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (20a).
[0102] Isolated as a colorless solid: mp 194-195° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.50 (s, 3 H), 3.67 (s, 3 H), 3.68 (s, 3 H), 6.50 (d, 1 H, J=12 Hz), 6.70 (d, 1 H, J=12 Hz), 6.72 (s, 1 H), 6.77 (s, 1 H), 6.79 (s, 1 H), 7.01 (s, 1 H) and 7.13 (s, 1 H).
[0103] Lithium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate (11c).
[0104] Discovered as a colorless solid: mp 245-275° C. (dec); 1 H-NMR (400 MHz, D 2 O) δ 3.50 (s, 3 H), 3.62 (s, 3 H), 3.66 (s, 3 H), 6.33 (d, 1 H, J=12 Hz). 6.49 (d, 1 H, J=12 Hz), 6.70 (s, 2 H), 6.83 (s, 1 H), 7.20 (s, 1 H) and 7.22 (s, 1 H).
[0105] Morpholine 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate.
[0106] Another colorless oil: 1 H-NMR (300 MHz , D 2 O) δ 3.11-3.15 (m, 8 H), 3.50 (s, 3 H), 3.63 (s, 3 H), 3.68 (s, 3 H), 3.77-3.81 (m, 8 H), 6.33 (d, 1 H, J 12 Hz), 6.50 (d, 1 H, J12 Hz), 6.73 (s, 2 H), 6.82 (s, 1 H), 7.18 (s, 1 H) and 7.20 (s, 1 H).
[0107] Piperidene 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate.
[0108] Colorless oil: 1 H-NMR (300 MHz, D 2 O) δ 1.51 (m, 4 H), 1.62 (m, 8 H), 3.00 (t, 8 H, J=6 Hz), 3.51 (s, 3 H), 3.63 (s, 3 H), 3.67 (s, 3 H), 6.34 (d, 1 H, J=12.6 Hz), 6.51 (d, 1 H, J=12.6 Hz), 6.72 (s, 2 H), 6.83 (s, 1 H) and 7.21 (s, 1 H).
[0109] Glycine-OMe 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate.
[0110] Obtained as a colorless solid: mp 74-78° C.; 1 H-NMR (300 MHz, D 2 O) δ 3.48 (s, 3 H), 3.61 (s, 3 H), 3.67 (s, 3 H), 3.68 (s, 3 H), 3.76 (s, 2 H), 6.30 (d, 1 H, J=12 Hz), 6.46 (d, 1 H, J=12 Hz), 6.69-6.77 (m, 3 H), 7.10 (s, 1 H) and 7.16 (s, 1 H).
[0111] Tryptophan-OMe 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate.
[0112] Colorless solid: mp 108-112° C.; 1 H-NMR (300 MHz, DMSO) δ 3.19 (d, 2 H, J=6.3 Hz), 3.56 (s, 3 H), 3.61 (s, 3 H), 3.66 (s, 3 H), 3.70 (s, 3 H), 4.09 (t, 1 H, J=6 Hz), 6.35 (d, 1 H, J=12 Hz), 6.47 (d, 1 H, J=12 Hz), 6.81-6.85 (m, 2 H), 6.98 (t, 1 H, J=7.2 Hz), 7.07 (t, 1 H, J=8.1 Hz), 7.18 (s, 1 H), 7.22 (s, 1 H), 7.34 (d, 1 H, J=8.1 Hz), 7.40 (s, 1 H) and 7.46 (d, 1 H, J=7.2 Hz).
[0113] Tris 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate.
[0114] Colorless solid: mp 75-81° C.; 1 H-NMR (300 MHz, DMSO) δ 3.42 (s, 9 H), 3.57 (s, 3 H), 3.67 (s, 3 H), 3.70 (s, 3 H), 6.35 (d, 1 H, J=12 Hz), 6.48 (d, 1 H, J=12 Hz), 6.76 (d, 1 H, J=8.4 Hz), 6.81 (d, 1 H, J=8.7 Hz), 6.92 (s, 1 H), 7.22 (s, 1 H) and 7.42 (s, 1 H).
[0115] Potassium 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0116] Phosphate (0.20 g, 80%) was obtained from appropriate ester 9c (0.29 g, 0.38 mmol) as described above for the synthesis of 20c, except the phosphoric acid was insoluble in EtOAc and DCM, so the aqueous phase was extracted with butyl alcohol (3×25 mL). The potassium salt was a colorless solid: mp 210-215° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.69 (s, 6 H), 6.27 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.64 (s, 2 H), 7.20 (s, 1 H) and 7.62 (s, 2 H); 31 P-NMR (162 MHz, D 2 0) δ 0.973.
[0117] Sodium 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0118] Obtained as a colorless solid: mp 215-234° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.69 (s, 3 H), 3.72 (s, 3 H), 6.29 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.69 (s, 2 H), 7.20 (s, 1 H) and 7.64 (s, 2 H).
[0119] Lithium 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0120] A colorless solid melting at 250-270° C. (dec); 1 H-NMR (300 MHz, D 2 O) δ 3.68 (s, 3 H), 3.71 (s, 3 H), 6.28 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.68 (s, 2 H), 7.19 (s, 1 H) and 7.64 (s, 2 H). 31 P NMR (162 MHz, D 2 0) δ 0.96.
[0121] Morpholine 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0122] Colorless waxy solid; mp 75-80° C.; 1 H-NMR (300 MHz, DMSO) δ 2.96-2.99 (m, 8 H), 3.74-3.77 (m, 8 H), 3.82 (s, 3 H), 3.83 (s, 3 H), 6.43 (d, 1 H, J=12.5 Hz), 6.60 (d, 1 H, J=12.5 Hz), 6.86 (d, 1 H, J=8.2 Hz), 6.93 (d, 1 H, J=8.2 Hz), 7.49 (s, 1 H) and 7.78 (s, 2 H).
[0123] Piperidine 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0124] Isolated as a colorless oil; 1 H-NMR (300 MHz, DMSO) δ 1.51 (br s, 12 H), 2.79-2.81 (m, 8 H), 3.70 (s, 3 H), 3.72 (s, 3 H), 6.31 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.73 (d, 1 H, J=8.4 Hz), 6.80 (d, 1 H, J=8.4 Hz), 7.40 (s, 1 H) and 7.61 (s, 1 H).
[0125] Glycine-OMe 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0126] Colorless solid; mp 90-97° C.; 1 H-NMR (300 MHz, DMSO) δ 3.61 (s, 4 H), 3.68 (s, 6 H), 3.70 (s, 3 H), 3.72 (s, 3 H), 6.31 (d, 1 H, J=12 Hz), 6.49 (d, 1 H, J=12 Hz), 6.72 (d, 1 H, J=9.6 Hz), 6.80 (d, 1 H, J=8.1 Hz), 7.37 (s, 1 H) and 7.67 (s, 1 H).
[0127] Tryptophan-OMe 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0128] Collected as a colorless solid; melting at 125-130° C.; 1 H-NMR (300 MHz, DMSO) δ 3.34 (d, 1 H, J=6.5 Hz), 3.36 (d, 1 H, J=6.5 Hz), 3.66 (s, 3 H), 3.70 (s, 3 H), 3.72 (s, 3 H), 4.32 (t, 1 H, J=6.5 Hz), 6.31 (d, 1 H, J=12 Hz), 6.48 (d, 1 H, J=12 Hz), 6.78-6.81 (m, 2 H), 7.01 (s, 1 H), 7.05 (t, 1 H, J=7 Hz), 7.13 (t, 1 H, J=7 Hz), 7.39 (d, 1 H, J=7.5 Hz), 7.47 (d, 1 H, J=8 Hz) and 7.60 (s, 1 H).
[0129] Tris 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate.
[0130] Colorless solid; mp 115-120° C.; 1 H-NMR (300 MHz, DMSO) δ 3.34 (s, 18 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 6.30 (d, 1 H, J=12 Hz), 6.47 (d, 1 H, J=12 Hz), 6.70 (d, 1 H, J=8.1 Hz), 6.78 (d, 1 H, J=8.1 Hz), 7.37 (s, 1 H) and 7.67 (s, 2 H).
[0131] Cancer Cell Line Procedures
[0132] Inhibition of human cancer cell growth was assessed using the National Cancer Institute's standard sulforhodamine B assay. After 48 hours, the plates were fixed with trichloracetic acid, stained with sulforhodamine B and read with an automated microplate reader. A growth inhibition of 50% (GI 50 or the drug concentration causing a 50% reduction in the net protein increase) was calculated from optical density data with Immunosoft software. Inhibition of the mouse leukemia P388 cells was assessed in a 10% horse serum/Fisher medium soution for 24 hours, followed by a 48 hour incubation with serial dilutions of the compounds. Cell growth inhibition (ED 50 ) was then calculated using a Z1 Beckman/Coulter particle counter.
[0133] Tubulin Evaluations: Tubulin polymerization was evaluated by turbidimetry at 35 nm using Beckman DU7400/7500 spectrophotometers as known to one of skill in the art. Varying concentrations of the compound were preincubated with 10 μM. Incubation was for 10 minutes at 37° C.
[0134] Antiangiogenesis
[0135] HUVEC Procedures
[0136] In vitro Matrigel antiangiogenesis assays were implemented according to the Developmental Therapeutics Program NCI/NIH protocols known to one of skill in the art. Matrigel, a basement membrane matrix, was obtained from BD Biosciences. Growth inhibition and cord formation assays were conducted using human umbilical vein endothelial cells obtained from GlycoTech. HUVEC cells were grown in EGM-2 medium.
[0137] Cord Formation Assay
[0138] An aliquot of sixty microliters was placed in each well of an ice-cold 96-well plate. The plates were then left for 15 minutes at room temperature, then incubated for 30 minutes at 37° C. to permit the matrigel to polymerize. Meanwhile, HUVEC cells were harvested and diluted to a concentration of 2×10 5 cells/ml. A solution of 100 μL containing the compounds to be tested was added next. After 24 hours incubation, pictures were taken for each concentration using an inverted Nikon Diaphot microscope and D100 digital camera. Drug effect was assessed, compared to untreated controls, by measuring the length of cords formed and number of junctions.
[0139] The standard sulforhodamine B assay (see Cancer Cell Line Procedures above) was used to evaluate results using HUVEC cells. IC 50 or ED 50 (drug concentration causing 50% inhibition) was calculated from the plotted data.
ADMINISTRATION
[0140] Dosages
[0141] The dosage to be administered to humans and other animals requiring treatment will depend upon the identity of the neoplastic disease or microbial infection; the type of host involved, including its age, health and weight; the kind of concurrent treatment, if any; the frequency of treatment and therapeutic ratio. Hereinafter are described various possible dosages and methods of administration, with the understanding that the following are intended to be illustrative only, and that the actual dosages to be administered, and methods of administration or delivery may vary therefrom. The proper dosages and administration forms and methods may be determined by one of skill in the art.
[0142] Illustratively, anticipated dosage levels of the administered active ingredients may be in the following ranges: intravenous, 0.1 to about 200 mg/kg; intramuscular, 1 to about 500 mg/kg; orally, 5 to about 1000 mg/kg; intranasal instillation, 5 to about 1000 mg/kg; and aerosol, 5 to about 1000 mg/k of host body weight.
[0143] Expressed in terms of concentration, an active ingredient can be present in the compositions of the present invention for localized use about the cutis, intranasally, pharyngolaryngeally, bronchially, intravaginally, rectally, or ocularly in concentration of from about 0.01 to about 50% w/w of the composition; preferably about 1 to about 20% w/w of the composition; and for parenteral use in a concentration of from about 0.05 to about 50% w/v of the composition and preferably from about 5 to about 20% w/v.
[0144] The compositions of the present invention are intended to be presented for administration to humans and animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, suppositories, sterile parenteral solutions or suspensions, sterile non-parenteral solutions of suspensions, and oral solutions or suspensions and the like, containing suitable quantities of an active ingredient. Other dosage forms known in the art may be used.
[0145] For oral administration either solid or fluid unit dosage forms may be prepared.
[0146] Powders may be prepared by comminuting the active ingredient to a suitably fine size and mixing with a similarly comminuted diluent. The diluent can be an edible carbohydrate material such as lactose or starch. Advantageously, a sweetening agent or sugar is present as well as a flavoring oil.
[0147] Capsules may be produced by preparing a powder mixture as hereinbefore described and filling into formed gelatin sheaths. Advantageously, as an adjuvant to the filling operation, a lubricant such as talc, magnesium stearate, calcium stearate and the like is added to the powder mixture before the filling operation.
[0148] Soft gelatin capsules may be prepared by machine encapsulation of a slurry of active ingredients with an acceptable vegetable oil, light liquid petrolatum or other inert oil or triglyceride or other pharmaceutically acceptable carrier.
[0149] Tablets may be made by preparing a powder mixture, granulating or slugging, adding a lubricant and pressing into tablets. The powder mixture may be prepared by mixing an active ingredient, suitably comminuted, with a diluent or base such as starch, lactose, kaolin, dicalcium phosphate and the like. The powder mixture can be granulated by wetting with a binder such as corn syrup, gelatin solution, methylcellulose solution or acacia mucilage and forcing through a screen. As an alternative to granulating, the powder mixture may be slugged, i.e., run through the tablet machine and the resulting imperfectly formed tablets broken into pieces (slugs). The slugs can be lubricated to prevent sticking to the tablet-forming dies by means of the addition of stearic acid, a stearic salt, talc or mineral oil. The lubricated mixture is then compressed into tablets.
[0150] Advantageously, for protection of the tablet itself and/or to ease swallowing, the tablet can be provided with a pharmaceutically acceptable coating such as a sealing coat or enteric coat of shellac, a coating of sugar and methylcellulose and polish coating of carnauba wax.
[0151] Fluid unit dosage forms for oral administration such as in syrups, elixirs and suspensions may be prepared wherein each teaspoonful of composition contains a predetermined amount of an active ingredient for administration.
[0152] The water-soluble forms may be dissolved in an aqueous vehicle together with sugar, flavoring agents and preservatives to form a syrup. An elixir is prepared by using a hydroalcoholic vehicle with suitable sweeteners together with a flavoring agent. Suspensions may be prepared of the insoluble forms with a suitable vehicle with the aid of a pharmaceutically acceptable suspending agent such as acacia, tragacanth, methylcellulose and the like.
[0153] For parenteral administration, fluid unit dosage forms may be prepared utilizing an active ingredient and a sterile vehicle, for example, water. The active ingredient, depending on the form and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions the water-soluble active ingredient can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampule and sealing. Advantageously, adjuvants such as a local anesthetic, preservative and buffering agents can be dissolved in the vehicle. Parenteral suspensions may be prepared in substantially the same manner except that an active ingredient is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration. The active ingredient may be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle. Advantageously, a pharmaceutically acceptable surfactant or wetting agent may be included in the composition to facilitate uniform distribution of the active ingredient.
[0154] In addition to oral and parenteral administration, the rectal and vaginal routes can be utilized. An active ingredient can be administered by means of a suppository. A vehicle which has a melting point at about body temperature or one that is readily soluble can be utilized. For example, cocoa butter and various polyethylene glycols (Carbowaxes) can serve as the vehicle.
[0155] For intranasal installation, a fluid unit dosage form may be prepared utilizing an active ingredient and a suitable pharmaceutical vehicle, such as purified water, a dry powder, can be formulated when insufflation is the administration of choice.
[0156] For use as aerosols, the active ingredients may be packaged in a pressurized aerosal container together with a gaseous or liquefied propellant, for example, dichlorodifluoromethane, carbon dioxide, nitrogen, propane, and the like, with the usual adjuvants such as cosolvents and wetting agents, as may be necessary or desirable.
[0157] The term “unit dosage form” as used in the specification and claims refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle. The specifications for the novel unit dosage forms of this invention are dictated by and are directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitation inherent in the art of compounding such an active material for therapeutic use in humans, as disclosed in this specification, these being features of the present invention. Examples of suitable unit dosage forms in accord with this invention are tablets, capsules, troches, suppositories, powder packets, wafers, cachets, teaspoonfuls, tablespoonfuls, dropperfuls, ampules, vials, segregated multiples of any of the foregoing, and other forms as herein described.
[0158] The active ingredients to be employed as antineoplastic agents may be prepared in such unit dosage form with the employment of pharmaceutical materials which themselves are available in the art and can be prepared by established procedures. The following preparations are illustrative of the preparation of the unit dosage forms of the present invention, and not as a limitation thereof. Shown in the following are examples of dosage forms for the compounds of the present invention, in which the notation “active ingredient” signifies the compounds described herein.
COMPOSITION “A”
Hard-Gelatin Capsules
[0159] One thousand two-piece hard gelatin capsules for oral use, each capsule containing 200 mg of an active ingredient may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 200 g Corn Starch 20 g Talc 20 g Magnesium stearate 2 g
[0160] The active ingredient, finely divided by means of an air micronizer, is added to the other finely powdered ingredients, mixed thoroughly and then encapsulated in the usual manner.
[0161] Using the procedure above, capsules may be similarly prepared containing an active ingredient in 50, 250 and 500 mg amounts by substituting 50 g, 250 g and 500 g of an active ingredient for the 200 g used above.
COMPOSITION “B”
Soft Gelatin Capsules
[0162] One-piece soft gelatin capsules for oral use, each containing 200 mg of an active ingredient, finely divided by means of an air micronizer, may prepared by first suspending the compound in 0.5 ml of corn oil to render the material capsulatable and then encapsulating in the above manner.
COMPOSITION “C”
Tablets
[0163] One thousand tablets, each containing 200 mg of an active ingredient, may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 200 g Lactose 300 g Corn starch 50 g Magnesium stearate 4 g Light liquid petrolatum 5 g
[0164] The active ingredient, finely divided by means of an air micronizer, is added to the other ingredients and then thoroughly mixed and slugged. The slugs are broken down by forcing them through a Number Sixteen screen. The resulting granules are then compressed into tablets, each tablet containing 200 mg of the active ingredient.
[0165] Using the procedure above, tablets may similarly prepared containing an active ingredient in 250 mg and 100 mg amounts by substituting 250 g and 100 g of an active ingredient for the 200 g used above.
COMPOSITION “D”
Oral Suspension
[0166] One liter of an aqueous suspension for oral use, containing in each teaspoonful (5 ml) dose, 50 mg of an active ingredient, may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 10 g Citric acid 2 g Benzoic acid 1 g Sucrose 790 g Tragacanth 5 g Lemon Oil 2 g Deionized water, q.s. 1000 ml
[0167] The citric acid, benzoic acid, sucrose, tragacanth and lemon oil are dispersed in sufficient water to make 850 ml of suspension. The active ingredient, finely divided by means of an air micronizer, is stirred into the syrup unit uniformly distributed. Sufficient water is added to make 1000 ml.
COMPOSITION “E”
Parenteral Product
[0168] A sterile aqueous suspension for parenteral injection, containing 30 mg of an active ingredient in each milliliter for treating a neoplastic disease, may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 30 g POLYSORBATE 80 5 g Methylparaben 2.5 g Propylparaben 0.17 g Water for injection, q.s. 1000 ml.
[0169] All the ingredients, except the active ingredient, are dissolved in the water and the solution sterilized by filtration. To the sterile solution is added the sterilized active ingredient, finely divided by means of an air micronizer, and the final suspension is filled into sterile vials and the vials sealed.
COMPOSITION “F”
Suppository, Rectal and Vaginal
[0170] One thousand suppositories, each weighing 2.5 g and containing 200 mg of an active ingredient may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 15 g Propylene glycol 150 g Polyethylene glycol #4000, q.s. 2,500 g
[0171] The active ingredient is finely divided by means of an air micronizer and added to the propylene glycol and the mixture passed through a colloid mill until uniformly dispersed. The polyethylene glycol is melted and the propylene glycol dispersion is added slowly with stirring. The suspension is poured into unchilled molds at 40° C. The composition is allowed to cool and solidify and then removed from the mold and each suppository foil wrapped.
COMPOSITION “G”
Intranasal Suspension
[0172] One liter of a sterile aqueous suspension for intranasal instillation, containing 20 mg of an active ingredient in each milliliter, may be prepared from the following types and amounts of ingredients:
Active ingredient, micronized 15 g POLYSORBATE 80 5 g Methylparaben 2.5 g Propylparaben 0.17 g Deionized water, q.s. 1000 ml.
[0173] All the ingredients, except the active ingredient, are dissolved in the water and the solution sterilized by filtration. To the sterile solution is added the sterilized active ingredient, finely divided by means of an air micronizer, and the final suspension is aseptically filled into sterile containers.
COMPOSITION “H”
Powder
[0174] Five grams of active ingredient in bulk form is finely divided by means of an air micronizer. The micronized powder is placed in a shaker-type container.
COMPOSITION “I”
Oral Powder
[0175] One hundred grams of an active ingredient in bulk form may be finely divided by means of an air micronizer. The micronized powder is divided into individual doses of 200 mg and packaged.
COMPOSITION “J”
Insulation
[0176] One hundred grams of an active ingredient in bulk form is finely divided by means of an air micronizer.
[0177] It is of course understood that such modifications, alterations and adaptations as will readily occur to the artisan confronted with this disclosure are intended within the spirit of the present invention.
TABLE I Human cancer cell line inhibition (GI 50 μg/mL) and murine P388 lymphocytic leukemia inhibitory activity (ED 50 μg/ml) of halocombstatins and other compounds. Leukemia Pancreas- Breast adn CNS Lung-NSC Colon Prostate Compound P388 a BXPC-3 MCF-7 SF268 NCI-H460 KM20L2 DU-145 1a 0.0003 0.39 — <0.001 0.0006 0.061 0.0008 1b 0.0004 — — 0.036 0.029 0.034 — 2a 0.251 4.4 — — 0.74 0.061 0.17 2b <0.01 1.5 0.024 0.036 0.038 0.53 0.034 3a 0.257 2.3 0.49 0.0083 0.19 1.2 0.0043 3b 0.305 2.8 0.92 0.052 0.45 3.5 0.048 11a <0.01 0.016 <0.01 <0.01 <0.01 1.1 <0.01 11b 0.253 2.2 0.051 0.35 0.18 0.53 0.18 12a <0.01 0.043 <0.001 <0.001 <0.001 0.15 <0.001 12b 0.027 0.59 0.041 0.048 0.034 1.4 0.038 13a <0.01 0.16 <0.001 <0.001 <0.001 0.086 <0.001 13b 0.0174 1.6 0.14 0.18 0.15 1.2 0.13 14a <0.01 0.11 0.00022 0.00035 0.00019 0.15 0.00052 14b 0.189 2.7 0.18 0.55 0.21 1.7 0.27 18a 0.0298 0.59 0.0044 0.0051 0.0094 1.5 0.0036 19a <0.01 0.093 0.0041 0.0034 0.0028 0.23 0.0046 19b <0.01 0.13 0.0039 0.0030 0.0026 0.11 0.0066 19c <0.01 0.20 0.0035 0.0032 0.0029 0.24 0.0028 19d <0.01 0.15 0.0044 0.0064 0.0066 0.48 0.0079 19e <0.01 0.56 0.043 0.023 0.041 2.6 0.042 19f 0.288 <0.001 0.0022 0.0022 0.0068 0.37 0.0063 19g <0.01 0.074 0.0045 0.0053 0.0039 0.27 0.0045 19h <0.01 0.17 0.0049 0.0067 0.0047 0.45 0.0049 19i 2.22 >10 3.2 4.1 2.9 >10 2.8 20a <0.01 0.47 0.012 0.0052 0.0031 0.37 0.0078
[0178]
TABLE Ia
Solubilities of some of the synthetic modifications, human cancer cell line growth
inhibition (GI 50 μg/mL) and murine P388 lymphocytic leukemia inhibitory activity (ED 50 μg/ml).
Solubility a
Leukemia
Pancreas
Breast
CNS
Lung-NSC
Colon
Prostate
Compound
(mg/mL)
P388
BXPC-3
MCF-7
SF268
NCI-H460
KM20L2
DU-145
A
—
0.0003
0.39
—
<0.001
0.0006
0.061
0.0048
B
—
0.0004
—
—
0.036
0.029
0.034
—
C
—
0.26
2.3
0.49
0.0083
0.19
1.2
0.0043
D
—
0.0020
0.745
0.0027
0.0016
0.0032
>1
0.019
E
—
0.0020
0.048
0.00022
0.00018
0.00029
0.328
0.00018
F
—
0.189
2.7
0.18
0.55
0.21
1.7
0.27
G
—
0.0028
0.038
0.0027
0.0036
0.0034
0.15
0.0021
H
—
>10
3.0
0.94
3.3
3.4
>10
5.8
I
—
0.0089
0.040
0.00053
0.0023
0.0032
0.075
0.0020
J
—
0.022
0.080
<0.0001
0.0002
0.00031
0.16
0.00026
K
14
0.0021
0.381
0.0064
0.0057
0.0043
>1
0.0038
L
2
0.0020
0.469
0.018
0.018
0.017
>1
0.011
M
≧2.4
0.017
0.490
0.0038
0.0040
0.0039
>1
0.0043
N
—
0.0032
0.21
0.0047
0.0037
0.0036
0.24
0.0026
O
≧4
0.0026
0.32
0.0065
0.0044
0.0036
0.51
0.0029
P
≧2
0.0026
0.16
0.0044
0.0033
0.0031
0.32
0.0021
Q
—
0.0022
0.26
0.035
0.0097
0.0034
0.59
0.0030
R
—
0.0029
0.37
0.0048
0.0043
0.0040
0.40
0.0047
S
22
0.0034
0.44
0.050
0.053
0.046
>1
0.028
T
2
0.030
>1
0.066
0.051
0.327
>1
0.242
U
≧4
0.021
0.37
0.051
0.050
0.050
>1
0.032
V
—
0.014
0.35
0.066
0.054
0.033
>1
0.028
W
—
0.011
0.33
0.070
0.041
0.025
>1
0.025
X
—
0.011
0.36
0.10
0.054
0.030
>1
0.023
Y
—
0.017
0.37
0.22
0.086
0.033
>1
0.026
Z
—
0.026
0.33
0.047
0.040
0.025
0.94
0.021
a Solubility values were obtained using 1 mL D 2 O at 25° C.
Key to Table Ia
A = combretastatin A-4
B = sodium combretastatin A-4 phosphate
C = combretastatin A3
D = fluorocombstatin
E = 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-Z-stilbene
F = 3-Iodo-4,4′,5-trimethoxy-3′-hydroxy-E-stilbene
G = 3,5-diiodo-4,4′-dimethoxy-3′-hydroxy-Z-stilbene
H = 3,5-diiodo-4,4′-dimethoxy-3′-hydroxy-E-stilbene
I = 3,5-diiodo-4,4′-dimethoxy-3′-acetyl-Z-stilbene
J = 3-iodo-4,4′,5-trimethoxy-3′acetyl-Z-stilbene
K = Potassium 3-iodo, 4,4′,5 trimethoxy-Z-stilbene 3′-O-phosphate
L = Sodium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
M = Lithium 3 iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
N = Morpholine 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
O = Piperidine 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
P = Glycine-O-Me-3-iodo, 4,4′,5-trimethoxy-Z-stilbene-3′-O-phosphate
Q = Tryptophan-O-Me-3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
R = Tris-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
S = Potassium 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
T = Sodium 3,5-diiodo-4,4′-dimethoxy-Z-stilbene 3′-O-phosphate
U = Lithium 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
V = Morpholine 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
W = Piperidine 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
X = Glycine-O-Me 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
Y = Tryptophan-OMe-3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
Z = Tris 3,5 diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
[0179]
TABLE II
Inhibition of tubulin polymerization and binding of [ 3 H]colchicine
to tubulin by halocombstatins
Inhibition of
Inhibition of polymerization
colchicine binding
Compound
IC 50 (μM) ± S.D.
% inhibition ± S.D.
1a
1.8 ± 0.2
81 ± 3
11a
1.5 ± 0.2
75 ± 6
12a
1.6 ± 0.3
85 ± 4
13a
1.5 ± 0.2
89 ± 2
14a
1.6 ± 0.2
84 ± 7
[0180]
TABLE III
Antimicrobial activities of halocombstatins and other compounds
Range of minimum inhibitory concentration (μg/ml)
Compound
Microorganism
11a
11b
12a
14a
14b
13a
13b
18a
20a
Cryptococcus neoformans
64
64
64
32-64
64
*
*
*
*
Candida albicans
*
*
*
*
*
*
*
*
*
Staphylococcus aureus
*
32-64
*
*
8-64
*
*
*
*
Streptococcus pneumoniae
64
64
32-64
64
*
*
*
*
*
Enterococcus faecalis
*
*
*
*
*
*
*
*
*
Micrococcus luteus
32-64
16-32
32
16-32
4-8
32-64
*
*
*
Escherichia coli
*
*
*
*
*
*
*
*
*
Enterobacter cloacae
*
*
*
*
*
*
*
*
*
Stenotrophomonas
*
*
*
*
*
*
*
*
*
maltophilia
Neisseria gonorrhoeae
32
8-16
16
16-32
4-16
32-64
*
16
16-32
* = no inhibition at 64 μg/ml
[0181]
TABLE IV
Human Anaplastic Thyroid Carcinoma Cell Line Inhibition Values
(GI 50 ) expressed in μg/mL.
Compound
KAT-4
SW1736
3-Iodo-4,4′,5-trimethoxy-3′-
0.089-0.14
2.2
hydroxy-Z-stilbene
3,5-diiodo-4,4′-dimethoxy-
0.039-0.063
1.2
3′-hydroxy-Z-stilbene
Potassium 3-iodo-4,4′,5-trimethoxy-
0.37-0.43
>10
Z-stilbene 3′-O-phosphate
Potassium 3,5-diiodo-4,4′dimethoxy-
0.38-0.44
>10
Z-stilbene 3′-O-phosphate
[0182]
TABLE V
Human Umbilical Vein Endothelial Cell (HUVEC)
Inhibition Values (GI 50 ) expressed in μg/mL.
Compound
HUVEC
3-Iodo-4,4′,5-trimethoxy-3′hydroxyl-Z-stilbene
0.000040
3,5-diiodo-4,4′-dimethoxy-3′-hydroxy-Z-stilbene
0.00028
Potassium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
0.00025
Sodium 3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
0.00035
Potassium 3,5-diiodo-4,4′dimethoxy-Z-stilbene 3′-O-phosphate
0.0049
Sodium 3,5-diiodo-4,4′dimethoxy-Z-stilbenes 3′-O-phosphate
0.051
[0183]
TABLE VI
Length of Cords Formed, Number of Junctions
and Relative Percent Growth
Lengths
Relative
Drug
of
Number of
%
concentration
Cords
junctions
Growth
3-Iodo-4,4′,5-trimethoxy-
0.01 μg/ml
−
−
14
3′-hydroxy-Z-stilbene
0.001 μg/ml
+
+
14
0.0001 μg/ml
++(+)
++(+)
18
0.00001 μg/ml
90
3,5-diiodo-4,
0.01 μg/ml
−
−
4
4′dimethoxy-
0.001 μg/ml
+
(+)
8
3′-hydroxy-Z-stilbene
0.0001 μg/ml
+++
+++
84
0.00001 μg/ml
87
Potassium 3-iodo-4,4′,5-
0.01 μg/ml
1
trimethoxy-Z-stilbene-
0.001 μg/ml
++
++(+)
10
3′-O-phosphate
0.0001 μg/ml
+++
+++
77
0.00001 μg/ml
+++
+++
95
Sodium 3-iodo-4,4′,5-
0.1 μg/ml
−
−
7
trimethoxy-Z-stilbene-
0.01 μg/ml
−
−
14
3′-O-phosphate
0.001 μg/ml
+
+
5
0.0001 μg/ml
104
Potassium 3,5-diiodo-
0.1 μg/ml
−
−
15
4,4′dimethoxy-Z-
0.01 μg/ml
++(+)
++(+)
33
stilbene 3′-O-phosphate
0.001 μg/ml
+++
+++
88
0.0001 μg/ml
96
Sodium 3,5-diiodo-4,4′-
1 μg/ml
−
−
−7
dimethoxy-Z-stilbene 3′-
0.1 μg/ml
+
(+)
−2
O-phosphate
0.01 μg/ml
++(+)
++(+)
>100
0.0001 μg/ml
>100
Lengths of
Number of
Legend
Cords
junctions
−
No Cords
No
Junctions
+
Small
Few
++
˜50% of
˜50% of
Control
Control
+++
Same as Control
Same as Control
[0184]
TABLE VII
Antimicrobial activities of iodocomstatins
ATCC
or
Range of MIC (μg/ml)
(Presque
Compound
Microorganism
Isle)#
A
B
C
D
E
F
G
H
I
J
K
L
Cryptococcus
90112
*
64
*
*
*
*
*
*
*
*
*
*
neoformans
Candida
90028
*
*
*
*
*
*
*
*
*
*
*
*
albicans
Staphylococcus
29213
*
*
*
*
*
*
*
*
*
*
*
*
aureus
Streptococcus
6303
*
*
*
*
*
*
*
*
*
*
*
*
pneumoniae
Enterococcus
29212
*
*
*
*
*
*
*
*
*
*
*
*
faecalis
Micrococcus
(456)
*
*
4-16
2-4
*
*
*
*
*
*
*
*
luteus
Escherichia
25922
*
*
*
*
*
*
*
*
*
*
*
*
coli
Enterobacter
13047
*
*
*
*
*
*
*
*
*
*
*
*
cloacae
Stenotrophomonas
13637
*
*
*
*
*
*
*
*
*
*
*
*
maltophilia
Neisseria
49226
64
*
*
*
*
*
*
*
16-32
*
*
4-8
gonorrhoeae
Range of MIC (μg/ml)
Compound
Microorganism
M
N
O
P
Q
R
S
T
U
Cryptococcus
*
*
*
*
*
*
*
*
*
neoformans
Candida
*
*
*
*
*
*
*
*
*
albicans
Staphylococcus
*
*
*
*
*
*
*
*
*
aureus
Streptococcus
*
*
*
*
*
*
*
*
*
pneumoniae
Enterococcus
*
*
*
*
*
*
*
*
*
faecalis
Micrococcus
*
*
*
*
*
*
*
*
*
luteus
Escherichia
*
*
*
*
*
*
*
*
*
coli
Enterobacter
*
*
*
*
*
*
*
*
*
cloacae
Stenotrophomonas
*
*
*
*
*
*
*
*
*
maltophilia
Neisseria
32-64
<0.5-4
32-64
<0.5-2
<0.5
<0.5
<0.5-1
<0.5
<0.5-2
gonorrhoeae
Key for Table VII
B 3-iodo-4,4′5-trimethoxy-3′-hydroxy-Z-stilbene
C 3,5-diiodo-4,4′-dimethoxy-3′ hydroxy-Z-stilbene
D 3,5-diiodo-4,4′-dimethoxy-3′ hydroxy-E-stilbene
E 3,5-diiodo-4,4′-dimethoxy-3′-acetyl-Z-stilbene
F Potassium 3 iodo-4,4′5-trimethoxy-Z-stilbene 3′-O-phosphate
G Sodium 3 iodo-4,4′,5 trimethoxy-Z-stilbene-3′-O-phosphate
H Lithium-3-iodo-4,4′5 trimethoxy-Z-stilbene 3′O-phosphate
I Morpholine 3 iodo-4,4′5-trimethoxy-Z-stilbene-3′-O phosphate
J Piperidene 3-iodo-4,4′,5-trimethoxy-Z-stilbene-3′O phosphate
K Glycine-O-Me-3-iodo-4,4′,5-trimethoxy-Z-stilbene-3′-O-phosphate
L Tryptophan-O-Me-3′-iodo-4,4′,5 trimethoxy-Z-stilbene 3′-O-phosphate
M Tris-3-iodo-4,4′,5-trimethoxy-Z-stilbene 3′-O-phosphate
N Potassium 3,5 diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
O Sodium 3,5-diiodo-4,4′ dimethoxy-Z-stilbene 3′-O-phosphate
P Lithium 3,5-diiodo-4, 4′ dimethoxy-Z-stilbene 3′O phosphate
Q Morpholine 3,5 diiodo-4,4′ dimethoxy-Z-stilbene 3-O-phosphate
R Piperdine 3,5 diiodo-4,4′ dimethoxy-Z-stilbene 3′O-phosphate
S Glycine O Me 3,5-diiodo-4,4′ dimethoxy-Z-stilbene-3′-O-phosphate
T Tryptophan-O Me 3,5 diiodo 4,4′ dimethoxy-Z-stilbene-3′-O-phosphate
U Tris 3,5-diodo-4,4′ methoxy-Z-stilbene 3′O-phosphate
|
The invention relates to novel compounds denominated halocombstatins. The halocombstatins are derivatives of combretastatin A-3, and include compounds that exhibit cancer growth cell inhibition against a panel of human cancer cell lines and the murine P388 leukemia, as well as activity as inhibitors of tubulin polymerization and inhibitors of the binding of colchicine to tubulin.
| 2
|
This is a continuation-in-part of PCT/IL97/00403, filed Dec. 9, 1997.
FIELD AND BACKGROUND OF THE INVENTION
The present invention is related to filtering means, in particular to composite polymeric fiber filters, and to the technology for their manufacture.
The creation of filtering materials capable of trapping particles of 0.1-10 microns in size and their increasing use is related to increasingly stringent requirements for quality and reliability of manufactured commodities, as well as to the rapid development of modern technology and production processes, such as, but not limited to, electronics, aviation, automobile industry, electrochemical industry, biotechnology, medicine, etc.
The main industrial manufacturing methods for such materials include production from polymer solutions (V. P. Dubyaga et al., Polymer Membranes , “Chemistry” Publishing House, Moscow, 1981 (in Russian); V. E. Gul and V. P. Dyakonova, Physical and Chemical Principles of Polymer Films Manufacture , “Higher School Publishing House, Moscow, 1978 (in Russian); German patent DE 3,023,788, “Cationic absorbent for removing acid dyes etc. From waste water—prepared from aminoplast precondensate and amine-amide compound”), from powders and powder polymer composites (P. B. Zhivotinskiy, Porous Partitions and Membranes in Electrochemical Equipment , “Chemistry” Publishing House, Leningrad, 1978 (in Russian); Encyclopedia of Polymer Science and Engineering , Wiley, N.Y., 1987, Vol. 8 p. 533), from macromonolithic films (I. Cabasso and A. F. Turbak, “Synthetic membranes”, Vol. 1, ACS Symposium, Ser . 154, Washington D.C., 1981, p. 267), and from fibers and dispersions of fibrous polymers (T. Miura, “Totally dry unwoven system combines air-laid and thermobonding technology”, Unwoven World Vol . 73 (March 1988) p.46). The latter method is the most widespread, since it facilitates the manufacture of materials with the optimal cost-quality ratio.
Great interest is also being expressed in the extension of the traditional uses of filtering, materials, especially to combination functions of trapping micro-particles in gaseous and liquid media with the adsorption of molecular admixtures, for example, in the removal of mercaptans, as substrate for catalytic reactions, in the enhancement of the bactericidal effect of the filtering material, etc. Fulfillment of these additional functions is possible due to the introduction into the fiber matrix of fillers of some sort or functional groups giving the formation of additional solid phase, i.e., as a result of manufacturing of composite filtering materials.
At present, high efficiency polymeric filtering materials are manufactured from synthetic fibers by means of a technology that is similar in many aspects to the traditional technology applied in the pulp and paper industry. A long fiber thread is cut into pieces of a given length, which are then subjected to some basic and supplementary operations out of more than 50 possibilities, which may include chemical processing for modification of surface properties, mixing with binding and stabilizing compositions, calendaring, drying process, etc. (O. I. Nachinkin, Polymer Microfilters , “Chemistry” Publishing House, Moscow, 1985 (in Russian), pp. 157-158). The complexity of such a technological process hampers the manufacture of materials with stable characteristics for subsequent exploitation; results in the high cost of manufactured filtering materials; and practically excludes the manufacture of composites with fillers sensitive to moist, thermal processing.
Low efficiency filtering materials (class ASHRAE) are manufactured by melt blow or spun-bonded processes.
There is, however, a method for the manufacture of ultra-thin synthetic fibers (and devices for their production), which facilitates the combination of the process of fiber manufacture with the formation of a microporous filtering material, and thus reduces the number of technological operations, precludes the necessity for aqueous reaction media, and increases the stability of properties of the product being manufactured (see, for example, U.S. Pat. No. 2,349,950). According to this method, known as “electrocapillary spinning”, fibers of a given length are formed during the process of polymer solution flow from capillary apertures under electric forces and fall on a receptor to form an unwoven polymer material, the basic properties of which may be effectively changed.
With this method, fiber formation takes place in the gaps between each capillary, being under negative potential, and a grounded antielectrode in the form of a thin wire, i.e., in the presence of a heterogeneous field, being accompanied by corona discharge. However, the process of solvent evaporation takes place very rapidly, and as a result the fiber is subjected to varying electric and aerodynamic forces, which leads to anisotropy along the fiber width and formation of short fibers.
Manufacture of high-quality filtering materials from such fibers is thus impossible because the electric charge of the fibers is low, such that the process of forming the filtering material is not controlled by electrical force and consequently the filtering material is not uniform.
Exploitation of a device for executing the method described above is complicated by a number of technological difficulties:
1. Capillary apertures become blocked by polymer films that form under any deviation from the technological process conditions—concentration and temperature of solution, atmospheric humidity, intensity of electric field, etc.
2. The presence of a large number of such formations leads to a complete halt of the technological process or drops form as a consequence of the rupture of the aforementioned films.
3. The presence of high intensity electric field in the area of the precipitation electrode limits the productivity of the method.
Therefore, the manufacture of synthetic fibers by this method is possible from only a very limited number of polymers, for example, cellulose acetate and low molecular weight polycarbonate, which are not prone to the defects described above.
It is necessary to take into account the fact that such an important parameter of filtering materials as monodispersity of the pores (and the resultant separation efficiency of the product) has, in this case, a weak dependency on fiber characteristics and is largely determined by the purely probabilistic process of fiber stacking.
Modern filtering materials are subject to strict, frequently contradictory, requirements. In addition to high efficiency of separation of heterogeneous liquid and gas systems, they are required to provide low hydro- (or aero-) dynamic resistance of the filter, good mechanical strength and technical properties (e.g., pleatability), chemical stability, good dirt absorption capacity, and universality of application, together with low cost.
The manufacture of such products is conditional on the use of high-quality long and thin fibers with an isometric cross-section, containing monodispersed pores and exhibiting high porosity. The practical value of this product may be greatly increased as possible applications are expanded due to the formation of additional phases, i.e., in the manufacture of the above-mentioned composite filtering materials.
At present there is a high demand to high efficiency particulate air (HEPA) filters which are defined as capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec. Such a requirement is met, for example, by glass-fiber based filters, however on the expense of a high pressure drop, in a range of 30-40 mm H 2 O.
U.S. Pat. Nos. 4,874,659 and 4,178,157 both teach high efficiency particulate air filters capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec, characterized by lower pressure drop in a range of 5-10 mm H 2 O. These filters are made of nonwoven web (U.S. Pat. No. 4,874,659) or sliced films (U.S. Pat. No. 4,178,157) made of polyolefines, such as polyethylene or polypropylene, which are partially melted by heating to about 100° C. and are thereafter subjected to an immense electrical field which electrically charges the polymer. The result is a filter media, characterized by thick fibers (10-200 μm) in diameter, low porosity and being electrically charged. The latter property, provides these filters with the high efficiency particulate air (HEPA) qualities. However, such filters suffer few limitations. First, being based on the electrical charge for effective capture of particulates, the performances of such filters are greatly influenced by air humidity, causing charge dissipation. Second, due to their mode of action and to being relatively thin, such filters are characterized by low dust load (the weigh of dust per area of filter causing a two fold increase in pressure drop) per filter weight per area ratio of about 0.8, wherein typically the dust load of such filters is about 50-80 g/m 2 and their weight per area is about 80-130 g/m 2 .
Therefore, the main objective of the proposed technical solution is removal of the above-listed defects of known solutions for filtering applications (primarily directed at the manufacture of microfilters from polymer fibers) and other purposes, including application as micro-filtering means, i.e., the creation of means and the meeting of the above-listed requirements for technical means for the manufacture of micro-filtering materials with new consumer properties.
SUMMARY OF THE INVENTION
According to one aspect of the present invention there is provided a device for transforming a liquefied polymer into a fiber structure, including (a) a substantially planar precipitation electrode; (b) a first mechanism for charging the liquefied polymer to a first electrical potential relative to the precipitation electrode; (c) a second mechanism for forming a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn by the first electrical potential to the precipitation electrode; wherein the first and second mechanisms are designed such that when a plurality of fibers are precipitated on the precipitation electrode, a high efficiency particulate air unwoven fiber structure, capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec is obtainable.
According to further features in preferred embodiments of the invention described below, the first mechanism for charging the liquefied polymer to a first electrical potential relative to the precipitation electrode includes in combination (i) a source of high voltage; and (ii) a charge control agent mixed with the liquefied polymer.
According to still further features in the described preferred embodiments the first mechanism for charging the liquefied polymer to a first electrical potential relative to the precipitation electrode further includes (iii) a source of ionized air being in contact with the liquefied polymer.
According to still further features in the described preferred. embodiments the second mechanism is effected by at least one rotating wheel having a rim formed with a plurality of protrusions.
According to still further features in the described preferred embodiments each of the protrusions is formed with a liquefied polymer collecting cavity.
According to still further features in the described preferred embodiments each of the at least one wheel is tilted with respect to the precipitation electrode.
According to still further features in the described preferred embodiments each of the at least one wheel includes a dielectric core.
According to still further features in the described preferred embodiments the second mechanism is effected by a gas bubbles generating mechanism.
According to still further features in the described preferred embodiments the second mechanism is effected by a rotating strap formed with a plurality of protrusions.
The basic device of the present invention includes a grounded moving belt that acts as a precipitation electrode, and an electrode-collector for charging a polymer solution negatively with respect to the moving belt and for producing areas of high surface curvature in the polymer solution.
In one embodiment of the device, the areas of high surface curvature are formed by forcing the polymer solution through a bank of nozzles. The nozzles of the electrode-collector are inserted lengthwise in cylindrical holes sited at intervals in a negatively charged cover plate of the electrode-collector. The source of solvent vapors is connected to the holes. In an alternative configuration, the nozzles are connected by a system of open channels to the solvent vessel.
In one of the implementations, the device is provided with an additional grounded electrode (or alternatively an under potential electrode, of the same polarity of the high voltage electrode, but with lower voltage) which is placed in parallel to the surface of the nozzles of the electrode-collector and which is able to move in the direction normal to the plane of the electrode-collector's nozzles.
In order to improve the manufacturing process, the additional electrode may take the form of a single wire stretched over the inter-electrode space.
The additional electrode may also take the form of a perforated plate with flange, in which case the surface of the additional electrode, the flange, and the electrode-collector form a closed cavity, and the apertures of the perforated plate are co-axial to the apertures of electrode-collector.
Preferably, a device of the present invention also includes an aerosol generator, made in the form of a hollow apparatus (fluidized bed layer) divided into two parts by a porous electro-conducting partition, which is connected to a mainly positive high-voltage source. The lower part of the cavity forms a pressure chamber, which is connected to a compressor, and the upper part of the cavity is filled with the dispersible filler, for example, polymer powder.
Alternatively, the aerosol generator may be made in the form of a slot sprayer, connected to a positive high-voltage source and a dry fluid feeder, provided with an ejector for supplying powder to the sprayer.
Secondly, the objective put forward in the current invention is obtained by the suggested method of manufacturing of a composite filtering material, stipulating the following operations (stages) (a) preparation of a polymer solution from a polymer, an organic solvent and solubilizing additives, for example, by mixing at elevated temperatures; (b) pouring the polymer solution into the electrode-collector and introducing the dispersible filler, for example, from a polymer of the same chemical composition as that in the solution, into the cavity of electrified aerosol generator; (c) supply of negative high voltage to the electrode-collector, and creation of hydrostatic pressure to facilitate ejection of the polymer solution through the electrode-collector nozzles to produce polymer fibers with a negative electric charge; (d) transfer of the aforementioned fibers under the action of electric and, inertial forces to the precipitation electrode and chaotic stacking of the fibers on its surface to transform the fibers into an unwoven polymer material; (e) displacement of above-described polymer material with the help of the precipitation electrode, followed by interaction of the polymer material with the electrified aerosol cloud formed from the dispersible filler in the aerosol generator under positive high voltage and air pressure, accompanied by penetration of the aerosol cloud into the structure of the negatively charged unwoven polymer material to form a homogeneous composite filtering material.
Thus, according to another aspect of the present invention there is provided a method for forming a polymer into a high efficiency particulate air unwoven fiber structure capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec, comprising the steps of (a) liquefying the polymer, thereby producing a liquefied polymer; (b) supplementing the liquefied polymer with a charge control agent; (c) providing a precipitation electrode; (d) charging the liquefied polymer to a first electrical potential relative to the precipitation electrode; and (e) forming a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn to the precipitation electrode by the first electrical potential difference, thereby forming the unwoven fiber structure capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec on the precipitation electrode.
According to further features in preferred embodiments of the invention described below, the liquefying is effected by dissolving the polymer in a solvent, thereby creating a polymer solution.
According to still further features in the described preferred embodiments the method further comprising the step of (f) providing vapors of the solvent proximate to the surface of high curvature.
According to still further features in the described preferred embodiments the charge control agent is selected from the group consisting of biscationic amides, phenol and uryl sulfide derivatives, metal complex compounds, triphenylmethanes, dimethylmidazole and ethoxytrimethylsians.
According to still further features in the described preferred embodiments the forming of the surface of high curvature is effected by causing the liquefied polymer to emerge from a nozzle, the surface of high curvature being a meniscus of the liquefied polymer.
According to still further features in the described preferred embodiments the forming of the surface of high curvature is effected by wetting a protrusion having a tip with the liquefied polymer, the surface of high curvature being a surface of the liquefied polymer adjacent to the tip.
According to still further features in the described preferred embodiments the method further comprising the step of (f) moving the precipitation electrode so that the unwoven fiber structure is formed on the precipitation electrode as a sheet.
According to still further features in the described preferred embodiments the method further comprising the step of (f) vibrating the surface of high curvature.
According to still further features in the described preferred embodiments the vibrating is effected at a frequency between about 5000 Hz and about 30,000 Hz.
According to still further features in the described preferred embodiments charging the liquefied polymer to a first electrical potential relative to the precipitation electrode is followed by recharging the liquefied polymer to a second electrical potential relative to the precipitation electrode, the second electrical potential is similar in magnitude, yet opposite in sign with respect to first electrical potential. Preferably the s charge is oscillated between the first and second electrical potentials in a frequency of about 0.1-10 Hz, preferably about 1 Hz.
According to still further features in the described preferred embodiments the method further comprising the steps of (f) charging a filler powder to a second electrical potential relative to the collection surface, the second electrical potential being opposite in sign to the first electrical potential, thereby creating a charged filler powder; and (g) exposing the unwoven fiber structure on the precipitation electrode to the charged powder, thereby attracting the charged filler powder to the unwoven fiber structure.
According to still further features in the described preferred embodiments the method further comprising the steps of (f) supplementing the liquefied polymer with an additive selected from the group consisting of a viscosity reducing additive, a conductivity regulating additive and a fiber surface tension regulating additive.
According to still further features in the described preferred embodiments the viscosity reducing additive is polyoxyalkylein, the conductivity regulating additive is an amine salt and the fiber surface tension regulating additive is a surfactant.
According to still further features in the described preferred embodiments the liquefied polymer is charged negatively relative to the precipitation electrode and wherein the charged powder is charged positively relative to the precipitation electrode.
According to still another aspect of the present invention there is provided a high efficiency particulate air filter comprising unwoven fibers of a polymer, the filter being capable of filtering out at least 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec and having a pressure drop of about 0.75 mm H 2 O to about 13 mm H 2 O.
According to still further features in the described preferred embodiments the filter is substantially electrically neutral.
According to still further features in the described preferred embodiments the, fibers have a diameter of about 0.1 μm to about 10 μm
According to yet another aspect of the present invention there is provided a high efficiency particulate air filter comprising unwoven fibers of a polymer, the filter being capable of filtering out at least 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec and having a pressure drop of about 0.75 mm H 2 O to about 13 mm H 2 O, wherein at least about 90% of the fibers having a diameter in a range of X and 2X, where X is in a range of about 0.1 μm and about 10 μm.
According to still another aspect of the present invention there is provided a high efficiency particulate air filter comprising unwoven, fibers of a polymer, the filter being capable of filtering out at least 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec and having a pressure drop of about 0.75 mm H 2 O to about 13 mm H 2 O, the filter featuring pores formed among the fibers, wherein at least about 90% of the pores having a diameter in a range of Y and 2Y, where Y is in a range of about 0.2 μm and about 10 μm.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein:
FIG. 1 is a schematic diagram of a device of the present invention, including two alternative electrified aerosol generators;
FIG. 2 a is a top view of the electrode-collector of the device of FIG. 1;
FIG. 2 b is a lateral cross section of the electrode-collector of FIG. 2 a;
FIGS. 3 and 4 are lateral cross sections of alternative nozzle-based electrode-collectors;
FIG. 5 is a lateral cross section of an electrode-collector based on a rotating wheel;
FIG. 6 is a lateral cross section of: an electrode-collector based on reciprocating needles;
FIG. 7 is an electron micrograph of a filter according to the present invention;
FIG. 8 is a cross section of a preferred embodiment of the device according to the present invention, adapted for manufacturing a layered filter having a support layer and a prefilter layer surrounding a middle layer of high efficiency particulate air filter;
FIG. 9 a is a cross section of a preferred embodiment of the device according to the present invention, including an air ionizer to increase the charging of the liquefied polymer and thereby to enable more homogenic precipitation thereof on a precipitation electrode;
FIG. 9 b is an enlarged view of circle I of FIG. 9 a , showing an air ionizer in greater detail;
FIG. 10 is a cross section of a mechanism for forming a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn to the precipitation electrode effected via generation of bubbles in the liquefied polymer;
FIG. 11 is a cross section of a device according to the present invention including a plurality of tilted circular wheels;
FIGS. 12 a-b are side view and cross section of a wheel according to a preferred embodiment of the invention, including a dielectric core;
FIG. 13 is a cross section of a device according to the present invention including a plurality of tilted circular wheels in a different configuration;
FIG. 14 is a side view of a wheel according to a preferred embodiment of the invention, including liquefied polymer collecting cavities; and
FIG. 15 is a perspective view of yet another mechanism for forming a surface on the liquefied polymer of sufficiently high curvature which includes a rotateable strap of a conductive material formed with a plurality of protrusions rotating in parallel to the precipitation electrode.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is of a high efficiency particulate air filter, which is also referred to herein as unwoven polymer structure and further of a device and process for the electrostatic precipitation of fibers thereof. Specifically, the present invention can be used to make a composite unwoven filter.
The principles and operation of the present invention may be better understood with reference to the drawings and the accompanying description.
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 the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.
According to the present invention there is provided high efficiency particulate air filter comprising unwoven fibers of a polymer. The filter according to the present invention is capable of filtering out at least 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec and has a pressure drop of 13 mm H 2 O, preferably of about 10 mm H 2 O, more preferably of about 5 mm H 2 O, most preferably of about 2 mm H 2 O, optimally of about 0.75 mm H 2 O, or less. Thus a pressure drop of any value in a range of about 0.75 mm H 2 O and about 13 mm H 2 O is within the scope of the present invention.
The filter according to the present invention preferably has a dust load to filter weight per area ratio of about 1 to about 1.8. Any value within this range is within the scope of the present invention. For example, a filter according to the present invention weighting 100 grams/m 2 and having a 1.5 dust load to filter weight per area ratio suffers a two fold increase in its pressure drop when loaded with 150 grams/m 2 of dust.
It will be appreciated that the filters disclosed in U.S. Pat. Nos. 4,874,659 and 4,178,157 described in the Background section above are characterized by a dust load to filter weight per area ratio of less than 0.8.
According to a preferred embodiment of the present invention the filter is substantially electrically neutral and therefore its characteristics as a filter are much less affected by air humidity as compared with the filters disclosed in U.S. Pat. Nos. 4,874,659 and 4,178,157, described in the Background section above, which owe their performances to the charges associated therewith. The filter of the present invention becomes electrically neutral typically within 5-10 minutes after its precipitation on a precipitation electrode, as further described hereinunder.
According to another preferred embodiment of the present invention the fibers have a diameter of about 0.1 μm to about 20 μm. Fibers having a diameter of about 0.1-0.5 μm, about 0.5-2 μm, about 2-5 μm and about 5-20 μm, are all within the scope of the present invention, and are obtainable by selecting appropriate process parameters as further detailed hereinunder. It will be appreciated that the filters disclosed in U.S. Pat. Nos. 4,874,659 and 4,178,157, described in the Background section above are characterized by diameters in a range more than 10 to about 200 μm.
According to yet another preferred embodiment of the present invention, at least about 90% of the fibers have a diameter in a range of X and 2X, where X is any value in a range of about 0.1 μm and about 10 μm. According to still another preferred embodiment of the present invention, the filter featuring pores formed among the fibers, wherein at least about 90% of the pores have a diameter in a range of Y and 2Y, where Y is any value in a range of about 0.2 μm and about 10 μm. These latter features of the filter according to the present invention are effected by the preferred method of its manufacture, as further detailed hereinunder. The filters disclosed in described in the Background section above fail to enjoy the described homogeneity in fiber and pore diameters.
FIG. 7 provides a 4000 fold magnification of the filter described herein. Please note that many of the fibers shown have a 1 μm thickness (equals to 4 mm in the electron micrograph) and that the deviation is low. Such magnifications were employed to extract the above listed features and ranges describing the physical properties of the filter according to the present invention, and which distinct the filter according to the present invention from prior art filters.
According to a preferred embodiment of the present invention the filter is further supplemented with a filler, which, as described hereinabove and further detailed hereinunder, is useful in the removal of mercaptans, as substrate for catalytic reactions, in the enhancement of the bactericidal effect of the filtering material, etc.
The technological process of preparation of the composite filtering material according to the present invention includes two basic stages, which take place simultaneously. The first consists of the formation and precipitation on a constantly moving surface (base) of ultra-thin fibers (typically in a range of 0.1-10 μm) from the polymer solution that flows out of the capillary apertures under the action of an electric field.
The second operation is the introduction of micro-dispersed particles of filler of a particular composition into the fiber structure (matrix) formed previously in the first stage of production.
A basic variant of the device of the present invention (FIG. 1) includes a high-voltage electrode-collector 1 , manufactured as a bath, filled with the polymer solution (or melted polymer) and provided with a base 2 and a cover 2 ′. The electrode-collector is connected to a feeder 3 (shown in FIG. 2 b ) by a flexible pipe, installed so as to allow vertical movement, and a source 4 of high voltage of negative polarity.
Spinnerets 5 with nozzles 6 having capillary apertures are screwed into threaded openings formed in cover 2 ′ of the electrode-collector as on a chess board (FIG. 2 ). Because the height of the spinnerets is slightly less than the width of cover 2 ′ and the length of each nozzle 6 exceeds the width of cover 2 ′, the nozzle section is placed above cover 2 ′ on the axis of cylindrical depressions 7 , connected to each other by a system of open channels 8 (FIG. 2 a ). The solvent is fed into this system of channels from a vessel 9
A precipitation electrode 10 is situated at a certain distance (e.g., about 15-50 cm) above cover 2 ′. Precipitation electrode 10 is manufactured in the form of a constantly moving surface (when in the operating mode), for example, a belt made of electrical conducting material. Precipitation electrode 10 is grounded. Shafts 11 and 12 , connected to an electrical motor (not depicted on drawings), are responsible for driving precipitation electrode 10 , keeping precipitation electrode 10 under tension, and preliminary compression of the material on precipitation electrode 10 .
A part of precipitation electrode 10 is wound around shaft 13 , which has a large diameter, and is thus immersed in the rectangular cavity of the electrified aerosol generator. The cavity of the electrified aerosol generator is divided into two sections by a porous conducting partition 15 . The latter is connected to a high-voltage source 16 of positive polarity. The lower part 14 of the electrified aerosol generator, forming pressure chamber 17 , is connected to a compressor (not shown on drawings). A micro-dispersible filler is poured onto the surface of the porous partition 15 in the upper part of the generator. The entire device depicted in FIG. 1 is preferably contained in a hermetically sealed container, provided with a suction unit and a settling chamber for trapping and re-circulation of the solvent vapors (not shown on drawings).
The electrified aerosol generator may also be implemented in the form of a slot sprayer 18 , connected by a pipe to a dry powder ejection feeder 19 and a source of positive high voltage 16 . The use of the slot sprayer with a charging of aerosol in the field of the corona discharge is preferred in the case of metallic powders (including graphite powder) and powders that are not easily fluidized.
It was experimentally found that in filters with high pleatability performances are achievable by adding to the basic layer of polymer a minute quantity (say about 2-3%) of a powder, such as polypropylene powder, epoxy powder and/or phenolformaldehyde powder, and further adding about 5-6% of a second powder such as talc powder, zinc powder and/or titanium oxide powder and thereafter heating the powders loaded filter to about 70-80% of the melting temperature of the polymer employed in the basic layer.
The heating rate of any of the above powders depends on the powder's dispersion and specific heat characteristics. So, for polymer powders with high dispersion (root mean square diameter of 1-5 μm) heating is low. Coarser metallic and oxide powders require relatively higher temperatures.
The direction of fiber feeding on the vertical surface may be reversed, and the dimensions of the electrode-collector and the number of capillaries may be minimized with the help of the device depicted in FIG. 3 . The device consists of an electrode-collector frame 20 , manufactured from a dielectric material and having a central channel 21 , for example, of cylindrical shape. This channel is connected by a pipe to a feeder (not shown on the drawing) and is provided with aperture 22 to facilitate exchange of gases with the atmosphere. A busbar 23 with spinnerets 5 and nozzles having capillary apertures is installed in the lower part of frame 20 . The nozzles are connected to a source of high voltage (not shown on the drawing). Cover 24 with apertures 25 is placed before the busbar. Nozzles 6 are placed in these apertures with coaxial clearance. The internal surface of the cover and busbar form a cavity 26 , which is connected to a saturator (not shown on drawing) by a pipe.
In a number of cases, the process of manufacturing the composite filtering material may be improved by implementation of the device shown in FIG. 4 . Here, a dielectric flange 28 serves as a base for a perforated grounded plate 27 (or alternatively an under potential plate, of the same polarity of the high voltage electrode, but with lower voltage), which is installed, with a certain clearance C, say about 0.5-3 cm, parallel to the surfaces of the electrode-collector 20 and the busbar 23 . Plate 27 rests on the flange in such a way as to provide for vertical movement for regulation of the size of the clearance C. Apertures 29 of the perforated plate are co-axial to the apertures of electrode-collector's nozzles. The internal surface of perforated plate 27 and busbar 23 form a cavity 26 , which is connected by a pipe to a saturator.
The proposed device in its basic form functions as follows: From feeder 3 (FIG. 2 b ), the polymer solution runs into electrode-collector bath 1 , and under the action of hydrostatic pressure the polymer solution begins to be extruded through the capillary apertures of nozzles 6 . As soon as a meniscus forms in the polymer solution, the process of solvent evaporation starts. This process is accompanied by the creation of capsules with a semi-rigid envelope, the dimensions of which are determined, on the one hand, by hydrostatic pressure, the concentration of the original solution and the value of the surface tension, and, on the other hand, by the concentration of the solvent vapor in the area of the capillary apertures. The latter parameter is optimized by choice of the area of free evaporation from cover 2 ′ and of the solvent temperature. Alternatively or additionally it is optimized by covering the device and supplementing its atmosphere with solvent vapor (e.g., via a solvent vapor generator).
An electric field, accompanied by a unipolar corona discharge in the area of nozzle 6 , is generated between cover 2 ′ and precipitation electrode 10 by switching on high-voltage source 4 . Because the polymer solution possesses a certain electric conductivity, the above-described capsules become charged. Coulombic forces of repulsion within the capsules lead to a drastic increase in hydrostatic pressure. The semi-rigid envelopes are stretched, and a number of point microruptures (from 2 to 10) are formed on the surface of each envelope. Ultra-thin jets of polymer solution start to spray out through these apertures. Moving with high velocity in the inter-electrode interval, these jets start to lose solvent and form fibers that are chaotically precipitated on the surface of the moving precipitation electrode 10 , forming a sheet-like fiber matrix. Since the polymer fiber posses high surface electric resistance and the volume of material in physical contact with precipitation electrode surface is small, the fiber matrix preserves the negative electric charge for a long time, about 5-10 minutes. It will be appreciated that the electrical resistnce can be regulated by special additives.
When compressed air is fed into pressure chamber 17 of electrified aerosol generator 14 and high-voltage source 16 is switched on, the micro-dispersible filler becomes fluidized and acquires a positive electric charge. Under the action of electric and aerodynamic forces, the filler particles move to the surface of precipitation electrode 10 , which holds the fiber matrix. As a result of the action of Coulombic forces, the filler particles interact with the fiber matrix, penetrate its structure, and form a composite material.
When the belt of precipitation electrode 10 passes between shafts 11 , preliminary material compression takes place, accompanied by re-distribution of the filler particles in the matrix volume. Spherical particles, attached to the fiber material solely by electrical forces, move along paths of least resistance into micro-zones having a minimum volume density of matrix material, filling large pores, and thus improving the homogeneity of the composite and the degree of micro-dispersity of the pores.
The micro-dispersible powders from the following materials may be used as fillers: a polymer of the same chemical composition as that in the matrix, polymer latexes, glass, or Teflon, as well as active fillers that lead to the production of composite microfiltering materials with new consumer properties. These new materials may find application as adsorbents, indicators, catalysts, ion-exchange resins, pigments bactericides, etc.
The use of an electrified aerosol generator, as described above with the fluidized layer, facilitates high productivity of the process and product homogeneity. However, several powders have difficulty in forming a fluidized layer: metallic powders, particularly catalytic metals, can be subjected to electric precipitation only in the field of a unipolar corona discharge. Therefore, in these cases, as well as in the case in which it is necessary to measure out exact amounts of filler, it is worthwhile to use a slot sprayer 18 as the electrified aerosol generator (FIG. 1 ).
When compressed air from a compressor is fed into the dry powder feeder and the high voltage source is switched on, the powdered filler is ejected into slot sprayer 18 . The aerosol cloud coming out of the sprayer apertures becomes charged in the unipolar corona discharge field, and under the action of electric and aerodynamic forces is transferred to the precipitation electrode, where it interacts with the fiber matrix as described above.
The functioning of the device described in FIG. 3 corresponds, in the main aspects, with the operation of the basic device. The main difference is as follows: solvent vapor from the saturator under slight excess pressure is fed into cavity 26 and exits via aperture 25 , flowing over the edges of the apertures of nozzles 6 . Alternatively or additionally the device is covered and its atmosphere supplemented with solvent vapor (e.g., via a solvent vapor generator).
The advantage of this configuration lies in the facts that it provides the possibility of easy spatial re-orientation and fiber feeding in any direction and that it can be manufactured in compact form with a small number of capillaries. A device of this type is not efficient in installations aimed at high throughput due to difficulties in obtaining homogenous distribution of the vapor-air mixture through a large number of apertures and to the possibility of vapor condensation in pipes and subsequent falling of drops.
Intensification of the fiber matrix manufacturing process and a reduction of fiber width in order to produce filtering materials with a minimum pore size assumes, on the one hand, that the intensity of the electric field should be increased to values close to the level at which electrical discharges would begin to form between the emerging fibers and precipitation electrode 10 and, on the other hand, that the concentration of solvent vapors in the inter-electrode interval be increased in order to maintain the capability of consolidating fiber formation. Increasing the solvent vapors in the inter-electrode interval can be effected, for example, by covering the device and supplementing its atmosphere with solvent vapor (e.g., via a solvent vapor generator). The optimal electric field strength, both between electrode-collector 1 and precipitation electrode 10 , and between the electrified aerosol generator and precipitation electrode 10 , is between about 2.5 KV/cm and about 4 KV/cm.
An increase in the average intensity and heterogeneity of the electric field, leading to corona discharge, may be realized by installing, in the inter-electrode interval, one or more grounded electrodes (or alternatively under potential electrodes, of the same polarity of the high voltage electrode, but with lower voltage) manufactured, for instance, in the form of wires. This solution facilitates an increase in the productivity of the process by 1.5-2 times, but it does not lead to formation of short fibers with, varying strength and size parameters. The negative effect of using a linear grounded electrode instead of a planar grounded electrode, thereby producing a non-homogeneous electrical field, may be reduced by increasing the solvent vapor concentration in the fiber-formation area, which is difficult in open devices and increases solvent consumption and in some cases danger of fire. Increasing the solvent vapor concentration in the fiber-formation area can be effected by, for example, covering the device and supplementing its atmosphere with solvent vapor (e.g., via a solvent vapor generator).
This deficiency may be overcome by application of the device described above and depicted in FIG. 4 .
Switching on the high-voltage source 4 in the C clearance produces an homogeneous electric field, the intensity of which may be easily increased to 10-15 KV/cm. Under these conditions, the impact of the electric field upon the jet of polymer solution increases significantly. The fiber comes out thinner and more homogeneous along its length. The initial fiber velocity also increases, and thereafter it comes through apertures 29 of perforated plate 27 and is stacked on precipitation electrode surface as described above. A change of the size of clearance C facilitates regulation of fiber thickness and device productivity, as well as the degree of material porosity.
The present invention may be used to produce the polymer fiber structure from a much wider range of polymers than is possible using the prior art of U.S. Pat. No. 2,349,950.
While reducing the present invention into practice, it was found that for obtaining a high efficiency particulate air unwoven fiber structure, capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec, and further having the above described features, improved charging of the polymer is required. Improved charging is effected according to the present invention by mixing the liquefied polymer with a charge control agent (e.g., a dipolar additive) to form, for example, a polymer-dipolar additive complex which apparently better interacts with ionized air molecules formed under the influence of the electric field. It is assumed, in a non-limiting fashion, that the extra-charge attributed to the newly formed fibers is responsible for their more homogenous precipitation on the precipitation electrode, wherein a fiber is better attracted to a local maximum, which is a local position most under represented by older precipitated fibers, which, as will be recalled, keep their charge for 5-10 minutes. The charge control agent is typically added in the grams equivalent per liter range, say, in the range of from about 0.01 to about 0.2 normal per liter, depending on the respective molecular weights of the polymer and the charge control agent used.
U.S. Pat. Nos. 5,726,107; 5,554,722; and 5,558,809 teach the use of charge control agents in combination with polycondensation processes in the production of electret fibers, which are fibers characterized in a permanent electric charge, using melt spinning and other processes devoid of the use of an precipitation electrode. A charge control agent is added in such a way that it is incorporated into the melted or partially melted fibers and remains incorporated therein to provide the fibers with electrostatic charge which is not dissipating for prolonged time periods, say months.
In sharp distinction, the charge control agents according to the present invention transiently bind to the outer surface of the fibers and therefore the charge dissipates shortly thereafter (within minutes). This is because polycondensation is not exercised at all such that chemical intereaction between the agent and the polymer is absent, and further due to the low concentration of charge control agent employed. The resulting filter is therefore substantially charge free.
Thus, a mechanism for charging the liquefied polymer to a first electrical potential relative to the precipitation electrode according to the present invention preferably includes a source of high voltage, as described above, and a charge control agent mixed with the liquefied polymer.
Suitable charge control agents include, but are not limited to, mono- and poly-cyclic radicals that can bind to the polymer molecule via, for example, —C═C—, ═C—SH— or —CO—NH— groups, including biscationic amides, phenol and uryl sulfide derivatives, metal complex compounds, triphenylmethanes, dimethylmidazole and ethoxytrimethylsians. Conductivity control additives as further described below may also be employed.
The functionality of biscationic amides, for example, was experimentally evaluated. To this end, a 14% solution of a branched polycarbonate polymer (MW=ca. 110,000) in chloroform was prepared (viscosity was 180 cP). The above solution, supplemented with increasing concentration of bicationic acid amide was used in combination with a device as depicted in, and as described with relation to, FIG. 3 to precipitate filters, which were thereafter inspected for physical and functional properties. The examination included estimation of fiber diameter and uniformity of distribution, as well as, pressure drop evaluations. The addition of increasing amounts of bicationic acid amide did not alter fiber diameter, however, it had a striking effect on uniformity of distribution which resulted in lowering the pressure drop values associated with such filters, as exemplified in Table 1, below:
TABLE 1
Concentration of bicationic acid
Pressure drop for 100 g/m 2
amide (N · 10 −2 )
filters (mm H 2 O)
0
22
0.1
22
0.2
18
0.3
6
0.5
5
0.6
5
0.7
6
1.0
5
It is evident from Table 1 that the added charge control agent improves the filter product in terms of pressure drop. It is further clear that the influence of the charge control agent reaches its maximal effectiveness in a low concentration and that increasing its concentration above that value fails to further improve the quality of the product in terms of pressure drop.
In a similar experiment, the functionality of metal complex compound (iron salicylic acid complex), for example, was experimentally evaluated. To this end, a 12% solution of a polysulfone polymer (MW=ca. 80,000) in chloroform was prepared (viscosity was 140 cP, conductivity was 0.32 μS). The above solution, supplemented with increasing concentration of the metal complex compound was used in combination with a device as depicted in, and as described with relation to, FIG. 3 to precipitate filters, which were thereafter inspected for physical and functional properties. The examination included estimation of fiber diameter and uniformity of distribution, as well as, pressure drop evaluations. As before, the addition of increasing amounts of the charge control agent did not alter fiber diameter, however, it had a striking effect on uniformity of distribution which resulted in lowering the pressure drop values associated with such filters, as exemplified in Table 2, below:
TABLE 2
Concentration of iron salicylic
Pressure drop for 100 g/m 2
acid complex (N · 10 −2 )
filters (mm H 2 O)
0
18
0.1
9
0.2
3
0.3
3
0.5
3
0.6
3
0.7
3
1.0
3
It is evident from Table 2 that the added charge control agent improves the filter product in terms of pressure drop. It is further clear that the influence of the charge control agent reaches its maximal effectiveness in a low concentration and that increasing its concentration above that value fails to further improve the quality of the product in terms of pressure drop.
This phenomenon can be explained by saturation of the polymer fiber surface by the charge control agent and further by loss of access charge to the surrounding atmosphere.
The charge (or its absence) can be measured by a dedicated device namely a gauge for measuring electric field intensities. The end value of the electric charge or rate of loss does not reflect on homogenous fiber distribution. Only the initial rate of the charge is important to this end. The time required for charge dissipation is about few minutes.
The device and method according to the present invention differ from those disclosed in U.S. Pat. Nos. 4,043,331 and 4,127,706 to Martin et al. and U.S. Pat. No. 1,975,504 to Anton Formhals in that it enables manufacturing a high efficiency particulate air unwoven fiber structure, capable of filtering out 99.97% of 0.3 μm particulates in air flowing at 5 cm/sec and which further enjoy the physical features described hereinabove.
The devices and methods disclosed in the above patents are only capable of providing lower grade filters which fail to meet the requirements of high efficiency particulate air filters as described herein.
According to a preferred embodiment of the present invention, charging the liquefied polymer to a first electrical potential relative to the precipitation electrode is followed by recharging the liquefied polymer to a second electrical potential relative to the precipitation electrode, the second electrical potential is similar in magnitude, yet opposite in sign with respect to first electrical potential. Preferably the charge is oscillated between the first and second electrical potentials in a frequency of about 0.1-10 Hz, preferably about 1 Hz. The charge oscillation results in process productivity, more homogeneous distribution of precipitated fibers and yielding filters with improved qualities as described hereinabove.
Polymers amenable to the present invention include polysulfone, polyphenyl sulfone, polyether sulfone, polycarbonate in general, ABS, polystyrene, polyvynilidene fluoride, postchlorinated polyvinyl chloride and polyacrilonitrile. Suitable solvents include, inter alia, chloroform, benzene, acetone and dimethylformamide. The optimal concentration of the solution depends on the specific polymer and solvent used. Generally, the higher the concentration of polymer in the solution, the higher the process yield and the lower the product porosity. Concentrations of between about 10% and about 12% have been found optimal for the polymer solution used in electrode-collector 1 . Melted polymers such as, but not limited to, polyolefins, including polyethylene and polypropylene, are also amenable to the process according to the present invention.
It has been found advantageous to add certain additives to the solutions of these polymers. Amine salts such as tetraethyl ammonium bromide and benzyltriethylammonium bromide, are used to regulate the conductivity of the polymer solution, as described above. Small amounts of high molecular weight (order of 500,000) polyoxyalkylene additives, such as polyethylene glycol and polyvinyl pyrrolidone promote the formation of the polymer solution jets by reducing intermolecular friction. Surfactants such as dimethylmidazole and ethoxytrimethylsilane enhance fiber thickness and uniformity. Using additives reducing viscosity and surface tension it is possible to increase the polymer concentration up to about 17-18%.
More generally, the scope of the present invention includes the manufacture of the polymer fiber structure from a liquefied polymer, and not just from a polymer solution. By a liquefied polymer is meant a polymer put into a liquid state by any means, including dissolving the polymer in a solvent, as described above, and melting the polymer.
Also more generally, the scope of the present invention includes the formation of a surface on the liquefied polymer, of sufficient curvature to initiate the process discussed above of the charged capsules, leading to the formation of the jets of liquefied polymer that turn into fibers and precipitate onto precipitation electrode 10 . As discussed above, if the liquefied polymer is a polymer solution, the fibers are formed by evaporation of the solvent. If the liquefied polymer is a melt, the fibers are formed by solidification of the jets.
In the process of the present invention as described above, the highly curved surfaces are the menisci of polymer solution emerging from nozzles 6 . Other mechanisms for forming these highly curved surfaces are illustrated in FIGS. 5 and 6. FIG. 5 illustrates a variant of electrode-collector 1 in which the polymer solution, stored in a tank 33 , is pumped by a pump 32 through a feed pipe 31 to a delivery chamber 36 . Rotateably mounted in delivery chamber 36 is a circular wheel 30 made of an electrically conductive material. Mounted on rim 38 of wheel 30 are triangular protrusions 40 made of a material that is wetted by the polymer solution. Tips 42 of protrusions 40 point radially outward from wheel 30 . Wheel 30 is charged negatively by source 4 . As the polymer solution is delivered to chamber 36 , wheel 30 rotates and each of protrusions 40 is successively coated with a layer of the polymer solution, which in turn acquires a negative charge. The surface of the portion of this polymer solution layer that surrounds tip 42 constitutes the highly curved surface whence the charged jets emerge. Polymer solution not consumed in the course of precipitating fibers onto precipitation electrode 10 is returned to tank 33 via an outlet pipe 35 by a pump 34 . The optimal concentration of polymer solution used in this variant of electrode-collector 1 generally has been between about 14% and about 17%.
FIG. 6 is a partial illustration, in cross-section, similar to the cross-section of FIG. 2 b , of a variant of electrode-collector 1 in which nozzles 6 are replaced by reciprocating needles 40 , made of an electrically conductive material that is wetted by the polymer solution. Each needle 40 is provided with a mechanism 42 for raising and lowering needle 40 . When a needle 40 is lowered, the sharpened tip 44 thereof is wetted and coated by the polymer is solution. The surface of the polymer solution is highly curved at tip 44 . When a needle 40 is raised towards precipitation electrode 10 , the high voltage difference between needle 40 and precipitation electrode 10 causes jets of the polymer solution to emerge from the polymer solution surrounding tip 44 and to stream towards precipitation electrode 10 . It should be noted that in this variant of electrode-collector 1 , only needles 40 , and hence the polymer solution thereon, are negatively charged by source 4 .
Also shown in FIG. 6 is a speaker 50 of a system for producing acoustical vibrations in the air above electrode-collector 1 . Speaker 50 emits a tone of a single frequency, preferably in the range between about 5000 Hz and about 30,000 Hz, towards needles 40 . The vibrations thus induced in the highly curved surfaces of the polymer solution on tips 44 have been found to stimulate the emission of jets of polymer solution towards precipitation collector 10 .
FIGS. 8-15 teach additional preferred embodiments of the device and method according to the present invention.
Thus, as shown in FIG. 8, for the formation of a multilayered filter having a prefilter layer and a support layer surrounding a middle layer of high efficiency particulate air filter, a triple configuration of the device described above, with some modifications described hereinunder is provided. Thus, electrode-collector 1 is replaced according to this configuration by three electrode-collectors 100 a , 100 b and 100 c , each designed for precipitation of one of the above layers of the layered filter. Via a suitable source of high voltage, electrode-collectors 100 a , 100 b and 100 c are provided with, for example, a negative potential of, for example, —100 KV. Precipitation electrode 10 according to this embodiment is replaced by a modified version having three independent precipitation electrodes 102 a , 102 b and 102 c and a revolving belt 104 , wound around revolving shafts 106 . The location of precipitation electrodes 102 a , 102 b and 102 c is selected above electrode-collectors 100 a , 100 b and 100 c and via independent sources of high voltage they are provided with positive, negative and negative potentials, say (+1)−(+5), (−1)−(−2) and (−2)−(−5) KV, respectively, generating, for example, 101-105, 98-99 and 95-98 KV potential differences with their respective electrode-collectors 100 a , 100 b and 100 c . These potential differences in combination with the potential drop with distance and with variable polymer solutions are sufficient to induce marked changes upon the precipitated fibers as follows.
In electrode systems such as point-plate with abrupt non-uniform electrical field the intensity drop in the area near the plate electrode is small, so the relative potential can provide sufficient accelerating or decelerating effect.
Thus, fibers resulting from pair 100 a - 102 a form a prefilter structure or layer made of relatively refined and coarse (e.g., 8-10 μm fibers), having a large volume (porosity 0.96), low aerodynamic resistance and high dust loading capacity (40-50% of total mass).
Fibers resulting from pair 100 b - 102 b form a high efficiency particulate air filter made of fine fibers (e.g. 1-3 μm in diameter), having lower porosity (e.g., about 0.85-0.88), higher aerodynamic resistance, and a dust loading capacity of about, e.g., 20-30%.
Whereas fibers resulting from pair 100 c - 102 c form a support film or layer for providing the multilayer filter with mechanical strength and technical properties, such as pleatability, characterized by coarse fibers (10-20 μm in diameter), porosity of 0.9-0.92 and dust loading capacity of about 20-30%.
In fact, this version of the device according to the present invention combines three individual devices as described herein, each with somewhat modified properties, into a single device enabling the continuous manufacturing of three (or more) layered filter structures, each of the three or more layers featuring different properties and serving a different purpose. Any suitable number, e.g., from 2 to 10, of combined devices in envisaged for different application. In any case, according to this embodiment of the present invention, each of the layers is completely precipitated before turning to the precipitation of another layer, therefore, the properties of the device are selected such that the efficiency of precipitation is as high as required to complete a layer's precipitation in each of the stations in a single round (e.g., by controlling the length of each section or individual device). The resulting filter 105 is rolled over an additional rotating shaft 107 .
As shown in FIGS. 9 a-b , according to another preferred embodiment of the present invention ionized air generated by an air ionizer 110 , including an air inlet 112 , a grounded net structure 114 , an ionizing electrode 116 generating a potential of e.g., 15 KV/cm, and an air outlet 117 , as well known in the art, is used to increase the charging of the liquefied polymer (or fibers) and thereby to enable more homogenic precipitation thereof on a precipitation electrode. To this end, a bath 118 , in which the liquefied polymer 119 is held, and from which aliquots thereof are collected via a rotating wheel 120 featuring triangular protrusions 122 , as further detailed above with respect to FIG. 5 (wheel 30 ) is contained in a housing 122 supplemented with ionized air via air ionizer 110 . As before, increasing the solvent vapors in the inter-electrode interval can be effected, for example, by covering the device and supplementing its atmosphere with solvent vapor (e.g., via a solvent vapor generator).
As shown in FIG. 10, according to another preferred embodiment of the present invention, a mechanism for forming a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn by an electrical potential to the precipitation electrode is provided, in which gas (preferably solvent saturated vapor) bubbles formed in the liquefied polymer provide the required surfaces.
To this end, an electrode-collector or bath 130 in which the liquefied polymer 132 (typically but not obligatory a melted polymer in this case) is held is provided with a compressed gas releasing mechanism 134 , typically in a form of a pipe 136 supplemented with a plurality of bubbles 137 generating openings 138 . When reaching the surface of the liquefied polymer, the bubbles form a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn by the electrical potential to the precipitation electrode.
As shown in FIGS. 11 and 12 a-b and 13 , according to yet another preferred embodiment of the present invention, rotateably mounted in delivery chamber 146 is a plurality of circular wheels 140 . Mounted on rim 148 of wheels 140 are triangular protrusions 150 made of a conductive material that is wetted by the polymer solution. Tips 152 of protrusions 150 point radially outward from wheels 140 . Wheels 140 are charged negatively by a source 149 . Wheels 140 are provided in a tilted orientation with respect to a precipitation electrode 160 , such that as the polymer solution is delivered to chamber 146 , wheels 140 rotates and each of protrusions 150 is successively coated with a layer of the polymer solution, which in turn acquires a negative charge, yet, due to the tilted configuration, in general, protrusions 150 which are not dipped in the polymer solution are positioned more evenly apart from electrode 160 , as compared with the vertical configuration, shown, for example, in FIG. 5 . This, in turn, results in more homogenous fiber precipitation and more homogenous fiber thickness or diameter. In order to avoid electric field superposition effects while implementing this configuration of a plurality of wheels 140 , cores 162 of wheels 140 is made of a dielectric substance, whereas outer rims 148 thereof, including protrusions 150 , are made of an electric substance. In a somewhat different configuration shown in FIG. 13 the superposition effect is eliminated by selecting an appropriately non shielding wheels tilt arrangement.
As shown in FIG. 14, according to yet another preferred embodiment of the present invention, each of protrusions 150 is formed with a liquefied polymer collecting cavity 151 , for facilitating the collection of a measured amount of liquefied polymer. The advantage of this embodiment of the present invention is that it delays the process of fiber formation, such that a protrusion will generate fibers only when about to reenter the liquefied polymer, such that all fibers will be generated from a similar location and distance with respect to the precipitation electrode, thereby improved homogeneity is achievable.
As shown in FIG. 15, according to yet another preferred embodiment of the present invention, a mechanism for forming a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn by the electrical potential to the precipitation electrode includes a rotateable strap 170 of a conductive material, formed with a plurality of protrusions 171 , rotating around at least two shafts 172 and connected to a source 174 . Protrusions 171 are pointed at a direction of a precipitating electrode 176 , such that when strap 170 is rotated through a reservoir 178 including a liquefied polymer, aliquots thereof accumulate over protrusions 171 to thereby generate the a surface on the liquefied polymer of sufficiently high curvature to cause at least one jet of the liquefied polymer to be drawn to precipitation electrode 176 . Since the field is oriented perpendicular to the direction of rotation of strap 170 , strap 170 can be rotated at higher speeds, resulting in even more homogenous polymer fiber distribution over electrode 176 . According to a preferred embodiment, just before entering reservoir 178 , strap 170 is wiped from remnants of polymer by a wiper 180 , made, for example, of an adsorbing material.
Thus, the distance between the rotating strap and the precipitation electrode is constant at all locations, so that the electric field intensity experienced at each location is similar, resulting in more uniform fiber thickness. Furthermore, since there is no centrifugal force in the direction of the precipitation electrode, it is possible to increase the speed of the rotating strap to thereby improve mass distribution and productivity.
Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.
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A device for producing a porous fiber structure. One or more points of high surface curvature is produced in a liquefied polymer, such as a polymer solution or a polymer melt. The points of high surface curvature may be produced by forcing the liquefied polymer through narrow nozzles, or by wetting sharp protrusions with the liquefied polymer. The liquefied polymer is charged to a high negative electrical potential relative to a grounded moving belt. Thin jets of liquefied polymer emerge from the points of high surface curvature to impinge as fibers on the moving belt, thereby forming a nonwoven fiber structure of relatively uniform porosity. A powdered aerosol is charged to a high positive electrical potential relative to the moving belt. As the belt moves past the aerosol, the aerosol particles are attracted to fill interstices in the fiber structure, thereby creating a composite filtering material.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a mower unit attachable to a vehicle body and including a mower deck having a top board and one front wall and one side wall depending from the top board. The mower deck defines a grass discharge opening opposed to the side wall, and contains a plurality of rotary blades arranged side by side to be rotatable about vertical axes. All these rotary blades are rotatable in the same direction so that the front half, with respect to a traveling direction of the vehicle, of a rotating track of each blade points toward the side defining the grass discharge opening.
2. Description of the Related Art
In a mower unit of the type noted above, as disclosed in Japanese Patent Publication (Unexamined) No. 8-280225, for example, the top board of the mower deck has a front portion arched to define a tunnel therein extending to the grass discharge opening at one side of the deck. Grass clippings flying from the front half of the rotating track of each rotary blade are transported along the tunnel to the grass discharge opening. Such a mower unit is known as the side discharge type and is in wide use.
A mulching operation is sometimes required to cut grass clippings into minute pieces (mulch) and leave them along swaths in order to make a collection of grass clippings unnecessary and to utilize the grass clippings as compost. For this purpose, as disclosed in Japanese Patent Publication (Unexamined) No. 6-14634, a proposal has been made to provide mulching baffles inside the mower deck to define a mulching chamber (enclosure) for each rotary blade.
The above-noted mower deck having a tunnel for transporting grass clippings is capable of transporting the grass clippings smoothly and promptly along the tunnel, with little chance of the grass clippings entrained by the rotary blades. This mower deck has an advantage of cutting tall grass or lawn in a neglected condition, with little power loss due to the clippings being entrained by the rotary blades. However, this mower deck is ill-suited for an operation to cut only upper part of grass under good care, and discharge and scatter the clippings evenly in an inconspicuous way.
When a mulching operation is carried out by using the mower deck with a tunnel, mulching chambers are formed by installing baffles rearwardly of the tunnel, i.e. in regions of small depth. It is difficult to retain grass clippings in the mulching chambers for a sufficiently long time. It is thus difficult to secure a long mulching time for improved mulching efficiency.
Further, U.S. Pat. Nos. 5,845,475 and 5,987,863 disclose mower units of the side discharge type convertible to the mulching type by mounting mulching baffles in the mower deck. However, such a mulching mower unit with mulching baffles mounted in the mower deck has a flow control baffle for use in the side discharge remaining fixed, which is inconvenient for a mulching operation.
SUMMARY OF THE INVENTION
This invention has been made having regard to the state of the art noted above, and its object is to provide a mower unit convertible to the side discharge type or mulching type reliably and efficiently.
Another object of this invention is to provide a mower unit of the mulching type having an improved flow of grass clippings.
The first-mentioned object is fulfilled, according to this invention, by a mower unit attachable to a vehicle body comprising:
a mower deck having a top board and one front wall and one side wall depending from the top board, the mower deck defining a grass discharge opening at an opposite side of the side wall; a plurality of rotary blades juxtaposed inside the mower deck to be rotatable about vertical axes, all of the rotary blades being rotatable in the same direction so that a front half, with respect to a traveling direction, of a track of rotation of each rotary blade points toward the side having the grass discharge opening; a rear baffle depending from the top board for enclosing the rotary blades in combination with the front wall, and surrounding, in form of a concentric part circle, a rear portion of the track of rotation of each rotary blade; and a front baffle and a mulching baffle selectively attachable to the mower deck to be located forwardly of the tracks of rotation of the rotary blades; the front baffle including curved segments each for surrounding, in form of a concentric part circle, a front portion of the track of rotation of one rotary blade, and counter curved segments for connecting the curved segments, thereby to guide grass clippings cut by the rotary blades located upstream with respect to a grass discharging direction, into areas of rotation of the rotary blades located downstream with respect to the grass discharging direction; the mulching baffle, in combination with the rear baffle, defining a mulching chamber surrounding the track of rotation of each rotary blade.
With this construction, selection may be made as appropriate between a shredding side discharge mode using the front baffle attached to the deck, and a mulching mode with the mulching baffle attached in place of the front baffle. The shredding side discharge mode with the front baffle attached may be selected when, for example, upper part of grass under good care or light grass is cut, shredded and discharged. The mulching mode with the mulching baffle attached may be selected when shredding grass clippings into especially fine pieces and leaving them along swaths.
In the shredding side discharge mode, the mulching baffle is removed completely. In the mulching mode, the front baffle is removed completely. Each mode is free from the inconvenience of the unnecessary member remaining attached.
The front wall may be shaped, in combination with the top board, the side wall and the rear baffle, for transmitting grass clippings cut by the rotary blades to the grass discharge opening when both the front baffle and the mulching baffle are removed. Then, a standard side discharge mode is produced by removing the front baffle and mulching baffle. This side discharge mode may be used with advantage when simply cutting tall grass or lawn in a neglected condition.
In a preferred embodiment of the invention, the counter curved segments of the front baffle have a radius substantially corresponding to a radius of rotation of the rotary blades. In the shredding side discharge mode with the front baffle attached, according to this construction, grass clippings reaped by the rotary blades located upstream in the grass discharging direction are fed into the area of rotation of the rotary blades located downstream in the grass discharge direction. As the grass clippings arrive at the counter curved segments, the smoothly extending guide surfaces of the counter curved segments, while scattering the clippings over large ranges and feed the clippings into the areas of rotation of the downstream rotary blades for shredding action.
In another preferred embodiment of the invention, three rotary blades are juxtaposed inside the mower deck, and when the mulching baffle is attached, portions of the mulching baffles and portions of the rear baffle define circular mulching chambers of left and right rotary blades concentric with tracks of rotation of the left and right rotary blades, and a remaining portion of the mulching baffle and a remaining portion of the rear baffle define a mulching chamber of the middle rotary blade having a shape partly encroached on by the mulching chambers of the left and right rotary blades. With this construction, cutting winds produced in the circular mulching chambers of the left and right rotary blades tend to enter the middle mulching chamber slightly deviating from a circle, and circulate therein smoothly. The grass clippings are shredded and scattered more effectively in the circular mulching chambers than in the middle mulching chamber. Thus, the left and right rotary blades leave an excellent finish of cutting performance.
This type of mower unit is often attached between front and rear wheels of a vehicle body. With a three rotary-blade type mower unit, the left and right rotary blades have working ranges overlapping the tracks of the front and rear wheels. Grass trampled down by the front wheels may not be cut reliably, or shredded grass clippings may concentrate on the tracks of the front wheels. Lumps of grass clippings may be formed as a result of the rear wheels treading on the swaths. Such inconveniences are obviated or mitigated by improving the reaping and shredding performance and clippings scattering performance in the circular, left and right mulching chambers.
Each of the front baffle and mulching baffle may be made dividable into at least two segments. This provides convenience for storing the front baffle or mulching baffle when out of use.
The second object noted hereinbefore is fulfilled by a mower unit attachable to a vehicle body comprising:
a mower deck having a top board and one front wall and one side wall depending from the top board, the mower deck defining a grass discharge opening at an opposite side of the side wall; a plurality of rotary blades juxtaposed inside the mower deck to be rotatable about vertical axes, all of the rotary blades being rotatable in the same direction so that a front half, with respect to a traveling direction, of a track of rotation of each rotary blade points toward the side having the grass discharge opening; a rear baffle depending from the top board for enclosing the rotary blades in combination with the front wall, and surrounding, in form of a concentric part circle, a rear portion of the track of rotation of each rotary blade; and a front baffle attached to the mower deck to be located forwardly of the tracks of rotation of the rotary blades; the front baffle including curved segments each for surrounding, in form of a concentric part circle, a front portion of the track of rotation of one rotary blade, and counter curved segments for connecting the curved segments, thereby to guide grass clippings cut by the rotary blades located upstream with respect to a grass discharging direction, into areas of rotation of the rotary blades located downstream with respect to the grass discharging direction.
Other features and advantages of this invention will be apparent from the following description of the embodiment to be taken with reference to the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation of a riding lawn mower with a mower unit according to this invention;
FIG. 2 is a plan view of the riding lawn mower shown in FIG. 1 ;
FIG. 3 is a plan view of the mower unit;
FIG. 4 is a schematic view of a transmission structure;
FIG. 5 is a side view, partly in section, of the mower unit in a raised position;
FIG. 6 is a cross-sectional plan view of the mower unit in a shredding side discharge mode;
FIG. 7 is a rear view in vertical section of the mower unit in the shredding side discharge mode;
FIG. 8 is a side view in vertical section taken in a sideways middle position of the mower unit in the shredding side discharge mode;
FIG. 9 is a cross-sectional plan view of the mower unit in a mulching mode;
FIG. 10 is a side view in vertical section taken in the sideways middle position of the mower unit in the mulching mode;
FIG. 11 is a cross-sectional plan view showing part of a mulching baffle;
FIG. 12 is a side view in vertical section of a guide member provided for a mulching baffle;
FIG. 13 is a perspective view showing part of a mulching baffle;
FIG. 14 is an exploded plan view showing components of a mulching baffle; and
FIG. 15 is a cross-sectional plan view of the mower unit in a standard side discharge mode.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a side elevation of a riding lawn mower with a mower unit M according to this invention. FIG. 2 shows a plan view of the riding lawn mower. This lawn mower includes a pair of right and left front wheels 1 in the form of casters, a pair of right and left drive rear wheels 2 , and a vehicle body 3 supported by these wheels. The mower unit M is suspended from the vehicle body 3 between the front and rear wheels by a four-point link mechanism 4 . The mower unit M may be moved up and down substantially parallel by vertically moving the link mechanism 4 with hydraulic pressure or manually. An engine 5 is mounted in a rearward position of the vehicle body 3 , and a driver's seat 6 disposed forwardly of the engine 5 .
A rear transmission structure is supported by a pair of right and left rear frames 3 b extending rearward and downward from main frames 3 a of the vehicle body 3 . The transmission structure is schematically shown in FIG. 4 . Output of the engine 5 is inputted to a counter case 7 to be divided to a propelling line and a working line. The power for the propelling line is converted into sideways rotary power, and inputted to a pair of right and left hydrostatic stepless transmissions (HSTs) 8 . Power output in variable speed of each transmission 8 is transmitted to one of the rear wheels 2 through a reduction case 9 . Each reduction case 9 includes a brake 10 for acting on the right or left rear wheel 2 . The power for the working line is transmitted through a PTO clutch 11 and outputted forward from a PTO shaft 12 .
The right and left stepless transmissions 8 are shiftable by propelling levers 13 arranged at opposite sides of the driver's seat 6 to be rockable fore and aft, respectively. Thus, the right and left rear wheels 2 are driven forward and backward in varied speeds independently of each other. When the right and left propelling levers 13 are rocked by the same amount forward, the right and left rear wheels 2 are driven at the same speed forward to move the vehicle body 3 straight forward. When the right and left propelling levers 13 are rocked by the same amount backward, the vehicle body 3 moves straight backward. When the right and left propelling levers 13 are rocked by different amounts, the right and left rear wheels 2 are driven at different speeds to turn the vehicle body 3 in a selected direction. Particularly when one of the propelling levers 13 is placed in a neutral stop position and the other propelling lever 13 is rocked to a forward or backward drive range, the vehicle body 3 makes a pivot turn about the rear wheel 2 standing still. When the propelling levers 13 are rocked in opposite directions from the neutral position, the right and left rear wheels 2 are driven in opposite directions to cause the vehicle body 3 to make a spin turn about a midpoint between the right and left rear wheels 2 .
The mower unit M has a mower deck 15 opening downward and containing three rotary blades 16 , 17 and 18 rotatable about vertical axes. The rotary blades 16 , 17 and 18 are in a triangular arrangement in plan view, with the middle rotary blade 17 offset slightly forward. The mower deck 15 is a flat deck having a larger vertical depth than the mower deck with a tunnel, and a top board even in height over the ground as a whole. The mower deck 15 has a grass discharge opening d formed at the right-hand end thereof.
The working power taken from the PTO shaft 12 is transmitted to an input shaft 20 extending rearward from a bevel gear case 19 disposed centrally of an upper surface of the mower deck 15 , through a pair of universal joints 21 and 22 and a telescopic transmission shaft 23 . The bevel gear case 19 converts the power into rotation of a vertical shaft, and transmits the rotation to a rotary shaft 17 a of the middle rotary blade 12 . This rotary shaft 17 a and rotary shafts 16 a and 18 a of the left and right rotary blades 16 and 18 are interlocked by a belt 24 wound thereon. All of the rotary blades 16 , 17 and 18 are rotated in the same direction (clockwise as seen from above) and at the same speed, so that the front halves of the tracks of rotation of the rotary blades 16 , 17 and 18 point toward the grass discharge opening d.
The mower deck 15 has a trapezoidal recess “a” formed in a sideways middle region at the rear end thereof. This recess “a” has a depth to lie forward of the rear universal joint 22 . Thus, as shown in FIG. 5 , the mower unit M may be raised to such a large extent that the rear universal joint 22 enters the recess “a.”
The mower deck 15 has obstacle-riding idle rollers (anti-scalp rollers) 25 and 26 arranged in a middle position and adjacent right and left ends at the front end thereof, and obstacle-riding idle rollers 27 arranged in right and left positions adjacent the middle at the rear end. When the mower unit M vertically movable suspended by the link mechanism 4 approaches a slope or a ridge, one or more of the idle rollers 25 , 26 and 27 ride(s) the ridge or the like to raise the mower unit M. This prevents the mower deck 15 from directly contacting and scraping the ground. The idle roller 25 in the middle position at the front of the deck 15 and the right and left idle rollers 27 at the rear are fixed against swiveling, while the right and left idle rollers 26 at the front are casters. When the idle rollers 26 engage the ground in time of a sharp turn such as a pivot turn or spin turn of the vehicle body 3 , the idle rollers 26 smoothly roll and change directions, following the turning movement of the mower unit M. This avoids scraping of grass by the idle rollers 26 moving extensively.
This mower unit M can vary interior specifications of the mower deck 15 to offer the option of three different modes of grass cutting operation. Each operating mode will be described hereinafter.
[Shredding Side Discharge Mode]
FIG. 6 shows a cross-sectional plan view of the mower unit M in a shredding side discharge mode suited for cutting upper part of grass under good care, cutting the clippings into relatively small pieces, and discharging and scattering the clippings from the grass discharge opening d. This mower unit M has a rear baffle 29 fixedly welded to a rear position in the mower deck 15 for concentrically surrounding rear parts of the tracks of rotation of the rotary blades 16 , 17 and 18 , and a front baffle 30 detachably attached to a front position in the mower deck 15 for surrounding front parts of the tracks of rotation of the rotary blades 16 , 17 and 18 .
This front baffle 30 is in the form of a vertical plate curved into an undulating shape, and includes curved segments for concentrically surrounding the front parts of the tracks of rotation of the rotary blades 16 , 17 and 18 , and counter curved segments connecting these curved segments. As seen from FIG. 6 , the curved segments and counter curved segments are curved in opposite directions. The curved segments have a radius of curvature slightly larger than the radius of rotation of the rotary blades 16 , 17 and 18 . The radius of curvature of the counter curved segments is approximately the same as the radius of rotation of the corresponding rotary blades 16 , 17 and 18 . One of the counter curved segments connects two adjacent curved segments smoothly.
A first front baffle 30 a opposed to the front part of the rotary blade 16 most upstream (left end) in the grass transport direction and a second front baffle 30 b opposed the front parts of the rotary blades 17 and 18 in the middle and most downstream (right end) in the grass transport direction are in abutment and connected to each other by a bolt 31 . The first front baffle 30 a and second front baffle 30 b have mounting bolts 32 fixedly welded to front surfaces thereof. On the other hand, the top board 15 a of the mower deck 15 defines mounting bores 33 for receiving the bolts 32 . The bolts 32 of the front baffle 30 are inserted into the bores 33 from inside the deck 15 , and nuts 34 are fastened to projecting ends of the bolts 32 . The mower deck 15 has a mounting bracket 35 fixedly welded to a left side wall 15 b thereof for abutting on the left end of the first front baffle 30 a , while the second front baffle 30 b has a mounting bracket 36 fixedly welded to a front surface at the right end thereof. The left end of the first front baffle 30 a is fastened to the mounting bracket 35 with a bolt 37 . The bracket 36 is fastened to the front wall 15 b of the mower deck 15 with a bolt 38 . Thus, the front baffle 30 is firmly fixed to the inside of the deck 15 .
The front baffle 30 with the undulating shape has crest portions e protruding inwardly of the deck 15 , i.e. the portions opposed to areas between adjacent rotary blades, having a large curvature substantially corresponding to the radius of blade rotation. Part of grass clippings cut by the upstream rotary blades are guided by inwardly curved surfaces of the front baffle 30 to be entrained and cut into small pieces by the rotating blades. Part of the grass clippings are guided by the smoothly protruding crest portions e to be distributed to the areas of rotation of the downstream rotary blades to be cut into small pieces.
[Mulching Mode]
FIG. 9 shows a cross-sectional plan view of the mower unit M in a mulching mode for cutting grass clippings into sufficiently small pieces and leaving them along the track of the mower. In this mode, the foregoing front baffle 30 is replaced by a mulching baffle 40 for forming, in combination with the rear baffle 29 , circular mulching chambers g, h and i surrounding the tracks of rotation of the rotary blades 16 , 17 and 18 , respectively.
As shown in FIG. 14 , the above mulching baffle 40 includes a left mulching baffle 40 a , a right mulching baffle 40 b , and a middle mulching baffle 40 c . These baffles are secured to the deck 15 by using the mounting bores 33 .
The left mulching baffle 40 a is attached to the mounting bores 33 of the top board 15 a by using bolts 41 fixed to the front surface of the baffle 40 a . The left end of the left mulching baffle 40 a is connected to the bracket 35 on the deck 15 by a bolt 42 . The left mulching baffle 40 a has a patch 43 fixedly welded to the right end thereof and fastened to the rear baffle 29 by a bolt 44 .
The right mulching baffle 40 b is attached to one of the mounting bores 33 of the top board 15 a by using a bolt 46 fixed to the front surface of the baffle 40 b through a support bracket 45 . The right mulching baffle 40 b has a patch 47 fixedly welded to the left end thereof and fastened to the rear baffle 29 by a bolt 48 , and a patch 49 fixedly welded to the right end of the right mulching baffle 40 b and fastened to a position rearwardly of the grass discharge opening d by a bolt 50 .
The middle mulching baffle 40 c is attached to the mounting bores 33 of the top board 15 a by using a bolt 51 directly fixed to the front surface of the baffle 40 c and bolts 51 fixed to the front surface through support brackets 52 . The middle mulching baffle 40 c has guide members 53 fixedly welded to the left and right ends thereof for filling forward-facing V-shaped spaces j formed in junctions between the left and right mulching baffles 40 a and 40 b and middle mulching baffle 40 c . As shown in FIGS. 11 and 12 , each guide member 53 is formed of an L-shaped plate defining a front plate portion 53 a for closing the front opening of the V-shaped space j, and a bottom plate portion 53 b for closing the bottom of the V-shaped space j. The guide members 53 prevent grass having passed by the front wall 15 c of the mower deck 15 and having been introduced into the deck 15 from gathering into the V-shaped spaces j. This effectively reduces the chance of leaving the grass unreaped.
In this case, the bottom plate portions 53 b perform the function to check the grass standing up and entering the V-shaped spaces j after passing by the front plate portions 53 a.
The mulching chambers g and i of the left and right rotary blades 16 and 18 are formed circular and concentric with the tracks of rotation of the blades. The mulching chamber h of the middle rotary blade 17 has a shape partly encroached on by the mulching chambers g and i of the left and right rotary blades 16 and 18 . The left and right mulching baffles 40 a and 40 b have cutouts k formed in lower positions of the portions thereof encroaching on the mulching chamber h of the middle rotary blade 17 in order to avoid interference with the middle rotary blade 17 .
[Standard Side Discharge Mode]
FIG. 15 shows a cross-sectional plan view of the mower unit M in a standard side discharge mode for cutting long grass and discharging the clippings from the grass discharge opening d. In this mode, the front baffle 30 and the mulching baffle 40 are removed. The grass clippings cut by the upstream rotary blades are transported quickly along the top board 15 a and front wall 15 c to the grass discharge opening d of the deck to be discharged therefrom without being guided to the cutting areas of the downstream rotary blades. Thus, long grass may be reaped without causing a useless shredding load.
[Other Embodiments]
This invention may be implemented in the following forms:
(1) The front baffle 30 may have an integral construction without being divided into two parts. Conversely, the front baffle 30 may have a three-part construction to be storable in a small bulk after detachment.
(2) The left and right mulching baffles 40 a and 40 b and middle mulching baffle 40 c of the mulching baffle 40 may be integrated beforehand such as by welding. In this case, the guide members 53 may be used as connecting and reinforcing members of the left and right mulching baffles 40 a and 40 b and middle mulching baffle 40 c . This renders the mulching baffle 40 highly rigid, while avoiding large quantities of grass gathering in the V-shaped spaces g.
(3) The device for attaching and detaching the front baffle 30 and mulching baffle 40 to/from the mower deck 15 is not limited to what is described hereinbefore. For example, nuts may be fixedly welded to the upper ends the front baffle 30 and mulching baffle 40 , with bolts inserted through the mounting bores 33 of the top board 15 a of the deck from above, and tightened into the nuts of the front baffle 30 and mulching baffle 40 .
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A mower unit attachable to a vehicle body includes a mower deck. The mower deck defines a grass discharge opening at an opposite side of one side wall, and has a plurality of rotary blades juxtaposed inside the mower deck to be rotatable about vertical axes. All of the rotary blades are rotatable in the same direction so that a front half, with respect to a traveling direction, of a track of rotation of each rotary blade points toward the side having the grass discharge opening. A rear baffle depends from a top board of the mower deck for enclosing the rotary blades in combination with a front wall, and surrounds, in form of a concentric part circle, a rear portion of the track of rotation of each rotary blade. A front baffle and a mulching baffle are provided to be selectively attached to the mower deck to be located forwardly of the tracks of rotation of the rotary blades. The front baffle includes curved segments each for surrounding, in form of a concentric part circle, a front portion of the track of rotation of one rotary blade, and counter curved segments for connecting the curved segments. The mulching baffle, in combination with the rear baffle, defines a mulching chamber surrounding the track of rotation of each rotary blade.
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BACKGROUND OF THE INVENTION
German Pat. No. 2,249,396 and European Patent Publication 40325 disclose N 6 -bicycloalkyl adenosine derivatives having circulatory, antilipolytic, anticonvulsant, muscle relaxant, and sedative activity. U.S. Pat. No. 3,840,521 discloses N 6 -methyl-N 6 -[bicyclo(2.2.1)-heptyl-2]adenosine having antilipolytic, antihyperlipemic, and antihypercholesterolemic activity.
The compounds of the instant invention are adenosine analogs having some of the same activity as adenosine, but having a significantly longer duration of action. A distinguishing feature of these compounds from other adenosine analogs previously described, is the discovery that N 6 -bicycloadenosines have favorable ratio of affinities at A1 and A2 receptors and highly desirable analgesic and antiinflammatory properties.
SUMMARY OF THE INVENTION
Accordingly the present invention relates to compound of the formula ##STR1## wherein R 1 is of formula ##STR2## in which ˜NH-- is either endo or exo; is a double or single bond; n is zero, one, or two; A and B are either both hydrogen or both methyl; D and E are also either both hydrogen or both methyl; C is hydrogen or methyl; and with the proviso that when D and E are methyl then A and B are both hydrogen and C is methyl, but when D ane E are hydrogen then A, B, and C are all hydrogen or all methyl; X is --C(CH 3 ) 2 --, --CH 2 --, --CH 2 --CH 2 --, --CH═CH--. R 2 is hydrogen, halogen, SR where R is hydrogen or lower alkyl, NR i R ii where R i and R ii are independently hydrogen, lower alkyl, phenyl or phenyl substituted by lower alkyl, lower alkoxy, halogen, or trifluoromethyl; R 2 ' and R 3 ' are independently hydrogen, lower alkanoyl, benzoyl, or benzoyl substituted by lower alkyl, lower alkoxy, halogen, or trifluoromethyl, or when taken together, R 2 ' and R 3 ' may be lower alkylidene, such as isopropylidene; R 6 ' is hydrogen, halogen or R 5 'O wherein R 5 ' is hydrogen, lower alkanoyl, benzoyl, or benzoyl substituted by lower alkyl, lower alkoxy, halogen, or trifluoromethyl; and the ˜NH-- in the Formula IIB is attached to either one of the carbons adjacent; its individual diastereomers or mixtures thereof, or a pharmaceutically acceptable acid addition salt thereof.
The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the above Formula I with a pharmaceutically acceptable carrier, and to a method of treating mammals by administering to such mammals a dosage form of a compound of the Formula I as defined above.
DETAILED DESCRIPTION
In the compounds of the Formula I, the term "lower alkyl" is meant to include a straight or branched alkyl group having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, amyl, isoamyl, neopentyl, hexyl, and the like.
Halogen includes particularly fluorine, chlorine or bromine.
Lower alkoxy is 0-alkyl from 1 to 6 carbon atoms as defined above for "lower alkyl."
Lower alkanoyl is a straight or branched ##STR3## group of from 1 to 6 carbon atoms in the alkyl chain as defined above.
The term "and the ˜NH-- in the Formula IIB is attached to either one or the other of the adjacent carbons" means ##STR4##
The compounds of Formula I are useful both in the free base form and in the form of acid addition salts. Both forms are within the scope of the invention. In practice, use of the salt form amounts to use of the base form. Appropriate pharmaceutically acceptable salts within the scope of the invention are those derived from mineral acids such as hydrochloric acid and sulfuric acid; and organic acids such as ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like, giving the hydrochloride, sulfamate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and the like, respectively.
The acid addition salts of said basic compounds are prepared either by dissolving the free base in aqueous or aqueous alcohol solution or other suitable solvents containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and acid in an organic solvent, in which case the salt separates directly or can be obtained by concentration of the solution.
The compounds of the invention may contain asymmetric carbon atoms. The invention includes the individual diastereomers, the pure S, the pure R isomer, and mixtures thereof. The individual diastereomers may be prepared or isolated by methods known in the art.
Under certain circumstances it is necessary to protect either the N or O of intermediates in the above noted process with suitable protecting groups which are known. Introduction and removal of such suitable oxygen and nitrogen protecting groups are well known in the art of organic chemistry; see for example, (1) "Protective Groups in Organic Chemistry," J. F. W. McOmie, ed., (New York, 1973), pp 43ff, 95ff; (2) J. F. W. McOmie, Advances in Organic Chemistry, Vol. 3, 191-281 (1963); (3) R. A. Borssonas, Advances in Organic Chemistry, Vol. 3, 159-190 (1963); and (4) J. F. W. McOmie, Chem. & Ind., 603 (1979).
Examples of suitable oxygen protecting groups are benzyl, t-butyldimethylsilyl, methyl, isopropyl, ethyl, tertiary butyl, ethoxyethyl, and the like. Protection of an N-H containing moiety is necessary for some of the processes described herein for the preparation of compounds of this invention. Suitable nitrogen protecting groups are benzyl, triphenylmethyl, trialkylsilyl, trichloroethylcarbamate, trichloroethoxycarbonyl, vinyloxycarbamate, and the like.
Under certain circumstances it is necessary to protect two different oxygens with dissimilar protecting groups such that one can be selectively removed while leaving the other in place. The benzyl and t-butyldimethylsilyl groups are used in this way; either is removable in the presence of the other, benzyl being removed by catalytic hydrogenolysis, and t-butyldimethylsilyl being removed by reaction with, for example, tetra-n-butylammonium fluoride.
In the process described herein for the preparation of compounds of this invention the requirements for protective groups are generally well recognized by one skilled in the art of organic chemistry, and accordingly the use of appropriate protecting groups is necessarily implied by the processes of the charts herein, although not expressly illustrated.
The products of the reactions described herein are isolated by conventional means such as extraction, distillation, chromatography, and the like.
A preferred embodiment of the present invention is a compound of Formula I wherein R 1 is of Formula IIA; ˜NH-- is either endo or exo; A, B, C, D, and E are all hydrogen; R 2 is hydrogen, R 6 ' is chloro; and R 2 ' and R 3 ' are as defined above.
A particular embodiment includes N 6 -endo-bicyclo[2.2.1]heptyladenosine, N 6 -exo-bicyclo[2.2.1]heptyladenosine, and N 6 -endo-bicyclo[2.2.1]heptyl-5'-chloroadenosine. The N 6 -endo-bicyclo[2.2.1]heptyl-5'-chloroadenosine is the most preferred embodiment.
The compounds of Formula I may be conveniently synthesized by reacting a 6-halopurine riboside of Formula III with bicyclo amine of Formula IVA or IVB as shown hereinafter where A, B, C, D, E, and X is as defined above in an inert solvent such as alcohol, or an aprotic solvent such as dimethylformamide between about 25 to about 130° C. for from 1-48 hours. The bicyclo amines of Formula IVA or Formula IVB above are commercially available, may be made by known methods or may be made by methods analogous to those known in the art. It is useful to add a base such as triethylamine, or calcium carbonate to neutralize the hydrogen halide formed as a byproduct of the reaction, but this can also be accomplished by using an extra equivalent of the alkylamine. It is also convenient, although not necessary, to protect the ribofuranose hydroxyl groups as acetate or benzoate esters which can be removed with ammonium hydroxide or sodium methoxide following the synthesis of the N 6 -substituted adenosine. The reaction is illustrated as follows: ##STR5## wherein Hal is halogen, preferably chlorine or bromine, and A, B, C, D, E, R 2 , R 2 ', R 3 ', and R 5 ' are as defined for Formula I.
In addition, compounds of formula I wherein R 6 ' is halogen may also be prepared from a compound Formula I where R 6 ' is R 5 'O where R 2 ', R 3 ', and R 5 ' are all hydrogen, in a stepwise manner, by first reacting with the compound to form a protecting group for the oxygen of OR 2 ' and OR 3 ', i.e., where R 2 ' and R 3 ' are other than hydrogen, e.g., dimethoxy propane, in acetone to give a compound of Formula I having protected groups followed by chlorinating the 5'-hydroxymethyl using thionyl chloride in tetrahydrofuran, and removing the protecting group under aqueous acid condition using acids, for example, hydrochloric, acetic, sulfuric, and the like as illustrated below. ##STR6##
In addition, compounds of Formula I wherein R 2 is other than hydrogen or halogen, may also be prepared from 2,6-dichloropurine riboside triacetate of Formula V in a stepwise manner, by first reacting a compound of the Formula V with bicycloamine of Formula IVa or IVb to give a compound of Formula VI, followed by replacing the chlorine atom at C 2 with the group R 2 using nucleophilic displacement conditions, and removing a protecting group, i.e., the acetate, as illustrated below. ##STR7##
The compounds of Formula I wherein R 6 ' is hydrogen are prepared according to the following scheme: ##STR8##
Generally the conditions of the above scheme are analogous to those known in the art.
The compounds of Formula I have been found to possess differing affinities for adenosine receptors (designated A 1 and A 2 receptors for convenience). These compounds are active in animal tests as having analgesic properties and as such, are useful in the treatment of pain and inflammation.
PHARMACOLOGICAL EVALUATION
Adenosine Receptor Binding--A 1 Receptor Affinity (RBA1)
Preparation of Membranes
Whole brain minus cerebellum and brainstem from male Long Evans rats (150-200 g) was homogenized in 30 volumes of ice-cold 0.05M Tris-HCl buffer pH 7.7 using a Brinkman Polytron PT-10, (setting number 6 for 20 seconds) and centrifuged for ten minutes at 20,000×g (Sorvall RC-2), 4° C. The supernatant was discarded, and the pellet was resuspended and centrifuged as before. The pellet was resuspended in 20 ml Tris-HCl buffer containing two International Units/ml of adenosine deaminase (Sigma type III from calf intestinal mucosa), incubated at 37° C. for 30 minutes, then subsequently at 0° C. for ten minutes. The homogenate was again centrifuged, and the final pellet was resuspended in ice-cold 0.05M Tris-HCl buffer pH 7.7 to a concentration of 20 mg/ml original wet tissue weight and used immediately.
Assay Conditions
Tissue homogenate (10 mg/ml) was incubated in 0.05M Tris-HCl buffer pH 7.7 containing 1.0 nM [ 3 H]-N 6 -cyclohexyladenosine ([ 3 H]-CHA) with or without test agents in triplicate for one hour at 25° C. Incubation volume was 2 ml. Unbound [ 3 H]-CHA was separated by rapid filtration under reduced pressure through Whatman glass fiber (GF/B) filters. The filters were rinsed three times with 5 ml of ice cold 0.05M Tris-HCl buffer pH 7.7. The radiolabeled ligand retained on the filter was measured by liquid scintillation spectrophotometry after shaking the filters for one hour or longer on a mechanical shaker in 10 ml of Beckman Ready-Solv HP scintillation cocktail.
Calculations
Nonspecific binding was defined as the binding which occurred in the presence of 1 mM theophylline. The concentration of test agent which inhibited 50% of the specific binding (IC 50 ) was determined by nonlinear computer curve fit. The Scatchard plot was calculated by linear regression of the line obtained by plotting the amount of radioligand bound (pmoles/gram of tissue) versus ##EQU1## Since the amount of radioligand bound was a small fraction of the total amount added, free radioligand was defined as the concentration (nM) of radioligand added to the incubation mixture. The Hill coefficient was calculated by linear regression of the line obtained by plotting the log of the bound radioligand vs the log of the ##STR9## The maximal number of binding sites (B max ) was calculated from the Scatchard plot.
Adenosine Receptor Binding--A 2 Receptor Affinity (RBA2)
Tissue Preparation
Brains from 200-500 g mixed sex Sprague-Dawley rats were purchased from Pel-Freez (Rogers, Arkansas). Fresh brains from male Long-Evans hooded rats (Blue Spruce Farms, Altamont, NY) gave essentially identical results. Brains were thawed and then kept on ice while the striata were dissected out. Striata were disrupted in 10 vol of ice-cold 50 mM Tris.HCl (pH 7.7 at 25° C., pH 8.26 at 5° C.) (Tris) for 30 seconds in a Polytron PT-10 (Brinkmann) at setting 5. The suspension was centrifuged at 50,000×g for ten minutes, the supernatant discarded, the pellet resuspended in 10 vol ice-cold Tris as above, recentrifuged, resuspended at 1 g/5 ml, and stored in plastic vials at -70° C. (stable for at least six months). When needed, tissue was thawed at room temperature, disrupted in a Polytron, and kept on ice until used.
Incubation Conditions
All incubations were for 60 minutes at 25° C. in 12×75 mm glass tubes containing 1 ml Tris with 5 mg original tissue weight of rat weight of rat striatal membranes, 4 nM [ 3 H]-N-ethyl adenosine-5'-carboxamide ([ 3 H]NECA), 50 nM N 6 -cyclopentyladenosine (to eliminate A 1 receptor binding), 10 mM mgCl 2 , 0.1 units/ml of adenosine deaminase and 1% dimethylsulfoxide. N 6 -Cyclopentyladenosine was dissolved at 10 mM in 0.02N HCl and diluted in Tris. Stock solutions and dilutions of N 6 -cyclopentyladenosine could be stored at -20° C. for several months. Test compounds were dissolved at 10 mM in dimethylsulfoxide on the same day as the experiment, and diluted in dimethylsulfoxide to 100× the final incubation concentration. Control incubations received an equal volume (10 μl) of dimethylsulfoxide; the resulting concentration of dimethylsulfoxide had no effect on binding. [ 3 H]NECA was diluted to 40 nM in Tris. The membrane suspension (5 mg/0.79 ml) contained sufficient MgCl 2 and adenosine deaminase to give 10 mM and 0.1 units/ml, respectively, final concentration in the incubation. For test compounds with IC 50 values less than 1 l μM, the order of additions was test compound (10 μl), N 6 -cyclopentyladenosine (100 μl), [ 3 H]NECA (100 μl), and membranes (0.79 ml). For test compounds with IC 50 values greater than 1 μM and limited water solubility, the order of additions (same volumes) was test compound, membranes, N 6 -cyclopentyladenosine, and [ 3 H]NECA. After all additions, the rack of tubes was vortexed, and the tubes were then incubated for 60 min at 25° C. in a shaking water bath. The rack of tubes was vortexed an additional time halfway through the incubation.
Incubations were terminated by filtration through 2.4 cm GF/B filters under reduced pressure. Each tube was filtered as follows: the contents of the tube were poured onto the filter, 4 ml of ice-cold Tris were added to the tube and the contents poured onto the filter, and the filter was washed twice with 4 ml of ice-cold Tris. The filtration was complete in about twelve seconds. Filters were put in scintillation vials, 8 ml of Formula 947 scintillation fluid added, and the vials left overnight, shaken, and counted in a liquid scintillation counter at 40% efficiency.
Data Analysis
Nonspecific binding was defined as binding in the presence of 100 μM N 6 -cyclopentyladenosine, and specific binding was defined as total binding minus nonspecific binding. The IC 50 was calculated by weighted nonlinear least squares curve-fitting to the mass-action equation. ##EQU2## where Y is cpm bound
T is cpm total binding without drug
S is cpm specific binding without drug
D is the concentration of drug and
K is the IC 50 of the drug
Weighting factors were calculated under the assumption that the standard deviation was proportional to the predicted value of Y. Nonspecific binding was treated as a very large (infinite) concentration of drug in the computer analysis.
The IC 50 values (nM) for adenosine A 1 and A 2 receptor affinity are reported in the table.
ANALGESIC EVALUATION
The antiwrithing (AW) test provides preliminary assessment of compounds with potential analgesic activity. The test is performed in male Swiss-Webster mice. Compounds are administered subcutaneously in aqueous 0.2% methylcellulose or other appropriate vehicles in volumes of 10 ml/kg. Dosages represent active moiety.
Acetic acid (0.6%, 10 ml/kg) is injected intraperitoneally 20 minutes after administration of the adenosine agonist. Writhing movements are counted for five minutes starting seven minutes after the acetic acid injection. Writhing is defined as abdominal constriction and stretching of the body and hind legs with concave arching of the back. Data are expressed as ED 50 values, where the ED 50 is the dose necessary to suppress writhing by 50% relative to vehicle controls. ED 50 values are calculated by nonlinear regression analysis.
ANTIINFLAMMATORY ASSAY
Assessment of immunoinflammatory or antiinflammatory activity is provided by the carrageenan pleurisy assay. Carrageenan pleurisy is induced as previously described by Carter, G. W., et al., in J. Pharm. Pharmacol 34:66-67, 1982. Carrageenan (310 μg/rat) is injected intrapleurally in a 0.25 ml volume of pyrogen-free saline. Four hours later, the rats are sacrificed and 2 ml of a phenol red solution (325 mg phenol red in 1 liter of 0.05M phosphate buffered saline) are added to each pleural cavity. The contents of the cavities are mixed and transferred to glass test tubes. A 50 μl aliquot is removed from each tube and exudate cells are counted after red blood cells lysis (with Zapoglobin; Coulter Electronics, Hialeah FL) using a Coulter model ZBI counter. The remaining exudate-phenol red mixture is centrifuged at 750×g for 15 minutes. One hundred μl of the supernatent fluid is diluted with 3.9 ml of phosphate buffer (0.072M of tribasic sodium phosphate, Na 3 PO 4 .12H 2 O, in water) and the absorbance is measured at 560 nm.
Exudate volume is calculated as follows: ##EQU3## where V 1 =unknown volume of exudate, V 2 =volume of dye added to cavity (2 ml), A 1 =absorbance of exudate (assumed to be zero), A 2 =absorbance of the phenol red solution, A 3 =absorbance of exudate and phenol red solution.
Inhibition of exudate or formation is calculated by the following equations: ##EQU4## ID 50 values are calculated by Probit analysis.
The compound of Example 1 was administered one hour prior to carrageenan injection.
The biological data are summarized in the Table. Accordingly, the present invention also includes a pharmaceutical composition for treating pain, and inflammation comprising a corresponding analgesic or antiinflammatory effective amount of a compound of the Formula I as defined above together with a pharmaceutically acceptable carrier.
______________________________________Receptor BindingExample RBA-1 (nM) RBA-2 (nM)______________________________________1 0.85 13002 1.4 14005 0.69 3093______________________________________AW Test (Analgesic Test) AW ED.sub.50 Example mg/kg______________________________________ 1 0.03______________________________________Carrageenan Pleurisy Assay(Immunoinflammatory Test) ID.sub.50 (mg/kg)Example Exudate WBC______________________________________1 0.15 0.12______________________________________
or specifically for various doses as follows:
______________________________________Carrageenan Pleurisy Assy Dose % InhibitionExample mg/kg Exudate WBC______________________________________1 0.1 49.3 74.1 0.2 60.0 70.0 0.4 81.3 90.0 0.8 42.7 68.42 0.3 24.3 25.7 1.0 22.9 52.95 0.1 11.7 18.4 0.3 16.8 40.0______________________________________
The present invention further includes a method for treating pain or inflammation in mammals suffering therefrom comprising administering to such mammals either orally or parenterally a corresponding pharmaceutical composition containing a compound of the Formula I as defined above in appropriate unit dosage form.
For preparing pharmaceutical compositions from the compounds described by this invention, inert, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets, and suppositories. A solid carrier can be one or more substances which may also act as diluents, flavoring agents, solublizers, lubricants, suspending agents, binders or tablet disintegrating agents; it can also be encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with the finely divided active compound. In the tablet the active compound is mixed with carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain from 5 or 10 to about 70 percent of the active ingredient. Suitable solid carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component (with or without other carriers) is surrounded by carrier, which is thus in association with it. Similarly, cachets are included. Tablets, powders, cachets, and capsules can be used as solid dosage forms suitable for oral administration.
For preparing suppositories, a low melting wax such as a mixture of fatty acid glycerides or cocoa butter is first melted, and the active ingredient is dispersed homogeneously therein as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool and thereby to solidify.
Liquid form preparations include solutions, suspensions, and emulsions. As an example may be mentioned water or water propylene glycol solutions for parenteral injection. Liquid preparations can also be formulated in solution in aqueous polyethylene glycol solution. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, i.e., natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.
Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration. Such liquid forms include solutions, suspensions, and emulsions. These particular solid form preparations are most conveniently provided in unit dose form and as such are used to provide a single liquid dosage unit. Alternately, sufficient solid may be provided so that after conversion to liquid form, multiple individual liquid doses may be obtained by measuring predetermined volumes of the liquid form preparation as with a syringe, teaspoon, or other volumetric container. When multiple liquid doses are so prepared, it is preferred to maintain the unused portion of said liquid doses at low temperature (i.e., under refrigeration) in order to retard possible decomposition. The solid form preparations intended to be converted to liquid form may contain, in addition to the active material, flavorants, colorants, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. The liquid utilized for preparing the liquid form preparation may be water, isotonic water, ethanol, glycerine, propylene glycol, and the like as well as mixtures thereof. Naturally, the liquid utilized will be chosen with regard to the route of administration, for example, liquid preparations containing large amounts of ethanol are not suitable for parenteral use.
Preferably, the pharmaceutical preparation is in unit dosage form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, for example, packeted tablets, capsules, and powders in vials or ampoules. The unit dosage form can also be a capsule, cachet, or tablet itself or it can be the appropriate number of any of these in packaged form.
The quantity of active compound in a unit dose of preparation may be varied or adjusted from 1 mg to 500 mg preferably to 5 to 100 mg according to the particular application and the potency of the active ingredient. The compositions can, if desired, also contain other compatible therapeutic agents.
In therapeutic use as described above, the mammalian dosage range for a 70 kg subject is from 0.1 to 150 mg/kg of body weight per day or preferably 1 to 50 mg/kg of body weight per day. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the art. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter the dosage is increased by small increments until the optimum effect under the circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day if desired.
The following Examples further illustrate the invention.
EXAMPLE 1
N 6 -endo-Bicyclo[2.2.1]heptyl adenosine
A mixture of 4.0 g of 6-chloropurine riboside, 2.57 g endo-2-aminonorbornane hydrochloride and 3.53 g triethylamine is refluxed in 100 ml ethanol under nitrogen for 20 hours. The solvent is evaporated to dryness. Residual solid material is dissolved in minimum of 2-propanol and diluted with excess cold water. Clear aqueous solution is decanted off. The residual solid is dissolved in ethanol and volatiles are evaporated. This is repeated once more yielding 3.8 g (75%) of N-6-endobicyclo[2.2.1]heptyladenosine having a melting point of 128°-130° C.
Analysis calculated for C 17 H 23 N 5 O 4 : C, 56.49; H, 6.41; N, 19.37; Found: C, 56.44; H, 6.81; N, 18.78.
EXAMPLE 2
N 6 -exo-Bicyclo[2.2.1]heptyladenosine
A mixture of 4.0 g of 6-chloropurine riboside, 1.8 g exo-2-aminonorbornane and 2.1 g of triethylamine is refluxed in 100 ml ethanol under nitrogen for 20 hours. The solvent is evaporated to dryness. The residual solid is treated with 50 ml of cold H 2 O. Clear aqueous solution is decanted off and the solid material is dissolved in ethanol. Volatiles are evaporated under vacuo. This is repeated twice yielding solid material which is crystallized from ethanolethyl acetate-hexane affording 4.1 g (81%) of N 6 -exo-bicyclo[2.2.1]heptyladenosine having a melting point of 110°-112° C.
Analysis calculated for C 17 H 23 N 5 O 4 : C, 56.49; H, 6.41; N, 19.37; Found: C, 55.88; H, 5.89; N, 18.59.
EXAMPLE 3
N 6 -2-(endo)-norbornyl-2',3'-O-isopopylidene adenosine
N 6 -2-(endo)norbornyladenosine (12.7 g, 35 mmol), 2,2-dimethoxy propane (35 ml) and bis-p-nitrophenylphosphate hydrate (12.8 g, 38 mmol) were stirred in acetone (150 ml) at room temperature 18 hours. The reaction was quenched with 0.1N NaHCO 3 (100 ml) and stirred for one hour. The acetone was evaporated in vacuo and the aqueous solution extracted with methylene chloride (200 ml). The organics were dried over magnesium sulfate and evaporated in vacuo to give an off white foam. The foam was dissolved in methanol (100 ml) and poured through a plug of Dowex 1×8 (NaHCO 3 form) resin. The resin was washed with methanol (300 ml) and the combined filtrates evaporated in vacuo to give 10.6 g (75%) of a white solid, mp 90°-98° C.
Analysis calculated for C 20 H 27 N 5 O 4 : C, 59.84; H, 6.78; N, 17.45; Found: C, 59.48; H, 6.71; N, 17.24.
EXAMPLE 4
N 6 -2-(endo)-norbornyl-5'-chloro-5'-deoxy-2',3'-O-isopropylidene adenosine
The isopropylidene analog, as prepared in Example 3 above, (6.3 g, 15.7 mmol) was stirred in THF (100 ml) and treated with thionylchloride (2.8 g, 23.5 mmol). The reaction stirred at room temperature, overnight. The solvent was evaporated in vacuo and the residue dissolved in methylene chloride (100 ml), and washed with water (2×100 ml). The organic dried over magnesium sulfate and evaporated in vacuo. The residue dissolved in ethyl acetate (25 ml) and purified by prep 500A chromatography (silica gel, 1 column, 100 ml/min). The slow running fraction was isolated by evaporation of solvent to give 4.4 g (67%) of a white foam, mp 61°-70° C. Analysis calculated for C 20 H 26 ClN 5 O 3 : C, 57.20; H, 6.24; N, 16.68; Cl, 8.44; Found: C, 56.97; H, 6.13; N, 16.59; Cl, 8.62.
EXAMPLE 5
N 6 -2-endo-norbornyl-5'-chloro-5' -deoxy-adenosine
The 5'-chloro-isopropylidene analog, as prepared in Example 4 above, (4.3 g, 10.2 mmol) was stirred in 50% formic acid (100 ml) at 50° C. for four hours. The acid was evaporated in vacuo and the residue coevaporated with methanol (2×50 ml) to give an off-white foam. The foam was dissolved in acetone (25 ml) and purified by prep 500A chromatography (silica gel, 1 column, 100 ml/min). The major refraction index active fraction was isolated by evaporation of solvent to give 2.4 g (62%) of a white solid, mp 96°-99° C.
Analysis calculated for C 17 H 22 ClN 5 O 3 : C, 53.75; H, 5.84; N, 18.44; Found: C, 53.89; H, 6.05; N, 18.23.
EXAMPLE 6
N 6 -(endo)norbornyl-5'-deoxyadenosine
Six chloropurine (2.3 g, 15 mmol), triethyl amine (3.5 g, 35 mmol) and 2-endo-aminonorbornane hydrochloride (2.5 g, 17 mmol) were stirred at reflux in 100 ml of ethanol for 72 hours. The solution was cooled to room temperature and the ethanol was evaporated in vacuo. The residue was dissolved in chloroform and washed with water (100 ml). The organics were dried over magnesium sulfate and the solvent was evaporated in vacuo. The residue was dried at 65° C. in vacuo overnight to give 2.1 g (62%) of a light green solid, mp 217°-219° C.
The adenine (4.4 g, 19.1 mmol) and 5' deoxy ribose (6.1 g, 23 mmol) were melted and stirred at 200° C. To the melt was added one micro drop of concentrated sulfuric acid and the acetic acid formed was removed in a gentle stream of nitrogen. The solution was stirred for four hours before cooling to room temperature. The glassy residue was broken up in 100 ml of ethyl acetate in an ultrasonic bath. The solution was then purified by chromatography to give after evaporation of the solvent 1.6 g of an off-white foam, identified in Example 7 hereinafter. The foam (1.4 g, 3.3 mmol) was then dissolved in 100 ml of methanolic ammonia (saturated at 0° C.) and the solution was stirred at room temperature for six hours. The solution was evaporated in vacuo and the residue purified by chromatography to give, after evaporation of solvent 0.9 g (18%) of a hygroscopic white solid, mp 93°-101° C.
EXAMPLE 7
N 6 -Endo-norbornyl-5'-deoxyadenosine-2',3'-di-O-acetyl
Compound 7 from Example 6 was analyzed to give the product N 6 -(2-endo-norbornyl)-5'-deoxy-2',3'-diacetyl adenosine 1.6 g (19.5%), mp 68°-77° C.
Analysis calculated for C 21 H 27 N 5 O 5 : C, 58.34; H, 6.60; N, 14.79; Found: C, 58.32; H, 6.48; N, 14.86.
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N 6 -Bicyclo adenosines and pharmaceutically acceptable acid addition salts having highly desirable antiinflammatory and analgesic activity and processes for their manufacture as well as pharmaceutical compositions and methods for using said compounds and compositions are described.
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This is a continuation of application Ser. No. 08/245,978 filed May 19, 1994 now abandoned.
TECHNICAL FIELD
This invention relates to label pads for labelling magnetic recording media.
BACKGROUND OF THE INVENTION
One of the useful features of magnetic recording media is that it can be re-used many times, by recording new material over previously recorded material. As a result, it is desirable that any labelling of the magnetic media, such as adhesive labels attached to videocassettes, should be readily alterable, to accurately describe the material currently recorded on the magnetic media.
One alterable label for a rerecordable medium is disclosed in U.S. Pat. No. 5,195,265, in which a pad having several layers of adhesively attached labels is attached to a videocassette. Initially, the top label in the pad is used to indicate the recorded contents of the videocassette. If the recorded contents are altered, the top label is peeled off, exposing the next label, upon which new labelling information can be written. Peeling off of the top label is facilitated by a nonadhesive tab at one edge of the label, which enables the top label to be easily selected and firmly grasped for removal. A disadvantage of this system is that the nonadhesive tabs may get folded outwardly and catch on various objects, such as the apparatus used to record or play the cassette.
A pad of peelable labels without nonadhesive tabs is disclosed in U.S. Pat. No. 4,973,088. Here separation of the top label from the next label is facilitated by a stepped, or staggered, configuration. The top label is indented slightly from the next label, which is, in turn, indented slightly from the label below it. This allows a fingernail or sharp object to rest upon the second label while being inserted beneath the first label, to enable the top label to be removed without disturbing the next label in the pad.
Regardless of the particular configuration used for videocassette labels, it is preferred that the label be made of paper, since paper is low in cost and easily written upon by a variety of writing instruments. Paper, however, is temperature and humidity sensitive. With very long paper labels, such as described above, which might be used to label a videocassette, the expansion and contraction of the paper can lead to curling of the labels, which is detrimental to the appearance of the videocassette, and can reduce label adhesion. An additional disadvantage of known labels for magnetic recording media is that when relabelling, the entire label must be replaced, even when only a portion of the recorded material has been altered.
SUMMARY OF THE INVENTION
The present invention is a changeable label pad having a base label layer which can be adhesively attached to an information container such as a recording media container. A first adhesive having a first strength attaches the base label layer to the information container. At least two label segments are attached to the base label layer. The label segments combine to cover most of the base label layer and the label segments are separated from each other by at least a separation. A second adhesive having a second strength which is weaker than that of the first adhesive attaches the label segments to the base label layer.
In one embodiment, at least two stacks of label segments are attached to the base label layer. Adjacent label segments in each layer of the stack are separated from each other by at least a separation. The separation can be a transverse gap. The separation of the label layers into label segments reduces curling of the labels under conditions of extreme variations in humidity and temperature, and allows a portion of a label to be changed without requiring the entire label to be rewritten.
The total area of all of the label segments in a first layer of label segments is less than the total area of all of the label segments in a second layer of label segments to which the first layer is adhered to form peeling steps. The peeling steps can be formed at the longitudinal ends of the label pad or adjacent the transverse gap of the label pad. Also, an identification area can formed on the base layer and extend beyond the first layer of label segments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a pad of labels according to the present invention being applied to the edge label area of a VHS videocassette.
FIG. 2 is a top view of the pad of labels.
FIG. 3 is a side view of the pad of labels of FIG. 2.
FIG. 4 is a top view of another embodiment of a pad of labels according to the present invention.
FIG. 5 is a side view of the pad of labels of FIG. 4.
FIG. 6 is a top view of another embodiment of a pad of labels according to the present invention.
FIG. 7 is a side view of the pad of labels of FIG. 6.
FIG. 8 is a top view of another embodiment of a pad of labels according to the present invention.
FIG. 9 is a side view of the pad of labels of FIG. 8.
FIG. 10 is a top view of another embodiment of a pad of labels according to the present invention.
FIG. 11 is a side view of the pad of labels of FIG. 10.
FIG. 12 is a top view of another embodiment of a pad of labels according to the present invention.
FIG. 13 is a side view of the pad of labels of FIG. 12.
FIG. 14 is a top view of another embodiment of a pad of labels according to the present invention.
DETAILED DESCRIPTION
FIG. 1 shows a VHS videocassette 10, including a base 12, a cover 14, a door 16, an indented cover label area 18, and an indented rear side label area 20. A label pad 22 is positioned for attachment to an indented edge label area 20 of the cassette 10. Additionally, the label pad 22 can be used with other format cassettes, diskettes, folders, and any other information containers requiring multiple relabeling and the labels can be any shape, whether for aesthetics or to accommodate a particular use. The label pad 22 is a changeable, reusable pad. It is readily alterable to accurately describe the material currently recorded on the magnetic media.
To accommodate manufacturing and label placement tolerances, as well as expansion and contraction of the label material under varying environmental conditions, the length L and width W of the label pad 22, shown in FIG. 2, should be slightly less than the corresponding dimensions of the indented label area 20. A suitable length L for the label pad 22 is 136 mm (5.35 in), and a suitable width W is 19 mm (0.75 in). Typical corresponding dimensions of the label area 20 are 150 mm (5.9 in) and 21 mm (0.83 in), respectively. Thus, the length L and width W of the label pad 22 are about 10% less than the corresponding dimensions of the label area 20. This dimensional allowance is based upon the use of paper as the label material. If other less humidity-sensitive material is used, the length L and width W of the label pad 22 can be slightly greater, coinciding more nearly with the corresponding dimensions of the indented area 20. Also, as shown, the labels can have rounded corners.
Referring to FIGS. 2 and 3, the label pad 22 includes a base label layer 24, which can be adhesively attached to the cassette label area 20 by a relatively strong adhesive layer 26. The adhesive layer 26 is preferably a pressure sensitive label adhesive of the type well-known in the art such as 3M material #AP380 acrylic.
A pair of label segments 28, separated by a transverse gap 30, are attached to the base label layer 24 by a lower strength, peelable adhesive 32. The transverse gap 30 runs transverse to the length L of the label pad 22. The peelable adhesive 32 can be any adhesive which allows a label layer to be peeled from the next lower label layer without damage to the lower layer. Suitable peelable adhesives are disclosed in U.S. Pat. No. 4,599,265, assigned to Minnesota Mining and Manufacturing Company, St. Paul, Minn. The label segments 28 are separate from each other and from the base label layer 24. The label segments 28 are adhered to the base label layer 24 but are not connected to it such as through perforated label connections. The label segments 28 can abut each other but also are not connected to each other such as through perforated label connections.
Similarly, a pair of label segments 34 are adhesively attached to the label segments 28, again separated by transverse gap 30, using peelable adhesive 32, and top label segments 36 are similarly attached to label segments 34, separated by the transverse gap 30, using peelable adhesive 32. The label segments 34 are not connected to adjacent layers of label segments or to each other such as through perforated label connections. Additional pairs of label segments 34 can be adhesively attached to lower pairs of label segments 34 to form a stack. Label pads 22, having up to eight total layers of label segments, have been made. By changing the adhesives and the label thickness, additional layers can be added.
Top label segments 36 are used as the label when the cassette is first recorded upon. The recorded information is identified on this label segment. When changes are made to the recorded material, as might occur when a portion of the media is recorded over, the label segment 36 containing the changed material is peeled from the pad and the new label information is written on the next label segment 34 which becomes the top label segment 36. It is an advantage of the present invention that only the label segment 36 containing altered information needs to be removed. Where the original information is written on only one of the pairs of label segments 36, the new label information can be written on the other of the label segments 36. In this situation, it may not be necessary to remove the label segment 36 with the old information.
The total area of all of the label segments 28, 34, 36 in a layer of label segments is less than the total area of all of the label segments in the underlying layer of label segments closer to the base label layer 24 to which the first layer is adhered. Successive layers of label segments are staggered. This forms a series of peeling steps 38. Peeling of the label segment 36 from the label segment 34 can be performed by resting an object, such as a fingernail or thin or sharp tools, on a peeling step 38. Then, the object is moved toward the layer of label segments 36, and the top label segment is lifted to a position such as shown at 36'. Here, it can be grasped and peeled from the underlying layer of label segments 34 or from the base label layer 24 if no other underlying label segments 34 exist. The transverse gap 30 allows the other, non-peeled label segment 36 to remain unchanged, obviating the need for rewriting of this portion of the label.
An additional advantage of the transverse gap 30 is that it enables the label pad 22 to withstand extremes of temperature and humidity without suffering the curling or other damage which has been found to occur in peelable labels having a large length L. A suitable width G for the transverse gap 30 is 1.6 mm (0.0625 in). Paper videocassette labels having a length L of 136 mm, but without a transverse gap 30, were found to curl and exhibit a damaged appearance when subjected to an environment of 40° C. (104° F.) and 80% humidity for 4 days. Paper videocassette labels having substantially the same dimensions as those which curled in the humidity test, but with the added feature of transverse gap 30, were found to withstand an environment of 40° C. and 80% humidity for 4 days without visible damage.
In an alternative embodiment, shown in FIGS. 4 and 5, peeling steps 38 can be placed in the transverse gap 30 area, so that peeling is initiated from the center of the label area, rather than from the end. In the embodiment of FIGS. 6 and 7, peeling steps 38 can be provided at both the ends of the labels and in the center.
In the embodiments of FIGS. 3-7, an identification area 40 is provided as part of the base label layer 24. It is not necessary to provide an identification area 40, and in some cases it might be preferable to eliminate it, to provide a larger area for user-written labels, as in the embodiments shown in FIGS. 8-13. The embodiments of FIGS. 8 and 9, 10 and 11, and 12 and 13 correspond to those of FIGS. 2 and 3, 4 and 5, and 6 and 7, respectively.
In the embodiment shown in FIG. 14, each label layer has four separate label segments. Each layer includes labels 42, 44, 46, 48 with the labels 42 and 44 being separated from the labels 46 and 48 by the transverse gap 30. The labels 42 are separated from the labels 44 by a longitudinal separation 50 such as a cut, and the labels 46 are separated from the labels 48 by longitudinal separation 52 such as a cut.
The number of separate label segments into which each label layer is divided is not critical, but is limited by the resulting size of the labels. While the disclosed embodiments provide only one transverse gap 30, it is possible that more than one transverse gap, additional transverse slits, or other separations could be used to provide any number of labels. Also, the number of label layers is not critical, but is limited by the allowable overall thickness of the label pad, since excessively thick label pads could interfere with use of a videocassette, or could be susceptible to damage. Fewer than three label layers could be used, but this could inconvenience the user if the magnetic medium is relabelled many times.
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A changeable label pad has a base label layer which can be adhesively attached to a recording media container. A first adhesive having a first strength attaches the base label layer to the container. At least two label segments are attached to the base label layer. The label segments combine to cover most of the base label layer and the label segments are separated from each other. A second adhesive having a second strength which is weaker than that of the first adhesive attaches the label segments to the base label layer. The total area of all of the label segments in a layer of label segments is less than the total area of all of the label segments in an underlying layer of label segments.
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CROSS REFERENCE TO RELATED APPLICATION
The present application claims priority to U.S. Provisional Patent Application No. 60/447,151 filed Feb. 13, 2003, which is incorporated herein by reference in its entirety.
BACKGROUND
The subject invention generally and in various embodiments relates to housings, and more particularly to devices for supporting and mounting telecommunications modules.
Many telecommunications providers are using optical networks to provide multiple and high bandwidth telecommunications services to businesses or homes. To accommodate the increasing numbers of customers using such services, some telecommunications providers are bringing more optical fibers to Remote Terminal (RTs) or remote cabinets to facilitate the delivery of high bandwidth services to subscribers. The RTs may be used to provide traditional voice as well as Digital Subscriber Line (DSL) services, so that RTs used to provide a local loop of 500 to 2000 homes are not uncommon. Additionally, the RTs may serve business customers with dedicated fibers. To increase the capacity of the fibers that are taken to the RTs, Wavelength Division Multiplexing (WDM) modules, or cassettes, may be implemented. Such multiplexing modules increase the data-carrying capacity of an optical fiber by concurrently transmitting signals at different wavelengths through the same fiber. These multiplexing modules are housed in RT cabinets, which also include the fiber termination shelves, power shelves, and other hardware and electronics. A jumble of various components is often the result in crowded RT cabinets.
SUMMARY
Embodiments of the present invention may also include an apparatus for supporting and mounting at least one module on a surface. The apparatus may comprise a housing that may be attachable to a portion of the surface. The housing may have a channel therein that may be sized to receive and support at least a portion of at least one module therein. The apparatus may also include at least one mounting member on the housing for attaching the housing to the surface.
Embodiments of the present invention may include a housing for supporting and mounting at least one module. The housing may include a first panel member, a second panel member that may be connected to the first panel member, and a third panel member that may be connected to the second panel member opposite the first panel member. A slot may be formed between the first and third panel members and may also be capable of receiving at least one module. The housing may also include at least one mounting member that may be capable of mounting the housing to a surface.
Embodiments of the present invention may also include an apparatus for mounting at least one module on a surface. The apparatus may comprise housing means that may be attachable to the surface for forming a channel for receiving at least a portion of the at least one module therein, between a portion of the housing means and the surface. The apparatus may further include means for mounting the housing means to the surface.
Embodiments of the present invention may further include a method of mounting at least one module on an RT cabinet. The method may comprise forming an open ended channel on a portion of the cabinet, inserting at least a portion of the at least one module into the open ended channel and retaining the at least one module within the open ended channel.
Other systems, methods, and/or computer program products according to embodiments will be or become apparent to one with skill in the art upon review of the following drawings and detailed description. It is intended that all such additional systems, methods, and/or computer program products be included within this description, be within the scope of the present invention, and be protected by the accompanying claims.
BRIEF DESCRIPTION OF THE DRAWINGS
In the accompanying Figures, there are shown embodiments of the present invention wherein like reference numerals are employed to designate like parts and wherein:
FIG. 1 is a perspective view of embodiments of a housing for a module according to the invention;
FIG. 2 is a perspective view of embodiments of a module;
FIG. 3 is a front view of embodiments of the housing of FIG. 1 , shown mounted on a surface of a telecommunications Remote Terminal cabinet;
FIG. 4 is a front view of embodiments of the Remote Terminal cabinet showing the housing of FIG. 1 ; and
FIG. 5 is a side view of embodiments of the housing shown in FIG. 3 .
DETAILED DESCRIPTION
Referring now to the drawings for the purpose of illustrating the invention and not for the purpose of limiting the same, it is to be understood that standard components or features that are within the purview of an artisan of ordinary skill and do not contribute to the understanding of the various embodiments of the invention are omitted from the drawings to enhance clarity. In addition, it will be appreciated that the characterizations of various components and orientations described herein as being “vertical” or “horizontal”, “right” or “left”, “side”, “top”, “bottom”, “upper” or “lower” are relative characterizations only based upon the particular position or orientation of a given component for a particular application.
FIG. 1 shows an embodiment of a housing 100 for a WDM-type, splitter or multiplexing module 200 , an embodiment of which is shown in FIG. 2 . The housing 100 may include a channel or slot 102 that may be defined by first, second and third panels 104 , 106 and 108 , respectively. The slot 102 may be, for example, U-shaped. The first arid second panels 104 and 106 may be parallel and may be joined to the third panel 108 to form the slot 102 . The second panel 106 may be solid, as shown in FIG. 1 , or may have one or more apertures therethrough to receive input to a module 200 . The housing 100 may be configured to accommodate the module 200 , or several modules 200 . The housing 100 may include a back cover panel 110 attached to the first, second and third panels 104 , 106 , 108 .
The housing 100 may include a first magnet 112 attached to a first side 114 of the third panel 108 . The first side 114 may extended further toward the first panel 104 , much like a flange, to assist in supporting the module 200 . See FIG. 5 . The magnet 112 may be, for example, in the form of a magnetic strip with adhesive backing for attachment to the housing 100 . It would be appreciated that other types of magnets, such as solid magnets or electromagnets, for example, and other methods of attachment to the housing 100 may be used for mounting the housing 100 such as, for example, screws, hook and loop fasteners, etc. The magnet 112 may make it possible to removably mount the housing 100 to a magnet-attracting surface, such as a ferrous surface 126 next to or on a fiber optic termination shelf 300 in an RT cabinet 400 or other bandwidth distribution center, which is fabricated from, for example, steel or the like.
The module 200 may include a rectangular box 202 , which may contain various multiplexing, splitting and other components, and a face plate 204 attached to the box 202 . The face plate 204 may support two standardized fasteners 206 , such as, for example, push-on pins, quick-connect plungers, etc., and may include a number of fiber connectors 208 connected with fiber jumpers 302 to the fiber optic termination shelf 300 . The module 200 may be slid into the slot 102 such that the fasteners 206 may be inserted into corresponding orifices 120 , which may be provided in the first and third panels 104 , 108 of the housing 100 , thereby providing a means for receiving the fasteners 206 and locking the module 200 in the housing 100 . Other means for receiving fasteners 206 may be provided for the particular fastener that may be employed on the module 200 .
In another embodiment, the housing 100 may include a second magnet 122 attached to a first side 124 of the first panel 104 to provide additional support for mounting the housing 100 on the metal surface 126 . See FIG. 3 and FIG. 5 . The first side 124 may extended further toward the third panel 108 , much like a flange, to assist in supporting the module 200 . See FIG. 5 . Yet other embodiments may include, for example, three or more magnets, magnetized surfaces, hook and loop fasteners, etc. Permanent mounting may also be provided by fastening the housing 100 to the surface 126 through holes 140 on the first and third panels 104 and 108 or on the cover panel 110 through rear holes 125 .
The housing 100 of the invention, in various and several embodiments, may provide an inexpensive and convenient device for mounting modules 200 and similar devices inside RT cabinets 400 , such as the one shown in FIG. 4 , in an orderly manner. The housing 100 may be fabricated, for example, as one piece by injection molded plastic, although other materials, including, for example, metals, sheet metals, and methods of manufacture that are available to a skilled artisan may also be used.
Whereas particular embodiments of the invention have been described herein for the purpose of illustrating the invention and not for the purpose of limiting the same, it will be appreciated by those of ordinary skill in the art that numerous variations of the details, materials, configurations and arrangement of parts may be made within the principle and scope of the invention without departing from the spirit of the invention. The preceding description, therefore, is not meant to limit the scope of the invention.
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An apparatus for supporting and mounting at least one module on a surface may be provided. The apparatus may comprise a housing that may be attachable to a portion of the surface. The housing may have a channel that may be sized to receive and support at least a portion of at least one module. The apparatus may also include at least one mounting member on the housing for attaching the housing to the surface.
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BACKGROUND OF THE INVENTION
This invention relates to removal of offshore structures after the useful life of the structures in their original offshore location. More particularly, the invention is directed to a method of removing piling-anchored offshore platforms in an environmentally acceptable manner.
Many drilling and/or production platforms used in drilling for and/or producing oil and gas in shallow or moderately deep water are anchored to the seabed by large steel pilings which extend into the seabed and which support the platforms. Such platforms have a finite useful life, and after that are preferably removed to a new location or scrapped. In either event it is necessary to separate the platform from its anchoring pilings
Environmental regulations require that pilings be cut at a specified depth, typically about 5 meters, below the seabed.
Various cutting techniques have been utilized, with varying degrees of success. The most common piling cutting technique uses explosives to sever the pilings at the required depth. Environmental and regulatory groups have objected to this technique as harmful to marine life.
Non-explosive cutters using mechanical cutters or abrasive fluid jets have been tried, but are costly and difficult to use, particularly in deeper waters.
SUMMARY OF THE INVENTION
In accordance with the present invention, an improved non-explosive process for cutting pilings is provided. This process involves chilling the piling at the desired cutting level to a temperature such that its toughness against brittle fracture is greatly reduced, and then applying a fracturing force to the chilled section of the piling to break it at the desired depth. The process can be applied to one or more or all of the pilings at a time, and the fracturing force can be applied in any of a variety of ways.
It is accordingly an object of the invention to provide an efficient, environmentally acceptable method for cutting platform-supporting pilings.
It is a further object to provide such a method which involves chilling the piling to a temperature low enough to greatly reduce the piling's toughness against brittle fracture, and applying a fracturing force to the piling.
The foregoing as well as additional objects and advantages are achieved by the invention as will be apparent from consideration of the following detailed description thereof.
THE DRAWINGS
FIG. 1 is a side elevational view, partially cut away and partially reduced in scale, illustrating the environment where the invention is to be utilized.
FIG. 2 is a cross sectional view showing details of an apparatus for chilling a piling at a desired depth.
FIG. 3 is a perspective view illustrating an embodiment of applying a pile fracturing force to an offshore structure.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The process of the invention will be described with reference to the several views of the drawings.
FIGS. 1 and 3 show a platform 10 which is to be removed because drilling and/or production from the platform is no longer to be carried out. As shown, the platform has already been stripped of most of its drilling and/or processing equipment, and is to be removed to eliminate it as a potential hazard to navigation. It will be appreciated that FIGS. 1 and 3 do not show structural details of the platform which are not relevant to the invention. Platform 10 includes a deck 12 supported by legs or jackets 14.
As best seen in FIGS. 1 and 2, each leg 14 is supported on a piling 16 by conventional structure (not shown) and further supported by grouting 18 between piling 16 and leg 14.
In installing platform 10, pilings 16 are driven a predetermined depth into the sea floor 20, and platform legs or jackets 14 are then installed over and supported by the pilings to provide a solid foundation for the platform.
When it is desired to remove the obsolete platform 10, in accordance with this invention a self-contained piling chilling device 22 is lowered by cable 24 or other suitable means through leg 14 and piling 16 to a depth sufficiently below the sea floor that the resulting piling fracture will be at least as deep as the required depth illustrated by the arrows as noted at 26 in FIGS. 1 and 2.
Piling chiller 22, as seen in FIG. 2, includes a tank 28 supported within cylindrical member 30. Seals 32 and 34 are located at the top and bottom of cylinder 30 to seal off an annulus between cylindrical member 30 and piling 16. In some cases only a top seal is needed. The seals may be hydraulically or pheumatically operated, or may be formed of oversized compressible material. A control valve 36 operated remotely through control line 38 controls discharge of cooling fluid from tank 28 through conduit 40 into the annulus between cylindrical member 30 and piling 16. A vent 42 in cylindrical member 30 allows cooling gas to be discharged from the annulus into the open space in piling 16.
It will be appreciated that piling chiller 22 could be varied in many respects from the version shown in FIG. 2, which is merely illustrative of an suitable device for chilling the piling 16.
In carrying out the process of the invention, preferably after platform 10 has been stripped of most or all of the heavy drilling, processing or other equipment, a piling chiller is lowered into one or some or all of the pilings 16 to a depth below the required removal point. In some cases, water or mud may have to be removed from the interior of the piling, and structural obstacles on the platform or in the jacket or piling may have to be removed. After access is provided, piling chiller 22 is lowered and sealed in position, and a cryogenic fluid from tank 28 is discharged into the annulus to chill the adjacent section of piling to a point where its toughness against brittle fracture is greatly reduced. Any cryogenic fluid may be used, but liquid nitrogen is normally the fluid of choice for reasons of cost and availability.
After the piling (or pilings) has been sufficiently chilled, a fracturing force is applied to fracture the piling and release the leg or platform from the sea floor. Obviously, care must be taken to prevent sudden vertical movement or overturning of the platform. The fracturing force can be applied in any manner, such as by impact or by suddenly applied tension. FIG. 3 illustrates a preferred impacting technique in which the platform is simply rammed by a large ship 42. In actual practice, a bumper type structure on both the platform and the ship would be used to protect the ship and to properly distribute the fracturing force. Alternatively, a sudden application or release of tension by manipulation of cables, or use of large hydraulic rams, could be used to apply the necessary fracturing force.
In some instances, it may be desirable to carry out a fracture initiating step to the chilled section of piling prior to application of the fracturing force. This fracture initiating step may comprise scoring the chilled section of piling, or applying a localized blow to the chilled section.
Variations of the above-described embodiments will be apparent to those skilled in the art, and are intended to be included within the scope of the invention as defined by the appended claims.
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A method for removing obsolete piling-anchored offshore platforms. The pilings at a desired cutoff point below the seabed are chilled to the point that toughness against brittle fracture is greatly reduced, and then a fracturing force is applied to the chilled section of piling.
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FIELD OF THE INVENTION
[0001] This invention relates to the field of light source used in illumination and display, and in particular, it relates to projection system, light source system and light source assembly.
DESCRIPTION OF THE RELATED ART
[0002] Currently, projectors are widely used in various applications, including playing movies, meeting and public events, etc. Phosphor color wheels are often used as the light source of projectors for providing a color light sequence. In such a device, different segments of the phosphor color wheel are alternately and periodically provided in the propagation path of the excitation light, on which the phosphor material coated are excited by the excitation light in order to generate color fluorescent light. However, because the spectral range of the fluorescent light generated by the phosphor material is wide, the color purity of the fluorescent light is poor, which result in an insufficient color gamut of the light source. In this case, color filters are needed to filter the fluorescent light, so that the color purity of the fluorescent light can be improved. However, because the spectral ranges of different colored fluorescent light are partly overlapped, they cannot be filter using a same color filter, so that different colored fluorescent light needs different color filter. In a conventional device, a color filter wheel composed of different color filters is provided in the entrance of the light homogenization rob, and a driving device of the color filter wheel and a driving device the phosphor color wheel are synchronized by electronic circuits. The above method has the following disadvantages: the structure is complex, it is difficult to achieve, and the synchronization effect is poor.
[0003] As the projector industry is increasingly competitive, manufacturers have to improve the quality of the projector to enhance their competitiveness. The inventors of the present invention in the process of actively seeking to improve the quality of the projector found that: in the prior art, the synchronization architecture of the phosphor color wheel and the color filter wheel of the projector light source has the technical problem: the structure is complex, it is difficult to achieve, and the synchronization effect is poor.
[0004] So, a projection system, a light source system and the light source devices are needed to solve the above technical problem existing in the synchronization architecture of the phosphor color wheel and the color filter wheel of the projector light source in the prior art.
SUMMARY OF THE INVENTION
[0005] The present invention seeks to solve the problem by providing a projection system, a light source system and light source assembly to simplify the synchronization architecture of the wavelength conversion device and the color filtering device, and improve the synchronization effect.
[0006] To solve the above problem, the present invention adopts a technical solution: providing a light source system, which includes an excitation light source, a wavelength conversion device, a color filter device, a driving device and a first optical assembly. The excitation light source is for generating an excitation light. The wavelength conversion device includes at least one wavelength conversion area. The color filter device is fixed with respected to the wavelength conversion device, and includes at least one color filter area. The driving device is for driving the color filter device and the wavelength conversion device and makes them move synchronously. The wavelength conversion areas are provided in the propagation path of the excitation light periodically in order to convert the excitation light into converted light. The first optical assembly is used to guide the converted light to the first color filter area, and the first color filter area filters the converted light to improve its color purity.
[0007] In some embodiments, the wavelength conversion device and the color filter device are two ring structures fixed coaxially.
[0008] In some embodiments, the driving device is a rotation device with a rotating shaft, and the two ring structures are coaxially fixed to the rotating shaft.
[0009] In some embodiments, the wavelength conversion area and the first color filter area are located at 180-degree angle from each other with respect to a centre of the two ring structures. A light spot formed by the excitation light on the wavelength conversion device and a light spot formed by the converted light on the color filter device after being directed by the first optical assembly are located at 180-degree angle from each other with respect to the center of the two ring structures.
[0010] In some embodiments, the wavelength conversion area and the first color filter area are located at 0-degree angle from each other with respect to a center of the two ring structures. A light spot formed by the excitation light on the wavelength conversion device and a light spot formed by the converted light on the color filter device after being directed by the first optical assembly are located at 0-degree angle from each other with respect to the center of the two ring structures.
[0011] In some embodiments, the wavelength conversion device and the color filter device are spaced apart along an axial direction of the driving device; the first optical assembly includes at least one light collecting device disposed between the wavelength conversion device and the color filter device; and the light collecting device collects the converted light so that an energy of the converted light incident on the color filter device with less than or equal to 60-degree incident angles is more than 90% of a total energy of the converted light.
[0012] In some embodiments, the wavelength conversion area reflects the converted light so that a direction of the converted light emitted from the wavelength conversion area is opposite to a direction of the excitation light incident on the wavelength conversion area.
[0013] In some embodiments, the wavelength conversion area transmits the converted light so that a direction of the converted light emitted from the wavelength conversion area is the same as a direction of the excitation light incident on the wavelength conversion area.
[0014] In some embodiments, the first optical assembly includes at least one light collecting device which collects the converted light so that an energy of the converted light incident on the color filter device with less than or equal to 60-degree incident angles is more than 90% of a total energy of the converted light.
[0015] In some embodiments, the first optical assembly includes at least one reflecting device which reflects the converted light to change a propagation direction of the converted light, and the reflecting device is a planar reflecting device or a semi-ellipsoidal or hemispherical reflecting device with a reflecting surface facing inside.
[0016] In some embodiments, the planar reflecting device includes a dichroic mirror or a reflecting mirror.
[0017] In some embodiments, the semi-ellipsoidal or hemispherical reflecting device with the reflecting surface facing inside is provided with a light entrance port through which the excitation light is incident on the wavelength conversion device.
[0018] In some embodiments, the wavelength conversion device further includes a first light transmission area which is periodically disposed in the propagation path of the excitation light under the driving of the driving device and which transmits the excitation light.
[0019] In some embodiments, the system further includes a second optical assembly which combines the excitation light transmitted by the first light transmission area and the converted light filtered by the first color filter area.
[0020] In some embodiments, the color filter device includes a second light transmission area or a second color filter area, and the first optical assembly guides the excitation light transmitted by the first light transmission area, along the same propagation path of the converted light, to the second light transmission area or the second color filter area to be transmitted or filtered.
[0021] In some embodiments, the system further includes an illumination light source which generates an illumination light; the wavelength conversion device further includes a first light transmission area which is periodically disposed in a propagation path of the illumination light under the driving of the driving device, the first light transmission area transmitting the illumination light; the color filter device further includes a second light transmission area or a second color filter area; and the first optical assembly guides the illumination light transmitted by the first light transmission area, along the same propagation path of the converted light, to the second light transmission area or the second color filter area to be transmitted or filtered.
[0022] In some embodiments, the system further includes: an illumination light source generating an illumination light, and a second optical assembly which combines the illumination light and the converted light filtered by the first color filter area into one beam of light.
[0023] In some embodiments, the wavelength conversion device is a cylindrical structure and the color filter device is a ring structure which is coaxial fixed with the cylindrical structure so that they rotate coaxially and synchronously under the driving of the driving device.
[0024] In some embodiments, the wavelength conversion area is provided on an outer surface of a sidewall of the cylindrical structure and reflects the converted light, and the first color filter area is provided on the ring structure located outside of the cylindrical structure to receive the converted light.
[0025] In some embodiments, the wavelength conversion device and the color filter device are two cylindrical structures coaxially fixed and nested within each other to rotate coaxially and synchronously under the driving of the driving device; the wavelength conversion area and the first color filter area are respectively provided on sidewalls of the two cylindrical structure; and the converted light is transmitted by the wavelength conversion area and incident on the first color filter area.
[0026] In some embodiments, the wavelength conversion device and the color filter device are two strip structures adjoined side by side, on which the wavelength conversion area and the first color filter area are provided side by side, the two strip structures move in an oscillating linear translational motion under the driving of the driving device.
[0027] The present invention also provides a source module, which includes: wavelength conversion device including at least one wavelength conversion area, and a color filter device fixed with respected to the wavelength conversion device and including at least one color filter, where the wavelength conversion area and the color filter area move synchronously under the driving of a driving device.
[0028] In some embodiments, the wavelength conversion device and the color filter device are two ring structures fixed coaxially.
[0029] In some embodiments, the wavelength conversion device is a cylindrical structure and the color filter device is a ring structure which is fixed coaxially with the cylindrical structure.
[0030] In some embodiments, the wavelength conversion area is provided on an outer surface of a sidewall of the cylindrical structure, and the color filter area is provided on the ring structure located outside of the cylindrical structure.
[0031] In some embodiments, the wavelength conversion device and the color filter device are two cylindrical structures which are fixed coaxially and nested within each other, and the wavelength conversion area and the color filter area are provided on sidewalls of the two cylindrical structures respectively.
[0032] In some embodiments, the wavelength conversion device and the color filter device are two strip structures adjoined side by side, on which the wavelength conversion area and the color filter area are provided side by side.
[0033] The present invention also provides a projection system, which includes a light source system described above.
[0034] The advantage of the present invention is: different from the prior art, in the projection system, the light source system and the light source assembly of the present invention, the color filter device and the wavelength conversion device are fixed with each other, and driven by the same driving device, which can bring the advantages: the structure is simple, it is easy to implement, and the synchronization effect is excellent.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] FIG. 1 illustrates the structure of a light source system according to a first embodiment of the present invention.
[0036] FIG. 2 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 1 .
[0037] FIG. 3 illustrates the structure of a light source system according to a second embodiment of the present invention.
[0038] FIG. 4 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 3 .
[0039] FIG. 5 illustrates the structure of a light source system according to a third embodiment of the present invention.
[0040] FIG. 6 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 5 .
[0041] FIG. 7 illustrates the structure of a light source system according to a fourth embodiment of the present invention.
[0042] FIG. 8 illustrates the structure of a light source system according to a fifth embodiment of the present invention.
[0043] FIG. 9 illustrates the structure of a light source system according to a sixth embodiment of the present invention.
[0044] FIG. 10 illustrates the structure of a light source system according to a seventh embodiment of the present invention.
[0045] FIG. 11 illustrates the structure of a light source system according to an eighth embodiment of the present invention.
[0046] FIG. 12 illustrates the structure of a light source system according to a ninth embodiment of the present invention.
[0047] FIG. 13 illustrates the structure of a light source system according to a tenth embodiment of the present invention.
[0048] FIG. 14 illustrates the structure of a light source system according to an eleventh embodiment of the present invention.
[0049] FIG. 15 illustrates the structure of a light source system according to a twelfth embodiment of the present invention.
[0050] FIG. 16 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 15 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0051] Referring to FIG. 1 and FIG. 2 , FIG. 1 illustrates the structure of a light source system according to a first embodiment of the present invention, and FIG. 2 is a front view of the wavelength conversion device and the color filter device in the light source system shown in FIG. 1 . As show in FIG. 1 , the light source system in this embodiment mainly includes an excitation light source 101 , a dichroic mirror 102 , a mirror 104 , lenses 103 and 105 , a wavelength conversion device 106 , a color filter device 107 , a driving device 108 and a light homogenization device 109 .
[0052] The excitation light source 101 is for generating an excitation light. In this embodiment, the excitation light source 101 is ultraviolet or near-ultraviolet laser diode or ultraviolet or near-ultraviolet light emitting diode, in order to generate ultraviolet or near-ultraviolet excitation light.
[0053] As show in FIG. 2 , the wavelength conversion device 106 has a ring structure, including at least one wavelength conversion area. In the present embodiment, the wavelength conversion device 106 includes a red wavelength conversion area, a green wavelength conversion area, a blue wavelength conversion area and a yellow wavelength conversion area, which are provided in circumferential subsections of the ring structure. Different wavelength conversion materials are coated on the wavelength conversion areas respectively (for example, phosphor materials or nanomaterials). The wavelength conversion materials can convert the ultraviolet or near-ultraviolet excitation light that illuminate them into the converted light of corresponding color. Specifically, the red wavelength conversion area converts the ultraviolet or near-ultraviolet excitation light incident to it into red converted light, the green wavelength conversion area converts the ultraviolet or near-ultraviolet excitation light incident to it into green converted light, the blue wavelength conversion area converts the ultraviolet or near-ultraviolet excitation light incident to it into blue converted light, and the yellow wavelength conversion area converts the ultraviolet or near-ultraviolet excitation light incident to it into yellow converted light. In the present embodiment, a reflective substrate is provided under the wavelength conversion materials in order to reflect the converted light generated by the wavelength conversion materials, so that the exit direction of the converted light output from the wavelength conversion area is opposite to the incident direction of the excitation light incident to the wavelength conversion area.
[0054] As show in FIG. 2 , the color filter device 107 has a ring structure, coaxially fixed with the wavelength conversion device 106 , and disposed outside the ring of the wavelength conversion device 106 . In other embodiments, the color filter device 107 can also be disposed inside the ring of the wavelength conversion device 106 . The color filter device 107 includes at least one color filter area. In the present embodiment, the color filter device 107 includes a red filter area, a green filter area, a blue filter area and a yellow filter area, which are provided in circumferential subsections of the ring structure. Each color filter area corresponds to a wavelength conversion area of the wavelength conversion device 106 . In the present embodiment, the color filter area and the wavelength conversion area of the same color are set at a 180-degree angle from each other with respect to the center of the ring structures of the wavelength conversion device 106 and the color filter device 107 . The different color filter areas have different spectral responses, and filter the converted light of corresponding colors, in order to improve the color purity of the converted lights.
[0055] Of course, the color filter area and the wavelength conversion area of the same color can be set at angles with respect to the center of the ring structures of the wavelength conversion device 106 and the color filter device 107 .
[0056] As show in FIG. 1 , the driving device 108 is a rotary device which has a rotary shaft 1081 , for example, a rotary motor. The wavelength conversion device 106 and the color filter device 107 are coaxially fixed on the rotary shaft 1081 , and rotate synchronously under the driving of the rotary shaft 1081 .
[0057] In the working process of the light source system 100 shown in FIG. 1 , the ultraviolet or near-ultraviolet excitation light generated by the excitation light source 101 is transmitted through the dichroic mirror 102 , converged by the lens 103 , incident on the wavelength conversion device 106 , to form a light spot 101 A on the wavelength conversion device 106 as shown in FIG. 2 . The wavelength conversion device 106 and the color filter device 107 rotate synchronously under the driving of the driving device 108 , so that the wavelength conversion areas of the wavelength conversion device 106 and the color filter areas of the color filter device 107 can rotate synchronously. When the wavelength conversion device 106 and the color filter device 107 rotate, the wavelength conversion areas of the wavelength conversion device 106 are disposed in the propagation path of the ultraviolet or near-ultraviolet excitation light generated by the excitation light source 101 sequentially and periodically, so that the ultraviolet or near-ultraviolet excitation light can be converted into the converted light of different colors sequentially by the respective wavelength conversion areas. The converted lights of different colors are further reflected by the wavelength conversion areas respectively, guided by the first optical assembly which is composed of lenses 103 and 105 , dichroic mirror 102 , and reflecting mirror 104 , then incident on the light filer device 107 and form a light spot 101 B as shown in FIG. 2 .
[0058] In the first optical assembly, the lenses 103 and 105 are used for collecting and condensing the converted light respectively, so that the divergence angle of the converted light can be decreased. The dichroic mirror 102 and the reflecting mirror 104 are used for reflecting the converted light, so that the propagation direction of the converted light can be changed. In the present embodiment, the dichroic mirror 102 and the reflecting mirror 104 are set at a 90-degree angle to each other and 45-degree angle to the incident direction of the converted light. In the present embodiment, because of the reflection of the dichroic mirror 102 and the reflecting mirror 104 , the propagation direction of the converted light is shifted by a predetermined distance and inverted by 180-degree angle, and the light spot 101 A is set at 180-degree angle to the light spot 101 B with respect to the center of the ring structures of the wavelength conversion device 106 and the color filter device 107 .
[0059] In this case, the wavelength conversion device 106 is fixed with respect to the color filter device 107 , and the wavelength conversion areas of the wavelength conversion device 106 and the color filter areas of the color filter device 107 with the same colors are set at 180-degree angle from each other with respect to the center of the ring structures of the wavelength conversion device 106 and the color filter device 107 and rotate synchronously, so that the converted light of different colors generated by the wavelength conversion areas of the wavelength conversion device 106 are incident on the color filter areas of the color filter device 107 with the same colors after they pass through the dichroic mirror 102 and the reflecting mirror 104 , and the color purity is improved by the color filter area with the same color filtering the light. After filtering by the color filter area of the color filter device 107 , the converted light then is incident on the light homogenization device 109 to be made uniform.
[0060] In the light source system 100 of the present embodiment, the wavelength conversion device 106 and the color filter device 107 are fixed with respect to each other and driven synchronously by the same driving device. At the same time, the wavelength conversion area and the color filter area of the same color are synchronized by the first optical assembly. It has the advantages that: the structure is simple, it is easy to implement and the synchronization effect is excellent. In addition, each element of the first optical assembly is stationary with respect to the excitation light source, and do not rotate with the rotation of the wavelength conversion device 106 and the color filter device 107 , so the optical stability is improved.
[0061] Further, since the converted light generated through wavelength conversion generally has an approximately Lambertian distribution, if the converted light is directly incident on the color filter area, the incident angle will be distributed in the range of 0 degree to 90 degrees. However, the transmittance of the color filter area will shift with the increase of the incident angle, so in the present embodiment, the first optical assembly further includes a light convergence device (for example, a lens 105 ) to converge the converted light, which can decrease the incident angle of the converted light incidence on the color filter area and further improve the color filter effect. In a preferred embodiment, by adjusting the first optical assembly, the energy of the converted light that is incident on the light filter 107 with incident angles less than or equal to 60 degrees can be more than 90% of the total energy of the converted light. In the present embodiment, the dichroic mirror 102 and the reflecting mirror 104 can be replaced by other forms of planar reflecting device, and the lenses 103 and 105 can be replaced by other forms of optical devices. For example, the lens 105 may be replaced by various forms of light convergence devices like a solid or hollow tapered light guide, a lens or lens group, a hollow or solid composite light condenser, or a curved reflecting mirror, etc.
[0062] In addition, in the present embodiment, the wavelength conversion areas of the wavelength conversion device 106 can be a combination of one or more of the red wavelength conversion area, the green wavelength conversion area, the blue wavelength conversion area and the yellow wavelength conversion area, and the excitation light source can be another suitable light source. Alternatively, those skilled in the art can select the wavelength conversion area and the excitation light source with other colors as desired. In this case, the color filter areas of the color filter device 107 are configured according to the colors of the converted light generated by the wavelength conversion areas of the wavelength conversion device 106 , and the present invention shall not be limited to any specific arrangement.
[0063] Referring to in FIG. 3 and FIG. 4 , FIG. 3 is a schematic structural view of the second embodiment of the light source system of the present invention, and FIG. 4 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 3 . The light source system 200 of the present embodiment and the light source system 100 as shown in FIG. 1 and FIG. 2 differ in that: the excitation light source 201 is a blue laser or blue light-emitting diode in order to generate a blue excitation light. As show in FIG. 4 , in the present embodiment, besides of a red wavelength conversion area, a yellow wavelength conversion area and a green wavelength conversion area, the wavelength conversion device 206 further includes a blue light transmission area. The color filter device 207 includes a red color filter area, a yellow color filter area and a green color filter area. In the present embodiment, the area of the color filter device 207 which is corresponding to the blue light transmission area of the wavelength conversion device 206 is not required to have a particular optical property, and it can be provided as a counterweight balance area for rotation balance, so it should have the same or similar weight as the other color filter areas. In the present embodiment, the wavelength conversion device 206 and the color filter device 207 rotate synchronously under the driving of the driving device 208 , so that the wavelength conversion areas and the blue light transmission area of the wavelength conversion device 206 are sequentially and periodically disposed in the propagation path of the blue excitation light generated by the excitation light source 201 . The wavelength conversion areas convert the blue excitation light incident on them into the converted light of corresponding colors and reflect them, and the blue light transmission area transmits the blue excitation light incident on it. The blue light transmission area can be provided with appropriate scattering materials to destroy the collimation of the blue excitation light. The converted light reflected by the wavelength conversion device 206 is guided by the first optical assembly comprised of lenses 203 and 205 , dichroic mirror 202 and reflecting mirror 204 and incident on the color filter area of corresponding color on the color filter device 207 , so that it is filtered by the color filter area to improve its color purity. The blue excitation light transmitted by the wavelength conversion device 206 is guided by the second optical assembly comprised of lenses 210 and 213 , reflecting mirror 211 and dichroic mirror 212 , and is combined with the converted light filtered by the color filter device 207 into one light beam, which is incident on the light homogenization device 209 to be made uniform.
[0064] Of the second optical assembly, the lenses 210 and 213 are used for collecting and converging the blue excitation light transmitted by the wavelength conversion device 206 , and the reflecting mirror 211 and the dichroic mirror 212 are used to reflect the blue excitation light transmitted by the wavelength conversion device 206 to change its propagation path. In the present embodiment, the reflecting mirror 211 and the dichroic mirror 212 are arranged in parallel with each other and they are set at 45 degrees to the incident direction of the blue excitation light so that the propagation direction of the blue excitation light is shifted by a predetermined distance but its propagation direction remains the same.
[0065] In the present embodiment, the blue excitation light generated by the excitation light source 201 is directly outputted as the blue light through transmission. In the present embodiment, the reflecting mirror 211 and the dichroic mirror 212 can be replaced by other forms of planar reflecting devices, and the lenses 210 and 213 can be replaced by other forms of optical devices. In addition, the above-described structure is also applicable to the light source system in which excitation light sources of other colors are used.
[0066] Referring to FIG. 5 and FIG. 6 , FIG. 5 is a schematic structural view of the light source system according to the third embodiment of the present invention, FIG. 6 is a front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 5 . The light source system 300 of the present embodiment and the light source system 200 shown in FIG. 3 and FIG. 4 differ in that: the light source 300 further includes. in addition to the excitation light source 301 , a red illumination light source 315 (for example, a red laser or a red light emitting diode) in order to generate a red illumination light. The red illumination light source 315 and the excitation light source 301 are respectively provided on the opposite sides of the wavelength conversion device 306 and the color filter device 307 . The red illumination light generated by the red illumination light source 315 passes through the lens 314 , the dichroic mirror 311 , the lens 310 to be incident on the wavelength conversion device 306 ; its incident direction is opposite to that of the excitation light generated by the excitation light source 301 .
[0067] In the present embodiment, the wavelength conversion device 306 includes a red light transmission area, a yellow wavelength conversion area, a green wavelength conversion area and a blue light transmission area. The color filter device 307 includes a red light transmission area, a yellow color filter area, a green color filter area and a counterweight balance area. In the present embodiment, under the driving of the driving device 308 , the wavelength conversion device 306 and the color filter device 307 rotate synchronously, so that the wavelength conversion areas, the red light transmission area and the blue light transmission area of the wavelength conversion device 306 are disposed in the propagation path of the blue excitation light generated by the excitation light source 301 and the red illumination light generated by the red illumination light source 315 sequentially and periodically. The various wavelength conversion areas convert the blue excitation light incident on them into the converted light of corresponding color and reflect it, the blue light transmission area transmits the blue excitation light incident on it, and the red light transmission area transmits the red illumination light incident on it. The blue light transmission area and the red light transmission area can be provided with appropriate scattering materials to destroy the collimation of the blue excitation light and the red illumination light. The converted light reflected by the wavelength conversion device 306 is guided by the first optical assembly comprised of lenses 303 and 305 , dichroic mirror 302 and reflecting mirror 304 and incident on the color filter area of corresponding color on the color filter device 307 , so that it is filtered by the color filter area to improve its color purity. The red illumination light transmitted by the wavelength conversion device 306 is guided by the first optical assembly comprised of lens 303 and 305 , dichroic mirror 302 and reflecting mirror 304 and incident to the red light transmission area of the color filter device 307 along the same propagation path of the converted light, then transmitted by the red light transmission area. The blue excitation light transmitted by the wavelength conversion device 306 is guided by the second optical assembly comprised of lenses 310 and 313 , dichroic mirrors 311 and 312 , and combined with the converted light filtered by the color filter device 307 and the red illumination light transmitted by the color filter device 307 into one light beam, which is incident on the light homogenization device 309 to be made uniform.
[0068] In a preferred embodiment, in order to ensure that the light homogenization device 309 receives only one color light at any time, the rotation position of the wavelength conversion device 306 is detected, and a synchronization signal is generated based on the detection. The excitation light source 301 and the red illumination light source 315 are turned on and off in a time-division manner according to the synchronization signal. Specifically, the red illumination light source 315 is turned on only when the red light transmission area is in the propagation path of the red illumination light generated by the red illumination light source 315 , and is turned off when the yellow wavelength conversion area, the green wavelength conversion area and the blue light transmission area are in the propagation path of the red illumination light. The excitation light source 301 is turned on only when the yellow wavelength conversion area, the green wavelength conversion area and the blue light transmission area are in the propagation path of the blue excitation light generated by the blue excitation light source, and is turned off when the red light transmission area is in the propagation path of the blue excitation light. In addition, in another preferred embodiment, a dichroic filter which transmits the red illumination light and reflects the blue excitation light can be provided in the red light transmission area, a reflecting mirror which reflects the red illumination light can be provided for the yellow wavelength conversion area and the green wavelength conversion area on the side facing the red illumination light source 315 , and a dichroic filter that transmits the blue excitation light and reflects the red illumination light can be provided in the blue light transmission area.
[0069] In the present embodiment, the red light outputted from the light source system 300 is supplied directly by the red illumination light source 315 , which can avoid the problem of low conversion efficiency of the red wavelength conversion material. Of course, when it needs to improve the color purity, the red light transmission area can be replaced by a red color filter area. In the present embodiment, those skilled in the art can use other illumination light source to generate the illumination light of other colors.
[0070] Referring to FIG. 7 , FIG. 7 is a schematic structural view of the light source system according to the fourth embodiment of the present invention. The light source system 400 of the present embodiment and the light source system 300 shown in FIG. 5 and FIG. 6 differ in that: the excitation light source 401 of the present embodiment is an ultraviolet or blue excitation light source. At the same time, the wavelength conversion device 406 in the present embodiment is provided with a yellow wavelength conversion area, a green wavelength conversion area and a red light transmission area. So the excitation light source 401 is only used to excite the yellow wavelength conversion area and the green wavelength conversion area to generate yellow converted light and green converted light. The light source system 400 in the present embodiment further includes a blue illumination light source 416 in addition to the excitation light source 401 and the red illumination light source 415 . The blue illumination light generated by the blue illumination light source 416 passes through the second optical assembly comprised of lenses 417 and 418 and dichroic mirror 419 , is combined with the converted light filtered by the color filter device 407 and the red illumination light transmitted or filtered by the color filter device 407 into one light beam, which is incident on the light homogenization device 409 to be made uniform. In the present embodiment, the excitation light source 401 , the red illumination light source 415 and the blue illumination light source 416 can also be turned on and off in a time-division manner similar to the third embodiment.
[0071] In the present embodiment, the red light outputted from the light source system 400 is supplied directly by the red illumination light source 415 and the blue light outputted from the light source system 400 is supplied directly by the blue illumination light source 416 , which can avoid the problem of low conversion efficiency of the wavelength conversion materials, and is more suitable for the display field.
[0072] Referring to FIG. 8 , FIG. 8 is a schematic structural view of the light source system according to the fifth embodiment of the present invention. The light source system 500 of the present embodiment and the light source system 100 shown in FIG. 1 and FIG. 2 differ in that: the wavelength conversion device 506 converts the excitation light generated by the excitation light source 501 into the converted light and transmits it. The converted light transmitted by the wavelength conversion device 506 is guided by the first optical assembly comprised of lenses 503 and 505 and reflecting mirror 502 and 504 and incident on the color filter area of the same color on the color filter device 507 . After filtering by the color filter area it is incident on the light homogenization device 509 .
[0073] In addition, the excitation light source 501 can also be a blue light source. A light transmission area can be further provided on the wavelength conversion device 506 . The light transmission area is provided in the propagation path of the excitation light generated by the excitation light source 501 periodically and transmits it. After being transmitted by the light transmission area, the excitation light passes through the first optical assembly comprised of lenses 503 and 505 and reflecting mirror 502 and 504 , and is guided to another light transmission area or color filter area on the color filter device 507 along the same propagation path as the converted light, to be is transmitted or filtered.
[0074] Referring to FIG. 9 , FIG. 9 is a schematic structural view of the light source system according to the sixth embodiment of the present invention. The light source system 600 of the present embodiment and the light source system 500 shown in FIG. 8 differ in that: the light source system 600 of the present embodiment further includes, in addition to the excitation light source 601 , a red illumination light source 615 in order to generate a red illumination light. The red illumination light source 615 and the excitation light source 601 are provided on the same side of the wavelength conversion device 606 and the color filter device 607 . The red illumination light generated by the red light illumination light source 615 is reflected by the dichroic mirror 613 , converged by the lens 611 , then incident on the wavelength conversion device 606 along the same direction as the excitation light generated by the excitation light source 601 . The excitation light generated by the excitation light source 601 is converted into the converted light by the wavelength conversion area of the wavelength conversion device 606 , and is transmitted by the wavelength conversion device 606 . The red illumination light generated by the red illumination light source 615 is transmitted directly by the red light transmission area of the wavelength conversion device 606 . The converted light transmitted by the wavelength conversion device 606 and the red illumination light is guided by the first optical assembly comprised of reflecting mirror 602 and 604 and lenses 603 and 605 , and incident on the color filter area and the red light transmission area of the color filter device 607 . The converted light filtered by the color filter area and the red illumination light transmitted by the red light transmission area are further incident on the light homogenization device 609 . In addition, the red light transmission area can be replaced by a red color filter area. In addition, the excitation light source 601 and the red illumination light source 615 in the present embodiment can also be turned on and off in a time-division manner similar to the third embodiment.
[0075] Referring to FIG. 10 , FIG. 10 is a schematic structural view of the light source system according to the seventh embodiment of the present invention. The light source system 700 of the present embodiment and the light source system 600 shown in FIG. 9 differ in that: the light source system 700 of the present embodiment further includes a blue illumination light source 716 in addition to the excitation light source 701 and the red illumination light source 715 . The blue illumination light generated by the blue illumination light source 716 passes through the second optical assembly comprised of lens 717 and dichroic mirror 718 , and is combined with the converted light filtered by the color filter device 707 and the red illumination light filtered or transmitted by the color filter device 707 into one light beam, which is incident on the light homogenization device 709 to be made uniform. In the present embodiment, the excitation light source 701 , the red illumination light source 715 and the blue illumination light source 716 can be turned on and off in a time-division manner similar to the third embodiment.
[0076] Referring to FIG. 11 , FIG. 11 is a schematic structural view of the light source system according to the eighth embodiment of the present invention. The light source system 800 of the present embodiment and the light source system 100 shown in FIG. 1 and FIG. 2 differ in that: in the present embodiment the excitation light generated by the excitation light source 801 is converged by the fly eye lenses 803 and 804 and converging lens 805 , then incident on the wavelength conversion device 806 through the light entrance port on the reflecting device 802 . The converted light reflected by the wavelength conversion device 806 is then reflected by the reflecting device 802 and incident on the color filter device 807 . The reflecting device 802 is semi-ellipsoidal or hemispherical and its reflecting surface faces inside. The converted light filtered by the color filter device 807 is further incident to the tapered light guide rod 809 . When the reflecting device 802 is semi-ellipsoidal, the converted light from the vicinity of one focus point of the reflecting device 802 can be reflected to the vicinity of the other focus point; when the reflecting device 802 is hemispherical, if two points are located near the center of the sphere and symmetrical with respect to the center of the sphere, then the reflecting device 802 can approximately reflect the converted light from one symmetrical point to the other. In addition, in other embodiments, the reflecting device 802 can be provided without a light entrance port, and the excitation light source 801 and the reflecting device 802 are provided on the opposite sides of the wavelength conversion device 806 . The excitation light generated by the excitation light source 801 is incident on the wavelength conversion device 806 and the converted light is then transmitted through the wavelength conversion device to the reflecting device 802 .
[0077] It's worth noting that, under the reflection of the reflecting device 802 , the light spot formed by the excitation light generated by the excitation light source 801 incident on the wavelength conversion device 806 and the light spot formed by the converted light incident on the color filter device 807 are located at 0 degree from each other with respect to the center of the ring structure of the wavelength conversion device 806 and the color filter device 807 ; thus, the wavelength conversion area and color filter area of the same color on the wavelength conversion device 806 and color filter device 807 also need to be set at 0 degree from each other with respect to the center of the ring structure of the wavelength conversion device 806 and the color filter device 807 .
[0078] Of course, in other embodiments, through appropriate optical arrangement, the light spot formed by the excitation light incident to the wavelength conversion device 806 and the light spot formed by the converted light incident to the color filter device 807 can be set at any angle from each other with respect to the center of the ring structure of the wavelength conversion device 806 and the color filter device 807 , so the wavelength conversion area and the color filter area of the same color on the wavelength conversion device 806 and color filter device 807 can be set at any angle with respect to the center of the ring structure of the wavelength conversion device 806 and the color filter device 807 .
[0079] Referring to FIG. 12 , FIG. 12 is a schematic structural view of the light source system according to the ninth embodiment of the present invention. The light source system 900 of the present embodiment and the light source system 800 shown in FIG. 11 differ in that: the wavelength conversion device 906 and the color filter device 907 are fixed coaxially by the bracket 908 , and are spaced apart along the axial direction. A tapered light guide rod 909 is provided between the wavelength conversion device 906 and the color filter device 907 . The excitation light generated by the excitation light source 901 is converged by the fly eye lens 903 and 904 and the converging lens 905 , then incident on the wavelength conversion device 906 through the light entrance port on the reflecting device 902 . The converted light reflected by the wavelength conversion device 906 is incident on the reflecting device 902 and reflected. The converted light reflected by the reflecting device 902 is first incident to the light guide rod 909 . The light guide rod 909 collects the converted light in order to reduce the divergence angle of the converted light. After guided by the light guide rod 909 , the converted light is incident on the color filter device 907 , so that the incident angle on the color filter device 907 is smaller, and the filtering effect is improved. In the present embodiment, the light guide rod 909 can also be replaced by other optical device that is able to achieve the functions described above. Further, in the present embodiment, if the wavelength conversion device 906 is a transmission type, the reflecting device 902 can be omitted, and then the converted light is transmitted by the wavelength conversion device 906 and incident on the light guide rod 909 directly.
[0080] As described above, in the embodiment shown in FIG. 11 and FIG. 12 , an illumination light source can be further provided in addition to the excitation light sources 801 and 901 , such as a red illumination light source or a blue illumination light source.
[0081] Referring to FIG. 13 , FIG. 13 is a schematic structural view of the light source system according to the tenth embodiment of the present invention. The light source system 1000 of the present embodiment and the light source system 100 shown in FIG. 1 and FIG. 2 differ in that: the wavelength conversion device 1006 of the present embodiment is a cylindrical structure, and the wavelength conversion areas are provided on the outside surface of the sidewall of the cylindrical structure. The color filter device 1007 has a ring structure. The wavelength conversion device 1006 and the color filter device 1007 are further coaxially fixed on the rotating shaft of the driving device 1008 , and rotate coaxially and synchronously under the driving of the driving device 1008 .
[0082] In the working process of the light source system 1000 according to the present embodiment, the excitation light generated by the excitation light source 1001 is transmitted by the dichroic mirror 1002 , converged by the lens 1003 , then incident on the outside surface of the sidewall of the wavelength conversion device 1006 . The wavelength conversion areas on the outside surface of the sidewall of the wavelength conversion device 1006 convert the excitation light into the converted light and reflect it. After reflected by the wavelength conversion device 1006 , the converted light is guided by the first optical assembly which is comprised of lens 1003 and 1004 and the dichroic mirror 1002 , and incident on the color filter device 1007 . The color filter areas on the color filter device 1007 are provided outside of the cylindrical structure of the wavelength conversion device 1006 , so that the converted light can be incident on them and filtered to improve the color purity. After filtered by the color filter areas of the color filter device 1007 , the converted light is further incident on the light homogenization device 1009 to be made uniform. In other embodiments, the wavelength conversion device 1006 can also transmit the converted light to the color filter device 1007 .
[0083] Referring to FIG. 14 , FIG. 14 is a schematic structural view of the light source system according to the eleventh embodiment of the present invention. The light source system 1100 of the present embodiment and the light source system 100 shown in FIG. 1 and FIG. 2 differ in that: in the present embodiment the wavelength conversion device 1106 and the color filter device 1107 are two cylindrical structures which are fixed coaxially and nested within each other, and the wavelength conversion areas and the first color filter areas are provided on the sidewalls of the two cylindrical structures respectively. The color filter device 1107 is located outside of the wavelength conversion device 1106 . The wavelength conversion device 1106 and the color filter device 1107 are further coaxially fixed on the rotating shaft of the driving device 1108 , and rotate coaxially and synchronously under the driving of the driving device 1108 .
[0084] In the working process of the light source system 1100 according to the present embodiment, the excitation light generated by the excitation light source 1101 is reflected by the reflecting mirror 1102 , converged by the lens 1103 , then incident on the wavelength conversion device 1106 . The wavelength conversion areas of the wavelength conversion device 1106 convert the excitation light into the converted light and transmit it. After being transmitted by the wavelength conversion device 1106 , the converted light is guided by the first optical assembly comprised of lens 1104 and incident on the color filter device 1107 . The color filter areas of the color filter device 1107 filter the converted light to improve its color purity. After filtering by the color filter areas of the color filter device 1107 , the converted light is further incident on the light homogenization device 1109 to be made uniform.
[0085] Referring to in FIG. 15 and FIG. 16 , FIG. 15 is a schematic structural view of the light source system according to the twelfth embodiment of the present invention, and FIG. 16 is the front view of the wavelength conversion device and the color filter device of the light source system shown in FIG. 15 . The light source system 1200 of the present embodiment and the light source system 200 shown in FIG. 3 and FIG. 4 differ in that: in the present embodiment, the wavelength conversion device 1206 and the color filter device 1207 are two strip structures adjoined side by side, where the wavelength conversion areas and the first color filter areas are arranged side by side in the two strip structures. In the present embodiment, the wavelength conversion device 1206 includes a red wavelength conversion area, a green wavelength conversion area, a blue light transmission area and a yellow wavelength conversion area which are arranged side by side sequentially from top to bottom. The color filter device 1207 includes a red color filter area, a green color filter area, a blank area and a yellow color filter area which are arranged side by side sequentially from top to bottom.
[0086] The wavelength conversion device 1206 and the color filter device 1207 move in an oscillating linear translational motion under the driving of a suitable driving device (e.g. a linear motor), so that the red wavelength conversion area, the green wavelength conversion area, the blue light transmission area and the yellow wavelength conversion area of the wavelength conversion device 1206 are periodically provided in the propagation path of the blue excitation light generated by the excitation light source 1201 . The wavelength conversion areas convert the blue excitation light incident on them into converted light of corresponding colors and reflect them, and the blue light transmission area transmits the blue excitation light incident on it. The blue light transmission area can be provided with an appropriate scattering material to destroy the collimation of the blue excitation light. The converted light reflected by the wavelength conversion device 1206 is guided by the first optical assembly comprised of lenses 1203 and 1205 , dichroic mirror 1202 and reflecting mirror 1204 , then incident on the color filter area of corresponding color on the color filter device 1207 , so that it is filtered by the color filter area to improve its color purity. The blue excitation light transmitted by the wavelength conversion device 1206 is guided by the second optical assembly comprised of lens 1210 and 1213 , reflecting mirror 1211 and dichroic mirror 1212 , and combined with the converted light filtered by the color filter device 1207 into one beam of light, which is incident to the light homogenization device 1209 to be made uniform. In the present embodiment, the structure of the wavelength conversion device 1206 and the color filter device 1207 can also be applied to the other embodiments described above, which is not described.
[0087] The present invention further provides a light source assembly constituted by the wavelength conversion device and the color filter device which are described in the above embodiments.
[0088] In summary, in the light source system and the light source assembly of the present invention, the color filter device and the wavelength conversion device are fixed with respect to each other, and they are driven by a same driving device, which can bring the advantages that: the structure is simple, it is easy to implement, and the synchronization effect is excellent.
[0089] The invention is not limited to the above described embodiments. Various modification and variations can be made in the light source device and system of the present invention based on the above descriptions. Thus, it is intended that the present invention cover modifications and variations that come within the scope of the appended claims and their equivalents, as well as the direct or indirect application of the embodiment in other related technical fields.
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Provided is a projection system, a light source system, and a light source assembly. The light source system ( 100 ) comprises an excitation light source ( 101 ), a wavelength conversion device ( 106 ), a color filtering device ( 107 ), a drive device ( 108 ), and a first optical assembly. The wavelength conversion device ( 106 ) comprises at least one wavelength conversion region. The optical filtering device ( 107 ) is fixed face-to-face with the wavelength conversion device ( 106 ), and comprises at least a first optical filtering region. The drive device ( 108 ) drives the wavelength conversion device ( 106 ) and the optical filtering device ( 107 ), allowing the wavelength conversion region and the first optical filtering region to act synchronously, and the wavelength conversion region is periodically set on the propagation path of the excitation light, thereby converting the excitation light wavelength into converted light. The first optical assembly allows the converted light to be incident on the first optical filtering region. The first optical filtering region filters the converted light, so as to enhance the color purity of the converted light. The light source system is simple in structure, easy to implement, and highly synchronous.
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TECHNICAL FIELD
Embodiments of the present disclosure pertain to medical injection systems and more particularly to the pumps employed therein.
BACKGROUND
FIG. 1 is a perspective view of an exemplary medical injection system 100 (the ACIST CVO system) for delivering a contrast agent into a patient's vascular system for medical imaging. FIG. 1 illustrates a first fluid reservoir 132 for supplying a syringe-type positive displacement pump of a pressurizing unit 130 , via a fill tubing line 27 -F, and an injection tubing line 27 -I coupled to unit 130 for injection of, for example, a radiopaque contrast agent, into a patient's vascular system via an inserted catheter (not shown), for example, coupled to a patient tubing line 122 at a connector 120 thereof. FIG. 1 further illustrates a second fluid reservoir 138 from which a diluent, such as saline, is drawn by a peristaltic pump 106 through yet another tubing line 128 that feeds into tubing line 122 . A manifold valve 124 and associated sensor 114 control the flow of fluids into tubing line 122 , from pressurizing unit 130 and from tubing line 128 .
SUMMARY
According to preferred embodiments and methods of the present disclosure, a medical injection system employs a single pump for the injection of multiple fluids, rather than employing a pump for each type of fluid, for example, like the prior art system described above. Embodiments of pumps disclosed herein preferably include a disposable pump cartridge configured to be contained within a hull of a medical injection system, wherein the hull may be formed when a pressure plate member is closed against a base plate; and, when the pressure plate member is opened with respect to the base plate, the disposable pump cartridge may be removed and replaced.
The disposable pump cartridge preferably includes a shell and a piston, wherein the piston is contained within an inner surface of the shell and includes a bore that is adapted to be operably engaged by a drive member and a fixed gear of the injection system; each of the fixed gear and the drive member are inserted through a corresponding opening formed through the shell, when the cartridge is contained within the hull. The drive member is preferably coupled to a free end of a motor drive shaft, which extends through the base plate, and the fixed gear is preferably mounted to the pressure plate member. According to some preferred embodiments, the disposable pump cartridge is configured to function as a Limaçon-to-Limaçon machine, wherein sliding and rotational motion of the piston is driven by an eccentric drive member of the injection system to create expanding and contracting cavities during pump operation. The piston further includes a pressure seal that extends thereover and is configured to be in sliding and sealing engagement with the inner surface of the shell to seal the expanding and contracting cavities from one another within the shell, and to seal the cavities from the first and second openings of the shell. Fill and injection ports of the shell are preferably located at opposite ends of a long axis of the piston, when the piston is in a position where the contracting cavity is at a maximum volume and the expanding cavity is at a minimum volume.
According to some embodiments, each of the fill and injection ports includes a channel and one or more apertures formed in the inner surface of a perimeter wall of the shell, wherein each channel extends from the corresponding one or more apertures to a corresponding opening in outside the shell. When the disposable cartridge is contained in the hull of the system, the fill and injection ports preferably extend through openings in the pressure plate member, and each has a fitting outside the hull for coupling to a fill and an injection tubing line, respectively, of the system.
BRIEF DESCRIPTION OF THE DRAWINGS
The following drawings are illustrative of particular methods and embodiments of the present disclosure and, therefore, do not limit the scope. The drawings are not to scale (unless so stated) and are intended for use in conjunction with the explanations in the following detailed description. Methods and embodiments will hereinafter be described in conjunction with the appended drawings, wherein like numerals denote like elements, and:
FIG. 1 is a perspective view of an exemplary prior art medical injection system;
FIG. 2A is a schematic depicting a medical injection system, according to some embodiments of the present disclosure;
FIG. 2B is an exploded perspective view of a disposable pump cartridge that may be employed by the system depicted in FIG. 2A , according to some embodiments;
FIG. 2C is a perspective view of a pressure seal that may be incorporated in the disposable pump cartridge of FIG. 2B , according to some embodiments;
FIG. 2D is an exploded perspective view of a portion of a medical injection system, according to some embodiments;
FIG. 3A is a cut-away plan view of an interior of a disposable pump cartridge, according to some embodiments;
FIGS. 3B-C are schematics depicting exemplary expanding and contracting cavities of the pump cartridge;
FIG. 4A is a cross-section view through section line A-A of FIG. 3A , when the disposable pump cartridge is assembled into a hull of the system of FIG. 4A , according to some embodiments;
FIG. 4B is a cross-section view through section line B-B of FIG. 3A , according to some embodiments; and
FIG. 4C is an enlarged detail of a portion of a pump cartridge, according to some embodiments.
DETAILED DESCRIPTION
The following detailed description is exemplary in nature and is not intended to limit the scope, applicability, or configuration of the disclosure in any way. Rather, the following description provides practical illustrations for implementing exemplary methods and embodiments. Examples of constructions, materials and dimensions are provided for selected elements, and all other elements employ that which is known to those skilled in the art. Those skilled in the art will recognize that many of the examples provided have suitable alternatives that can be utilized.
FIG. 2A is a schematic depicting a medical injection system 200 , according to some embodiments. FIG. 2A illustrates system 200 including a single pump 230 , which is coupled between a fill tubing line 217 F and an injection tubing line 217 I, and which is formed by a hull 25 and a disposable pump cartridge 23 (shown with dashed lines) contained therein. Hull 25 may be formed by a base plate 42 and a pressure plate member 41 that may be opened and closed with respect to base plate 42 to remove and install disposable pump cartridges 23 . FIG. 2A further illustrates system 200 including a plurality of fluid reservoirs, for example, two types of contrast agent reservoirs 232 A, 232 B and a saline reservoir 238 , connected to fill tubing line 217 F via a manifold assembly 224 (i.e. an inlet stop cock valve) that couples each reservoir 232 A, 232 B, 238 to pump 230 . According to the illustrated embodiment, manifold assembly 224 is controllable to select one of reservoirs 232 A, 232 B, 238 for filling pump 230 and, once primed, pump 230 is operable simultaneously fill and inject fluid from the selected reservoir.
FIG. 2A shows each of fill tubing line 217 F and injection tubing line 217 I preferably extending over a limited length, for example, less than approximately 25 mm, and injection tubing line 217 I transitioning into a dual lumen line 227 I wherein a first lumen is dedicated to contrast agent and a second lumen to saline. Dual lumen line 227 I is shown coupled to injection line 217 I via a stop-cock valve 274 that can be switched back and forth between the lumens of line 227 I, depending on the type of fluid that is being pumped, saline or contrast agent, so as to prevent excessive waste of contrast agent. FIG. 2A further illustrates a y-connector 265 coupling dual lumen line 227 I to a patient line 269 . According to the illustrated embodiment, y-connector 265 preferably includes a check valve to prevent backflow into dual lumen line 227 I. Furthermore, when a pressure transducer is incorporated in line 269 for patient blood pressure monitoring, the check valve helps to improve hemodynamic signal quality by isolating line 269 from line 227 I.
FIG. 2B is an exploded perspective view of disposable pump cartridge 23 , according to some embodiments. FIG. 2B illustrates cartridge 23 including a shell that has a first sidewall SW 1 , a second sidewall SW 2 and a perimeter wall PW, and a piston 28 configured to be contained within the shell and moved therein to form two dynamically expanding and contracting cavities for drawing in and injecting out, respectively, fluid from any of the aforementioned fluid reservoirs 232 A, 232 B, 238 . With further reference to FIG. 2B , when the shell contains piston 28 , a first side 281 of piston 28 extends adjacent to an inner surface 211 of first sidewall SW 1 , a second side 282 of piston 28 extends adjacent to an inner surface 221 of second sidewall SW 2 , and an outer perimeter edge 83 of piston 28 extends adjacent to an inner surface 251 of perimeter wall PW. Furthermore an inner perimeter edge of piston 28 , which forms a bore 810 through piston 28 , includes a first portion 811 , located in proximity to a first opening 201 formed through first sidewall SW 1 of shell, and a second portion 812 located in proximity to a second opening 202 formed through second sidewall SW 2 of shell. According to the illustrated embodiment, first opening 201 allows insertion therethrough of a fixed gear 340 ( FIGS. 2D, 4A ) to mate with first portion 812 of the inner perimeter edge of piston 28 , and second opening 202 allows insertion therethrough of a drive member 442 ( FIGS. 2D, 4A ) to mate with second portion 812 of the inner perimeter edge, for the operation of pump 230 , which is described below.
FIG. 2D is an exploded perspective view of a portion of pump 230 , wherein fixed gear 340 may be seen mounted on pressure plate member 41 , and drive member 442 , which is coupled to a free end of a motor drive shaft 441 , is illustrated with dashed lines on a side of base plate 42 that faces second opening 202 of the shell of pump cartridge 23 for the aforementioned engagement with piston 28 . It should be noted that suitable bearing supports, known to those skilled in the art of mechanical design, may be employed to support drive shaft 441 as it passes through base plate 41 and to support drive member 442 mounted on the free end of drive shaft 441 . With reference to FIGS. 2A and 2D , base plate 42 may be part of a housing 24 that contains the motor from which drive shaft 441 extends, and pressure plate member 41 is coupled to base plate 42 , for example, by a hinge and pull action toggle clamp or a pull action cam clamp to form hull 25 that contains pump cartridge 23 and holds pressure during pump operation, and to allow opening and closing of hull 25 for the replacement of disposable pump cartridge 23 , for example, after the completion of each imaging procedure. According to preferred embodiments, drive member 442 is a roller bearing mounted eccentric adapted for a toothless engagement with second portion 812 of the inner perimeter edge of piston 28 that facilitates alignment when disposable cartridge 23 is assembled into hull 25 .
According to an exemplary embodiment, hull 25 may be formed of stainless steel, while piston 28 and first and second sidewalls SW 1 , SW 2 and perimeter wall PW of the shell are preferably formed, for example by injection molding, from a polycarbonate material, such as APEC® 1745. Each wall of the shell may have a nominal thickness of between approximately 0.070 inch and approximately 0.080 inch, which is preferably uniform along both sidewalls SW 1 , SW 2 and perimeter wall PW, for example, to avoid sink discontinuities from forming during injection molding of the shell. According to the illustrated embodiment, second sidewall SW 2 of shell may be formed independently of first sidewall SW 1 and perimeter wall PW and then attached about a facing edge 27 of perimeter wall PW, for example by tongue-in-groove engagement and ultrasonic welding or adhesive bonding, wherein the adhesive may be a cyanoacrylate or a UV cure adhesive, or any suitable adhesive known in the art.
With further reference to FIG. 2B , piston 28 includes a pressure seal 288 formed thereover for sliding and sealing engagement with each of the aforementioned inner surfaces of the shell. FIG. 2C is a perspective view of pressure seal 288 separated from piston 28 . FIGS. 2B-C illustrate pressure seal 288 including a first seal ring portion SR 1 that extends about a perimeter of first side 281 of piston 28 , a second seal ring portion SR 2 that extends about a perimeter of second side 282 of piston 28 , and a pair of seal strip portions SS that extend between first and second seal ring portions SR 1 , SR 2 and along outer perimeter edge 83 of piston 28 opposite one another at either end of a long axis of piston 28 . The seal rings and strips of pressure seal 288 are preferably integrally over-molded onto the piston; and, according to an exemplary embodiment, are formed of 917CK silicone rubber (Minnesota Rubber & Plastics of Minneapolis, Minn.) having a hardness of 75+5 on a Shore A scale. According to the illustrated embodiment, pressure seal 288 engages with the inner surfaces of the shell to seal expanding and contracting cavities, which are created by the movement of piston 28 within the shell, from one another and from openings 201 , 202 .
According to some preferred embodiments, disposable pump cartridge 23 is configured to function as a Limaçon-to-Limaçon machine, wherein drive member 442 eccentrically engages with second portion 812 of the inner perimeter edge of piston 28 to cause a sliding and rotational motion thereof, which creates expanding and contracting cavities during pump operation. FIG. 3A is a cut-away plan view of an interior of disposable pump cartridge 23 in which fixed gear 340 is shown engaged with first portion 811 of the inner perimeter edge of the piston 28 ; and FIGS. 3B-C are schematics showing subsequent positions of piston 28 , relative to fixed gear 340 and the shell, as moved by drive member 442 —sliding per arrow S and rotating per arrow R ( FIG. 3A ), to create an expanding cavity E and a contracting cavity C.
With reference to FIG. 3A , a profile of inner surface 251 of perimeter wall PW of the shell conforms to a shape defined by a Limaçon curve in an X-axis, Y-axis coordinate system, wherein the Limaçon is traced by end points of a cord that extends along the X-axis, through the origin of the X-Y coordinate system (over a length equal to twice the length L), and is divided in half by the origin. The Limaçon is represented by the following Cartesian equations:
X=r ×sin(2θ)+ L ×cos(θ), and
Y=r−r ×cos(2θ)+ L ×sin(θ);
wherein r is a radius of a base circle having a perimeter along which a center point of the cord slides as the end points of the cord rotate about the center point of the cord to trace the Limaçon; r divided by L is less than or equal to 0.25; and θ extends from 0 to 2π. FIG. 3A further illustrates the long axis of piston 28 being approximately the length of the cord (2×L) and having a shape symmetrical across the cord, wherein the curvature of the shape on each side of the cord also conforms to the Limaçon represented by the above equations, but wherein θ extends from π to 2π. Such a Limaçon-to-Limaçon machine is further detailed by Ibrahim A. Sultan in Profiling Rotors for Limaçon - to - Limaçon Compression - Expansion Machines , Journal of Mechanical Design, July 2006, Volume 128, pp. 787-793, © 2006 by ASME, which is hereby incorporated by reference. With further reference to FIG. 3A , an injection port IP is located at one end of the long axis of piston 28 , and a fill port FP is located at the opposite end of the long axis of piston 28 , when piston 28 is at the illustrated dead center position.
With reference to FIG. 3B , piston 28 has been moved counter-clockwise from the dead center position, which is shown in FIG. 3A , to a position at which contracting cavity C is in fluid communication with injection port IP and is beginning to be compressed for injection of fluid, per arrow I, while expanding cavity E is in fluid communication with fill port FP and beginning to be enlarged to draw in fluid, per arrow F. FIG. 3C illustrates a subsequent position of piston 28 , having been moved through the position shown with dotted lines in FIG. 3B , at which contracting cavity C is approaching a minimum volume and expanding cavity E is approaching a maximum volume at which it becomes the contracting cavity C of FIG. 3A . The maximum volume of contracting cavity C may be between approximately 2 cubic centimeters and approximately 10 cubic centimeters, wherein a volume closer to 2 cubic centimeters may be preferred for less stress on the shell and piston 28 , and in order reduce a waste of fluid when switching from one type to another, for example, from a contrast agent 232 A or 232 B to saline 238 ( FIG. 2A ); yet, a volume closer to 10 cubic centimeters will allow the piston to move more slowly thereby reducing wear on pressure seal 288 and decreasing the possibility of fluid cavitation. It should be noted that the volume may be modified by changing the radius r and length L ( FIG. 3A ) and/or by modifying a height H of inner surface 251 of perimeter wall PW along with a corresponding increase in a thickness t of piston 28 ( FIG. 4C ).
Turning now to FIGS. 4A-B , which are cross-section views through section lines A-A and B-B, respectively, engagement of the parts of pump 230 may be seen. FIG. 4A illustrates pressure plate member 41 in a closed position with respect to base plate 42 after disposable pump cartridge 23 has been mounted on eccentric drive member 442 , by insertion of drive member 442 in through opening 202 of second sidewall SW 2 of the shell to engage with second portion 812 of the inner perimeter edge of piston 28 . When pressure plate member 41 is closed with respect to base plate 42 , fixed gear 340 passes through opening 201 of first sidewall SW 1 of the shell to engage with the toothed first portion 811 of the inner perimeter edge of piston 28 , wherein the engagement of gear 340 and first portion 811 keep piston 28 ‘on track’ to slide about radius r ( FIG. 3A ) as drive member 442 rotates piston 28 . FIGS. 4A-B further illustrate the engagement of first and second seal ring portions SR 1 , SR 2 of pressure seal 288 extending outward from piston 28 to engage with inner surfaces 211 , 221 of first and second shell sidewalls SW 1 , SW 2 . According to FIG. 4B , in some embodiments, each of seal rings SR 1 , SR 2 is seated in a groove formed at the intersection of the corresponding one of the first and second sides 281 , 282 of piston 28 with outer perimeter edge 83 of piston 28 , and a cross-section of each of seal rings SR 1 , SR 2 is preferably oval. The cross-section of seal strips SS may also be oval-shaped, and each may be seated in a corresponding groove extending along outer perimeter edge 83 between first and second sides 281 , 282 . According to some embodiments each of seal rings SR 1 , SR 2 and seal strips SS extends out from the corresponding groove to contact with corresponding inner surfaces of the shell with a standard compression of approximately 20%, and pressure seal 288 preferably forms the only interface between piston 28 and the inner surfaces of the shell. According to a preferred embodiment, wherein piston 28 is formed from the aforementioned polycarbonate and pressure seal 288 of the aforementioned silicone rubber, pressure seal 288 is directly bonded to piston 28 , for example, within the above-described grooves, during the process of over-molding seal 288 onto piston 28 .
FIG. 4A further illustrates injection port IP and fill port FP, according to some preferred embodiments, wherein each includes a channel 43 that extends from a corresponding one or more apertures 40 , preferably a plurality of apertures, formed in inner surface 251 ( FIG. 2B ) of perimeter wall PW, such that the above-described fluid communication between each port IP, FP and the corresponding cavity C, E is provided by the corresponding one or more apertures 40 . According to the illustrated embodiment, each channel 43 further extends through first sidewall SW 1 of the shell and through a corresponding opening formed through pressure plate member 41 . With further reference to FIG. 4A , a first fitting 431 is coupled to channel 43 of injection port IP and a second fitting 432 is coupled to channel 43 of fill port FP, wherein first fitting 431 is adapted to couple with injection tubing line 217 I and second fitting 432 with fill tubing line 217 F outside hull 25 ( FIG. 2A ). Fittings 431 , 432 are preferably different types to assist in the proper connection of injection tubing lines 217 F and 217 I.
FIG. 4C is an enlarged detail view of one of channels 43 and the corresponding plurality of apertures 40 , according to some embodiments, wherein each aperture has an oval shape with chamfered edges to prevent damage to seal strips SS as each end of the long axis of piston 28 moves past apertures 40 . Channel 43 of fill port FP is preferably larger than that of injection port IP, and, according to an exemplary embodiment, a diameter of channel 43 for fill port FP is approximately 8 millimeters and each of the corresponding plurality of apertures 40 is approximately 2 millimeters by 6 millimeters, while a diameter of channel 43 for injection port IP is approximately 3 millimeters and each of the corresponding plurality of apertures is approximately 1 millimeter by 2 millimeters.
In the foregoing detailed description, disclosure subject matter has been described with reference to specific embodiments. However, it may be appreciated that various modifications and changes can be made without departing from the scope of the invention as set forth in the appended claims.
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According to preferred embodiments and methods of the present disclosure, a medical injection system employs a single pump for the injection of multiple fluids, rather than employing a pump for each type of fluid, for example, like the prior art system described above. Embodiments of pumps disclosed herein preferably include a disposable pump cartridge configured to be contained within a hull of a medical injection system, wherein the hull may be formed when a pressure plate member is closed against a base plate; and, when the pressure plate member is opened with respect to the base plate, the disposable pump cartridge may be removed and replaced.
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FIELD OF THE INVENTION
[0001] The present invention relates to instant coffee and coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content wherein the carcinogenic and cytotoxic process components found in heat treated roasted foodstuffs especially such as coffee are minimized, and production method thereof.
BACKGROUND OF THE INVENTION
[0002] The method used in production of instant coffee in today's technology comprises a series of processes such as roasting of raw coffee beans, grinding, aroma separation, extraction, concentration and drying. During roasting of coffee beans, acrylamide and HMF are formed at varying concentrations depending on the intensity of the heat treatment that is applied. After the Swedish scientists (Tareke et al, 2002) determined presence of acrylamide, which is announced to be a potential carcinogen (International Agency for Research on Cancer, IARC, 1994), in heat treated foods; determination of the amount of acrylamide in various foods has gained importance. Taking into consideration the incidence of consumption of foods which contain a high concentration of acrylamide such as french fries, many bakery products and coffee, it is obviously necessary to reduce the amount of acrylamide in these foods. In addition to acrylamide, since HMF is also cytotoxic and mutagen, its amount should also be limited. Maximum limit specified for HMF is 40 ppm in honey and 20 ppm in fruit juices.
[0003] Studies are intensively carried out for reducing concentrations of acrylamide and HMF in various products. It has been concluded that reduction of heat treatment time and temperature (Surdyk et al., 2004; Taubert et al., 2004) and reduction of pH value (Jung et al., 2003; Rydberg et al., 2003) reduce formation of acrylamide. Use of asparaginase enzyme (Zyzak et al., 2003; Ciesarova et al., 2006) was also developed as another strategy. By using asparaginase, the asparagine amino acid playing a key role in acrylamide formation is converted to aspartic acid. There is a United States patent document numbered US20040081724 which discloses that roasted coffee beans having reduced amount of acrylamide can be obtained by using the said method.
[0004] United States patent document no. US20070178219, which is another patent document in the state of the art, discloses that acrylamide can be reduced by a method which eliminates asparagine by weakening the cell wall of asparagine-containing plants by microwave energy, ultrasonic energy, pressure force or an enzyme. The principle of this technique is the prevention of asparagine from entering into Maillard reaction. Asparagine is decomposed by asparaginase enzyme or a competitive medium is created to inhibit Maillard reaction of asparagine by using cysteine, lysine or glycine amino acids. It is disclosed that this method was tried for french fries and that it is also applicable for coffee beans.
[0005] In another related study conducted (Gökmen and Senyuva 2007a,b; Park et al., 2005), results are obtained demonstrating that divalent cations reduce acrylamide formation. Making use of this information, European patent document no. EP2160948 discloses that acrylamide formation is reduced by soaking chicory beans into solutions containing Ca 2+ and Mg 2+ before roasting.
[0006] In the Japanese patent document no. JP2007282537, superheated steam was used for roasting and it is mentioned that by means of this method while acrylamide content decreases, chlorogenic acid content increases.
[0007] In the International patent document no. WO2005094591, acrylamide content can also be reduced by 48% by fermenting the coffee beans with lactic acid bacteria before roasting. By means of this process, pH of the medium decreases and thus Maillard reaction slows down. When the coffee beans are roasted after fermentation, less color formation is observed.
[0008] In addition to all of these, in a research (Quarta and Anese, 2012) conducted, vacuum application for reducing furfural and HMF content in coffee is tried and it is determined that it is not very effective in reduction of HMF in soluble coffee. When coffee sample was hydrated before vacuum application, furfural content could be reduced by 100% and HMF content by 20%. However it is reported that serious losses occurred in the volatile smell and aroma components of coffee in this technique.
[0009] Upon consideration of practiced techniques today; firstly decreasing the heat treatment load was tried for reducing acrylamide and HMF, however this was not found to be very useful since it also reduced the benefits provided by heat treatment. Reducing the thermal load also reduces the rate of Maillard reaction and thus concentrations of Maillard reaction products, which are responsible for development of the taste and smell desired in the product. This is the most significant disadvantage of changing the heat treatment parameters.
[0010] Since asparagine amino acid in food plays a key role in production of acrylamide, asparagine removal is used as an alternative technique for limiting acrylamide amount. Asparagine in the food is converted into aspartic acid by using asparaginase enzyme and it is prevented from entering into Maillard reaction. This method is applied in production of biscuits and it is stated that it can be applied in foods, which include dough production in their process such as cakes, breads. However it is stated that its applicability in french fries is difficult. Additionally, when it is used in production of coffee beans with reduced asparagine and thus acrylamide content, since Maillard reaction is again limited, loss of taste, smell and aroma occurs in instant coffee production.
[0011] Strategy of reducing acrylamide by immersing the raw material in solutions containing divalent cations (Ca 2+ etc.) may cause taste defects when used in production of instant coffee. Additionally, cations such as Ca 2+ , Mg 2+ promote glucose dehydration, and thus accelerate HMF formation.
[0012] It is observed that generally mitigation strategies for acrylamide and HMF content in foods is based on limiting Maillard reaction. As Maillard reaction is responsible for formation of the desired taste-smell in the product, use of these techniques especially in considerably aromatic products such as coffee is disadvantageous.
SUMMARY OF THE INVENTION
[0013] The objective of the present invention is to provide instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof which is performed without requiring any change in heat treatment (such as roasting).
[0014] Another objective of the present invention is to provide instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof without any loss of taste, smell or aroma.
[0015] A further objective of the present invention is to provide instant coffee or coffee substitute whose harms on human health are reduced or completely eliminated and acrylamide and hydroxymethyl furfural (HMF) contents are reduced, and production method thereof.
[0016] Another objective of the present invention is to provide instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof wherein extracts obtained from grains or grainlike roasted foodstuffs are fermented.
DETAILED DESCRIPTION OF THE INVENTION
[0017] The inventive instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof is illustrated in the accompanying figure wherein
[0018] FIG. 1 is the flow chart of the production method.
[0019] Instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof ( 100 ) developed to fulfill the objective of the present invention comprises the steps of
roasting the input material ( 101 ), grinding the roasted material ( 102 ), extraction of the ground material ( 103 ), yeasting the extract ( 104 ), fermentation ( 105 ), filtration ( 106 ), drying the filtrate ( 107 ).
[0027] In the inventive instant coffee or coffee substitute production method ( 100 ) firstly roasting ( 101 ) is performed. Seeds, beans and/or fruits obtained from different plants and trees can be used as the input materials. In the preferred embodiment of the invention, coffee beans that are obtained from the seeds of the fruits of coffee trees are used. After the mature coffee beans are collected, they are cleaned by being processed according to wet or dry processing technique. The roasting ( 101 ) process is required for the said cleaned coffee beans to give taste, smell and aroma to the final product. Roasting ( 101 ) can be carried out at different temperature and time conditions. In the preferred embodiment of the invention, temperatures in the range of 200-250° C. are used to obtain the taste and smell specific to the material. Formation of the taste and smell specific to coffee is provided by Maillard reaction. Maillard reaction takes place between free amino groups and carbonyl groups and accelerates as the temperature rises. While enabling formation of the features desired in the product, these reactions also cause formation of various carcinogenic compounds. Acrylamide and hydroxymethyl furfural (HMF) are the most known among these compounds.
[0028] The roasted material is then ground by the help of a grinder ( 102 ) and broken up into smaller particles.
[0029] The ground material is subjected to extraction ( 103 ) under a certain pressure and temperature, and then all soluble components of the coffee are taken into a liquid medium, whereas the insoluble components are removed. In the preferred embodiment of the invention, extraction ( 103 ) is carried out by using water at 10-15 bar pressure and 90-150° C. temperature. The final concentration of the extract is adjusted so that it will contain 10-20% soluble solid.
[0030] The extract containing 10-20% soluble solid obtained after extraction ( 103 ) is taken to the step of yeasting ( 104 ). In this step ( 104 ), mixtures are prepared by adding sucrose and yeast to the extracts. In the preferred embodiment of the invention, baker's yeast ( Saccharomyces cerevisiae ), which does not have any harm on human health and which is used in production of many fermented products, is used as the yeast. Baker's yeast basically needs carbon and nitrogen source and is easily active at such mediums. In the preferred embodiment of the invention, the extract containing 10-20% soluble solid is mixed with % 0.5-1 yeast (w/v) and 1-10% sucrose (w/v) and thereby fermentation takes place.
[0031] The mixtures that are prepared are fermented ( 105 ) with the impact of the step of yeasting ( 104 ), and at the same time acrylamide and HMF formed after roasting ( 102 ) are reduced by being metabolized by the yeast. In the preferred embodiment of the invention, fermentation ( 105 ) continues for 12-48 hours at temperatures 25-30° C.
[0032] After fermentation ( 105 ) ceases, filtration ( 106 ) is carried out in order to separate and remove the yeast cells from the product.
[0033] The filtrate which is cleaned from the yeast cells is finally dried ( 107 ). Drying can be applied in two different ways, namely spray drying or freeze drying.
[0034] Following drying ( 107 ), the final product is obtained such that there is no loss of taste-smell and aroma and that it is mostly cleared of the undesirable carcinogenic and cytotoxic substances.
[0035] Acrylamide and HMF concentration in the final product can be adjusted by changing the percentages of extract, yeast and sucrose in the mixtures prepared during the step of yeasting ( 104 ). Examples and results pertaining to the mixtures wherein the extracts obtained from the coffee beans are used are given below.
EXAMPLE 1
[0036] A mixture is prepared by 20% coffee extract (w/v), 10% sucrose (w/v) and 1% baker's yeast (w/v); and is allowed to ferment for 12 hours. The HMF content in the final product, which is thus produced, is observed to decrease by 94% relative to the HMF content in the roasted coffee.
EXAMPLE 2
[0037] A mixture is prepared by 20% coffee extract (w/v), 10% sucrose (w/v) and 1% baker's yeast (w/v); and the extract is allowed to ferment for 24 hours. The acrylamide content in the final product, which is thus produced, is observed to decrease by 52% relative to the acrylamide content in the roasted coffee. HMF content decreased by 98.6%.
EXAMPLE 3
[0038] A mixture is prepared by 20% coffee extract (w/v), 10% sucrose (w/v) and 1% baker's yeast (w/v); and the extract is allowed to ferment for 48 hours. The acrylamide content in the final product, which is thus produced, is observed to decrease by 72.7% relative to the acrylamide content in the roasted coffee. HMF content decreased by 100%.
[0039] As it is seen from the above given examples, fermentation time plays a significant role in reducing acrylamide and HMF content in the product.
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The present invention relates to the instant coffee or coffee substitute with reduced acrylamide and hydroxymethyl furfural (HMF) content and production method thereof which comprises the steps of roasting the input material, grinding the roasted material, extracting the ground material, yeasting the extract, fermentation, filtration, drying the filtrate; and wherein carcinogenic and cytotoxic process components, which are found in heat treated foods especially in instant coffees, are minimized.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention, in general, relates to a method of determining the weight of laundry in the drum of a washing machine and, more particularly, to a method of determining the weight of laundry in a washing drum rotatably mounted within a sudsing container suspended in the housing of a washing machine by springs in its upper region and in its lower region by at least one shock absorber consisting of a cylindrical housing and a frictionally coated piston rod reciprocally movable therein between two abutments with associated spring elements, the drum cooperating with a system for defining the weight of the laundry in the drum with a measuring circuit for determining the lowering of the sudsing container as a function of the weight.
2. The Prior Art
A washing machine including a system for determining the weight of laundry contained in the drum is manufactured and sold under the designation W 377 WPS by the assignee of the instant application. It is also known from German patent specification DE 199 46 245 A1. Washing machines of this type are provided with a displacement sensor arranged parallel to the shock absorber. The sudsing container with the washing drum rotatably mounted therein is connected to the housing by springs. As soon as laundry is placed in the drum the total mass of the sudsing container changes. As a result of the increasing mass the springs are extended or displaced further so that as the amount of the laundry placed into the drum is increased the downward movement of the sudsing container increases as well. The resulting level of the sudsing container is determined by means of the displacement sensor. Accordingly, the displacement sensor releases a signal the difference of which relative to a zero position, i.e. the empty drum, is proportional to the weight of the deposited laundry.
For a spinning operation it is necessary to attenuate or dampen the oscillating amplitude at least during transition through the critical number of rotations (resonance of the spring-mass-system consisting of the springs and the mass of the filled sudsing container). This is accomplished by at least one shock absorber positioned between the sudsing container and the bottom of the housing. Weighing of the laundry takes place while the sudsing container is at rest. At this point in time, the shock absorbers must not generate any forces, as they would have to be overcome by the force of the weight of the laundry before the sudsing container could move downwardly and thereby generate a displacement signal measurable by the displacement sensor. Therefore, the W 377 WPS washing machine uses oil-hydraulic shock absorbers of velocity proportional damping power the damping power of which is very low when they are not moved. Ideally, there would be no attenuation at all. Only when the sudsing container is lowered, velocities arise which generate of counter forces which limit the oscillating amplitude. The disadvantages of the oil-hydraulic shock absorbers reside in their high price, low damping action, acoustic problems and low environmental compatibility because of special requirements relating to the disposal of the oil.
German patent specification DE 49 18 599 A1 discloses a so-called dash-pot damper. It is, in fact, a frictional damper in which the frictional coating is movably mounted on a piston rod between two spring elements, each spring element being supported by an abutment connected to the piston rod. Such an arrangement results in a damping action which is dependent upon amplitude.
From German patent specification DE 100 46 712 A1 it is known to use a dash-pot damper in combination with a displacement sensor. The disadvantage of this measuring system of a dash-pot damper with but one displacement sensor is its undefined initial state. If the drum is empty, it is possible that the frictional coatings are in a position which does not correspond to the zero position of the sudsing container. The suspension springs then exert a force upon the sudsing container which is less than the frictional force of the friction coating. Thus, there is an undefined force which act against the system and which leads to an additional extension of the springs on which the assembly is suspended. The extension of the springs, in turn, is added to the displacement measured by the displacement sensor. Unlike arrangements utilizing a velocity proportional damper (e.g. an oil-hydraulic damper) it is thus not possible to define the weight of the deposited laundry. Hence, the weight of the laundry can only be determined with an initially empty drum which is filled afterwards. However, if the washing machine in its idle state is used as a laundry collector or hamper, it will not be possible subsequently to switch on the washing machine and to obtain a correct reading of the weight of the laundry. Hence, such a machine is of limited utility.
German patent specification DE 101 22 749 A1 discloses a washing machine and, in connection therewith, a method of determining the weight of laundry in which a dash-pot damper is used which is provided with two displacement sensors. Displacement sensors are relatively expensive components, and their added costs take away any economic advantage otherwise to be derived from cost-efficient shock absorbers.
OBJECTS OF THE INVENTION
It is thus an object of the invention to provide for a method of the kind referred to supra which, the use of a dash-pot damper with but one way sensor notwithstanding, makes possible a precise determination of the weight of laundry in a washing machine.
BRIEF SUMMARY OF THE INVENTION
In accordance with the invention, the object is accomplished by a system which determines a positional value corresponding to the highest position of the sudsing container during a given section of a washing program and which feeds this value to a non-volatile storage or memory in the system, and by this positional value being used in a subsequent washing cycle as the value corresponding to a zero value.
Additional advantageous embodiments and improvements may be gathered from the subsequent sub-claims.
Other advantages will, in part be obvious and will in part appear hereinafter.
BRIEF SUMMARY OF THE INVENTION
The advantages to be derived from practicing the invention are the result of precise measurements obtained by simple means and using only one displacement sensor.
In an advantageous embodiment of the method in accordance with the invention the comparison means determines the positional value corresponding to the highest position of the sudsing container at the end of a washing program.
In a further advantageous embodiment of the method in accordance with the invention the comparison means recognizes rising of the position of the sudsing container after connection of the washing machine to network current at the beginning of a subsequent washing cycle and feeds the value corresponding to the highest position of the sudsing container to an evaluation circuit which writes the newly determined value over the zero position value determined during the previous washing program. In this manner it is possible to sense the actual zero position even if the user removes the laundry from the drum prior to executing a washing cycle and after having connected the washing machine to power. This could be the case, for instance, if following a preceding washing cycle, laundry has remained in the drum or if the drum has been used as laundry storage.
DESCRIPTION OF THE SEVERAL DRAWINGS
The novel features which are considered to be characteristic of the invention are set forth with particularity in the appended claims. The invention itself, however, in respect of its structure, construction and lay-out as well as manufacturing techniques, together with other objects and advantages thereof, will be best understood from the following description of preferred embodiments when read in connection with the appended drawings, in which:
FIG. 1 is a schematic representation of a washing machine for carrying out the method in accordance with the invention;
FIG. 2 is a schematic representation of a dash-pot damper in longitudinal section;
FIG. 3 is a force-displacement diagram of a dash-pot damper; and
FIG. 4 Is a block diagram of a washing machine control circuit.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 depicts a washing machine provided with a sudsing container 4 with a washing drum 5 rotatably mounted therein. The sudsing container 4 is suspended at its upper section from the housing 1 of the washing machine by springs 2 , 3 . As laundry 6 is deposited into the drum 5 , the total mass of the sudsing container 4 consisting of the mass m LB of the empty sudsing container 4 and the mass m w of the laundry 6 changes. The increase in mass leads to a further extension of the springs 2 , 3 so that the sudsing container 4 will hang the lower the greater is the mass of the deposited laundry 6 . The downward movement Δs of the sudsing container 4 in response to the force of the weight of the laundry is detected by a displacement sensor 9 . The displacement sensor 9 thus releases a signal proportional to the weight m w of the deposited laundry to a measuring circuit M. The measuring circuit M is integrated in the micro processor control MC of the washing machine and it determined a value representative of the weight on the basis of the downward movement Δs and the spring constant or constants. The weight value is either used in a display (not shown) as user information or by the micro processor control MC directly for controlling the washing program.
For the spinning operation the oscillating amplitude must be limited at least during the transition through the critical range of the number of rotations (resonance of the spring mass system consisting of the springs 2 , 3 and the mass of the filled sudsing container 4 ). This limitation is provided by two shock absorbers 7 , 8 structured as dash-pot shock absorbers and arranged between the sudsing container 4 and the bottom of the housing 1 b.
FIG. 2 depicts a spring loaded dash-pot damper or shock absorber 80 of the kind known from German patent specification No.: DE 40 18 599 A1, but which, in an improved structure, is part of the assignee's patent portfolio (see the older post-published application DE 102 25 335 A1). It consists of a cylindrical damper housing 81 and a piston rod 82 axially movable in the housing 81 . The piston rod 82 is mounted on the sudsing container 4 by a knuckle 82 , and by a knuckle 84 the damper housing 81 is mounted on the bottom 1 b of the housing. The piston rod 82 is provided with two rigidly mounted spring plates 87 , 88 . Between them, two spring elements 85 , 86 are seated on the piston rod 82 which between them retain a coated block 89 . The coated block 89 supports frictional coatings 90 which engage the interior wall of the housing 81 of the damper. Any movement of the sudsing container 4 is transmitted by the piston rod 82 to the two spring elements 85 , 86 which, in turn, transmit the force onto the moveably mounted coated block 89 . Movement of the piston rod 82 in a given direction initially causes the spring elements to be respectively extended and compressed in the same direction. Once the built-up force has reached a level which exceeds the frictional force between the coated block 89 and the interior wall of the cylinder 81 , the coated block 89 and its frictional coating 90 will move as well.
FIG. 3 shows an idealized force-displacement diagram of the dash-pot damper 80 . The difference relative to a simple frictional damper is that a displacement s occurs at the initial stage of small forces F between F R and −F R is traveled. The spring elements 85 , 86 provide for a transitional range in which the damper 80 operates linearly. Hence, utilization of dash-pot dampers 80 in a washing machine of the kind shown in FIG. 1 , causes the sudsing container 4 to move downwardly while laundry 6 is being deposited into it. This can be measured as a change in displacement, so that, taking into account the spring constant, the weight of the load in the drum can be calculated. The displacement sensor 9 may, as shown in FIG. 1 , either be positioned substantially parallel to one of the shock absorbers, or it may be integrated into it in two different ways (not shown): One way is an arrangement between the piston rod 82 and the housing 81 of the damper; another way is an arrangement between the piston rod 82 and one of the frictional coatings 90 . Regardless of where the sensor is mounted, the following disadvantages will result:
If the force of the dash-pot damper 80 at the beginning of loading is close to the frictional force, the force exerted by a small additional weight of deposited laundry 6 will suffice to cause the frictional coating 90 to slide and movement out of the linear range. The initial state is not defined. If the drum ( 5 ) is empty, a force between −F R and +F R will arise in the dash-pot damper 80 . Hence, there is an undefined force in the range between −F R to +F R which acts in an offsetting way on the system and which is thus incorporated in the displacement of the springs 2 , 3 by which the sudsing container 4 is suspended. In order to define the weight of the laundry, the extension of the tension springs 2 , 3 when the drum is empty or, alternatively, the force of the weight transmitted by the sudsing container 4 to the housing (either will hereafter be referred to as “zero position”) must be known in order determine the weight of the laundry on the basis of the measured downward movement Δs (alternatively the force of the weight) and the previously determined zero position. The extension of the springs is incorporated in the displacement measured by the displacement sensor. Unlike with velocity-proportional dampers (e.g. an oil-hydraulic damper), an absolute determination of the mass of the deposited laundry is thus not possible. In other words, it is possible to determine the weight of laundry if the drum is initially empty and filled subsequently. However, if the drum in its idle state is used as a laundry collector or hamper, it is not possible to switch on the washing machine and to obtain a correct reading of the weight of the laundry. Such a system is, therefore, of limited usefulness.
This is the basis of the present invention which eliminates these disadvantages. For purposes of carrying out the method, a comparison circuit V is integrated in the washing machine controls MC (see FIG. 4 ) aside from the measuring circuit M for determining the weight of the laundry. The comparison circuit V, in turn, is connected to a non-volatile storage or memory SP. In addition, the measuring circuit M and the comparison circuit V are connected to an evaluation circuit A.
When the drum is unloaded at a predetermined point in time prior to termination of a washing program, for instance after a final spin cycle, the contents of the non-volatile memory SP are erased first. Thereafter, the displacement sensor 9 measures the downward movement Δs of the sudsing container at 1 second intervals and feeds its measured values to the measuring circuit M which, on the basis of these values, determines the weight. The comparison circuit V now either compares the weight or the downward movement Δs as a positional value with the value of the non-volatile memory SP. Whenever the actual positional value corresponds to a higher sudsing container position and, therefore, to a lower weight of the laundry than the value present in the memory SP, the comparison circuit overwrites the value in the memory SP with the actual value. Following termination of a current program, a positional value is stored in the memory SP which corresponds to the highest position of the sudsing container in the last section of the washing program. In an ideal case, i.e. at a completely emptied drum, it corresponds to a zero weight of the laundry. At the start of the following program this value will be used by the measuring circuit as the value corresponding to the zero position.
For safety reasons the comparison circuit V is also activated at the start of a program, i.e. after connecting the washing machine to network current. Initially the contents of the non-volatile memory SP is not erased and the positional value determined in the previous washing program is initially retained. The comparison circuit V is designed to recognize upward movement in the position of the sudsing container so that the positional value corresponding to the highest position of the sudsing container is fed to the evaluation circuit A which then overwrites the zero position value stored during the previous washing program with the newly determined value.
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A method of determining the weight of laundry placed in the drum rotatably mounted in a vertically moveable sudsing container of a washing machine, in which a value representative of the highest position attained by the sudsing container in a previous washing cycle or after connecting the washing machine to network current is compared against the position attained by the sudsing container after laundry has been placed in the drum to derive from the difference a value representative of the weight of the laundry.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to semiconductor devices having element isolation regions, and to techniques for fabricating the semiconductor devices.
[0003] 2. Description of the Related Art
[0004] With recent progress in enhanced performances and multi-functionalization of mobile instruments and personal audio equipments, there are strong needs of reducing power consumption and of enhancing performances of LSIs used for such instruments or equipment. CMOS devices fabricated using bulk substrate are suffering from a problem of increase in power consumption, due to higher degrees of integration and faster operational speed as a result of dimensional shrinkage of semiconductor processes. Accordingly, a CMOS device having a novel structure, operable at low power consumption, is strongly expected. In this situation, semiconductor devices (called “SOI devices”) fabricated by using SOI (Silicon On Insulator or Semiconductor On Insulator) substrates having buried insulating films therein are expected as devices capable of achieving low power consumption and dimensional shrinkage of LSIs. Advantages of the SOI device reside in complete electrical isolation of elements such as PMOS transistor and NMOS transistor, and implementation of high-density layout, without causing latch-up, by virtue of provision of the buried insulating film (e.g., a BOX film).
[0005] SOI devices can be classified into partially depleted SOI (PD-SOI) devices and fully depleted SOI (FD-SOI) devices. Both types of the SOI device have a body region surrounded by a gate insulating film, a source diffusion region, a drain diffusion region, and a buried insulating film, directly under a gate electrode. The PD-SOI device has a partially-depleted body region, and suffers for example from degradation of sub-threshold characteristic (i.e., S factor) during operation of the device, due to floating body effect. On the other hand, the FD-SOI device will cause no floating body effect, since the body region is completely depleted, and has an advantage of capable of operating at low voltage and low current consumption.
[0006] The element isolation structure can be formed by LOCOS (Local Oxidation Of Silicon) or STI (Shallow Trench Isolation). LOCOS refers to a method of forming an insulating film for element isolation, by thermally oxidizing the surface of the semiconductor substrate, whereas STI refers to a method of forming a shallow trench in the semiconductor substrate, and then filling the trench with an insulating film.
[0007] Prior art documents regarding the SOI device and the element isolation techniques are exemplified by Japanese Patent Application Publication Nos. 2003-289144 and H06 (1994)-140427.
[0008] Besides the above-described element isolation techniques such as LOCOS and STI, another possible method can be used such as selective etching of the surface of a semiconductor substrate so as to form a mesa-shape semiconductor layer that is used as an active region (element region) (“mesa isolation process”). A transistor structure can be fabricated by forming a gate structure (a gate insulating film and a gate electrode) on the mesa-shape semiconductor layer, and introducing impurities into the semiconductor layer on both sides of the gate structure, to thereby form source/drain diffusion regions. The source/drain diffusion regions are electrically connected through contact plugs to upper interconnects. The contact plugs can be formed typically by selectively etching an insulating interlayer which covers the source/drain diffusion regions to thereby form contact holes, and by filling the contact holes with an electro-conductive material such as tungsten.
[0009] When the transistor structure is formed on the SOI substrate by the mesa isolation process, the semiconductor layer in the process of forming the mesa is etched, until the top surface of the buried insulating film in the SOI substrate exposes in the element isolation region, as detailed later. Formation of the transistor structure using the mesa-shape semiconductor layer is followed by a process of depositing an insulating interlayer over the entire surface, and a process of selectively etching the insulating interlayer to thereby form the contact holes which reach the source/drain diffusion regions. The contact holes can, however, occasionally be misaligned, and the region for forming the contact holes can overlap the buried insulating film which exposes in the element isolation region. In this case, element characteristics can degrade if the buried insulating film is excessively etched together with the insulating interlayer in the process of forming the contact holes.
[0010] Also in the transistor structure having the element isolation region formed by LOCOS or STI, such misalignment of the contact holes can result in overlapping of the region for forming the contact holes with the element isolation insulating film. Also in this case, the element characteristics possibly degrades if the element isolation insulating film is excessively etched together with the insulating interlayer in the process of forming the contact holes.
[0011] In view of the foregoing, it is an object of the present invention to provide a SOI substrate and a method of fabricating the same, and a semiconductor device and a method of fabricating the same which are capable of suppressing degradation of device characteristics, even if misalignment of a contact hole formed in an insulating interlayer over a substrate should occur, thus forming an overlapping region between a contact hole and an element isolation region.
SUMMARY OF THE INVENTION
[0012] According to a first aspect of the present invention, there is provided an SOI substrate which includes: a semiconductor base; a semiconductor layer formed over the semiconductor base; and a buried insulating film which is disposed between the semiconductor base and the semiconductor layer, so as to electrically isolate the semiconductor layer from the semiconductor base. The buried insulating film contains a nitride film.
[0013] According to a second aspect of the present invention, there is provided a semiconductor device which includes: the SOI substrate; and a semiconductor element structure formed on the SOI substrate.
[0014] According to a third aspect of the present invention, there is provided a method of manufacturing a semiconductor device which includes: preparing the SOI substrate; and forming a semiconductor element structure on the SOI substrate.
[0015] According to a fourth aspect of the present invention, there is provided a method of manufacturing an SOI substrate which includes: preparing a first semiconductor base which includes a semiconductor layer; forming an insulating film which includes a nitride film, on a main surface of a second semiconductor base; and bonding the insulating film on the second semiconductor base and the semiconductor layer of the first semiconductor base. The insulating film is formed so as to electrically isolate the semiconductor layer from the second semiconductor base.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The above and other objects, advantages and features of the present invention will be more apparent from the following description of certain preferred embodiments taken in conjunction with the accompanying drawings, in which:
[0017] FIG. 1 is a cross sectional view schematically illustrating a structure of a semiconductor device according to an embodiment of the present invention;
[0018] FIG. 2 to FIG. 11 are cross sectional views schematically illustrating a fabrication process of the semiconductor device of the embodiment;
[0019] FIGS. 12A , 12 B to FIG. 14 are cross sectional views, each schematically illustrating part of steps of fabricating the SOI substrate according to the embodiment;
[0020] FIG. 15 is a cross sectional view schematically illustrating a structure of a semiconductor device according to a comparative example; and
[0021] FIG. 16 is a cross sectional view schematically illustrating a structure of a semiconductor device according to another embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Embodiments of the invention will now be described with reference to the attached drawings, in which like elements are indicated by like reference characters.
[0023] FIG. 1 is a cross sectional view schematically illustrating a structure of a semiconductor device (SOI transistor) 1 according to an embodiment of the present invention. The semiconductor device 1 has a semiconductor base (supporting substrate) 11 , a buried insulating film 12 arranged on the semiconductor base 11 , and a semiconductor layer (SOI layer) 16 arranged on the buried insulating film 12 . The semiconductor layer 16 is a convex portion patterned into a mesa shape, on which a gate structure 20 of the SOI transistor 1 is formed. The SOI transistor 1 of the embodiment uses the mesa-shape semiconductor layer 16 as an active region (element region), wherein the mesa shape of the semiconductor layer 16 determines an element isolation region other than the active region.
[0024] The buried insulating film 12 has a function of electrically isolating the semiconductor layer 16 on the top surface from the semiconductor base 11 on the back surface, and contains a lower insulating film 13 , an etching barrier film 14 and an upper insulating film 15 , as illustrated in FIG. 1 . The lower insulating film 13 and the upper insulating film 15 are typically composed of a silicon oxide film, whereas the etching barrier film 14 is composed of an insulating material which is more dense than the upper insulating film 15 (a nitride film, for example). As described later, the etching barrier film 14 functions as an etching stopper, when contact holes 41 A, 41 B are formed by anisotropic etching in an insulating interlayer 40 .
[0025] The gate structure 20 is configured by a gate insulating film 21 formed on the semiconductor layer 16 , a gate electrode 22 formed on the gate insulating film 21 , and a pair of sidewall spacers 23 A, 23 B formed on both sides of the gate electrode 22 . The gate insulating film 21 can have a thickness of 1 nm (nanometer) to several tens of nanometers. Constitutive materials adoptable to the gate insulating film 21 include silicon oxide, silicon nitride, and high-k material having a dielectric constant larger than that of silicon oxide (hafnium oxide-based material such as nitrogen-added hafnium silicate, for example). The gate electrode 22 can have a thickness of 50 nm to 500 nm or around, and can be formed using polysilicon heavily doped with impurity, or a refractory metal material such as titanium.
[0026] The semiconductor layer 16 has a thickness of several nanometers to several hundreds of nanometers, and is typically composed of a single-crystalline silicon material. The semiconductor layer 16 have formed therein a source diffusion region 16 s and a drain diffusion region 16 d having p-type or n-type conductivity, and a body region 16 b held between the source diffusion region 16 s and the drain diffusion region 16 d . An LDD (Lightly Doped Drain) region or an extension region 16 se is formed so as to extend from the source diffusion region 16 s towards the drain diffusion region 16 d , and an LDD region or an extension region 16 de is formed so as to extend from the drain diffusion region 16 d towards the source diffusion region 16 s . The body region 16 b in the embodiment is given as an almost completely depleted region.
[0027] On both sides of the gate structure 20 in the gate length-wise direction, epitaxial layers 31 A, 31 B are formed. The epitaxial layers 31 A, 31 B are formed mainly for the purpose of lowering parasitic resistance.
[0028] An insulating interlayer 40 is formed so as to cover the gate structure 20 , the semiconductor layer 16 , and the element isolation region (the region having no mesa-shape semiconductor layer 16 ). The insulating interlayer 40 can typically have a thickness of 500 nm. to 1500 nm, and can be composed of an insulating material such as SiO 2 , SiOC, SiC or SiCN. The insulating interlayer 40 has formed therein the contact holes 41 A, 41 B which respectively reach the top surfaces of the epitaxial layers 31 A, 31 B. The contact holes 41 A, 41 B are filled with contact plugs 42 A, 42 B composed of a refractory metal material such as tungsten or tantalum. The bottom ends of the contact plugs 42 A, 42 B are electrically connected through the epitaxial layers 31 A, 31 B respectively to the source diffusion region 16 s and the drain diffusion region 16 d , whereas the top ends of the contact plugs 42 A, 42 B are electrically connected to upper interconnects 50 A, 50 B, respectively.
[0029] In the semiconductor device 1 of the embodiment, a region for forming the contact hole 41 B shifts from an exact position and overlaps the element isolation region, due to misalignment of a reticle used in a semiconductor lithographic process such as a typical photolithographic process. Accordingly, in the process of forming the contact holes 41 A, 41 B by etching, the SOI substrate 10 is etched to a depth of the upper insulating film 15 , but the contact hole 41 B is prevented from penetrating the buried insulating film 12 , by the etching barrier film 14 .
[0030] Next, an exemplary method of fabricating the semiconductor device 1 of the embodiment will be explained, referring to FIG. 2 to FIG. 11 which are cross sectional views schematically illustrating processes of fabricating the semiconductor device 1 of the embodiment.
[0031] First, as illustrated in FIG. 2 , the SOI substrate 10 configured by stacking the semiconductor base 11 , the buried insulating film 12 and the semiconductor layer 16 P is prepared. The semiconductor base 11 and the semiconductor layer 16 P are composed of a single-crystalline silicon material. A method of fabricating the SOI substrate 10 will be described later. Next, a resist pattern 19 , used for etching of the semiconductor layer 16 P into the mesa shape, is formed on the semiconductor layer 16 P by a semiconductor lithographic process using a radiation such as X-ray or EUV (Extreme Ultra Violet) ( FIG. 3 ). The semiconductor layer 16 P is then anisotropically etched using the resist pattern 19 as a mask. As a consequence, the semiconductor layer 16 is given in the form of mesa-shape convex portion, used as the active region, as illustrated in FIG. 4 .
[0032] Thereafter, as illustrated in FIG. 5 , typically by the CVD (Chemical Vapor Deposition) process, an insulating film 21 P of several nanometers thick typically composed of a high-k material such as hafnium silicate, and an electro-conductive layer 22 P of approximately 100 nm thick are sequentially formed on the structure illustrated in FIG. 4 . The electro-conductive layer 22 P can be formed using polysilicon or titanium nitride. Next, a resist pattern (not illustrated) is formed by photolighography on the structure illustrated in FIG. 5 , followed by etching using the resist pattern as a mask, for forming the gate insulating film 21 and the gate electrode 22 as illustrated in FIG. 6 . An impurity 60 is then introduced by ion implantation into the semiconductor layer 16 on both sides of the gate electrode 22 , while using the gate insulating film 21 and the gate electrode 22 as a mask, and then activating the impurity to thereby form the impurity-diffused regions 16 se , 16 de for forming the LDD regions or extension regions.
[0033] An insulating film (not illustrated) of approximately 10 nm to 300 nm thick, composed of an insulating material such as silicon oxide, is formed on the structure illustrated in FIG. 7 typically by CVD, and the insulating film is then anisotropically etched back. The sidewall spacers 23 A, 239 are consequently formed on both side faces of the gate electrode 22 , as illustrated in FIG. 8 . The gate structure 20 is configured by the sidewall spacers 23 A, 23 B, the gate insulating film 21 and the gate electrode 22 .
[0034] Next, the epitaxial layers 31 A, 31 B are formed by the selective epitaxial growth (SEG) process using the exposed surface of the semiconductor layer 16 as an underlying layer, as illustrated in FIG. 9 . The selective epitaxial growth process is exemplified by CVD process using a source gas which contains a silane-based gas (silane gas, disilane gas, or dichlorosilane gas, for example) and a chlorine-containing gas. Next, an impurity is introduced by ion implantation through the epitaxial layers 31 A, 31 B into the semiconductor layer 16 , while using the gate structure 20 as a mask, and then activating the impurity to thereby form the source diffusion region 16 s and the drain diffusion region 16 d on both sides of the gate structure 20 . The source diffusion region 16 s and the drain diffusion region 16 d can be inverted vice versa.
[0035] Next, an insulating interlayer 40 of approximately 500 nm to 1500 nm thick, composed of a SiO 2 -based material, is formed typically by plasma CVD, on the structure illustrated in FIG. 9 . The top surface of the insulating interlayer 40 is optionally planarized, typically by CMP (Chemical Mechanical Polishing). Next, a resist pattern (not illustrated) is formed by a semiconductor lithographic process using a radiation such as X-ray or EUV, on the insulating interlayer 40 , and the insulating interlayer 40 is patterned by anisotropic etching using the resist pattern as a mask. As a consequence, as illustrated in FIG. 11 , the contact holes 41 A, 41 B which later allows therethrough electrical connection, via the epitaxial layers 31 A, 31 B with the source diffusion region 16 s and the drain diffusion region 16 d , are formed.
[0036] For example, a barrier film typically composed of a nitride film is formed over the inner surface of the contact holes 41 A, 41 B, and the contact holes 41 A, 41 B are then filled with a refractory metal material such as tungsten, typically by CVD, to thereby form the contact plugs 42 A, 42 B illustrated in FIG. 1 . Thereafter, the upper interconnects 50 A, 50 B composed of an interconnect material such as copper or aluminum are formed.
[0037] In the fabrication process of the semiconductor device 1 of the embodiment, the etching for forming the mesa-shape semiconductor layer 16 is proceeded until the top surface of the buried insulating film 12 in the SOI substrate 10 exposes, as illustrated in FIG. 3 and FIG. 4 . In addition, the region for forming the contact hole 41 B overlaps the region for forming the element isolation region, as illustrated in FIG. 11 , due to misalignment of the reticle used in the photolithography. Accordingly, not only the insulating interlayer 40 , but also the upper insulating film 15 are etched. However, since the etching barrier film 14 serves as the etching stopper, the contact hole 41 B is prevented from penetrating the buried insulating film 12 . Since short-circuiting between the semiconductor base 11 and the semiconductor layer (SOI layer) 16 is exactly avoidable in this way, yield ratio of the semiconductor device 1 can be improved.
[0038] For an exemplary case where the thickness of the etching barrier film 14 is approximately several nanometers to 50 nm (more preferably 5 nm to 10 nm or around), the contact hole 41 B can be prevented from penetrating the etching barrier film 14 , by adjusting a ratio (=R 2 /R 1 ) of an etching rate of the upper insulating film 15 (=R 2 ) relative to an etching rate of the barrier film 14 (=R 1 ), or so-called “selectivity”, to a range from 5 to 40 or around, more preferably a range from 10 to 20 or around. The present inventors experimentally confirmed that the contact hole 41 B was successfully prevented from penetrating the etching barrier film 14 , when the insulating interlayer (silicon oxide film) 40 was anisotropically etched while adjusting the substrate temperature to 50° C., and using an etching gas which contains C 4 F 8 gas (flow rate: 26 sccm), Ar gas (flow rate: 500 scorn) and O 2 gas (flow rate: 10 sccm).
[0039] If the buried insulating film 12 is sufficiently thin, the semiconductor base 11 can be used as a back-gate. More specifically, by applying a bias voltage to the semiconductor base (supporting substrate) 11 , the threshold current of the SOI transistor 1 becomes controllable, and degradation or variation in the element characteristics can be improved. For an exemplary case where the upper insulating film 15 and the lower insulating film 13 are composed of a silicon oxide film having a dielectric constant of 3.9, and the etching barrier film 14 is composed of a silicon nitride film having a dielectric constant of 7.5, the back-gate effect is supposed to be obtainable even if the thickness of the etching barrier film 14 is adjusted twice as large as the total thickness of the upper insulating film 15 and the lower insulating film 13 , since the silicon nitride film has a dielectric constant approximately twice as large as that of the silicon oxide film. From the viewpoint of obtaining the back-gate effect, the upper limit of the thickness of the buried insulating film 12 as a whole is preferably adjusted, for example, to 10 nm to 20 nm or around.
[0040] It is to be noted that any material alternative to silicon nitride can be used as a constituent material for the etching barrier film 14 . In this case, the thickness of the etching barrier film 14 is adjustable to a value correspondent to the ratio of dielectric constant of the material relative to the dielectric constant of silicon oxide film.
[0041] Next, a method of fabricating the SOI substrate 10 used for fabrication of the semiconductor device 1 of the embodiment will be explained with reference to FIGS. 12A , 12 B, 13 , and 14 . FIGS. 12A , 12 B, 13 , and 14 are cross sectional views schematically illustrating processes for fabricating the SOI substrate 10 .
[0042] First, as illustrated in FIG. 12A , the main surface of the semiconductor base 11 , which is a single-crystalline silicon wafer, is thermally oxidized to thereby form a lower insulating film (thermal oxide film) 13 . Next, the etching barrier film 14 composed of a nitride film is formed typically by CVD, on the lower insulating film 13 . On the other hand, as illustrated in FIG. 12B , the main surface of another semiconductor base 17 , which is composed of a single-crystalline silicon material, is thermally oxidized to thereby form the upper insulating film (thermal oxide film) 15 . Hydrogen ion 18 is then bombarded through the upper insulating film 15 into the semiconductor base 17 , to thereby form a defect layer 17 d which distributes at a predetermined depth (0.1 μm to several micrometers deep from the surface, for example).
[0043] Next, as illustrated in FIG. 13 , the etching barrier film 14 on the semiconductor base 11 and the upper insulating film 15 on the semiconductor base 17 are bonded. The bonded article is annealed, and then split at the defect layer 17 d so as to separate the semiconductor layer 16 P from the semiconductor base 11 , to thereby produce the SOI substrate 10 illustrated in FIG. 14 . The surface of the semiconductor layer 16 P is polished if necessary.
[0044] In the SOI substrate 10 illustrated in FIG. 14 , the etching barrier film 14 is held between the lower insulating film 13 and the upper insulating film 15 . The configuration is aimed at suppressing surface state between the nitride film and silicon from affecting the element characteristics. For the case where the surface state between the nitride film and silicon hardly affects the element characteristics, either one or both of the lower insulating film 13 and the upper insulating film 15 are omissible.
[0045] As explained in the above, since the semiconductor device 1 of the embodiment is fabricating using the SOI substrate 10 having the buried insulating film 12 which contains a nitride film, so that the contact hole 418 can be prevented from penetrating the buried insulating film 12 , even if the region for forming the contact hole 41 B overlaps the element isolation region. FIG. 15 is a cross sectional view schematically illustrating a structure of a semiconductor device 100 according to a comparative example. The structure illustrated in FIG. 15 is same as that of the semiconductor device 1 of the embodiment, except that the buried insulating film 12 P is composed only of a silicon oxide film. As illustrated in FIG. 15 , since the semiconductor device 100 have no etching barrier film, the contact hole 41 B penetrates the buried insulating film 12 P to reach the upper region of the semiconductor base 11 . There can be a problem of causing short-circuiting between the semiconductor base 11 and the semiconductor layer 16 , and producing defective products.
[0046] In contrast, the semiconductor device 1 of the embodiment can successfully prevent the penetration of the buried insulating film 12 by the contact hole 418 , even if the SOI substrate 10 having an extremely thin buried insulating film 12 is used for the purpose of implementing the back-gate effect. Accordingly, the short-circuiting between the semiconductor base 11 and the semiconductor layer 16 is avoidable, and thereby the yield ratio of the semiconductor device 1 can be improved.
[0047] While the embodiments of the present invention were explained referring to the attached drawings, they are merely for the exemplary purposes, without precluding any other various configurations to be adopted. For example, while the embodiments described in the above adopted the SOI transistor structure based on the mesa isolation process, also an SOI transistor structure having an element isolation insulating film formed by the STI or LOCOS process, in place of the mesa isolation process, can prevent the contact hole from penetrating the buried insulating film in the SOI substrate, similarly to the embodiment described in the above.
[0048] FIG. 16 is a cross sectional view schematically illustrating an exemplary configuration of a semiconductor device 2 having STI structures 33 , 34 for forming the element isolation region. In the semiconductor device 2 , the STI structures 33 , 36 extend from the top surface of the semiconductor layer 16 P towards the buried insulating film 12 . One STI structure 33 has a trench 34 and an element isolation insulating film 35 composed of a SiO 2 -based material filled in the trench 34 , and also the other STI structure 36 has a trench 37 and an element isolation insulating film 38 composed of a SiO 2 -based material filled in the trench 37 .
[0049] The method of fabricating the STI structures 34 , 37 is not specifically limited, and instead any widely-known process can be used. For example, a silicon oxide film and a silicon nitride film are sequentially formed on the SOI substrate 10 illustrated in FIG. 2 , and silicon oxide film and the silicon nitride film and the SOI substrate 10 are selectively removed by using photolithographic technique and etching technique, to thereby form the trenches 34 , 37 for element isolation. The inner wall of the trenches 34 , 37 are then thermally oxidized. An insulating film typically composed of silicon oxide is then deposited by CVD in the trenches 34 , 37 . The top surface of the insulating film is then planarized by, for example, CMP (chemical mechanical polishing, or chemical mechanical planarization). The silicon oxide film and the silicon nitride film are then removed respectively by wet etching. As a result of these processes, the STI structures 33 , 36 illustrated in FIG. 16 can be formed.
[0050] A gate structure 70 which is composed of a gate insulating film 71 , a gate electrode 72 and sidewall spacers 73 A, 73 B, is formed in the region on the semiconductor layer 16 P which falls within the STI structures 33 , 36 . On both sides of the gate structure 70 , a source diffusion region 160 s and a drain diffusion region 160 d are formed. Also extension regions 160 se , 160 de are formed so as to extend respectively from the source diffusion region 160 s and the drain diffusion region 160 d towards the region directly under the gate electrode 72 . A body region 160 b herein refers to a region surrounded by the source diffusion region 160 s , the drain diffusion region 160 d , the extension regions 160 se , 160 de , and the buried insulating film 12 .
[0051] In the semiconductor device 2 , an insulating interlayer 80 composed of a SiO 2 -based material is formed so as to cover the gate structure 70 , the semiconductor layer 16 P, and the STI structures 33 , 36 . In the insulating interlayer 80 , contact holes 81 A, 81 B which respectively reach the top surface of the source diffusion region 160 sa and the top surface of the drain diffusion region 160 d are formed, and the contact holes 81 A, 81 B are respectively filled with contact plugs 82 A, 82 B composed of a refractory metal material such as tungsten or tantalum. The upper ends of the contact plugs 82 A, 82 B are electrically connected respectively to upper interconnects 90 A, 90 E.
[0052] Now as illustrated in FIG. 16 , a region for forming the contact hole 81 B overlaps the STI structure 36 , due to misalignment of a reticle used in the lithographic process. For this reason, the element isolation insulating film 38 is etched to a depth of the etching barrier film 14 when the contact holes 81 A, 81 B are formed by etching. The contact hole 81 B is, however, prevented from penetrating the buried insulating film 12 , by the etching barrier film 14 .
[0053] While the semiconductor device I of the embodiment and the semiconductor device 2 in the modified embodiment have the gate structures 20 , 70 on the SOI substrates, the present invention is not limited thereto. Even if the region for forming the contact hole accidentally overlaps the element isolation region, in configurations having semiconductor element structures other than the gate structures 20 , 70 formed on the SOI substrate 10 , the contact hole can be prevented from penetrating the buried insulating film 12 .
[0054] According to the present invention, since the nitride film acts as an etching stopper, even if the SOT substrate should accidentally be etched in the element isolation region due to misalignment of the contact holes formed in the insulating interlayer, so that element characteristics can be suppressed from degrading.
[0055] It is apparent that the present invention is not limited to the above embodiments, that can be modified and changed without departing from the scope and spirit of the invention.
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Disclosed is an SOI substrate which includes a semiconductor base; a semiconductor layer formed over the semiconductor base; and a buried insulating film which is disposed between the semiconductor base and the semiconductor layer, so as to electrically isolate the semiconductor layer from the semiconductor base, where the buried insulating film contains a nitride film.
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BACKGROUND OF THE INVENTION
[0001] This application relates to an improved motor, wherein the stator windings of a multi-phase motor are spaced axially along a rotational axis of the motor. In addition, a cooling fluid is circulated through the stator windings.
[0002] Traction motors are often required to provide electrical to mechanical conversion for commercial vehicle drive trains. Typically the traction motors used in drive train applications have been three phase AC induction machines. A three phase AC induction machine is a machine that utilizes an induction motor to turn three phase electrical energy into mechanical motion. The primary reason for the use of AC induction machines as traction motors is that AC induction machines are easy to build and use well established technology. The fact that the technology behind AC induction machines is well established and has a large infrastructure allows them to be produced relatively cheaply.
[0003] On the other hand, large cost, size, and weight penalties are incurred when standard AC induction machines are adapted to vehicle drive trains. As such, much research has been put into developing new motor designs that can satisfy the cost, size and weight requirements of commercial vehicles.
[0004] Typically a goal has been to make induction machines more effective by increasing the output torque while decreasing the overall weight and cost of the machine. Transverse flux machines are the most viable method to fulfill this goal. Two types of transverse flux machines are known in the art, the permanent magnet transverse flux machine and the switched reluctance transverse flux machine. Permanent magnet transverse flux machines are transverse flux machines which utilize a permanent magnet, usually constructed out of rare-earth materials, as part of their rotor construction. Permanent magnet transverse flux machines achieve a high torque per weight ratio. However, permanent magnet transverse flux machines are not optimal. They are difficult to manufacture due to the complex magnet mounting methods used to construct the windings required for machine construction. Also, the torque output of a machine is temperature dependant, and they are highly intolerant of electrical fault conditions.
[0005] Switched reluctance machines have several distinct advantages over permanent magnet machines. First, switched reluctance machines provide relatively temperature independent torque, and second, switched reluctance machines are more tolerant of fault conditions. Switched reluctance motors work on the principle that a rotor pole pair has a tendency to align with a charged stator pole pair. By sequentially energizing stator windings the rotor is turned as it realigns itself with the newly energized stator poles in each energization. This allows the production of mechanical movement within the machine without the use of rare-earth materials. Switched reluctance machines have not been developed as much as permanent magnet machines due to, among other reasons, high investment costs in the electronic controls development Current switched reluctance machines use radially spaced phases and have multiple windings per phase that are more difficult to assemble.
SUMMARY OF THE INVENTION
[0006] The goal of the current invention is to design a switched reluctance transverse flux machine that is lighter in weight and produces higher torque. Additionally the goal of the present invention is to reduce assembly costs, and reduce the space required for the machine.
[0007] The invention relates to an axially spaced, transverse flux, switched reluctance, traction motor utilizing a single simple wound bobbin coil for each phase winding. As a separate inventive feature, an integral cooling loop is built into each phase winding. Transverse flux, switched reluctance machines are known in the art and provide a variety of benefits including simple design and an acceptable power to weight ratio. Some downsides of using switched reluctance machines are that they have a difficult assembly processes, do not have as high a power efficiency as permanent magnet transverse flux machines, and have high assembly costs.
[0008] It is known in the art to create a switched reluctance machine by spacing the phases radially around the rotor. The present invention spaces the phases axially along the rotor. Axial spacing allows the switched reluctance machine to be arranged in such a way that the machine can be constructed using a modular construction technique. The modular construction technique allows each phase to be assembled individually and then be “snapped” together with the other phases. Additional construction techniques not using modular assembly are possible with axially spaced phases, all of which are easier than the assembly techniques of the prior art switched reluctance machines.
[0009] A feature of the phase winding construction is made possible by the axial spacing and contributes to the ease in assembly. Known switched reluctance machines, as well as permanent magnet systems, use ‘daisy chained’ windings, or even more complex and intricate coil winding arrangements. The axial spaced windings with only one coil per phase allows a simple wound bobbin coil to be used for the windings. In this case the windings are circular and easy to assemble. This simple wound bobbin coil not only aids in ease of assembly but uses less copper wire, and reduces the overall weight of the switched reluctance machine. A third benefit resulting from the simple wound bobbin coils is the possibility of adding an integrated cooling loop within the electrical windings.
[0010] An integrated cooling loop is a hollow loop wound around the bobbin and embedded within the coil. The loop can be constructed of any material capable of being formed into a tube, having good heat transfer characteristics, and being capable of containing a refrigerant gas or liquid without leakage. The material would also provide benefits if non-conductive to electricity. The embedded cooling loop allows a refrigerant to be pumped through the coil while the switched reluctance machine is in operation. While the refrigerant is pumped through the coils heat is transferred from the coils to the refrigerant, thus cooling the overall system. The hot refrigerant then flows outside the coils. Once outside the coils, the refrigerant is cooled via a heat exchanger and pumped back through the embedded cooling loop. This allows temperature regulation within the coils themselves, providing for higher efficiency and a higher torque output. It is also envisioned that a similar effect could be accomplished using hollow wires to create the winding and pumping the cooling refrigerant directly through the winding wires themselves.
[0011] An integrated cooling loop is possible in any motor/generator system implementing simple wound bobbin coils and all motor/generator systems known in the art can benefit from the internal temperature regulation provided by an integrated cooling loop. The benefits provided by an internal temperature regulation system include, but are not limited to, a steadier torque output level due to a constant temperature, the capability of placing the motor/generator in locations where a typical motor/generator would be subject to overheating, and increased efficiency.
[0012] These and other features of the present invention can be best understood from the following specification and drawings, the following of which is a brief description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 illustrates a possible use for and deployment of an embodiment of the present invention.
[0014] FIG. 2 illustrates a simple radially spaced switched reluctance machine as found in the prior art.
[0015] FIG. 3 illustrates an embodiment of the present invention utilizing C shaped stators and C shaped rotors
[0016] FIG. 4 illustrates a potential layout of phases around the rotor shaft for a three phase embodiment of the present invention.
[0017] FIG. 5 illustrates a toroidal core for one phase of an axially spaced switched reluctance machine.
[0018] FIG. 6 illustrates multiple views of a single wound bobbin coil contained within the toroidal core of FIG. 3 .
[0019] FIG. 7 illustrates a modular assembly embodiment of the present invention.
[0020] FIG. 8 illustrates an embodiment of the present invention utilizing C shaped stators and I shaped rotors.
[0021] FIG. 9 illustrates a cooling circuit.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0022] The embodiment of FIG. 1 relates to a traction motor for use in an electric drive train for an automobile. Traction motor 10 is placed on a shaft 30 near each of four wheels 20 . In the illustrated example the motor is being used in a hybrid electromechanical braking system. The current invention could be utilized in any number of different applications, and provides benefits anywhere a switched reluctance transverse flux machine would be beneficial.
[0023] As shown in FIG. 2 , known standard switched reluctance motors in the prior art are composed of a set of three phase windings 53 , 54 , 55 , each of which is wound on a stator pole 51 . Each switched reluctance machine design has a certain number of suitable combinations of stator poles 51 and rotor poles 52 . The motor is excited (caused to move) by a sequence of current pulses applied at each phase winding 53 , 54 , 55 . The individual phase windings 53 , 54 , 55 are consequentially energized, forcing the electric field within the switched reluctance machine to change alignment. The rotor poles 52 then shift to align themselves with the newly changed electric field and rotational motion is created.
[0024] When each new phase charges up, the electric field within the switched reluctance machine realigns itself with the stators that correspond with the charged phase causing the rotor poles 52 to shift and realign themselves with the electric field. Using this process the rotor 56 can be made to sequentially shift alignment from one phase to the next; causing a full 360 degrees of rotation after each phase has been activated twice. If the phase windings 53 , 54 , 55 are sequentially charged and discharged fast enough then the rotation can reach sufficient speeds and generate sufficient torque for most applications. Typically the phases are spread radially in a single ring around the shaft as illustrated in FIG. 2 . This design introduces downsides including a very harsh fault intolerance, and the necessity of intricate phase windings to accommodate for adjacent phases.
[0025] In the present invention the phases 530 , 540 , 550 are spaced axially along the shaft 590 as illustrated FIG. 3 . In a design such as the illustrated embodiment each phase 530 , 540 , 550 consists of its own toroidal core 580 around the rotor shaft 590 . The stators 510 , 511 , 512 for each phase 530 , 540 , 550 are aligned with each other, and the rotors 520 , 521 522 on the shaft 590 are offset for each phase 530 , 540 , 550 as illustrated in FIG. 4 . The number of rotors 520 , 521 , 522 and stators 510 , 511 , 512 per phase in FIG. 4 is reduced for illustration purposes. Each phase 530 , 540 , 550 is fired up sequentially as in a radially spaced switched reluctance machine. This forces a mechanical rotation similar to the rotation in a radially spaced transverse flux machine.
[0026] FIG. 4 shows a three dimensional view of how the stators 510 and rotors 520 could be positioned to allow for this effect. Each stator 510 is lined up with the other phase's stators 511 , 512 in a column parallel to the rotor shaft 590 . The rotors 520 for phase 530 start lined up with the stators 510 . The next phase placed axially on the shaft 590 has its rotors 521 offset from the first phase's 530 rotors 520 . The third phase 550 placed axially along the shaft 590 has its stators 512 offset from both the first phase 530 and the second phase, 540 . The pattern can be modified to allow for any number of phases. However, the industry standard is to use three phases.
[0027] FIG. 5 illustrates a toroidal core 580 utilized in each phase of the illustrated embodiment of the invention. The toroidal core consists of a ring shaped housing containing individual simple wound bobbin coils 320 about which the stators are placed. The toroidal core contains one simple wound bobbin coil 320 for each stator 520 , 521 , 522 which will be placed around the toroid. The coils are connected to each other essentially creating one coil that runs throughout the housing. This connection scheme can be accomplished using a simple input and output connection within the housing for each winding. This setup would connect the input of a given coil with the output of the coil immediately before it in the circle. The first and last coil in the toroid would not be connected to each other, but would instead be connected to an input and output of the core. The coils could also be connected to each other through some other means known in the art to provide a similar effect of connecting the coils together. The stators are placed outside a toroidal core housing 310 and are typically U, or C shaped.
[0028] The axial spacing of the three phases 530 , 540 , 550 allows the machine to be built out of less material, and dramatically reduces the complexity of the windings. Radially spaced windings (like the ones utilized in FIG. 2 ) needed to be complex for the phase windings 53 , 54 , 55 to accommodate each of the phases immediately adjacent to them. In the present invention the windings can be constructed of simple wound bobbin coils dramatically reducing the complexity. This allows for a lighter design as less material in the windings is wasted in non-essential winding components, such as end turn windings. Lighter design and the simpler winding allows additional features to be implemented that were previously impractical or impossible.
[0029] Additionally made possible by the axial spacing of the phases is a modular assembly design. FIG. 7 illustrates a modular assembly consisting of three phases 610 , 611 , 612 . Each phase 610 , 611 , 612 is assembled in an identical fashion and then the phases are “snapped” together to form the three phase switched reluctance machine. The modular assembly consists of a housing 620 containing the stator poles 621 which are C shaped. Contained within the center of the C of the stator poles 621 are the coils 622 . Attached to the rotor 623 is a rotor pole 624 . The rotor pole 624 is I shaped, and attached to the motor shaft 680 . Once each phase 610 , 611 , 612 has been assembled they are offset around the shaft 680 as described above and fixed into place. This method provides for an easier and faster method of assembling the switched reluctance machine than has previously been available, allowing for a quicker and cheaper manufacturing process.
[0030] It is additionally possible to construct an axially spaced switched reluctance machine using non-modular assembly. A non-modular assembly requires the switched reluctance machine to be assembled as one step. A benefit provided by a non-modular assembly is that the switched reluctance machine can be built smaller. This is made possible because certain components built into each module which are necessary for a modular design are not necessary and can be removed. Removing the modular components allows a smaller construction and a lighter weight. Additionally non-modular assemblies can be “tailor made” to specific applications much easier than modular assemblies. FIG. 3 and FIG. 8 illustrate two possible non-modular designs. FIG. 8 uses a standard rotor shaft 700 with C shaped rotors 702 attached corresponding to each phase. Also, a C shaped stator 704 design is used. The design of FIG. 8 results in both a radial and an axial air gap.
[0031] FIG. 3 uses a standard rotor shaft with I shaped rotors 520 , 521 , 522 and C shaped stators 510 , 511 , 512 . The design of FIG. 3 results in a radial air gap. The advantages and disadvantages of each design vary dependant on the particular application. A person skilled in the art would be capable of determining an appropriate stator/rotor configuration for any given application. Radial gaps are more tolerant of axial runnout. Axial gaps are more tolerant of radial runnout.
[0032] Axial spacing of the phase windings also allows for the use of toroidal cores 580 containing simple wound bobbin coils 320 . Because each phase is axially spaced along the shaft, each phase has its own toroidal core 580 . This design allows for the windings to be simple wound bobbin coils as the windings do not need to accommodate adjacent phases. An illustration of a toroidal core using simple wound bobbin coils is shown in FIG. 6 . FIG. 6 illustrates a section of the toroidal core with three separate views. View A shows the placement of a simple wound bobbin coil 410 within the toroidal core housing 470 . A bobbin is placed in the middle of each C shaped stator 420 , resulting in the coil 450 being centered in the middle of the stator 420 . In an embodiment using a toroidal core, the toroidal core is placed around the rotor shaft and then the C shaped stators 420 are put into place around each of the simple wound bobbin coils 410 . The rotor poles 430 do not need to be aligned at this step as they will automatically align when the motor is turned on. View B illustrates the positioning and orientation of the simple wound bobbin coil 410 relative to the toroidal core housing 310 . The windings are arranged such that each wire in the winding runs parallel to the toroidal core housing 470 in the plane formed by the X-axis and the Y-axis and perpendicular to the toroidal core housing 470 in the Z-axis. This orientation aligns the electric field to properly induce motion when the simple wound bobbin coils 410 are charged. View C illustrates a single stator 420 and rotor pole 430 with a simple wound bobbin coil 410 within the C shape of the stator 420 . View C is rotated 90 degrees about the Y-axis relative to the rest of the drawing. As shown in view C the coil 450 is wrapped around a bobbin 460 , which is snapped into place inside the toroidal core housing 470 . An integrated cooling loop 440 is contained within the coils 450 to ensure sufficient temperature regulation. The axial or radial gaps can occur at any points around a closed circuit path form by section of the C and I laminations.
[0033] In the present invention a cooling loop 440 may be integrated in the coils 450 . Alternatively, a dedicated cooling tube may be included in the coils 450 . This is made possible because of the reduced weight and the simple winding design. The cooling loop 440 may consist of any flexible non permeable hollow tubing with adequate heat transfer characteristics. A refrigerant can then be pumped through the cooling loop 440 using any number of available means.
[0034] As illustrated schematically in FIG. 9 , a cooling circuit can be provided with fluid path 804 , and a pump 802 removing cooling fluid through the coils 450 , and outwardly to a heat exchanger 800 . Heat is taken out of the refrigerant circulated through the circuit 804 at heat exchanger 800 . Any number of methods for taking heat out of the refrigerant can be utilized. As an example, the heat exchanger could be placed in the path of a fan driven by the motor shaft. Also, more elaborate refrigerant systems including a compressor, an expansion device, etc. can be utilized. Again, a worker of ordinary skill in the art would recognize how to prepare an appropriate refrigerant system. The present invention is directed to the application of a refrigerant system within the coils of an electric motor.
[0035] If the coils 450 are constructed out of hollow wires, a similar system can be achieved without the use of an embedded cooling loop. In such a case the refrigerant would be cycled through the hollow wires instead of a cooling loop using a similar method and system as the system used for the embedded cooling loop described above. This would provide for better heat regulation than an embedded cooling loop as the cooled refrigerant would be distributed evenly throughout the coil 450 . Additionally this would distribute the cooling refrigerant throughout a larger area and reduce the quantity of materials required for construction of the coils.
[0036] Although several embodiments of this invention have been disclosed, a worker of ordinary skill in this art would recognize that certain modifications would come within the scope of this invention. For that reason, the following claims should be studied to determine the true scope and content of this invention.
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The present invention deals with a transverse flux machine of the switched reluctance variety. The transverse flux machine consists of multiple phases where each phase is spaced axially along the shaft. Axial spacing provides many benefits including a decreased weight and a capability to use simple wound bobbin coils for the windings. An embedded cooling loop is provided within the coils themselves. This cooling loop provides internal temperature regulation for the windings and allows for a higher efficiency among other benefits.
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CROSS-REFERENCE TO RELATED FOREIGN APPLICATION
This application is a non-provisional application that claims priority benefits under Title 35, United States Code, Section 119(a)-(d) from Taiwanese Patent Application entitled “METHOD AND COMPUTER SYSTEM FOR DYNAMICALLY PROVIDING ALGORITHM-BASED PASSWORD/CHALLENGE AUTHENTICATION”, by Winson C W CHAO, Wei-Shiau SUEN, Ming-Hsun WU, Ying-Hung YU, and Ta-Wei LIN, having Taiwan Patent Application Serial No. 100131432, filed on Aug. 31, 2011, which Taiwanese Patent Application is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a computer program product, method and system for dynamically providing algorithm-based password/challenge authentication.
2. Description of the Related Art
Daily life requires the use of a wide variety of information devices, such as mobile phones, personal computers, notebook computers, and tablet computers. The information devices may keep users' personal data and identity data. Due to the prevalence of networks, an increasing number of network functions are performed on-line. In particular, servers have to store users' personal data and identity data in order to provide network services, such as social networking services, webpage/email services, mobile commerce services, banking on-line transaction services, database access services, or content and information provider services. Hence, to ensure security and privacy, the servers usually require that, before accessing the services provided by the servers, users have to follow an authentication procedure for recognizing the users' identity. At present, the commonest authentication procedure is a password-based challenge authentication procedure whereby a server typically requires that, before accessing its services, users ought to enter a username and a password for identity recognition (or known as “login”), in order to prevent user personal data from being stolen or fraudulently changed.
With network coverage and accessibility increasing rapidly, hackers are becoming more likely to target a user's password with a view to faking the user's identity. Therefore, simple passwords no longer provide adequate protection. For this reason, various mechanisms are put forth to provide better protection. For example, users are required to create a password that meets the requirements of password length, complexity, and unpredictability, such that the strength of the password is sufficient to fend off brute-force search attacks and dictionary attacks. Furthermore, users are required to change their passwords regularly to invalidate old passwords, thereby reducing the chance that their passwords will be cracked. The aforesaid mechanisms enhance security and thus help users protect their accounts.
However, referring to FIG. 1 , a client end 100 requests access to different web services and an authentication procedure of a username/password 102 provided by website A 110 , website B 120 , and website C 130 through a network 140 by means of a challenge 101 . In practices, most users usually use different usernames/passwords to log in website A 110 , website B 120 , and website C 130 , respectively. The mechanisms require users to memorize passwords for accessing the web services of different websites, respectively. Furthermore, users usually log in a small number of websites on a daily basis, and thus are unlikely to memorize accurately the passwords of those websites which are seldom visited by them. Because of this, they have to guess the rarely-used passwords, not to mention that their accounts would be locked out after incorrect password entries.
Therefore, there is a need in the art to assist users in memorizing troublesome passwords while ensuring security. A solution lies in conventional one-time password (OTP) technology. However, OTP technology can provide passwords to users only when additional technology is accessible. In most circumstances, OTP technology requires an electronic device. Chances are the electronic device will get lost, and thus present the risk of losing the passwords. Furthermore, it is unlikely for an organization to share its OTP generation mechanism with another organization. Thus, to access web services provided by different websites, a user has to use different electronic devices. Therefore, users have to carry multiple portable electronic devices, thereby adding to a risk of loss.
Another solution is provided by a password hint mechanism. However, the mechanism works at the cost of undermining password security, because unauthorized persons can also see the password hint and therefore help a hacker crack the password. Furthermore, the mechanism is not effective in giving an appropriate password hint to a complicated password. Therefore, sensitive systems nowadays seldom use the mechanism.
There are numerous conventional methods of password-based challenges for providing better protection. Examples are Patent Cooperation Treaty (PCT) Publications WO 2006/020096 and, WO 2002/017556, U.S. Pat. Nos. 5,841,871 and 6,094,721, and U.S. Patent Pub. No. 2007/0011724.
SUMMARY
Provided are a computer program product, method and system for dynamically providing algorithm-based password/challenge authentication. A page is provided to authenticate a presenter of a username including a string and a field for entry of a password. An entered password entered into the page is received. An algorithm associated with the username is applied to the string included in the page to generate a generated password. A determination is made as to whether the entered password matches the generated password. The username is successfully authenticated in response to determining that the entered password matches the generated password.
BRIEF DESCRIPTION OF THE DRAWINGS
In order that the advantages of the invention will be readily understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments that are illustrated in the appended drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered to be limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings.
FIG. 1 is a schematic view of a conventional system of password/challenge authentication as known in the prior art.
FIG. 2 is an embodiment of a hardware environment of a service-provider server.
FIG. 3 is an embodiment of a system of password/challenge authentication.
FIG. 4A and FIG. 4B are embodiments of flow charts of a method of registration and login of password/challenge authentication.
FIG. 5 is an embodiment of an execution frame of registration.
FIG. 6 is an embodiment of an execution frame of verification.
FIG. 7A and FIG. 7B are embodiments of execution frames of login.
DETAILED DESCRIPTION
Reference throughout this specification to features, advantages, or similar language does not imply that all of the features and advantages that may be realized with the present invention should be or are in any single embodiment of the invention. Rather, language referring to the features and advantages is understood to mean that a specific feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present invention. Thus, discussion of the features and advantages, and similar language, throughout this specification may, but do not necessarily, refer to the same embodiment.
Furthermore, the described features, advantages, and characteristics of the invention may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize that the invention may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the invention.
The described embodiments provide a novel password-based challenge mechanism for recognizing a user identity. The mechanism requires users to memorize a single algorithm instead of multiple passwords for accessing the web services of different websites. The algorithm is stored in a server that provides authentication of a user's authority to access a web service. After a user has logged in a webpage, the server gives the user a randomly generated seed string (comprising a character, a symbol, and a number) that functions as a prompt. Then, the user enters a first string converted from the seed string with the user-memorized algorithm and treated as a password. Afterward, the server compares a correct password (a second string) converted from the seed string with the stored algorithm with the password (i.e. the first string) entered by the user. A close match indicates that the login is successful.
One embodiment provides a method for dynamically providing algorithm-based password/challenge authentication in a server, the comprising:
(a) sending a login webpage in response to a login request to access a web service from a client computer, the login webpage comprising a field for displaying a seed string generated randomly and a username entry field; (b) sending the seed string generated randomly and displayed in the seed string display field in response to a username from the client computer; and (c) comparing a first string with a second string which is converted from the seed string with an algorithm stored in a server in advance and associated with the username in response to the first string converted from the seed string with the algorithm and treated as a password and the username from the client computer.
Another embodiment provides a method for dynamically providing algorithm-based password/challenge authentication in a server, comprising:
(a) sending a login webpage in response to a login request to access a web service from a client computer, the login webpage comprising a seed string generated randomly and a username entry field; and (b) comparing a first string with a second string which is converted from the seed string with an algorithm stored in the server in advance and associated with the username in response to the first string converted from the seed string with the algorithm and treated as a password and the username from the client computer.
A yet further embodiments provides a method for dynamically providing algorithm-based password/challenge authentication in a computer system, comprising:
(a) sending a login window in response to a login request from a user, the login window comprising a display field displaying a seed string generated randomly and a username entry field; (b) sending a seed string generated randomly and displayed in the seed string display field in response to a username entered by the user; and (c) comparing a first string with a second string which is converted from the seed string with an algorithm stored in the server in advance and associated with the username in response to the first string converted from the seed string with the algorithm and treated as a password and the username from the user.
A further embodiment provides a method for dynamically providing algorithm-based password/challenge authentication in a computer system, comprising:
(a) sending a login window in response to a login request from a user, the login window comprising a seed string generated randomly and a username entry field; and (b) comparing a first string with a second string which is converted from the seed string with an algorithm stored in a server in advance and associated with the username in response to the first string converted from the seed string with the algorithm and treated as a password and the username from the user.
A still further embodiment provides a method of registering an algorithm for password-based challenge in a server, comprising:
(a) sending a registration webpage in response to a request to access a web service from a client computer, the registration webpage comprising a plurality of conversion operators, a plurality of operands, and a logical operator which are required for creating an algorithm; (b) sending a verification webpage in response to an algorithm and a username from the client computer, the verification webpage comprising a seed string generated randomly, provided to the client computer, and treated as a prompt for verifying the algorithm; (c) comparing by the server a first string with a second string which is converted from the seed string with the algorithm so as to verify the algorithm in response to the first string converted from the seed string with the algorithm and treated as a password from the client computer; and (d) storing the username and the algorithm in response to the verification.
A further embodiment provides a method of registering an algorithm for password-based challenge in a computer system, comprising:
(a) sending a login window in response to a request to access a web service from a user, the login window comprising a plurality of conversion operators, a plurality of operands, and a logical operator which are required for creating an algorithm; (b) sending a verification window in response to an algorithm and a username entered by the user, the verification window comprising a seed string generated randomly, provided to the client computer, and treated as a prompt for verifying the algorithm; (c) comparing by the computer system a first string with a second string which is converted from the seed string with the algorithm so as to verify the algorithm in response to the first string converted from the seed string with the algorithm, treated as a password, and entered by the user; and (d) storing the username and the algorithm in response to the verification.
The following description, the appended claims, and the embodiments of the present invention further illustrate the features and advantages of the present invention.
Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.
As will be appreciated by one skilled in the art, the present invention may be embodied as a computer device, a method or a computer program product. Accordingly, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, the present invention may take the form of a computer program product embodied in any tangible medium of expression having computer-usable program code embodied in the medium.
Any combination of one or more computer usable or computer readable medium(s) may be utilized. The computer-usable or computer-readable medium may be, for example but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, device, or propagation medium. More specific examples (a non-exhaustive list) of the computer-readable medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a transmission media such as those supporting the Internet or an intranet, or a magnetic storage device. Note that the computer-usable or computer-readable medium could even be paper or another suitable medium upon which the program is printed, as the program can be electronically captured, via, for instance, optical scanning of the paper or other medium, then compiled, interpreted, or otherwise processed in a suitable manner, if necessary, and then stored in a computer memory. In the context of this document, a computer-usable or computer-readable medium may be any medium that can contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device. The computer-usable medium may include a propagated data signal with the computer-usable program code embodied therewith, either in baseband or as part of a carrier wave. The computer usable program code may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc.
Computer program code for carrying out operations of the present invention may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the “C” programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer or server may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).
The embodiments of the present invention are described below with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.
These computer program instructions may also be stored in a computer-readable medium that can direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable medium produce an article of manufacture including instruction means which implement the function/act specified in the flowchart and/or block diagram block or blocks.
The computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.
Referring now to FIG. 2 through FIG. 7B , computer devices, methods, and computer program products are illustrated as structural or functional block diagrams or process flowcharts according to various embodiments of the present invention. The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
Computer System
FIG. 2 is a block diagram of an illustrative embodiment of hardware environment of a service-provider server 202 . In an exemplary embodiment, a server is a universal desktop computer comprising: a processor for executing various applications; a storage device for storing various information and program code; a display device, a communication device, an input/output device which function as interfaces for communicating with a user; and a peripheral component or other components serving a specific purpose. In another embodiment, the present invention is implemented in another way and thus having less or more other devices or components. The network can also be implemented in any form of a connection, including a fixed connection, such as a local area network (LAN) or a wide area network (WAN), or getting connected to the Internet through a dial-up connection provided by an Internet service provider (ISP). The network connection is not restricted to cable connection and wireless connection; instead, it can also be implemented by wireless connection in the form of a GSM connection or a Wi-Fi connection for communicating with a client computer. The network further comprises other hardware and software components (not shown), such as an additional computer system, router, and firewall.
As shown in FIG. 2 , a server 202 includes a processor unit 204 coupled to a system bus 206 . Also coupled to system bus 206 is a video adapter 208 , which drives/supports a display 210 . System bus 206 is coupled via a bus bridge 212 to an Input/Output (I/O) bus 214 . Coupled to I/O bus 214 is an I/O interface 216 , which affords communication with various I/O devices, including a keyboard 218 , a mouse 220 , a Compact Disk-Read Only Memory (CD-ROM) 222 , a floppy disk drive 224 , and a flash drive memory 226 . The format of the ports connected to I/O interface 216 may be any known to those skilled in the art of computer architecture, including but not limited to Universal Serial Bus (USB) ports.
The server 202 is able to communicate with a service provider server 252 via a network 228 using a network interface 230 , which is coupled to system bus 206 . Network 228 may be an external network such as the Internet, or an internal network such as an Ethernet or a Virtual Private Network (VPN). Using network 228 , the server 202 is able to access service provider server 252 .
A hard drive interface 232 is also coupled to system bus 206 . Hard drive interface 232 interfaces with a hard drive 234 . In a preferred embodiment, hard drive 234 populates a system memory 236 , which is also coupled to system bus 206 . Data that populates system memory 236 includes client computer 202 's operating system (OS) 238 and application programs 244 .
OS 238 includes a shell 240 , for providing transparent user access to resources such as application programs 244 . Generally, shell 240 is a program that provides an interpreter and an interface between the user and the operating system. More specifically, shell 240 executes commands that are entered into a command line user interface or from a file. Thus, shell 240 (as it is called in UNIX®), also called a command processor in Windows®, is generally the highest level of the operating system software hierarchy and serves as a command interpreter. The shell provides a system prompt, interprets commands entered by keyboard, mouse, or other user input media, and sends the interpreted command(s) to the appropriate lower levels of the operating system (e.g., a kernel 242 ) for processing. Note that while shell 240 is a text-based, line-oriented user interface, embodiments will equally well support other user interface modes, such as graphical, voice, gestural, etc. As depicted, OS 238 also includes kernel 242 , which includes lower levels of functionality for OS 238 , including providing essential services required by other parts of OS 238 and application programs 244 , including memory management, process and task management, disk management, and mouse and keyboard management.
The hardware framework of a client computer 252 is identical or similar to that of the server 202 , or is any conventional basic framework, and the present invention is not limited thereto. For example, the client computer 252 is a desktop computer, a notebook computer, a personal digital assistant (PDA), or a smartphone. However, FIG. 2 and the above examples are not restrictive of the embodiments. The client computer 252 comprises a browser. The browser comprises a program module and instructions. The program module and commands comply with the Hypertext Transfer Protocol (HTTP) whereby a World Wide Web (WWW) client (i.e., the client computer 252 ) sends and receives web-based messages through the Internet, thereby effectuating communication with the server 202 .
An application 244 comprises a password-based challenge module 246 of the present invention. The password-based challenge module 246 comprises a program module and commands. The program module and commands can communicate with the client computer 252 , so as to recognize a user's identity. The password-based challenge module 246 is a module in the application, or is implemented in the form of a daemon. In another embodiment, the password-based challenge module 246 is implemented as a program in another form. The password-based challenge module 246 comprises a code for executing the procedures described below and depicted with FIG. 4A and FIG. 4B .
The hardware elements depicted in the server 202 are not intended to be exhaustive, but rather are representative to highlight essential components required by the present invention. For instance, client computer 202 may include alternate memory storage devices such as magnetic cassettes, Digital Versatile Disks (DVDs), Bernoulli cartridges, and the like. These and other variations are intended to be within the spirit and scope of the present invention.
Password/Challenge Authentication Process Flow
FIG. 4A and FIG. 4B are flow charts of a method illustrated with FIG. 3 and performed at the server 202 with a password-based challenge module. FIG. 5 and FIG. 6 show execution frames of registration and verification prompted by a server and can be read in conjunction with FIG. 4A .
FIG. 4A is a flow chart of a method of registration of password/challenge authentication according to a specific embodiment.
Step 400 : the server 202 end receives a request to access a web service from the client computer 252 .
Step 402 : the server 202 sends a registration webpage 500 in response to the request (as shown in FIG. 5 ). A user of the client computer 252 enters a username and creates an intended algorithm on the registration webpage 500 .
Step 404 : the server 202 sends a verification webpage 600 in response to the algorithm created by the user of the client computer 252 (as shown in FIG. 6 ) and provides a randomly generated seed string to the user of the client computer 252 as a prompt for verifying the algorithm. Then, the user enters a first string converted from the seed string with the user-memorized algorithm and treated as a password.
Step 406 : the server 202 compares a second string converted from the seed string with the algorithm entered by the user with the first string entered by the user. A close match indicates a successful verification. The server 202 stores the username and the algorithm in response to the successful verification.
Referring to FIG. 5 , the registration webpage 500 comprises a conversion operator 510 , an operand Which 520 , an operand Where 530 , and a logical operator AND 540 which are required for an algorithm. The conversion operator 510 comprises Move, Append, Convert, Add_, Sub_ and Square, but the described embodiments are not limited to these operators.
The operand Which 520 indicates which portion of a seed string has to be converted by the conversion operator, such as the whole string (All), only characters (Character), only numbers (Number), only alphabets (Alphabet), only upper case (Upper Case), only lower case (Lower Case), the “_” string (The “_”th), the first “_” symbol (The first “_”symbol), the last “_” symbol (The last “_” symbol), and a fixed string (or “Pattern_” for short) where “_” denotes a numeric number, but the present invention is not limited thereto.
The operand Where 530 indicates the destination of conversion or the manner of conversion pertaining to the seed string portion to be converted by the conversion operator, such as head, tail, converted to upper case, converted to lower case, converted to a numeric number, converted to an alphabet letter, converted to the “_” place (The “_”th place), and converted to “Pattern_”, but the present invention is not limited thereto.
According to a specific embodiment, the webpage (not shown) to which a user enters a username is different from the registration webpage for use with an intended algorithm to be created by the user. In another embodiment, the webpage to which a username is entered can be the same as the registration webpage.
As mentioned earlier, the user of the client computer 252 enters a username, applies the conversion operator 510 , the operand Which 520 , the operand Where 530 , and the logical operator AND 540 to the registration webpage 500 , and creates an intended algorithm 550 . Furthermore, with an addition symbol 560 , the user creates an algorithm comprising a plurality of equations. After the user has created the intended algorithm, the user can enter a verification webpage 600 for performing the verification of the algorithm.
Referring to FIG. 6 , the verification webpage 600 comprises an algorithm 610 created by the user and comprising a plurality of equations and a verification box 620 , but the described embodiments are not limited thereto. The verification box 620 comprises a seed string box, a password entry box, a second string display box converted by the server 202 from the seed string with the algorithm entered by the user, and a comparison result box. For example, the server 202 generates a first string “6kq3U&;1” randomly, and converts it into a second string “LOL@35kq8U;0XD” with the algorithm 610 entered by the user. That is to say, the verification process comprises the steps of: subtracting one from the square of each of the numeric numbers in the seed string according to the first equation of the algorithm 610 ; converting the first symbol (“&” in this embodiment) in the seed string into “XD” with the second equation of the algorithm 610 and moving “XD” to the tail of the seed string; and moving “LOL@” to the head of the seed string with the second equation.
The seed string box contains seed strings generated randomly by three said servers 202 for the user to verify the algorithm. The present invention is not restrictive of the quantity of the seed strings contained in the seed string box. The seed strings of the present invention are generated randomly by any conventional technology; for further details, please read the webpage http://www.random.org/strings/ for a random string generator described therein. The described embodiments provide a string as a seed, and thus is also applicable to any environment where a user logs in a server by means of a terminal. The present invention further provides a conventional “CAPTCHA” image as a seed for use by the user. For further details of the “CAPTCHA” image, please make reference to related conventional “CAPTCHA” image production technology.
FIG. 4B is a flow chart of a method of login of password/challenge authentication according to a specific embodiment of the present invention. FIG. 4B is a flow chart of the method illustrated with FIG. 3 and performed at the server 202 . FIG. 3 is a schematic view of a system of password/challenge authentication according to a specific embodiment.
Step 410 : a server 310 sends a login webpage 700 in response to a login request to access a web service from a client computer 300 (as shown in FIG. 7A ). The login webpage 700 comprises a seed string display field 710 , a username entry field 720 , and a password entry field 730 which are generated randomly by the server 310 .
Step 412 : the server 310 sends a seed string 301 generated randomly and displayed in the seed string display field 710 in response to a username entered by a user. Alternatively, the server 310 sends a login webpage comprising the randomly generated seed string and username entry field in response to a login request to access a web service from a client computer.
Step 414 : in response to a username and a first string 303 (i.e., f(seed)) treated as a password which is converted from the seed string with the user-memorized algorithm and entered by the user, the server 310 compares a correct password (i.e., the second character string, or known as F(seed)), converted from the seed string with the stored algorithm associated with the username, with the password (i.e., the first character string, or known as f(seed)) entered by the user. A close match (that is, f(seed)=F(seed)) indicates that the login is successful.
Step 416 : in case of a login failure, the server 310 will send a login webpage 700 ′ (as shown in FIG. 7B ). Repeat step 412 and step 414 .
In the described embodiment, what is shared by and between a user and a server is an algorithm created by the user rather than any password which has to be changed regularly. In described embodiments, a password transmitted by a network is created by an algorithm and thus is a one-time password that is valid for only one login session. Therefore, even if the password is exposed, no hacker can continue to use it. Thus, described embodiments dispense with the regular changing of a password. Furthermore, the user can apply the algorithm to all websites and thus no longer needs to memorize numerous passwords for logging into different websites to access web services. Therefore, described embodiments have the advantages of a conventional OTP but dispense with the need for an electronic device, which is disadvantageous.
Furthermore, described embodiments are also applicable to a wide variety of information devices which are not Web-based, such as mobile phones, personal computers, notebook computers, and tablet computers. The information devices keep users' personal data and identity data, and thus can also provide single-machine application by means of a password-based challenge module of the described embodiments. The password-based challenge module 246 can be a module in an application. However, in another embodiment, the password-based challenge module 246 can also be implemented as a program in another form, for example, being integrated into an operating system level and adapted to challenge a user when starting the operating system.
The foregoing described embodiments are provided to illustrate and disclose the technical features of the present invention, and are not intended to be restrictive of the scope of the present invention. Hence, all equivalent variations or modifications made to the foregoing embodiments without departing from the spirit embodied in the disclosure of the present invention should fall within the scope of the present invention as set forth in the appended claims.
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Provided are a computer program product, method and system for dynamically providing algorithm-based password/challenge authentication. A page is provided to authenticate a presenter of a username including a string and a field for entry of a password. An entered password entered into the page is received. An algorithm associated with the username is applied to the string included in the page to generate a generated password. A determination is made as to whether the entered password matches the generated password. The username is successfully authenticated in response to determining that the entered password matches the generated password.
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CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit under 35 U.S.C. §119(e) of U.S. provisional application No. 61/916,889, filed Dec. 17, 2013, which is incorporated herein in its entirety by reference.
TECHNICAL FIELD
This disclosure relates to manufacturing magnetic nanocolloids and magnetic nanocomposite nanocolloids using pulsed laser ablation.
BACKGROUND
Magnetic assays can be used to identify, locate or quantify biological materials by binding a magnetic particle to a biologic analyte and using a magnetic sensor to detect the magnetic particle and thereby quantify the biologic analyte. This can be an effective manner with which to detect biologic analyte since biological materials generally do not exhibit natural magnetism, therefore any magnetic signal sensed can be assumed to originate from the magnetic nanoparticle tag.
Amorphous metals can have many desirable properties for a variety of industrial applications. An “amorphous metal” is a metal which has a disordered atomic structure. Related materials include “magnetic nanocomposites” which consist of metal crystals grown in an amorphous metal matrix. The metal crystals typically having a size of 1 to 5 nm.
Amorphous metals and magnetic nanocomposites can be used in electronic devices. For example, amorphous metals can be used in high efficiency power transformers. Magnetic nanocomposites can be used in power transformers which operate at temperatures above 400° C. Amorphous metals can also be used in anti-theft tags, for example.
SUMMARY
Aspects of disclosed implementations include magnetic particles with the composition X 1-a Y a , where X is one of the elements Co or Fe or a combination thereof, Y is a transition metal which forms a eutectic with Co or Fe, such as Zr, Ti, Sc, Ta, Hf, Y, La, Si, B or Nd or a combination thereof and wherein the value of a is between 0.4 and 0.02. The particles can have an average size between 15 and 45 nm and can be spherical or nearly spherical, with an aspect ratio less than 5:1, or more particularly having an aspect ratio of less than 1.3:1. The atomic structure of these particles can be amorphous. These particles can exist as a colloidal suspension in liquid or as a dry powder. The particles can be coated with an inert material such as Au, SiO 2 or carbon. In addition, organic molecules, for example proteins or nucleic acid, can be attached to the surface of the particles or to the surface of the inert material that coats the particles to create a targeted magnetic particle.
Another aspect of disclosed implementations include magnetic nanocomposites particles with the composition X 1-a-b Y a Z b , where X is one of the elements Co, Fe, Ni or a combination thereof; wherein Y is a transition metal such as Zr, Ti, Sc, Ta, Hf, Y, La or Nd, which can form a eutectic with Co or Fe, or a glass former such as Si or B, or a combination of these elements; where Z is one of the group of elements Au, Ag and Cu; wherein the value of a is between 0.4 and 0.02 and the value of b is between 0.05 and 0.001. The particles can have an average size between 15 and 45 nm and are spherical or nearly spherical with an aspect ratio less than 2:1, or more particularly having an aspect ratio of less than 1.3:1. These particles can exist as a colloidal suspension in liquid or as a dry powder. The atomic structure can be a mixture of crystalline and amorphous volumes distributed through the particle. The particles can be coated with an inert material such as Au, SiO 2 or carbon. Furthermore, organic molecules, for example proteins, can be attached to the surface of the particles or to the surface of the inert material that coats the particles.
Aspects of disclosed implementations include systems, methods, and apparatuses for manufacturing a colloidal suspension of isotropic magnetic particles including irradiating, with a pulsed laser, a target in a solvent wherein the pulsed laser can produce laser pulses having a pulse duration between 1 ps and 1 μs at a wavelength between 200 nm and 1500 nm at a pulse repetition rate of at least 10 Hz and a fluence greater than 2 J/cm 2 . The laser beam can be scanned across the surface of the target, where the target can include a metallic composite with the composition X 1-a Y a , where X is one of the group of elements Co, Fe, Ni, or a combination thereof, Y is an element from the group of Zr, Ti, Sc, Ta, Hf, Y, La, Nd or a combination thereof and a has a value between 0.4 and 0.02. The solvent can be an organic solvent and photothermal fragmentation can be used to modify the size or shape of the particles included in the colloidal suspension. Centrifugation can be used to further modify the size of the particles included in the colloidal suspension. The surface of the particles or the composition of the solvent can be changed to suit the application after the desired size distribution has been obtained, which can include modifying the surface of the particles with Au, SiO 2 or carbon or can include replacing part or the entirety of the solvent with a polymer or another solvent. The technique can further include attaching organic molecules including proteins to the surface of the particles or to the surface of the Au, SiO 2 or carbon which can coat the particles.
Other aspects of disclosed implementations include systems, methods, and apparatuses for manufacturing a colloidal suspension of nanocomposite particles including irradiating, with a pulsed laser, a target in a solvent wherein the pulsed laser produces laser pulses having a pulse duration between 1 ps and 1 μs at a wavelength between 200 nm and 1500 nm and a fluence of at least 2 J/cm 2 with a repetition rate greater than 10 Hz. The beam can be scanned across the surface of the target and the target can include a metallic composite with the composition X 1-a-b Y a Z b , where X can be the magnetic elements Co, Fe or Ni or a mixture thereof, Y is a transition metal or glass former which forms a eutectic with the elements of X, such as the transition metals Zr, Ti, Sc, Ta, Hf, Y, La, Nd or the glass formers Si or B or a combination thereof; where Z is one of the group of elements Au, Ag and Cu; where a has a value between 0.4 and 0.02 and b has a value between 0.05 and 0.001. The solvent can be an organic solvent and photothermal fragmentation can be used to modify the size or shape of the particles which comprise the colloidal suspension. Centrifugation can be used to further modify the size of the particles included in the colloidal suspension. After the desired size distribution is obtained, the particles can be sealed in a high pressure vial and heated to between 100 and 800° C. for at least 2 min to induce nucleation of metal crystallites in the particle. The surface of the particles or the composition of the solvent can be changed to suit the application, which can include modifying the surface of the particles with Au, SiO 2 , C or a polymer, or can include replacing part or the entirety of the solvent with a polymer or another solvent. The method can further include attaching organic molecules including proteins to the surface of the particles or to the surface of the Au, SiO 2 , C or polymer which coats the particles.
BRIEF DESCRIPTION OF THE DRAWINGS
The various features, advantages and other uses of the present apparatus will become more apparent by referring to the following detailed description and drawing in which:
FIG. 1 is the calculated DC hysteresis curve for 20 nm isotropic Co 92 Zr 8 particles in accordance with one disclosed implementation;
FIG. 2 is a flowchart diagram of a process for manufacturing a colloidal suspension of isotropic magnetic particles in accordance with one disclosed implementation;
FIG. 3 is a diagram of a system for manufacturing a colloidal suspension of magnetic nanocomposite particles in accordance with one disclosed implementation;
FIG. 4 is a diagram of critical size vs. saturation magnetization in accordance with one disclosed implementation;
FIG. 5 is a diagram of laser ablation of a target in a solution in accordance with one disclosed implementation;
FIG. 6 is a flowchart diagram of a process for manufacturing a colloidal suspension of isotropic magnetic particles in accordance with one disclosed implementation; and
FIG. 7 is a diagram of magnetic particles with vortex and collinear magnetization.
DETAILED DESCRIPTION
The following terms are defined as follows herein:
“Nanoparticles” refers to objects having a size in the range of 1 nm to 1000 nm in at least one dimension.
“Colloidal suspension” refers to particles suspended in a liquid by Brownian motion. Therefore, a colloidal suspension of gold particles refers to gold particles suspended in a liquid by Brownian motion.
“Amorphous” refers to particles with no regular ordering over distances greater than 1 nm. For the purposes of this document, a material can be considered amorphous if it has no identifiable lattice fringes when examined with high resolution electron microscopy or the material exhibits a select area electron diffraction pattern which consists of a single diffuse ring with a roughly Gaussian intensity distribution.
“Magnetic Nanocomposite” refers to a material that is a mixture of amorphous and crystalline regions. These materials can have numerous small crystals on the order of 1 to 5 nm dispersed in an amorphous matrix. Magnetic nanocomposite can be materials that have at least one identifiable amorphous region and at least one identifiable crystalline region, thereby making them a composite of amorphous and crystalline structures.
“Aspect Ratio” refers to the ratio between a particle's longest axis and shortest axis.
“Polydispersity” refers to the weight average molecular weight (M w ) divided by the number average molecular weight (M n ). The polydispersity of a colloidal suspension can be improved by making the c ratio of M w /M n closer to 1. Monodisperse refers to particles with a polydispersity less than 1.3.
“Isotropic” refers to a material which has no preferred direction. As used herein it can refer to particles that have a spherical or nearly spherical physical shape, and an amorphous atomic structure. Amorphous structures can be isotropic because the distribution of atoms can be random and uniform in every direction. Crystalline structures can be anisotropic because the crystalline lattice is not uniform in every direction. Spheres can be isotropic and shapes other than a sphere can be anisotropic.
Quantitative detection of proteins in blood and other bodily fluids can be used in the diagnosis of health issues, as it can identify diseases like cancer and bacterial infections before symptoms present. Properties of detection techniques include sufficient sensitivity, multiplexing capacity, and ease of use. Detection techniques include ELISAs, protein microarrays, and quantum dot detection platforms. In these detection techniques, a fluorescent or colorimetric signal can be complicated by autofluorescence or optical absorption from the biological matrix. Similarly, detection techniques including nanowires, microcantilevers, carbon nanotubes, and electrochemical sensors can rely on charge transfer between the sensor and the protein, or tag, of interest. Accurate measurement with these devices can require precise control of sample pH and ionic strength, which can be an unrealistic requirement in practical clinical medicine.
Magnetic assays can be a promising new method because the technology is based on mature electronics technologies and the measurement is simple to perform. Biological samples lack any magnetic background, which can eliminate the need to perform a background calibration or modify the sample before the assay is performed.
Magnetic assays can be limited by the soft magnetic nanoparticles used in their operation, therefore integrating nanoparticle tags with better high frequency susceptibility and magnetic moment can improve the detection limits and sensitivity of this assay.
Other applications for soft magnetic nanoparticles include cored inductors on integrated circuits for high frequency electronic circuits, like those used in cell phones for example, and MEMS on-board power converters. The primary goal in a power conversion circuit can be to change or control the voltage or current levels while minimizing power loss. Two common options are switched-capacitor converters and inductors. Switched-capacitor converters have become the dominant passive component because they are easier scale to smaller sizes but they suffer from fundamental limitations in power conversion efficiency. One of the problems with inductors has been the absence of magnetic core materials which can operate at frequencies above 1 MHz. Air-core inductors, which do not rely on magnetic core materials can be too large for modern integrated circuits. While some amorphous metals used in magnetic sensors can operate at frequencies above 1 MHz, it can be difficult to cheaply and easily integrate these materials into microscale and nanoscale integrated circuits.
One aspect of the disclosed invention is a colloidal suspension of spherical or nearly spherical and amorphous Co 91 Zr 9 , Co 80 Ti 20 , or Co 86 Sc 14 particles. The particles can be amorphous and spherical or nearly spherical to reduce anisotropy energy. An amorphous atomic structure eliminates magnetocrystalline anisotropy and a sphere has no shape anisotropy. If the anisotropy energy of a single particle is reduced below 1 to 2 kT and the magnetization remains collinear, then the equilibrium magnetization can be described by the Langevin function:
M z ( H,T )= M sat L (μ H z /kT) (1)
where M z is the magnetization projection onto the field direction (along the z-axis), M sat is the saturation magnetization, L=coth(x)−1/x is the Langevin function, μ is the particle magnetic moment, and H is the applied field. Since μ is related to the particle size and saturation magnetization, increasing the particle size or saturation magnetization also increases the magnetic permeability. However, when the demagnetizing field energy of a homogeneously magnetized particle becomes larger than the exchange stiffness energy of the bended magnetization configuration, the magnetization state becomes a vortex or a multi-domain, as demonstrated in FIG. 7 . Therefore, in an amorphous particle, the size of μ can be limited by the exchange stiffness constant.
In summary, the material used to form the particles can to be chosen such that: it has a large saturation magnetization, it has a large exchange stiffness, it will form a long lived amorphous state when rapidly cooled, and it is malleable enough to form nearly spherical particles. The material Co 91 Zr 9 exemplifies these properties with Co 80 Ti 20 and Co 86 Sc 14 being good related materials. Small variations in composition produce similar properties, and so the material may more generally be written as Co 1-a Zr a where larger percentages of Co yield better magnetic properties. Pure Co does not tend to remain amorphous, necessitating some concentration of Zr, so a may be in the range of 0.02 to 0.4. FIG. 1 is a diagram comparing magnetization on the vertical axis vs. magnetic field strength for isotropic (Co 92 Zr 8 ) based on simulation data.
The magnetization of larger particles can become a vortex or multiple domain. The critical size for this to occur can be estimated by micromagnetic simulations. For Co 93 Zr 9 this critical size can be between 30 and 36 nm as determined from simulations. When the magnetization/saturation magnetization drops below 1, the magnetization is no longer collinear. The desired particle size therefore can be the largest size before value of magnetization/saturation magnetization drops below 1. The desired size range from simulations can therefore be in the range of 25 nm to 38 nm. The average size of the particles that comprise the colloidal suspension may more generally be from 15 to 45 nm, as smaller sized particles can have a collinear magnetization and larger sized particles can still have a collinear magnetization due to small variations in physical properties.
More generally, the composition may be written as X 1-a Y a ; where X is one of the two elements Co, Fe, Ni or a combination thereof, Y is a transition metal which forms a eutectic with the elements of X, such as Zr, Ti, Sc, Ta, Hf, Y, La, Nd, or a combination thereof and where a is in the range of 0.02 to 0.4. Like Zr, these other elements form a eutectic with Co or Fe and may also create long lived metastable amorphous metal particles when rapidly cooled. The aspect ratio of an ideally spherical particle is 1:1 and it's desirable to have particles which are as close to prefect spheres as possible, although it's difficult to have a colloidal suspension where the particles are all ideal spheres. Therefore, the average aspect ratio of the particles is less than 2:1 or more particularly less than 1.3:1.
Colloidal suspensions of amorphous and spherical or nearly spherical Co 91 Zr 9 can improve on existing technology because common commercial Fe 3 O 4 particles exhibit decreasing magnetic permeability above 20 nm, which can be due to the increasing magnetocrystalline anisotropy energy. For applications which require both a high magnetic moment per particle and high magnetic permeability, amorphous Co 91 Zr 9 particles exhibit both an increasing magnetic moment per particle and increasing magnetic permeability up to 30 nm or greater.
These magnetic particles can also have the surface of the particles or the solvent is which the particles are suspended modified for various applications. The particles can be coated with Au, SiO 2 or carbon, and organic molecules can be attached to the Au, SiO 2 or carbon. These particles can be used in biomedical devices such as magnetic immunoassay sensors. The particles can also be dispersed in a polymer for use as a magnetic paste in integrated circuits, for example.
Examples of proteins that can be attached directly to the surface of the particle or to an Au, SiO 2 or carbon layer that coats the particle include the following; Anti-CEA and Anti-TIMP1 for the detection of cancer, Anti-PfHRP2 and Anti-PGluDH for the detection of malaria, Anti-cTnl and Anti-hFABP for the detection of cardiac problems, and Anti-ALK and Anti-KRAS for the detection of lung cancer.
Aspects of disclosed implementations provide for the production of a colloidal suspension of isotropic magnetic particles by pulsed laser ablation in liquid. FIG. 4 is a flowchart diagram of a process 400 for manufacturing a colloidal suspension of isotropic magnetic particles. Implementations of this disclosure may change the order of execution of steps of FIG. 4 without departing from the meaning and intent of this disclosure.
At step 401 , a desired particle size can be determined using a micromagnetic simulation package, such as the object oriented micromagnetic framework (OOMMF). Knowledge of the target material's saturation magnetization and exchange stiffness can be required. A simulation package is used to determine the size where a bended magnetization configuration becomes the lowest energy state, thereby setting an upper bound for the desired particle size during the production process. Alternatively, the desired size can be determined empirically by examining the magnetic properties of various sized colloids or simply determined based on previous results.
At step 402 a target with the composition X 1-a Y a , where X is one of the group of elements Co, Fe, Ni or a combination thereof, Y is an element from the group of Zr, Ti, Sc, Ta, Hf, Y, La, Nd, or a mixture thereof and a has a value between 0.4 and 0.02 is placed in an organic solvent, for example acetonitrile. The target can have a crystalline or amorphous atomic structure, as steps 402 or 404 can create particles with an amorphous atomic structure. An example of a laser that can be used to irradiate the target is a Ytterbium fiber laser that produces pulses 1 ps to 1 μs in duration at a pulse repetition rate of 10 Hz-200 kHz. The laser can produce an average power of 20 watts and can be focused using laser beam optics to provide pulses having a fluence of at least 10 J/cm 2 at the surface of the target. Irradiating the surface of the target creates a colloidal suspension of magnetic nanoparticles in the organic solvent. The beam can be scanned across the surface of the metal so the target face is evenly ablated. FIG. 5 shows a colloidal suspension 900 that includes a target 902 in a solvent 904 being impinged by a laser pulse 906 to create molten particles 908 that quickly cool to form amorphous particles 910 .
At this point the colloidal suspension of isotropic magnetic particles can be suboptimal in the sense that the distribution of particles may be broad and particles larger than the desired size can be mixed with particles of the desired size, the colloidal suspension of amorphous magnetic particles can be useful for some applications. At set 402 A if it is determined that further processing is desired, the process 400 can proceed to step 404 . If no further processing is desired, the process can proceed to step 408 .
At step 404 , the particle size distribution can be improved by photothermally fragmenting the particles which are too large. To photothermally fragment a particle, the energy absorbed by the particle needs to be larger than the energy necessary to evaporate metal from the surface of the particle. The energy necessary to evaporate metal from the surface of the particle can be calculated from the particle size, the material's boiling point, specific heat capacity, heat of fusion, boiling point, and melting point. The energy that a laser pulse imparts to a particle can be calculated from the absorption cross section of particle, the laser intensity, and pulse duration, for example. The absorption cross section of the particle can be calculated from Mie theory and depends on the particle size. The laser beam diameter in solution can be adjusted to create the desired intensity and thereby fragment particles larger than the desired size. This intensity can be a lower bound, since the particles can also cool during this time and thereby require a greater intensity to fragment.
This photothermal fragmentation process can be allowed to occur for a predetermined time in order to remove particles larger than the desired size and also potentially make particles smaller than the desired size more spherical, as smaller particles may melt and change shape. Step 404 may use the same or a different laser then the one used in step 402 . For example, the ablation step may require 5 to 15 minutes, but after the colloid reaches a certain density, the intensity can be attenuated at the target surface by the metal particles created by the laser pulses in solution so ablation is slowed or does not continue. The laser intensity can be attenuated by metal particles absorbing laser energy and thereby beginning to photothermally fragment as described in step 404 while the particle production rate decreases. In this way, during a 1 hour ablation, the first 15 minutes can correspond to step 402 but the remaining 45 minutes can correspond to step 404 . In other aspects of disclosed implementations the irradiation at step 402 can be performed using a different laser than the photothermal treatment step at step 404 . For example, step 402 can use a pulsed fiber laser and step 404 can use a continuous wave CO 2 laser.
An example of step 404 is as follows: the total energy needed to begin evaporation of a 30 nm cobalt particle is determined to be approximately 1.9E-12 J and these particles are known to have an absorption cross section of approximately 50 nm 2 at a wavelength of 1060 nm. A 1 ns pulse with a pulse energy of 1 mJ at a wavelength of 1060 nm and a beam diameter of 1 mm provides approximately 3.18E-12 J of energy to the particle, thereby reducing its size though evaporation of metal. This process can also make the particles more spherical, since particles below 30 nm can be melted and amorphous particles favor cooling as spheres. For example, the total energy needed to melt a 22 nm cobalt particle is approximately 3.57E-13 J and the same laser producing pulses with a 1 ns duration and with a pulse energy of 1 mJ and a beam diameter of 1 mm can provide approximately 5E-13 J of energy to the 22 nm particle. Since the 22 nm particle has an absorption cross section of approximately 20 nm 2 , the laser pulses can at least partially melt the particle and potentially make it more spherical.
At step 404 A the process can decide whether or not the size distribution is adequate for the intended application similarly to step 402 A. If it is decided that the particles size distribution is adequate for the intended application, the process 400 passes to step 408 . If it is decided that further conditioning of the size distribution of particles is required, at step 406 the colloidal suspension of isotropic magnetic particles can be optionally conditioned to remove particles larger than the target size by using a centrifuge or other means to remove particles larger than a desired size. The centrifuge speed necessary to remove particles larger than the desired size determined in step 406 can be calculated or determined empirically.
At step 408 the surface chemistry or solvent can be modified to fit the application. For example, to be used as tags for detecting cancer in magnetic immunoassays, the particles can be dispersed as a stable colloidal suspension in water and proteins can be bound to the particle surface. At step 408 the particles surface can be coated with an inert layer such as Au, SiO 2 or carbon. At step 410 the particles can be transferred to water from the solvent. At step 412 proteins can be conjugated to the Au, SiO 2 or carbon surface of the particles.
Examples of proteins that may be attached directly to the surface of the particle or to the Au, SiO 2 or carbon layer which coats the particle include the following; Anti-CEA and Anti-TIMP1 for the detection of cancer, Anti-PfHRP2 and Anti-PGluDH for the detection of malaria, Anti-cTnl and Anti-hFABP for the detection of cardiac problems, and Anti-ALK and Anti-KRAS for the detection of lung cancer.
Alternatively, the acetonitrile solvent can be replaced with a polymer or a mixture of a polymer and solvent which can dry as a hard paste. This paste can be incorporated into inductors on integrated circuits, or more generally used as a magnetic paste, for example.
Another aspect of disclosed implementations includes spherical or nearly spherical magnetic nanocomposite particles; wherein the particle composition may be written as X 1-a-b Y a Z b where X is Fe, Co, Ni or a combination thereof, Y includes the transition metals Zr, Ti, Sc, Ta, Hf, Y, La, or Nb and can also include the glass formers B or Si, or a combination thereof, Z is one or more noble metals Cu, Ag, Au or a combination thereof, a is in the range of 0.4 to 0.02, and b is in the range of 0.05 to 0.001. The atomic structure of the particles can be a mixture of amorphous and crystalline regions distributed though the particle's volume, making them a composite of crystalline and amorphous regions. The metal crystals may be Fe, Co, or FeCo depending on the identity of the elements which compose X. One example is the composition Co 44 Fe 44 Zr 6 B 5 Cu 1 . In this example, the amorphous matrix is composed of CoFeZrBCu and the metal crystals are composed of α-FeCo (BCC) and α′-FeCo (B2). The particles can be spherical or nearly spherical to reduce shape anisotropy, having an aspect ratio less than 2:1 or more particularly having an aspect ratio less than 1.3:1. The exchange stiffness is estimated to be between 1.1 J m −1 and 2.2 J m −1 , making the desired average size between 10 to 40 nm or more particularly 24 and 30 nm. The variation is size ranges can be because the magnetization of particles smaller than 24 nm can be collinear and particles slightly larger than 30 nm can still be collinear due to small variations in materials.
Compared to the Co 91 Zr 9 particles discussed previously, the exchange stiffness of the magnetic nanocomposite particles with the composition Co 44 Fe 44 Zr 6 B 5 Cu 1 can be lower, but the crystallization temperature can be higher, therefore the magnetophoretic mobility can be higher because the saturation magnetization is higher. These particles can be useful for lab-on-a-chip devices which use magnetic fields to both detect and manipulate particles, for example. In this case, they can have organic molecules, such as proteins, bound to their surface, or the particle can be coated with a biologically inert material such as Au, SiO 2 or carbon and then the organic molecules can be attached to this biologically inert surface. The large saturation magnetization also makes them useful in integrated circuits and for this application the particles can be dispersed in a mixture of a solvent and polymer, for example.
Another aspect of disclosed implementations is a technique for producing a colloidal suspension of magnetic nanocomposite particles by pulsed laser ablation in liquid and subsequent thermal treatment. FIG. 6 shows magnetic nanocomposite particles produced by adapting process 400 to form process 800 by specifying additional thermal treatment. At step 801 the target particle size can be determined as described above. At step 802 , a target of the form X 1-a-b Y a Z b , where X is Co, Fe, or a combination thereof, Y includes the transition metals Zr, Ti, Sc, Ta, Hf, Y, La, and Nb, and can also include the glass formers B or Si, or a combination thereof, Z is one or more noble metals Cu, Ag, Au, or a combination thereof, a is in the range of 0.4 to 0.02, and b is in the range of 0.05 to 0.001 is irradiated by laser pulses as shown in FIG. 9 ; An example of one such target can be Co 44 Fe 44 Zr 6 B 5 Cu 1 . As was describe above, the atomic structure of the target may be crystalline or amorphous. If it is determined at step 802 A that the particles require further processing to make the particle size more consistent, at step 804 the particles in solvent are heated as described above.
Other aspects of disclosed implementations include systems, methods, and apparatuses for manufacturing a colloidal suspension of nanocomposite particles including irradiating, with a pulsed laser, a target in a solvent wherein the pulsed laser produces laser pulses having a pulse duration between 1 ps and 1 μs at a wavelength between 200 nm and 1500 nm and a fluence of at least 2 J/cm 2 with a repetition rate greater than 10 Hz. The beam can be scanned across the surface of the target and the target can include a metallic composite with the composition X 1-a-b Y a Z b , where X can be the magnetic elements Co, Fe or Ni or a mixture thereof, Y is a transition metal or glass former which forms a eutectic with the elements of X, such as the transition metals Zr, Ti, Sc, Ta, Hf, Y, La, Nd or the glass formers Si or B or a combination thereof; where Z is one of the group of elements Au, Ag and Cu; where a has a value between 0.4 and 0.02 and b has a value between 0.05 and 0.001. The solvent can be an organic solvent and photothermal fragmentation can be used to modify the size or shape of the particles which comprise the colloidal suspension. Centrifugation can be used to further modify the size of the particles included in the colloidal suspension. After the desired size distribution is obtained, the particles can be sealed in a high pressure vial and heated to between 100 and 800° C. for at least 2 min to induce nucleation of metal crystallites in the particle. The surface of the particles or the composition of the solvent can be changed to suit the application, which can include modifying the surface of the particles with Au, SiO 2 , C or a polymer, or can include replacing part or the entirety of the solvent with a polymer or another solvent. The method can further include attaching organic molecules including proteins to the surface of the particles or to the surface of the Au, SiO 2 , C or polymer which coats the particles.
FIG. 3 is a diagram of a system 500 for manufacturing magnetic nanocomposite particles according disclosed implementations. System 500 includes a laser 502 that emits a pulsed laser beam 504 under the control of a controller 520 . The laser 502 can be an Ytterbium fiber laser, for example. The controller 520 can be a computing device having a CPU and memory, the CPU operative to execute instructions stored in the memory to direct the system 500 perform the activities related to manufacturing nanocomposite materials disclosed herein. The pulsed laser beam 504 can be directed to a specimen 512 by laser optics 506 . Laser optics 506 can include beam and pulse shaping optics that shape the laser beam pulses temporally and spatially to direct the pulsed laser beam 504 to a focal point at or near the surface of the specimen 512 . The laser optics 506 may also include a scanner. The specimen 512 can be included in a specimen container 508 that holds an organic solvent 510 within which the specimen 512 is submerged. The pulsed laser beam 504 creates a colloidal suspension of magnetic nanoparticles in the organic solvent 510 by impacting the surface of the specimen 512 .
System 500 also includes a high pressure container 514 and a heat source 516 for heating the colloidal suspension nanoparticles resulting from applying the pulsed laser beam 504 to the specimen 512 in the organic solvent 510 . Also included in system 500 is a centrifuge 518 which can be used to further condition the size distribution of the magnetic nanoparticles in colloidal suspension in the organic solvent 510 .
FIG. 4 is a graph of critical sizes for three particles with a saturation magnetization of 1422E3 A m −1 and exchange stiffness constants of 2.2E-11, 3.0E-11, and 1.1E-11 respectively. As can be seen from FIG. 4 , as particle size increases saturation magnetization decreases, with the onset and rate of decrease dependent upon exchange stiffness constants for each particle. Critical size can be determined for each particle by the largest size achievable before saturation magnetization begins to decline. The critical sizes, J m −1 , for these three particles are 30 nm, 36 nm, and 25 nm, respectively.
FIG. 7 is a diagram of two particles, one with a collinear magnetization 702 and one with a vortex magnetization 704 . Particles with collinear magnetization can correspond to particles under the critical size as determined by the graph in FIG. 6 , for example. Particles with a vortex magnetization are too large as determined by the graph in FIG. 6 and can be removed from the solution using techniques described above
The words “example” or “exemplary” are used herein to mean serving as an example, instance, or illustration. Any aspect or design described herein as “example’ or “exemplary” is not necessarily to be construed as preferred or advantageous over other aspects or designs. Rather, use of the words “example” or “exemplary” is intended to present concepts in a concrete fashion. As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”. That is, unless specified otherwise, or clear from context, “X includes A or B” is intended to mean any of the natural inclusive permutations. That is, if X includes A; X includes B; or X includes both A and B, then “X includes A or B” is satisfied under any of the foregoing instances. In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form. Moreover, use of the term “an embodiment” or “one embodiment” or “an implementation” or “one implementation” throughout is not intended to mean the same embodiment or implementation unless described as such.
A computing device implementing the techniques disclosed herein (and the algorithms, methods, instructions, etc. stored thereon and/or executed thereby) can be realized in hardware, software, or any combination thereof including, for example, IP cores, ASICS, programmable logic arrays, optical processors, molecular processors, quantum processors, programmable logic controllers, microcode, firmware, microcontrollers, servers, microprocessors, digital signal processors or any other suitable circuit or other information processing device, now existing or hereafter developed. In the claims, the term “processor” should be understood as encompassing any the foregoing hardware, either singly or in combination. The terms “signal” and “data” are used interchangeably.
Further, in one embodiment, for example, the techniques described herein can be implemented using a general purpose computer or general purpose processor with a computer program that, when executed, carries out any of the respective methods, algorithms and/or instructions described herein. In addition or alternatively, for example, a special purpose computer/processor can be utilized which can contain specialized hardware for carrying out any of the methods, algorithms, or instructions described herein.
Further, all or a portion of embodiments of the present disclosure can take the form of a computer program product accessible from, for example, a tangible computer-usable or computer-readable medium. A computer-usable or computer-readable medium can be any device that can, for example, tangibly contain, store, communicate, or transport the program for use by or in connection with any processor. The medium can be, for example, an electronic, magnetic, optical, electromagnetic, or a semiconductor device. Other suitable mediums are also available.
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Disclosed herein are systems, methods, and apparatuses for manufacturing highly isotropic magnetic nanoparticles. In particular, manufacturing of spherical and amorphous particles suspended in a solvent by irradiating alloy targets submerged in a solvent using nanosecond-scale laser pulses is disclosed. The absence of shape and crystalline anisotropy in the particles yields a colloidal suspension with excellent soft magnetic properties which can be used to improve the performance of various medical diagnostic devices and consumer electronics.
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FIELD OF THE INVENTION
[0001] The present invention relates to novel salt forms of atorvastatin which is known by the chemical name [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, useful as pharmaceutical agents, to methods for their production and isolation to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, as well as methods of using such compositions to treat subjects, including human subjects, suffering from hyperlipidemia, hypercholesterolemia, benign prostatic hyperplasia, osteoporosis, and Alzheimer's Disease.
BACKGROUND OF THE INVENTION
[0002] The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents.
[0003] Atorvastatin calcium is currently sold as Lipitor® having the chemical name [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid calcium salt (2:1) trihydrate and the formula:
[0000]
[0004] The nonproprietary name designated by USAN (United States Adopted Names) is atorvastatin calcium and by INN (International Nonproprietary Name) is atorvastatin. Under the established guiding principles of USAN, the salt is included in the name whereas under INN guidelines, a salt description is not included in the name.
[0005] Atovastatin calcium is a selective, competitive inhibitor of HMG-CoA reductase. As such, atorvastatin calcium is a potent lipid lowering compound and is thus useful as a hypolipidemic and/or hypocholesterolemic agent, as well as in the treatment of osteoporosis, benign prostatic hyperplasia, and Alzheimer's disease.
[0006] A number of patents have issued disclosing atorvastatin calcium, formulations of atorvastatin calcium, as well as processes and key intermediates for preparing atorvastatin calcium. These include: U.S. Pat. Nos. 4,681,893; 5,273,995; 5,003,080; 5,097,045; 5,103,024; 5,124,482; 5,149,837; 5,155,251; 5,216,174; 5,245,047; 5,248,793; 5,280,126; 5,397,792; 5,342,952; 5,298,627; 5,446,054; 5,470,981; 5,489,690; 5,489,691; 5,510,488; 5,686,104; 5,998,633; 6,087,511; 6,126,971; 6,433,213; and 6,476,235, which are herein incorporated by reference.
[0007] Atorvastatin calcium can exist in crystalline, liquid-crystalline, non-crystalline and amorphous forms.
[0008] Crystalline forms of atorvastatin calcium are disclosed in U.S. Pat. Nos. 5,969,156, 6,121,461, and 6,605,729 which are herein incorporated by reference.
[0009] Additionally, a number of published International Patent Applications have disclosed crystalline forms of atorvastatin calcium, as well as processes for preparing amorphous atorvastatin calcium. These include: WO 00/71116; WO 01/28999; WO 01/36384; WO 01/42209; WO 02/41834; WO 02/43667; WO 02/43732; WO 02/051804; WO 02/057228; WO 02/057229; WO 02/057274; WO 02/059087; WO 02/072073; WO 02/083637; WO 02/083638; and WO 02/089788.
[0010] Atorvastatin is prepared as its calcium salt, i.e., [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-1-heptanoic acid calcium salt (2:1). The calcium salt is desirable since it enables atorvastatin to be conveniently formulated in, for example, tablets, capsules, lozenges, powders, and the like for oral administration.
[0011] U.S. Pat. No. 5,273,995 discloses the mono-sodium, mono-potassium, hemi-calcium, N-methylglucamine, hemi-magnesium, hemi-zinc, and the 1-deoxy-1-(methylamino)-D-glucitol (N-methylglucamine) salts of atorvastatin.
[0012] Also, atorvastatin free acid, disclosed in U.S. Pat. No. 5,273,995, can be used to prepare these salts of atorvastatin.
[0013] Additionally, U.S. Pat. No. 6,583,295 B1 discloses a series of amine salts of HMG-CoA reductase inhibitors which are used in a process for isolation and/or purification of these HMG-CoA reductase. The tertiary butylamine and dicyclohexylamine salts of atorvastatin are disclosed.
[0014] We have now surprisingly and unexpectedly found novel salt forms of atorvastatin including salts with ammonium, benethamine, benzathine, dibenzylamine, diethylamine, L-lysine, morpholine, olamine, piperazine, and 2-amino-2-methylpropan-1-ol which have desirable properties. Additionally, we have surprisingly and unexpectedly found novel crystalline forms of atorvastatin which include salts with erbumine and sodium which have desirable properties. As such, these salt forms are pharmaceutically acceptable and can be used to prepare pharmaceutical formulations. Thus, the present invention provides basic salts of atorvastatin that are pure, have good stability, and have advantageous formulation properties compared to prior salt forms of atorvastatin.
SUMMARY OF THE INVENTION
[0015] Accordingly, a first aspect of the invention is directed to atorvastatin ammonium and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >30% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>30%)
3.5
49.0
4.4
34.8
7.4
36.5
7.8
58.0
8.8
53.9
9.3
44.1
9.9
43.8
10.6
80.3
12.4
35.1
14.1
30.1
16.8
54.5
18.3
56.2
19.0
67.8
19.5
100.0
20.3
81.4
21.4
69.0
21.6
63.8
23.1
65.5
23.9
63.8
24.8
69.0
[0016] In a second aspect, the invention is directed to Form A atorvastatin benethamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >8% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>8%)
4.7
42.2
5.3
21.7
6.0
12.9
7.8
9.6
8.9
53.3
9.5
84.4
10.5
10.6
12.0
11.5
13.8
12.1
14.3
13.3
15.6
20.1
16.7
24.6
16.9
19.9
17.6
52.7
17.8
53.1
18.1
59.7
18.8
100.0
19.1
39.1
19.9
42.4
21.3
36.2
21.9
22.8
22.7
19.8
23.6
52.4
24.3
23.5
25.9
23.5
26.3
36.2
27.0
13.5
27.9
11.8
28.8
9.4
29.6
9.8
[0017] In a third aspect, the invention is directed to Form A atorvastatin benethamine and hydrates thereof characterized by the following solid-state 13 C nuclear magnetic resonance (SSNMR) spectrum wherein chemical shift is expressed in parts per million (ppm):
[0000]
Peak #
ppm*
1
180.1
2
178.8
3
165.1
4
164.1
5
162.8
6
161.7
7
160.7
8
140.6
9
139.6
10
137.9
11
136.1
12
133.0
13
129.6
14
127.3
15
126.4
16
125.4
17
123.1
18
122.5
19
121.6
20
121.1
21
119.9
22
116.4
23
115.4
24
114.5
25
114.0
26
66.0
27
65.5
28
64.6
29
53.6
30
51.5
31
51.0
32
47.8
33
44.6
34
43.3
35
41.4
36
40.9
37
38.5
38
37.7
39
36.8
40
34.0
41
32.7
42
26.5
43
25.1
44
23.5
45
23.1
46
19.7
47
19.1
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0018] In a fourth aspect, the present invention is directed to Form A atorvastatin benethamine and hydrates thereof characterized by the following solid-state 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−113.2
2
−114.2
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0019] In a fifth aspect, the invention is directed to Form B atorvastatin benethamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >6% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>6%)
4.1
9.8
5.0
11.3
5.8
8.8
7.1
10.4
8.4
13.3
8.9
53.2
10.0
8.1
11.6
13.6
12.6
16.6
14.4
46.3
14.8
13.5
16.5
15.4
17.7
23.6
18.6
20.2
20.2
100.0
21.4
30.6
21.6
24.7
22.3
5.9
22.7
6.3
23.4
8.4
23.6
12.8
25.0
10.2
25.2
12.2
25.9
19.2
26.2
30.1
28.0
6.9
28.3
5.4
29.3
6.4
29.7
5.9
31.8
5.3
33.5
12.1
35.2
6.6
35.8
5.9
[0020] In a sixth aspect, the invention is directed to Form B atorvastatin benethamine and hydrates thereof characterized by the following solid-state 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
179.4
2
165.6
3
162.4
4
140.1
5
138.6
6
133.6
7
132.8
8
129.9
9
128.2
10
125.7
11
123.6
12
114.8
13
69.6
14
69.0
15
52.3
16
49.8
17
43.1
18
42.2
19
39.6
20
38.9
21
31.5
22
26.5
23
23.5
24
19.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0021] In a seventh aspect, the invention is directed to Form B atorvastatin benethamine and hydrates thereof characterized by the following solid-state 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−113.7
2
−114.4
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0022] In a eighth aspect, the invention is directed to Form A atorvastatin benzathine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >12% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>12%)
9.1
97.5
14.0
40.3
15.1
13.8
15.5
13.7
16.1
15.3
16.4
16.8
18.2
40.0
19.1
58.5
19.6
18.1
20.5
100.0
21.3
66.3
22.1
15.5
22.5
21.7
23.0
43.8
25.2
18.8
25.9
12.9
26.1
15.6
26.5
14.4
28.0
14.2
28.6
17.1
[0023] In a ninth aspect, the invention is directed to Form B atorvastatin benzathine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >9% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>9%)
8.3
100.0
9.1
9.4
10.2
62.6
11.7
9.1
13.2
10.2
14.4
21.1
15.8
18.1
16.6
20.0
17.1
14.8
18.6
34.0
19.1
40.7
19.4
23.0
19.7
14.8
20.6
24.0
20.9
13.1
21.4
28.8
21.8
29.3
22.3
24.9
22.6
29.2
23.3
46.1
23.5
31.3
24.3
11.0
25.0
18.9
26.5
14.8
26.8
11.6
27.4
13.2
27.9
12.3
28.2
9.3
28.9
9.3
29.1
9.8
29.7
10.9
[0024] In a tenth aspect, the invention is directed to Form C atorvastatin benzathine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >13% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>13%)
3.9
59.5
6.9
23.3
7.9
30.5
9.7
70.6
11.9
100.0
12.8
17.8
13.2
41.4
15.5
15.3
16.3
13.1
16.8
17.4
17.2
39.5
18.9
18.4
19.5
31.5
19.9
31.7
20.4
58.2
20.7
43.9
21.4
29.2
23.0
19.0
23.4
18.7
24.0
26.6
24.3
33.6
24.6
41.4
25.9
21.5
26.2
28.4
[0025] In an eleventh aspect, the invention is directed to atorvastatin dibenzylamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >8% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>8%)
4.6
10.6
8.3
50.8
9.6
13.8
9.8
10.0
10.3
14.9
10.4
12.1
10.6
19.8
11.8
13.9
12.4
7.7
13.3
10.0
14.5
10.2
14.9
11.6
15.9
11.8
16.7
10.4
17.4
23.6
18.4
19.7
18.7
38.5
19.4
24.2
19.8
48.0
20.7
100.0
21.3
56.4
21.6
26.7
22.1
13.4
22.5
21.9
23.0
9.7
23.4
29.5
23.7
29.7
24.3
11.0
24.6
13.6
25.1
13.0
25.8
31.9
26.7
8.5
28.0
10.8
29.2
12.2
33.4
9.8
34.6
8.1
34.8
9.1
[0026] In a twelfth aspect, the invention is directed to atorvastatin dibenzylamine and hydrates thereof characterized by the following solid-state 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
179.1
2
166.2
3
163.1
4
160.8
5
140.6
6
135.2
7
134.3
8
133.4
9
131.9
10
131.1
11
129.4
12
128.3
13
125.6
14
124.2
15
122.9
16
119.7
17
115.4
18
69.7
19
68.6
20
52.6
21
51.3
22
43.0
23
41.9
24
38.8
25
38.2
26
26.7
27
23.3
28
20.0
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0027] In a thirteenth aspect, the invention is directed to atorvastatin dibenzylamine and hydrates thereof characterized by the following solid-state 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−107.8
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0028] In a fourteenth aspect, the invention is directed to Form A atorvastatin diethylamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >20% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>20%)
7.0
53.0
8.2
32.0
10.8
59.3
12.3
36.0
13.3
60.8
14.4
56.0
16.1
35.5
16.5
39.3
17.0
40.0
18.2
49.3
18.4
100.0
19.4
23.0
20.0
20.5
21.0
54.5
21.7
24.5
22.3
30.5
23.0
68.8
24.3
25.5
25.1
38.5
25.4
26.9
26.3
41.3
26.8
21.8
28.4
23.8
[0029] In an fifteenth aspect, the invention is directed to Form B atorvastatin diethylamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >8% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>8%)
6.1
8.3
7.0
10.6
8.3
26.0
10.8
8.5
11.5
21.4
12.2
28.2
12.5
12.7
13.4
16.5
14.5
10.0
15.3
34.2
16.1
17.1
16.6
12.8
16.8
16.6
17.4
17.3
17.9
8.1
18.4
12.8
18.7
8.5
19.3
52.2
20.5
21.4
21.0
100.0
22.3
13.0
23.2
34.2
24.6
23.7
25.4
8.2
25.9
8.1
26.4
16.9
27.6
25.6
29.2
10.6
31.2
8.5
32.8
9.1
[0030] In an sixteenth aspect, the invention is directed to atorvastatin erbumine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >6% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>6%)
5.4
11.9
7.3
12.0
9.5
100.0
12.6
14.3
15.2
15.6
16.6
13.7
17.8
21.0
18.6
20.2
19.2
77.6
20.0
28.3
20.4
8.2
20.9
22.3
21.6
14.3
22.2
26.6
22.4
13.3
22.6
14.5
23.7
8.7
24.2
31.6
25.0
15.5
26.5
12.3
28.2
7.9
29.5
6.3
30.6
6.5
[0031] In a seventeenth aspect, the invention is directed to atorvastatin erbumine and hydrates thereof characterized by the following solid-state 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
179.3
2
164.5
3
163.0
4
160.9
5
141.3
6
140.9
7
135.3
8
134.5
9
132.8
10
129.0
11
127.7
12
124.5
13
121.8
14
120.2
15
116.5
16
115.5
17
112.4
18
71.3
19
50.3
20
47.7
21
42.6
22
41.0
23
28.5
24
26.4
25
22.6
26
21.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0032] In a eighteenth aspect, the invention is directed to atorvastatin erbumine and hydrates thereof characterized by the following solid-state 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−110.4
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0033] In a nineteenth aspect, the invention is directed to atorvastatin L-lysine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >40% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>40%)
6.7
100.0
9.5
62.1
9.8
74.3
17.1
80.4
18.7
86.5
19.6
76.8
21.1
77.1
22.1
72.1
22.5
77.9
24.0
59.5
[0034] In a twentieth aspect, the invention is directed to atorvastatin morpholine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >9% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>9%)
4.8
15.9
5.7
10.7
6.4
11.6
8.6
9.2
9.7
52.5
12.8
6.8
14.1
10.3
14.6
22.5
16.0
42.1
16.3
26.7
16.5
21.3
17.3
19.6
17.5
29.3
18.1
16.5
18.9
46.1
19.2
27.3
19.6
85.9
19.9
19.8
20.8
42.2
21.2
16.9
22.1
89.9
23.1
19.6
23.9
100.0
24.6
26.0
25.0
39.0
25.7
11.0
27.0
14.1
28.1
10.1
28.5
25.8
29.6
11.8
30.1
9.9
30.9
13.4
31.0
14.1
32.0
13.0
32.4
16.5
33.4
14.1
33.9
11.0
34.6
18.0
35.4
14.3
36.8
18.2
37.6
11.4
[0035] In a twenty-first aspect, the invention is directed to atorvastatin morpholine and hydrates thereof characterized by the following solid-state 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
179.3
2
165.9
3
162.7
4
160.5
5
139.6
6
137.8
7
134.3
8
131.2
9
129.6
10
128.7
11
127.4
12
122.9
13
120.8
14
117.9
15
116.3
16
70.8
17
69.5
18
63.4
19
42.4
20
41.2
21
40.5
22
24.8
23
20.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0036] In a twenty-second aspect, the invention is directed to atorvastatin morpholine and hydrates thereof characterized by the following 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−117.6
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0037] In a twenty-third aspect, the invention is directed to atorvastatin olamine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >15% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>15%)
8.5
100.0
9.8
74.7
11.4
17.3
12.0
15.6
16.3
27.7
17.4
43.9
18.6
85.5
19.6
45.8
20.1
43.9
20.9
96.0
21.4
31.6
22.0
30.5
22.5
66.1
22.8
35.6
23.5
20.5
24.1
42.7
25.1
23.3
25.9
25.0
26.2
33.1
27.8
19.3
28.8
27.5
29.6
20.0
31.7
20.5
37.7
22.5
[0038] In a twenty-fourth aspect, the invention is directed to atorvastatin olamine and hydrates thereof characterized by the following 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
182.0
2
178.9
3
165.4
4
161.6
5
159.5
6
137.4
7
134.8
8
133.8
9
131.0
10
128.7
11
128.0
12
127.0
13
123.1
14
122.6
15
121.9
16
120.9
17
120.1
18
117.3
19
115.6
20
114.3
21
66.5
22
66.0
23
65.2
24
58.5
25
58.2
26
51.1
27
47.8
28
46.0
29
43.9
30
42.4
31
41.3
32
40.6
33
39.8
34
25.7
35
23.1
36
21.1
37
20.7
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0039] In a twenty-fifth aspect, the invention is directed to atorvastatin olamine and hydrates thereof characterized by the following 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−118.7
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0040] In a twenty-sixth aspect, the invention is directed to atorvastatin piperazine and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >20% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>20%)
4.4
20.4
7.8
25.5
9.3
27.2
11.8
29.7
13.2
22.9
16.1
30.0
17.7
30.9
19.7
100.0
20.4
55.0
22.2
31.9
22.9
36.2
23.8
30.7
26.4
32.6
[0041] In a twenty-seventh aspect, the invention is directed to atorvastatin sodium and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >25% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>25%)
3.4
57.8
4.1
29.2
4.9
53.0
5.6
32.4
6.8
25.2
7.6
68.5
8.0
75.7
8.5
42.0
9.9
66.1
10.4
51.5
12.8
25.5
18.9
100.0
19.7
64.5
21.2
32.8
22.1
33.3
22.9
45.4
23.3
43.6
24.0
42.7
25.2
26.1
[0042] In a twenty-eighth aspect, the invention is directed to atorvastatin 2-amino-2-methylpropan-1-ol and hydrates thereof characterized by the following x-ray powder diffraction pattern expressed in terms of the 2θ and relative intensities with a relative intensity of >20% measured on a Bruker D5000 diffractometer with CuK α radiation:
[0000]
Relative
Degree
Intensity
2θ
(>20%)
4.2
95.2
6.0
59.9
6.2
43.7
8.3
26.3
11.5
20.9
12.5
36.5
12.6
31.1
16.0
44.4
17.5
54.3
18.3
52.8
18.8
34.0
19.4
55.3
19.7
100.0
21.3
26.7
22.0
31.3
22.8
21.7
23.4
29.7
23.8
28.6
[0043] In a twenty-ninth aspect, the invention is directed to atorvastatin 2-amino-2-methylpropan-1-ol and hydrates thereof characterized by the following 13 C nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
179.8
2
166.3
3
163.3
4
161.5
5
161.2
6
140.5
7
139.5
8
134.4
9
132.3
10
131.6
11
129.8
12
128.1
13
126.1
14
125.1
15
122.2
16
120.7
17
116.4
18
114.0
19
113.4
20
72.6
21
71.4
22
67.6
23
66.3
24
64.7
25
64.4
26
53.1
27
46.9
28
43.9
29
43.5
30
42.7
31
39.7
32
36.1
33
26.8
34
26.3
35
24.3
36
23.8
37
23.1
38
{dot over (2)}{dot over (2)}{dot over (.)}{dot over (0)}
39
{dot over (2)}{dot over (0)}{dot over (.)}{dot over (4)}
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0044] In a thirtieth aspect, the invention is directed to atorvastatin 2-amino-2-methylpropan-1-ol and hydrates thereof characterized by the following 19 F nuclear magnetic resonance spectrum wherein chemical shift is expressed in parts per million:
[0000]
Peak #
ppm*
1
−113.6
2
−116.5
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0045] As inhibitors of HMG-CoA reductase, the novel salt forms of atorvastatin are useful as hypolipidemic and hypocholesterolemic agents, as well as agents in the treatment of osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.
[0046] A still further embodiment of the present invention is a pharmaceutical composition for administering an effective amount of an atorvastatin salt in unit dosage form in the treatment methods mentioned above. Finally, the present invention is directed to methods for production of salt forms of atorvastatin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] The invention is further described by the following nonlimiting examples which refer to the accompanying FIGS. 1 to 30 , short particulars of which are given below.
[0048]
FIG. 1
[0049] Diffractogram of atorvastatin ammonium carried out on a Bruker D5000 diffractometer.
[0050]
FIG. 2
[0051] Diffractogram of Form A atorvastatin benethamine carried out on a Bruker D5000 diffractometer.
[0052]
FIG. 3
[0053] Solid-state 13 C nuclear magnetic resonance spectrum of Form A atorvastatin benethamine.
[0054]
FIG. 4
[0055] Solid-state 19 F nuclear magnetic resonance spectrum of Form A atorvastatin benethamine.
[0056]
FIG. 5
[0057] Diffractogram of Form B atorvastatin benethamine carried out on a Bruker D5000 diffractometer.
[0058]
FIG. 6
[0059] Solid-state 13 C nuclear magnetic resonance spectrum of Form B atorvastatin benethamine.
[0060]
FIG. 7
[0061] Solid-state 19 F nuclear magnetic resonance spectrum of Form B atorvastatin benethamine.
[0062]
FIG. 8
[0063] Diffractogram of Form A atorvastatin benzathine carried out on a Bruker D5000 diffractometer.
[0064]
FIG. 9
[0065] Diffractogram of Form B atorvastatin benzathine carried out on a Bruker D5000 diffractometer.
[0066]
FIG. 10
[0067] Diffractogram of Form C atorvastatin benzathine carried out on a Bruker D5000 diffractometer.
[0068]
FIG. 11
[0069] Diffractogram of atorvastatin dibenzylamine carried out on a Bruker D5000 diffractometer.
[0070]
FIG. 12
[0071] Solid-state 13 C nuclear magnetic resonance spectrum of atorvastatin dibenzylamine.
[0072]
FIG. 13
[0073] Solid-state 19 F nuclear magnetic resonance spectrum of atorvastatin dibenzylamine.
[0074]
FIG. 14
[0075] Diffractogram of Form A atorvastatin diethylamine carried out on a Bruker D5000 diffractometer.
[0076]
FIG. 15
[0077] Diffractogram of Form B atorvastatin diethylamine carried out on a Bruker D5000 diffractometer.
[0078]
FIG. 16
[0079] Diffractogram of atorvastatin erbumine carried out on a Bruker D5000 diffractometer.
[0080]
FIG. 17
[0081] Solid-state 13 C nuclear magnetic resonance spectrum of atorvastatin erbumine.
[0082]
FIG. 18
[0083] Solid-state 19 F nuclear magnetic resonance spectrum of atorvastatin erbumine.
[0084]
FIG. 19
[0085] Diffractogram of atorvastatin L-lysine carried out on a Bruker D5000 diffractometer.
[0086]
FIG. 20
[0087] Diffractogram of atorvastatin morpholine carried out on a Bruker D5000 diffractometer.
[0088]
FIG. 21
[0089] Solid-state 13 C nuclear magnetic resonance spectrum of atorvastatin morpholine.
[0090]
FIG. 22
[0091] Solid-state 19 F nuclear magnetic resonance spectrum of atorvastatin morpholine.
[0092]
FIG. 23
[0093] Diffractogram of atorvastatin olamine carried out on a Bruker D5000 diffractometer.
[0094]
FIG. 24
[0095] Solid-state 13 C nuclear magnetic resonance spectrum of atorvastatin olamine.
[0096]
FIG. 25
[0097] Solid-state 19 F nuclear magnetic resonance spectrum of atorvastatin olamine.
[0098]
FIG. 26
[0099] Diffractogram of atorvastatin piperazine carried out on a Bruker D5000 diffractometer.
[0100]
FIG. 27
[0101] Diffractogram of atorvastatin sodium carried out on a Bruker D5000 diffractometer.
[0102]
FIG. 28
[0103] Diffractogram of atorvastatin 2-amino-2-methylpropan-1-ol carried out on a Bruker D5000 diffractometer.
[0104]
FIG. 29
[0105] Solid-state 13 C nuclear magnetic resonance spectrum of atorvastatin 2-amino-2-methylpropan-1-ol.
[0106]
FIG. 30
[0107] Solid-state 19 F nuclear magnetic resonance spectrum of atorvastatin 2-amino-2-methylpropan-1-ol.
DETAILED DESCRIPTION OF THE INVENTION
[0108] The novel salt forms of atorvastatin may be characterized by their x-ray powder diffraction patterns and/or by their solid-state nuclear magnetic resonance spectra.
Powder X-Ray Diffraction
[0109] Atorvastatin salts were characterized by their powder x-ray diffraction patterns. Thus, the x-ray diffraction pattern was carried out on a Bruker D5000 diffractometer using copper radiation (wavelength 1:1.54056). The tube voltage and amperage were set to 40 kV and 50 mA, respectively. The divergence and scattering slits were set at 1 mm, and the receiving slit was set at 0.6 mm. Diffracted radiation was detected by a Kevex PSI detector. A theta-two theta continuous scan at 2.4°/min (1 sec/0.04° step) from 3.0 to 40° 2θ was used. An alumina standard was analyzed to check the instrument alignment. Data were collected and analyzed using Bruker axis software Version 7.0. Samples were prepared by placing them in a quartz holder. It should be noted that Bruker Instruments purchased Siemans; thus, Bruker D5000 instrument is essentially the same as a Siemans D5000.
[0110] The following tables list the 2θ and intensities of lines for the atorvastatin salts and hydrates thereof. Additionally, there are tables which list individual 2θ peaks for the atorvastatin salts and hydrates thereof. In cases were there are two or more crystalline forms of an atorvastatin salt or hydrate thereof, each form can be identified and distinguished from the other crystalline form by either a single x-ray diffraction line, a combination of lines, or a pattern that is different from the x-ray powder diffraction of the other forms.
[0111] Table 1 lists the 2θ and relative intensities of all lines that have a relative intensity of >30% in the sample for atorvastatin ammonium and hydrates thereof:
[0000]
TABLE 1
INTENSITIES AND PEAK LOCATIONS OF
DIFFRACTION LINES IN ATORVASTATIN
AMMONIUM AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>30%)
3.5
49.0
4.4
34.8
7.4
36.5
7.8
58.0
8.8
53.9
9.3
44.1
9.9
43.8
10.6
80.3
12.4
35.1
14.1
30.1
16.8
54.5
18.3
56.2
19.0
67.8
19.5
100.0
20.3
81.4
21.4
69.0
21.6
63.8
23.1
65.5
23.9
63.8
24.8
69.0
[0112] Table 2 lists individual peaks for atorvastatin ammonium and hydrates thereof:
[0000]
TABLE 2
ATORVASTATIN AMMONIUM
AND HYDRATES THEREOF
DEGREE
2θ
7.8
8.8
9.3
9.9
10.6
12.4
19.5
[0113] Table 3 lists the 2θ and relative intensities of all lines that have a relative intensity of >8% in the sample for atorvastatin benethamine Forms A and B and hydrates thereof:
[0000]
TABLE 3
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION
LINES FOR ATORVASTATIN BENETHAMINE,
FORMS A AND B AND HYDRATES THEREOF
Form A
Form B
Relative
Relative
Degree
Intensity
Degree
Intensity
2θ
(>8%)
2θ
(>6%)
4.7
42.2
4.1
9.8
5.3
21.7
5.0
11.3
6.0
12.9
5.8
8.8
7.8
9.6
7.1
10.4
8.9
53.3
8.4
13.3
9.5
84.4
8.9
53.2
10.5
10.6
10.0
8.1
12.0
11.5
11.6
13.6
13.8
12.1
12.6
16.6
14.3
13.3
14.4
46.3
15.6
20.1
14.8
13.5
16.7
24.6
16.5
15.4
16.9
19.9
17.7
23.6
17.6
52.7
18.6
20.2
17.8
53.1
20.2
100.0
18.1
59.7
21.4
30.6
18.8
100.0
21.6
24.7
19.1
39.1
22.3
5.9
19.9
42.4
22.7
6.3
21.3
36.2
23.4
8.4
21.9
22.8
23.6
12.8
22.7
19.8
25.0
10.2
23.6
52.4
25.2
12.2
24.3
23.5
25.9
19.2
25.9
23.5
26.2
30.1
26.3
36.2
28.0
6.9
27.0
13.5
28.3
5.4
27.9
11.8
29.3
6.4
28.8
9.4
29.7
5.9
29.6
9.8
31.8
5.3
33.5
12.1
35.2
6.6
35.8
5.9
[0114] Table 4 lists individual 2θ peaks for atorvastatin benethamine, Forms A and B and hydrates thereof.
[0000]
TABLE 4
FORMS A and B ATORVASTATIN BENETHAMINE
AND HYDRATES THEREOF
Form A
Form B
Degree
Degree
2θ
2θ
4.7
5.0
5.3
7.1
9.5
8.4
12.0
10.0
15.6
11.6
18.1
12.6
19.9
14.8
20.2
[0115] Table 5 lists the 2θ and relative intensities of all lines that have a relative intensity of >9% in the sample for atorvastatin benzathine Forms A, B, and C and hydrates thereof:
[0000]
TABLE 5
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION
LINES FOR ATORVASTATIN BENZATHINE,
FORMS A, B, AND C AND HYDRATES THEREOF
Form A
Form B
Form C
Relative
Relative
Relative
Degree
Intensity
Degree
Intensity
Degree
Intensity
2θ
(>12%)
2θ
(>9%)
2θ
(>13%)
9.1
97.5
8.3
100.0
3.9
59.5
14.0
40.3
9.1
9.4
6.9
23.3
15.1
13.8
10.2
62.6
7.9
30.5
15.5
13.7
11.7
9.1
9.7
70.6
16.1
15.3
13.2
10.2
11.9
100.0
16.4
16.8
14.4
21.1
12.8
17.8
18.2
40.0
15.8
18.1
13.2
41.4
19.1
58.5
16.6
20.0
15.5
15.3
19.6
18.1
17.1
14.8
16.3
13.1
20.5
100.0
18.6
34.0
16.8
17.4
21.3
66.3
19.1
40.7
17.2
39.5
22.1
15.5
19.4
23.0
18.9
18.4
22.5
21.7
19.7
14.8
19.5
31.5
23.0
43.8
20.6
24.0
19.9
31.7
25.2
18.8
20.9
13.1
20.4
58.2
25.9
12.9
21.4
28.8
20.7
43.9
26.1
15.6
21.8
29.3
21.4
29.2
26.5
14.4
22.3
24.9
23.0
19.0
28.0
14.2
22.6
29.2
23.4
18.7
28.6
17.1
23.3
46.1
24.0
26.6
23.5
31.3
24.3
33.6
24.3
11.0
24.6
41.4
25.0
18.9
25.9
21.5
26.5
14.8
26.2
28.4
26.8
11.6
27.4
13.2
27.9
12.3
28.2
9.3
28.9
9.3
29.1
9.8
29.7
10.9
[0116] Table 6 lists individual 2θ peaks for atorvastatin benzathine, Forms A, B, and C and hydrates thereof.
[0000]
TABLE 6
FORMS A, B, and C ATORVASTATIN BENZATHINE
AND HYDRATES THEREOF
Form A
Form B
Form C
Degree
Degree
Degree
2θ
2θ
2θ
14.0
8.3
3.9
15.1
10.2
6.9
14.4
7.9
15.8
9.7
18.6
12.8
21.8
23.3
[0117] Table 7 lists the 2θ and relative intensities of all lines that have a relative intensity of >8% in the sample for atorvastatin dibenzylamine and hydrates thereof:
[0000]
TABLE 7
INTENSITIES AND PEAK LOCATIONS OF
DIFFRACTION LINES FOR ATORVASTATIN
DIBENZYLAMINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>8%)
4.6
10.6
8.3
50.8
9.6
13.8
9.8
10.0
10.3
14.9
10.4
12.1
10.6
19.8
11.8
13.9
12.4
7.7
13.3
10.0
14.5
10.2
14.9
11.6
15.9
11.8
16.7
10.4
17.4
23.6
18.4
19.7
18.7
38.5
19.4
24.2
19.8
48.0
20.7
100.0
21.3
56.4
21.6
26.7
22.1
13.4
22.5
21.9
23.0
9.7
23.4
29.5
23.7
29.7
24.3
11.0
24.6
13.6
25.1
13.0
25.8
31.9
26.7
8.5
28.0
10.8
29.2
12.2
33.4
9.8
34.6
8.1
34.8
9.1
[0118] Table 8 lists the individual 2θ peaks for atorvastatin dibenzylamine and hydrates thereof:
[0000]
TABLE 8
ATORVASTATIN DIBENZYLAMINE
AND HYDRATES THEREOF
Degree
2θ
8.3
18.7
19.8
20.7
21.3
25.8
[0119] Table 9 lists the 2θ and relative intensities of all lines that have a relative intensity of >8% in the sample for atorvastatin diethylamine Forms A and B and hydrates thereof:
[0000]
TABLE 9
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION
LINES FOR ATORVASTATIN DIETHYLAMINE,
FORMS A AND B AND HYDRATES THEREOF
Form A
Form B
Relative
Relative
Degree
Intensity
Degree
Intensity
2θ
(>20%)
2θ
(>8%)
7.0
53.0
6.1
8.3
8.2
32.0
7.0
10.6
10.8
59.3
8.3
26.0
12.3
36.0
10.8
8.5
13.3
60.8
11.5
21.4
14.4
56.0
12.2
28.2
16.1
35.5
12.5
12.7
16.5
39.3
13.4
16.5
17.0
40.0
14.5
10.0
18.2
49.3
15.3
34.2
18.4
100.0
16.1
17.1
19.4
23.0
16.6
12.8
20.0
20.5
16.8
16.6
21.0
54.5
17.4
17.3
21.7
24.5
17.9
8.1
22.3
30.5
18.4
12.8
23.0
68.8
18.7
8.5
24.3
25.5
19.3
52.2
25.1
38.5
20.5
21.4
25.4
26.9
21.0
100.0
26.3
41.3
22.3
13.0
26.8
21.8
23.2
34.2
28.4
23.8
24.6
23.7
25.4
8.2
25.9
8.1
26.4
16.9
27.6
25.6
29.2
10.6
31.2
8.5
32.8
9.1
[0120] Table 10 lists individual 2θ peaks for atorvastatin diethylamine, Forms A, B, and C and hydrates thereof.
[0000]
TABLE 10
FORMS A AND B ATORVASTATIN DIETHYLAMINE
AND HYDRATES THEREOF
Form A
Form B
Degree
Degree
2θ
2θ
17.0
6.1
18.2
11.5
20.0
15.3
21.7
17.4
23.0
20.5
23.2
27.6
[0121] Table 11 lists the 2θ and relative intensities of all lines that have a relative intensity>6% in the sample for atorvastatin erbumine and hydrates thereof:
[0000]
TABLE 11
INTENSITIES AND PEAK LOCATIONS OF
DIFFRACTION LINES FOR ATORVASTATIN
ERBUMINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>6%)
5.4
11.9
7.3
12.0
9.5
100.0
12.6
14.3
15.2
15.6
16.6
13.7
17.8
21.0
18.6
20.2
19.2
77.6
20.0
28.3
20.4
8.2
20.9
22.3
21.6
14.3
22.2
26.6
22.4
13.3
22.6
14.5
23.7
8.7
24.2
31.6
25.0
15.5
26.5
12.3
28.2
7.9
29.5
6.3
30.6
6.5
[0122] Table 12 lists individual 2θ peaks for atorvastatin erbumine and hydrates thereof:
[0000]
TABLE 12
ATORVASTATIN ERBUMINE
AND HYDRATES THEREOF
Degree
2θ
5.4
7.3
9.5
17.8
19.2
20.0
22.2
24.2
[0123] Table 13 lists 2θ and relative intensities of all lines that have a relative intensity of >40% in the sample for atorvastatin L-lysine and hydrates thereof:
[0000]
TABLE 13
INTENSITIES AND PEAK LOCATIONS OF
DIFFRACTION LINES FOR ATORVASTATIN
L-LYSINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>40%)
6.7
100.0
9.5
62.1
9.8
74.3
17.1
80.4
18.7
86.5
19.6
76.8
21.1
77.1
22.1
72.1
22.5
77.9
24.0
59.5
[0124] Table 14 lists individual 2θ peaks for atorvastatin L-Lysine and hydrates thereof:
[0000]
TABLE 14
ATORVASTATIN L-LYSINE
AND HYDRATES THEREOF
Degree
2θ
6.7
9.8
17.1
24.0
[0125] Table 15 lists the 2θ and relative intensities of all lines that have a relative intensity of >9% in the sample for atorvastatin morpholine and hydrates thereof:
[0000]
TABLE 15
INTENSITIES AND PEAK LOCATIONS OF
DIFFRACTION LINES FOR ATORVASTATIN
MORPHOLINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>9%)
4.8
15.9
5.7
10.7
6.4
11.6
8.6
9.2
9.7
52.5
12.8
6.8
14.1
10.3
14.6
22.5
16.0
42.1
16.3
26.7
16.5
21.3
17.3
19.6
17.5
29.3
18.1
16.5
18.9
46.1
19.2
27.3
19.6
85.9
19.9
19.8
20.8
42.2
21.2
16.9
22.1
89.9
23.1
19.6
23.9
100.0
24.6
26.0
25.0
39.0
25.7
11.0
27.0
14.1
28.1
10.1
28.5
25.8
29.6
11.8
30.1
9.9
30.9
13.4
31.0
14.1
32.0
13.0
32.4
16.5
33.4
14.1
33.9
11.0
34.6
18.0
35.4
14.3
36.8
18.2
37.6
11.4
[0126] Table 16 lists individual 2θ peaks for atorvastatin morpholine and hydrates thereof:
[0000]
TABLE 16
ATORVASTATIN MORPHOLINE AND HYDRATES THEREOF
Degree
2θ
9.7
16.0
18.9
19.6
20.8
22.1
23.9
25.0
[0127] Table 17 lists the 2θ and relative intensities of all lines that have a relative intensity of >15% in the sample for atoraystatin olamine and hydrates thereof:
[0000]
TABLE 17
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION LINES
FOR ATORVASTATIN OLAMINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>15%)
8.5
100.0
9.8
74.7
11.4
17.3
12.0
15.6
16.3
27.7
17.4
43.9
18.6
85.5
19.6
45.8
20.1
43.9
20.9
96.0
21.4
31.6
22.0
30.5
22.5
66.1
22.8
35.6
23.5
20.5
24.1
42.7
25.1
23.3
25.9
25.0
26.2
33.1
27.8
19.3
28.8
27.5
29.6
20.0
31.7
20.5
37.7
22.5
[0128] Table 18 lists individual 2θ peaks for atorvastatin olamine and hydrates thereof:
[0000]
TABLE 18
ATORVASTATIN OLAMINE AND HYDRATES THEREOF
Degree
2θ
8.5
9.8
17.4
18.6
20.9
22.5
24.1
[0129] Table 19 lists the 2θ and relative intensities of all lines that have a relative intensity of >20% in the sample for atorvastatin piperazine and hydrates thereof:
[0000]
TABLE 19
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION LINES
FOR ATORVASTATIN PIPERAZINE AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>20%)
4.4
20.4
7.8
25.5
9.3
27.2
11.8
29.7
13.2
22.9
16.1
30.0
17.7
30.9
19.7
100.0
20.4
55.0
22.2
31.9
22.9
36.2
23.8
30.7
26.4
32.6
[0130] Table 20 lists the individual 2θ peaks for atorvastatin piperazine and hydrates thereof:
[0000]
TABLE 20
ATORVASTATIN PIPERAZINE AND HYDRATES THEREOF
Degree
2θ
7.8
9.3
11.8
16.1
19.7
[0131] Table 21 lists the 2θ and relative intensities of all lines that have a relative intensity of >25% in the sample for atoravastatin sodium and hydrates thereof:
[0000]
TABLE 21
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION LINES
FOR ATORVASTATIN SODIUM AND HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>25%)
3.4
57.8
4.1
29.2
4.9
53.0
5.6
32.4
6.8
25.2
7.6
68.5
8.0
75.7
8.5
42.0
9.9
66.1
10.4
51.5
12.8
25.5
18.9
100.0
19.7
64.5
21.2
32.8
22.1
33.3
22.9
45.4
23.3
43.6
24.0
42.7
25.2
26.1
[0132] Table 22 lists individual 2θ peaks for atorvastatin sodium and hydrates thereof:
[0000]
TABLE 22
ATORVASTATIN SODIUM AND HYDRATES THEREOF
Degree
2θ
3.4
4.9
7.6
8.0
9.9
18.9
19.7
[0133] Table 23 lists the 2θ and relative intensities of all lines that have a relative intensity of >25% in the sample for atorvastatin 2-amino-2-methylpropan-1-ol and hydrates thereof:
[0000]
TABLE 23
INTENSITIES AND PEAK LOCATIONS OF DIFFRACTION LINES
FOR ATORVASTATIN 2-AMINO-2-METHYLPROPAN-1-OL AND
HYDRATES THEREOF
Relative
Degree
Intensity
2θ
(>20%)
4.2
95.2
6.0
59.9
6.2
43.7
8.3
26.3
11.5
20.9
12.5
36.5
12.6
31.1
16.0
44.4
17.5
54.3
18.3
52.8
18.8
34.0
19.4
55.3
19.7
100.0
21.3
26.7
22.0
31.3
22.8
21.7
23.4
29.7
23.8
28.6
[0134] Table 24 lists individual peaks for atorvastatin 2-amino-2-methylpropan-1-ol and hydrates thereof:
[0000]
TABLE 24
ATORVASTATIN 2-AMINO-2-METHYLPROPAN-1-OL AND
HYDRATES THEREOF
Degree
2θ
4.2
8.3
16.0
17.5
18.3
19.4
19.7
Solid State Nuclear Magnetic Resonance
[0135] The novel salt forms of atorvastatin may also be characterized by their solid-state nuclear magnetic resonance spectra. Thus, the solid-state nuclear magnetic resonance spectra of the salt forms of atorvastatin were carried out on a Bruker-Biospin Avance DSX 500 MHz NMR spectrometer.
19 F SSNMR
[0136] Approximately 15 mg of sample were tightly packed into a 2.5 mm ZrO spinner for each sample analyzed. One-dimensional 19 F spectra were collected at 295 K and ambient pressure on a Bruker-Biospin 2.5 mm BL cross-polarization magic angle spinning (CPMAS) probe positioned into a wide-bore Bruker-Biospin Avance DSX 500 MHz NMR spectrometer. The samples were positioned at the magic angle and spun at 35.0 kHz with no cross-polarization from protons, corresponding to the maximum specified spinning speed for the 2.5 mm spinners. The fast spinning speed minimized the intensities of the spinning side bands and provided almost complete decoupling of 19 F signals from protons. The number of scans were individually adjusted for each sample to obtain adequate single/noise (S/N). Typically, 150 scans were acquired. Prior to 19 F acquisition, 19 F relaxation times were measured by an inversion recovery technique. The recycle delay for each sample was then adjusted to five times the longest 19 F relaxation time in the sample, which ensured acquisition of quantitative spectra. A fluorine probe background was subtracted in each alternate scan after presaturating the 19 F signal. The spectra were referenced using an external sample of trifluoroacetic acid (diluted to 50% V/V by H 2 O), setting its resonance to −76.54 ppm.
13 C SSNMR
[0137] Approximately 80 mg of sample were tightly packed into a 4 mm ZrO spinner for each sample analyzed. One-dimensional 13 C spectra were collected at ambient pressure using 1 H- 13 C CPMAS at 295 K on a Bruker 4 mm BL CPMAS probe positioned into a wide-bore Bruker-Biospin Avance DSX 500 MHZ NMR spectrometer. The samples were spun at 15.0 kHz corresponding to the maximum specified spinning speed for the 7 mm spinners. The fast spinning speed minimized the intensities of the spinning side bands. To optimize the signal sensitivity, the cross-polarization contact time was adjusted to 1.5 ms, and the proton decoupling power was set to 100 kHz. The number of scans were individually adjusted for each sample to obtain adequate S/N. Typically, 1900 scans were acquired with a recycle delay of 5 seconds. The spectra were referenced using an external sample of adamantane, setting its upfield resonance at 29.5 ppm.
[0138] Table 25 and Table 25a lists the 13 C NMR chemical shifts for Form A and B atorvastatin benethamine and hydrates thereof:
[0000]
TABLE 25
FORM A BENETHAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
180.1
2
178.8
3
165.1
4
164.1
5
162.8
6
161.7
7
160.7
8
140.6
9
139.6
10
137.9
11
136.1
12
133.0
13
129.6
14
127.3
15
126.4
16
125.4
17
123.1
18
122.5
19
121.6
20
121.1
21
119.9
22
116.4
23
115.4
24
114.5
25
114.0
26
66.0
27
65.5
28
64.6
29
53.6
30
51.5
31
51.0
32
47.8
33
44.6
34
43.3
35
41.4
36
40.9
37
38.5
38
37.7
39
36.8
40
34.0
41
32.7
42
26.5
43
25.1
44
23.5
45
23.1
46
19.7
47
19.1
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0000]
TABLE 25a
FORM B BENETHAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.4
2
165.6
3
162.4
4
140.1
5
138.6
6
133.6
7
132.8
8
129.9
9
128.2
10
125.7
11
123.6
12
114.8
13
69.6
14
69.0
15
52.3
16
49.8
17
43.1
18
42.2
19
39.6
20
38.9
21
31.5
22
26.5
23
23.5
24
19.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0139] Table 26 lists individual 13 C NMR chemical shifts for Form A atorvastatin benethamine:
[0000]
TABLE 26
FORM A ATORVASTATIN BENETHAMINE AND HYDRATES
THEREOF
Peak #
ppm*
1
180.1
2
178.8
3
165.1
4
164.1
5
161.7
6
160.7
7
26.5
8
25.1
9
23.5
10
23.1
11
19.7
12
19.1
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0140] Table 27 lists individual 13 C NMR chemical shifts for Form B atorvastatin benethamine:
[0000]
TABLE 27
FORM B ATORVASTATIN BENETHAMINE AND
HYDRATES THEREOF
Peak #
ppm*
1
179.4
2
165.6
22
26.5
23
23.5
24
19.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0141] Table 28 and 28a lists the 19 F NMR chemical shifts for Forms A and B atorvastatin benethamine and hydrates thereof:
[0000]
TABLE 28
FORM A ATORVASTATIN BENETHAMINE AND HYDRATES
THEREOF
Peak #
ppm*
1
−113.2
2
−114.2
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0000]
TABLE 28a
FORM B ATORVASTATIN BENETHAMINE AND HYDRATES
THEREOF
Peak #
ppm*
1
−113.7
2
−114.4
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0142] Table 29 lists the 13 C NMR chemical shifts for atorvastatin dibenzylamine and hydrates thereof:
[0000]
TABLE 29
ATORVASTATIN DIBENZYLAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.1
2
166.2
3
163.1
4
160.8
5
140.6
6
135.2
7
134.3
8
133.4
9
131.9
10
131.1
11
129.4
12
128.3
13
125.6
14
124.2
15
122.9
16
119.7
17
115.4
18
69.7
19
68.6
20
52.6
21
51.3
22
43.0
23
41.9
24
38.8
25
38.2
26
26.7
27
23.3
28
20.0
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0143] Table 30 lists individual 13 C NMR chemical shifts for atorvastatin dibenzylamine and hydrates thereof:
[0000]
TABLE 30
ATORVASTATIN DIBENZYLAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.1
2
166.2
3
163.1
4
160.8
26
26.7
27
23.3
28
20.0
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0144] Table 31 lists the 13 F NMR chemical shifts for atorvastatin dibenzylamine and hydrates thereof:
[0000]
TABLE 31
ATORVASTATIN DIBENZYLAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
−107.8
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0145] Table 32 lists the 13 C NMR chemical shifts for atorvastatin erbumine and hydrates thereof:
[0000]
TABLE 32
ATORVASTATIN ERBUMINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.3
2
164.5
3
163.0
4
160.9
5
141.3
6
140.9
7
135.3
8
134.5
9
132.8
10
129.0
11
127.7
12
124.5
13
121.8
14
120.2
15
116.5
16
115.5
17
112.4
18
71.3
19
50.3
20
47.7
21
42.6
22
41.0
23
28.5
24
26.4
25
22.6
26
21.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0146] Table 33 lists individual 13 C NMR chemical shifts for atorvastatin erbumine and hydrates thereof:
[0000]
TABLE 33
ATORVASTATIN ERBUMINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.3
2
164.5
3
163.0
4
160.9
23
28.5
24
26.4
25
22.6
26
21.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0147] Table 34 lists the 19 F NMR chemical shifts for atorvastatin erbumine and hydrates thereof:
[0000]
TABLE 34
ATORVASTATIN ERBUMINE AND HYDRATES THEREOF
Peak #
ppm*
1
−110.4
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0148] Table 35 lists the 13 C NMR chemical shifts for atorvastatin morpholine and hydrates thereof:
[0000]
TABLE 35
ATORVASTATIN MORPHOLINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.3
2
165.9
3
162.7
4
160.5
5
139.6
6
137.8
7
134.3
8
131.2
9
129.6
10
128.7
11
127.4
12
122.9
13
120.8
14
117.9
15
116.3
16
70.8
17
69.5
18
63.4
19
42.4
20
41.2
21
40.5
22
24.8
23
20.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0149] Table 36 lists individual 13 C NMR chemical shifts for atorvastatin morpholine and hydrates thereof:
[0000]
TABLE 36
ATORVASTATIN MORPHOLINE AND HYDRATES THEREOF
Peak #
ppm*
1
179.3
2
165.9
4
160.5
22
24.8
23
20.6
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0150] Table 37 lists individual 13 F NMR chemical shifts for atorvastatin morpholine and hydrates thereof:
[0000]
TABLE 37
ATORVASTATIN MORPHOLINE AND HYDRATES THEREOF
Peak #
ppm*
1
−117.6
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0151] Table 38 lists the 13 C NMR chemical shifts for atorvastatin olamine and hydrates thereof:
[0000]
TABLE 38
ATORVASTATIN OLAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
182.0
2
178.9
3
165.4
4
161.6
5
159.5
6
137.4
7
134.8
8
133.8
9
131.0
10
128.7
11
128.0
12
127.0
13
123.1
14
122.6
15
121.9
16
120.9
17
120.1
18
117.3
19
115.6
20
114.3
21
66.5
22
66.0
23
65.2
24
58.5
25
58.2
26
51.1
27
47.8
28
46.0
29
43.9
30
42.4
31
41.3
32
40.6
33
39.8
34
25.7
35
23.1
36
21.1
37
20.7
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0152] Table 39 lists the individual 13 C NMR chemical shifts for atorvastatin olamine and hydrates thereof:
[0000]
TABLE 39
ATORVASTATIN OLAMINE AND HYDRATES THEREOF
Peak #
PPM#
1
182.0
2
178.9
3
165.4
4
161.6
5
159.5
34
25.7
35
23.1
36
21.1
37
20.7
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0153] Table 40 lists the 19 F NMR chemical shifts for atorvastatin olamine and hydrates thereof:
[0000]
TABLE 40
ATORVASTATIN OLAMINE AND HYDRATES THEREOF
Peak #
ppm*
1
−118.7
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0154] Table 41 lists the 13 C NMR chemical shifts for atorvastatin 2-amino-2-methyl-propan-1-ol and hydrates thereof:
[0000]
TABLE 41
ATORVASTATIN 2-AMINO-2-METHYL-PROPAN-1-OL AND
HYDRATES THEREOF
Peak #
ppm*
1
179.8
2
166.3
3
163.3
4
161.5
5
161.2
6
140.5
7
139.5
8
134.4
9
132.3
10
131.6
11
129.8
12
128.1
13
126.1
14
125.1
15
122.2
16
120.7
17
116.4
18
114.0
19
113.4
20
72.6
21
71.4
22
67.6
23
66.3
24
64.7
25
64.4
26
53.1
27
46.9
28
43.9
29
43.5
30
42.7
31
39.7
32
36.1
33
26.8
34
26.3
35
24.3
36
23.8
37
23.1
38
{dot over (2)}{dot over (2)}{dot over (.)}{dot over (0)}
39
{dot over (2)}{dot over (0)}{dot over (.)}{dot over (4)}
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0155] Table 42 lists individual 13 C NMR chemical shifts for atorvastatin 2-amino-2-methyl-propan-1-ol and hydrates thereof:
[0000]
TABLE 42
ATORVASTATIN 2-AMINO-2-METHYL-PROPAN-1-OL AND
HYDRATES THEREOF
Peak #
ppm*
1
179.8
2
166.3
3
163.3
38
{dot over (2)}{dot over (2)}{dot over (.)}{dot over (0)}
39
{dot over (2)}{dot over (0)}{dot over (.)}{dot over (4)}
*Values in ppm with respect to trimethylsilane (TMS) at 0 ppm; referenced using an external sample of adamantane, setting is upfield resonance to 29.5 ppm.
[0156] Table 43 lists the 19 F NMR chemical shifts for atorvastatin 2-amino-2-methyl-propan-1-ol and hydrates thereof:
[0000]
TABLE 43
ATORVASTATIN 2-AMINO-2-METHYL-PROPAN-1-OL AND
HYDRATES THEREOF
Peak #
ppm*
1
−113.6
2
−116.5
*Values in ppm with respect to CCl 3 F at 0 ppm, referenced using an external standard of trifluoroacetic acid (50% V/V in water) at −76.54 ppm.
[0157] Additionally, Form A & B atorvastatin benethamine, atorvastatin dibenzylamine, atorvastatin erbumine, atorvastatin morpholine, atorvastatin olamine, and atorvastatin 2-amino-2-methyl-propan-1-ol or a hydrate thereof of the aforementioned salts may be characterized by an x-ray powder diffraction pattern or a solid state 19 F nuclear magnetic resonance spectrum. For example:
[0158] An atorvastatin ammonium or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 7.8, 8.8, 9.3, 9.9, 10.6, 12.4, and 19.5.
[0159] A Form A atorvastatin benethamine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 4.7, 5.3, 9.5, 12.0, 15.6, 18.1, and 19.9, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: −113.2 and −114.2.
[0160] A Form B atorvastatin benethamine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 5.0, 7.1, 8.4, 10.0, 11.6, 12.6, 14.8, and 20.2, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: −113.7 and −114.4.
[0161] A Form A atorvastatin benzathine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 14.0 and 15.1.
[0162] A Form B atorvastatin benzathine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 8.3, 10.2, 14.4, 15.8, 18.6, 21.8, and 23.3.
[0163] A Form C atorvastatin benzathine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 3.9, 6.9, 7.9, 9.7, and 12.8.
[0164] An atorvastatin dibenzylamine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 8.3, 18.7, 19.8, 20.7, 21.3, and 25.8, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: −107.8.
[0165] A compound selected from the group consisting of:
(a) Form A atorvastatin diethylamine or hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 17.0, 18.2, 20.0, 21.7, and 23.0; and (b) Form B atorvastatin diethylamine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 6.1, 11.5, 15.3, 17.4, 20.5, 23.2, and 27.6.
[0168] An atorvastatin erbumine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 5.4, 7.3, 9.5, 17.8, 19.2, 20.0, 22.2, and 24.2, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: −110.4.
[0169] An atorvastatin L-lysine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 6.7, 9.8, 17.1, and 24.0.
[0170] An atorvastatin morpholine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 9.7, 16.0, 18.9, 19.6, 20.8, 22.1, 23.9, and 25.0, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts expressed in parts per million: −117.6.
[0171] An atorvastatin olamine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 8.5, 9.8, 17.4, 18.6, 20.9, 22.5, and 24.1, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts measured in parts per million: −118.7.
[0172] An atorvastatin piperazine or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 7.8, 9.3, 11.8, 16.1, and 19.7.
[0173] An atorvastatin sodium or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 3.4, 4.9, 7.6, 8.0, 9.9, 18.9, and 19.7.
[0174] An atorvastatin 2-amino-2-methylpropan-1-ol or a hydrate thereof having an x-ray powder diffraction pattern containing the following 2θ peaks measured using CuK α radiation: 4.2, 8.3, 16.0, 17.5, 18.3, 19.4, and 19.7, or a solid state 19 F nuclear magnetic resonance having the following chemical shifts measured in parts per million: −113.6 and −116.5.
[0175] The salt forms of atorvastatin of the present invention, regardless of the extent of hydration and/or solvation having equivalent x-ray powder diffractograms, or SSNMR, are within the scope of the present invention.
[0176] The new salt forms of atorvastatin described herein have advantageous properties. For example, the benethamine, benzathine, dibenzylamine, diethylamine, erbumine, and morpholine salts were determined to be anhydrous, high melting as well as considered to be non-hygroscopic compounds. The olamine and 2-amino-2-methylpropan-1-ol salts were determined to be anhydrous and high melting as well. Also, the diethylamine, erbumine, morpholine, olamine, and 2-amino-2-methylpropan-1-ol salts of atorvastatin exhibited higher aqueous solubility compared to Form I atorvastatin calcium (disclosed in U.S. Pat. No. 5,969,156).
[0177] The present invention provides a process for the preparation of the salt forms of atorvastatin which comprises preparing a solution of atorvastatin free acid (U.S. Pat. No. 5,213,995) in one of the following solvents: acetone, acetonitrile, THF, 1:1 acetone/water (v/v), isopropanol (IPA), or chloroform. The cationic counterion solutions were prepared using either 0.5 or 1.0 equivalent in the same solvent. Water was added to some counterions to increase their solubility. The atorvastatin free acid solution was added to the counterion solution while stirring. The reaction was stirred for at least 48 hours at ambient temperature. Samples containing solids were vacuum filtered, washed with the reaction solvent, and air-dried overnight at ambient conditions. If precipitation was not present after ˜2 weeks, the solution was slowly evaporated. All samples were stored at ambient temperature and characterized as described hereinafter.
[0000]
TABLE 44
Structure of Counterions used in the preparation of Atorvastatin salts.
Common
Structure
Name
Name
+ NH 4
Ammonium
Ammonium
N-benzyl-2-Phenylethylamine
Benethamine
N,N′-Bis(phenylmethyl)-1,2- ethanediamine
Benzathine
N-(Phenylmethyl) benzenemethanamine
Dibenzylamine
N-Ethylethanamine
Diethylamine
tert-butylamine
Erbumine
(S)-2,6-diaminohexanoic acid
L-Lysine
Tetrahydro-2H-1,4-oxazine
Morpholine
2-aminoethanol
Olamine
Na
Sodium
Sodium
Hexahydropyrazine
Piperazine
2,2-Diethylethanolamine
2-amino-2methylpropan- 1-ol
[0178] The compounds of the present invention can be prepared and administered in a wide variety of oral and parenteral dosage forms. Thus, the compounds of the present invention can be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compounds of the present invention can be administered by inhalation, for example, intranasally. Additionally, the compounds of the present invention can be administered transdermally.
[0179] For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
[0180] In powders, the carrier is a finely divided solid which is in a mixture with the finely divided active component.
[0181] In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.
[0182] The powders and tablets preferably contain from two or ten to about seventy percent of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term “preparation” is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component, with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.
[0183] For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogenous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify.
[0184] Liquid form preparations include solutions, suspensions, retention enemas, and emulsions, for example water or water propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution.
[0185] Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing, and thickening agents as desired.
[0186] Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.
[0187] Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.
[0188] The pharmaceutical preparation is preferably in unit dosage form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.
[0189] The quantity of active component in a unit dose preparation may be varied or adjusted from 0.5 mg to 100 mg, preferably 2.5 mg to 80 mg according to the particular application and the potency of the active component. The composition can, if desired, also contain other compatible therapeutic agents.
[0190] In therapeutic use as hypolipidemic and/or hypocholesterolemic agents and agents to treat osteoporosis, benign prostatic hyperplasia, and Alzheimer's disease, the salt forms of atorvastatin utilized in the pharmaceutical method of this invention are administered at the initial dosage of about 2.5 mg to about 80 mg daily. A daily dose range of about 2.5 mg to about 20 mg is preferred. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the art. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstance is reached. For convenience, the total daily dosage may be divided and administered in portions during the day if desired.
[0191] The following nonlimiting examples illustrate the inventors' preferred methods for preparing the compounds of the invention.
Example 1
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, ammonium salt (atorvastatin ammonium)
[0192] The ammonium salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (ACN) (0.634 g in 25 mL of ACN). A solution was prepared by dissolving 12.04 mg of ammonium hydroxide (1.0 equivalents) in acetonitrile (0.5 mL). The stock solution of atorvastatin free acid (2.24 mL) was added to the counterion solution with stirring. If a gel formed, additional acetonitrile and water was added as necessary. After 2 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with acetonitrile and air dried at ambient conditions to afford atorvastatin ammonium.
Example 2
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, N-benzyl-2-phenylethylamine (atorvastatin benethamine)
[0193] Method A:
[0194] The benethamine salt of atorvastatin (Form A) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of N-benzyl-2-phenylethylamine (benethamine) was prepared by dissolving 378.59 mg (1.0 equivalents) in acetonitrile (10 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Over time, an additional 40 mL of acetonitrile was added to prevent the formation of a gel. After 5 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin benethamine Form A.
[0195] Method B:
[0196] The benethamine salt of atorvastatin (Form B) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in 2-propanol (IPA) (1 g in 40 mL of IPA). A solution of N-benzyl-2-phenylethylamine (benethamine) was prepared by dissolving 388.68 mg (1.1 equivalents) in 2-propanol (100 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Seed crystals of the benethamine salt were added. The mixture was reduced to a wet solid under a nitrogen bleed, and the resulting solids were slurried in 2-propanol (40 mL). After 7 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with 2-propanol (25 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin benethamine Form B.
Example 3
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid,N,N 1 -bis(phenylmethyl)-1,2-ethanediamine (atorvastatin benzathine)
[0197] Method A:
[0198] The benzathine salt of atorvastatin (Form A) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of N,N′-bis(phenylmethyl)-1,2-ethanediamine (benzathine) was prepared by dissolving 220.64 mg (0.5 equivalents) in acetonitrile (80 mL) and water (20 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. After 2 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford benzathine Form A.
[0199] Method B:
[0200] The benzathine salt of atorvastatin (Form B) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of N,N′-bis(phenylmethyl-1,2-ethanediamine (benzathine) was prepared by dissolving 220.64 mg (0.5 equivalents) in acetonitrile (80 mL) and water (20 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. After 2 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL) to afford atorvastatin benzathine Form B. Note that this procedure is the same as above except that the sample was not oven dried.
[0201] Method C:
[0202] The benzathine salt of atorvastatin (Form C) was synthesized by adding Form A atorvastatin benzathine to 3 mL of deionized water in excess of its solubility. The slurry was stirred at room temperature for 2 days, isolated by vacuum filtration, and dried under ambient conditions to yield atorvastatin benzathine Form C.
Example 4
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid,N-(phenylmethyl)benzenemethanamine (atorvastatin dibenzylamine)
[0203] The dibenzylamine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of dibenzylamine was prepared by dissolving 351.05 mg (1.0 equivalents) in acetonitrile (100 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Over time, additional acetonitrile was added to prevent formation of a gel (100 mL), and the solid was allowed to stir. After 4 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin dibenzylamine.
Example 5
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid,N-ethylethanamine (atorvastatin diethylamine)
[0204] Method A:
[0205] The diethylamine salt of atorvastatin (Form A) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of diethylamine was prepared by dissolving 132.33 mg (1.0 equivalents) in acetonitrile (20 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Over time, an additional 40 mL of acetonitrile was added to prevent the formation of a gel. After 5 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin diethylamine Form A.
[0206] Method B:
[0207] The diethylamine salt of atorvastatin (Form B) was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of diethylamine was prepared by dissolving 132.33 mg (1.0 equivalents) in acetonitrile (20 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Over time, an additional 40 mL of acetonitrile was added to prevent the formation of a gel. After 5 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL) to afford atorvastatin diethylamine Form B. Note that this procedure is the same as above except that the sample was not oven dried.
Example 6
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, tertiary-butylamine (atorvastatin erbumine)
[0208] The erbumine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of tert-butylamine (erbumine) was prepared by dissolving 128.00 mg (1.0 equivalents) in acetonitrile (10 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Over time, an additional 120 mL of acetonitrile was added to prevent the formation of a gel. After 5 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin erbumine.
Example 7
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, L-lysine (atorvastatin L-lysine)
[0209] The L-lysine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in isopropyl alcohol (IPA) (2.577 g in 50 mL of IPA). A solution of L-lysine was prepared by dissolving 28.0 mg (1.0 equivalents) in isopropyl alcohol (1 mL). The stock solution of atorvastatin free acid (2.08 mL) was added to the counterion solution with stirring. After 7 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with IPA and allowed to air dry at ambient temperature to afford L-lysine.
Example 8
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, tetrahydro-2H-1,4-oxazine (atorvastatin morpholine)
[0210] The morpholine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of morpholine was prepared by dissolving 160.28 mg (1.1 equivalents) in acetonitrile (100 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. No salt formed, so the solution was evaporated under N 2 until a white solid formed. Acetonitrile was then added to the solid (50 mL), and the solid was allowed to stir. After 3 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (25 mL), and placed in a 25° C. oven under nitrogen to dry overnight to afford atorvastatin morpholine.
Example 9
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, 2-aminoethanol (atorvastatin olamine)
[0211] Method A—
[0212] The olamine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (0.8 g in 25 mL of ACN). A solution of olamine was prepared by dissolving 15.0 mg of olamine (˜2.7 equivalents) in 0.5 mL of acetonitrile. The stock solution of atorvastatin free acid (3.0 mL) was added to the counterion solution with stirring. If a gel formed, additional acetonitrile was added as necessary. After 6 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with acetonitrile and air dried at ambient conditions to afford atorvastatin olamine.
[0213] Method B—
[0214] The olamine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of 2-aminoethanol (olamine) was prepared by dissolving 139.77 mg (1.1 equivalents) in acetonitrile (100 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Seed crystals of the olamine salt were added. Over time, additional acetonitrile was added to aid in stirring (300 mL), and the solid was allowed to stir. After 4 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry for two days to afford atorvastatin olamine.
Example 10
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, piperazine (atorvastatin piperazine)
[0215] The piperazine salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in isopropyl alcohol (2.577 g in 50 mL of IPA). A solution of piperazine was prepared by dissolving 14.4 mg (1.0 equivalents) in isopropyl alcohol (1 mL). The stock solution of atorvastatin free acid (1.85 mL) was added to the counterion solution with stirring. After 7 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with isopropyl alcohol and air dried at ambient conditions to afford atorvastatin piperazine.
Example 11
[R—(R′,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, sodium (atorvastatin sodium)
[0216] The sodium salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (0.634 g in 25 mL of ACN). A solution was prepared by dissolving 2.67 mg of sodium hydroxide (1.0 equivalents) in 0.5 mL of acetonitrile and 0.05 mL of water. The stock solution of atorvastatin free acid (1.55 mL) was added to the counterion solution with stirring. If a gel formed, additional acetonitrile and water was added as necessary. After 6 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with acetonitrile and air dried at ambient conditions to afford atorvastatin sodium.
Example 12
[R—(R*,R*)]-2-(4-Fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, 2-amino-2-methylpropan-1-ol (atorvastatin 2-amino-2-methylpropan-1-ol)
[0217] Method A—
[0218] The 2-amino-2-methylpropan-1-ol salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (0.8 g in 25 mL of ACN). A solution of 2-amino-2-methylpropan-1-ol was prepared by dissolving 6.1 mg of 2-amino-2-methylpropan-1-01 (1 equivalents) in 0.5 mL of acetonitrile. The stock solution of atorvastatin free acid (1.21 mL) was added to the counterion solution with stirring. If a gel formed, additional acetonitrile was added as necessary. After 6 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a 0.45 μm nylon 66 membrane filter. The solids were rinsed with acetonitrile and air dried at ambient conditions to afford atoravastatin 2-amino-2-methylpropan-1-01.
[0219] Method B—
[0220] The 2-amino-2-methylpropan-1-ol salt of atorvastatin was synthesized by preparing a stock solution of the free acid of atorvastatin (U.S. Pat. No. 5,273,995) in acetonitrile (1 g in 40 mL of ACN). A solution of 2-amino-2-methylpropan-1-ol was prepared by dissolving 173.08 mg (1.1 equivalents) in acetonitrile (100 mL). The stock solution of atorvastatin free acid was added to the counterion solution with stirring. Seed crystals of the 2-amino-2-methylpropan-1-ol salt were added. Over time, additional acetonitrile was added to aid in stirring (100 mL), and the solid was allowed to stir. After 4 days of stirring at ambient temperature, the solids were isolated by vacuum filtration using a Buchner funnel fitted with a paper filter (#2 Whatman). The solids were rinsed with acetonitrile (75 mL), and placed in a 25° C. oven under nitrogen to dry for two days to afford atorvastatin 2-amino-2-methylpropan-1-ol.
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Novel salt forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid characterized by their X-ray powder diffraction pattern and solid-state NMR spectra are described, as well as methods for the preparation and pharmaceutical composition of the same, which are useful as agents for treating hyperlipidemia, hypercholesterolemia, osteoporosis, benign prostatic hyperplasia, and Alzheimer's Disease.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to an image signal transmission apparatus for transmitting image signals produced in a personal computer to a display device, such as a liquid crystal projector, plasma display panel (PDP) or the like, which is relatively remote from the personal computer.
2. Description of the Prior Art
[1] In a case of transmitting image signals produced in a personal computer to a display device via an analog transmission cable, if the analog transmission cable is long, it is apt to cause image deterioration. Such image deterioration will be noticeable especially on the display device having a high resolution of 1024.times.768 pixels (XGA), 1280.times.1024 pixels (SXGA) or the like.
Some image signal transmission apparatus have already been developed that cause no image deterioration even when the transmission cables are long. An example of those apparatus is “PanelLink” by Silicon Image, Inc. in the United States, which has been developed based on a signal transmission technology called TMDS (Transition Minimized Differential Signaling).
According to this signal transmission technology of TMDS, red, blue and green signals (RGB) and a clock signal are serially transmitted in a differential method. This differential method, which is a method for transmitting a single signal by use of two transmission lines, realizes noise immunity and a stable signal transmission and further achieves a high transmission speed and a long-distance cable transmission. It becomes, however, difficult for this method to provide such transmissions if the resolution of image data is further raised up to an ultrahigh resolution of 1600.times.1200 pixels (UXGA), 2048.times.1536 pixels (QXGA) or the like which causes the transmission cable to reach its own physical limit. As a solution to this problem, there has been proposed “Dual Link Method” by the DDWG (Digital Display Working Group) in its DVI (Digital Visual Interface) specification. Unlike the conventional “PanelLink” (which will be referred to as “Single Link” method in contrast to the “Dual Link” method hereinafter), the “Dual Link” method transmits the R, G, and B signals, by use of not a respective single channel for each signal, that is, three channels but two channels for each signal, that is, six channels, after performing a one-phase to two-phase conversion of each signal. In this way, the “Dual Link” method can ensure a bandwidth that is twice as wide as that of the “Single Link” method, allowing the image transmission of an ultrahigh resolution, such as UXGA, QXGA or the like. Additionally, the one-phase to two-phase conversion of each signal can reduce the required transmission rate and hence realizes the signal transmission through a longer cable.
FIGS. 1 and 2 show the structures of signal transmission apparatus employing the “Single Link” and “Dual Link” methods, respectively.
In the signal transmission apparatus employing the “Single Link” method, a PanelLink transmitter 301 receives image data represented by parallel signals and performs a parallel-serial conversion of the image data from the parallel signals to serial signals. The image data of serial-converted signals are transmitted through a cable 302 to a PanelLink receiver 303 . The cable 302 comprises three pairs of signal lines for transmitting the image data and one pair of signal lines for transmitting a clock signal. The PanelLink receiver 303 performs a serial-parallel conversion of the received serial signals to the parallel signals.
In the signal transmission apparatus employing the “Dual Link” method, the even data of image data represented by parallel signals are applied to a PanelLink transmitter 401 , while the odd data of the image data are applied to a PanelLink transmitter 402 . The PanelLink transmitters 401 and 402 each perform a parallel-serial conversion of the received image data from the parallel signals to serial signals.
The even data of the image data that have been converted into the serial signals by the PanelLink transmitter 401 are transmitted through a cable 403 to a PanelLink receiver 404 . The odd data of the image data that have been converted into the serial signals by the PanelLink transmitter 402 are transmitted through the cable 403 to a PanelLink receiver 405 . The cable 403 comprises six pairs of signal lines for transmitting the image data and one pair of signal lines for transmitting a clock signal. The PanelLink receivers 404 and 405 each perform a serial-parallel conversion of the received serial signals to the parallel signals.
The object of the present invention is to provide an image signal transmission apparatus that allows the transmission of image signals to be done by use of a transmission method suitable for the resolution of the image signals.
[2] If, in the “Dual Link” method of FIG. 2, the RGB image data represented by the parallel signals are not separated into even and odd data but are applied to the PanelLink transmitter 401 as they are, and if the PanelLink receiver 404 only is activated, while the PanelLink transmitter 402 and PanelLink receiver 405 not being activated, then it would correspond to the “Single Link” method of FIG. 1 .
It is difficult for the “PanelLink” method to effect the transmission of an ultrahigh resolution, such as UXGA, QXGA or the like, and/or effect a long-distance transmission. Thus, in the case of effecting such an ultrahigh resolution transmission and/or a long-distance transmission, the “Dual Link” method is effective.
On the other hand, in the case of transmitting the signal of a low-resolution, such as VGA or the like, the “Single Link” method works to a sufficient degree. In addition, because of an increasing demand for portability of the apparatus on the image transmitting side, such as a personal computer or the like, and that on the image receiving side, such as a liquid crystal projector or the like, the need to reduce the power consumption has become important. Thus, when a low-resolution signal is transmitted or when no long-distance transmission is required, it is more desirable to effect the signal transmission by use of the “Single Link” method.
The object of the present invention is to provide an image signal transmission apparatus that allows the transmission of image signals to be done by use of a transmission method suitable for the resolution of the image signals and for the cable length. [3] In a case of transmitting image signals produced in a personal computer to a liquid crystal projector via an analog transmission cable, if the analog transmission cable is long, it is apt to cause image deterioration. Such image deterioration will be noticeable especially on the liquid crystal projector having a high resolution of 1024.times.768 pixels (XGA), 1280.times.1024 pixels (SXGA) or the like.
There have already been developed some image signal transmission apparatus that can avoid image deterioration even when the transmission cable is long. An example thereof is “FPDLink” developed by National Semiconductor Corp. in the United States. This image signal transmission apparatus is also called “LVDS.”
Another example is “PanelLink” by Silicon Image, Inc. in the United States.
FIG. 3 shows the structure of “PanelLink,” which comprises a graphics controller (graphics board) 151 built in a personal computer, a transmitting-side unit 152 , a receiving-side unit 153 , and a cable 154 for connecting the transmitting-side unit 152 and the receiving-side unit 153 .
The transmitting-side unit 152 includes an encoding/parallel-serial converting circuit 161 , a PLL circuit 162 , and an amplitude control circuit 163 . The encoding/parallel-serial converting circuit 161 receives image data, DE (i.e., a display enable signal for discriminating between a display mode and a standby mode), and a control signal from the graphics controller 151 .
In the encoding/parallel-serial converting circuit 161 , a parallel-serial conversion of the 24-bit parallel image data is performed, whereby the number of signal lines can be reduced and hence the signal transmission can be effected through a thin cable. Then, the signal amplitude is reduced so as to reduce EMI noise. Additionally, the encoding is performed at the time of the parallel-serial conversion. When the encoding is performed, the variation of the level of the signals to be transmitted is reduced so as to further reduce the EMI noise.
The PLL circuit 162 generates a clock signal for the encoding/parallel-serial converting circuit 161 on the basis of a clock signal applied from the graphics controller 151 .
The cable 154 comprises three pairs of signal lines for transmitting the codes including the image data and the control signal, and one pair of signal lines for transmitting the clock signal generated by the PLL circuit 162 .
The amplitude control circuit 163 adjusts, in accordance with the resistance value of a single external resistor 165 , the amplitude of the signals (i.e., the codes including the image data and the control signal, and the clock signal) to be applied from the transmitting-side unit 152 to the cable 154 . Specifically, the signal amplitude can be adjusted within a range between 0.5 V and 2.5 V by establishing the resistance value of the single external resistor 165 .
The receiving-side unit 153 includes a data extracting/serial-parallel converting/decoding circuit 181 and a PLL circuit 182 . The data extracting/serial-parallel converting/decoding circuit 181 performs a data extraction, a serial-parallel conversion and a decoding with respect to the codes applied from the transmitting-side unit 152 to produce the image data, DE and the control signal.
The PLL circuit 182 produces a clock signal for the data extracting/serial-parallel converting/decoding circuit 181 on the basis of the clock signal applied from the transmitting-side unit 152 .
The image data, DE and control signal produced by the data extracting/serial-parallel converting/decoding circuit 181 and the clock signal produced by the PLL circuit 182 are applied to a liquid crystal panel 155 of digital drive type.
The “LVDS” method is similar to the “PanelLink” method but different therefrom in that the total number of the signal lines in the cable is five because of performing neither encoding nor decoding.
FIG. 4 shows the structure of an image signal transmission apparatus that has already been developed by the Applicant of the subject application (See Japanese Official Gazette of Laid Open Patent Application, TOKUKAI, No. 2000-341177.) In FIG. 4, elements corresponding to the same elements in FIG. 3 are identified by the same reference designations, and the explanation of those elements is omitted.
The image signal transmission apparatus of FIG. 4, which utilizes the conventional “PanelLink”, comprises a transmission unit 10 set in a personal computer (which is not shown and which will be referred to as “PC” hereinafter) 1 , a receiving-side unit 153 set in a liquid crystal projector 20 , and a cable 154 for connecting the transmission unit 10 and the receiving-side unit 153 .
The transmission unit 10 comprises a graphics controller (graphics board) 151 and a transmitting-side unit 152 connected thereto. The graphics controller 151 is connected to a main CPU 2 in the PC 1 via a bus 3 also therein. The transmitting-side unit 152 in the transmission unit 10 is connected to the receiving-side unit 153 via the cable 154 .
The receiving-side unit 153 in the liquid crystal projector 20 is connected to a liquid crystal panel 155 of digital drive type also in the liquid crystal projector 20 .
An amplitude control circuit 163 adjusts, in accordance with the resistance value of an external variable resistor circuit 164 , the amplitude of the signals (i.e., the codes including the image data and the control signal, and the clock signal) to be provided from the transmitting-side unit 152 to the cable 154 . The variable resistor circuit 164 can be switched, for example, between two resistance values to thereby switch, between two values, the amplitude of the signals to be provided from the transmitting-side unit 152 to the cable 154 .
An application software for setting the cable length has been installed on the PC 1 . When setting the cable length, the user initiates this application software. When this application software is initiated, the PC 1 produces, on its display device, an on-screen selection guide for instructing the user to designate the length of the cable 154 actually being used. The user selects a cable length, following the on-screen selection guide.
When the user selects the cable length, the PC 1 sends a command signal (amplitude command signal) responsive to the cable length selected by the user to the graphics controller 151 via the bus 3 . Receiving this command signal, the graphics controller 151 sends an amplitude control signal responsive to the command signal to the variable resistor circuit 164 to change the resistance value thereof.
According to the image signal transmission apparatus of FIG. 4, the user can adjust, in accordance with the cable length, the amplitude of the signals to be provided from the transmitting-side unit 152 to the cable 154 by operating the PC 1 in which the graphics controller 151 has been disposed.
Meanwhile, in the image signal transmission apparatus of the “LVDS” or “PanelLink” method, if the amplitude of signals to be transmitted is enlarged, it increases the possible distance of transmission by the cable but also increases unwanted radiation signals. In contrast to this, if the amplitude of signals to be transmitted is reduced, it reduces the unwanted radiation signals but also reduces the possible transmission distance.
Thus, it is desirable to optimize the signal amplitude according to the cable length. The “LVDS” method, however, has no function to adjust the signal amplitude. As described above, the “PanelLink” method indeed has the function to adjust the signal amplitude by use of the single external resistor 165 . However, since the external resistor 165 is disposed at the stage of design, it is difficult for the user to adjust the signal amplitude according to the cable length.
Additionally, in the case of the image signal transmission apparatus of FIG. 4, it was necessary for the user to enter into the PC 1 the amplitude control command for changing the amplitudes of the signals to be provided from the transmitting-side unit to the cable, according to the cable length.
It was, therefore, necessary to preinstall the cable length setting application software onto the PC 1 . Additionally, at the time of setting the cable length, it was necessary for the user to initiate this cable length setting application software to cause the on-screen selection guide for setting the cable length to be displayed on the PC 1 , and then select the cable length, following this on-screen selection guide.
Moreover, each time changing a cable for another having a different length, the user had to enter an amplitude control command into the computer.
The object of the present invention is to provide an image signal transmission apparatus that does not necessitate the user's setting of the cable length but automatically adjusts the amplitude of signals to be applied from the image transmitting-side unit in response to the level of the received signals that varies with the cable length.
SUMMARY OF THE INVENTION
A first image signal transmission apparatus according to the present invention performs a parallel-serial conversion of parallel image data by use of an image-transmitting-side device, thereafter transmits the image data to an image-receiving-side device via a cable, and then performs a serial-parallel conversion of the received image data by use of the image-receiving-side device, said image-transmitting-side device comprising: a one-phase to two-phase converter circuit for separating the parallel image data, which are to be transmitted, into even and odd data; a first parallel-serial converting circuit; a second parallel-serial converting circuit; means for allowing a user to select, as the resolution mode for the image data to be transmitted, one of a first resolution mode and a second resolution mode that is higher in resolution than the first resolution mode; and switch means for applying the parallel image data, which are to be transmitted, to the first parallel-serial converting circuit when the first resolution mode is selected, and for applying the parallel image data, which are to be transmitted, to the one-phase to two-phase converter circuit when the second resolution mode is selected; wherein when the second resolution mode is selected, the even data obtained by the one-phase to two-phase converter circuit are applied to one of the first and second parallel-serial converting circuits, and the odd data obtained by the one-phase to two-phase converter circuit are applied to the other parallel-serial converting circuit.
A second image signal transmission apparatus according to the present invention performs a parallel-serial conversion of parallel image data by use of an image-transmitting-side device, thereafter transmits the image data to an image-receiving-side device via a cable, and then performs a serial-parallel conversion of the received image data by use of the image-receiving-side device, said image-transmitting-side device comprising: a one-phase to two-phase converter circuit for separating the parallel image data, which are to be transmitted, into even and odd data; a first parallel-serial converting circuit; a second parallel-serial converting circuit; means for automatically determining the resolution of the image data to be transmitted, and then automatically selecting, as the resolution mode for the image data to be transmitted, one of a first resolution mode and a second resolution mode that is higher in resolution than the first resolution mode; and switch means for applying the parallel image data, which are to be transmitted, to the first parallel-serial converting circuit when the first resolution mode is selected, and for applying the parallel image data, which are to be transmitted, to the one-phase to two-phase converter circuit when the second resolution mode is selected; wherein when the second resolution mode is selected, the even data obtained by the one-phase to two-phase converter circuit are applied to one of the first and second parallel-serial converting circuits, and the odd data obtained by the one-phase to two-phase converter circuit are applied to the other parallel-serial converting circuit.
In the above-described first or second image signal transmission apparatus, said image-receiving-side device comprises: a first serial-parallel converting circuit for converting the serial data, transmitted from the first parallel-serial converting circuit via the cable, to the parallel data; and a second serial-parallel converting circuit for converting the serial data, transmitted from the second parallel-serial converting circuit via the cable, to the parallel data.
The above-described first serial-parallel converting circuit includes means for performing a one-phase to two-phase conversion of the parallel data obtained by the serial-parallel conversion to provide separated even and odd data in the case when the first resolution mode is selected.
A third image signal transmission apparatus according to the present invention performs a parallel-serial conversion of parallel image data by use of an image-transmitting-side device, thereafter transmits the image data to an image-receiving-side device via a cable, and then performs a serial-parallel conversion of the received image data by use of the image-receiving-side device,
said image-receiving-side device comprising: means for detecting the level of the signals transmitted from the image-transmitting-side device through the cable to the image-receiving-side device and for generating an operation mode control signal for designating a first operation mode when the detected signal level is higher than a predetermined value and for designating a second operation mode when the detected signal level is equal to or lower than the predetermined value; and means for transmitting the operation mode control signal to the image-transmitting-side device,
said image-transmitting-side device comprising: a one-phase to two-phase converter circuit for separating the parallel image data, which are to be transmitted, into even and odd data; a first parallel-serial converting circuit; a second parallel-serial converting circuit; and switch means for applying the parallel image data, which are to be transmitted, to the first parallel-serial converting circuit when the operation mode control signal from the image-receiving-side device designates the first operation mode, and for applying the parallel image data, which are to be transmitted, to the one-phase to two-phase converter circuit when the operation mode control signal from the image-receiving-side device designates the second operation mode,
wherein when the operation mode control signal from the image-receiving-side device designates the second operation mode, the even data obtained by the one-phase to two-phase converter circuit are applied to one of the first and second parallel-serial converting circuits, and the odd data obtained by the one-phase to two-phase converter circuit are applied to the other parallel-serial converting circuit.
In the above-described third image signal transmission apparatus, said image-receiving-side device comprises: a first serial-parallel converting circuit for converting the serial data, transmitted from the first parallel-serial converting circuit via the cable, to the parallel data; and a second serial-parallel converting circuit for converting the serial data, transmitted from the second parallel-serial converting circuit via the cable, to the parallel data.
The above-described first serial-parallel converting circuit includes means for performing a one-phase to two-phase conversion of the parallel data obtained by the serial-parallel conversion to provide separated even and odd data in the case when the first operation mode is selected.
The above-described means for transmitting the operation mode control signal to the image-transmitting-side device may transmit the operation mode control signal by wire or by wireless.
A fourth image signal transmission apparatus according to the present invention comprises comprising an image-transmitting-side device, an image-receiving-side device, and a cable connecting the image-transmitting-side device with the image-receiving-side device,
said image-receiving-side device comprising: means for detecting the level of the signals transmitted from the image-transmitting-side device through the cable to the image-receiving-side device and for generating, in accordance with the detected signal level, a control signal for controlling the amplitude of the signals to be applied from the image-transmitting-side device to the cable; and means for transmitting the control signal to the image-transmitting-side device,
said image-transmitting-side device having amplitude control means for controlling, in accordance with the control signal from the image-receiving-side device, the amplitude of the signals to be applied from the image-transmitting-side device to the cable.
In the above-described fourth image signal transmission apparatus, said amplitude control means may comprise: for example, an amplitude control circuit for changing, in accordance with the resistance value of an external amplitude control resistor, the amplitude of the signals to be applied from the image-transmitting-side device to the cable; a variable resistor circuit disposed, as the amplitude control resistor, externally to the amplitude control circuit; and means for controlling the resistance value of the variable resistor circuit in accordance with the control signal from the image-receiving-side device.
The above-described means for transmitting the control signal to the image-transmitting-side device may transmit the control signal by wire or by wireless.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing the structure of an image signal transmission apparatus employing the “Single Link” method.
FIG. 2 is a block diagram showing the structure of an image signal transmission apparatus employing the “Dual Link” method.
FIG. 3 is a block diagram showing the structure of “PanelLink.”
FIG. 4 is a block diagram showing the structure of an image transmitting system that has already been developed by the Applicant of the subject application.
FIG. 5, showing a first embodiment, is a block diagram showing the structure of a digital image signal transmission apparatus.
FIG. 6 is a block diagram showing the data flow in a case when CPU 13 detects that the image signals to be transmitted are of a high resolution (equal to or lower than the resolution of SXGA).
FIG. 7 is a block diagram showing the data flow in a case when CPU 13 detects that the image signals to be transmitted are of an ultrahigh resolution (equal to or higher than the resolution of UXGA).
FIG. 8, showing a second embodiment, is a block diagram showing the structure of a digital image signal transmission apparatus.
FIG. 9 is a block diagram showing the structure of a signal level detection.
FIG. 10 is a block diagram showing an example of modification of the second embodiment.
FIG. 11, showing a third embodiment, is a block diagram showing the structure of an image transmitting system.
FIG. 12 is a block diagram showing the structure of a transmission apparatus.
FIG. 13 is a block diagram showing the structure of a signal level detection.
FIG. 14 is a block diagram showing an example of modification of the third embodiment.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[1] Description of First Embodiment
A first embodiment of the present invention will be described below with reference to FIGS. 5 to 7 .
FIG. 5 shows the structure of a digital image signal transmission apparatus. This image signal transmission apparatus comprises a transmission unit 10 set in a personal computer, a liquid crystal projector 20 and a cable 30 connecting them.
The transmission unit 10 includes a VGA controller (graphic chip) 11 , a switch circuit 12 , a CPU 13 , a one-phase to two-phase converter circuit 14 , a first PanelLink transmitter 15 and a second PanelLink transmitter 16 .
The liquid crystal projector 20 includes a first PanelLink receiver 21 , a second PanelLink receiver 22 and a liquid crystal panel 23 of digital drive type. The first PanelLink receiver 21 incorporates a one-phase to two-phase converter circuit 21 a.
The cable 30 comprises six pairs of signal lines for transmitting image data and one pair of signal lines for transmitting a clock signal.
The CPU 13 detects which the image signals to be transmitted are of, a high resolution (equal to or lower than the resolution of SXGA) or an ultrahigh resolution (equal to or higher than the resolution of UXGA), on the basis of a control signal (or both of the control signal and image data) applied from the VGA controller 11 . The CPU 13 controls the switch circuit 12 in accordance with the result of this detection.
FIG. 6 shows the data flow of a case when the CPU 13 detects that the image signals to be transmitted is of a high resolution (equal to or lower than the resolution of SXGA).
Parallel image data (R, G, B) output by the VGA controller 11 are input to the first PanelLink transmitter 15 via the switch circuit 12 . The PanelLink transmitter 15 converts the image data from the parallel signals to serial ones. The resultant serial R, G, and B signals each for a respective channel are transmitted through the cable 30 to the first PanelLink receiver 21 , which converts the received serial signals into the parallel ones.
When the second PanelLink receiver 22 receives no image signals, the first PanelLink receiver 21 uses the one-phase to two-phase converter circuit 21 a to perform a one-phase to two-phase conversion of the obtained parallel signals, thereby obtaining the RGB even and odd data, which are then applied to the liquid crystal panel 23 of digital drive type.
The information as to whether or not the second PanelLink receiver 22 receives any image signals is sent therefrom to the first PanelLink receiver 21 .
In a case when the second PanelLink receiver 22 does receive the image signals, the first PanelLink receiver 21 applies the obtained parallel signals, as they are, to the liquid crystal panel 23 .
FIG. 7 shows the data flow of a case when the CPU 13 detects that the image signals to be transmitted is of an ultrahigh resolution (equal to or higher than the resolution of UXGA).
Parallel image data (R, G, B) output by the VGA controller 11 are applied through the switch circuit 12 to the one-phase to two-phase converter circuit 14 , being separated into even and odd data. The even data are applied to the first PanelLink transmitter 15 , while the odd data are applied to the second PanelLink transmitter 16 .
The first PanelLink transmitter 15 converts the even data from the parallel signals to serial ones. The second PanelLink transmitter 16 converts the odd data from the parallel signals to serial ones.
The serial R, G and B signals, each for two channels, obtained by PanelLink transmitters 15 and 16 are transmitted through the cable 30 to the first and second PanelLink receivers 21 and 22 .
The first PanelLink receiver 21 converts the received even data from the serial signals to the parallel signals, while the second PanelLink receiver 22 converts the received odd data from the serial signals to the parallel signals.
The parallel signals, RGB even and odd data, thus obtained by the first and second PanelLink receivers 21 and 22 are applied to the liquid crystal panel 23 .
In the above-described embodiment, when it is detected that the image data to be transmitted are of a high resolution, the image data are transmitted by use of the “Single Link” method. When it is detected that the image data to be transmitted are of an ultrahigh resolution, the image data are transmitted by use of the “Dual Link” method.
In the above-described first embodiment, the CPU 13 detected which the image signals to be transmitted were of, a high resolution (equal to or lower than the resolution of SXGA) or an ultrahigh resolution (equal to or higher than the resolution of UXGA), and the result of this detection was used to control the switch circuit 12 . Instead, it may be arranged that the user selects, according to the resolution of the image signals to be transmitted, the high or ultrahigh resolution and that the switch circuit 12 is controlled based on his selected resolution.
[2] Description of Second Embodiment
A second embodiment will be described below with reference to FIGS. 8 to 10 .
FIG. 8 shows the structure of a digital image signal transmission apparatus.
This image signal transmission apparatus comprises a transmission unit 10 set in a personal computer (PC) 1 , a receiving-side unit 105 set in a liquid crystal projector 20 , and a cable 30 connecting the transmission unit 10 and the receiving-side unit 105 .
The transmission unit 10 includes a graphics controller (graphic board) 101 , a switch circuit 102 , a one-phase to two-phase converter circuit 103 and a transmitting-side unit 104 . The graphics controller 101 is connected to a main CPU 2 in the PC 1 via a bus 3 also therein. The main CPU 2 is connected to a line receiver 146 . The transmitting-side unit 104 includes first and second PanelLink transmitters 111 and 112 , respectively.
The receiving-side unit 105 in the liquid crystal projector 20 is connected to a liquid crystal panel 106 of digital drive type in the liquid crystal projector 20 . The receiving-side unit 105 includes a first PanelLink receiver 131 , a second PanelLink receiver 132 and a coupler 141 . The first PanelLink receiver 131 incorporates a one-phase to two-phase converter circuit 131 a . The liquid crystal projector 20 also includes a detector circuit 142 , an A/D converter 143 , a CPU 144 and a line driver 145 .
The transmitting-side unit 104 in the transmission unit 10 is connected through the cable 30 to the receiving-side unit 105 in the liquid crystal projector 20 . The cable 30 comprises six pairs of signal lines for transmitting the image data and one pair of signal lines for transmitting the clock signal.
This image signal transmission apparatus has, as its operation modes, a DualLink mode for performing the signal transmission by use of the Dual Link method, and a SingleLink mode for performing the signal transmission by use of the Single Link method.
When the SingleLink mode is selected as the operation mode, the parallel image data (R, G, B), the clock signal and the control signals (H, V, DE (Display Enable)) from the graphics controller 101 are applied through the switch circuit 102 directly to the first PanelLink transmitter 111 without being applied to the one-phase to two-phase converter circuit 103 . In that case, the second PanelLink transmitter 112 is inactive in a power down mode.
The first PanelLink transmitter 111 encodes the image data and clock signal, and performs a parallel-serial conversion that converts the image data from the parallel signals to serial ones. The thus obtained serial R, G and B signals each for a respective channel are transmitted through the cable 30 to the first PanelLink receiver 131 in the receiving-side unit 105 . In that case, the second PanelLink receiver 132 is inactive, entering the power down mode. The first PanelLink receiver 131 performs a data extraction, a serial-parallel conversion and a decoding with respect to the codes applied from the first PanelLink transmitter 111 in the transmitting-side unit 104 , thereby producing the parallel image data, H, V and DE.
When the second PanelLink receiver 132 receives no image signals, the first PanelLink receiver 131 uses the one-phase to two-phase converter circuit 131 a to perform a one-phase to two-phase conversion of the produced parallel image signals, and then applies the thus obtained RGB even and odd data to the liquid crystal panel 106 . The first PanelLink receiver 131 also uses the one-phase to two-phase converter circuit 131 a to perform one-half frequency divisions of the produced H, V and DE and of the received clock signal, and then applies them to the liquid crystal panel 106 .
The information as to whether or not the second PanelLink receiver 132 receives any image signals is sent therefrom to the first PanelLink receiver 131 .
In a case when the second PanelLink receiver 132 does receive the image signals, the first PanelLink receiver 131 applies its obtained parallel signals, as they are, to the liquid crystal panel 106 .
When the DualLink mode is selected as the operation mode, the parallel image data (R, G, B) output by the graphics controller 101 are applied through the switch circuit 102 to the one-phase to two-phase converter circuit 103 , being separated thereby into even and odd data. The even data are applied to the first PanelLink transmitter 111 in the transmitting-side unit 104 , while the odd data are applied to the second PanelLink transmitter 112 also in the transmitting-side unit 104 .
In the meantime, the clock signal and control signals (H, V, DE (Display Enable)) output by the graphics controller 101 are applied to the one-phase to two-phase converter circuit 103 , being one-half frequency divided thereby, and then being applied to the first and second PanelLink transmitters 111 and 112 in the transmitting-side unit 104 .
The first PanelLink transmitter 111 encodes the even data and clock signal, and performs a parallel-serial conversion that converts the even data from the parallel signals to serial ones. The second PanelLink transmitter 112 encodes the odd data and clock signal, and performs a parallel-serial conversion that converts the odd data from the parallel signals to serial ones.
The R, G and B serial signals each for two channels, obtained by the first and second PanelLink transmitters 111 and 112 , are transmitted through the cable 30 to the first and second PanelLink receivers 131 and 132 in the receiving-side unit 105 .
The first PanelLink receiver 131 performs a data extraction, a serial-parallel conversion and a decoding with respect to the codes applied from the first PanelLink transmitter 111 , thereby producing the parallel signals with respect to the even data and also producing H, V and DE. The second PanelLink receiver 132 performs a data extraction, a serial-parallel conversion and a decoding with respect to the codes applied from the second PanelLink transmitter 112 , thereby producing the parallel signals with respect to the odd data.
The parallel signals (RGB even and odd data) obtained by the first and second PanelLink receivers 131 and 132 are applied to the liquid crystal panel 106 . The control signals (H, V and DE) produced by the first PanelLink receiver 131 and the clock signal received thereby are also applied to the liquid crystal panel 106 .
Incidentally, the three pairs of image data of the R, G and B signals and one pair of clock signals each are transmitted as a pair of differential signals from the transmitting-side unit 104 to the receiving-side unit 105 , and hence are almost at the same signal level. The transmission speed of the digital image data (the serial image data) along the cable 30 is, for example in the case of UXGA, 1.65 Gbps in the SingleLink mode, and half the same, 825 Mbps, in the DualLink mode.
In this embodiment, the coupler 141 is located on one of two signal lines for the pair of differential signals, CLK+ and CLK−, received as the clock signal, specifically, on the signal line of signal CLK−, as shown in FIG. 9, and its coupling output is applied to the detector circuit 142 . The CLK+ and CLK−signal lines each exhibit a characteristic impedance of 50 ohms at the single end, and a terminating resistor 141 a of the coupler 141 exhibits, for example, 50 ohms.
The detector circuit 142 converts the CLK−coupling output signal into an analog signal of a DC voltage proportional to the amplitude level of the CLK−coupling output signal. The detector circuit 142 may comprise, for example, an IC of AD8313 available from Analog Devices Inc.
The detection signal output by the detection circuit 142 is converted into a digital signal by the A/D converter circuit 143 and then applied to an input port of the CPU 144 . The CPU 144 compares the level of the received CLK−signal with a predetermined threshold value and provides a control signal for switching the operation mode (from the SingleLink mode to the DualLink mode or vice versa). This control signal is transmitted through the line driver 145 to the line receiver 146 in the PC 1 on the transmitting side as a feedback signal.
As to the transmission of the control signal responsive to the level of the received signals to the line receiver 146 in the PC 1 , in a case of using, for example, a 24-pin connector of Digital Visual Interface (DVI) standard specified as a digital interface between PCs and liquid crystal projectors or the like in the United States, its unused pin terminal 8 (NC) can be utilized, without any additional wiring, to effect a serial transmission of the one-bit control signal. Instead, however, an additional signal wiring may be used as the interface for transmitting the control signal.
The control signal received by the line receiver 146 in the PC 1 is applied to the main CPU 2 . On the basis of the control signal applied to the main CPU 2 , the PC 1 sends an operation mode switch signal for switching between the SingleLink mode and the DualLink mode to the graphics controller 101 via the bus 3 . When receiving the operation mode switch signal, the graphics controller 101 sends a control signal responsive to this operation mode switch signal to the switch circuit 102 .
In this embodiment, the initial operation mode of the transmission unit 10 has been set to the SingleLink mode. When the transmission of image data to the liquid crystal projector 20 is started for the first time after turn-on of the transmission unit 10 , it is decided which mode should be used as the operation mode.
In a case of using a short cable of three meters or less as the cable 30 , even when the image signals to be transmitted are of a high resolution of UXGA that exhibits a transmission speed of 1.65 Gbps in the Single Link method, the attenuation amount of the signals transmitted through the cable 30 is less than five or six dB. Thus, the SingleLink mode can be used to provide a sufficient C/N ratio to reproduce the received signals without any errors.
In such a case, the amplitude of a CLK−coupling output signal developed by the coupler 141 is large, and the amplitude level of a signal output by the detector circuit 142 is high. Thus, the CPU 144 develops a control signal for selecting the SingleLink mode as the operation mode. This control signal is conveyed through the line driver 145 to the transmitting side. When receiving this control signal, the main CPU 2 in the PC 1 selects the SingleLink mode as the operation mode and applies an operation mode switch signal responsive to this mode selection to the graphics controller 101 . The graphics controller 101 then applies a switch control signal for the SingleLink mode to the switch circuit 102 . As a result, the initial operation mode (SingleLink mode) remains unchanged.
In a case of using a long cable of ten meters or more as the cable 30 , when the image signals to be transmitted are of a high resolution of UXGA that exhibits a transmission speed of 1.65 Gbps in the Single Link method, the attenuation amount of the signals transmitted through the cable 30 is 20 dB or so. Thus, the SingleLink mode cannot be used to provide any sufficient C/N ratio to reproduce the received signals to a normal degree.
In such a case, the amplitude of a CLK−coupling output signal developed by the coupler 141 is small, and the amplitude level of a signal output by the detector circuit 142 is low. Thus, the CPU 144 develops a control signal for selecting the DualLink mode as the operation mode. This control signal is conveyed through the line driver 145 to the transmitting side. When receiving this control signal, the main CPU 2 in the PC 1 selects the DualLink mode as the operation mode and applies an operation mode switch signal responsive to this mode selection to the graphics controller 101 . The graphics controller 101 then applies a switch control signal for the DualLink mode to the switch circuit 102 . As a result, the initial operation mode (SingleLink mode) is switched to the DualLink mode.
When the operation mode is thus switched to the DualLink mode, the transmission speed of the signals through the cable 30 is reduced to 825 Mbps, and the attenuation amount of the signals through the cable 30 is reduced to, for example, 10 dB or so, resulting in a sufficient C/N ratio to reproduce the received signals.
In a case of using a cable of five meters as the cable 30 , it is possible for the Single Link method to transmit UXGA resolution signals. However, when QXGA resolution signals, the transmission speed of which is higher, are transmitted, the amplitude of a CLK−coupling output signal developed by the coupler 141 is small and hence the amplitude level of a signal output by the detector circuit 142 is low. Consequently, the operation mode is automatically switched from the SingleLink mode to the DualLink mode in the same manner as stated above, resulting in a reproduction of the received signals without any errors.
According to the second embodiment described above, an appropriate transmission method, either the Single Link method or the Dual Link method, can automatically be selected, as the method for transmitting the signals from the transmitting-side unit, in accordance with the resolution of the image data to be transmitted and the length of the cable actually used.
In the second embodiment described above, the coupler 141 was located on the CLK− signal line, but it may be located on the CLK+signal line, or on any one of the other RXR+, RXR−, RXG+, RXG−, RXB+, and RXB−image signal lines.
Additionally, as shown in FIG. 10, the transmission of the control signal from the liquid crystal projector 20 on the receiving side to the PC 1 on the transmitting side may be effected by use of a wireless interface such that the control signal output by the CPU 144 is transmitted from a wireless transmitter 147 and received by a wireless receiver 148 .
[3] Description of Third Embodiment
A third embodiment will be described blow with reference to FIGS. 11 to 14 .
FIG. 11 shows the structure of an image signal transmission apparatus. In FIG. 11, elements corresponding to the same elements in FIGS. 3 and 4 are identified by the same reference designations.
This image signal transmission apparatus comprises a transmission unit 10 set in a personal computer PC 1 , a receiving-side unit 153 set in a liquid crystal projector 20 , and a cable 154 connecting the transmission unit 10 and the receiving-side unit 153 .
The transmission unit 10 comprises a graphics controller (graphics board) 151 and a transmitting-side unit 152 connected thereto. The graphics controller 151 is connected to a main CPU 2 in the PC 1 via a bus 3 also therein. The transmitting-side unit 152 in the transmission unit 10 is connected to the receiving-side unit 153 via the cable 154 . The main CPU 2 is connected to a line receiver 196 .
The receiving-side unit 153 in the liquid crystal projector 20 is connected to a liquid crystal panel 155 of digital drive type in the liquid crystal projector 20 . The liquid crystal projector 20 also includes a detector circuit 192 , an A/D converter 193 , a CPU 194 and a line driver 195 .
The transmitting-side unit 152 includes an encoding/parallel-serial converting circuit 161 , a PLL circuit 162 , and an amplitude control circuit 163 . The encoding/parallel-serial converting circuit 161 receives image data, DE (a display enable signal) and a control signal from the graphics controller 151 . In the encoding/parallel-serial converting circuit 161 , a parallel-serial conversion of the 24-bit parallel image data is performed. Then, the signal amplitude is reduced so as to effect a reduction of EMI noise. Additionally, an encoding is performed at the time of the parallel-serial conversion. When this encoding is performed, the variation of the level of the signals to be transmitted is reduced so as to further reduce the EMI noise.
The PLL circuit 162 generates a clock signal for the encoding/parallel-serial converting circuit 161 on the basis of a clock signal applied from the graphics controller 151 .
The cable 154 comprises three pairs of signal lines for transmitting the codes including both the image data and the control signal, and one pair of signal lines for transmitting the clock signal generated by the PLL circuit 162 .
The amplitude control circuit 163 adjusts, in accordance with the resistance value of an external variable resistor circuit 164 , the amplitude of the signals (i.e., the codes including both the image data and the control signal, and the clock signal) to be applied from the transmitting-side unit 152 to the cable 154 . As shown in FIG. 12, the variable resistor circuit 164 comprises a parallel combination of a series circuit of a first resistor 201 and a first switch 205 , a series circuit of a second resistor 202 and a second switch 206 , a series circuit of a third resistor 203 and a third switch 207 , and a series circuit of a fourth resistor 204 and a fourth switch 208 .
For example, the resistance value of the first resistor 201 is 820 ohms, that of the second resistor 202 is 620 ohms, that of the third resistor 203 is 390 ohms, and that of the fourth resistor 204 is 180 ohms.
The switches 205 to 208 are controlled by a 2-bit amplitude control signal (00, 01, 10, 11). When the amplitude control signal is, for example, “00”, the first switch 205 only is turned on, the other switches 206 , 207 and 208 being turned off. In that case, the variable resistor circuit 164 exhibits the resistance value of 820 ohms.
When the amplitude control signal is, for example, “01”, the second switch 206 only is turned on, the other switches 205 , 207 and 208 being turned off. In that case, the variable resistor circuit 164 exhibits the resistance value of 620 ohms.
When the amplitude control signal is, for example, “10”, the third switch 207 only is turned on, the other switches 205 , 206 and 208 being turned off. In that case, the variable resistor circuit 164 exhibits the resistance value of 390 ohms.
When the amplitude control signal is, for example, “11”, the fourth switch 208 only is turned on, the other switches 205 , 206 and 207 being turned off. In that case, the variable resistor circuit 164 exhibits the resistance value of 180 ohms.
In this way, the resistance value of the variable resistor circuit 164 can be switched among the four values. In other words, the on/off control of the switches 205 , 206 , 207 and 208 can switch, among four values, the amplitude of the signals to be applied from the transmitting-side unit 152 to the cable 154 .
The receiving-side unit 153 includes a data extracting/serial-parallel converting/decoding circuit 181 , a PLL circuit 182 and a coupler 191 . The data extracting/serial-parallel converting/decoding circuit 181 performs a data extraction, a serial-parallel conversion and a decoding with respect to the codes applied from the transmitting-side unit 152 to produce the image data, DE and the control signal.
The PLL circuit 182 produces a clock signal for the data extracting/serial-parallel converting/decoding circuit 181 on the basis of the clock signal applied from the transmitting-side unit 152 . The image data, DE and control signal produced by the data extracting/serial-parallel converting/decoding circuit 181 and the clock signal produced by the PLL circuit 182 are applied to the liquid crystal panel 155 .
The three pairs of image data of R, G and B signals each pair are transmitted as a pair of differential signals from the transmitting-side unit 152 to the receiving-side unit 153 , and hence are almost at the same signal level. The transmission speed of the digital image data (the serial image data) along the cable is, for example in a case of SXGA signals, 1.08 Gbps.
In this embodiment, the coupler 191 is located on one of two signal lines for the pair of differential signals, RXR+and RXR−, received as the R signal, specifically, on the line for the signal RXR−, as shown in FIG. 13, and its coupling output is applied to the detector circuit 192 . The RXR+and RXR−signal lines each exhibit a characteristic impedance of 50 ohms at the single end, and a terminating resistor 501 of the coupler 191 exhibits, for example, 50 ohms.
The detector circuit 192 converts the RXR−coupling output signal into an analog signal of a DC voltage proportional to the amplitude level of the RXR−coupling output signal. The detector circuit 192 may comprise, for example, an IC of AD8313 available from Analog Devices Inc.
A detection signal output by the detection circuit 192 is converted into a digital signal by the AID converter circuit 193 and then applied to an input port of the CPU 194 . The CPU 194 provides, in response to the level of the RXR−received signal, a control signal to be conveyed so as to change the level of the signals to be transmitted from the transmitting side. This control signal is conveyed through the line driver 195 to the line receiver 196 in the PC 1 on the transmitting side as a feedback signal.
As to the transmission of the control signal responsive to the level of the received signals to the line receiver 196 in the PC 1 , in a case of using, for example, a 24-pin connector of Digital Visual Interface (DVI) standard specified as a digital interface between PCs and liquid crystal projectors or the like in the United States, its unused pin terminal 8 (NC) can be utilized, without any additional wiring, to effect a serial transmission of the one-bit control signal. Instead, however, an additional signal wiring may be used as the interface for transmitting the control signal.
The control signal received by the line receiver 196 in the PC 1 is applied to the main CPU 2 . On the basis of the control signal applied to the main CPU 2 , the PC 1 sends a command signal (amplitude command signal) to the graphics controller 151 via the bus 3 . When receiving the command signal, the graphics controller 151 applies an amplitude control signal responsive to this command signal to the variable resistor circuit 164 .
In a case of using a short cable of one meter or less as the cable 154 , the amplitude of a RXR−coupling output signal developed by the coupler 191 is large, and the amplitude level of the signal output by the detector circuit 192 is high. Thus, the aforementioned control signal, developed by the CPU 194 , to be conveyed so as to change the level of the signals to be transmitted from the transmitting side is conveyed through the line driver 195 to the transmitting side so as to reduce the amplitude level of the signals to be transmitted from the transmitting side.
On the basis of the control signal conveyed from the receiving side, the PC 1 applies a command signal (amplitude command signal) through the bus 3 to the graphics controller 151 , which then provides a 2-bit amplitude control signal of “00”. In that case, the switch 205 is in the on-state, while the other switches 206 to 208 being in the off-state. Thus, the variable resistor circuit 164 exhibits the largest one of the four resistance values, 820 ohms, so that the amplitude of the signals to be applied from the transmitting-side unit 152 to the cable 154 becomes the smallest one of the four amplitude values.
In a case of using a long cable of ten meters or more as the cable 154 , the amplitude of a RXR− coupling output signal developed by the coupler 191 is small, and the amplitude level of a signal output by the detector circuit 192 is low. Thus, the aforementioned control signal, developed by the CPU 194 , to be conveyed so as to change the level of the signals to be transmitted from the transmitting side is conveyed through the line driver 195 to the transmitting side so as to raise the amplitude level of the signals to be transmitted from the transmitting side.
On the basis of the control signal conveyed from the receiving side, the PC 1 applies a command signal (amplitude command signal) through the bus 3 to the graphics controller 151 , which then provides a 2-bit amplitude control signal of “11”. In that case, the switch 208 is in the on-state, while the other switches 205 to 207 being in the off-state. Thus, the variable resistor circuit 164 exhibits the smallest one of the four resistance values, 180 ohms, so that the amplitude of the signals to be applied from the transmitting-side unit 152 to the cable 154 is the largest one of the four amplitude values.
According to the third embodiment described above, the PC 1 , in which the graphics controller 151 has been set, can automatically adjust the amplitude of the signals to be applied from the transmitting-side unit 152 to the cable 154 so that the amplitude level of the image data will be appropriate on the receiving side.
The third embodiment was described above with respect to the case of adjusting, among the four values, the amplitude of the signals to be applied from the transmitting-side unit 152 to the cable 154 . The present invention, however, is not limited only to this number of signal amplitude values but may be applied to any other number of signal amplitude values.
In the third embodiment described above, the coupler 191 was located on the RXR−signal line, but it may be located on the RXR+ signal line, or on any one of the other RXG+, RXG−, RXB+, and RXB− image signal lines.
Additionally, as shown in FIG. 14, the transmission of the control signal from the liquid crystal projector 20 on the receiving side to the PC 1 on the transmitting side may be effected by use of a wireless interface such that the control signal output by the CPU 194 is transmitted from a wireless transmitter 197 and received by a wireless receiver 198 .
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An image-transmitting-side device comprises: a one-phase to two-phase converter circuit for separating parallel image data, which are to be transmitted, into even and odd data; a first parallel-serial converting circuit; a second parallel-serial converting circuit; means for allowing a user to select, as the resolution mode for the image data to be transmitted, one of a first resolution mode and a second resolution mode that is higher in resolution than the first resolution mode; and switch means for applying the parallel image data, which are to be transmitted, to the first parallel-serial converting circuit when the first resolution mode is selected, and for applying the parallel image data, which are to be transmitted, to the one-phase to two-phase converter circuit when the second resolution mode is selected.
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This is a divisional of application Ser. No. 08/828,705 filed on Mar. 31, 1997, now U.S. Pat. No. 5,818,162.
FIELD OF THE INVENTION
The present claimed invention relates to the field of flat panel displays. More particularly, the present claimed invention relates to the black matrix of a flat panel display screen structure.
BACKGROUND ART
Sub-pixel regions on the faceplate of a flat panel display are typically separated by an opaque mesh-like structure commonly referred to as a black matrix. By separating sub-pixel regions, the black matrix prevents electrons directed at one sub-pixel from being "back-scattered" and striking another sub-pixel. In so doing, a conventional black matrix helps maintain a flat panel display with sharp resolution. In addition, the black matrix is also used as a base on which to locate structures such as, for example, support walls.
In one prior art black matrix, a very thin layer (e.g. approximately 2-3 microns) of a conductive material is applied to the interior surface of the faceplate surrounding the sub-pixel regions. Typically, the conductive black matrix is formed of a conductive graphite material. By having a conductive black matrix, excess charges induced by electrons striking the top or sides of the black matrix can be easily drained from the interior surface of the faceplate. Additionally, by having a conductive black matrix, electrical arcs occurring between field emitters of the flat panel display and the faceplate will be more likely to strike the black matrix. By having the electrical arcing occur between the black matrix and the field emitters instead of between the sub-pixels and the field emitters, the integrity of the phosphors and the overlying aluminum layer is maintained. Unfortunately, due to the relatively low height of such a prior art conductive black matrix, arcing can still occur from the field emitter to the sub-pixel regions. As a result of such arcing, phosphors and the overlying aluminum layer can be damaged. As mentioned above, however, the black matrix is also intended to prevent back-scattering of electrons from one sub-pixel to another sub-pixel. Thus, it is desirable to have a black matrix with a height which sufficiently isolates each sub-pixel from respective neighboring sub-pixels. However, due to the physical property of the conductive graphite material, the height of the black matrix is limited to the aforementioned 2-3 microns.
In another prior art black matrix, a non-conductive polyimide material is patterned across the interior surface of the black matrix In such a conventional black matrix, the black matrix has a uniform height of approximately 20-40 microns. Thus, the height of such a black matrix is well suited to isolating each sub-pixel from respective neighboring sub-pixels. As a result, such a black matrix configuration effectively prevents unwanted back-scattering of electrons into neighboring sub-pixels. Unfortunately, prior art polyimide black matrices are not conductive. As a result, even though the top edge of the polyimide black matrix is much closer than the sub-pixel region is to the field emitter, unwanted arcing can still occur from the field emitter to the sub-pixel regions. In a prior art attempt to prevent such arcing, a conductive coating (i.e. indium tin oxide (ITO)) is applied to the non-conductive polyimide black matrix ITO coated non-conductive black matrices are not without problems, however. For example, coating a non-conductive matrix with ITO adds increased complexity and cost to the flat panel display manufacturing process. Also, the high atomic weight of ITO results in unwanted back-scattering of electrons. Furthermore, ITO has a undesirably high secondary emission coefficient, δ.
Thus, a need exists for conductive black matrix structure having sufficient height to effectively separate neighboring sub-pixels. A further need exists for a black matrix structure which reduces arcing from the field emitters to the sub-pixels. Still another need exists for a conductive black matrix which does not have the increased cost and complexity, the increased back-scattering rate, and the undesirably high secondary emission coefficient associated with an ITO coated black matrix structure.
SUMMARY OF INVENTION
The present invention provides a conductive black matrix structure having sufficient height to effectively separate neighboring sub-pixels. The present invention also provides a black matrix structure which reduces arcing from the field emitters to the sub-pixels. The present invention further provides a conductive black matrix which does not have the increased cost and complexity, the increased back-scattering rate, and the undesirably high secondary emission coefficient associated with an ITO coated black matrix structure.
Specifically, in one embodiment, the present invention is formed partially of a first plurality of conductive ridges which are disposed on the faceplate between respective adjacent rows of sub-pixel regions. The present invention is further formed of a second plurality of conductive ridges which are orthogonally oriented with respect to and integral with the first plurality of conductive ridges such that a matrix structure is formed. In the conductive matrix of the present invention, the second plurality of conductive ridges have a height which is greater than the height of the first plurality of conductive ridges such that a multi-level conductive matrix is formed. However, the height of the second plurality of conductive ridges decreases to approximately the height of the first plurality of conductive ridges at respective intersections of the first and second plurality of conductive ridges. In so doing, the present invention provides a multi-level conductive matrix for separating rows and columns of sub-pixels on the faceplate of a flat panel display device.
In another embodiment, the present invention includes the features of the above-described embodiment, and further recites that each of the first plurality of conductive ridges disposed between the respective rows of the sub-pixel regions has a height of approximately 18-20 microns. In this embodiment, each of the second plurality of conductive ridges disposed between the respective columns of the sub-pixel regions has a maximum height of approximately 30-40 microns.
In yet another embodiment, the present invention provides a method for forming a multi-level conductive matrix structure for separating rows and columns of sub-pixels on the faceplate of a flat panel display device. In this embodiment, the present invention defines sub-pixel regions on the interior surface of the faceplate of the flat panel display device by forming rows and columns of photoresist structures thereon. The photoresist structures are formed on the faceplate directly overlying the areas which are to be used as sub-pixel regions. Conductive material is then applied between the photoresist structures, and is slightly hardened. In this embodiment, the photoresist structures are spaced such that the conductive material resides at a first height between the rows of the photoresist structures, and resides at a second height between the columns of the photoresist structures, wherein the first height is less than the second height. After the hardening step, acetone is applied to the photoresist structures to remove the photoresist structures from the faceplate. In so doing, the present invention forms a multi-level matrix of the conductive material on the faceplate of the flat panel display structure.
In still another embodiment, the present invention includes all of the steps of the above-described method, and further recites that rows of the photoresist structures are separated from adjacent rows of the photoresist structures by a distance of approximately 75-80 microns. In this embodiment, columns of the photoresist structures are separated from adjacent columns of the photoresist structures by a distance of approximately 25-30 microns. Additionally, in this embodiment, the second height of the conductive material residing between the columns of the photoresist structures decreases to the first height at respective locations where the conductive material residing between the columns of the photoresist structures intersects the conductive material residing between the rows of the photoresist structures.
These and other objects and advantages of the present invention will no doubt become obvious to those of ordinary skill in the art after having read the following detailed description of the preferred embodiments which are illustrated in the various drawing figures.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and form a part of this specification, illustrates embodiments of the invention and, together with the description, serve to explain the principles of the invention:
FIG. 1 is a simplified perspective view of photoresist structures created during the formation of a multi-level conductive matrix structure in accordance with the present claimed invention.
FIG. 2 is a simplified perspective view of the photoresist structures of FIG. 1 with a layer of conductive material disposed thereon in accordance with the present claimed invention.
FIG. 3 is a perspective view of a multi-level conductive matrix structure in accordance with the present claimed invention.
FIG. 4 is a perspective view of a multi-level conductive matrix structure having a support structure disposed thereon in accordance with the present claimed invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Reference will now be made in detail to the preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. While the invention will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the invention to these embodiments. On the contrary, the invention is intended to cover alternatives, modifications and equivalents, which may be included within the spirit and scope of the invention as defined by the appended claims. Furthermore, in the following detailed description of the present invention, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be obvious to one of ordinary skill in the art that the present invention may be practiced without these specific details. In other instances, well known methods, procedures, components, and circuits have not been described in detail as not to unnecessarily obscure aspects of the present invention.
With reference to FIG. 1 of the present embodiment, a simplified perspective view of photoresist structures 100 created during the formation of a multi-level conductive matrix structure in accordance with the present claimed invention is shown. The present invention is comprised of a multi-level conductive black matrix for separating rows and columns of sub-pixels on the faceplate of a flat panel display device. Although a the present invention is referred to as a black matrix, it will be understood that the term "black" refers to the opaque characteristic of the matrix. Thus, the present invention is also well suited to having a color other than black. To form the present invention, photoresist structures 100 are formed on the interior surface 102 of a faceplate 104. Only a portion of the interior surface of a faceplate is shown in FIG. 1 for purposes of clarity. In the present embodiment, photoresist structures 100 are formed by applying a photoresist such as, for example, AZ4620 Photoresist, available from Hoechst-Celanese of Somerville, N.J., to interior surface 102 of faceplate 104. Next, the photoresist is cured, soft-baked, exposed, and developed such that only hardened photoresist structures 100 remain on faceplate 104. In the present invention photoresist structures 100 are formed on faceplate 104 directly overlying the regions in which sub-pixels are to be formed. Furthermore, in the present embodiment, photoresist structures 100 are formed having a width, w, of approximately 65 microns, a height, h, of approximately 40 microns, and a length, l, of approximately 215 microns. Although such dimensions are specified for photoresist structures 100 in the present embodiment, the present invention is also well suited to using various other dimensions for photoresist structures 100.
With reference still to FIG. 1, photoresist structures 100 are formed on faceplate 104 arranged in rows (shown as 106 and 108) and columns (shown as 110 through 122). Although only two rows, 106 and 108, and only seven columns 110 through 122 of photoresist structures are shown in FIG. 1 for purposes of clarity, it will be understood that numerous rows and columns of photoresist structures will be formed on the interior surface of a faceplate. In one embodiment, adjacent rows 106 and 108 of photoresist structures 100 are separated from each other by a first distance, d 1 . Simiarly, adjacent columns (e.g. columns 110 and 112) are separated by a second distance, d 2 . In the present embodiment, d 2 is less than d 1 . More specifically, in the present embodiment, adjacent rows 106 and 108 of photoresist structures 100 are separated by a distance of approximately 75-80 microns. Adjacent columns (e.g. columns 110 and 112) are separated by a distance of approximately 25-30 microns. Although such row and column separation distances are specified in the present embodiment, the present invention is also well suited to separating adjacent rows and adjacent columns by various other distances.
With reference next to FIG. 2, after photoresist structures 100 have been formed, a conductive material 200 is applied between photoresist structures 100. More specifically, in one embodiment, conductive material 200 is sprayed over the interior surface of faceplate 104 and photoresist structures 100 such that the conductive material is disposed over and between photoresist structures 100. In the present embodiment, conductive material 200 is comprised of, for example, a CB800A DAG made by Acheson Colloids of Port Huron, Mich. Next, in the present embodiment, excess conductive material 200 disposed above and/or on top of photoresist structures 100 is removed by squeegeeing conductive material 200 from the top surface of photoresist structures 100. Although the present embodiment specifically recites spraying DAG over the interior surface of faceplate 200, the present invention is also well suited to using various other deposition methods to deposit various other conductive materials over the interior surface of faceplate 104 and between photoresist structures 100.
Referring still to FIG. 2, due to the difference in separation distances between adjacent rows (106 and 108) and adjacent columns (e.g., 110 and 112), the conductive material resides at a first height between the rows 106 and 108 of photoresist structures 100, and resides at a second height between columns 110 and 122 of photoresist structures 100. The first height of conductive material 200 between the rows of photoresist structures 100 is less than the second height of conductive material 200 between the columns of photoresist structures 100. That is, capillary action causes conductive material 200 located between the narrowly separated columns 110-122 of photoresist structures 100 to reside at a greater height than the height at which conductive material 200 resides between the more widely separated rows 106 and 108 of photoresist structures 100. In the present embodiment, the first height of conductive material 200 residing between the rows of photoresist structures 100 is approximately 18-20 microns. The second height of conductive material 100 residing between the columns of photoresist structures 100 is approximately 30-40 microns. Although such heights are recited in the present embodiment, the present invention is also well suited to varying the height of conductive material 200. Such variations in the height of conductive material 200 are achieved by, for example, varying the amount of conductive material applied to faceplate 104, varying the viscosity of conductive material 200, or varying the spacing between photoresist structures 100.
With reference still to FIG. 2, at various locations, the conductive material residing between columns 110-122 of photoresist structures 100 intersects the conductive material residing between rows 106 and 108 of photoresist structures 100. Area 202 of FIG. 2 represents a location where conductive material residing between columns 116 and 118 intersects the conductive material residing between rows 106 and 108. At such an area (i.e., an intersection) the height of the conductive material residing between the columns of photoresist structures 100 decreases to the height of the conductive material residing between the rows. Thus, in the present embodiment, at area 202, the height of the conductive material residing between columns 116 and 118 decreases to approximately 18-20 microns.
After conductive material 200 has been applied, conductive material residing between photoresist structures 100 is hardened In the present embodiment, the DAG is baked at approximately 80-90 degrees Celsius for approximately 4-5 minutes. As a result, a hardened multi-level conductive matrix is formed overlying faceplate 104.
After conductive material 200 is hardened, the present invention removes photoresist structures 100. In the present embodiment, a technical grade acetone is applied to photoresist structures 100 to remove photoresist structures 100 from faceplate 104. As a result, only the present multi-level conductive matrix remains on faceplate 104. During subsequent processing steps, the sub-pixels of the flat panel display are formed in the gaps or openings resulting from the removal of photoresist structures 100. Thus, the multi-level conductive matrix of the present invention defines the locations of the sub-pixels to be formed on the surface of the faceplate.
With reference now to FIG. 3, a perspective view of the present multi-level conductive matrix 300 of the present invention is shown disposed on a faceplate 104. As shown in FIG. 3, multi-level conductive matrix 300 has portions, typically shown as 304a and 304b, which separate columns of sub-pixels. Multi-level conductive matrix 300 also has portions, typically shown as 302a and 302b which separates row of sub-pixels. As shown in FIG. 3, column separating portions 304a and 304b of the present multi-level conductive matrix 300 are taller than row separating portions 302a and 302b. More specifically, as mentioned above, the height of conductive material 200 forming the present multi-level conductive matrix is approximately 18-20 microns along row separating portions 302a and 302b. The height of conductive material 200 forming the present multi-level conductive matrix is approximately 30-40 microns along column separating portions 304a and 304b. The substantial height of the present multi-level conductive matrix 300 effectively isolates neighboring sub-pixels and prevents unwanted back-scattering. The substantial height and conductivity of the present multi-level conductive matrix prevent arcing from the field emitters to the faceplate. By preventing arcing from the field emitters to the faceplate, the present invention increases the high voltage robustness of the flat panel display in which multi-level conductive matrix 300 is employed. Furthermore, the conductive nature of the present invention 300 allows excess charge to be readily removed from the faceplate of the flat panel display. The present invention achieves the above-mentioned accomplishments without requiring the application of an ITO coating.
Referring still to FIG. 3, at area 202, for example, column separating portion 304b intersects row separating portion 302a. At area 202 the height of column separating portion 304b decreases to the height of row separating portion 302a. Thus, in the present embodiment, at area 202, the height of column separating portion 304b decreases to approximately 18-20 microns.
Referring next to FIG. 4, in the present invention, the trough or dip in the height of column separating portions 304a and 304b at the intersections with row separating portions 302a and 302b is significantly advantageous. Specifically, the taller height of column separating portions 304a and 304b near the intersection with row separating portions 302a and 302b provides buttressing for support structures 400a and 400b disposed along row separating portions 302a and 302b. That is, a wall or rib (400a and 400b), or other support structure commonly located on row separating portions 302a and 302b is stabilized or buttressed by taller proximately located column separating portions 304a and 304b.
With reference back to FIG. 3, due to the aforementioned differences in separation distances between rows and columns of photoresist structures, multi-level conductive matrix 300 also has a varying thickness. That is, in the present embodiment, row separating portions 302a and 302b have a thickness of approximately 75-80 microns. Column separating portions 304a and 304b, on the other hand, have a thickness of approximately 25-30 microns.
Thus, the present invention provides a conductive black matrix structure having sufficient height to effectively separate neighboring sub-pixels. The present invention also provides a black matrix structure which reduces arcing from the field emitters to the sub-pixels. The present invention further provides a conductive black matrix which does not have the increased cost and complexity, the increased back-scattering rate, and the undesirably high secondary emission coefficient associated with an ITO coated black matrix structure.
The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the Claims appended hereto and their equivalents.
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A multi-level conductive matrix structure for separating rows and columns of sub-pixels on the faceplate of a flat panel display device. In one embodiment, the present invention is formed partially of a first plurality of conductive ridges which are disposed on the faceplate between respective adjacent rows of sub-pixel regions. The present invention is further formed of a second plurality of conductive ridges which are orthogonally oriented with respect to and integral with the first plurality of conductive ridges such that a matrix structure is formed. In the conductive matrix of the present invention, the second plurality of conductive ridges have a height which is greater than the height of the first plurality of conductive ridges such that a multi-level conductive matrix is formed. However, the height of the second plurality of conductive ridges decreases to approximately the height of the first plurality of conductive ridges at respective intersections of the first and second plurality of conductive ridges. In so doing, the present invention provides a multi-level conductive matrix for separating rows and columns of sub-pixels on the faceplate of a flat panel display device.
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FIELD OF THE INVENTION
THIS INVENTION relates to a peptide obtained from a strain of Enterococcus mundtii and to a probiotic composition of a strain of Enterococcus mundtii . More particularly, the invention relates to a peptide obtained from a strain of Enterococcus mundtii , the gene coding for the peptide and various applications of the strain which produces the peptide and the peptide itself.
BACKGROUND TO THE INVENTION
Lactic acid bacteria play an important role in maintaining the balance of normal gastro-intestinal microflora. Diet, stress, microbial infection and intestinal diseases disturb the microbial balance, which often leads to a decrease in the number of viable lactic acid bacteria (especially lactobacilli and bifidobacteria) in the intestinal tract. The subsequent uncontrolled proliferation of pathogenic bacteria then leads to diarrhea and other clinical disorders such as cancer, inflammatory disease and ulcerative colitis.
One of the key properties of probiotic lactic acid bacteria is the adhesion of cells to epithelial cells or intestinal mucus. This requires strong interaction between receptor molecules on epithelial cells and bacterial surfaces. Adhesion of probiotic cells prevent the adhesion of pathogens and stimulate the immune system. The latter is achieved by interacting with mucosal membranes, which in turn sensitises the lymphoids. Another important characteristic of probiotics is survival at low pH and high bile salts.
Certain strains of bifidobacteria, lactobacilli and enterococci associated with the intestines of humans and animals are known to produce bacteriocins (antimicrobial peptides). The role of these peptides, and their significance in controlling the proliferation of pathogenic bacteria in the intestinal tract, is uncertain. However, as concluded from recent reports on bacteriocins active against Gram-negative bacteria, there may be renewed interest in these peptides and their interaction with intestinal pathogens. Many of the latter bacteriocins are produced by lactic acid bacteria normally present in the intestinal tract, viz. the Lactobacillus acidophilus -group, Lactobacillus reuteri, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacilsus pentosus, Lactobacillus paracasei subsp. paracasei and Enterococcus faecalis.
The invention describes a strain of Enterococcus mundtii that resists intestinal stress conditions (e.g. low pH, bile salts, salts, pancreatic enzymes) and produces a broad-spectrum antibacterial peptide (peptide ST4SA).
BRIEF DESCRIPTION OF THE INVENTION
According to one aspect of the present invention there is provided an isolated peptide from the bacterium Enterococcus mundtii , said peptide having the following amino acid sequence:
(SEQ. ID. NO. 12)
MSQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWK
S;
a fragment thereof having antimicrobial activity;
muteins and derivatives thereof having antimicrobial activity;
covalently bound bridge constructs thereof having antimicrobial activity; or
sequences having more than about 95% homology, preferably more than 85% homology, most preferably more than about 75% homology to said amino acid sequence, having antimicrobial activity.
According to another aspect of the present invention there is provided an isolated nucleotide sequence which codes for peptide ST4SA of the bacterium Enterococcus mundtii.
The isolated nucleotide sequence may comprise the following nucleotide sequence:
(SEQ. ID. NO. 11)
ATGTCACAAGTAGTAGGTGGAAAATACTACGGTAATGGAGTCTCATGTAA
TAAAAAAGGGTGCAGTGTTGATTGGGGAAAAGCTATTGGCATTATTGGAA
ATAATTCTGCTGCGAATTTAGCTACTGGTGGAGCAGCTGGTTGGAAAAG
T;
the complement thereof;
a fragment thereof capable of producing, following expression thereof, a peptide having antimicrobial activity; or
nucleotide sequences which hybridize under strict hybridization conditions thereto.
Strict hybridization conditions correspond to a wash of 2×SSC, 0.1% SDS, at 50° C.
The nucleotide sequence may be included in a vector, such as an expression vector or transfer vector in the form of a plasmid. The vector may include nucleic acid sequences encoding selection attributes, such as antibiotic resistance selection attributes, or other marker genes. Accordingly, the invention extends to a recombinant plasmid adapted for transformation of a microbial host cell, said plasmid comprising a plasmid vector into which a nucleotide sequence which codes for the antimicrobial peptide of the invention has been inserted.
The cell may be a prokaryotic or a eukaryotic cell, such as a bacterial cell or yeast cell. The nucleotide sequence may be incorporated transiently or constitutively into the genome of the cell. Accordingly, the invention extends to a transformed microbial cell which includes a recombinant plasmid, said plasmid comprising a plasmid vector into which a nucleotide sequence which codes for the antimicrobial peptide of the invention has been inserted.
According to a further aspect of the invention there is provided an isolated peptide from the bacterium Enterococcus mundtii , the peptide having antimicrobial activity.
The bacterium Enterococcus mundtii which produces the isolated peptide identified above has been deposited with the ATCC, 10801 University Boulevard, Manassas, Va. 20110, on Dec. 13, 2005, under the assigned number PTA-7278, in accordance with the Budapest Treaty deposit requirements. All restrictions upon public access to the deposit will be removed and sample replaced if viable samples cannot be dispersed by the depository, as necessary, upon allowance of the present application. The specific strain of the bacterium Enterococcus mundtii that produces the isolated peptide identified above has been designated as strain ST4SA. Accordingly, the invention extends to a substantially pure culture of Enterococcus mundtii strain ST4SA deposited with the ATCC under the assigned number PTA-7278, said culture capable of producing peptide ST4SA in a recoverable quantity upon fermentation in a nutrient medium containing assimilable sources of carbon, nitrogen, and inorganic substances.
Another aspect of the invention relates to a process for the production of a peptide of the invention which comprises cultivating Enterococcus mundtii strain ST4SA in a nutrient medium under micro-aerophilic conditions at a temperature of between 10° C. and 45° C., until a recoverable quantity of said peptide is produced, and recovering said peptide. Preferably the cultivation occurs at a temperature of about 37° C.
The nutrient medium may be selected from any one or more of the group including: corn steep liquor; cheese whey powder; MRS broth; yeast extract; and molasses. Preferably, the nutrient medium is MRS broth at pH 6 to 6.5.
The isolated peptide of the invention may be used as an antimicrobial agent in a liquid formulation or a gel formulation as a topical treatment for, for example, ear infections, such as mid-ear infections, and also throat, eye, or skin infections. The liquid formulation may also be for use as a liquid supplement to meals. The peptide may also further be used as an antimicrobial agent in a spray for treatment of, for example, sinus infections, sinusitis, tonsillitis, throat infections or rhinitis. The peptide may also be in the form of a lyophilized powder.
The isolated peptide may also be used as an antimicrobial agent following encapsulation in a polymer. The invention extends, according to another aspect thereof, to a polymer having incorporated therein an antimicrobial amount of peptide ST4SA. This polymer may then be used in a formulation for topical treatment of infections such as, for example, skin infections, or may be used for incorporation in implants or medical devices such as, for example, ear grommets, catheters, ostomy tubes and pouches, stents, suture material, hygiene products such as feminine hygiene products, contact lenses, contact lens solution, or for incorporation in wound dressings. The encapsulation of the antimicrobial peptide in the polymer leads to a slow release of the antimicrobial peptide and an extended period of treatment of a microbial infection.
The isolated peptide may be included in a concentration of 100 000 AU/ml (Arbitrary Units) to 300 000 AU/ml of polymer, preferably about 200 000 AU/ml of polymer.
The peptide further may be used as an antimicrobial agent by being incorporated into ointment, lotion, or cream formulations. These ointment, lotion, or cream formulations may be used to treat infections. The peptide may also further be used as an antimicrobial agent by being incorporated into liquid formulations such as, for example, contact lens rinsing fluid, or it may be incorporated into the contact lenses themselves. Accordingly, the invention provides, as another aspect thereof, an antimicrobial ointment, lotion, or cream containing an antimicrobial peptide of the invention.
In another form of the invention the peptide may be used as an antimicrobial agent by being incorporated into packaging material such as, for example, plastic, for use in the manufacture of aseptic packaging.
In an even further form of the invention the peptide may be used as part of a broad-spectrum probiotic of the bacterium Enterococcus mundtii in a tablet form or in a capsule form or it may be in an edible form such as, for example, a sweet or chewing gum.
According to a further aspect of the invention there is provided a probiotic composition including a biologically pure culture comprising a therapeutically effective concentration of Enterococcus mundtii strain ST4SA. The strain may be included in a concentration of about 10 6 to 10 9 , preferably about 10 8 viable cells (cfu) per ml of probiotic composition.
In one form of the invention the probiotic composition may be used to reduce pathogenic bacteria in an animal or a human.
In another form of the invention the probiotic composition may be used to reduce pathogenic viruses in an animal or a human.
The probiotic composition may be in the form of a powder, a liquid, a gel, a tablet, or may be incorporated into a foodstuff. The probiotic composition in a liquid form may be used as a liquid supplement to meals. The strain may be included in a concentration of about 10 6 to 10 9 , preferably about 10 8 viable cells (cfu) per ml of liquid supplement.
The probiotic composition may be administered to an animal or human at a final concentration of between 10 3 and 10 6 cfu/ml, preferably between 10 5 and 10 6 cfu/ml, most preferably about 3×10 5 cfu/ml.
According to another aspect of the invention there is provided a method of treating a bacterial infection condition in an animal or human, the method including the step of exposing an infected area of the animal or human to a substance or composition selected from the group comprising any one or more of:
a pharmaceutically effective amount of the Enterococcus mundtii strain of the invention; and a pharmaceutically effective amount of the antimicrobial peptide of the invention.
Accordingly, the invention extends also to use of a therapeutically effective amount of the Enterococcus mundtii strain of the invention in the manufacture of a medicament for use in a method of treating a bacterial infection in an animal or human.
The method may include the step of exposing bacterial species to the antimicrobial peptide of the invention at a concentration of 100 000 to 300 000 AU/ml, preferably about 200 000 AU/ml.
The invention extends also to use of a therapeutically effective amount of the antimicrobial peptide of the invention in the manufacture of a medicament for use in a method of treating a bacterial infection in an animal or human.
The invention further provides a substance or composition for use in a method of treating a bacterial infection in an animal or human, said substance or composition comprising the Enterococcus mundtii strain of the invention, and said method comprising administering a therapeutically effective amount of the substance or composition to the animal or human.
The invention further provides a substance or composition for use in a method of treating a bacterial infection in an animal or human, said substance or composition comprising the antimicrobial peptide of the invention, and said method comprising administering a therapeutically effective amount of the substance or composition to the animal or human.
The bacterial infection may be an infection caused by any one or more of: Acinetobacter baumanii; Bacillus cereus; Clostridium tyrobutyricum; Enterobacter cloacae; Escherichia coli; Klebsiella pneumoniae; Listeria innocua; Pseudomonas aruginosa; Staphylococcus aureus; Staphylococcus camosus; Streptococcus caprinus; Streptococcus ( Enterococcus ) faecalis ; or Streptococcus pneumoniae.
According to a still further aspect of the invention there is provided a method of inhibiting growth of bacterial species, the method including the step of exposing bacterial species to an effective amount of the antimicrobial peptide of the invention. The bacterial species may be selected from the group including:
Acinetobacter baumanii; Bacillus cereus; Clostridium tyrobutytricum; Enterobacter cloacae; Escherichia coli; Klebsiella pneumoniae; Listeria innocua; Pseudomonas aruginosa; Staphylococcus aureus; Staphylococcus carnosus; Streptococcus caprinus; Streptococcus ( Enterococcus ) faecalis ; and Streptococcus pneumoniae.
The method may include the step of exposing bacterial species to the antimicrobial peptide of the invention at a concentration of 100 000 to 300 000 AU/ml, preferably about 200 000 AU/ml.
According to one aspect of the present invention there is provided an isolated transporter peptide from the bacterium Enterococcus mundtii , said peptide having the amino acid sequence of SEQ. ID. NO. 14:
a fragment thereof; muteins and derivatives thereof; or sequences having more than about 90% homology, preferably more than 80% homology, most preferably more than about 70% homology to said amino acid sequence, having antimicrobial activity.
According to another aspect of the present invention there is provided an isolated nucleotide sequence which codes for ST4SA transporter peptide of the bacterium Enterococcus mundtii . The isolated nucleotide sequence may comprise the nucleotide sequence of SEQ. ID. NO. 13;
the complement thereof; a fragment thereof; or nucleotide sequences which hybridize under strict hybridization conditions thereto.
According to one aspect of the present invention there is provided an isolated immunity peptide from the bacterium Enterococcus mundtii , said peptide having the amino acid sequence of SEQ. ID. NO. 16:
a fragment thereof; muteins and derivatives thereof; or sequences having more than about 90% homology, preferably more than 80% homology, most preferably more than about 70% homology to said amino acid sequence, having antimicrobial activity.
According to another aspect of the present invention there is provided an isolated nucleotide sequence which codes for ST4SA immunity/adhesion peptide of the bacterium Enterococcus mundtii . The isolated nucleotide sequence may comprise the nucleotide sequence of SEQ. ID. NO. 15;
the complement thereof a fragment thereof; or nucleotide sequences which hybridize under strict hybridization conditions thereto.
The invention extends, according to another aspect thereof, to a primer selected from the group consisting of SEQ. ID. NO. 1 to SEQ. ID. NO. 10. Accordingly, the invention extends also to a primer pair selected from the following group:
primer pair comprising SEQ. ID. NO. 1 and SEQ. ID. NO. 2;
primer pair comprising SEQ. ID. NO. 3 and SEQ. ID. NO. 4;
primer pair comprising SEQ. ID. NO. 5 and SEQ. ID. NO. 6;
primer pair comprising SEQ. ID. NO. 7 and SEQ. ID. NO. 8; and
primer pair comprising SEQ. ID. NO. 9 and SEQ. ID. NO. 10.
The invention extends also to the use of the primer pair of SEQ. ID. NO. 1 and SEQ. ID. NO. 2 in the identification of Enterococcus mundtii.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the present invention, and to show how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings and tables in which;
FIG. 1 is an image of cell morphology of Enterococcus mundtii strain ST4SA as observed by SEM (scanning electron microscopy);
FIG. 2 is a photograph of an agarose gel showing a PCR product (DNA fragment) obtained by using genus-specific primers. A genus-specific DNA band of 112 kb, specific for Enterococcus , was obtained;
FIG. 3 is a photograph of an agarose gel showing a PCR product (DNA fragment) obtained by using species-specific primers. A species-specific DNA band of 306 bp, specific for Enterococcus mundtii , was obtained;
FIG. 4 is a graphic representation of peptide ST4SA separated by gel filtration (AKTA-purifier);
FIG. 5 is a photograph of a SDS-polyacrylamide gel showing the position of peptide ST4SA;
FIG. 6A is a photograph of an agarose gel showing the plasmid profile of E. mundtii ST4SA;
FIG. 6B is a Southern blot showing the location of the structural gene on the chromosome (genome) of strain ST4SA;
FIG. 7 is a diagrammatic representation of the amino acid sequence of E. mundtii peptide ST4SA;
FIG. 8 is a DNA sequence of the peptide ST4SA structural gene (A), transporter gene (B) and immunity gene (C);
FIGS. 9A and 9B show the influence of growth medium components on peptide ST4 production;
FIG. 10 is a graphic presentation of the production of peptide ST4SA in MRS broth;
FIG. 11 is a photograph of an agarose gel showing a DNA fragment which may contain the putative adhesion gene;
FIG. 12 is a graph showing the stability of peptide ST4SA (crude extract suspended in sterile distilled water) at different temperatures;
FIG. 13 is a photograph of inhibition zones recorded against Pseudomonas sp. on an agar plate;
FIG. 14 is a photograph of Streptococcus pneumoniae treated with peptide ST4SA (409 600 AU/ml) and leakage of the cytoplasm is indicated by the arrows;
FIG. 15 is a graph showing the growth inhibition of Streptococcus pneumoniae (pathogen 27);
FIG. 16 is a graph showing the growth inhibition of Streptococcus pneumoniae (pathogen 29);
FIG. 17 is a graph showing the growth inhibition of Klebsiella pneumoniae (pathogen 30);
FIG. 18 is a graph showing the growth inhibition of middle ear isolate (pathogen 40);
FIG. 19 is a graph showing the growth inhibition of middle ear isolate (pathogen BW);
FIG. 20 is a graph showing the growth inhibition of middle ear isolate (pathogen E);
FIG. 21 is a graph showing the growth inhibition of middle ear isolate (pathogen F);
FIG. 22 is a graph showing the growth inhibition of middle ear isolate (pathogen GW);
FIG. 23 is a graph showing growth inhibition of middle ear isolate (pathogen HW);
FIG. 24 is a graph showing growth of strain ST4SA in the presence of Listeria innocua LMG 13568 and production of peptide ST4SA. Symbols: -♦-=growth of strain ST4SA in the presence of L. innocua LMG 13568, -▪-=growth inhibition of L. innocua LMG 13568; -●-=changes in pH, ▮=production of peptide ST4SA;
FIG. 25 is a schematic presentation of a gastro-intestinal model (GIM) developed for evaluation of probiotic strain ST4SA;
FIG. 26 is a schematic presentation showing blocking of the Lipid II target site with vancomycin and its affect on the mode of action (antimicrobial activity) of peptide ST4SA. % Leakage refers to cytoplasmic leakage, as recorded by increased DNA and β-galactosidase activity levels.
FIG. 27 is a schematic representation of a disulfide bridge that was introduced into the peptide that covalently linked amino acids 9 (cysteine) and 14 (cysteine);
FIG. 28 shows a hydrophobicity plot of ST4SA;
FIG. 29 shows the results of L. monocytogenes challenge with ST4SA and survival in an in vitro GIT model;
FIG. 30 shows growth curves of E. mundtii ST4SA in MRS broth and CSL media;
FIG. 31 shows hemolysin and eosin stained sections of (A) Control Colon (B) Strain ST4SA fed colon (C) Control Ileum (D) Strain ST4SA fed Ileum (E) Control Liver (F) Strain ST4SA fed liver (G) Control Spleen (H) Strain ST4SA Spleen at 60× magnification;
Table 1 shows phenotypic characteristics of strain ST4SA (sugar fermentation reactions);
Table 2 shows differential characteristics of strain ST4SA;
Table 3 shows the effect of enzymes, temperature, pH and detergents on peptide ST4SA;
Table 4 shows an activity spectrum of peptide ST4SA;
Table 5 shows activity of peptide ST4SA on paper disks;
Table 6 shows the comparison of the activity of peptide ST4SA to commonly used antibiotics;
Table 7 shows adhesion of peptide ST4SA to pathogens;
Table 8 shows extracellular DNA recorded after treatment of pathogens with peptide ST4SA;
Table 9 shows β-galactosidase activity recorded after the treatment of pathogens with peptide ST4SA;
Table 10 shows operation of the GIM (computerized);
Table 11 shows survival of strain ST4SA and production of peptide ST4SA in the GIM— Listeria monocytogenes was used as target organism (pathogen). The values are an average of three trials. The nutrients used were NAN Pelargon (Nestlé) and MRS (De Man Rogosa medium, Biolab), respectively;
Table 12 shows antibiotic resistance of strain ST4SA;
Table 13 shows growth of strain ST4SA in the presence of different concentrations of Trimethoprim-sulfamethoxazole (TMP-SMX) and Metronidazole;
Table 14 shows virulence factors that were assayed;
Table 15 shows the adhesion of strain ST4SA to Caco-2 cell lines by plate counting (control);
Table 16 shows competitive exclusion of strain ST4SA and L. monocytogenes;
Table 17 shows weight figures for rats administered strain ST4SA, Lactovita or unsupplemented water;
Table 18 shows β-glucuronidase activity in faecal samples of male Wistar rats during a (A) 107 day Lactovita study and (B) a 50 day strain ST4SA study. Values are mM ρ-nitrophenol released per 2 hours. Standard error values are shown in parenthesis;
Table 19 shows the purification of peptide ST4SA in MRSf (MRS filtrate) medium;
Table 20 shows results for pure CSL, molasses and CWp tested as growth media for peptide ST4SA production;
Table 21 shows a full factorial design (FFD) with CSL and CWp as components to determine which media had the most significant effect on peptide ST4SA production;
Table 22 shows the results of CSL supplemented with MRS components for ST4SA activity optimization;
Table 23 shows high and low concentrations of MRS components and CSL;
Table 24 shows the 2 10-5 FrFD design;
Table 25 shows an analysis of Variance Table for a 2 10-5 FrFD design;
Table 26 shows a 2 2 FFD with 3 centre points for determination of CSL and YE concentrations;
Table 27 shows the uptake of carbon during fermentation;
Table 28 shows the results of resistance testing of E. mundtii ST4 against antibiotics and anti-inflammatory drugs;
Table 29 shows the effect of antibiotics and anti-inflammatory medicaments on adhesion of ST4SA to Caco-2 cells;
DETAILED DESCRIPTION OF THE INVENTION
The invention describes a strain of the bacterium Enterococcus mundtii that resists intestinal stress conditions (e.g. low pH, bile salts, salts, pancreatic enzymes) and produces a broad-spectrum antibacterial peptide, namely peptide ST4SA. The strain of Enterococcus mundtii which produces the peptide ST4SA has been deposited with the ATCC (American Type Culture Collection) and the assigned number is PTA-7278. Activity has been observed against a large number of Gram-positive and Gram-negative bacteria, most of these isolated from middle-ear infections and the intestine. Examples of bacteria inhibited are as follows: Acinetobacter baumanii, Bacillus cereus, Clostridium tyrobutyricum, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Listeria innocua, Pseudomonas aruginosa, Staphylococcus aureus, Staphylococcus carnosus, Streptococcus caprinus, Streptococcus ( Enterococcus ) faecalis, Streptococcus pneumoniae , and a number of clinical strains of unidentified Gram-positive and Gram-negative bacteria isolated from infected middle-ear fluid samples. This is a large spectrum of activity, specifically against such a variety of human pathogens.
A number of broad-spectrum antibacterial peptides with activity against Gram-negative bacteria have been described, e.g. pentocin 35d produced by Lactobacillus pentosus, bacteriocin ST151 BR produced by Lactobacillus pentosus ST151 BR, a bacteriocin produced by Lactobacillus paracasei subsp. paracasei , thermophylin produced by Streptococcus termophylus , peptide AS-48 produced by Enterococcus faecalis , a bacteriocin produced by Lactococcus lactis KCA2386 and enterocin CRL35 produced by Enterococcus faecium . However, the activity spectrum of these peptides are much narrower than that recorded for peptide ST4SA, as may be seen from the species sensitive to peptide ST4SA listed above. The broad spectrum of activity, especially against pathogenic bacteria, renders peptide ST4SA ideal for the control of bacterial infections, especially middle-ear infections (since the peptide is active against a large variety of middle-ear pathogens), as well as pathogens involved in secondary wound infections (the peptide inhibits the growth of a number of these pathogens). Pathogens isolated from infected middle-ear fluid were Acinetobacter baumanii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aruginosa, Staphylococcus aureus, Staphylococcus carnosus, Streptococcus pneumoniae , and a number of unidentified Gram-positive and Gram-negative bacteria.
Materials and Methods
Isolation of Strain ST4SA and Identification to Species Level
Soy bean extract; obtained from soy beans that have been immersed in sterile distilled water for 4 h, was serially diluted and plated onto MRS Agar (Biolab), Biolab Diagnostics, Midrand, SA), supplemented with 50 mg/l Natamycin (Delvocid®, Gist-brocades, B.V., Delft, The Netherlands) to prevent fungal growth. The plates were incubated at 30° C. and 37° C. for two days.
Colonies were at random selected from plates with between 50 and 300 cfu (colony forming units) and screened for antimicrobial activity by overlaying them with a second layer of MRS Agar, supplemented with Delvocid® (50 mg/l). The plates were incubated at 30° C. and 37° C. for 48 h, in an anaerobic flask (Oxoid, New Hampshire, England) in the presence of a Gas Generation Kit (Oxoid). The colonies were covered with a third layer (ca. 10 ml) semi-solid (1.0% agar, w/v) BHI medium (Merck, Darmstadt, Germany), supplemented with 1 ml active growing cells (ca. 10 6 cfu/ml) of Lactobacillus casei, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus , respectively. The plates were incubated at 37° C. for 24 h.
One of the colonies inhibited the largest variety of pathogens included in the test panel (Table 4) was re-inoculated into MRS broth (Biolab), followed by re-streaking to obtain pure cultures. The isolate was designated strain ST4SA. Antimicrobial activity was confirmed by using the agar-spot test method.
The cell morphology of strain ST4SA was studied by scanning electron microscopy (SEM) (see FIG. 1 ). Ten ml of an early-exponential phase (OD 600nm =0.2) culture of strain ST4SA was harvested by centrifugation and washed five times with sterile distilled water (3 000×g, 10 min, 4° C.). The pellet was resuspended in 500 μl sterile MilliQ water (Waters, Millipore) and then subjected to microscopy.
Further identification was accomplished by physiological (Table 2) and biochemical characteristics. Pigment formation was tested on Tryptic Soy Broth (Merck). Test for motility was also done. Sugar fermentation reactions (Table 1) were recorded by using the API 50 CHL and API 20 Strep test strips (Biomérieux, Marcy-l'Etiole, France) and compared with reactions listed for enterococci.
TABLE 1
Compound/Derivative
E. mundtii ST4SA fermentation
Control
Glycerol
+
Erythritol
D-arabinose
L-arabinose
++
Ribose
+++
D-xylose
++
L-xylose
Adonitol
Methyl-xyloside
Galactose
++
D-glucose
+++
D-fructose
+++
D-mannose
++
L-sorbose
Rhamnose
++
Dulcitol
Inositol
Mannitol
++
Sorbitol
++
Methyl-D-mannoside
++
Methyl-D-glucoside
Acetyl glucosamine
++
Amygdaline
+++
Arbutine
+++
Esculine
+++
Salicine
+++
Cellobiose
+++
Maltose
+++
Lactose
+++
Melibiose
++
Saccharose
+++
Trehalose
++
Inuline
Melezitose
D-raffinose
Amidon
+
Glycogen
Xylitol
B Gentiobiose
+++
D-turanose
D-lyxose
D-tagatose
D-fucose
L-fucose
D-arabitol
L-arabitol
Gluconate
2 ceto-gluconate
5 ceto-gluconate
TABLE 2
Characteristic
Strain ST4SA
CO 2 from glucose
−
Growth at 10° C.
+
Growth at 45° C.
+
Growth in 6.5% NaCl
+
Growth in 18% NaCl
−
Growth at pH 4.4
+
Growth at pH 9.6
+
Lactic acid configuration
L
Further identification was by DNA banding patterns generated with primers specific for Enterococcus ( FIG. 2 ) and Enterococcus mundtii ( FIG. 3 ). A 50 bp DNA fragment (Amersham Bioscience, UK Limited, UK) was used as marker. Primers used to generate the 306 bp fragment (shown in FIG. 3 ) were designed from suitably conserved regions on 16S rDNA.
SEQ. ID. NO. 1:
Forward primer:
AACGAGCGCAACCC;
SEQ. ID. NO. 2:
Reverse primer:
GACGGGCGGTGTGTAC
Sequencing of the DNA fragment revealed 98% homology with conserved 16S rDNA fragments in GenBank.
Expression of Antimicrobial Activity
Antimicrobial activity was expressed as arbitrary units (AU) per ml cell-free supernatant. One AU is defined as the reciprocal of the highest dilution showing a clear zone of growth inhibition and is calculated as follows:
a b ×100, where “a” represents the dilution factor and “b” the last dilution that produces an inhibition zone of at least 2 mm in diameter. Activity is expressed per ml by multiplication with 100. Lactobacillus casei LHS was used as indicator strain.
Characterization of the Antimicrobial Substance
Strain ST4SA was cultured in MRS broth (Biolab) for 24 and 48 h at 30° C. The cells were harvested (8 000×g, 4° C., 15 min) and the cell-free supernatants adjusted to pH 6.0 with 6M NaOH. One ml of each supernatant was treated with catalase (Boehringer Mannheim) at 0.1 mg/ml (final concentration), Proteinase K (Roche, Indianapolis, Ind., USA), pronase, papain, pepsin and trypsin (Boehringer Mannheim GmbH, Germany), at 1 mg/ml and 0.1 mg/ml (final concentration), respectively. After incubation the enzymes were heat-inactivated (3 min at 100° C.) and tested for antimicrobial activity, as described before. The results are listed in Table 3.
Aliquots of peptide ST4SA were exposed to heat treatments of 30° C., 60° C. and 100° C. for 10, 30 and 90 min, respectively, and 121° C. for 20 min (Table 3). The samples were then tested for antimicrobial activity, as described before.
TABLE 3
Treatment
Peptide ST4SA
Enzymes:
α-amylase
+
Proteinase K
−
pepsin
−
pronase
−
pH:
2.0-12.0
+
Heat:
30, 60, 100° C. for 10 min
+
30, 60, 100° C. for 30 min
+
30, 60, 100° C. for 90 min
+
121° C. for 20 min
−
Detergents (1%):
SDS
+
Tween 20, Tween 80
+
urea
+
Triton X-100
+
Triton X-114
−
EDTA:
0.1 mM, 1.0 mM, 2.0 mM
+
Key: − = no activity; + = activity zones of at least 5 mm in diameter
In a separate experiment, samples of peptide ST4SA were adjusted to pH values ranging from 2-12, incubated at 37° C. for 30 min, neutralised to pH 7, and then tested for antimicrobial activity (Table 3).
Isolation and Purification of Peptide ST4SA
A 24 h-old culture of strain ST4SA was inoculated (2%, v/v, OD 600nm =8.0) into MRS broth (Biolab). Incubation was at 37° C., without agitation, for 20 h. The cells were harvested (8 000×g, 10 min, 4° C.) and the peptide precipitated from the cell-free supernatant with 80% saturated ammonium sulphate. The precipitate was resuspended in one tenth volume 25 mM ammonium acetate (pH 6.5), desalted against distilled water by using a 1000 Da cut-off dialysis membrane (Spectrum Inc., CA, USA) and loaded on a SepPak C18 column (Water Millipore, Mass., USA). The column was washed with 20% (v/v) iso-propanol in 25 mM ammonium acetate (pH 6.5) and the bacteriocin eluted with 40% iso-propanol in 25 mM ammonium acetate (pH 6.5). After drying under vacuum (Speed-Vac; Savant), the fractions were pooled and dissolved in 50 mM phosphate buffer, pH 6.5. The active fractions were further separated by gel filtration chromatography in a Superdex™ 75 column (Amersham Pharmacia Biotech) linked to an ÄKTApurifier (Amersham) ( FIG. 4 ). Elution of the peptide from the column was with 50 mM phosphate buffer and 400 mM NaCl, pH 6.5. Peptides were detected at 254 nm and 280 nm, respectively. Fractions containing the active peptide were collected, dried under vacuum and stored at −20° C. Activity tests were performed by using the agar spot method.
Size Determination
Strain ST4SA was grown in MRS broth (Biolab) for 20 h at 30° C. The cells were harvested by centrifugation (8 000×g, 10 min, 4° C.) and peptide ST4SA precipitated from the cell-free supernatants with 80% saturated ammonium sulphate. The precipitate was resuspended in one tenth volume 25 mM ammonium acetate (pH 6.5), desalted against distilled water by using a 1000 Da cut-off dialysis membrane (Spectrum Inc., CA, USA) and separated by tricine-SDS-PAGE ( FIG. 5A ). A low molecular weight marker with sizes ranging from 2.35 to 46 kDa (Amersham International, UK) was used. The gels were fixed and one half overlaid with L. casei LHS (10 6 cfu/mL), embedded in Brain Heart Infusion (BHI) agar (Biolab), to determine the position of the active bacteriocin ( FIG. 5B ).
Cytotoxicity Tests on Peptide ST4SA
To determine if peptide ST4SA has cytotoxic properties, triplicate wells of confluent monolayers of monkey kidney Vero cells were grown in tissue culture plates for 48 h and then exposed to various concentrations of the antimicrobial peptide. After 48 h of incubation, cell viability was tested by treating the cells with tetrazolium salt MTT [3-(4,5-dimethylthiazol-2-gamma-2,5-diphenyl tetrazolium bromide] (Sigma). Production of a blue product (formazan), which forms after cleaving of MTT by succinate dehydrogenase was recorded.
The 50% cytotoxicity level (CC 50 ) was defined as the peptide concentration (μg/ml) required to reduce cell viability by 50%. According to the CC 50 results (cytotoxicity level), no cytotoxicity was recorded, that is, the peptide has zero (0) CC 50 .
Plasmid Isolation
Total DNA was isolated. Plasmid DNA was isolated, after which the DNA was further purified by CsCl density gradient centrifugation. The DNA was separated on an agarose gel ( FIG. 6 ). Lambda DNA digested with EcoRI and HindIII (Promega, Madison, USA) was used as molecular weight marker.
Plasmid Curing
Curing experiments were conducted. Cells of Ent. mundtii ST4SA were incubated in the presence of novobiocin (1-25 μg ml −1 ) for 72 h at 37° C. The culture which grew at the highest concentration of novobiocin was serially diluted with sterile saline and plated out onto MRS agar plates. After overnight incubation at 37° C., the colonies were replica-plated and the original plates overlaid with cells of Enterococcus faecalis LMG 13566. After a further 16 h of incubation at 37° C., the colonies were checked for loss of antimicrobial activity.
Conjugative Transfer Experiments
Filter mating experiments were done. An overnight grown culture (0.25 ml) of Ent. mundtii ST4SA and Ent. faecalis FA2-2 were added to 4.5 ml MRS, mixed and filtered through a 0.45 μm pore-size sterile membrane filter (HAWP, Millipore). The membrane was placed onto a MRS agar plate and incubated overnight at 37° C. The cells were washed from the filter into 1 ml MRS, serially diluted and plated onto MRS agar plates containing 25 μg ml −1 fusidic acid, 25 μg ml −1 rifampicin and 2000 AU ml −1 crude peptide ST4SA. The experiment was repeated with Ent faecalis OGX1 as recipient. In this case the selection was done on plates containing 1 mg ml −1 streptomycin and 2000 AU ml −1 crude peptide ST4SA. Colonies were selected at random and checked for production of peptide ST4SA and screened for plasmid content, as described before. A colony of conjugated cells of Ent. faecalis OGX1 which contained pST4SA was cultured and the cell-free supernatant was subjected to activity tests, as described before.
Detection of the Genetic Elements Encoding Peptide ST4SA and DNA Sequencing.
Total DNA was isolated. The DNA primers used to amplify the structural gene, transporter gene and immunity gene (listed below) by PCR, were designed based on partial sequences published for other antimicrobial peptides. Sequencing was performed with an ABI Pris™ BigDye™ Terminator Cycle Sequencing Ready Reaction kit on a ABI Prism™ 377 DNA Sequencer (PE Applied Biosystem, Foster City, USA). A database search was performed by using the BLASTN and BLASTX programs of the National Center for Biotechnology Information (NCBI), Bethesda, Md. 20894, USA.
Structural gene Primers: SEQ. ID. NO. 3: SG-a: TGAGAGAAGGTTTAAGTTTTGAAG AA (forward) SEQ. ID. NO. 4: SG-b: TCCACTGAAATCCATGAATGA (reverse) ABC transporter primers: SEQ. ID. NO. 5: ABC 1-a: TGATGGATTTCAGTGGAAGT (forward) SEQ. ID. NO. 6: ABC 1-b: ATCTCTTCTCCGTTTAATCG (reverse) SEQ. ID. NO. 7: ABC2-a: GTCATTGTTGTGGGGATTAT (forward) SEQ. ID. NO. 8: ABG2-b: TCTAGATACGTATCAAGTCC (reverse) Immunity primers: SEQ. ID. NO. 9: Immun-a: TTCCTGATGAACAAGAACTC (forward) SEQ. ID. NO. 10: Immun-b: GTCCCCACAACCAATAACTA (reverse)
Production of Peptide ST4SA in Different Growth Media and at Different Initial Growth pH values
An 18 h-old culture of strain ST4SA was inoculated (2%, v/v) into MRS broth, BHI broth and M17 broth (Merck, Darmstadt, Germany), respectively. Incubation was at 30° C. and 37° C., respectively, without agitation, for 28 h. Samples were taken every hour and examined for bacterial growth (OD at 600 nm), changes in culture pH, and antimicrobial activity (AU/ml) against L. casei LHS. The agar-spot test method was used as described before.
In a separate experiment, the effect of initial medium pH on the production of peptide ST4SA was determined. Volumes of 300 ml MRS broth were adjusted to pH 4.5, 5.0, 5.5, 6.0 and 6.5, respectively, with 6 M HCl or 6 M NaOH and then autoclaved ( FIG. 9A ). Each flask was inoculated with 2% (v/v) of an 18 h-old culture of strain ST4SA and incubated at 30° C. for 20 h without agitation. Changes in culture pH and production of peptide ST4SA, expressed as AU/ml, were determined every hour as described hereinbefore. All experiments were done in triplicate.
Effect of Medium Composition on the Production of Peptide ST4SA
Strain ST4SA was grown in 10 ml MRS broth for 18 h at 30° C., the cells harvested by centrifugation (8000×g, 10 min, 4° C.), and the pellet resuspended in 10 ml sterile peptone water. Four ml of this cell suspension was used to inoculate 200 ml of the following media: (a) MRS broth (De Man, Rogosa and Sharpe), without organic nutrients, supplemented with tryptone (20.0 g/l), meat extract (20.0 g/l), yeast extract (20.0 g/l), tryptone (12.5 g/l) plus meat extract (7.5 g/l), tryptone (12.5 g/l) plus yeast extract (7.5 g/l), meat extract (10.0 g/l) plus yeast extract (10.0 g/l), or a combination of tryptone (10.0 g/l), meat extract (5.0 g/l) and yeast extract (5.0 g/l), respectively; (b) MRS broth (Biolab), i.e. with 20.0 g/l glucose; (c) MRS broth (De Man, Rogosa and Sharpe) without glucose, supplemented with 20.0 g/l fructose, sucrose, lactose, mannose, and maltose, respectively; (d) MRS broth with 0.1-40.0 g/l fructose as sole carbon source; (e) MRS broth (De Man, Rogosa and Sharpe) with 2.0-50.0 g/l K 2 HPO 4 or 2.0-50.0 g/l KH s PO 4 ; and (f) MRS broth (De Man, Rogosa and Sharpe) supplemented with 0-50.0 g/l glycerol. In a separate experiment, the vitamins cyanocobalamin (Sigma, St. Louis, Mo.), L-ascorbic acid (BDH Chemicals Ltd, Poole, UK), thiamine (Sigma), DL-6,8-thioctic acid (Sigma) and Vitamin K 1 (Fluka Chemie AG, CH-9471 Buchs, Switzerland) were filter-sterilised and added to MRS broth at 1.0 mg/ml (final concentration). Incubation for all tests was at 30° C. for 20 h. Activity levels of peptide ST4SA were determined as described before. All experiments were done in triplicate.
Strain ST4SA was identified as a strain of the genus Enterococcus , based on morphology, as shown in FIG. 1 , non-motility, absence of pigment formation, and PCR with genus-specific primers ( FIG. 2 ) and species-specific primers ( FIG. 3 ). Further identification to species level was by sugar fermentation patterns as shown in Table 1 and physiological characteristics as shown in Table 2 above.
Peptide ST4SA was inactivated by treatment with proteolytic enzymes (Proteinase K, pepsin, pronase, papain and trypsin), Triton X-114 and after 20 min at 121° C., as can be seen in Table 3. The peptide remained active after treatment for 90 min at 100° C. and when treated with Tween 20, Tween 80, urea, EDTA and Triton X-100 (Table 3). No activity was lost after incubation at pH values ranging from 2.0 to 12.0 (Table 3).
Peptide ST4SA inhibited a large number of Gram-positive and Gram-negative bacteria as shown in Table 4.
TABLE 4
Organism
Temp.(° C.)
Medium, incubation
Peptide activity
Acinetobacter baumanii AB16
37
BHI, aerobic
+
Bacillus cereus LMG 13569
37
BHI, aerobic
+
Clostridium tyrobutyricum LMG 13571
30
RCM, anaerobic
+
Enterobacter cloacae 26
37
BHI
+
Enterococcus faecalis LMG 13566, E77, E80,
37
MRS, aerobic
+
E90, E92, FA2, 20, 21
Escherichia coli EC1
37
BHI
+
Klebsiela pneumoniae KP31
37
BHI
+
Lactobacillus acidophilus LMG 13550
37
MRS, anaerobic
−
Lactobacillus bulgaricus LMG 13551
37
MRS, anaerobic
−
Lactobacillus casei LMG 13552
37
MRS, anaerobic
−
Lactobacillus curvatus LMG 13553
30
MRS, anaerobic
−
Lactobacillus fermentum LMG 13554
37
MRS, anaerobic
−
Lactobacillus helveticus LMG 13555
42
MRS, anaerobic
−
Lactobacillus plantarum LMG 13556
37
MRS, anaerobic
−
Lactobacillus reuteri LMG 13557
37
MRS, anaerobic
−
Lactobacillus sakei LMG 13558
30
MRS, anaerobic
+
Leuconostoc mesenteroides subsp. cremoris
30
MRS, anaerobic
−
LMG 13562
Listeria innocua LMG 13568
30
BHI, aerobic
+
Pediococcus pentosaceus LMG 13560
30
MRS, anaerobic
−
Prop. acidipropionici LMG 13572
32
GYP, anaerobic
−
Propionibacterium sp. LMG 13574
32
GYP, anaerobic
+
Pseudomonas aeruginosa 1, 7
37
BHI, aerobic
+
Staphylococcus aureus 6, 13, 33-38
37
BHI
+
Staphylococcus carnosus LMG 13567
37
BHI, aerobic
+
Streptococcus caprinus TS1, TS2
37
BHI, aerobic
+
Streptococcus pneumoniae 3, 4, 27, 29
37
BHI, aerobic
+
Streptococcus thermophilus LMG 13565
42
MRS, anaerobic
−
Peptide ST4SA was purified by gel filtration shown in FIG. 4 and is in the range of 3400 Da, as seen from FIGS. 4 and 5 . The peptide had no cytotoxicity when tested on Vero cells as described hereinbefore.
Strain ST4SA has two plasmids as shown in FIG. 6A . Curing the strain of these plasmids did not result in loss of antimicrobial activity. Probing of the chromosome and plasmid DNA with a DNA fragment encoding the structural gene showed clear hybridization with the chromosome (genome) ( FIG. 6B ). This proved that the structural gene encoding peptide ST4SA is located on the genome. Furthermore, conjugation of these plasmids to E. faecalis (not shown) did not convert the strain to a peptide ST4SA producer, confirming that the genes encoding peptide ST4 production are located on the genome of strain ST4SA.
The sequence of peptide ST4SA is indicated in FIG. 7 and the sequence listing and is indexed as SEQ. ID. NO. 12 for the purposes of this invention. The sequence of the transporter and immunity peptides are indexed as SEQ. ID. NOs 14 and 16, respectively, for the purposes of this invention.
The DNA sequences of the structural, transporter and immunity genes are indicated in FIG. 8 and the sequence listing, and are indexed as SEQ. ID. NOs 11, 13 and 15, respectively, for the purposes of this specification.
Production of peptide ST4SA in different growth media is indicated in FIGS. 9A and 9B . The influence of initial growth pH on peptide ST4SA production is indicated in FIG. 9A . From these results, it is evident that peptide ST4SA is optimally produced in MRS broth at an initial pH of 6.0 and 6.5, and is stimulated by the presence of 10-20 g/l K 2 HPO 4 , 15.0-20.0 g/l fructose, or in the presence of vitamins C, B 1 and DL-6,8-thioctic acid.
Production of peptide ST4SA is indicated in FIG. 10 . Maximal production was recorded after 14 h of growth.
A DNA fragment containing an adhesion/immunity gene is indicated in FIG. 11 , and is indexed as SEQ. ID. NO. 15 for the purposes of this specification.
Enterococcus mundtii ST4SA produces a broad-spectrum antimicrobial peptide (peptide ST4SA) with activity against a number of pathogens. The structural gene encoding the leader peptide and propeptide (collectively known as the prepeptide) is located on the genome of strain ST4SA (see FIG. 6B ). Only one such gene structure was detected, suggesting that only one peptide is responsible for the broad spectrum of antimicrobial activity. Efforts were made to cure strain ST4SA from its 50 kb and 100 kb plasmids ( FIG. 1 ), but they failed. This suggests that the plasmid may play a major role in rendering immunity to peptide ST4SA, or harbours genes important in key metabolic reactions.
Further evidence that ST4SA is a strain of Enterococcus mundtii was obtained by species-specific PCR (polymerase chain reaction) with primers designed from conserved regions on 16S rDNA using:
SEQ. ID. NO. 1:
Forward primer:
AACGAGCGCAACCC;
SEQ. ID. NO. 2
Reverse primer:
GACGGGCGGTGTGTAC.
A 306 base-pair fragment was amplified (shown in FIG. 3 ). Sequencing of the DNA fragment yielded 98% homology with conserved 16S rDNA fragments in GenBank.
The structural gene (encoding the propeptide ST4SA), the transporter genes and the immunity gene have been sequenced and their respective amino acid sequences translated from the DNA sequences ( FIG. 8 ).
The stability of peptide ST4SA, suspended in sterile distilled water, was tested at temperatures ranging from −20° C. to 60° C. over 42 days ( FIG. 12 ). The peptide remained stable at −20° C. for 42 days and for three weeks at 4° C. Stability decreased after one week at 37° C. Peptide ST4SA in powder form did, however, remain stable for 6 months at room temperature (25° C.). Peptide ST4SA will be produced in powder form and marketed as such. Once dissolved in sterile distilled water, peptide ST4SA may be kept for three weeks at 4° C. (see FIG. 12 ).
The activity of peptide ST4SA on paper disks is listed in Table 5. Comparison of activity with antibiotics is listed in Table 6. Activity was tested against a Pseudomonas sp. isolated from infected middle-ear fluid. Images of the inhibition zones are shown in FIG. 13 .
TABLE 5
Activity of peptide ST4SA on paper disks.
Peptide ST4SA (AU/ml)
Freeze dried (AU/ml)
409600
Paper disk (2 cm × 2 cm; 700 μl)
286720
Paper disk (0.6 cm diameter)
20263
TABLE 6
Comparison of the activity of peptide
ST4SA to commonly used antibiotics.
Antibiotic
Diameter of inhibition zones (mm)
Ampicillin (10 μg)
24
Bacitracin (10 units)
10
Chloramphenicol (30 μg)
28
Erythromycin (15 μg)
No zone
Tetracycline (30 μg)
35
Peptide ST4SA
25
Binding of peptide ST4SA to target cells is important to ensure penetration of the peptide. The ability of peptide ST4SA to adhere to pathogens was studied and the results were expressed as a percentage binding to the pathogens (Table 7). Concluded from these results, at least 75% of peptide ST4SA binds to the pathogens tested. Adhesion of peptide ST4SA to the target cell leads to penetration and disruption of the cell membrane ( FIG. 14 ).
TABLE 7
Adhesion of peptide ST4SA to pathogens.
% Binding of peptide ST4SA
to the target cell (pathogen)
Peptide ST4SA
Peptide ST4SA
at 6 400 AU/mL
at 204 800 AU/ml
Pathogen
0
50
75
88
94
100
0
50
75
88
94
100
Strepto-
coccus
pneu-
moniae
27
+
+
29
+
+
D
+
+
Strepto-
coccus
pyo-
genes
20
+
+
21
+
+
Pseudo-
monas
auringi-
nosa
E
+
+
Klebsiella
pneu-
moniae
30
+
+
Middle ear
isolates
(unknown)
13
+
+
17
+
+
25
+
+
40
+
+
BW
+
+
CW
+
+
DW
F
+
+
HW
+
+
I
+
+
J
+
+
GW
+
+
K
+
+
L
+
+
M
+
+
Further evidence of cell membrane damage and leakage of cellular constituents was obtained by testing for extracellular DNA and extracellular β-galactosidase activity. The results are shown in Tables 8 and 9, respectively. The results indicate that DNA and α-galactosidase leaked from cells damaged by peptide ST4SA. α-galactosidase leakage was not recorded for all pathogens, due to the fact that not all species have high intracellular levels of this enzyme.
TABLE 8
Extracellular DNA recorded after treatment of
pathogens with peptide ST4SA.
Pathogen
DNA-leakage (O.D. readings at 260 nm)
Streptococcus pneumoniae
27
1.670
29
1.182
D
1.160
Streptococcus pyogenes
20
0.930
Pseudomonas auringinosa
E
0.187
Staphylococcus aureus
36
0.892
Klebsiella pneumoniae
30
1.01
Middle ear isolates
(unknown)
40
0.801
BW
1.186
DW
1.153
F
1.428
HW
1.559
GW
0.751
K
0.455
L
0.592
M
0.326
Control
Enterococcus spp. HKLHS
1.395
TABLE 9
Pathogen
β-galactosidase recorded at OD 420
Streptococcus pneumoniae
27
No leakage
29
No leakage
D
No leakage
Streptococcus pyogenes
20
No leakage
Staphylococcus aureus
36
No leakage
Klebsiella pneumoniae
30
No leakage
Middle ear isolates (unknown)
40
BW
0.370
DW
0.293
F
0.318
HW
0.235
GW
0.373
K
No leakage
L
No leakage
M
No leakage
Control
Enterococcus spp. HKLHS
No leakage
Cell lysis of different pathogens after treatment with peptide ST4SA are shown in FIGS. 15 to 23 . A 0.2% (v/v) inoculum of an overnight pathogen was inoculated into BHI broth. Peptide ST4SA was added to each pathogen at mid-exponential phase. From the results presented herein ( FIGS. 15 to 23 ), it is clear that peptide ST4SA acted in a bactericidal manner against most pathogens.
Production of peptide ST4SA was studied in the presence of Listeria innocua ( FIG. 24 ). Based on these results, L. innocua stimulated strain ST4SA to produce peptide ST4SA, during which L. innocua was inhibited.
Enterococcus Mundtii ST4SA as a Probiotic
The survival of Enterococcus mundtii ST4SA was evaluated in a computerized gastro-intestinal model (GIM, shown in FIG. 25 ).
The first vessel in the GIM simulates the stomach, the second vessel the duodenum, vessel number three the jejunum and ileum, and vessel four the colon. Flow of the nutrients was regulated by dedicated software. The pH in the different sections of the GIM was regulated by the peristaltic addition of sterile 1N HCl or 1N NaOH. Each section was fitted with a highly sensitive pH probe, linked to a control unit and computer. The flow rate of nutrients through the GIM was adjusted according to an infant's intestinal tract. Conditions simulating a short digestive tract were chosen to allow greater fluctuation and thus increased stress onto the probiotic. Four infant formulas (Lactogen2, NAN Pelargon, ALL110 and Alfare) were evaluated. Dosage with the probiotic bacterium (ST4SA) was according to prescription, i.e. 10 8 viable cells (cfu) per ml. The probiotic cells were suspended in saliva. The pancreatic-bile solution contained NaHCO 3 , pancreatin and oxgall, dissolved in distilled water. The conditions used in the GIM were as summarized in Tables 10 and 11.
TABLE 10
Time
Pancreatic-bile
(min.)
pH
Growth medium
solution
0-4
Nutrients pumped into stomach vessel.
Dosage with strain ST4SA (10 8 cfu/ml)
4-44
5.2
Incubation in stomach
44-64
4.9
64-108
4.5
108-128
4.1
128-154
3.7
154-156
Pancreatic-bile
solution pumped
into the
duodenum
154-158
Stomach contents pumped to
duodenum
158-274
6.5
Incubation in duodenum
274-280
Duodenum contents pumped to jejunum
280-394
6.5
Incubation in jejunum
394-401
Jejunum contents pumped to ileum
401-520
6.0
Incubation in ileum
TABLE 11
Bacteriocin
Cfu a /ml
activity
Bacteriocin
GIM
in NAN
(>25 600
Cfu/ml in
activity
section
Pelargon
AU b /ml)
MRS broth
(>25 600 AU/ml)
Inoculum
10 × 10 8
+
6.0 × 10 7
+
Stomach
1.2 × 10 7
+
3.7 × 10 7
+
Duodenum
2.5 × 10 6
+
1.0 × 10 8
+
Jejenum
1.0 × 10 7
+
1.3 × 10 8
+
Ileum
5.0 × 10 7
+
1.0 × 10 8
+
a Cfu = colony froming units (i.e. number of viable cells)
b AU = arbitrary units (thus reflecting antimicrobial activity)
Survival of strain ST4SA against a pathogen was tested by infecting the GIM with Listeria monocytogenes . The survival of strain ST4SA and its ability to produce the antimicrobial peptide ST4SA in the GIM was monitored (results shown in Table 12).
TABLE 12
Antibiotics
ST4
Ampicillin
+++
Bacitracin
++
Cephazolin
+
Chloramphenicol
+++
Ciprofloxzcin
+++
Cd. Sulphonamides
−
Cloxacillin
−
Erythromycin
+++
Metronidazole
−
Methicillin
−
Neomycin
−
Novobiocin
+++
Nystatin
−
Oflaxacin
++
Oxacillin
−
Rifampicin
+++
Tetracyclin
+++
Streptomycin
−
Vancomycin
++
Penicillin
+++
Key:
− = no zones (resistance to antibiotic);
+ = inhibition zone, diameter 1 to 11 mm;
++ = inhibition zone, diameter 12 to 16 mm;
+++ = inhibition zone, diameter larger than 17 mm.
As may be concluded from the results presented in Table 12, strain ST4SA survived in all sections of the intestinal tract. Antimicrobial peptide production was in excess of 25 600 AU (arbitrary units) per ml in all sections of the intestinal tract. Growth in NAN Palargon was slightly less optimal than in MRS. However, in both experiments the cell numbers did not decrease by more than one logarithmic cycle (see Table 13).
TABLE 13
Number of viable cells
Antibiotic (mg)
of strain ST4SA
Control
1 × 10 8
TMP-SMX 20/100
7 × 10 4
TMP-SMX 40/200
8 × 10 4
TMP-SMX 60/300
8 × 10 4
TMP-SMX 80/400
1.8 × 10 4
Metronidazole 50
1.3 × 10 4
Metronidazole 100
6 × 10 4
Metronidazole 200
3 × 10 4
Resistance of strain ST4SA to various antibiotics has been tested according to standard procedures (antibiotic discs, Oxoid). Concluded from these results, strain ST4SA is resistant to sulphonamides, cloxacillin, metronidazole, methicillin, neomycin, nystatin, oxacillin and streptomycin (Table 13).
Children with HIV/AIDS are treated with Trimethoprim-sulfamethoxazole (TMP-SMX) and/or Metronidazole to prevent diarrhea. NAN Palargon was supplemented with different concentrations of the latter antibiotics and the effect on strain ST4SA determined after 18 h at optimal growth temperature (37° C.).
As may be concluded from the results presented in Table 4, TMP-SMX and Metronidazole decreased the cell numbers of strain ST4SA with four log cycles. However, increased concentrations had no drastic effect on viability.
The Incidence of Virulence Factors in ST4SA
To develop strain ST4SA as a probiotic, it is important to know if there are any virulence factors associated therewith. Primers have been designed for the genes encoding the following virulence factors: Vancomycin resistance (VanA/VanB); production of gelatinase (Gel); aggregation substance (AS); adhesin of collagen from enterococci (Ace), enterococcus surface protein (Esp); haemolysin/bacteriocin (Cyl) and non-cytolysin beta hemolysin genes. The DNA of strain ST4SA amplified with the latter primers indicated that the strain does not have the genes encoding vancomycin resistance, gelatinase activity, an aggregation substance, and collagen adhesion. Based on present results, strain ST4SA is not pathogenic and should not cause allergic reactions when ingested.
As peptide ST4SA has a broad spectrum of antimicrobial activity, acting against a number of Gram-positive and Gram negative bacteria, the mode of action of peptide ST4SA appears to be different from other antimicrobial peptides thus far described for lactic acid bacteria. In addition, the site of recognition on the cell walls of sensitive cells may differ from the usual Lipid II anchor site used by other peptides of which the Applicant is aware ( FIG. 26 ).
To test this hypothesis, the Lipid II target site of Lactobacillus sakei DSM 20017 (sensitive to peptide ST 4SA) was blocked with vancomycin (see schematic presentation, FIG. 26 ). Vancomycin adheres to the amino acid side chain of the Lipid II molecule, which would, theoretically, prevent peptide ST4SA from binding to the same site (that is if Lipid II acts as receptor). Treatment of target cells ( L. sakei DSM 20017) with a combination of vancomycin and peptide ST4SA, however, resulted in growth inhibition (leakage of cytoplasm; see FIG. 26 ), suggesting that target sites other than Lipid II are acting as receptors for peptide ST4SA. The fact that peptide ST4SA binds to more than one anchoring site on the sensitive cell may explain why it has such a broad spectrum of antimicrobial activity (inhibitory to Gram-positive and Gram-negative bacteria). The Applicant is aware of the fact that Nisin (a antibiotic) binds to Lipid II, as shown in FIG. 26 in which treatment of L. sakei DSM 20017 with vancomycin prevented the binding of Nisin to the Lipid II target site.
Peptide ST4SA has two hydrophobic regions ( FIG. 27 ) which can intercalate with phospholipid-rich cell membranes after it has formed a reaction with the receptor site on the cell wall. The area between the two hydrophobic regions, more specifically between amino acid 29 (serine) and amino acid 30 (alanine) ( FIG. 27 ) is more flexible than the rest of the structure and may act as a hinge area, which would allow the C-terminal half of the peptide to bend and incorporate itself into the phospholipid-rich cell membrane. To test this hypothesis, the two sections of peptide ST4SA ( FIG. 27 ) were synthesized (listed hereinafter as Fragment 1 and Fragment 2), based on the amino acid sequence deduced from the DNA sequence of the structural gene.
As shown below, Fragment 1 consisted of the first 29 amino acids (from lysine to serine), just before the hinge area (viz. between the serine at position 29 and alanine at position 30). A disulfide bridge was introduced (connecting line, shown below) that covalently linked amino acids 9 (cysteine) and 14 (cysteine), also shown below in the full length peptide sequence:
The disulfide bridge served to stabilize the structure of the peptide. Fragment 1 contained the first hydrophobic region, indicated by the encircled region (six amino acids from position 21 to 26, viz. AIGIIG). This part of the molecule recognizes the receptor on the cell wall of the target (sensitive) organism.
Fragment 2 comprised the last 13 C-terminal amino acids in the second hydrophobic loop downstream of the hinge area, plus the preceding 11 amino acids just before the hinge area (between serine and alanine):
(SEQ ID NO: 18)
Fragment 2:
KAIGIIGNNS AANLATGGAAGWK S
Treatment of sensitive cells with these two fragments of peptide ST4SA indicated that both fragments (sections) of the molecule are needed for antimicrobial activity. It would thus seem that disruption of the cellular membrane is only possible once the N-terminal is anchored to the receptor on the cell surface.
Binding of Peptide ST4SA to Polyethylene (PE)
Binding of peptide ST4SA to polyethylene (PE) was tested. PE film was cut into sections of 5×5 cm and soaked for 1 h in a solution of 60% isopropanol and peptide ST4SA (activity level: 102 400 AU/ml). The PE sections were air-dried (20 min at 60° C.) and assayed for antimicrobial activity by using the standard agar diffusion method. The plates, seeded with L. sakei DSM 20017, were incubated for 24 h at 30° C. and examined for zones of growth inhibition.
Peptide ST4SA adsorbed to PE within 60 seconds to produce a film with high antimicrobial activity (large inhibition zones surrounding the PE section). The strength of binding was determined by soaking the peptide-coated PE film in SDS-buffer, followed by electro-eluting peptide ST4SA from the film with a current of 30 mA for 2 h (room temperature, i.e. ca. 25° C.). Samples were taken at regular time intervals and tested for antimicrobial activity. Protein concentrations were determined by using the Bradford method. Electro-eluted film was tested for antimicrobial activity by using the agar diffusion method as before.
Peptide ST4SA adhered strongly, and it would seem irreversibly, to the PE film. Release of peptide ST4SA from the surface of PE was only possible after 1 h with a current of 30 mA. In a challenge study with red meat as model, surface (PE)-bound peptide ST4SA prevented the growth of pathogenic bacteria ( Listeria, Bacillus and Staphylococcus ). This suggests that peptide ST4SA is usable in wound dressings to prevent or reduce microbial infections and also finds uses in other medical or aseptic applications such as, for example, implants, ear grommets, catheters, ostomy tubes and pouches, stents, suture material, hygiene products such as feminine hygiene products, contact lenses, contact lens rinsing solutions. The encapsulation of the antimicrobial peptide in the polymer leads to a slow release of the antimicrobial peptide and an extended period of treatment of a microbial infection. Furthermore, strong adherence of peptide ST4SA to PE shows that it acts as a slow-release antimicrobial agent.
Peptide ST4SA binds to more than one receptor site on a microbial cell and is typical of what one would expect from a broad-spectrum antimicrobial agent. The first section of peptide ST4SA (in front of the hinge area) binds to the receptor. The second part (downstream of the hinge area) has a bigger hydrophobic region and intercalates into the cell membrane and distorts the permeability, leading to cell death (visualized by DNA and enzyme leakage). Peptide ST4SA binds to PE in a stable and slow-release fashion and is suited for incorporation into wound dressings.
Development of Enterococcus mundtii ST4SA into a Probiotic
The survival of Enterococcus mundtii ST4SA was evaluated in a computerized gastro-intestinal model as shown. This phase comprised further in vitro and in vivo evaluation of strain ST4SA as a probiotic. Adhesion to mucus and epithelial cells were studied in vitro with human cell lines. In vivo studies were performed in rats.
The human intestinal cell lines used in the study were from the human colon adenocarcinoma and included Caco-2 cell lines, HT-29 and HT29-MTX (mucus-secreting cells). The cell-lines express morphological and functional differentiation when grown under standard culture conditions and show characteristics of mature enterocytes, which include polarization, a functional brush order and apical intestinal hydrolases.
Adherence of strain ST4SA to host cells is influenced by cell surface carbohydrates, the Efa A protein, the Ace (adhesin of collagen from enterococci) protein and aggregation substance (AS), related to pathogenicity. AS is an adhesin which mediates the formation of cell clumps that allows the highly efficient transfer of the sex pheromone plasmid on which AS is encoded.
In this study, strain ST4SA was screened for virulence traits, bile salt hydrolase (BSH) activity, and the ability to adhere to the human enterocyte-like cell line Caco-2, competitive exclusion while adhering to the Caco-2 cell line, and in the in vitro gastro-intestinal (GIT) model. In addition, cell surface hydrophobicity of ST4SA was determined.
Virulence Factors
The presence of virulence factors, viz. vancomycin resistance (VanA/VanB/VanC1/VanC2/VanC3), production of gelatinase (Gel), aggregation substance (AS), adhesin of collagen from enterococci (Ace), enterococcus surface protein (Esp), haemolysin/bacteriocin (Cyl) and non-cytolysin beta hemolysin genes were studied by in vitro tests and/or PCR screening. DNA was extracted from E. mundtii ST4 according to standard methods. The primers designed for amplification of the latter genes were as described. The results are shown in Table 14.
TABLE 14 Van Efa- Efa- Non- Van A Van B C1/2/3 Gel Afm Afs AS Ace Cyl Esp cyt ST4SA − − − − − − − − + − + Key: VanA/VanB: Vancomycin resistance Gel: Gelatinase production EfaAfm: E. faecium endocarditis antigen EfaAfs: E. faecalis endocarditis antigen As: Aggregation substance Ace: Adhesin to collagen from E. faecalis Cyl: Cytolysin (β-hemolysin activity) Esp: Enterococcus surface protein Non-Cyt: non-cytolysin beta hemolysin III
Production of Aggregation Substance (AS)
Production of AS was studied in a clumping assay in the presence of a sex pheromone. Sex pheromone was obtained by growing the pheromone producer, Enterococcus faecalis JH2-2, in MRS broth at 37° C. for 18 h. The supernatant of a pheromone producer, E. faecalis OG1X, was used in clumping assays in a microtiter plate. Two-hundred microliters were inoculated (0.5%, v/v) with strain ST4SA and microscopically examined for cell clumping after 2, 4, 8 and 24 h. No cell clumping was observed
Production of Gelatinase
Production of gelatinase was tested on MRS agar containing 30 g gelatin/liter. A clear zone surrounding the colonies after 18 h at 37° C. was considered a positive reaction. No production of gelatinase was detected.
Production of β-Hemolysin
Production of β-hemolysin was indicated by the formation of clear zones surrounding the colonies on blood agar plates. Blood agar plates were prepared using Columbia Blood Agar Base with 5% sheep blood. No production of β-hemolysin was observed.
It is evident that the Applicant has shown that strain ST4SA does not have the genes encoding vancomycin resistance, gelatinase production, production of the endocarditis antigen, forming of cell aggregates, adherence to collagen, and/or production of a surface protein. Genes encoding β-hemolysin activity and non-cytolysin beta hemolysin III were detected. However, the latter two genes are not expressed (no haemolytic activity was observed on blood agar plates—see below)
Determination of Bile-Salt Hydrolytic (BSH) Activity
Strain ST4SA was tested for BSH activity by spotting 10 μl of an overnight culture on MRS agar plates supplemented with 0.5% (w/v) sodium salt of taurodeoxycholic acid (TCDA) and 0.37 g/L CaCl 2 . Plates were incubated in anaerobic jars for 72 h at 37° C. The formation of precipitation zones were regarded BSH positive.
No bile salt hydrolytic (BSH) activity was observed for strain ST4SA. BSH activity may contribute to resistance of lactic acid bacteria to the toxicity of conjugated bile salts in the duodenum. However, bile salt hydrolase activity and resistance to bile salts are generally accepted as being unrelated.
Determination of Cell Surface Hydrophobicity
An overnight culture of E. mundtii ST4SA was washed twice with quarter-strength Ringer's solution (QSRS) and the OD 580nm determined. Equal volumes of suspension and n-hexadecane was added together and mixed for 2 min. The phases were allowed to separate at room temperature for 30 min., after which 1 ml of the water-phase was removed and the OD 580nm determined. The OD 580nm of duplicate assessments was averaged and used to calculate hydrophobicity:
% Hydrophobicity=[( OD 580nm reading1 −OD 580 reading2)/ OD 580nm reading1]×100.
From the results shown in FIG. 28 figure it is evident that strain ST4SA did not show signs of hydrophobicity. Accordingly, the cells do not stick permanently to surfaces in the GIT. The cells move freely (as planctonic cells) in the gut, which enhances the usefulness thereof as a good probiotic.
Adhesion of E. Mundtii ST4SA and Listeria monocytogenes to Caco-2 Cell Lines
Caco-2 cells (Highveld Biological Sciences) were seeded at a concentration of 5×10 5 cells per well to obtain confluence. Adherence was examined by adding 100 μl of bacterial suspension (1×10 5 cfu/ml of strain ST4SA and 1×10 3 cfu/ml of L. monocytogenes ) to the wells. After incubation at 37° C. for 2 h, the cell lines were washed twice with PBS. The bacterial cells were lysed with Triton-X 100 and plated onto MRS and BHI agar, respectively. Adhesion was calculated from the initial viable counts and the cell lysates.
Competitive exclusion of strain ST4SA and Listeria monocytogenes was determined by inoculating 100 μl of each strain to the cell monolayer. After a 2 h incubation period the cells were lysed and plated out on Enterococcus and Listeria specific medium, respectively.
Caco-2 cell monolayers were prepared on glass coverslips in 12-well tissue culture plates. A suspension of ST4SA cells was added to the wells. After a 2 h adhesion period, the cell lines were washed twice with PBS, fixed with 10% formalin and gram-stained. Adherent bacteria were examined microscopically. The results are shown in Table 15 and Table 16.
TABLE 15
Inoculum
Adhesion
Inoculum of L.
Adhesion of L.
Cfu/ml
of ST4
of ST4
Monocytogenes
monocytogenes
Experiment 1
1 × 10 6
2 × 10 4
1 × 10 5
3 × 10 2
Experiment 2
1 × 10 6
1 × 10 4
3 × 10 4
1 × 10 3
TABLE 16
Inoculum
Adhesion
Inoculum of L.
Adhesion of L.
Cfu/ml
of ST4
of ST4
Monocytogenes
monocytogenes
Experiment 1
1 × 10 6
8 × 10 3
1 × 10 5
4 × 10 1
Experiment 2
1 × 10 6
1 × 10 4
3 × 10 4
3 × 10 3
From the results presented in Tables 15 and 16 it is clear that E. mundtii ST4SA cells prevented the adhesion of Listeria to Caco-2 cells and that the cells successfully competed against Listeria for recognition sites on the human cell line. Strain ST4SA is thus able to out-compete Listeria.
L. monocytogenes Challenged with ST4SA and Survival in an In Vitro Gastro-Intestinal (GIT) Model
The antimicrobial activity of ST4SA against L. monocytogenes in an in vitro gastro-intestinal model was determined. ST4SA was inoculated in the stomach vessel as described hereinbefore. L. monocytogenes (1×10 4 ) was inoculated in the duodenum vessel of the GIT. Samples were taken from each vessel and plated out on Enterococcus and Listeria specific medium, respectively. As control, only L. monocytogenes was inoculated in the GIT model.
The L. monocytogenes challenge with ST4SA in the in vitro GIT model revealed that ST4 had an antimicrobial effect on L. monocytogenes (see graphs on next page). Growth was reduced from 8×10 4 to 2×10 4 in the jejunum vessel and L. monocytogenes was 1×10 1 cfu/ml lower in the ileum vessel when compared with the control, as shown in FIG. 29 .
In Vivo Assessment of the Safety, Bacterial Translocation, Survival and Immune Modulation Capacities of Orally Administered E. Mundtii ST4SA: Comparison to Lactovita
Materials and Methods
Animals
Ten male Wistar rats weighing between 318 g and 335 g were housed in groups of five in plastic cages with 12-hour light/dark cycle, in a controlled atmosphere (temperature 20° C.±3° C.). The animals were fed a standard diet, as well as autoclaved, reverse osmosis water either supplemented with probiotic or unsupplemented ad lib.
Bacterial Strains and Probiotic
Strain ST4SA was cultured in MRS Broth at 30° C. for 18 hours; the optical density was adjusted to 1.8 at 600 nm. Cells were harvested by centrifugation and washed in 20 mM phosphate buffer (pH 7.5). Washed cells were re-suspended in 100 mM sucrose, frozen in liquid nitrogen and lyophilized overnight. The cfu/ml value was determined by suspending a given mass of cells in 1 ml of phosphate buffer and spread plating dilutions on MRS solid media. Strain ST4SA was added to drinking water at a concentration of approximately 2×10 8 cfu/ml.
Three capsules containing a probiotic commercially available under the trade name Lactovita were opened and added to each bottle of drinking water. This resulted in approximately 3×10 5 cfu/ml being administered.
Experimental Design
Two separate studies were conducted. In each study 10 rats were randomly divided into two groups of five each. One group acted as a control and received unsupplemented water; the second group received water supplemented with either Lactovita capsules or lyophilized strain ST4SA. Each rat received a total of either 9.89×10 11 cfu of strain ST4 or 3.1×10 9 cfu of Lactovita over the study period. The rats were monitored daily for any abnormal activities, behaviours and general health status including ruffled coat, hunched posture, unstable movement, tremors or shaking, coughing or breathing difficulties, colour of extremities. Activity was monitored using a three-scale method: 1=lazy, moving slowly; 2=intermediate; 3=active moving or searching. Live weights and volume of water consumed were measured daily. The strain ST4SA study was conducted over 50 days and the Lactovita study over 108 days and the results are shown in Table 17.
TABLE 17 Control ST4 Control Lactovita Increase (g) 144 (7.22) 150.60 (9.34) 255.2 (21.88) 246 (44.42) Increase (%) 69.46 (1.10) 69.19 (1.05) 56.04 (2.59) 57.21 (5.60)
β-Glucuronidase Activity
Rats were placed in single cages overnight at specified sampling points and the 24 h faecal samples were collected to determine bacterial counts and β-glucuronidase activity. Faecal samples were homogenized in 20 mM phosphate buffer at a concentration of 100 mg faeces/ml buffer. Samples were stored at −20° C. until analysis. The faecal samples were pelleted by centrifugation and resuspended in 1 ml GUS extraction buffer (50 mM NaHPO 4 , 5 mM DTT, 1 mM EDTA, 0.1% Triton X-100), mixed and incubated at 22° C. for 10 minutes. Samples were frozen overnight at −20° C. and thawed before determining β-glucuronidase activity. β-Glucuronidase activity was assayed by incubating 100 μl of treated faecal suspension with 900 μl of reaction buffer (extraction buffer containing 1 mM ρ-nitrophenyl glucuronide) and incubating at 37° C. for 2 hours. The reaction was stopped by adding 2.5 ml 1M Tris, pH 10.4. The absorbance was determined at 415 nm and a standard curve was constructed using concentrations of 0.1, 0.2, 0.5, 1 and 10 mM ρ-nitrophenol.
Bacterial Translocation, Toxicological Study and Histology
After feeding with test strains for the specified time periods, animals were euthanized by pentobarbitone sodium overdose. Blood samples were obtained by cardiac puncture of the right ventricle. The gross anatomy of the visceral organs of each rat was checked and recorded. A sample of the liver, spleen, ileum, caecum and colon tissues was excised. The tissue samples were collected in cassettes and placed in a 4% formaldehyde (PBS) solution and then embedded in paraffin wax for histological analysis and FISH studies. A section of the ileum and colon were frozen in liquid nitrogen. Blood samples were spread plated on BHI solid media and incubated at 37° C. overnight.
Immune Modulation
Total RNA was extracted from the frozen ileum and colon samples using Trizol reagent. The concentration of RNA was determined by measuring the absorbance at 260 nm using a Nanodrop spectrophotometer, after DNase treatment had been completed. Each RNA sample was diluted to a concentration of 42 ng/μl. A total of 5 μg of each sample was transferred in triplicate onto a nylon membrane using a slot blot apparatus. The membrane was then probed with either a tumour necrosis factor (TNF), interferon γ (IFN) or β-actin DNA probe amplified from rat genomic DNA and labeled with DIG. The membrane was exposed to X-ray film overnight and developed.
Results
General Health Status and Weight Gain
Throughout the study period there were no noticeable behavioural or activity changes observed in the rats and there were no observable differences between experimental and control groups. No treatment-related illness or death occurred.
β-Glucuronidase Activity
Bacterial enzymes, including β-glucuronidase, are known to be involved in generating mutagens, carcinogens and tumour promoters from precursors found in the GIT and there presence may indicate toxicity of bacterial strains and can therefore be used as an indication of the safety of potential probiotics. Both strain ST4SA and a Lactovita suspension exhibited no β-glucuronidase activity in vitro (data not shown). However, rats given a Lactovita suspension showed an increase in β-glucuronidase activity in faecal samples compared to control rats (Table 18A). Control animals also showed a decrease in activity at day 107 of the study compared to activity at day 56, experimental animals showed slightly increase values at day 107 compared to day 56. Rats given a ST4 supplement showed higher β-glucuronidase activity compared to control groups (Table 18B), however, this activity was still lower at the end of the study compared to the values on day 0 of the study. The control group also showed lower activity at the end of the study compared to day 0.
TABLE 18 Table 18A Day 56 Day 77 Day 107 Lactovita 6.58 (0.34) 7.49 (0.23) 7.88 (0.36) Control 7.52 (0.26) 8.17 (0.08) 6.70 (0.32) Table 18B Day 0 Day 14 Day 30 Day 50 ST4 6.43 (0.52) 1.78 (0.45) 5.25 (0.57) 5.14 (0.83) Control 5.78 (0.50) 2.40 (0.76) 4.02 (0.62) 2.68 (0.15)
Bacterial Translocation, Toxicological Study and Histology
No bacteraemia was detected in any of the groups of animals. Macroscopic examination of the visceral organs indicated that the rats given strain ST4SA had significantly more pronounced MLN compared to control rats. The MLN were extremely difficult to identify in control rats. The spleen in the control group was narrower and both muscle mass and abdominal fat were less in the control group compared to the experimental group. In animals given Lactovita the MLN were less pronounced and the spleen smaller compared to the control group.
Lymphocytes enter the spleen and facilitate immune responses against blood antigens. An enlarged spleen may indicate increase immune system activity. This also correlates with pronounced MLN. MLN are also involved in immune function and may enlarge as a result of inflammation or infection. This enlargement is an indication that they are performing their function as expected. Therefore strain ST4SA may act as an immune stimulant. Rats receiving Lactovita supplements showed a smaller spleen and less pronounced MLN compared to the control rats. This indicates that Lactovita does not induce an immune reaction. However, the MLN and spleen of the control rats were enlarged and no symptoms of disease were observed in the absence of any immune stimulant.
Immune Modulation
Northern hybridization studies did not indicate any cytokine (TNF or IFN) expression in either the experimental ST4SA group or control group. Positive signals were detected of relatively the same intensity when RNA was probed with a β-actin DNA probe indicating the presence of RNA.
Cytokines are secreted proteins that mediate cell growth, inflammation, immunity, differentiation and repair. They often only require femtomolar concentrations to produce their required effects. Often they act in combination with cell surface receptors to produce changes in the pattern of RNA and protein synthesis. Because they are usually present in such low concentrations it may be more beneficial to determine the expression of additional genes that are under the influence of these proteins.
The results presented herein indicate that neither of the probiotics tested have any negative effects on the general health status of male Wistar rats.
In summary, strain ST4SA does not possess genes encoding vancomycin resistance. Genes encoding β-hemolysin activity and non-cytolysin beta hemolysin III were detected, but they remained silent (not expressed). Strain ST4SA has no bile salt hydrolytic (BSH) activity. This indicates that the strain would perform better in the lower sections of the GIT (ileum and colon). As shown above, the data indicate that E. mundtii strain ST4SA moves freely through the GIT and prevents the adhesion of Listeria to Caco-2 cells, while also successfully competing against Listeria from binding to receptors on human cells. Strain ST4SA had an antimicrobial effect on L. monocytogenes in gastro-intestinal model (GIM) studies. Strain ST4SA is not toxic, as shown with rat studies. No treatment-related illness or death occurred. Strain ST4SA also performed better than Lactovita as such, with rats being given Lactovita showing an increase in β-glucuronidase activity; strain ST4SA therefore stimulates the immune response in rats. Rats given Lactovita supplements showed a smaller spleen and less pronounced MLN compared to the control rats, which suggest that Lactovita does not induce an immune reaction.
As indicated above, peptide ST4SA inhibits the growth of a variety of bacteria and maximal production of peptide ST4SA (51 200 AU/ml) was recorded after 20 h of growth in MRS broth (Biolab), which was maintained throughout fermentation.
An 18-h-old culture of strain ST4SA was inoculated (2%, v/v, OD 600nm =2.0) into MRS broth (Biolab) and filtered MRS broth, respectively. MRS broth (Biolab) was filtered through a Minitan™ system (Millipore, BioSciences International), equipped with nitrocellulose membranes of 6000-8000 Da in pore size. The MRS filtrate (MRSf), containing proteins smaller than 8 000 Da was then autoclaved and inoculated as described before. Incubation in MRS broth and MRSf was at 30° C. and 37° C., without agitation, for 29 h. Peptide ST4SA activity was determined two-hourly.
Purification of Peptide ST4SA
One liter of MRSf was inoculated with Enterococcus mundtii ST4SA (OD 600nm =1.8) and incubated at 30° C. for 24 h. The cells were harvested by centrifugation (8 000×g, 4° C., 15 min) and the cell-free supernatant incubated at 80° C. for 10 min. Ammonium sulfate was gently added to the cell-free supernatant at 4° C. to a saturation level of 60%. After 4 h of slow stirring, the precipitate was collected by centrifugation (20 000×g, 1 h, 4° C.). The pellet was resuspended in one-tenth volume 25 mM ammonium acetate (pH 6.5) and desalted against sterile MilliQ water using a 1.0 kDa cut-off Spectra/Por dialysis membrane (Spectrum Inc., CA, USA). Further separation was by cation exchange chromatography in a 1 ml Resource S column (Amersham Biosciences) with an ÄKTApurifier (Amersham), as described hereinbefore.
Peptide ST4SA activity levels obtained after each purification step are indicated in Table 19.
TABLE 19
Activity
Total
(AU/
protein
Specific activity
Yield
Purification
Sample
ml)
(μg/ml)
(AU/μg protein)
(%)
Factor
Cell-free
12 800
10.77
1 188.49
100
1
supernatant
(450 ml)
Ammoniun
102 400
82.31
1 244.08
80
1.1
sulphate
precipitate
(45 ml)
Dialysate
102 400
35.77
2 862.73
80
2.4
(45 ml)
Active fractions collected from the ÄKTApurifier corresponded to the ST4SA peak and produced a 42-amino acid peptide, the expected size of peptide ST4SA.
Iso-electric Focusing of Peptide ST4SA
Iso-electric focusing of peptide ST4SA was done by using the Rotofor® electro-focusing cell (Bio-Rad, Hercules, Calif., USA). One liter of cell-free supernatant, obtained from strain ST4SA cultured in MRSf, and prepared as described before, was lyophilized and resuspended in 50 ml sterile distilled water with ampholytes (pH-range 3 to 10, Bio-Rad), according to instructions of the manufacturer. A constant current of 12 W was applied for 5 h at 8° C. After separation, a small volume from each of the collected fractions was adjusted to pH 7.0 with 3 N NaOH or 3 N HCl and tested for antimicrobial activity against Lactobacillus casei LHS. The fractions that tested positive were pooled, resuspended in de-ionized water to a total volume of 50 ml, again subjected to electro-focusing, the fractions collected and tested for antimicrobial activity. Samples were stored at −20° C.
Cost reduction of cultivation media forms an important part of media optimization. Media costs can be lowered by using industrial media as a carbon and/or nitrogen source. Corn steep liquor (CSL), cheese whey powder (CWp) and molasses are regularly used as part of growth media. CSL is a by-product formed during the milling of corn. It is mainly a nitrogen source, but also contains sugars (mainly sucrose), vitamins and minerals. Cheese whey, a by-product in the diary industry, is the most common fermentation medium for lactic acid (LA) production, and contains mainly lactose, proteins and salts. Molasses is a by-product containing mainly sucrose with traces of other minerals.
Culture and Media
Strain ST4SA was cultured in MRS broth (Biolab) and inoculated (2% v/v) into CSL, CWp and molasses, respectively.
Fermentations
Fermentations were conducted in test tubes containing 10 ml of media. The pH was adjusted with NaOH before sterilization (121° C. for 15 min). The concentration of NaOH depended on the buffer capacity of the media. A 24-hour-old culture was used for inoculation (2% v/v). Batch fermentations were conducted in test tubes at 30° C. for 16 hours, pH 6.5-7.0. The pH was not controlled. Optical density (OD) was measured at 600 nm.
Molasses and CSL at 10, 20 and 50 g·l −1 were evaluated as possible media for peptide ST4SA production (Table 20). Although the pH in molasses dropped during fermentation (thus indicating cell growth), no peptide ST4SA activity was recorded in the supernatant. CSL, on the other hand, produced a supernatant with activity of up to 3200 AU·ml −1 at a minimum concentration of 20 g·l −1 . As may be concluded from these results, a nitrogen source (CSL) is required to sustain peptide ST4SA production.
TABLE 20
pH
No.
Media
Initial
End
AU ml −1
g I −1
1
MRS (Control)
6.50
4.65
12800
2
CSL
10
6.50
4.38
1600
3
20
6.50
4.41
3200
4
50
6.50
4.56
3200
5
Molasses
10
6.50
4.82
0
6
20
6.50
5.01
0
7
50
6.50
4.97
0
g TS I −1
8
CWp
10
6.27
4.14
800
9
20
6.55
4.44
800
10
50
6.47
4.82
1600
In follow-up experiments, CWp was added to the list of industrial media and fermented at 10, 20 and 50 g TS·l −1 (Table 20). Peptide ST4SA activity of up to 1600 AU·ml −1 was recorded in CWp (Table 20).
A full factorial design (FFD) with CSL and CWp as components was used to determine which media had the most significant effect on peptide ST4SA production (Table 21). The FFD would also give an indication as to whether there was any interaction between the nutrients.
TABLE 21 2 2 FED with CSL and CWp PH No. CSL CWp Initial End AU ml −1 1 1 1 6.490 5.510 12800 2 −1 1 6.490 5.100 12800 3 1 −1 6.450 5.430 12800 4 −1 −1 6.480 5.090 12800 MRS 6.86 4.53 51200 CSL 5 g TS l −1 6.51 5.04 12800 CSL 10 g TS l −1 6.47 5.12 12800
The utilization of sugars was determined by using the following methods:
Phenol-sulphuric Acid Assay for Total Sugars
Phenol (500 μl of a 5%, v/v) and concentrated sulphuric acid (2.5 ml) were added to 500 μl of diluted sample in a test tube. The solutions were thoroughly vortexed and absorbancy readings taken at 490 nm (room temperature). Sugar concentration (g glucose·l −1 ) was calculated using a standard graph.
Dionex Determination of Monomer Sugars
A Dionex DX500 analyser with a CarboPac PA100 column was used to analyse the samples for monomer sugars. The eluent used was 250 mM NaOH, H 2 O and 1M NaOAc at a flow rate of 1 ml·min −1 . The Dionex was equipped with an auto sampler and the injection volume was 10 μl.
Total sugar concentrations varied between 5 and 10 g TS·l −1 (represented by “−1” and “1” respectively). The results (experiment performed in duplicate) suggested that the concentration of CSL and CWp had no effect on peptide ST4SA production (Table 21). CSL at 5 and 10 g TS·l −1 yielded peptide ST4SA activity similar to that recorded in the CSL and CWp combination (Table 21) and four-fold higher than recorded with 50 g·l −1 CSL (Table 20). As is evident from these results, CSL had the most significant effect on peptide ST4SA production.
Optimizing CSL
Peptide ST4SA activity of up to 12800 AU ml −1 was recorded in pure CSL at a concentration of 10 g TS·l −1 . This was, however, low compared to peptide ST4SA activity recorded in MRS (51200 AU·ml −1 ). In a preliminary experiment, MRS components (except glucose) were added to 10 and 40 g TS·l −1 CSL and CWp, respectively (Table 22). A two-fold increase in activity was observed for 10 g TS·l −1 CSL with supplements compared to pure CSL. In contrast, CSL at 40 g TS·l −1 with supplements yielded low activity. A high concentration of CSL inhibited growth (small decrease in pH) and, subsequently, also peptide ST4SA production. This may be due to inhibiting components in CSL. The same experiment was done with CWp (Table 22). With an increase in CWp concentration (from 10 to 40 g TS·l −1 ), no effect on peptide ST4SA production was recorded.
TABLE 22
CSL supplemented with MRS components
pH
No.
Carbon source
g TS l −1
Initial
End
AU ml −1
1
CSL
10
6.52
5.47
25600
2
40
6.55
6.26
800
3
CWp
10
6.51
4.92
12800
4
40
6.50
5.07
12800
At 10 g TS · l −1 CSL produced peptide ST4SA at twice the activity compared to CWp (25600 AU · ml −1 ). CSL was therefore chosen as medium for future experiments.
As not all of the MRS components played a role in improving peptide ST4SA production, a screening experiment was done to identify the significant components. This screening experiment was done via a 2 10-5 fractional factorial design (FrFD). The design made it possible to test 10 factors in only 32 runs, instead of the normal 1024 runs (Tables 23 and 24). It was also possible to determine if there were any interactions between components. Results were analyzed with ANOVA (Table 25).
TABLE 23
High and low concentrations of MRS components and CSL
MRS broth g l −1
Component
g l −1
1
−1
A
Special peptone
10
10
0
B
Beef extract
5
5
0
C
Yeast extract
5
5
0
D
CSL
—
6
3
E
Potassium phosphate
2
2
0
F
Tween80
1
1
0
G
tri-Ammonium citrate
2
2
0
H
MgSO 4
0.1
0.1
0
J
MnSO 4
0.05
0.05
0
K
Sodium acetate
5
5
0
Linear model in terms of coded values:
Activity = −1431.2 * B + 956.2 * C + 3831.2 * D − 2781.3 * E − 2243.8 * G − 2006.2 * K + 7668.8 [Equation 2]
R 2 = 0.73
Peptide ST4SA production was described using a linear model. Although the linear model could not accurately predict the activity (R 2 =0.73), it could still be used to evaluate the effect (positive or negative) of the components. Beef extract (B), potassium phosphate (E), tri-ammonium citrate (G) and sodium acetate (K) had negative coefficients in the linear model (equation 2) causing a decrease in the response variable. This reflected their negative effect on peptide ST4SA production. This meant that only yeast extract (YE) (C) and CSL (D) increased peptide ST4SA production.
TABLE 24
2 10−5 FrFD design
No.
A
B
C
D
E
F = ABCD
G = ABCE
H = ABDE
J = ACDE
K = BCDE
1
−1
−1
−1
−1
−1
1
1
1
1
1
2
1
−1
−1
−1
−1
−1
−1
−1
−1
1
3
−1
1
−1
−1
−1
−1
−1
−1
1
−1
4
1
1
−1
−1
−1
1
1
1
−1
−1
5
−1
−1
1
−1
−1
−1
−1
1
−1
−1
6
1
−1
1
−1
−1
1
1
−1
1
−1
7
−1
1
1
−1
−1
1
1
−1
−1
1
8
1
1
1
−1
−1
−1
−1
1
1
1
9
−1
−1
−1
1
−1
−1
1
−1
−1
−1
10
1
−1
−1
1
−1
1
−1
1
1
−1
11
−1
1
−1
1
−1
1
−1
1
−1
1
12
1
1
−1
1
−1
−1
1
−1
1
1
13
−1
−1
1
1
−1
1
−1
−1
1
1
14
1
−1
1
1
−1
−1
1
1
−1
1
15
−1
1
1
1
−1
−1
1
1
1
−1
16
1
1
1
1
−1
1
−1
−1
−1
−1
17
−1
−1
−1
−1
1
1
−1
−1
−1
−1
18
1
−1
−1
−1
1
−1
1
1
1
−1
19
−1
1
−1
−1
1
−1
1
1
−1
1
20
1
1
−1
−1
1
1
−1
−1
1
1
21
−1
−1
1
−1
1
−1
1
−1
1
1
22
1
−1
1
−1
1
1
−1
1
−1
1
23
−1
1
1
−1
1
1
−1
1
1
−1
24
1
1
1
−1
1
−1
1
−1
−1
−1
25
−1
−1
−1
1
1
−1
−1
1
1
1
26
1
−1
−1
1
1
1
1
−1
−1
1
27
−1
1
−1
1
1
1
1
−1
1
−1
28
1
1
−1
1
1
−1
−1
1
−1
−1
29
−1
−1
1
1
1
1
1
1
−1
−1
30
1
−1
1
1
1
−1
−1
−1
1
−1
31
−1
1
1
1
1
−1
−1
−1
−1
1
32
1
1
1
1
1
1
1
1
1
1
TABLE 25
Analysis of Variance Table for a 2 10-5 FrFD design
Response: Activity (AU ml −1 )
Component
Df
F value
Pr (>F)
A
1
0.950
0.334
B
1
8.858
0.004**
C
1
3.954
0.052.
D
1
63.474
1.435e−10***
E
1
33.450
4.221e−07***
F
1
0.162
0.689
G
1
21.770
2.191e−05***
H
1
0.207
0.651
J
1
0.008
0.928
K
1
17.405
0.000***
Reproducibility
1
1.338
0.253
Residuals
52
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘’ 1
The concentrations of CSL and YE were set with a 2 2 FFD (Table 26). The critical dilution method used for determination of peptide ST4SA activity did not yield accurate results. This made it impossible to fit a model relating the concentrations of CSL and YE to activity. Experimental results were used to fix the component concentrations. From Table 26 it can be seen that there was no clear effect when using low or high concentrations of CSL and YE. The average value was selected as the best, with a composition of CSL 7.5 g TS·l −1 and YE 6.5 g·l −1 .
TABLE 26
2 2 FFD with 3 centre points for determination of CSL and
YE concentrations
AU ml −1
g l −1
No.
C
D
Repl. 1
Repl. 2
Component
1
0
−1
1
−1
−1
25600
25600
C
CSL
10
6.5
3
2
−1
1
25600
25600
D
YE
10
7.5
5
3
1
−1
36204
12800
4
1
1
25600
36204
5
0
0
25600
25600
6
0
0
25600
36204
7
0
0
51200
25600
A growth curve with optimal media is shown in FIG. 30 . CSL-based media and MRS yielded similar growth kinetics.
Batch to Batch Variation
The composition of CSL may vary on a daily basis, as it is a waste product. A difference in composition has the potential of significantly affecting results. This was investigated by performing the same experiments on a second batch of CSL. This time ANOVA analysis identified YE, CSL, Tween80, MnSO 4 , and sodium acetate as the components having the most significant effect on bacteriocin production (P<0.1). Continued optimization showed that MnSO 4 was insignificant while sodium acetate caused a decrease in activity.
The final media consisted of the following three components: YE (C), CSL (D) and Tween80 (F). It was not surprising to find that yeast extract was once again one of the significant components. Tween80 has emulsifying properties. The final concentrations, as set in a 2 3 FFD design, was: YE 7.5 g·l 1 , CSL 10 g·l 1 and Tween80 2 g·l −1 .
Growth Limitations
The sugar content of the CSL medium was measured before and after fermentation. At the start of fermentation, CSL was made up to a concentration of 7.5 g TS·l −1 . The main monomer sugars present were glucose and fructose at a total concentration of 3.883 g·l −1 . Only about 51.8% of the total sugar was therefore in a fermentable form and not all sugars were metabolized during fermentation. At the end of fermentation (constant OD), the pH was 4.6 and the residual sugars left were 8.8%. Growth limitations were due to low pH and not due to a lack of nitrogen, minerals, vitamins or any other nutrients, and Table 27 shows the carbon uptake during fermentation.
TABLE 27
Carbon uptake during fermentation
Time
Glucose
Fructose
Total sugar
% Sugar
[h]
[g/l]
[g/l]
[g/l]
fermented
0
1.747
2.136
3.883
0.0
10
0.391
0.899
1.290
66.8
19
0.041
0.301
0.342
91.2
Accordingly, it is evident that CSL supplemented with YE could match high peptide ST4SA levels obtained in commercial MRS broth. Advantageously, this has the potential of significantly reducing costs associated with cultivation media. CSL was selected as growth medium for industrial production of peptide ST4SA.
Development of Enterococcus mundtii ST4SA into a Probiotic
An important criterion for the selection of probiotic strains is adhesion to epithelial cells. Probiotic bacteria may also compete with pathogenic bacteria for adhesion sites. Caco-2 cells, which originate from human colon adenocarcinoma, were used as an in vitro model to investigate the adhesion and competitive exclusion abilities of E. mundtii ST4SA to epithelial cells.
The results are expressed as percentage of adherence compared to the inoculum. E. mundtii ST4SA and L. monocytogenes Scott A were able to adhere and both showed 5% adhesion to the Caco-2 cells. The adhesion of E. mundtii ST4SA was lowered to 1% when the incubation time was only 1 h. Food material stays in the small intestine for 2 h and therefore would allow sufficient time for E. mundtii ST4 to adhere to the epithelial cells. However, E. mundtii ST4SA did not have an effect on the adhesion of L. monocytogenes Scott A regardless of whether the strain was added before, during or after the incubation with the pathogen. In the exclusion and displacement tests, L. monocytogenes Scott A showed 5% adhesion. The competition test showed no competition for adhesion as the percentage adhesion stayed the same as in the control. This can be explained by the fact that E. mundtii ST4SA and L. monocytogenes Scott A might bind to different receptors on the epithelial cell. E. mundtii ST4SA and L. monocytogenes Scott A would, therefore, not compete for similar receptors.
Resistance of E. Mundtii ST4 Against Antibiotics and Anti-Inflammatory Drugs
E. mundtii ST4SA showed resistance against two antibiotics (Cefasyn and Utin) and the inflammatory medicaments Rheugesic, Coxflam and Pynmed. The results are shown in Table 28. Antibiotics with the greatest growth inhibition on E. mundtii ST4SA are Promoxil, Cipadur, Roxibidd and Doximal.
Promoxil, Doximal, Cefasyn and Utin had no effect on the adhesion of ST4SA cells to Caco-2 cells compared to the control. Adhesion decreased with 10% in the presence of Cipadur, Roxibudd and Ibugestic syrup and 14% with a higher concentration of Cefasyn, as may also be seen in Table 29.
TABLE 28
Medicament
Strain ST4SA
Ibuprofen, 5 mg/ml
++
Aspirin, 5 mg/ml
+
Promoxil, 100 mg/ml
++++
Cipadur, 50 mg/ml
+++
Cefasyn, 100 mg/ml
−
Roxibidd, 30 mg/ml
+++
Doximal, 20 mg/ml
+++
Ciploxx, 100 mg/ml
+
Utin, 80 mg/ml
−
Rheugesic, 4 mg/ml
−
Coxflam, 1.5 mg/ml
−
K-fenak, 5 mg/ml
++
Preflam, 3 mg/ml
+
Ibugesic
++
Pynmed
−
− = no zones;
+ = diameters between 1 mm and 11 mm;
++ = diameters between 12 mm and 16 mm;
+++ = diameters of 17 mm and more.
TABLE 29 Medicament Strain ST4SA adhesion Inoculum 1 × 10 7 Control 5 × 10 4 Cipadur (5 mg/ml) 6 × 10 3 Roxibidd (10 mg/ml) 3 × 10 3 Promoxil (8 mg/ml) 1.25 × 10 4 Doximal (2 mg/ml) 1 × 10 4 Cefasyn (10 mg/ml) 1.2 × 10 4 Cefasyn (50 mg/ml) 7 × 10 2 Utin (8 mg/ml) 4 × 10 4 Utin (40 mg/ml) 3 × 10 4 Ibugestic syrup (100 μl) 6 × 10 3 K-fenak (0.5 mg/l) 3 × 10 4
In Vivo Assessment of the Safety, Toxicity, Bacterial Translocation and Survival, Immune Modulation Capacities and Efficacy of Orally Administered E. Mundtii ST4SA Cells—Comparisons with Lactovita.
Animals
Thirty six male Wistar rats weighing between 150 g and 180 g were housed in groups of six in plastic cages with 12-hour light/dark cycle, in a controlled atmosphere (temperature 20±3° C.). The animals were fed a standard diet and ad lib.
Bacterial Strains and Probiotic
E. mundtii strain ST4SA was cultured in MRS Broth at 30° C. for 18 hours; the optical density was adjusted to 1.8 at 600 nm. Cells were harvested by centrifugation and washed in 20 mM phosphate buffer (pH 7.5). Washed cells were resuspended in 100 mM sucrose, frozen at −80° C. and lyophilized overnight. The cfu/vial values were determined by suspending a given mass of cells in 1 ml of phosphate buffer and spread plating dilutions on MRS solid media. Lyophilized cells were resuspended in sterile skim milk (10%) and 2×10 8 cfu strain ST4SA was administered via intragastric gavage.
Lactovita capsules were emptied into a vial and resuspended in sterile skim milk (10%) and 2×10 8 cfu was administered via intragastric gavage.
Listeria monocytogenes Scott A was cultured in BHI Broth at 37° C. for 18 hours. Cells were harvested by centrifugation and washed in 20 mM phosphate buffer (pH 7.5). Washed cells were resuspended in 100 mM sucrose, frozen at −80° C. and lyophilized overnight. The number of cfu/vial was determined as described above. Lyophilised cells were resuspended in sterile skim milk (10%) and 10 4 cfu were administered via intragastric gavage.
Experimental Design
Two groups of animals received strain ST4 via intragastric gavage, two groups received Lactovita and the remaining two control groups received water for 7 consecutive days. On day 8, both control groups were infected with Listeria monocytogenes and one group from each of the strain ST4SA and Lactovita groups was also infected with L. monocytogenes via intragastric gavage. At this time the animals also received E. mundtii strain ST4SA, Lactovita or water. Probiotic or water was administered again on day 9 and 10. When the control groups began presenting symptoms, E. mundtii strain ST4SA was administered via intragastric gavage to one of the groups. This group was then monitored for alleviation of symptoms.
Animals were monitored twice daily for symptoms of listeriosis. Animals were sacrificed on day 11 (except the control group now receiving E. mundtii strain ST4SA). Blood was sampled from the right ventricle. Total blood counts were determined by a pathologist laboratory, a sample of blood was inoculated onto BHI solid media and Listeria selective agar base and the cfu/ml was determined. Plasma was collected and endotoxin levels as well as cytokine (IL-6 and IFN-α) levels were determined. The liver, spleen and sections of the gastrointestinal tract were excised and fixed in formaldehyde prior to paraffin embedding.
Sections were stained with hemolysin and eosin for histological analysis. The hemolysin and eosin analysis indicated that oral administration of strain ST4SA does not result in any structural damage to the liver, spleen or GIT (see FIG. 31 ). No differences were observed between animals that had been administered strain ST4SA and those receiving only unsupplemented water.
As described herein, the Enterococcus mundtii strain, ST4SA, isolated from soy bean extract, has been found by the Applicant to produce a useful antibacterial peptide, peptide ST4SA, which is active against a number of pathogenic organisms such as those isolated from human middle-ear infections and the human intestine. Advantageously, peptide ST4SA is not cytotoxic. The Enterococcus mundtii ST4SA strain has been distinguished by the Applicant from other strains of E. mundtii by sugar fermentation reactions, a number of biochemical tests, the presence of two plasmids (pST4SA1 and pST4SA2), and a unique gene (AdhST4SA), encoding adhesion to intestinal epithelial cells and mucus. Peptide ST4SA has been purified and sequenced, and contains two large hydrophobic regions. The Applicant has isolated and sequenced the nucleic acid sequence encoding peptide ST4SA, as well as the nucleic acid sequence encoding the transport of peptide ST4SA across the cell membrane, which serves to render immunity to the producer cell against its own peptide. All latter genes are located on the genome, since curing of the strain of its plasmids did not lead to loss in antimicrobial activity. Furthermore, transformation of the plasmids to a strain of Enterococcus faecalis did not convert the recipient into a peptide ST4SA producer, which is further evidence that the genes are not located on the plasmids. Loss in antimicrobial activity after treating the peptide with proteolytic enzymes confirmed that the activity is due to the peptide structure and not lipids or carbohydrates linked to the molecule. Surprisingly, the peptide remained active after 30 min of incubation in buffers between pH 2.0 and 12.0, and after 90 min at 100° C. Even more surprisingly, treatment with EDTA, SDS, Tween 20, Tween 80 and Triton X-100 did not lead to loss in antimicrobial activity. Strain ST4SA survives low pH conditions (pH 2.5), grows in medium adjusted from pH 4.0 to 9.6 in the presence of 6.5% NaCl, and is resistant to 1.0% (w/v) bile salts and pancreatic juice. Growth of strain ST4SA occurs at 10° C. (although slowly) and at 45° C., with optimal growth at 37° C. Only L(+)-lactic acid is produced from glucose. These strain characteristics, the rapid and stable production of peptide ST4SA, even when the strain is exposed to environmental stress, the fact that the peptide is non-cytotoxic, and that it is produced by an organism with GRAS (generally regarded as safe) status, renders the strain a useful probiotic.
The peptide also has use as an antimicrobial agent in a liquid formulation, as a topical treatment for, for example, middle-ear infections. This liquid formulation may be applied to the ear using an ear drop applicator. The liquid formulation is also included in a liquid form of the probiotic of Enterococcus mundtii for use as a liquid supplement to meals. The peptide further finds use as an antimicrobial agent in either a liquid or aspirated form in a nasal spray for treatment in, for example, sinus infections or sinusitis. The peptide is also used as an antimicrobial agent encapsulated in a polymer. This polymer is then used in a formulation for topical treatment of infections such as, for example, skin infections, or it may be used for incorporation in implants such as, for example, ear grommets, or for incorporation in wound dressings. The encapsulation of the antimicrobial peptide in the polymer leads to a slow release of the antimicrobial peptide and an extended period of treatment of a microbial infection. The peptide also finds use as an antimicrobial agent by being incorporated into ointment, lotion, or cream formulations and used to treat infections. The peptide may also further be used as an antimicrobial agent by being incorporated into liquid formulations such as, for example, contact lens rinsing fluid, or it may be incorporated into the contact lenses themselves. The peptide may also be used as an antimicrobial agent by being incorporated into packaging material such as plastic, for use in the manufacture of aseptic packaging. In an even further form of the invention the peptide may be used as part of a broad-spectrum probiotic of Enterococcus mundtii in a tablet form or in a capsule form or it may be in an edible form such as, for example, a sweet or chewing gum.
Sequence Listing
Enterococcus mundtii strain ST4SA (ATCC PTA-7278)
ribosome subunit 16S gene primers
SEQ. ID. NO. 1: Forward primer
AACGAGCGCAACCC
SEQ. ID. NO. 2: Reverse primer
GACGGGCGGTGTGTAC
Enterococcus mundtii strain ST4SA (ATCC PTA-7278)
structural gene primers
SEQ. ID. NO. 3: Forward primer
SG-a: TGAGAGAAGGTTTAAGTTTTGAAGAA
SEQ. ID. NO. 4: Reverse primer
SG-b: TCCDACTGAAATCCATGAATGA
Enterococcus mundtii strain ST4SA (ATCC PTA-7278)
ABC transporter gene primers
SEQ. ID. NO. 5: Forward primer
ABC1-a: TGATGGATTTCAGTGGAAGT
SEQ. ID. NO. 6: Reverse primer
ABC1-b: ATCTCTTCTCCGTTTAATCG
SEQ. ID. NO. 7: Forward primer
ABC2-a: GTCATTGTTGTGGGGATTAT
SEQ. ID. NO. 8: Reverse primer
ABC2-b: TCTAGATACGTATCAAGTCC
Enterococcus mundtii strain ST4SA (ATCC PTA-7278)
immunity gene primers
SEQ. ID. NO. 9: Forward primer
Immun-a: TTCCTGATGAACAAGAACTC
SEQ. ID. NO. 10: Reverse primer
Immun-b: GTCCCCACAACCAATAACTA
SEQ. ID. NO. 11
Polynucleotide encoding Enterococcus mundtii (ATCC
PTA-7278) antimicrobial peptide ST4SA
ATGTCACAAGTAGTAGGTGGAAAATACTACGGTAATGGAGTCTCATGTAA
TAAAAAAGGTGCAGTGTTGATTGGGGAAAAGCTATTGGCATTATTGGAAA
TAATTCTGCTGCGAATTTAGCTACTGGTGGAGCAGCTGGTTGGAAAAGTT
AA
SEQ. ID. NO. 12
Polypeptide encoded by Enterococcus mundtii (ATCC
PTA-7278) antimicrobial peptide ST4SA
MSQVVGGKYYGNGVSCNKKGCSVDWGKAIGIIGNNSAANLATGGAAGWKS
SEQ. ID. NO. 13
Polynucleotide encoding Enterococcus mundtii ST4SA
(ATCC PTA-7278) ABC transporter gene
ATGCAGATGATTTTAAATAATTTTCATTCATGGATTTCAGTGGAAGTTTT
AAGAGACTTAACTGAAACCGATTCTGAAGGTACCTGTGCATTAGGTATAG
TTAACGGATTTGCTAAATTAGGAATAAATTGTGAAGCCTATAAAGCTAAT
AGTGATGTATGGAAAGAAAATGAGTTCAATTATCCCGTAATTGCTAATAT
AGTAACGAATAATCAATTTCTTCATTATTGTATTGTATATGGTGTGAAAA
AAGAGAAATTGTTAATAGCTGACCCTGCGATTGGAAAATACAAAGAATCA
ATAGAAAAGTTCAACAACAAATGGACTGGTGTTATTTTAGTTGCTGAAAA
GACTCCTGATTTCCAACCCATAAATAATACAAAAAAAAGTTTTTTTTCTT
CAATAAGTTTATTAAAAGATCAATATAAAAAAATTTTATTGGTGATATTA
TCTTCATTAATAATAACAATTATAGGAATACTATCAAGTTACTATTTTAG
AATTTTAATAGATTGGTTACTTCCTGAAAAAGACTTTTTAAATCTATTTA
TGATATCAATTAGCTATATCATAGGCATTTTTATAACAAGTATATTTGAA
ATTACCAGAAGATATAATTTAGAAAAGCTAGGACAAGATGTAGGTAGAAG
CATTTTATTTAAATATTTAGAACATATTTTCATTTTACCAGCTTCCTTTT
TTTCTAAAAGAAAAACTGGAGATATTGTCTCTAGATTTTCTGATGCTAAT
AAAATTATAGAAGCTTTAGCTAGCTTTACTATATCTATTTTTTTAGATTT
AAGTTCAGTCATTGTTGTGGGGATTATATTGATCAATATTAATAAACAAT
TATTTTTAATAACGTTAAGTTCTATTCCATTTTATATACTAATTATATTA
GGATCAAATAAAAAAATGAGTCGATTAAACGGAGAAGAGATGCAAACAAA
TTCAATAGTTGATTCTAATTTTATTGAAGGATTAAACGGAATATATACTA
TAAAAGCACTTTGTAGTGAGAATAAGATTGTAAATCAAATATATAGAAGT
TTAAATAAATTTTTTGATGTATCACTAAAGAGAAATATGTATGATTCTAT
AATTCAAAATTTAAAAATTTTGGTTTCTCTTTTAACCTCGGCTTTTGTAT
TATGGCTTGGTTCGTATTATGTTATCAATGGAGAAATTACAATAGGAGAA
CTAATAACTTTCAATTCATTATCTATATTTTTTTCTACACCTCTACAAAA
TATAATAAATCTACAAGAAAAATTCCAAAAAGCACAAGTTGCAAATAATC
GGCTTAACGATGTATTTTCTATAAATAATGAAAATAAAGACAAGTTTATT
CATTTGGCTAAATTAACTGAAAAAGCAACGATTACATTTGAAAATGTATA
TTTTAGTTATTCTACTAAATATCCTAATGTGTTAGATAATATGAGTTTTT
CTCTACCTGTGAGTAAAAATATAGGAATAAAAGGTGATAGTGGTGCTGGG
AAATCAACTTTAGCACAACTTCTAGCTGGATTTTACTCTCCAGATAATGG
AAGAATTTGTATAAATGAGCAAAATATTGAAAATATTAATAGAAAAGATT
TACGTAAGTTGATTACCTATGTGCCTCAAGAATCTTTTATTATGAGTGGA
ACTATTAAAGACAATTTATTTTTAGGTTTAGAAAGTATTCCTGATGAACA
AGAACTCGAAAAAGTACTGAAAGATACTTGTTTATGGAGTTATATTACTG
CGCCTCCTCTAGGACTTGATACGTATCTAGAAGAAAATGGTGCGAATTTA
TCAGGTGGTCAAAAGCAAAGAATTGCTTTAGCAAGAGTTTTATTATTAGG
AAGTAAAATTTTATTATTAGATGAAGCTACGAGTGCTCTAGATTCTAAAA
CTGAAATGCTGATTTTAGAAAAATTATTAAAGTACCCTAATAAGTCAATC
ATTATGATATCTCATAATGATAAATTAATAGACAAGTGTGACTTAATCAT
TGATTTAGACGAAAGGGATTCATAA
SEQ. ID. NO. 14
Polypeptide encoded by Enterococcus mundtii ST4SA
(ATCC PTA-7278) ABC transporter gene
MQMILNNFHSWISVEVLRDLTETDSEGTCALGIVNGFAKLGINCEAYKAN
SDVWKENEFNYPVIANIVTNNQFLHYCIVYGVKKEKLLIADPAIGKYKES
IEKFNNKWTGVILVAEKTPDFQPINNTKKSFFSSISLLKDQYKKILLVIL
SSLIITIIGILSSYYFRILIDWLLPEKDFLNLFMISISYIIGIFITSIFE
ITRRYNLEKLGQDVGRSILFKYLEHIFILPASFFSKRKTGDIVSRFSDAN
KIIEALASFTISIFLDLSSVIVVGIILININKQLFLITLSSIPFYILIIL
GSNKKMSRLNGEEMQTNSIVDSNFIEGLNGIYTIKALCSENKIVNQIYRS
LNKFFDVSLKRNMYDSIIQNLKILVSLLTSAFVLWLGSYYVINGEITIGE
LITFNSLSIFFSTPLQNIINLQEKFQKAQVANNRLNDVFSINNENKDKFI
HLAKLTEKATITFENVYFSYSTKYPNVLDNMSFSLPVSKNIGIKGDSGAG
KSTLAQLLAGFYSPDNGRICINEQNIENINRKDLRKLITYVPQESFIMSG
TIKDNLFLGLESIPDEQELEKVLKDTCLWSYITAPPLGLDTYLEENGANL
SGGQKQRIALARVLLLGSKILLLDEATSALDSKTEMLILEKLLKYPNKSI
IMISHNDKLIDKCDLIIDLDERDS
SEQ. ID. NO. 15
Polynucleotide encoding Enterococcus mundtii ST4SA
(ATCC PTA-7278) immunity gene
ATGAGTAATTTAAAGTGGTTTTCTGGTGGAGACGATCGACGTAAAAAAGC
AGAAGTGATTATTACTGAATTATTAGATGATTTAGAGATAGATCTTGGAA
ATGAATCTCTTCGAAAAGTATTAGGCTCCTATCTTGAAAAGTGAAAAATG
AAGGAACTTCAGTTCCATTAGTTTTAAGTCGTATGAATATAGAGATATCT
AATGCAATAAAAAAAGACGGTGTATCGTTAAATGAAAATCAATCTAAAAA
ATTAAAAGAACTCATATCTATATCTAATATTAGATATGGATATTAG
SEQ. ID. NO. 16
Polypeptide encoded by Enterococcus mundtii ST4SA
immunity gene
MSNLKWFSGGDDRRKKAEVIITELLDDLEIDLGNESLRKVLGSYLEKLKN
EGTSVPLVLSRMNIEISNAIKKDGVSLNENQSKKLKELISISNIRYGY
SEQ. ID. NO. 17
Polypeptide encoded by Enterococcus mundtii ST4SA
(ATCC PTA-7278) antimicrobial peptide ST4SA
Fragment 1
KYYGNGVS C NKKG C SVDWGKAIGIIGNNS
SEQ. ID. NO. 18
Polypeptide encoded by Enterococcus mundtii ST4SA
(ATCC PTA-7278) antimicrobial peptide ST4SA
Fragment 2
KAIGIIGNNS AANLATGGAAGWK S
SEQ. ID. NO. 19
Polypeptide encoded by Enterococcus mundtii ST4SA
(ATCC PTA-7278) Fragment 1
AAATACTACGGTAATGGAGTCTCATGTAATAAAAAAGGGTGCAGTGTTG
ATTGGGGAAAAGCTATTGGCATTATTGGAAATAATTCT
SEQ. ID. NO. 20
Polypeptide encoded by Enterococcus mundtii ST4SA
(ATCC PTA-7278) Fragment 2
AAAGCTATTGGCATTATTGGAAATAATTCTGCTGCGAATTTAGCTACTG
GTGGAGCAGCTGGTTGGAAAAGT
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The invention relates to a strain of Enterococcus mundtii having probiotic qualities. The strain of E. mundtii (ST4SA) produces an antimicrobial peptide which exhibits antimicrobial activity against a broad range of bacteria. The invention also provides an isolated nucleotide sequence which codes for the antimicrobial peptide (peptide ST4SA). Another aspect of the invention relates to a process for the production of a peptide of the invention which comprises cultivating Enterococcus mundtii strain ST4SA in a nutrient medium under micro-aerophilic conditions at a temperature of between 100 C. and 45° C., until a recoverable quantity of said peptide is produced, and recovering said peptide. The isolated peptide of the invention may be used as an antimicrobial agent in a liquid formulation or a gel formulation as a topical treatment and may also be used as an antimicrobial agent following encapsulation in a polymer.
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RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 11/204,608, filed Aug. 16, 2005, now U.S. Pat. No. 7,746,194.
FIELD OF THE INVENTION
This invention relates to a signal splitter for reducing noise ingress and a cable television network incorporating such splitters.
BACKGROUND TO THE INVENTION
Cable television networks are no longer purely distribution networks used for TV and radio distribution, but now also provide access for the customer to the networks. Thus TV and radio signals are distributed from a local centre or optical node by way of a signal splitter with an output connected to each customer. Return traffic from each customer is returned through the splitter to the local centre or optical node and thence to the rest of the network. Such return traffic might include requests for pay-per-view television programmes.
Usually the traffic from the customer to the local centre or optical node is called “return path traffic” or “upstream signals”. The upstream signals are transported using a different frequency range than the distribution signals (usually called “downstream signals”) originating from the network provider. Modern cable TV networks typically use 5 MHz to 65 MHz for upstream signals and 85 MHz to 862 MHz for downstream signals, although other frequency ranges are also used.
All upstream signals, no matter how they originate, are transported to the local centre or optical node. Thus unwanted noise in upstream signals will also be injected into the network. The unwanted signals originate from various sources but a major part is due to radiation of outside transmitters in the used upstream frequency range. The total sum of these unwanted signals is known as “ingress”. The majority of ingress originates from the in-house installation of the customer and is therefore injected into the network at a customer access point. This ingress is a major problem in the network since all these unwanted signals are summed and will limit the signal to noise ratio (and therefore the capacity) of the upstream signals.
It is an aim of the present invention to provide a signal splitter which reduces noise ingress into a cable television distribution network.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided a signal splitter comprising an input and a plurality of outputs, wherein alternate outputs are connected to phase shifting devices. Where such a signal splitter is used in a cable television network, the phase shifting devices ensure that noise ingress in upstream signals, i.e. those originating from the customer, passing into the network is substantially reduced. The upstream signals are made up of signals from a number of different customers, each customer signal including data and noise components. The data components from different customers are unrelated in amplitude, phase, and frequency as they originate from different subscriber equipment. However the noise components in each customer signal are similar to one another because they originate for the most part from the same source, namely radio frequency electromagnetic radiation picked up by the equipment of the subscribers and the cables connecting such equipment to the outputs of the splitter. Introduction of a phase shift into the upstream signal before it reaches an output ensures that the noise components cancel one another when the upstream signals originating from the customers are summed by the splitter.
Preferably the phase shifting devices introduce a phase shift of 180°, so that noise components of alternate outputs are antiphase and cancel one another out almost entirely when the signals are summed.
Each phase shifting device may comprise a phase shifting transformer.
Where the splitter has an even number N of outputs, N/2 phase shifting devices will be required, N/2 being a whole number. Where the splitter has an odd number X of outputs, then the number of phase shifting devices used will be the nearest whole number above or below X/2.
If required the phase shifting devices may be permanently connected to their respective outputs and secured within a common housing to the outputs, so being built into the splitter. Alternatively the phase shifting devices may be separable from their respective outputs.
In accordance with another aspect of the invention, there is provided a cable television network incorporating a plurality of signal splitters comprising an input and a plurality of outputs, wherein alternate outputs are connected to phase shifting devices, the phase shifting devices acting in use to ensure that noise ingress in upstream signals, i.e. those originating from the customer, passing into the network is substantially reduced.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
The invention will now be described by way illustrative example and with reference to the attached drawing figures, in which:
FIGS. 1 and 2 are schematic diagrams of prior art signal splitters;
FIG. 3 is a schematic diagram of a signal splitter in accordance with the invention; and
FIGS. 4 and 5 are spectrum analyser traces showing the powers of the summed signals at the inputs, respectively, of a prior art signal splitter and a signal splitter according to the invention, when used in a cable television network.
DESCRIPTION
The prior art signal splitter 10 of FIGS. 1 and 2 comprises an input 12 and a large number of outputs, of which only a first output 14 and a second output 16 are shown for the purpose of clarity. In use these passive signal dividers 10 act as an interface between a local centre or node and a number of customers, each customer connected to one output of the splitter 10 , with the splitter input 12 connected to the node. Arrow 18 represents transmission of television signals (downstream signals) from the service provider to the input of the splitter where the signal is divided or split for onward transmission to the customer, arrows 18 a and 18 b representing transmission of split television signals from the first and second outputs 14 , 16 of the splitter 10 .
Dotted arrows 20 a and 20 b represent the return transmission of data signals (upstream signals) from the first and second subscribers to the first and second outputs of the splitter.
The splitter sums the data signals from all subscribers to which it is connected and applies them to the input of the splitter. Dotted arrow 20 c represents transmission of all summed data signals from the input of the splitter to the service provider.
Turning to FIG. 2 , short dotted arrows 22 a and 22 b represent noise components present in the data signals transmitted from the subscribers to the first and second inputs of the splitter. The splitter 10 not only sums the wanted data signal but also sums the noise components and applies them to the input 12 of the splitter. Long dotted arrow 22 c represents transmission of the summed noise signals from the input of the splitter to the service provider.
With a large number of outputs, the summed noise components applied to the input of the splitter (and hence transmitted from the input of the splitter to the service provider) become significant in comparison with the data signals, thus reducing the signal transmission capacity of the upstream channel between the splitter and the service provider. By way of example, suppose there are 1000 customers connected to a single local centre or optical node. If all customers produce the same amount of ingress then the total signal to noise ratio at the local centre or optical point will degrade with a factor 1000 or 30 dB.
A splitter 24 in accordance with the present invention is shown in FIG. 3 and comprises an input 26 , a plurality of outputs of which only five outputs 30 ′, 28 , 30 , 28 ′ and 30 ″ are shown for clarity, and a plurality of phase shift transformers connected to alternate outputs, of which only transformers 32 and 32 ′ connected to output 28 and output 28 ′ are shown. The outputs thus form first and second groups, the first group of outputs not connected to a transformer, the second group connected to a transformer. Each transformer is only connected to one output. The phase shift transformers can be built into the splitter and permanently associated with their respective outputs. Alternatively the transformers can be connected externally to existing outputs.
The phase shift transformers 32 , 32 ′ introduce a 180° phase shift into signals that pass through them. Thus split television signals applied to the second group of outputs 28 , 28 ′ are shifted in phase by 180° before being transmitted to the subscriber, and data signals transmitted by a subscriber's equipment connected to the first output 28 are shifted in phase by 180° before being applied to the outputs 28 , 28 ′.
As explained above, the data signals transmitted by the subscribers to the outputs of the splitter include noise components. The noise components have various sources, the most significant of which is radio frequency electromagnetic radiation, which can be picked up by the subscribers' equipment and the cables connecting the outputs of the splitter to the equipment of the subscribers. In most cases, a source of radio frequency electromagnetic radiation that is picked up by one such cable or subscriber's equipment will be picked up by a large number of other such cables or subscribers' equipment.
The signal characteristics of the noise components will be very similar because they arise for the most part from the same source. The noise components will have much the same frequency, amplitude and phase. The phase shift transformers connected to alternate outputs of the splitter give rise to two groups of noise components. The noise components of both groups have much the same frequency and amplitude, but the noise components of the first group are in antiphase with the noise components of the second group. When the noise components of both groups are summed, they cancel each other out so that the noise components of the summed signals applied to the input of the splitter are much reduced.
The wanted data signals originating from the customer are unaffected as the data components from different customers are unrelated in amplitude, phase, and frequency as they originate from different subscriber equipment. They are therefore not reduced by summation after phase shifting. The downstream signal is also not affected by the phase shift, and thus by using a phase shifting transformer mounted between the splitter output and the connected branch of the network, wanted downstream and upstream signals are unaffected whilst ingress is attenuated.
Of course, there are some localised sources of radio frequency electromagnetic radiation that are picked up by only one subscriber's equipment or one cable, such as an electric motor in an appliance in a house of a subscriber. The introduction of the phase shift cannot reduce such a noise component.
Many houses have connections to two outputs of the splitter, one connection being used for cable television and the other for telephone or internet service. Provided that one connection is to an output of the splitter with a phase shift transformer and the other connection is to an output without such a transformer, noise components due to even a localised source of radio frequency electromagnetic radiation can be reduced.
FIG. 4 shows the signal power at the input 12 of the prior art splitter 10 when used in a cable television network. The range of frequencies shown in the spectrum analyser trace is 0 to 70 MHz, which encompasses the frequency range used for the signal return path.
A peak of between 50 dB and 60 dB can be seen near to the middle of the trace i.e. at around 35 MHz. This is due to the summed noise components of the data signals transmitted to the splitter by the subscribers.
FIG. 5 shows the signal power at the input 26 of the splitter 24 of the invention when used in the same network. The signal power at around 35 MHz can be seen to be between 40 dB and 50 dB. The decrease of approximately 10 dB in the signal power at 35 MHz is due to the removal of 10 dB of the noise components by the splitter. In theory at least, this would result in an increase in the data transmission capacity of the channel between the input 26 and the service provider by a factor of 10.
The signal splitter of the invention is dependent for successful operation on similarity between the noise components of data signals applied to the outputs of the splitter. The reduction of the noise components in the summed data signals will be less pronounced if the noise components are of different amplitudes or experience different phase shifts during transmission from the subscribers' equipment to the outputs of the splitter. Nevertheless, a reduction of only 3 dB of the noise components can give rise to a doubling of the data transmission capacity of the upstream signal channel.
The reduction of the noise components is slightly less pronounced if the splitter has an odd number of outputs. In this case the number of phase shifters attached to the outputs should be as close as possible to half the number of outputs, for example two or three phase shifters for a splitter with five outputs. Of course, for a splitter with a larger odd number of outputs, the effect of having phase shifters attached to slightly less or more than half the outputs of the splitter decreases with increasing numbers of outputs.
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A signal splitter comprising an input and a plurality of outputs is provided, wherein alternate outputs are connected to phase shifting devices. The phase shifting devices preferably comprise phase shifting transformers and introduce a phase shift of 180°, so that noise components of alternate outputs are antiphase and cancel one another out almost entirely when the signals are summed. Also provided is a cable television network comprising a plurality of such signal splitters to ensure that noise ingress in upstream signals passing into the network is substantially reduced.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention relates to communication method.
[0003] 2. Description of the Related Art
[0004] A communication system can be seen as a facility that enables communication sessions between two or more entities such as user equipment and/or other nodes associated with the communication system. The communication may comprise, for example, communication of voice, data, multimedia and so on. A session may, for example, be a telephone call between users or multi-way conference session, or a communication session between user equipment and an application server (AS), for example a service provider server. The establishment of these sessions generally enables a user to be provided with various services.
[0005] A communication system typically operates in accordance with a given standard or specification which sets out what the various entities associated with the communication system are permitted to do and how that should be achieved. For example, the standard or specification may define if the user, or more precisely, user equipment is provided with a circuit switched service and/or a packet switched service. Communication protocols and/or parameters which shall be used for the connection may also be defined. In other words, a specific set of “rules” on which the communication can be based on needs to be defined to enable communication by means of the system.
[0006] Communication systems providing wireless communication for user equipment are known. An example of the wireless systems is the public land mobile network (PLMN). The PLMNs are typically based on cellular technology. In cellular systems, a base transceiver station (BTS) or similar access entity serves wireless user equipment (UE) known also as mobile stations (MS) via a wireless interface between these entities. The communication on the wireless interface between the user equipment and the elements of the communication network can be based on an appropriate communication protocol. The operation of the base station apparatus and other apparatus required for the communication can be controlled by one or several control entities. The various control entities may be interconnected.
[0007] One or more gateway nodes may also be provided for connecting the cellular network to other networks e.g. to a public switched telephone network (PSTN) and/or other communication networks such as an IP (Internet Protocol) and/or other packet switched data networks. In such arrangement the mobile communications network provides an access network enabling a user with a wireless user equipment to access external networks, hosts, or services offered by specific service providers. The access point or gateway node of the mobile communication network then provides further access to an external network or an external host. For example, if the requested service is provided by a service provider located in other network, the service request is routed via the gateway to the service provider. The routing may be based on definitions in the mobile subscriber data stored by a mobile network operator.
[0008] An example of the services that may be offered for user such as the subscribers to a communication systems is the so called multimedia services. Some of the communication systems enabled to offer multimedia services are known as Internet Protocol (IP) Multimedia networks. IP Multimedia (IM) functionalities can be provided by means of an IP Multimedia Core Network (CN) subsystem, or briefly IP Multimedia subsystem (IMS). The IMS includes various network entities for the provision of the multimedia services. The IMS services are intended to offer, among other services, IP connections between mobile user equipment.
[0009] The third generation partnership project (3GPP) has defined use of the general packet radio service (GPRS) for the provision of the IMS services, and therefore this will be used in the following as an example of a possible backbone communication network enabling the IMS services. The exemplifying general packet radio service (GPRS) operation environment comprises one or more sub-network service areas, which are interconnected by a GPRS backbone network. A sub-network comprises a number of packet data service nodes (SN). In this application the service nodes will be referred to as serving GPRS support nodes (SGSN). Each of the SGSNs is connected to at least one mobile communication network, typically to base station systems. The connection is typically by way of radio network controllers (RNC) or other access system controllers such as base stations controllers (BSC) in such a way that packet service can be provided for mobile user equipment via several base stations. The intermediate mobile communication network provides packet-switched data transmission between a support node and mobile user equipment. Different sub-networks are in turn connected to an external data network, e.g. to a public switched data network (PSPDN), via gateway GPRS support nodes (GGSN). The GPRS services thus allow packet data transmission between mobile data terminals and external data networks.
[0010] In such a network, a packet data session is established to carry traffic flows over the network. Such a packet data session is often referred as a packet data protocol (PDP) context. A PDP context may include a radio access bearer provided between the user equipment, the radio network controller and the SGSN, and switched packet data channels provided between the serving GPRS support node and the gateway GPRS support node.
[0011] A data communication session between the user equipment and other party would then be carried on the established PDP context. Each PDP context can carry more than one traffic flow, but all traffic flows within one particular PDP context are treated the same way as regards their transmission across the network. The PDP context treatment requirement is based on PDP context treatment attributes associated with the traffic flows, for example quality of service and/or charging attributes.
[0012] The Third Generation Partnership Project (3GPP) has also defined a reference architecture for the third generation (3G) core network which will provide the users of user equipment with access to the multimedia services. This core network is divided into three principal domains. These are the Circuit Switched (CS) domain, the Packet Switched (PS) domain and the Internet Protocol Multimedia (IM) domain. The latter of these, the IM domain, is for ensuring that multimedia services are adequately managed.
[0013] The IM domain supports the Session Initiation Protocol (SIP) as developed by the Internet Engineering Task Force (IETF). Session Initiation Protocol (SIP) is an application-layer control protocol for creating, modifying and terminating sessions with one or more participants (endpoints). SIP was generally developed to allow for initiating a session between two or more endpoints in the Internet by making these endpoints aware of the session semantics. A user connected to a SIP based communication system may communicate with various entities of the communication system based on standardised SIP messages. User equipment or users that run certain applications on the user equipment are registered with the SIP backbone so that an invitation to a particular session can be correctly delivered to these endpoints. To achieve this, SIP provides a registration mechanism for devices and users, and it applies mechanisms such as location servers and registrars to route the session invitations appropriately. Examples of the possible sessions that may be provided by means of SIP signalling include Internet multimedia conferences, Internet telephone calls, and multimedia distribution.
[0014] Reference is made to IETF document RFC 3325 which is hereby incorporated by reference. This document describes private extensions to SIP that enable a network of trusted SIP servers to assert the identity of end users or end systems, and to convey indications of end-user requested privacy. The use of these extensions is applicable inside a ‘Trust Domain’ as defined in Short term requirements for Network Asserted Identity. Nodes in such a Trust Domain are explicitly trusted by its users and end-systems to publicly assert the identity of each party, and to be responsible for withholding that identity outside of the Trust Domain when privacy is requested.
[0015] In order to be able to apply the privacy procedures described in RFC3325, there is a need to detect the trustworthiness of the next hop network. If the next hop is trusted, then the procedures related to the different privacy options are delegated to the next hop. Otherwise the privacy procedures need to be executed.
[0016] As an example, in case the caller asks for identity privacy, the P-Asserted-Identity header has to be removed before it reaches the called party. A message sent by the caller contains a header identifying the sender, called a P-Asserted-Identity header. The format of this header if the sender is a user with a publicly-known user identification is: <sip:user1_public1@home1.net> The home network of the caller has to remove the header only in case the home network of the called party is not trusted. If the home network of the called party (which is the next hop for the home network of the caller) is trusted, then the home network of the caller will not remove the header. This is needed to be compliant with RFC3325, which says that the P-Asserted-Identity header has to be removed by the last element in the trusted domain.
[0017] In RFC 3325, the mechanism proposed relies on the header field called ‘P-Asserted-Identity’ that contains a URI (commonly a SIP URI) and an optional display-name. A proxy server which handles a message can, after authenticating the originating user in some way (for example: Digest authentication), insert such a P-Asserted-Identity header field into the message and forward it to other trusted proxies. A proxy that is about to forward a message to a proxy server or UA that it does not trust removes all the P-Asserted-Identity header field values if the user requested that this information be kept private. Users can request this type of privacy.
[0018] For the procedures to be applied in the correct place, the trustworthiness of the next hop has to be detected in some way.
SUMMARY OF THE INVENTION
[0019] According to a first aspect of the invention, there is provided a method of communication between a calling party in a first network and a called party in a second network comprising the steps of:
determining in the first network an address associated with said called party; determining based on said address if said called party is in a trusted network; and controlling the communication between the called party and the calling party in dependence on if said called party is in a trusted network.
[0023] According to a second aspect, there is provided a communications system comprising a first network having a calling party and a second network having a calling party, said first network comprising:
determining means for determining an address associated with said called party; determining means for determining based on said address if said called party is in a trusted network; and control means for controlling the communication between the called party and the calling party in dependence on if said called party is in a trusted network.
[0027] According to a third aspect, there is provided a first network having a calling party arranged to call a calling party in a second network, said first network comprising:
determining means for determining an address associated with said called party; determining means for determining based on said address if said called party is in a trusted network; and control means for controlling the communication between the called party and the calling party in dependence on if said called party is in a trusted network.
[0031] According to a fourth aspect, there is provided a method of communication between a calling party in a first network and a called party in a second network comprising the steps of:
determining in the first network if there is a secure connection with said second network; and if it is determined that there is no secure connection with said second network discarding or modifying a message from the calling party to the called party.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] For better understanding of the invention, reference will now be made by way of example to the accompanying drawings in which:
[0035] FIG. 1 shows a communication system wherein the invention may be embodied;
[0036] FIG. 2 is a flowchart illustrating the operation of one embodiment of the invention;
[0037] FIG. 3 shows a context in which an embodiment of the invention may be provided.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0038] Embodiments of the present invention relate particularly but not exclusively to Rel-5 IMS networks. Embodiments of the invention may also be applicable to other versions of the IMS network. Embodiments of the invention may be applicable to other SIP networks. Some embodiments of the invention may find wider application outside the SIP and IMS environments.
[0039] Certain embodiments of the present invention will be described by way of example, with reference to the exemplifying architecture of a third generation (3G) mobile communications system. However, it will be understood that certain embodiments may be applied to any other suitable form of network. A mobile communication system is typically arranged to serve a plurality of mobile user equipment usually via a wireless interface between the user equipment and base station of the communication system. The mobile communication system may logically be divided between a radio access network (RAN) and a core network (CN).
[0040] Reference is made to FIG. 1 which shows an example of a network architecture wherein the invention may be embodied. FIG. 1 shows an IP Multimedia Network 45 for offering IP multimedia services for IP Multimedia Network subscribers. IP Multimedia (IM) functionalities can be provided by means of a Core Network (CN) subsystem including various entities for the provision of the service.
[0041] Base stations 31 and 43 are arranged to transmit signals to and receive signals from mobile user equipment 30 and 44 of mobile users i.e. subscribers via a wireless interface. Correspondingly, each of the mobile user equipment is able to transmit signals to and receive signals from the base station via the wireless interface. In the simplified presentation of FIG. 1 , the base stations 31 and 43 belong to different radio access networks (RAN). In the shown arrangement each of the user equipment 30 , 44 may access the IMS network 45 via the two access networks associated with base stations 31 and 43 , respectively. It shall be appreciated that, although, for clarity, FIG. 1 shows the base stations of only two radio access networks, a typical mobile communication network usually includes a number of radio access networks.
[0042] The 3G radio access network (RAN) is typically controlled by appropriate radio network controller (RNC). This controller is not shown in order to enhance clarity. A controller may be assigned for each base station or a controller can control a plurality of base stations. Solutions wherein controllers are provided both in individual base stations and in the radio access network level for controlling a plurality of base stations are also known. It shall thus be appreciated that the name, location and number of the network controllers depends on the system.
[0043] The mobile user may use any appropriate mobile device adapted for Internet Protocol (IP) communication to connect the network. For example, the mobile user may access the cellular network by means of a Personal computer (PC), Personal Data Assistant (PDA), mobile station (MS) and so on. The following examples are described in the context of mobile stations.
[0044] One skilled in the art is familiar with the features and operation of a typical mobile station. Thus, a detailed explanation of these features is not necessary. It is sufficient to note that the user may use a mobile station for tasks such as for making and receiving phone calls, for receiving and sending data from and to the network and for experiencing e.g. multimedia content. A mobile station is typically provided with processor and memory means for accomplishing these tasks. A mobile station may include antenna means for wirelessly receiving and transmitting signals from and to base stations of the mobile communication network. A mobile station may also be provided with a display for displaying images and other graphical information for the user of the mobile user equipment. Speaker means may are also be provided. The operation of a mobile station may be controlled by means of an appropriate user interface such as control buttons, voice commands and so on.
[0045] It shall be appreciated that although only two mobile stations are shown in FIG. 1 for clarity, a number of mobile stations may be in simultaneous communication with each base station of the mobile communication system. A mobile station may also have several simultaneous sessions, for example a number of SIP sessions and activated PDP contexts. The user may also have a phone call and be simultaneously connected to at least one other service.
[0046] The core network (CN) entities typically include various control entities and gateways for enabling the communication via a number of radio access networks and also for interfacing a single communication system with one or more communication system such as with other cellular systems and/or fixed line communication systems. In FIG. 1 serving GPRS support nodes 33 , 42 and gateway GPRS support nodes 34 , 40 are for provision of support for GPRS services 32 , 41 , respectively, in the network.
[0047] The radio access network controller is typically connected to an appropriate core network entity or entities such as, but not limited to, the serving general packet radio service support nodes (SGSN) 33 and 42 . Although not shown, each SGSN typically has access to designated subscriber database configured for storing information associated with the subscription of the respective user equipment.
[0048] User equipment within the radio access network may communicate with a radio network controller via radio network channels which are typically referred to as radio bearers (RB). Each user equipment may have one or more radio network channel open at any one time with the radio network controller. The radio access network controller is in communication with the serving GPRS support node via an appropriate interface, for example on an Iu interface.
[0049] The serving GPRS support node, in turn, typically communicates with a gateway GPRS support node via the GPRS backbone network 32 , 41 . This interface is commonly a switched packet data interface. The serving GPRS support node and/or the gateway GPRS support node are for provision of support for GPRS services in the network.
[0050] Overall communication between user equipment in an access entity and a gateway GPRS support node is generally provided by a packet data protocol (PDP) context. Each PDP context usually provides a communication pathway between particular user equipment and the gateway GPRS support node and, once established, can typically carry multiple flows. Each flow normally represents, for example, a particular service and/or a media component of a particular service. The PDP context therefore often represents a logical communication pathway for one or more flow across the network. To implement the PDP context between user equipment and the serving GPRS support node, radio access bearers (RAB) need to be established which commonly allow for data transfer for the user equipment. The implementation of these logical and physical channels is known to those skilled in the art and is therefore not discussed further herein.
[0051] The user equipment 30 , 44 may connect, via the GPRS network, to application servers that are generally connected to the IMS.
[0052] The communication systems have developed such that services may be provided for the user equipment by means of various functions of the network that are handled by network entities known as servers. For example, in the current third generation (3G) wireless multimedia network architectures it is assumed that several different servers are used for handling different functions. These include functions such as the call session control functions (CSCFs). The call session control functions may be divided into various categories such as a proxy call session control function (P-CSCF) 35 and 39 , interrogating call session control function (I-CSCF) 37 , and serving call session control function (S-CSCF) 36 and 38 . A user who wishes to use services provided by an application server via the IMS system may need to register with a serving control entity. The serving call session control function (S-CSCF) may form in the 3G IMS arrangements the entity a user needs to be registered with in order to be able to request for a service from the communication system. The CSCFs may define an IMS network of a UMTS system.
[0053] It shall be appreciated that similar function may be referred to in different systems with different names. For example, in certain applications the CSCFs may be referenced to as the call state control functions.
[0054] Communication systems may be arranged such that a user who has been provided with required communication resources by the backbone network has to initiate the use of services by sending a request for the desired service over the communication system. For example, a user may request for a session, transaction or other type of communications from an appropriate network entity.
[0055] In one embodiment of the present invention, there is a database at the S-CSCF of the home network of the calling party which lists all the known IMS network domain names and IP addresses the home network trusts.
[0056] A database containing the domain name of the IMS networks and the corresponding IP addresses of the I-CSCFs has to be maintained in a SIP level database. As SIP requests may contain either domain names or IP addresses in the Request (R)-universal resource indicator. It is not enough to store the domain names into the database. The calling party thus can check if the called party is in a trusted or untrusted network by seeing in the domain name or IP address associated with the called party are in the database.
[0057] It is however possible in an alternative embodiment of the invention to make reverse DNS domain name server queries whenever an IP address is received instead of a domain name in the R-URI. Thus, the following simplified solution is also possible which will be described with reference to FIG. 2 :
[0058] A database is kept with the domain names of the IMS networks the home network trusts.
[0059] In step S 1 it is determined in the request contains a domain name.
[0060] If so the next step is step S 2 where it is checked to see if the domain is in the database. If so the next hop is considered a trusted domain and the corresponding procedures are applied (step S 3 ). If the domain is not in the database, then consider the next hop an untrusted domain, and apply the corresponding procedures—step S 4 .
[0061] If the called party is an untrusted party, the message may be discarded or alternatively modified. If the message is modified, information identifying the calling party will be removed. This information may be the P-Asserted header. This will be done if the calling party has requested privacy, ie that their identity be kept private.
[0062] If the request does not contain the domain name it is determined if a request with an IP address in R-URI is received—step S 5 . Step S 5 and S 1 may be combined in a single step. If the request contains an IP address then a then a reverse DNS query is made to find out the corresponding domain—step 6 . That is a request is sent ot the Domain name server for the name of the domain associated with the IP address. The next step will then be step S 2 with the checking of the database.
[0063] In a further embodiment of the invention, a database is kept only at the S-CSCF of the home network which lists there all the known IMS network domain names the home network trusts.
[0064] If the R-URI contains an IP address instead of a domain name (and thus can not be checked in the database), then it is simply assumed that the next hop is an untrusted domain.
[0065] In a still further embodiment of the invention, the NDS network domain security is configured in the security gateways (SPD) in such a way, that an IP packet coming from a CSCF of the domain the gateway is part of, would be sent over a secure connection. If a secure connection towards the destination does not exists, the packet is simply discarded and an ICMP Internet control message protocol message generated. The ICMP is an Internet protocol which delivers error and control messages between a gateway or a destination host and the source host about IP datagram processing. ICMP can for example report an error in the IP datagram processing. ICMP is usually part of the IP protocol. Thus, the home network always assumes the next hop is trusted and does not remove the P-Asserted-Identity. If it happens that the next hop is not trusted, then the packet is discarded, and does not reach the called party.
[0066] The consequence of this solution is, that CSCF will only be able to communicate with SIP entities belonging to a trusted domain.
[0067] Reference is made to Third Generation Partnership Project specification number TS33.210 version 3.3.0 which is hereby incorporated by reference. The document describes a network domain security architecture outline. Reference is made to FIG. 3 which shows this architecture to which embodiments of the present invention can be applied.
[0068] An explanation will firstly be given regarding the Za and Zb interfaces that can exist between networks and within networks respectively. This explanation is taken from the 3GPP TS 33.210 V6.0.0 (2002-12) Technical Specification, Release 6 . FIG. 3 shows two security domains and the Za and Zb interfaces between entities of these domains.
[0069] The interfaces are defined for protection of native IP based protocols:
[heading-0070] Za-Interface (SEG-SEG)
[0071] The Za-interface covers all NDS/IP (Network Domain Security/Internet Protocol) traffic between security domains. The SEGs (Security Gateways) use IKE (Internet Key Exchange) to negotiate, establish and maintain a secure ESP (Encapsulating Security Payload) tunnel between them. Subject to roaming agreements, the inter-SEG tunnels would normally be available at all times, but they can also be established as needed. ESP shall be used with both encryption and authentication/integrity, but an authentication/integrity only mode is allowed. The tunnel is subsequently used for forwarding NDS/IP traffic between security domain A and security domain B.
[0072] One SEG can be dedicated to only serve a certain subset of all roaming partners. This will limit the number of SAs and tunnels that need to be maintained.
[0073] All security domains compliant with this specification shall operate the Za-interface.
[heading-0074] Zb-Interface (NE-SEG/NE-NE)
[0075] The Zb-interface is located between SEGs and NEs and between NEs within the same security domain. The Zb-interface is optional for implementation. If implemented, it shall implement ESP+IKE.
[0076] On the Zb-interface, ESP shall always be used with authentication/integrity protection. The use of encryption is optional. The ESP Security Association shall be used for all control plane traffic that needs security protection.
[0077] Whether the Security Association is established when needed or a priori is for the security domain operator to decide. The Security Association is subsequently used for exchange of NDS/IP traffic between the NEs.
[0078] The security policy established over the Za-interface is subject to roaming agreements. This differs from the security policy enforced over the Zb-interface, which is unilaterally decided by the security domain operator.
[0079] The basic idea to the NDS/IP architecture is to provide hop-by-hop security. This is in accordance with the chained-tunnels or hub-and-spoke models of operation. The use of hop-by-hop security also makes it easy to operate separate security policies internally and towards other external security domains.
[0080] In NDS/IP only the Security Gateways (SEGs) shall engage in direct communication with entities in other security domains for NDS/IP traffic. The SEGs will then establish and maintain IPsec secured ESP Security Association in tunnel mode between security domains. SEGs will normally maintain at least one IPsec tunnel available at all times to a particular peer SEG. The SEG will maintain logically separate SAD and SPD databases for each interface.
[0081] The NEs may be able to establish and maintain ESP Security Associations as needed towards a SEG or other NEs within the same security domain. All NDS/IP traffic from a NE in one security domain towards a NE in a different security domain will be routed via a SEG and will be afforded hop-by-hop security protection towards the final destination.
[0082] Operators may decide to establish only one ESP Security Association between two communicating security domains. This would make for coarse-grained security granularity. The benefits to this is that it gives a certain amount of protection against traffic flow analysis while the drawback is that one will not be able to differentiate the security protection given between the communicating entities. This does not preclude negotiation of finer grained security granularity at the discretion of the communicating entities.
[0083] In embodiments of the invention, the SEG of the calling party will determine if the packet for the called party is to be sent over a secure connection to the SEG of the called party. If there is no secure connection the packet is discarded. If there is a secure connection the packet is sent.
[0084] In one modification, if there is no secure connection, the SEG of the calling party will remove the identity information from the message, that is the P-Asserted header. The modified message is then sent to the called party.
[0085] In embodiments of the invention, P-asserted header information is removed from the packet. In alternative embodiments of the invention which do not have the P-Asserted information, identification information relating to the identity of the calling party will be removed.
[0086] The database is described as storing the identity of trusted parties only. In one modification it could store only the identity of untrusted parties or both the untrusted and trusted parties along with information indicating if they are trusted or not.
[0087] It should be appreciated that the description of one embodiment where there is a GPRS system is by way of example only and other systems may be used in alternative embodiments of the invention.
[0088] It should be appreciated that while embodiments of the invention have been described in relation to user equipment such as mobile stations, embodiments of the invention are applicable to any other suitable type of user equipment.
[0089] The examples of the invention have been described in the context of an IMS system and GPRS networks. This invention is also applicable to any other access techniques. Furthermore, the given examples are described in the context of SIP networks with SIP capable entities. This invention is also applicable to any other appropriate communication systems, either wireless or fixed line systems and standards and protocols.
[0090] The embodiments of the invention have been discussed in the context of call state control functions. Embodiments of the invention can be applicable to other network elements where applicable.
[0091] It is also noted herein that while the above describes exemplifying embodiments of the invention, there are several variations and modifications which may be made to the disclosed solution without departing from the scope of the invention as defined in the appended claims.
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A method of communication between a calling party in a first network and a called party in a second network is disclosed. The method comprises determining in the first network an address associated with the called party. The method also comprises determining, based on the address, if the called party is in a trusted network, and controlling the communication between the called party and the calling party in dependence on if the called party is in a trusted network.
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CROSS REFERENCE TO APPLICATIONS
This application is related to, and claims priority from, U.S. Provisional Patent Application No. 61/231,474 filed on Aug. 5, 2009 by E. Rzhanov et al. titled “High Safety Files for Root Canal Treatment”, the contents of which are hereby incorporated by reference.
TECHNICAL FIELD
The present invention relates to endodontic instruments and their method of manufacture, and more particularly, to rotatable endodontic instruments having radius profiles and structures that produce a favorable distribution of torsion angle per unit length along the length of the instrument and/or reduce metal fatigue associated with repeated use of the instrument.
BACKGROUND ART
Endodontic therapy is a dental procedure, colloquially know as a “root canal”, undertaken to repair and save a tooth by removing and replacing infected dental pulp.
FIG. 1 a show a cross-section of an exemplary healthy tooth 10 . The main body 12 of the tooth is composed of dentin, a matrix of mineralized connective tissue, that supports an overlay of hard, brittle tooth enamel 14 . The main body 12 of the tooth is supported by the gums 16 that cover the jaw bone 18 , and also contains dental pulp 20 , a soft connective tissue. Nerves in the dental pulp 20 connect with the rest of the body via one or more canals 22 located in the roots of the tooth 24 .
When dental pulp 20 becomes irritated, it swells up. Since the dental pulp 20 is encased in a rigid matrix of dentin, there is little or no room for expansion and the nerves in the dental pulp 20 are squeezed or pinched, causing a great deal of pain. A “root canal” is an endodontic procedure designed to alleviate this pain and save the tooth by removing the dental pulp 20 and replacing it with a bio-inert material such as gutta-percha.
FIG. 1 b shows the first step in a typical root canal procedure. A portion of the tooth enamel 14 has been removed, along with a portion of the main body 12 of the tooth and the bulk of the dental pulp 20 . This removal is typically effected using a tungsten carbide, or diamond, tipped dental bur 26 , a.k.a. a dental drill bit.
FIG. 1 c shows a further step in a typical root canal procedure. At this stage, the dental pulp 20 has been removed from the right hand canal 22 , and the dental pulp 20 is in the process of being removed from the left hand canal 22 by means of an endodontic instrument 28 .
FIG. 1 d shows a completed root canal treatment. The dental pulp 20 has been completely removed and replaced by a bio-inert material 34 .
FIG. 2 a shows an exemplary, prior art, endodontic instrument 28 used to remove dental pulp 20 from the canals 22 in a root canal procedure. The endodontic instrument 28 has a shank 42 , a quick change, cam drill holder 44 , a cylindrical shaft 46 and a flexible cutting bit 48 . The cam drill holder 44 may be one of the standard handles for connecting the endodontic instrument 28 to an endomotor.
Prior art endodontic instruments 28 are typically made from a Nickel-Titanium (NiTi) alloy. NiTi alloys are more flexible than more conventional stainless steels, but are subject to metal fatigue and may break after repeated use, or after a number of flexures in a single use. Prior art endodontic instruments 28 also typically have screw shaped flexible cutting bits 48 that may result in the bit becoming “screwed in” to the canals 22 , creating a situation where the flexible cutting bit 48 may be torsionally overloaded. Prior art endodontic instruments 28 typically have a tapered, or conical, flexible cutting bit 48 that narrows down from the proximate end of the bit to the distal end.
FIG. 2 b shows a close-up view of the distal end of a prior art endodontic instrument 28 . FIG. 2 b clearly showing the screw shaped cutting edge 50 .
FIG. 2 c shows a close-up view of a cross-section of the flexible cutting bit 48 of a prior art endodontic instrument 28 showing the cutting edges 50 .
FIG. 2 d shows a close up view of the flexible cutting bit 48 of a traditional rotary NiTi endodontic instrument 28 . FIG. 2 d clearly shows the tapered, or conical, flexible cutting bit 48 that narrows down from the proximate end of the bit to the distal end.
In use, the endodontic instrument 28 may be attached by the cam drill holder 44 to a rotary drill or rotary endomotor. The endomotor, which may be an electrically powered drill, applies a torque to the endodontic instrument 28 that is transmitted via the handle the shank 42 to the flexible cutting bit 48 . The applied torque results in a slight twisting of the flexible cutting bit 48 as the cutting edges 50 engage the dental pulp 20 in the canals 22 and the surrounding dentin in the main body 12 .
FIG. 3 a shows a plot of c(z), the torsional rigidity of a NiTi flexible cutting bit 48 , measured in dyne·cm 2 , as a function of distance along the axis 52 of the flexible cutting bit 48 , measured in cm.
The plot 56 is calculated for a NiTi flexible cutting bit 48 having a diameter D 0 at the distal end 54 of 0.25 mm. The distal end 54 is also where z, the distance along the axis 52 , is taken to be zero. The length L of the flexible cutting bit is 16 mm and the cone shape of the flexible cutting bit 48 is 2%, i.e., the radius of cross-section increases by 0.02 mm along each mm from the tip of instrument.
From plot 56 , it is evident that the torsional rigidity of the flexible cutting bit 48 is at its least at the distal end 54 , where the radius of the flexible cutting bit 48 is smallest.
FIG. 3 b shows τ(z), the torsion angle per unit length, of the same NiTi flexible cutting bit 48 , plotted as a function of distance z, measured in cm, along the axis 52 of the flexible cutting bit 48 . τ(z), the torsion angle per unit length, is shown for two different values of applied torque when the tip of the endodontic instrument 28 is held stationary.
Plot 58 shows the torsion angle per unit length τ(z) of the typical, conical endodontic instrument 28 when a torque of 100 dyne·cm is applied to the shank 42 while the distal end 54 is held stationary.
Plot 60 shows the torsion angle per unit length τ(z) of the typical, conical endodontic instrument 28 when a torque of 150 dyne·cm is applied to the shank 42 while the distal end 54 is held stationary. These plots are based on mathematical analysis shown in detail in, for instance, U.S. Provisional Patent Application No. 61/231,474 filed on Aug. 5, 2009 by E. Rzhanov et al. titled “High Safety Files for Root Canal Treatment”, the contents of which are hereby incorporated by reference.
From these plots, it is evident that the torsion angle per unit length τ(z) will most probably first exceed some upper critical value in the vicinity of the distal end 54 of the endodontic instrument 28 . This is where the flexible cutting bit 48 is located. The flexible cutting bit 48 , particularly the distal end of the flexible cutting bit 48 , is, therefore, where any excessive torque applied to the endodontic instrument 28 will most likely begin to deform the endodontic instrument 28 , and it is also the region where any breakage is most likely to occur.
When a flexible cutting bit 48 breaks deep in a canal 22 , it is often impossible to retrieve the broken portion. The broken, distal portion of the flexible cutting bit 48 , therefore, often has to be left in place where it broke in the canal 22 . This is not a very satisfactory outcome for the patient as it sometimes means that the tooth then has to be removed, which is what the root canal procedure was intended to avoid.
An endodontic instrument 28 with a cutting bit that is flexible, robust and not inclined to break is, therefore, highly desired. It is further highly desired that the endodontic instrument 28 is manufactured so that, if breakage does occur, the distal portion of the broken instrument may be easily removed from the patient's tooth.
SUMMARY OF INVENTION
Technical Problem
The technical problem addressed by the present invention includes, but is not limited to, providing a flexible cutting bit suitable for endodontic therapy, that is shaped, or constructed, so as to minimize the possibility of the bit breaking. Significant causes of bit breakage include excessive torsional force and metal fatigue from repeated flexing. Moreover, the flexible cutting bit is preferably shaped, or constructed, so that, if breakage does occur, it will most likely occur in a portion of the endodontic instrument that allows the distal portion of the broken bit to be easily removed from the tooth, even when the distal end of the tip is trapped deep in a dental pulp canal.
Solution to Problem
The present invention solves the technical problem by providing a quasi-hyperbolic endodontic instrument having a cylindrical, elongated shaft with a radius that is a smooth, continuous curve. Moreover, the radius of the elongated shaft is larger near the working, or distal, portion of the file than near the handle, or proximate end, of the instrument. The distal radius may, for instance, be 10% or more, larger than the proximal radius. This design provides a flexible instrument that reduces the possibility of the instrument breaking, and helps ensure that if breakage does occur, it will occur near the handle, allowing the broken bit to be easily removed from the tooth canal.
In a preferred version, the working portion of the instrument, i.e., the portion located near the shaft's distal end, extends less than one-third of the way along the shaft and is shaped to have at least one cutting surface. The instrument may also have a capture node, located near the handle, or proximal end, of the shaft. The capture node may have an effective radius that is 10% or more larger than the radius of the shaft at the place where the shaft joins the capture node. The endodontic instrument of this invention may also have a region of weakest torsional rigidity located between the capture node and the proximal end of the shaft, ensuring that if the file does break, the capture node will remain attached to the broken off end that is lodged in the tooth canal. The capture node may have one or more flat or grippable facets on its outer surface, so that tweezers, flat pliers, or a specially designed capture tool, may easily grip and remove the broken end from the tooth canal.
In a further embodiment of the invention, the technical problem may be solved by providing a flexible endodontic instrument having a metal cable. A cutting head may be attached to the distal end of the cable, while the proximal end of the cable may be attached to a handle.
In a further preferred embodiment of the invention, the cable may have at least seven strands of metal wire of equal lengths, with six of the strands being helically wound around the seventh strand, to form the cable.
The handle may be made of a tube surrounding, and attached to, the cable. The tube forming the handle may extend for a third or more of the length of the cable. The tube may ensure the endodontic instrument is of the required length, while the length of the free cable from the handle to the cutting blade is of sufficient length to provide the required stiffness and flexibility.
The cable connection between the handle and the blade provides flexibility. It also tends to increase the safety of the file, as the fibers in a cable tend to be tension loaded. The torsion loading on the cable is, therefore, significantly less than it would be on a solid rod made of the same material. This allows each of the cable fibers to work within the elastic range of the metal it is made from, thereby avoiding any accumulating damage and significantly reducing the probability of deformation or breakage of the instrument.
In further embodiments, the invention may combine or incorporate elements from each of the embodiments described above.
Advantageous Effects of Invention
Advantages effects of the invention include, but are not limited to, providing endodontic instruments that have the required flexibility and cutting ability but are less susceptible to breakage than existing endodontic instruments.
These and other features of the invention will be more fully understood by references to the following drawings.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 a shows a schematic cross-section of an exemplary healthy tooth.
FIG. 1 b shows a schematic view of a first step in a root canal procedure.
FIG. 1 c shows a schematic view of an endodontic instrument being used to remove dental pulp from a tooth canal.
FIG. 1 d shows a schematic view of a final stage of a root canal in which the dental pulp has been replaced by a bio-inert material.
FIG. 2 a shows a schematic side view of an exemplary, prior art, endodontic instrument.
FIG. 2 b shows a schematic close-up view of the distal end of a prior art flexible cutting bit.
FIG. 2 c shows a schematic close-up view of a cross-section of a prior art flexible cutting bit.
FIG. 2 d shows a schematic close up view of a prior art flexible cutting bit.
FIG. 3 a shows a plot of c(z), the torsional rigidity, of a prior art NiTi flexible cutting bit as a function of distance along the axis.
FIG. 3 b shows plots of τ (z) ,and τ 1(z) as a function of distance (z) along the axis.
FIG. 4 a shows a schematic, 3D, view of an exemplary quasi-hyperbolic endodontic instrument of the present invention.
FIG. 4 b show a plot of radius as a function of distance for an exemplary quasi-hyperbolic endodontic instrument.
FIG. 4 c shows a plot of torsional rigidity as a function of position along the central axis an NiTi flexible shaft having the radius profile shown in FIG. 4 b.
FIG. 4 d show plots of τ(z), the torsion angle per unit length as a function of position along the central axis an NiTi flexible shaft having the radius profile shown in FIG. 4 b.
FIG. 5 a shows a schematic, side view of an exemplary quasi-hyperbolic endodontic instrument of the present invention.
FIG. 5 b shows a schematic side view of an exemplary quasi-hyperbolic endodontic file
FIG. 5 c shows a schematic, close-up view of the working portion of the quasi-hyperbolic endodontic file.
FIG. 5 d shows a close-up schematic view of the proximal end of the quasi-hyperbolic endodontic file.
FIG. 5 e shows a cross-sectional view drawn on “AA”.
FIG. 5 f shows a cross-sectional view drawn on “BB”.
FIG. 6 a shows a schematic, sectional side view of a cable endodontic instrument of the present invention.
FIG. 6 b shows a view of an exemplary cable endodontic file of the present invention.
FIG. 6 c shows the cable 106 attached to the working portion 66 of the cable endodontic file.
FIG. 6 d shows a cross section on “CC”.
FIG. 6 e shows a cross-section on “DD”.
FIG. 6 f shows a cross-section view of a cable have seven strands of metal wire.
FIG. 6 g shows a cross-section view of a cable 106 have nineteen strands of metal wire 112 .
DESCRIPTION OF EMBODIMENTS
Embodiments of the present invention will now be described in detail by reference to the accompanying drawings in which, as far as possible, like elements are designated by like numbers.
FIG. 4 a shows a schematic, 3D, view of an exemplary quasi-hyperbolic endodontic instrument 62 of the present invention. The quasi-hyperbolic endodontic instrument 62 includes a working portion 66 , a flexible shaft 70 , a handle 72 and a drill attachment mechanism 74 . The quasi-hyperbolic endodontic instrument 62 may also include a capture node 64 and a region of weakest torsional rigidity 68 . The capture node 64 may be located near the proximal end 78 of the flexible shaft 70 . The working portion 66 of the reverse curved endodontic instrument 62 may be located near the distal end 76 of the flexible shaft 70 . The working portion 66 may have one or more cutting edges, and typically extends for as little as 5% of the flexible shaft 70 , though it may be as much as 20% or even 33% of the length of the flexible shaft 70 . The flexible shaft 70 is preferably made from a suitable metal or metal alloy such as, but not limited to, a NiTi alloy, a stainless steel alloy, silver, gold, titanium or a super-elastic Nickel, Titanium and Niobium alloy or some combination thereof. The flexible shaft 70 may be rotationally symmetric about a central axis 82 . The radius of the flexible shaft 70 at its distal end 76 may be about 10% or more larger than the radius of the flexible shaft 70 near its junction with the capture node 64 . The capture node 64 may have one or more flat or grippable surfaces. In a preferred embodiment the cross-section of the capture node 64 may be a polygon, and preferably a regular polygon, such as, but not limited to, a triangle, a square, a pentagon, a hexagon, or an octagon. The handle 72 of the reverse curved endodontic instrument 62 may also include a depth indicator 80 .
FIG. 4 b show a plot 84 of r(z), the radius r as a function of z, the position along the central axis 82 of the flexible shaft 70 , of an exemplary quasi-hyperbolic endodontic instrument 62 .
In a preferred embodiment, the flexible shaft 70 has a circular cross-section. The radius profile of the flexible shaft 70 is a smooth curve that is larger at the distal end (z=0) than at the proximal end (z=20). In the example shown, the distal radius is approximately 25% larger than the proximal radius. In various embodiments of the present invention, the distal radius may be only 10% larger the proximal radius, or it may be larger by a factor greater than 10% depending on factors such as, but not limited to, the material the flexible shaft 70 is made from, its length, the required flexibility or some combination thereof.
FIG. 4 c shows a plot 86 of c(z), the torsional rigidity as a function of position along the central axis 82 for a NiTi flexible shaft 70 having the radius profile in FIG. 4 b . The torsional rigidity is greatest at the distal end of the flexible shaft 70 and a minimum at the proximal end of the flexible shaft 70 .
FIG. 4 d show plots of τ(z), the torsion angle per unit length as a function of z, the position along the central axis 82 .
Plot 90 of τ(z) corresponds to a NiTi flexible shaft 70 having a radius profile corresponding to the hyperbolic function 91 :
r
(
z
)
=
k
z
+
a
4
and a torque load of 1000 dyne·mm. _k and a are engineering parameters that determine the radius of the flexible shaft 70 at the distal end 76 and the region adjacent to the capture node 64 respectively.
In plot 90 , torsion angle per unit length τ increases substantially linearly with z. Torque loading on the flexible shaft 70 is, therefore, greatest near the handle and decreases toward the distal end of the flexible shaft 70 . If the quasi-hyperbolic endodontic instrument 62 is subject to excess torque, breakage will, most likely, occur at the proximal end of the flexible shaft 70 . As the proximal end tends to usually be clear of the tooth canal 22 , there should usually be an exposed portion of the broken flexible shaft 70 that may be used to extract it from the tooth.
The hyperbolic function 91 corresponds to the optimum radius profile for the flexible shaft 70 based on equations derived in, for instance, U.S. Provisional Patent Application No. 61/231,474 filed on Aug. 5, 2009 by E. Rzhanov et al. titled “High Safety Files for Root Canal Treatment”, the contents of which are hereby incorporated by reference.
Such equations include, for instance, a fundamental relation relating torsional rigidity c(z) and the torsion angle per unit length τ(z) to the applied torque M:
C ( z )·τ( z )= M
Other related or similar radius profiles may be used so long as they provide a uniform distribution of torsion rigidity, having no extremes, or discontinuities, along the flexible shaft 70 . Moreover, the distribution of torsion angle per unit length on the flexible shaft 70 should be a slightly increasing function of z such as, but not limited to, a linear function with a small inclination. The slight increase of torsion angle per unit length τ(z) with z compensates for practical uncertainties such as, but not limited to, inhomogeneity of the material used to manufacture the flexible shaft 70 , defects introduced during manufacture, damage as a result of storage, transportation, packaging or prior use, or some combination thereof. The slight increase of torsion angle per unit length τ(z) helps ensure that any breakage is most likely to occur at the proximal end of the flexible shaft 70 , close to the handle, allowing for easy retrieval of the broken bit.
In order to minimize the effect of uncertainties associated with manufacture, the flexible shaft 70 is preferably made by grinding and polishing a substrate to the correct shape and surface smoothness. Good surface smoothness helps ensure that the correct torque is applied to the working portion 66 during an endodontic procedure. The instruments should also be carefully examined using instrumentation designed for nondestructive testing and detection of flaws in metal objects such as, but not limited to, the well known supersonic reflectoscope and the well known phased-array, ultrasonic test instruments, or some combination thereof.
Plot 88 of τ(z) corresponds to a NiTi flexible shaft 70 having a radius profile corresponding to the hyperbolic function and a torque load of 1500 dyne·mm.
FIG. 5 a shows a schematic, side view of an exemplary quasi-hyperbolic endodontic instrument 62 of the present invention. The quasi-hyperbolic endodontic instrument 62 includes a working portion 66 , a flexible shaft 70 , a handle 72 and a drill attachment mechanism 74 . The quasi-hyperbolic endodontic instrument 62 may also include a capture node 64 and a region of weakest torsional rigidity 68 .
FIG. 5 b shows a schematic side view of an exemplary quasi-hyperbolic endodontic instrument 92 .
In one embodiment of the present invention, there is a pilot tip 100 . The pilot tip 100 may be shaped as a portion of a sphere, such as, but not limited to, a hemisphere. The pilot tip 100 preferably has a diameter that is about 50% of the largest diameter of the flexible shaft 70 , though it may vary from 20% to 80% of that diameter. The pilot tip 100 is intended to help guide the reverse-curved endodontic instrument 62 down the canals 22 during removal of the dental pulp 20 , and avoid, for instance, the instrument being misdirected down a side canal.
In one embodiment of the present invention, there is a capture node 64 that is hexagonal in cross-section. The capture node 64 may serve as a clamping point during calibration of the quasi-hyperbolic endodontic instrument 92 to determine permissible torque loads. As the region of weakest torsional rigidity 68 is located between the capture node 64 and the handle 72 , if breakage does occur, the capture node 64 will most likely stay attached to the portion of the quasi-hyperbolic endodontic instrument 92 that has lodged in the tooth canal. The broken quasi-hyperbolic endodontic instrument 92 may, therefore, be easily removed using a tool such as, but not limited to, a pair of tweezers, a pair of flat nosed pliers or a specially designed tool such as, but not limited to, the special removal tool described in, for instance, U.S. Provisional Patent Application No. 61/231,474 filed on Aug. 5, 2009 by E. Rzhanov et al. titled “High Safety Files for Root Canal Treatment”, the contents of which are hereby incorporated by reference, or some combination thereof.
The capture node 64 may be joined to the flexible shaft 70 by means of a smooth curve 96 that avoids any discontinuities in the torsion angle per unit length τ(z). Similarly, on the proximal side of the capture node 64 , it may be joined to the region of weakest torsional rigidity 68 by a suitable smooth curve 96 .
The cutting edges 94 may vary in detailed shape to allow files that cut smoothly, or aggressively or have more of a rasping action. Such cutting edge variations are well known in the art. Each type of cutting edges 94 may be useful at various stages of removing the dental pulp 20 from the canals 22 .
The shaft to handle transition 98 should also be by means of a smooth curve 96 that avoids any discontinuities in the torsion angle per unit length τ(z) as such discontinuities may result in concentration of torque forces and lead to deformation or breakage.
FIG. 5 c shows a close-up schematic view of the working portion 66 of the quasi-hyperbolic endodontic instrument 92 , showing the cutting edges 94 and the pilot tip 100 .
FIG. 5 d shows a close-up schematic view of the proximal end of the quasi-hyperbolic endodontic instrument 92 . The view shows the smooth curve 96 that connects the capture node 64 to the flexible shaft 70 , as well as the smooth curve 96 that connects the capture node 64 to the region of weakest torsional rigidity 68 . The view also shows the shaft to handle transition 98 that is a smooth curve connecting the region of weakest torsional rigidity 68 to the handle 72 .
FIG. 5 e shows a cross-sectional view drawn on “AA” showing the cutting edges 94 formed by four grooves ground into the working portion 66 of the flexible shaft 70 .
FIG. 5 f shows a cross-sectional view drawn on “BB” showing flat facets 102 and an hexagonal cross section. The flat facets 102 that may facilitate both clamping during calibration of the quasi-hyperbolic endodontic instrument 92 , and the removal of the broken quasi-hyperbolic endodontic instrument 92 .
FIG. 6 a shows a schematic, sectional side view of a cable endodontic instrument 104 of the present invention. In a preferred embodiment, the cable endodontic instrument 104 may have a cable 106 . The proximal end 78 of the cable 106 may be enclosed by a cylindrical tube 108 . The cylindrical tube 108 in turn may fit into a handle 72 that is attached to a drill attachment mechanism 74 . The handle 72 may have a slideably attached depth indicator 80 . At the distal end 76 of the cable 106 a working portion 66 may be attached to the cable 106 .
FIG. 6 b shows a view of an exemplary flexible endodontic file 110 of the present invention.
The cable 106 may be made from a number of strands of metal wire 112 . The strands of metal wire 112 may be made from suitable metal or metal alloys such as, but not limited to, stainless steel, TiNi alloy or a super-elastic Nickel, Titanium and Niobium alloy or some combination thereof. The strands of metal wire 112 may be substantially equal in length and may be helically wound around a central strand. The cable 106 is substantially uniform in cross-section and therefore has a substantially uniform torsion angle per unit length τ(z).
The proximal end 78 of the cable 106 may be encased in a cylindrical metal tube made from a suitable metal or metal alloys such as, but not limited to, stainless steel, TiNi alloy, silver, gold, titanium or a super-elastic Nickel, Titanium and Niobium alloy or some combination thereof. The cable 106 may be fixed to the cylindrical tube 108 by, for instance, welding. The cylindrical tube 108 allows the flexible endodontic file 110 to have the required stiffness for cutting and the necessary overall length.
The distal end 76 of the cable 106 may be attached to the cutting head 67 of the flexible endodontic file 110 . The cutting head 67 may include one or more cutting blades 114 and a pilot tip 100 . The pilot tip 100 may be shaped as a portion of a sphere, such as, but not limited to, a hemisphere. The pilot tip 100 preferably has a diameter that is about 50% of the diameter of the cable 106 , though it may vary from 20% to 80% of the diameter. The cutting blades 114 may be made from a suitable metal or metal alloys such as, but not limited to, stainless steel, TiNi alloy, silver, gold, titanium or a super-elastic Nickel, Titanium and Niobium alloy or some combination thereof, and may be attached to the cable 106 by, for instance, welding or brazing. Stainless steels typically contain elements selected from a group such as, but not limited to, Chrome, Nickel, Molybdenum and Titanium or a combination thereof. The amount of such elements may vary from as little as 1% to as much as 20%. Chrome may, for instance, be incorporated in a steel alloy at a percentage of weight ranging from 10% to 15%.
The cutting head 67 with the cutting blades 114 may, for instance, be turned from a stainless steal tube that may be soldered on to the distal end of the cable 106 . In an alternate embodiment, the cutting head 67 may be made form the cable 106 by, for instance welding and grinding.
FIG. 6 c shows the cable 106 attached to the working portion 66 of the flexible endodontic file 110 showing the strands of metal wire 112 of the cable, the cutting blades 114 and the pilot tip 100 .
FIG. 6 d shows a cross section on “CC”, showing the cutting blades 114 .
FIG. 6 e shows a cross-section on “DD”, showing the cylindrical tube 108 and the strands of metal wire 112 .
FIG. 6 f shows a cross-section view of a cable 106 have seven strands of metal wire 112 . The six outer strands of metal wire 112 are helically wound around the central strand of metal wire 112 .
FIG. 6 g shows a cross-section view of a cable 106 have nineteen strands of metal wire 112 .
The cable endodontic instruments 104 are preferably made to satisfy ISO standards and be manufactured having cutting diameters such as, but not limited to, diameters of 0.08 mm, 0.1 mm, 0.15 mm, 0.2 mm and 0.25 mm.
TABLE 1
Thickness
Thickness
Strain in
No
of wire
of cable
Kind of tubing
fiber
Comments
1
16 μm
1×19 = 80 μm
32 REG, ACCU-TUBE
0.4%
R = 2
mm
2
20 μm
1×19 = 100 μm
17-7, ACCU-TUBE
0.5%
R = 2
mm
3
30 μm
1×19 = 150 μm
29 REG, ACCU-TUBE
0.75%
R = 2
mm
4
38 μm
1×19 = 190 μm
27 REG, ACCU-TUBE
0.95%
R = 2
mm,
head = 200
μm
5
46 μm
1×19 = 230 μm
26 REG, ACCU-TUBE
1.15%
R = 2
mm,
head = 250
μm
6
66 μm
1×19 = 330 μm
24 TW, ACCU-TUBE
0.85%
R = 4
mm,
head = 350
μm
Table 1 shows the calculated strain in cable fibers for cables corresponding to the ISO standard sizes detailed above. The calculations are shown in detail in, for instance, U.S. Provisional Patent Application No. 61/231,474 filed on Aug. 5, 2009 by E. Rzhanov et al. titled “High Safety Files for Root Canal Treatment”, the contents of which are hereby incorporated by reference, or some combination thereof. The depend on the derived relationship:
σ
zz
max
=
E
·
r
R
in which r represents the radius of the strands of metal wire 112 , R represents the radius curvature of the canals 22 that the instrument is working on E represents Young's modulus of elasticity for the material that the strands of metal wire 112 are made of, and σ zz max represents the maximum stress in the strands of metal wire 112 . In Table 1, R is either 2 mm or 4 mm.
Permissible stress for stainless steel has experimentally been found to be 1.5 to 2.0%. This is the strain at which stainless steel will begin to deform non-elastically.
As can be seen from Table 1, for a seventeen strand cable, the maximum strain in each strand for all the ISO radius instruments, is well below the maximum permissible strain for the practical flexibility needed in performing endodontic procedures on teeth.
Although the invention has been described in language specific to structural features and/or methodological acts, it is to be understood that the invention defined in the appended claims is not necessarily limited to the specific features or acts described. Rather, the specific features and acts are disclosed as exemplary forms of implementing the claimed invention. Modifications may readily be devised by those ordinarily skilled in the art without departing from the spirit or scope of the present invention.
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A quasi-hyperbolic endodontic instrument having a cylindrical, elongated shaft with a radius that varies as a smooth, continuous curve along the length of the shaft and is larger near the distal portion of the file than near the proximal end of the file. The distal radius may be 10% or more larger than the proximal radius. This design provides a flexible file that minimizes the possibility of breaking, and ensures that if breakage does occur, it will occur near the handle, allowing the broken bit to be easily removed from the tooth canal. The instrument may further, or instead, have a metal cable connecting the cutting head to the handle to help reduce metal fatigue.
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FIELD OF THE INVENTION
[0001] The present invention generally relates to data processing, and more particularly, to fault recovery in a data processing system.
BACKGROUND OF THE INVENTION
[0002] A popular design for central processing units is reduced instruction set computer (RISC) processors using a pipeline architecture. With pipeline architecture, the tasks performed by a processor are broken down into a sequence of functional units referred to as stages or pipeline stages. Each functional unit receives one or more inputs from the previous stage and produces one or more outputs which may then be used by the subsequent stage. Thus, one stage's output is usually the next stage's input. Consequently, all of the stages are able to work in parallel on different, although typically sequential, instructions in order to provide greater throughput.
[0003] Typical stages of a RISC processor pipeline include instruction fetch, register fetch, arithmetic execution, and write-back to registers. In order to improve performance, the pipeline receives a continuous stream of instructions fetched from sequential locations in memory using addresses that are typically stored in a program counter or other suitable device. When several instructions are being concurrently processed in the pipeline and each pipeline stage is performing its designated task, a single instruction can be executed approximately every clock cycle. This design offers greater efficiency than other architectures, such as complex instruction set computer (CISC) architectures, which require more than one clock cycle to execute an instruction.
[0004] Because of its many advantages, only a few of which are discussed above, the RISC architecture enjoys a wide variety of applications including those with safety critical implications such as health care, transportation, military, space, and some manufacturing environments.
[0005] The increased reliance on RISC processor-based automated data processing systems in safety critical applications raises the need for the system to be dependable; that they perform their expected task(s) correctly with a high degree of confidence. Design for dependability is one of the many drivers that define the specifications of the RISC processor-based system. Fault avoidance, removal, and tolerance are three approaches that improve system dependability. Fault avoidance is usually achieved by processes and methods used to generate the design of the system such as adherence to proven design and development processes or the use of formal methods to validate the correctness of a design. Fault removal is usually achieved by extensive system testing. A fault is removed once it is discovered during system test. Fault tolerance is achieved by incorporating features in the design that enable continued correct system operation in spite of the occurrence of a fault.
[0006] A fault may be permanent or transient. A permanent fault is one that causes the RISC processor's behavior to permanently deviate from its specifications, and typically requires human intervention to ameliorate its effect. A transient fault, on the other hand, causes the behavior deviation for a limited time period. The processor typically resumes its behavior as specified once the cause of the fault disappears and the effect of the fault is removed from the system.
[0007] Transient faults are typically caused by an event in the processor's physical environment. For example, in an industrial application, many transient faults are due to the electrically noisy environment where equipment switching causes voltage spikes that impact the processor's power supply, and thus causing a transient fault in the microelectronics circuitry that make up the processor. A single event upset (SEU) is yet another cause of transient faults in the microelectronics circuitry of a RISC processor. SEUs are usually caused by a natural or man-made radiation particle that changes the state of a processor by altering its memory content, such as a bit in one of its data or control registers, while it travels through space. Once the radiation particle passes through the circuitry, it no longer affects the microelectronics device. In either of these cases, as well as others, the transient fault may cause the processor to exhibit an error in its processing. In safety critical applications, declaring a processor as permanently failed due to a transient fault may not be a suitable course of action for reasons such as the lack of spare processors to continue operation. This is particularly true in space applications where processors are expected to operate for an extended time period to justify the cost of the mission. Thus, given the existence of transient faults in certain computing environments, it is desirable to be able to detect and recover from transient faults as quickly and as efficiently as possible so that the performance of the processor is not significantly hampered or degraded.
[0008] The impact on the performance of a processor from a transient fault depends upon the overhead associated with recovery. Two factors which largely control the overhead of transient fault recovery are: (1) the time spent to continually gather the data necessary in anticipation of recovering from a transient fault, and (2) the actual recovery time, i.e., the time it takes the processor to remove the effect of the fault from its memory and to be ready to resume correct operation. Following are discussions of several techniques used for transient fault recovery.
[0009] A relatively common technique for transient fault recovery is checkpoint retry in which the current state data of a program is saved in a memory cache at various points in the execution of the program code. These points are referred to as checkpoints. Checkpoints are taken at the software level where the program is modified to permit the capture of checkpoints and the rollback to a suitable checkpoint during recovery. Typically, only the values of program variables that changed since the last checkpoint are stored at a next checkpoint. When an error is detected, the program state is restored (also referred to as rolled back) to the last checkpoint that preceded the error in the instruction stream. The amount of roll back necessary to reach the nearest checkpoint is called the rollback distance. The rollback distance may be measured by the number of instructions the effect of which must be nullified to reach the nearest checkpoint. Execution is resumed from the checkpoint once the program state is restored from the data stored at the checkpoint. A drawback to this technique is the complexity of the code necessary to allow the data to be gathered at each checkpoint. Another drawback is the relatively high overhead on system performance. The performance overhead of checkpoint retry is largely due to the overhead required for storing the data associated with all the instructions between consecutive checkpoints. This same data is also restored during an actual recovery which, likewise, is time consuming. Further, if more frequent checkpoints are used in order to reduce the amount of data which must be stored at every checkpoint and then restored in case of an error, then more of the processor's time is spent performing error checking. In computing applications requiring control based on precise time intervals, the recovery time spent error checking and rolling back to a checkpoint can be difficult to determine apriori. Finally, in environments where the processor's next task depends upon changes in its physical environment, such as the firing of a jet to correct a spacecraft's attitude or the reaction to a change in the state of a stage in a manufacturing assembly line, recovery times must be bounded to prevent the processor from reacting to a set of environmental conditions that does not truly reflect the processor's physical environment. The analysis and determination of proper recovery time bounds is very difficult.
[0010] Another recovery technique referred to as instruction retry is a variation on the checkpoint retry scheme in that the rollback distance is reduced to one instruction. In essence, a checkpoint is obtained prior to the execution of an instruction. The output of the processor is checked for correctness after the execution of the instruction. A detected error causes a checkpoint retry. The processor's state is restored to that which it was prior to the execution of the instruction, and the instruction is fetched again from the instruction memory for a re-execution. This approach minimizes the amount of data saved at every checkpoint by saving the values of variables that would be changed through the execution of the next instruction. The error detection mechanism is typically a comparator that compares the processor's outputs to those of a redundant processor in a master/checker (or duplicate) configuration. The processor's internal memory and register devices that would be affected by the upcoming instruction execution must also be saved by the checkpoint in order to restore the processor's execution environment correctly after rollback. While the recovery time for this technique is very short, its performance overhead is high. The program state data must be saved prior to the execution of an instruction. The output of every instruction is validated. The program's state is restored once recovery is initiated in reaction to a detected error. Establishing a checkpoint and validating every instruction reduces the processor's throughput.
[0011] Another recovery technique is to use a hardware-based checkpoint retry mechanism, also referred to as a micro-rollback mechanism. This technique is similar to the checkpoint retry techniques discussed above except that additional hardware is added for automating the storage of state information and data within the processor. Consequently, a disadvantage to a hardware checkpoint retry mechanism is that it utilizes valuable on-chip space for the additional hardware required, essentially denying its use to enhance the processor's functionality and deliver maximum performance. Further, if the error latency is high, more hardware is required to implement the micro-rollback mechanism because more processor data and state information is used and modified after the execution of the instruction in which an error occurs, but before the error is detected. Hardware based checkpoint retry mechanisms are further described in numerous publicly available writings such as, for example, in Y. Tamir et al., “The Implementation and Application of Micro Rollback and Fault-Tolerant VLSI Systems,” 18th Fault-Tolerant Computing Symposium, Tokyo, Japan, pp. 234-239, June 1988, where micro rollback is applied to a RISC processor.
[0012] The checkpoint retry technique and all its variants implement a recovery strategy that commits the results of one or more computational steps or instructions then react by rolling back the effect of these once an error is detected.
[0013] Forward error recovery is another recovery technique that does not rely on restoring the state of a program to one of its previous states, as captured by a checkpoint. Forward error recovery techniques reset the program state to a predetermined initial state based on the kind and location of an error in the code. This technique reduces the performance overhead due to the absence of checkpoint and restoration activities. However, it does introduce uncertainty in the robustness of recovery. The risk is that resetting the program state may not be appropriate for recovering from the particular error. It is very difficult to determine the proper reset data in reaction to every possible error, unless the system is trivially simple. Recovery is typically managed at the program level.
[0014] Therefore, a heretofore unresolved need existed in the industry for a recovery system and method that provides improved recovery from transient faults, such as in a pipelined RISC processor, with minimal performance and hardware overhead.
SUMMARY OF THE INVENTION
[0015] It is therefore an object of the present invention to provide improved transient fault recovery.
[0016] It is another object of the present invention to provide improved transient fault recovery by committing the results of a computation after it is verified to be correct.
[0017] It is yet another object of the present invention to reduce the recovery time from transient faults in a reduced instruction set computer (RISC) processor.
[0018] It is yet another object of the present invention to provide transient fault recovery systems and methods that can be easily integrated in a RISC processor with minimum hardware and performance penalty.
[0019] These and other objects of the present invention are provided by a transient fault recovery system. Processor state changes based on the execution of an instruction are not committed until the instruction is validated. The processor state data related to an instruction, i.e., the instruction state data, are saved as it moves through the pipeline stages. The instruction state data must contain all data necessary to enable the re-execution of the instruction beginning with the first pipeline stage, i.e., the instruction fetch stage in the RISC processor. If an error is detected in the execution of an instruction, then a copy of that instruction is retrieved using the address used to fetch the instruction previously, i.e., the instruction fetch address. The pipeline's upstream stages, i.e., the pipeline stages that are processing instructions that have been fetched subsequent to the instruction that is found to be in error, are purged. The processor is then restarted after its state is reset to a state where the execution can resume without the effect of the transient fault.
[0020] The verification of the correct execution, i.e., the validation, of an instruction is performed by one or more error detection mechanisms at every pipeline stage by using appropriate error detection techniques. For example, a simple parity check may be sufficient to validate the correct processing of the instruction by the instruction fetch stage. Parity check may also be sufficient to validate the instruction at the output of the register fetch stage. The output of the execution stage may also be validated by using a master/checker (or duplicate) configuration of the arithmetic transform operators, e.g., the arithmetic logic unit (ALU), and comparing the results. Alternatively, a checker with reduced functionality may be used to minimize the amount of hardware needed and provide an acceptable level of error detection. The amount of acceptable error detection logic at each pipeline stage depends on many factors, including the desired level of fault coverage and the amount of physical space available on the microcircuit to incorporate the logic. Detecting an error during validation will terminate the current execution of the instruction and will not commit any of its results.
[0021] The validation at each pipeline stage may take place within that stage, if it can be accomplished within the remaining part of the clock period used by the stage. For example, if the processor's clock period is N units of time and part of this period, say M units of time where M less than N, is consumed by the stage to generate its output(s), then the remaining units of time, (i.e., N−M), can be used to validate these outputs. However, if the number of remaining units of time, (i.e., N−M), is not sufficient for the validation, then enhancing the RISC pipeline with additional pipeline stages dedicated to validating the output of every stage may be necessary. In the worst case, these validation stages may be introduced between the instruction fetch and register fetch stages, between the register fetch and the execution stages, and/or between the execution and write-back stages.
[0022] In an embodiment of this invention, only the execution stage may need to be followed by a dedicated validation stage. This is due to the complex logic used by the arithmetic transform operators within the execution stage. A substantial part of the processor's clock period is consumed by this logic to generate results. This is unlike the instruction and register fetch stages where sufficient time would typically be left for the validation within the processor's clock period. Naturally, selecting a clock period that is optimal between the number of pipeline stages and the ability to validate a stage's output within the processor's clock period is critical to determining the processor's effective throughput. A sufficiently long processor clock period allocated to that stage eliminates the need for an additional validation stage, but may reduce the processor's throughput. A sufficiently short processor clock period would, in the worst case, require the addition of a validation stage after the instruction fetch, register fetch, and/or execution stages. The pipeline grows longer where the number of its stages increases. For example, a four-stage pipeline may grow to as many as seven stages. Therefore the processor's effective bandwidth may be reduced. This is because of the effect of the execution of branch instructions on the pipeline's stages as can be recognized by those skilled in the art.
[0023] In particular, a data processing system for re-executing an instruction if an error is detected in the prior execution of that instruction comprises the program counter value used to fetch the instruction, i.e., the instruction fetch address. It also includes a memory device referred to herein as the pipeline history cache, which contains the instruction fetch address. The data processing system may also include circuitry to detect errors such as parity code checkers or arithmetic transform operators (e.g., the Arithmetic Logic Unit (ALU)). Alternatively, the arithmetic transform operator circuitry of the data processing system may contain logic for at least partially executing the instruction.
[0024] In an embodiment of this invention, the error detection technique used in the execution stage relies on using master/checker configurations of the arithmetic transform operators where a comparator is necessary to validate the instruction prior to committing its results through the write-back stage. The comparator may compare the results of the executed instruction with reference results from the checker. The master/checker pair may be included in the chip's circuitry but would be located far apart to prevent common mode failures. It is noted that the checker may be another processor, provided the processor's clock period is sufficiently long to permit the data from the master and checker to travel to the comparator and for the comparator to produce the result. Error recovery logic is also necessary to reset the program counter to the instruction's fetch address stored in the pipeline history cache. As such, the instruction under execution, at the time an error is detected, can again be fetched and processed through the pipeline's stages.
[0025] In accordance with an aspect of the present invention, the transient fault recovery system may abort further execution of the instruction if an error is detected when validating the execution of the instruction. Further, the transient fault recovery system aborts the execution of all instructions in the pipeline subsequent to the instruction where an error is detected.
[0026] In yet another aspect of the present invention, a method of error recovery in a data processing system having a memory device, such as a pipeline history cache typically formed by a first-in, first-out (FIFO) cache, comprises of the steps of fetching an instruction using an instruction fetch address, storing the instruction fetch address in the memory device, at least partially executing the instruction, and validating the execution of the instruction prior to implementing a state change based upon the execution of the instruction. Moreover, if an error is detected in the execution of the instruction, then the method may also comprise the step of fetching of the instruction utilizing the instruction fetch address stored in the memory device and re-executing the fetched instruction. The step of validating the execution of the instruction may comprise the step of comparing the results from the execution of the instruction with reference results from, for instance, a redundant microcircuit.
[0027] In addition, the method of the present invention may also advantageously include the step of aborting the execution of the instruction if an error is detected in the step of validating the execution of the instruction. Similarly, the method may include the step of aborting the execution of instructions subsequent to the current instruction in the pipeline if an error is detected in the step of validating the execution of the current instruction.
[0028] Other features and advantages of the present invention will become apparent to one skilled in the art upon examination of the following drawings and detailed description. It is intended that all such features and advantages be included herein within the scope of the present invention, as defined by the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] The present invention can be better understood with references to the following drawings. The elements of the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present invention. Furthermore, like reference numerals designate corresponding parts throughout the several views.
[0030] [0030]FIG. 1 is a schematic illustration of a processor pipeline concurrently executing three instructions;
[0031] [0031]FIG. 2 is a schematic block diagram of a processor including a transient fault recovery system in accordance with an embodiment of the present invention;
[0032] [0032]FIG. 3 is a schematic block diagram of the pipeline history cache of the processor of FIG. 2 in accordance with the present invention;
[0033] [0033]FIG. 4 is a schematic illustration of the processor pipeline concurrently executing three instructions and including a validate stage after the execution stage to validate the instruction, in accordance with one aspect of the present invention; and
[0034] [0034]FIG. 5 is a flowchart of the operation of a reduced instruction set computer processor in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0035] The present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in different forms and should not be construed as limited by the embodiment set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
[0036] I. Architecture
[0037] Referring to FIG. 1, a schematic illustration of a reduced instruction set computer (RISC) pipeline is provided. In the architecture shown, there are four stages: an instruction fetch, a register fetch, an execution stage, and a write-back to register stage. These four stages are merely illustrative of the various stages that can be included as a part of a RISC pipeline architecture, as is appreciated by one skilled in the art.
[0038] In the instruction fetch stage, the next sequential instruction to be executed is retrieved, typically from an external or on-chip instruction cache associated with the processor. In the register fetch stage, the retrieved instruction is decoded and the appropriate operands are retrieved from a register file that is typically contained within the processor. In the execution stage, the operands are executed upon by an arithmetic logic unit (ALU), a multiply/divide unit (MDU), or a shifter. Upon completion of the execution stage, the write-back to register stage takes the results of the execution stage and writes them back to the register file utilized in the register fetch stage so as to cause a permanent state change. A permanent state change is defined herein as a general register, flag, or memory location that is modified as a result of the execution of an instruction.
[0039] In FIG. 1, instructions one, two, and three are being concurrently executed so as to take advantage of the pipeline architecture. Preferably, instructions one, two, and three are taken from sequential memory locations, typically in the instruction cache, and are a part of a larger substantially continuous stream of instructions that are being executed. The instructions are typically retrieved using instruction fetch addresses stored in program counter. Within the instruction cache, the instructions are usually stored in sequential order so that the next instruction to be retrieved is available.
[0040] Each stage of the pipeline is preferably implemented with independent hardware so that the instructions can be executed in a concurrent fashion. Thus, the instructions can go from stage to stage in sequential order with several instructions being executed concurrently. As a result, the effective execution time per instruction is approximately one clock cycle, regardless of pipeline length.
[0041] Once an instruction is executed, the results are available to subsequent instructions by reading the appropriate register file after the write-back stage or by bypassing the write-back stage and directly using the results of the execution stage in a subsequent instruction. Thus, if an error occurs in the execution of an instruction, the subsequent instructions in the pipeline may be corrupted by using the erroneous results of a previous instruction.
[0042] Moreover, the presence of an error in the execution of one or more instructions may interrupt the normal operation of the processor. For the purposes of the present disclosure, an error may be caused by a transient fault. Transient faults, as discussed in the Background section, appear only for a brief period of time and typically disappear before the instruction is retried. The potential does exist, however, for the instruction to be retried more than once should the transient fault last for a relatively long time, i.e., longer than a few clock periods. The error recovery logic 34 monitors the number of attempts to execute the instruction. The error is recoverable if the number of attempts does not exceed a predetermined threshold. The error is deemed unrecoverable if the threshold is exceeded. The error recovery logic 34 makes an unrecoverable error signal available on line 66 . In an embodiment of the present invention, the unrecoverable error signal is provided on one of the microcircuits' pin outs for use by other external recovery logic.
[0043] With reference to FIG. 2, a RISC processor 20 in accordance with an embodiment of the present invention is illustrated. The RISC processor 20 can be essentially any suitable processor for implementing the pipeline operation illustrated in FIG. 1. As shown, the RISC processor 20 includes an instruction fetch mechanism 22 , a register fetch mechanism 24 , an execution mechanism 26 , a write-back mechanism 32 , a comparator 28 , and error recovery logic 34 .
[0044] The instruction fetch mechanism 22 receives instructions from an instruction cache 36 , which may be external or internal to the processor. The instruction cache 36 stores instructions for fast retrieval by the instruction fetch 22 . Although the instruction fetch mechanism 22 preferably retrieves instructions from the instruction cache 36 since this retrieval process is quite quick, the instruction fetch can retrieve instructions from other memory devices which are not shown for purposes of brevity, though well known in the industry, if so desired. The instruction fetch mechanism 22 comprises a program counter 38 , and a pipeline history cache 40 . The program counter 38 is a register that contains the address of the next instruction to be fetched for execution. The program counter 38 is automatically incremented after each instruction is fetched so as to point to the next sequential instruction to be retrieved from the instruction cache 36 . Thus, the instruction fetch address of the next instruction to be executed is sent from the program counter 38 to the instruction cache 36 such that the next instruction can be retrieved and sent to register fetch 24 . The program counter 38 provides the instruction fetch address to the register fetch 24 and the pipeline history cache 40 .
[0045] The pipeline history cache 40 , in accordance with an embodiment of the present invention, stores a history of instructions being executed at each of the various stages in order to track an instruction in which an error occurs. The pipeline history cache 40 therefore receives the addresses of the instructions being executed from the program counter 38 and stores the addresses in sequential order.
[0046] In a preferred embodiment as illustrated in FIG. 3, the pipeline history cache 40 is a first-in, first-out (FIFO) register that individually stores the instruction fetch address of the instruction currently being operated on by the register fetch 24 in the register fetch stage history 50 , the instruction currently being operated on by the execution mechanism 26 in the execution stage history 52 , the instruction currently being operated on by the comparator 28 in the validate stage history 54 , and the instruction currently being operated on by the write-back mechanism 32 in the write-back stage history 56 . Thus, with every clock cycle, as each instruction moves to the next stage, the instruction fetch address associated with each instruction likewise moves to the next register of the pipeline history cache 40 . As described below, the output of the pipeline history cache 40 can be provided to both the program counter 38 for restarting the pipeline at the instruction in which an error occurred and the error recovery logic 34 for error reporting and other administrative needs.
[0047] Referring back to FIG. 2, the register fetch 24 receives the next instruction to be executed from the instruction fetch 22 . The register fetch 24 decodes the instruction to determine which type of operation to perform on the operands, and which operands to retrieve from the register file 25 associated with the instruction in register fetch 24 . In essence, the register file, as well known to one skilled in the art, is a memory device which provides persistent storage of the results of an executed instruction, including registers for storing the operands.
[0048] The operands retrieved by the register fetch 24 are then passed on to the execution mechanism 26 which typically comprises one or more of an arithmetic logic unit (ALU), a multiply/divide unit (MDU), and a shifter. Depending upon the particular instruction provided by the instruction fetch 22 , the operands will be directed to the appropriate device (e.g., the ALU, MDU, or shifter) for execution.
[0049] In accordance with an embodiment of the present invention, the comparator 28 receives the results of the execution of the instruction by the execution mechanism 26 . The comparator 28 validates or checks the results of the execution mechanism 26 prior to a permanent state change by the write-back mechanism 32 . The validation of the execution of the instruction by the comparator 28 can be implemented by comparing the output of the arithmetic operators in a master/checker configuration within the processor. Alternatively, the checker may be another processor.
[0050] In a preferred embodiment of the present invention shown in FIGS. 3 and 4, a validate stage is provided following the execution stage in order to permit using an optimally short processor clock period. At lower clock frequencies, the validate stage may be performed as a part of the execution stage or the write-back stage. However, the time required for data from the master and checker circuits of the execution mechanism 26 to reach the comparator, to be compared, and then for an error flag to be set to prevent the write-back mechanism 32 from completing the write-back stage may be longer than a suitable clock period, given processor throughput requirements. By adding the validate stage, a full clock period is available for performing the comparison. Consequently, the need to reduce the clock frequency is not necessary.
[0051] In the next clock cycle the write-back mechanism 32 reads the error flag to control the action of the write-back stage. The additional validate stage may not delay subsequent instructions from using the results of the execution stage because the validate stage can be bypassed via line 60 which provides the results of the execution mechanism 26 stage directly to the register fetch 24 for use in subsequent instructions, even though the write-back mechanism 32 has not yet overwritten the respective registers of the register file 25 . The write-back mechanism 32 receives the output from the execution mechanism on line 60 and waits for a signal from comparator 28 validating the output on line 62 . A valid output causes the write-back mechanism to commit the output to the register file 25 via line 64 .
[0052] In FIG. 4, a schematic illustration of a pipeline architecture including the validate stage is illustrated. Note that even with the additional stage, the pipeline architecture is still able to achieve the execution efficiency of one instruction per approximately every clock cycle due to concurrent execution.
[0053] Referring back to FIG. 2, if the comparator 28 detects an error in the execution of an instruction, an error flag is sent to the write-back mechanism 32 via line 62 so that the write-back mechanism 32 is prevented from updating the register file 25 (via the registr fetch 24 ) with the results received from the execution mechanism, thereby preventing a permanent state change. In addition, upon detecting an error, the comparator 28 sends a retry signal to the error recovery logic 34 . The error recovery logic 34 can perform numerous functions such as providing fault reports to outside agents for reporting and historically tracking the errors occurring within RISC processor 20 . In addition, the error recovery logic 34 determines which address in the pipeline history cache 40 must be loaded in the program counter 38 for re-execution. Further, the error recovery logic 34 sends a retry signal to the program counter 38 directing the program counter 38 to abort all ongoing operations and restart the pipeline with the instruction stored at the instruction fetch address provided by the pipeline history cache 40 . Because of the configuration of the pipeline history cache 40 as illustrated in FIG. 3, the output of the write-back stage history 56 is the instruction fetch address of the instruction last examined by the comparator 28 in the validate stage. That is, the pipeline history cache retains the instruction fetch address of the instruction to be processed by the corresponding pipeline stage. Therefore, by aborting all instructions in the pipeline that were subsequent to the instruction having the error, i.e., the instructions associated with the instruction fetch addresses in pipeline history cache registers 50 , 52 , and 54 , the RISC processor 20 is able to restart at the instruction following the last successfully executed instruction. The instruction fetch address of that instruction is in pipeline history cache register 56 .
[0054] Because no state has been permanently changed, the only information that is stored for the retry operation of the RISC processor 20 according to the present invention are the instruction fetch addresses stored in the pipeline history cache 40 . In other words, no operands or additional data need be stored for retrying an instruction, and therefore, no additional hardware for memory is necessary. Furthermore, the overhead associated with checkpointing is eliminated. The pipeline history cache 40 tracks the offending instruction at the execution stage so that following the detection of the error at the validate stage, the instruction fetch address of the erroneous instruction is at the output of the pipeline history 40 and is sent to the program counter 38 . The program counter 38 then restarts the pipeline at that instruction fetch address upon receiving an appropriate signal from the error recovery logic 34 .
[0055] It should be noted again that the validate stage may be performed as a part of the execution stage if the clock frequency of the RISC processor 20 is able to provide adequate time within a single clock period for the appropriate operations to be performed. Nonetheless, the addition of a stage may not adversely hinder the execution efficiency of the RISC processor 20 .
[0056] Augmenting the instruction fetch and register fetch stages with error detection logic may be possible. In the disclosed embodiment of this invention, both stages are not augmented with error detection logic to keep the logic simple. The advantage of additional error detection logic is that the error can be detected as early as possible. However, the additional complexity does not always justify the benefits gained from a shorter error latency period since the typical length of a processor's clock period is on the order of nanoseconds.
[0057] II. Operation
[0058] The preferred operation and sequence of events corresponding with the RISC processor 20 of the present invention and the associated methodology are described hereafter with reference to FIG. 5.
[0059] In operation, an instruction having an instruction fetch address is initially fetched, as indicated by block 70 . The instruction fetch address is stored in a memory device, such as a pipeline history cache, as indicated by block 72 . Next, as indicated by block 74 , the instruction is at least partially executed.
[0060] The execution of the instruction is then validated prior to implementing a state change based upon the execution of the instruction, as indicated in block 76 . At block 78 , if no error is detected in the step of validating the instruction, then the next instruction is fetched at block 70 and the process begins again at block 72 . If there are no more instructions to be executed, then the process ends. If an error is detected at block 78 , then the execution of subsequent instructions are aborted, as indicated by block 82 . The instruction fetch address stored in the write-back stage history within memory device is then used to fetch the instruction in which the error occurred, as indicated by block 84 . This technique essentially causes the processor to perform a restart of the pipeline at the instruction that experienced the error, beginning again at block 72 . Accordingly, the error recovery system and method of the present invention significantly reduces the amount of information and data that must be stored in comparison with conventional error recovery systems.
[0061] In the drawings specification, there had been disclosed typical preferred embodiments of the invention, and all of the specific terms are employed, they are used in a generic descriptive sense only and not for purposes of limitation, the scope of the invention being set forth in the following claims.
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Systems and methods for transient error recovery in pipelined reduced instruction set computer (RISC) processors prevent state changes based on the execution of an instruction until the execution of the instruction is validated. If a transient fault occurs causing an error to appear in an instruction execution, the instruction is retrieved using an instruction fetch address associated with that instruction and is stored in a pipeline history cache. The RISC processor pipeline is then restarted with that instruction. The validation of the execution of an instruction may take place in the execution stage, though processors with high clock frequencies may include a separate validate stage in the pipeline so that there is adequate time to validate the execution of the instruction without having to decrease the clock frequency.
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BACKGROUND OF THE INVENTION
The present invention relates to a pouch, coated with a film-forming mass, made of flexible packaging material and featuring a zone for tearing the pouch open.
Filling pouches such as tube-shaped pouches with foodstuffs and closing off the pouch by sealing is known. The contents may be removed for example by tearing the pouch open. Depending on the type of packaging material used, it may be difficult to tear open the pouch. Especially pouches made from flexible packaging materials employing highly elastic or tough plastics are difficult to tear open to remove the contents. For that reason an aid to tearing the plastic is often stamped onto a sealed seam on the package. This enables the pouch to be opened; often, however, the contents of the pouch cannot be removed without spillage e.g., or the pouch must be torn beyond the region offering assistance to tearing it open; very often this is problematic for the user. It has also already been proposed for example to provide the pouches with a tear-open strip. This tear-open strip may extend right round the pouch so that the packaging material separates leaving the pouch open. This is, however, a very complicated process as the tear-open strip has to be incorporated in the packaging laminate material.
The object of the present invention is to provide a pouch which contains an aid to tearing it open which may be placed at any desired place, advantageously at an edge region, and enables the pouch to be opened easily and makes the contents of the pouch accessible in such a manner that the contents may be removed without requiring any additional further manipulation to open the pouch.
SUMMARY OF THE INVENTION
That objective is achieved by way of the invention in that the zone for tearing the pouch open is a weakness in the packaging material and the region exhibiting the weakness is covered over with at least one film-forming mass and, after the packaging step, the contents of the pouch are protected by the pouch and, to remove the contents from the pouch, a pulling or snapping movement breaks the cover layer of film-forming mass, whereupon the contents of the pouch become accessible.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 to 6 illustrate the present invention further by way of example.
FIG. 1 shows schematically the production of a tube-shaped pouch;
FIG. 2 shows schematically a view of a tube-shaped pouch;
FIGS. 3, 4 and 5 show the front and rear of a further tube-shaped pouch and the same in the torn open state; and
FIG. 6 shows a section through the packaging material in the region of a weakness therein.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
In the present invention pouches are to be understood as for example flat pouches, edge-sealed pouches, pouches having volume or tube-shaped pouches. Preferred are edge-sealed pouches and tube-shaped pouches.
Essentially all known flexible packaging materials may be employed for flexible packaging material, packaging materials, packaging means, packaging films etc. The packaging materials should be useable on machines i.e. suitable for use on packaging machines. Packaging materials include those made from paper, if desired with barrier layers and/or clad with plastics or made from cellulose as cellophane, or packaging materials containing aluminum foils, such as aluminum foils having sealing layers and, if desired, further plastic layers or packaging materials made from plastic films or plastic films that are clad on one or both sides with paper or metal foils, or packaging materials made from plastics having a barrier layer such as a plastic barrier layer, ceramic barrier layer or a metallic barrier layer.
Plastics that may be used may be for example polyolefins, such as polyethylene or polypropylene, polyamide, polyvinylchloride or polyester etc., in each case as a monofilm or as a laminate or in the form of multilayer plastic laminates employing different plastics. Between at least two layers there may be barrier layers such as ethylvinyl-alcohol barrier layers, or ceramic or glass-like or metallic barrier layers. The plastic films or film laminates may have a thickness for example of 10 to 100 μm, preferably 30 to 50 μm.
The packaging material may be one sided or double sided, advantageously with a sealing layer on the side to become the side facing the inside of the pouch, said sealing layer being for example an organic sealing layer or sealing film for example of polyolefins such as polyethylenes. For example, for impermeable hot sealed pouches a sealing layer containing 6 to 7 g/m 2 sealing lacquer or varnish is adequate.
The packaging material is advantageously in the form of endless strip or in roll form.
The packaging material is provided with a weakness in the region intended for the tear-off zone on the pouch. The weakening of the packaging material may be made by mechanical means for example using a cutting blade, chemically for example using solvents, thermally for example using laser beams, in the form of separation, perforation, notching etc. Preferred is separation. The weakening may be in a straight line or curved and may be such that in the packaging made from the packaging material it extends around the whole periphery or parts of the periphery of the pouch.
The region of weakening on the pouch according to the invention is covered with a film-forming mass. By the region of weakening is meant not only the weakening itself, but also the neighboring parts of the packaging material, for example a region of 2 to 20 mm, advantageously 5 to 10 mm neighboring the weakening.
The pouch according to the invention may be coated with the film-forming mass only in the region of weakness; advantageous, however, is such a pouch which is completely coated with the film-forming mass. The film-forming mass is in particular in the form of the printing on the pouch.
In an advantageous form the film-forming mass in the region of the weakness is thicker than in the rest of the pouch. The film-forming mass may be one layer or a plurality of layers for example two, three, four, five, six etc., layers of film-forming masses. The film-forming mass covers over and closes off the previously made weakness and provides the packaging material again with tensile strength in the region of the weakness.
The film-forming mass or, if employing a plurality of superimposed layers of film-forming masses, the total amount thereof, may in the region of the weakness, advantageously amount to 2 to 8 g/m 2 , usefully 3 to 6 g/m 2 and advantageously 3.5 to 5 g/m 2 -Outside of the region of weakness the film forming mass may be present in amount e.g. of 1 to 7 g/m 2 , usefully 1 to 5 g/m 2 and advantageously 1 to 4 g/m 2 .
A film-forming mass may be produced using for example coatings, lacquers, varnishes, printing-inks and printing-colors containing volatile substances such as solvents and non-volatile substances such as film binders, resins, softeners, additives, colorants, pigments, fillers etc. Preferred film-forming masses are lacquers, varnishes, printing-inks or printing-colors containing colorants or pigments, solvents, fillers, further additives and binders. Advantageous binders are resins, varnishes, nitrocellulose, polyamides, vinyl-resins, colophony-resins, maleinic acid-resins, shellac etc. The lacquers are in particular printing-ink or printing-color materials and may be printed onto the previously weakened flexible pouch using a printing machine. The material applied during printing is not only the film-forming mass but at the same time also the decorative, in some cases also informative, printing applied to the pouch. The printing on the packaging material may be applied on the side of the pouch facing outwards or on the side facing inwards, or on both sides.
Substances in a plastic state may be applied as film-forming material for example deposited as a film in a softened or molten state onto the packaging material, onto the side that will face inwards or outwards on the pouch or on both sides.
The film-forming mass may be deposited by extrusion coating. Suitable for extrusion coating are for example polyolefins such as polyethylenes or polypropylenes or materials containing polyvinyl chloride.
Film-forming masses also include coatings of hot-melt masses. These are for example at normal temperatures solid, viscoelastic or viscoplastic materials, preferably on the basis of resins, waxes, thermoplastics and elastomers, if desired with additions of fillers, anti-oxidants, lubricants and the like which, when warmed on passing through a thermoplastic range, change over to become highly fluid melts.
Forming the film on the packaging material using film-forming masses may also take place using chemically drying coatings. The chemical drying coatings contain cross-linked macromolecules which are obtained by chemical reactions, in particular by polymerization.
The film-forming masses may also be films, in particular low tear strength films or highly brittle films. The thickness of the films may be for example from 5 to 20 μm. Preferred films may contain polyolefins such as polyethylenes or polypropylenes, polyesters or polyamides. The films may be applied to the sides of the packaging material that becomes the inward facing or the outward facing side of the pouch or on both sides thereof; the adhesion of the film or films on the packaging material may be effected by laminate adhesives and/or bonding agents, if desired by additional corona, flame plasma or ozone treatment. For example, the film may exhibit sealing layers, in particular when used on the side of the pouch facing inwards. The film also then represents a sealing layer. The film may also be applied as a further film-forming mass over the print-coating on the packaging material.
If film-forming masses are applied to both the inward facing and the outward facing sides of the packaging material, then these may be the same or different.
The materials of the film-forming masses are usefully of no physiological consequence when used on packaging materials for foodstuffs.
Further examples of film-forming masses on packaging materials are sealing layers or sealing films, e.g. of polyolefins such as polyethylenes, which are deposited on the printing.
The film-forming mass is preferably situated on the side of the pouch facing outwards. The film-forming mass may also be deposited on the side of the pouch facing inwards. It may also represent e.g. the printing-ink or printing-color of an image printed in reverse. A further film-forming mass in the form of a sealing layer may be applied to the printing-ink or printing-color creating the reverse image. The packaging material may also contain a layer of film-forming mass for example a printing-ink or a printing-color on the side of the pouch facing outwards, and a sealing layer on the side of the pouch facing inwards.
The present invention also relates to a process for creating a pouch according to the present invention. The process may be carried out advantageously in such a manner that a weakness is provided in the flexible packaging material and the weakness is subsequently covered over by at least one film-forming mass.
As film-forming mass one may employ for example the above mentioned lacquers, varnishes, printing-inks, printing-colors, extrusion layers, hot-melt masses etc. The deposition of the film-forming masses may be performed for example by centrifuging, slinging, flooding, casting, rolling, spraying, brushing, printing, extruding etc. As a rule, in the case of flexible packaging materials, the process concerns endless strip material, for which reason coating methods such as application extrusion, spraying, rolling, printing or casting are particularly suitable.
In a particularly preferred process the packaging material is provided with a weakness in a printing plant and the printing subsequently carried out using a printing-ink or printing-color as film-forming mass. In this process the flexible packaging material is introduced into a printing machine for example a relief printing machine, intaglio printing machine, offset printing equipment, in particular a flexo-printing machine. Examples of printing machines are auxiliary printing machines, multi-drum; single drum, in-line, flexo and vario printing machines or combinations thereof such as for example flexo and intaglio printing machines. Usefully, the weakness is provided in the flexible packaging material using a cutting blade in the region of the printing facility, prior to the start of printing, or in the case of multi-drum machines in the region of the first drum. Following that, the flexible packaging material has the printing applied to it, in the course of which the weakness in the material is covered over and the film forming mass, i.e. the printing-ink closes off the weakness. The film forming mass is applied in such a manner for example that in the region of the weakness the overall thickness of film forming mass is thicker than on the rest of the packaging material. By means of register control it is possible to regulate the printing process exactly and, apart from achieving a clear printed image, the film forming mass can be applied exactly to the weakness and the region around it.
The pouches obtained from the packaging material may be employed for holding foodstuffs in powder to solid form. A preferred application is the packaging of bars of chocolate, starch-containing foodstuffs, foodstuffs containing fats, or foodstuff preparations in the form of mixtures of chocolate with foodstuffs containing starch and/or fats, all foodstuff preparations advantageously being in the form of bars.
The packaging of bars of chocolate and the like is preferred because, on tearing open the packaging, in this case the chocolate bar serves as the means for snapping the pouch open. If the pouch is made from tube-shaped material, the pouches exhibit transverse sealed seams at the ends or, if the pouch is made from flat material, the pouches exhibit a longitudinal sealed seam and at the ends a transverse sealed seam. The sealing of the seams may be performed by cold sealing, hot sealing or by adhesive bonding.
When packaging for example chocolate bars, the weakness is advantageously situated in one of the end regions of the pouch i.e. about 10 to 30 mm from the end of the pouch which is sealed off by means of a transverse seam. Especially preferred are tube-shaped pouches having a longitudinal sealed seam and transverse sealed seams at the ends. If the pouch is torn open along the weakness, then the tear propagates at maximum around the whole circumference of the pouch; the longitudinal seam prevents the tear propagating any further. The part of the pouch torn open remains attached at the longitudinal seam and the sealing thereof. The contents of the pouch can now be pushed out easily or eaten directly from the packaging; the piece of the pouch that has been torn open remains attached to the rest of the pouch at the longitudinal seam and can not form an individual part be disposed of separately and does not fall to the ground as litter.
As shown in FIG. 1, the packaging material 10, which has already been provided with the weakening and for example a cover layer over the weakening in the form of multi-colored printing, is rolled from a stock roll and transported to the packaging stage. The arrow 11 indicates the insertion of the contents which is accompanied continuously by the longitudinal sealing 12 and the transverse seaming 13, as a result of which a packaging unit 14 is created. A cutting device 15 divides the material into tube-shaped pouches 16 with transverse seams 17 and the longitudinal seam 19.
FIG. 2 shows the tube-shaped pouch 16. The longitudinal seam 19 is on the rear side and the pouch 16 is closed at both ends by transverse seams 17. Shown by a broken line is the weakness 18 which is situated in the region of one end of the pouch 16 and is covered over for example by one or more layers of a printing-ink.
FIGS. 3 and 4 show a further tube-shaped pouch 16 with transverse seams 17 at both ends and a longitudinal seam 19. In FIG. 4 the weakness 18, situated below the printed image created by printing-inks, is indicated by a broken line. If the package is subjected to tensile force for example by holding the package at the transverse seams 17 and pulling, then the package separates along the line of weakness 18 and by pulling and for example simultaneously snapping backwards, the film material tears further, usually along a line 20 which is indicated by broken lines in FIG. 3. The line 20 terminates at the longitudinal seam 19 as there is an accumulation or thickening of material due to folding and sealing. As a result, the pouch 16 is open around its periphery up to the region of the longitudinal seam 19 and the contents can be easily removed for example by pushing it out from one end. Both parts of the tube-shaped pouch 16 are held together by the longitudinal seam 19 and can then be disposed of together.
FIG. 5 shows the tube-shaped pouch 16 with transverse seams 17 and longitudinal seam 19 in the opened state. The part 27 of the pouch 16 which has been snapped back is joined to the rest of the pouch 16 by means of the packaging material at the longitudinal seam 19. The tearing action took place along the line of weakness 18 and continued along line 20 up to the longitudinal seam 19. The contents 26, for example a bar of chocolate can now be removed easily from the package or eaten directly from the package.
FIG. 6 shows a section through the packaging material 10 in the region of the weakness 18. The weakness 18 was made for example in a plastic film 21 and takes the form of a separation of the plastic film. The plastic film 21 on the outward facing side of the pouch bears a multi-layered, as a rule multi-colored--printed image having layers 23, 24 and 25. On creating the image an additional layer of printing-ink 24 (as a film forming mass) was deposited in the region of the weakness 18; as a result, the overall thickness of the printing-ink is increased over that in the rest of the packaging material 10, the weakness definitely covered over, sealed and tensile strength again restored in the packaging material 10. If desired, the sealing layer 22, in particular a sealing lacquer or varnish may be deposited on the inward facing side of the packaging material. The organic sealing layer 22 is employed mainly for sealing the seams; its properties can, however, reinforce the action of the organic printing material 23, 24, 25. The pouches coated with film-forming masses are preferably tube-shaped pouches.
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Pouches of flexible packaging material exhibit a tearing zone in the form of a weakness such as perforations or a separation in the material, this in order to be able to remove the contents easily. The packaging material is covered over by at least one film-forming mass, at least in the region of weakness, in order that the package remains closed until the contents are to be used. The film-forming mass may be the decorative printing on the pouch. After packaging, the contents are protected by the pouch and, in order to remove the contents, the pouch may be opened readily by a pulling or snapping movement which causes the covering of film-forming mass to break.
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BACKGROUND
The user capacity of mobile radio communication systems is limited by the width of the frequency spectrum available for signal transmission. In order to maximize a system's capacity, therefore, it is desirable to utilize the available frequency band in the most efficient manner possible.
Cellular telephone systems in operation today commonly use an access technique known as Frequency Division Multiple Access (FDMA) to permit a base station to communicate with a plurality of mobile stations. In FDMA systems, each communication link is allocated a unique frequency slot of channel in the radio spectrum.
Newer systems use Time Division Multiple Access (TDMA), in which a base station communicates with a plurality of mobiles on the same frequency channel by dividing up a time cycle into time slots. The European GSM standard is an example of a system using FDMA and TDMA to allocate both frequency and time slots to mobile calls. The system uses 200 KHz wide frequency slots in each of which a 4.6 mS transmission cycle is divided into eight, 560 uS time slots, with short guard periods between each.
The guard periods in GSM are provided because base station transmission during a time cycle is not held at a constant power for all time slots, but instead changes the power level for each time slot based on the distance of the mobile station using that time slot from the base station. Moreover, for transmissions which employ frequency hopping, wherein the frequency channel employed for each 4.6 mS time cycle changes, a guard period of zero transmission power is provided whenever power or frequency is changed discontinuously to avoid spectral splatter into other frequency channels.
Another example of a system employing both TDMA and FDMA is the US Telecommunications Industry Association standard IS54. The IS54 standard describes a system having 30 KHz wide time slots, in each of which a base station employs a 20 mS transmission cycle divided into three, 6.6 mS time slots with no guard period between. The base station transmission in this system is actually just a continuous transmission of time-multiplexed data to three mobile stations. There is no guard period provided in TIA IS54 because frequency hopping is not employed, on the contrary, the system anticipates that the power level will be the same in all time slots.
U.S. Pat. No. 4,866,710 to Schaeffer describes a method of allocating frequencies and time slots to mobile stations such that all the time slots on a given frequency are filled first before allocating time slots on another frequency. By packing mobile stations preferentially in this way, the transmitters and frequencies that have not as yet allocated time slots can be switched off completely, reducing interference. This would reduce wasted capacity in the IS54 system arising from the requirement that base stations continually transmit on all three time slots even when only one is needed. However, it will be noted that the base station still transmits at one maximum power level for each frequency in use, irrespective of the power needs of each particular mobile, resulting in a higher net level of interference than if the power needs of each mobile were taken into account.
SUMMARY
Accordingly, it is an object of the present invention to achieve reduction of interference by a more effective strategy that works even when all time slots are filled. Exemplary methods according to the present invention allocate mobile stations to time slots on the same frequency as other mobile stations requiring similar base station transmitter power levels. In this way, mobiles which are allocated time slots on a given frequency channel will likely lie at similar distances from the base station. The base station transmitter power can then be chosen to be just sufficient for the mobile station on that frequency that needs the greatest power level. This provides a greater power margin than needed for the other mobiles on that frequency, but nevertheless allows a lower base station power than if mobiles had been allocated time slots and frequencies without regard to power needs. Thus, each frequency channel will serve a group of mobiles with similar base power transmission needs, and the base power can be correspondingly reduced on each frequency channel so as to be just sufficient for good signal transmission for the group. The cumulative reductions in power on every channel, therefore, will significantly reduce interference in the system.
According to an exemplary embodiment of the present invention, when the first mobile link with a given base is set up, the base chooses a frequency and time slot containing minimum interference. Commands are then issued to the mobile station to adjust its power level to a level sufficient for good received signal quality at the base. The mobile station in turn reports signal strength or quality received from the base station and the base station chooses a power level sufficient to provide good signal quality at the mobile.
When a second mobile link with the same base is set up, the base estimates the power level to be transmitted to that mobile and allocates to the second mobile another time slot on the same frequency if the power level to be transmitted is close to that used for the first mobile. If the required power level is slightly higher than that for the first mobile, the base smoothly increases the power transmitted to the higher level. If the second mobile requires a power sufficiently lower than the first mobile, it is allocated a time slot on a second frequency. The base then adapts its power and commands the mobile power to appropriate levels to maintain adequate signal quality in both directions.
According to exemplary embodiments, when a new mobile link is to be established with a base station already having a plurality of ongoing communications, the base station first estimates the power level that is appropriate for transmitting to that mobile. This is compared to the power level of all ongoing transmissions on frequencies that have at least one empty time slot. The mobile is then allocated a time slot on that frequency where the transmission power is greater than but closest to the estimated power. If no existing transmitter is of high enough power, the highest power transmission is smoothly increased to the estimated requirement for the new mobile, and the new mobile allocated an unused time slot on that frequency.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing, and other, objects, features and advantages of the present invention will be more readily understood upon reading the following detailed description in conjunction with the drawings in which:
FIG. 1(a) shows an exemplary pattern of base station power requirements for each time slot on four frequencies;
FIG. 1(b) illustrates actual transmission power used by a conventional base station for each of the time slots of FIG. 1(a);
FIG. 2(a) shows a pattern of base station power requirements for a scheme in which all time slots on a given frequency are filled before allocating time slots on another frequency;
FIG. 2(b) illustrates actual transmission power used by a conventional base station for the time slots of FIG. 2(a);
FIG. 3(a) shows an exemplary pattern of base station power profiles for mobiles which are allocated to time slots and frequencies according to the present invention;
FIG. 3(b) illustrates base transmission power according to an exemplary embodiment of the present invention for the time slots illustrated in FIG. 3(a); and
FIG. 4 shows an exemplary network block diagram according to the present invention.
DETAILED DESCRIPTION
In order to fully appreciate systems and methods according to the present invention, a more detailed description of conventional systems will first be provided.
FIGS. 1 and 2 illustrate conventional allocation schemes whereby the base station transmits at maximum power to the mobiles, irrespective of their power requirements. In FIG. 1 (a), mobiles are assigned frequencies (F1-F4) and time slots (Ts1-Ts3) essentially at random. Regardless of the power level required for each mobile, the base station transmits at the same maximum power level on all time slots as seen in FIG. 1(b). FIG. 2(a) illustrates allocating frequency and time slots to new mobiles so as to concentrate the mobiles on as few frequencies as possible in order to eliminate transmission on other frequencies. Note that all of the time slots on frequencies F1 and F2 and two of the three time slots on F3 have been filled. It can be seen in FIG. 2(b), however, that all base stations having at least one active time slot transmit at the same maximum power level according to this conventional scheme while those that have no active time slot are switched off. Moreover, neither conventional allocation scheme adjusts the power level transmitted by the base to be commensurate with that required by the mobiles.
FIG. 3(a) shows mobiles having the same power requirements as used in FIGS. 1(a) and 2(a) being allocated to time slots (Ts) and frequencies (F) according to an exemplary embodiment of the present invention. Note that the three mobiles (1, 7 and 4) requiting the most power are allocated time slots on frequency F1, the next highest three mobiles (8, 2 and 5) are allocated on frequency F2 and the mobiles requiting the lowest base transmit power (6 and 3) are allocated to frequency F3, illustrating that many transmitters transmit at lower than maximum power while those that have no active time slots do not transmit at all. Although the number of transmitters which have been switched off (one) is the same as in FIG. 2(b), an additional benefit is obtained by operating those transmitters that are active at reduced power levels.
According to an exemplary embodiment of the present invention, when the first mobile link with a given base is set up, the base either chooses a frequency and time slot at random, or chooses the frequency and time slot containing minimum interference. Commands are issued to the mobile station over the air to adjust its power level to a level sufficient for good received signal quality at the base. According to one embodiment, this power level can be that which is just high enough to provide good received signal quality at the base. The mobile station reports signal strength or quality received from the base station and the base station chooses a power level sufficient to provide good signal quality at the mobile. Again, this power level may be that which is only just sufficient for this purpose.
When the second mobile link with the same base is set up, the base estimates the power level to be transmitted to that mobile and, if, for example, within the range 6 dB higher to 10 dB lower than that used for the first mobile, the base allocates to the second mobile another time slot on the same frequency as the first mobile, preferably the time slot containing the lowest level of interference. Note in this regard the similarity in power requirements for each mobile on each frequency channel F1, F2 and F3 in FIG. 3(a). If the required power for the second mobile link level is, for example, 0 to 6 dB higher than that for the first mobile, the base smoothly increases the power transmitted to the higher level. If the second mobile requires a power more than, for example, 10 dB lower, or 6 dB higher, than the first mobile, it is allocated a time slot on a second frequency, preferably the time slot which contains the minimum level of interference. The base then adapts its power and commands the mobile power to appropriate levels to just maintain adequate signal quality in both directions, as before.
When the third mobile link with the same base is set up, the base estimates the power it will need to transmit to the third mobile. Assuming the first two mobiles are already using the same frequency, if the third mobile requirement is within the range of, for example, 12 dB greater than the weaker of the first two mobiles to 12 dB lower than the stronger of the first two mobiles, the third mobile is allocated another time slot on the same frequency and power levels are adapted appropriately as before. Otherwise, the third mobile is allocated a time slot on another frequency, preferably that having the lowest level of interference.
When a new mobile link is to be established with a base station already having a plurality of ongoing communications, the base station first estimates the power level that is appropriate for transmitting to that mobile. This is compared to the power level of all ongoing transmissions on frequencies that have at least one empty time slot. The mobile is then allocated a time slot on that frequency for which the transmit power is greater than but closest to the estimated power. If no existing transmitter is of high enough power, the highest power transmission is smoothly increased to the estimated requirement for the new mobile, and the new mobile allocated an unused time slot on that frequency, preferably that containing the least interference. The transmit power levels are then adjusted appropriately as before. Similarly, the transmission power can be ramped down for frequencies in which a highest power time slot becomes idle after a connection serviced on that time slot becomes disconnected.
FIG. 4 shows an exemplary network block diagram according to the present invention. A mobile switching center (MSC) 40 is connected by landline or other communication links to a number of base station sites referenced by numerals 41,42. Each base station site contains a number of TDMA transmitters, receivers and antennas for communicating with mobile stations M. The operating frequencies of each transmitter and receiver may be fixed according to a so-called cell plan or frequency-reuse pattern, but are preferably programmable to any channel in the allocated frequency band. The base station site may also contain a base station controller 43. The optional base station controller can be provided when it is desired to separate the intelligence for implementing the current invention from those functions normally performed by the MSC. When the MSC 40 is able to perform the functions required, the base station controller 43 may simply be a concentrator to funnel communications between the transceivers and the MSC.
As a further option, an interference assessment receiver 44 can be used to provide information via the base station controller to assist in the allocation of frequency and time slots to mobiles. The interference assessment receiver can be a scanning receiver, spectrum analyzer or multichannel device adapted to determine the interference energy levels in each of the presently unused frequencies and time slots at that base station site. This can be supplemented by measurements from the traffic receivers in unused time slots on their own frequencies.
The base station normally also contains a calling channel transmitter and random access receiver 45. The calling channel transmitter broadcasts information about the status of the base station to mobiles that may wish to establish communication. The random access receiver receives transmission from mobiles attempting to establish communication, before a traffic channel is allocated to the mobile according to this exemplary embodiment of the present invention. In the IS54 system, the calling channel is presently a non-TDMA transmission employing continuous transmission on a special frequency. The random access receiver operates on a corresponding frequency 45 MHz lower. Calling channel broadcasts and random access take place using Manchester code frequency modulated data transmission as in the US AMPS cellular system. At a later date it is probable that a TDMA calling channel will be introduced, together with a TDMA random access channel. If the TDMA calling channel uses, for example, only one out of three time slots while traffic is transmitted in the other two, then traffic requiring full power should be assigned to the remaining time slots on the calling channel frequency which typically requires full power.
It will be appreciated that the functions of the MSC and the base station controller as described above can be implemented conveniently with the aid of one or more microprocessors or computers and appropriate software e.g., processor 46 in FIG. 4. The processor or computer receives data messages transmitted by mobile stations requesting call set up or, for already existing communications, reporting signal strength or quality levels received from the base station. The computer or processor also receives data from the base station receivers which provides information pertaining to the signal strength or quality received from the mobiles, as well as interference levels in unused time slots.
According to this exemplary embodiment of the present invention, the computer processes this data to determine an appropriate frequency and time slot for communicating with a given mobile station, and sends control signals to the chosen base station transmitter-receiver so that it expects the mobile signal. The computer generates a message for transmission to the mobile to command it to operate in the chosen frequency and time slot. Messages are also generated for transmission to the mobile to command it to adjust its power level according to the received signal strength or quality at the base station receiver. Similar control signals are also sent to the base station transmitter so as to control its power level to be, for example, the minimum necessary to maintain signal quality as reported by the mobile on that frequency receiving the lowest quality. Alternatively, the power level can be selected to be some margin higher than this minimum necessary power.
When a base station maintains a large number of ongoing conversations with a multiplicity of mobile stations, there can arise reasons to change the frequency and timeslot allocations between mobile stations even when no old calls are terminating and no new calls are being initiated. Due to mobile motion, a mobile previously requiring high power may now be satisfied by lower base station power or vice versa. A simple systematic means to reshuffle frequency and timeslot allocations is for the network to maintain a list of ongoing conversations sorted by order of signal strength received from the mobiles, or, more accurately, sorted in order of radio propagation loss between the base station and the mobiles. The radio propagation loss may be computed from a knowledge of the received signal strength and the power level the mobile was previously commanded to adopt. A second check on this value may be computed from a knowledge of the signal quality reported back by the mobile and the transmitter power the network is transmitting to it. All such information may be utilized and averaged over a period of a few seconds to obtain a smoothed estimate of propagation loss.
Using the sorted list, the network ensures to the best of its ability that the top three mobiles on the list are allocated timeslots on the highest power carrier frequency; the next three mobiles in the list are allocated timeslots on the next strongest carrier frequency and so forth. If a Digital Control Channel is in use and transmitted on the strongest carrier, then the top two mobiles in the list are allocated the same carrier, the next three the second strongest carrier and so-on. The network may, if required, swap two mobiles between two carriers to achieve this. For example, if the highest power mobile X on carrier B due to relative movement now has a higher power requirement than the lowest power mobile Y on a stronger carrier A, then X and Y are caused to change frequency and timeslot allocations by issuing them with hand-off commands. Such hand-offs within the same base station area are called "internal handovers", and are made purely to achieve a more optimum frequency/timeslot packing that minimizes created interference with neighboring bases.
It has already been indicated above that an exception to the packing rule may be desirable if there is a large dB difference (e.g., >10 dB) between the carrier power and that needed by a mobile next on the list. It may be desirable to allocate that mobile to a lower power carrier together with the next two mobiles below it in the list. This results in an apparently unnecessary higher power transmission on a timeslot that is not allocated, but this departure from the absolute tightest packing algorithm has the advantage that a few unoccupied timeslots are distributed throughout the signal strength range and are thus available for allocating to new calls without having first to disturb a large number of ongoing conversations. It can even be adopted as a deliberate strategy, to leave a "hole" every 15 dB or so of propagation loss range, depending on the loading of the system, in order more rapidly to be able to accommodate new calls. If because of this coarse power step between "holes", a mobile has to be allocated to a "hole" on a carrier that is unnecessary, this will be corrected by the systematic resorting procedure that takes place on a slower timescale. Such a continuous resorting procedure also handles the event of a mobile call terminating. In principle all mobiles below it in the power/propagation loss list can be moved up, resulting in the highest of three perhaps receiving an internal handover to the next highest power carrier. This does not however take place all at once necessarily but gradually. The rate of handovers can be restricted so that no mobile receives a handover more often than, for example, say once per ten seconds. If a mobile has received an internal handover or handoff within the last ten seconds for example, it is not allowed to be a candidate for a handoff until ten seconds have passed. When the strongest of three mobiles on the three timeslots on a given carrier terminates its call, the power of the carrier may of course be regulated down to the stronger of the two remaining, thus reducing created interference levels.
The above-described exemplary embodiments are intended to be illustrative in all respects, rather than restrictive, of the present invention. Thus the present invention is capable of many variations in detailed implementation that can be derived from the description contained herein by a person skilled in the art. All such variations and modifications are considered to be within the scope and spirit of the present invention as defined by the following claims.
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Radio communication systems employing time division multiple access (TDMA) on several frequency channels are disclosed. The base station transmitting powers can be reduced when communicating with nearby mobile stations while still permitting the base station to employ a constant transmitting power in all time slots. This can be accomplished by, for example, grouping mobile stations having similar transmit power requirements together and allocating such groups to time slots on a same frequency. In this way, the base station can transmit at a constant power for each time slot on a frequency and provide acceptable communication quality, but without unnecessarily wasting base station transmitter power by transmitting to mobile stations having widely divergent power requirements.
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I. FIELD OF THE INVENTION
[0001] The present invention relates generally to selecting a TV channel by inputting a name or call sign of the channel instead of its channel number.
II. BACKGROUND OF THE INVENTION
[0002] The present invention critically recognizes that it is easier for humans to remember the name of something instead of a number. For example, it is easy to remember the call letters “ABC” as a TV station name but not always what channel number it is associated with in the local channel lineup. This is especially true when visiting someone who lives in an area with a different channel lineup from one's own.
[0003] As understood herein, a TV or set-top box can provide an on-screen guide which the user can access to search for a particular channel. However, this is slower than being able to key in the call letters directly and tune right away.
SUMMARY OF THE INVENTION
[0004] A method includes receiving, at a TV, a signal from a wireless commander, and determining an alphabetic station identification from the signal. Metadata in incoming TV signals is accessed to determine a channel number associated with the station identification. Then, the TV is tuned to the channel number.
[0005] In some embodiments the metadata is accessed dynamically after receipt of the signal from the wireless commander. The wireless commander can be, e.g., a wireless telephone or a TV remote control. The station identification typically is alphanumeric in that it includes at least one letter, and the metadata that is accessed to correlate the station identification to a channel number can be program and system information protocol (PSIP) data.
[0006] In another aspect, a system includes a TV display and a processor associated with the TV display. A tuner is controllable by the processor to cause programming from a tuned-to channel number to be presented on the display. The processor receives user-generated signals and correlates the signals to a station call sign. The processor then correlates the call sign to a channel number using information received in TV programming.
[0007] In still another aspect, an apparatus for obviating the need for a viewer to remember a channel number of a desired station having an alphabetic identification includes a TV receiving a signal from a viewer-operated input device. The signal is input by manipulation of one or more number keys. A processor associated with the TV correlates the signal to a character string that typically includes one or more letters of an alphabet. The processor causes the TV to tune to a channel number understood by the processor to be the channel number of the desired station based on metadata contained in television programming.
[0008] The details of the present invention, both as to its structure and operation, can best be understood in reference to the accompanying drawings, in which like reference numerals refer to like parts, and in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a non-limiting block diagram of a system in accordance with present principles;
[0010] FIG. 2 is a plan view of a non-limiting remote control that can be used in accordance with present principles; and
[0011] FIG. 3 is a flow chart of logic that may be employed by the system of FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0012] Referring initially to FIG. 1 , a system is shown, generally designated 10 , which includes a television 12 defining a TV chassis 14 and receiving, through a TV tuner 16 from a cable or satellite or other source or sources 18 audio video TV programming. The tuner 16 may be contained in the set box described below.
[0013] The TV 12 typically includes a TV processor 20 accessing a tangible computer readable medium 22 . The tangible computer readable medium 22 may be established by, without limitation, solid state storage, optical or hard disk storage, etc. The medium 22 may store software executable by the TV processor 20 to, e.g., control a display driver 24 that drives a TV visual display 26 in accordance with one or more settings such as brightness, contrast, and the like that may be stored in, e.g., the medium 22 . The display 26 may be a flat panel matrix display, cathode ray tube, or other appropriate video display, and typically is associated with one or more audio speakers 27 . The medium 22 may also contain additional code including backend software executable by the TV processor 20 for various non-limiting tasks. One or more of the processors described herein may execute the logic below, which may be stored as computer code on one or more the computer readable media described herein.
[0014] In the non-limiting embodiment shown in FIG. 1 the TV 12 may receive programming from external components such as but not limited to a video disk player 28 such as a Blu-Ray or DVD player and a personal video recorder (PVR) 30 that can contain audio-video streams on a hard disk drive.
[0015] Additionally, the TV 12 can communicate via a network such as the Internet with a server 32 . To this end, the TV 12 preferably is Internet-enabled, although it is to be understood that the server 32 may be combined with the TV program source 18 when the source 18 is a remote entity accessible over a wide area network, in which case no modem need be provided, with the TV sending signals through a reverse link to the source 18 /server 32 .
[0016] In the non-limiting embodiment shown, the server 32 is separate from the source 18 and the TV 12 communicates with the server 32 through a set-back box (SBB) 34 . In some implementations a set-top box (STB) may be used, and the SBB/STB may itself include the tuner 16 or otherwise communicate with the source 18 .
[0017] In any case, the SBB 34 shown in FIG. 1 may include a SBB processor 36 and SBB computer readable medium 38 , The SBB 34 may also include a network interface such as but not limited to a modem 40 to communicate with the server 32 over the Internet. In other implementations the modem 40 may be incorporated into the TV chassis 14 .
[0018] A wireless remote control 42 can be provided to input commands such as the below-described station commands into the system 10 . The remote control 42 can be a conventional remote control or other portable hand-held device such as a wireless telephone upgraded with an IR transmitter for TVs to permit a viewer to tune to a TV channel in accordance with principles below.
[0019] FIG. 2 shows an example remote control that includes ten number keys 44 with each number key being associated with respective alphabetic letters. In the embodiment shown, the number keys 44 are associated with the same letters typically associated with the number keys of a telephone. Accordingly, it will readily be appreciated that pressing the number “3”, for instance, can represent the numeral “3” and can also represent any one of the letters “d”, “e”, “f”. Less preferably, the remote control 42 may bear keys dedicated exclusively to letters.
[0020] For the embodiment shown, a “Mode” key 46 is also presented on the remote control 42 . A viewer manipulates the mode key 46 to generate a signal indicating that the viewer is using the remote in a letter input mode, so that signals from the number keys 44 are interpreted by the TV to represent letters. The mode key 46 may be a special purpose key or it may be an existing key not normally used for TV input, e.g., a star key on a wireless telephone.
[0021] With this understanding in mind, attention is now drawn to FIG. 3 , showing logic that may be employed by one or more of the processors described above to obviate the need for a viewer to remember which channel number a desired station is on. At block 48 the TV acquires available TV stations using, e.g., a Gemstar guide or through program and system information protocol (PSIP) data provided by the broadcaster. Proceeding to block 50 , the call letters (which may also include symbols such as exclamation marks, which may be correlated to the numeral “1” on the keypad of the remote control) are correlated to sequences of number keys when a remote control such as the one shown in FIG. 2 is to be used that has only number keys. Thus, for instance, when a ten numeral keypad remote control 42 is to be used, “ABC” would be correlated to a number sequence “1”, “1”, “1”. Similarly, “ESPN”, assuming the remote control 42 shown in FIG. 2 is to be used, would be correlated to “3”, 7, “7”, “6”. If an available local station is determined to be an affiliate of a national network, the call sign of the local station may be correlated to both the number string representing the call sign and to the number string representing the call sign of the national network.
[0022] As understood herein, a viewer preferably has the option to input the channel number of a desired station directly or to input the call sign of a desired station, and to this end if the viewer wishes to alert the TV that the command is for the latter, the viewer first manipulates the “mode” key 46 shown in FIG. 2 . The “mode” key 46 may act as a toggle. When it is toggled to “call sign” input, as opposed to “channel number” input, a user interface can be displayed on the TV so indicating. For example, an icon in the channel display banner can be presented indicating “call sign input mode”.
[0023] Assuming the viewer has entered the call sign entry mode, at block 52 remote commands are received from the remote control 42 . The received string of commands from the number keys 44 are correlated at block 54 to the associated call sign letters. The channel number associated with the call sign letters is then determined at block 56 and the TV tuned to the channel at block 58 . As numbers are entered, a user interface is displayed to list a choice of matching channels in alphabetical order. The user at this point can select one of the choices using the cursor keys or continue entering additional numbers to narrow down the list until only one entry exists at which point the TV can automatically tune to that entry. If no channel numbers are correlated to the call sign, the viewer is so informed by, e.g., an error message or audio cue, and the TV remains tuned to the current channel.
[0024] In one implementation, a lookup table derived from, e.g., an electronic program guide (EPG) that associates station call signs with channel numbers can be accessed to undertake the function of block 56 , but more preferably the association is undertaken dynamically after receiving the command representing the call sign input mode or even after receiving the desired station call sign. In one implementation metadata in the received televised stream is used to determine which station call sign is associated with which local channel number. For example, in digital TV signals, program and system information protocol (PSIP) data can be accessed, which indicates, for the stream on a given channel number, the call sign of the associated station.
[0025] While the particular CHANNEL SELECTION BY NAME is herein shown and described in detail, it is to be understood that the subject matter which is encompassed by the present invention is limited only by the claims.
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A method to directly tune to a specific station. Each number of a TV remote control keypad represents certain letters. A viewer enters the number that corresponds to each letter of the call letters of a desired TV station, and the TV uses metadata such as program and system information protocol (PSIP) information in received programming streams to dynamically correlate the station name to a channel number and tune to the channel number.
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TECHNICAL FIELD
The present disclosure relates to an anti-theft device for a tailgate cable of a pickup truck.
BACKGROUND
Vehicles, such as pickup trucks, include a box having a bed, opposing longitudinal sidewalls, a headboard, and a tailgate. The tailgate is pivotally attached to the sidewalls and movable between an open position and a closed position. Latches are disposed on an upper portion of the tailgate to hold the tailgate in the closed position, and tension members are connected between the sidewalls and the tailgate to support the tailgate when in the open position. Tailgates are typically removable from the box to increase utility of the pickup truck. This makes it possible for a thief to steal the tailgate by disconnecting the cables and removing the tailgate from the box.
An increased emphasis on fuel efficiency has led to a desire for lightweight vehicle components, such as aluminum-alloy components. Aluminum alloys are typically lighter than steel alloys. Consequently, aluminum alloy tailgates are lighter making them easier to steal.
SUMMARY
According to one embodiment, a tailgate assembly of a truck includes an anchor on the truck and a cable attachable between the tailgate and the anchor. A clip of the cable defines an opening for receiving the anchor. A finger secures the clip to the anchor and is deflectable to allow disconnection of the clip and the anchor. A lock is disposed on the clip and is slidable between a blocking position that prevents deflection of the finger and a releasable position that allows deflection of the finger.
According to another embodiment, a tailgate assembly of a truck includes a tailgate attachable to the truck, an anchor on the truck, and a tension member attachable between the tailgate and the anchor. A clip is attached to an end of the tension member and defines an opening for receiving the anchor. A finger is attached to the clip and engages with the anchor. The finger is deflectable to allow disconnection of the clip and anchor. A lock assembly is movable on the clip between a blocking position and a releasable position. The lock assembly prevents deflection of the finger when in the blocking position and allows deflection of the finger when in the releasable position. The lock assembly is affixed to the clip in the blocking position by a locking element.
According to yet another embodiment, a tailgate cable for a truck includes a clip and an anti-theft device. The clip is connectable to a post on the truck and has a finger biased to engage the post to prevent disconnection of the clip and post. The finger is deflectable to disengage the post. The anti-theft device surrounds four sides of the clip to prevent displacement of the finger locking the clip to the post. A threaded fastener is receivable through the body and finger to locate the device.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a rear perspective view of a portion of a pickup truck.
FIG. 2 is a perspective view of a tailgate cable.
FIG. 3 is a zoomed-in perspective view of the tailgate cable connected to a cable post of the truck.
FIG. 4 is a perspective of the tailgate cable of FIG. 2 with an anti-theft device installed.
FIG. 5 is a top view of the tailgate cable with the anti-theft device in the blocking position.
FIG. 6 is a section view of FIG. 5 along cut line 5 - 5 .
FIG. 7 is a top view of the tailgate cable with the anti-theft device in a releasable position.
DETAILED DESCRIPTION
The illustrated embodiments are disclosed with reference to the drawings. However, it is to be understood that the disclosed embodiments are intended to be merely examples that may be embodied in various and alternative forms. The figures are not necessarily to scale and some features may be exaggerated or minimized to show details of particular components. The specific structural and functional details disclosed are not to be interpreted as limiting, but as a representative basis for teaching one skilled in the art how to practice the disclosed concepts.
Referring to FIGS. 1 , 2 , and 3 a pickup-truck 20 includes a box 22 having a pair of sidewalls 24 and a bed 26 . A tailgate 28 is pivotally attached to each of the sidewalls 24 at a rear end of the box 22 . The tailgate 28 includes an interior side 30 , an exterior side 32 , and a pair of sidewalls 34 . Each of the sidewalls 34 includes a pin that is received in a corresponding socket of one of the sidewalls 24 . The tailgate 28 pivots between an open position and a closed position along the pins and sleeves. Each tailgate sidewall 34 includes a latch 36 that cooperates with a corresponding locking post 38 connected to one of the sidewalls 24 . The latch 36 and the locking post 38 engage to secure the tailgate 28 in the closed position. The tailgate 28 also includes a handle cooperating with the latches 36 to disengage the latches 36 from the locking posts 38 allowing the tailgate 28 to be opened.
The tailgate 28 includes a pair of tension members 40 that support the tailgate 28 when in the open position. Each tension members 40 may be a cable, a chain, a rope, or links that either telescope or fold relative to each other. Each tension member 40 includes a fixed end 42 attached to one of the sidewalls 34 of the tailgate 28 , and a free end 44 that has a clip 46 . The clip 46 is attachable to a cable post or anchor 48 that is disposed on one of the sidewalls 24 . The clip 46 defines a slot 50 that may have a larger portion 52 and a smaller portion 54 . The cable post 48 includes a shank 58 and a head 60 that has a diameter larger than the shank. The larger portion 52 is sized to be larger than the head 60 allowing the clip 46 to be received on and off of the post 48 . The smaller portion 54 is sized to substantially match the size of the shank 58 . The head 60 is larger than the smaller portion 54 preventing detachment of the clip 46 and the post 48 when the post is located within the smaller portion 54 . The clip 46 also includes a finger 56 extending over a portion of the larger portion 52 . The finger 56 may be a flexible metal strip, such as a flat spring. A tip 57 of the finger 56 engages with the post 48 to hold the post in the smaller portion preventing disconnection of the clip 46 from the post 48 .
Tailgate 28 is removable from the box 22 . The first step in removing the tailgate 28 is to disconnect the cables 40 from the cable post 48 . To disconnect, the finger 56 is bent away from the clip 46 , the post 48 is slid into the larger portion 52 , and the post 48 is removed from the slot 50 . Next, the pins are removed from the sockets. In some vehicles, one of the sockets includes a half-moon cutout allowing one pin to be lifted from the socket. After one pin is free, the other pin is pulled out of its respective socket to remove the tailgate 28 .
The tailgate removal process is fairly straightforward and can be accomplished in a short amount of time. This makes the tailgate an easy target for theft. Traditionally, a main deterrent to tailgate theft was the bulk and weight of the tailgate. Modern pickup trucks often employ lighter-weight materials such as aluminum alloys and thinner-gauge steel. Tailgates made from these materials are significantly lighter than their traditional counterparts and are easier to steal.
Tailgate theft can be deterred by increasing the time and difficulty of removing the cable clips 46 from the cable posts 48 . Referring to FIGS. 4 , 5 , 6 , and 7 , an anti-theft device or locking assembly 66 may be installed onto one or more of the clips 46 to prevent the finger 56 from deflecting, which prevents removal of the clip 46 from the post 48 . The anti-theft device 66 includes a sleeve 67 having a top 68 , a bottom 70 , and a pair of sidewalls 72 . The top, bottom, and sidewalls cooperate to define an interior 74 . The anti-theft device 66 can be installed by disconnecting the clip 46 from the post 48 and sliding the device 66 over the end of the clip 46 placing a portion of the clip is within the interior 74 . The top 68 or bottom 70 is adjacent to the finger 56 and can prevent deflection of the finger 56 depending upon the location of the device 66 relative to the clip 46 . For example, the finger 56 cannot be deflected when the anti-theft device 66 is located in a blocking position 78 , and can be deflected when the device 66 is slid to a releasable position 79 . The releasable position 79 may be any position outside of the blocking position—such as at or near the base 76 of the clip 46 . The blocking position 78 may be a range of positions located at the outer half of the finger 56 . A removable fastener 80 , such as a screw or bolt, is used to secure the anti-theft device 66 in the blocking position 78 . The screw 80 may be received within a threaded hole 82 defined in the top 68 or bottom 70 of the anti-theft device 66 and within a hole 84 defined in the finger 56 .
The tailgate anti-theft device 66 is designed to be removable without destroying any part of the device. Many pickup-truck users periodically remove the tailgate 28 to increase utility and functionality of the box 22 . Thus, a balance must be struck between theft deterrence and removability. If the anti-theft device 66 is too difficult to remove it may annoy authorized users when they wish to remove the tailgate 28 . This may cause the users to cease using the anti-theft device 66 rendering the tailgate more prone to theft. If the anti-theft device is not designed to be removed, the utility of the pickup truck is diminished.
The anti-theft device 66 is designed to increase tailgate removal time while still being removable using simple tools—such as a screwdriver, a hex wrench, a socket, etc. Even a slight increase in removal time may deter theft. As such, a permanent locking device may not be need or desirable.
A tailgate cable equipped with the anti-theft device 66 is removed by first removing the removable fastener 80 from the finger 56 . Next, the device 66 is slid towards the clip base 76 . The finger 56 is now deflected away from the clip 46 . With the finger deflected, the cable post 48 is slid from the smaller portion 54 to the larger portion 52 , and the post 48 is removed from the slot 50 of the clip 46 .
The embodiments described above are specific examples that do not describe all possible forms of the disclosure. The features of the illustrated embodiments may be combined to form further embodiments of the disclosed concepts. The words used in the specification are words of description rather than limitation. The scope of the following claims is broader than the specifically disclosed embodiments and also includes modifications of the illustrated embodiments.
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A tailgate assembly of a truck includes an anchor on the truck and a cable attachable between the tailgate and the anchor. A clip of the cable defines an opening for receiving the anchor. A finger secures the clip to the anchor and is deflectable to allow disconnection of the clip and the anchor. A lock is disposed on the clip and is slidable between a blocking position that prevents deflection of the finger and a releasable position that allows deflection of the finger.
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TECHNICAL FIELD
The present invention relates to control systems and methods for vehicles utilizing a hybrid powertrain, such as a modular hybrid transmission configuration with a traction motor between an engine and a transmission having a torque converter.
BACKGROUND
Conventional automatic vehicles may include a transmission having a torque converter to provide a hydrodynamic coupling with torque multiplication. The hydrodynamic coupling allows the engine to continue running while connected to the transmission when the vehicle is stationary. In addition, the torque converter provides torque multiplication to assist vehicle launch and provides damping of driveline torque disturbances. The torque multiplication or torque ratio varies with the speed difference or slip between the torque converter input element (impeller) and output element (turbine). A torque converter clutch or bypass clutch may be provided to mechanically or frictionally couple the impeller and the turbine to eliminate the slip and associated losses to improve efficiency. However, driveline torque disturbances are then more easily transmitted to the vehicle cabin and may result in noise, vibration, and harshness (NVH) and reduce vehicle driveability. As such, the torque converter bypass clutch is usually disengaged or released when the vehicle operating conditions are likely to produce driveline torque disturbances.
Various hybrid vehicle configurations have been developed that utilize both an engine and a motor to drive a vehicle through a transmission, which may be implemented by various types of transmissions that may or may not include a torque converter depending on the particular application. For example, a continuously variable transmission (CVT) or automated manual transmission (AMT) may not include a torque converter whereas a step-ratio automatic transmission having a torque converter may be used to provide similar advantages as in a conventional powertrain as previously described.
Hybrid vehicles generally include an electrical drive mode where the motor is used to power the vehicle and the engine is off. Applications having a torque converter bypass clutch may engage or lock the bypass clutch in the electrical drive mode to improve efficiency. Another hybrid vehicle operation mode uses both the engine and the motor to power the vehicle. A rolling engine start may be used when the vehicle is moving to transition from the electrical drive mode to the hybrid drive mode. The bypass clutch is typically disengaged during engine start to mitigate associated driveline torque disturbances. However, this reduces efficiency as previously described. As a rolling engine start event happens, the traditional control approach does not address the complexity of the power transition and its impact on the driveability.
SUMMARY
Embodiments according to the present disclosure include systems and methods for controlling a hybrid vehicle having a traction motor disposed between an engine and a transmission having a torque converter including an impeller and a turbine. In one embodiment, a method for controlling a hybrid vehicle includes controlling slip speed between the impeller and the turbine of the torque converter to maintain turbine torque substantially constant during starting of the engine.
In one embodiment, a method for controlling a hybrid vehicle having an engine selectively coupled by a disconnect clutch to a traction motor coupled to an automatic transmission having a torque converter with an impeller, a turbine, and a torque converter clutch, includes operating the vehicle to provide a driver demanded torque in an electric drive mode using only the traction motor with the disconnect clutch disengaged and the torque converter clutch locked with zero slip speed between the impeller and the turbine; engaging the disconnect clutch to start the engine using traction motor torque; controlling torque converter clutch apply pressure to control the slip speed and provide an associated converter torque ratio that maintains a substantially constant turbine torque to compensate for the traction motor torque used while starting the engine; controlling torque converter clutch apply pressure to control the slip speed and provide an associated converter torque ratio based on a combined engine torque and traction motor torque to provide the driver demanded torque after starting the engine; and controlling torque converter clutch apply pressure to lock the torque converter clutch and reduce the slip speed to zero after starting the engine.
Embodiments may also include a hybrid electric vehicle having an engine, an automatic transmission including a torque converter with an impeller, a turbine, and a bypass clutch, a traction motor coupled to the impeller and selectively coupled to the engine by a disconnect clutch, and a controller configured to control the bypass clutch to vary a speed difference between the impeller and the turbine to maintain turbine torque substantially constant while starting the engine using traction motor torque. In one embodiment, the controller is configured to control the bypass clutch to provide a desired converter torque ratio based on the speed difference, with the desired converter torque ratio being based on a driver demanded torque, current transmission gear ratio, transmission losses, and traction motor torque used to start the engine. In one embodiment, the controller is configured to modulate apply pressure of the bypass clutch to control the speed difference between the impeller and the turbine. The controller may also be configured to lock the bypass clutch to reduce the speed difference to zero after starting the engine. In various embodiments, the controller is configured to increase the speed difference while starting the engine by reducing the apply pressure of the bypass clutch.
The present invention resolves various challenges associated with prior engine start strategies by providing a modular hybrid transmission (MHT) configuration and a control system in a production hybrid vehicle. The modular hybrid transmission configuration includes an automatic transmission having a torque converter that couples input from one or both driving sources, in the form of an engine and a motor, to the transmission as determined by a powertrain controller.
In a modular hybrid transmission vehicle, that emphasizes both fuel economy and driveability, the control systems operate the engine, the motor, and clutches including the torque converter bypass clutch so that the driver feels that the vehicle operates smoothly and effectively in response to drive demands and to reduce noise, vibration and harshness (NVH) often attendant to mechanically connected driveline parts.
In one embodiment of the present invention, the transmission output may be coupled to a rear driveline including a geared differential. Such systems may require greater torque handling capacity than previously known front wheel drive hybrid vehicles. The powertrain controller includes computer-based processing of data, analyzing of sensed signals, and providing actuator signals. When fuel economy is emphasized by the powertrain controller, the torque converter is locked under most conditions, but unlocks to a controlled slip mode upon demand, and is controlled in accordance with a control algorithm to dampen driveline torque disturbances during engine starting while improving energy efficiency.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention may be more clearly understood by reference to the following detailed description of a preferred embodiment, when read in conjunction with the accompanying drawing figures, in which like reference characters refer to like parts throughout the views, and in which:
FIG. 1 is a diagrammatic view of a hybrid vehicle driveline with a modular hybrid transmission incorporating a control system operation according to the present invention; and
FIG. 2 is a flow chart of the control algorithm operating a driveline control according to a preferred embodiment of the present invention.
DETAILED DESCRIPTION
As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention that may be embodied in various and alternative forms. The figures are not necessarily to scale; some features may be exaggerated or minimized to show details of particular components. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present invention.
Referring first to FIG. 1 , a vehicle 10 is shown comprising a hybrid driveline 12 with a first power source in the form of internal combustion engine 14 and a second power source in the form of a battery 16 that powers a traction motor 18 . One or more of the power sources may be coupled together and disengaged from each other in the driveline by means of a disconnect clutch 20 . The disconnect clutch 20 may also be used to rotate the input shaft of the motor 18 by the clutch 20 so that operation of the engine 14 serves to charge the battery 16 as the motor 18 acts as a generator.
In the present embodiment, the disconnect clutch 20 disconnects the motor 18 and the engine 14 in the electrical drive mode whereby only the motor 18 is available to power the driveline. In the hybrid drive mode, the disconnect clutch 20 couples the engine 14 with the motor 18 when a rolling engine start command is generated from the powertrain controller 40 . The powertrain controller 40 generates a response when the need for more drive demand or the system demand is sensed. For example, a driver's manipulation of the actuator 42 , or the sensing of system demand, such as insufficient motor support for a demand due to the status of the battery 16 (that may include battery state of charge or SOC), may generate such a response.
The engine 14 and the motor 18 have an output coupled to a transmission mechanism 24 through the torque converter 26 . In the preferred embodiment, a modular hybrid transmission (MHT) 22 includes mechanical and hydraulic controls for a system of multiple, stepped ratio gears arranged for multiple forward speeds, reverse speed and a neutral position. In addition, MHT 22 includes a torque converter 26 . The torque converter 26 includes an impeller, and a turbine that rotates in response to fluid flow from the impeller to the turbine. A bypass clutch 27 provides a frictional coupling between the impeller and turbine of torque converter 26 and is controlled by the powertrain controller 40 .
The bypass clutch 27 manages fluid pressure between the impeller and turbine of the torque converter to provide three modes of bypass clutch operation, and torque multiplication may occur depending on the amount of slip between the impeller and turbine sides. In open mode, a maximum amount of fluid is carried by the torque converter housing, separating the impeller from the turbine. In a locked mode, the minimum fluid pressure is carried in the torque converter so the pressure does not separate the impeller from the turbine and they become frictionally or mechanically locked together to eliminate slip and associated losses to improve energy efficiency. In a slip mode, a target amount of slip may be employed between the impeller and the turbine, whereby the fluid may provide the target torque ratio for the torque multiplication, in addition to NVH damping, but fuel economy is reduced due to the heat generated as a result of a slipping.
At the rear portion of the driveline, a drive shaft output 28 is linked to a differential 30 in the well-known manner of engine powered production vehicle systems, and in turn drives both of the rear wheels 32 .
In accordance with a control system of one embodiment of the present invention, a powertrain controller 40 can include a distributed or consolidated set of operating systems including an engine control module (ECM), a transmission control module (TCM) and a vehicle systems controller (VSC), for example. In the representative embodiment illustrated, an input demand actuator 42 , such as an accelerator pedal, is linked either electronically, mechanically or by other systems to the powertrain controller 40 . In particular, the actuator 42 permits the driver to control powertrain power to the vehicle and governs performance of the vehicle. The present invention improves driveability, the driveline's ability to react with reduced noise, vibration or harshness (NVH) that may be perceived by the driver and affect the driver's sense of complete and accurate control of the numerous operations being conducted throughout the drivetrain 12 including a modular hybrid transmission with control methods of the present invention.
In a typical electrical drive mode at a higher selected stepped ratio transmission gear number (or lower gear ratio), a torque converter bypass clutch 27 is normally fully locked to improve the fuel economy. As a result, driveline torque disturbances resulting in noise, vibration and harshness may be felt as the engine 14 starts in a rolling start as the powertrain controller 40 reacts to the drive demand or the system demand and commands the power transition from the motor 18 only to the engine 14 or a combination of both the motor 18 and the engine 14 . According to various embodiments of the present invention, the bypass clutch 27 is controlled to set torque converter 26 in a controlled slip mode around a target slip during the rolling engine start event. This target slip will generate a speed differential between the impeller and turbine to provide a corresponding target converter torque ratio for the torque multiplication to adjust delivered torque towards a desired torque resulting from the torque demanded at the transmission output shaft, and compensating for the loss of the electrical motor torque due to the amount of torque used to assist in the quick rolling engine start ( 58 , FIG. 2 ). While in the controlled slip mode, the torque converter 26 provides damping of torque disturbances to reduce or eliminate any noise, vibration and harshness from engine start and power transition. In addition, controlled slip operation improves energy (battery and fuel) efficiency relative to completely disengaging the bypass clutch 27 .
Due to the nature of the two power sources of a conventional combustion engine 16 , and battery 18 powering electrical motor 20 , in the vehicle 10 , the driveability is a concern associated with the transition from one power source to the other power source. In a typical electrical drive mode, the vehicle is moving with a certain torque demand only supplied by the electrical motor 20 powered by the battery 18 with the torque converter 26 in locked mode to improve the fuel economy. When there is a need for engine power, the engine 14 has to quickly start and become a power source. During this rolling engine start event, the driveline 12 has to maintain substantially the same wheel torque while in the meantime robustly and quickly starting the engine 14 , and seamlessly completing the power transition through the driveline from one to the other, or combining both, power sources. In order to improve the driveability, the improvement is to control the torque converter 26 's slip speed and associated target torque ratio by operation of the bypass clutch 27 in the slip mode such that the torque converter 26 of the MHT 22 is used to maintain the wheel torque (and associated turbine torque) substantially constant while damping the noise, vibration and harshness during the power transition.
In contrast to various prior art control strategies that start the engine with the bypass clutch locked, or fully disengaged, when transitioning from electric mode to hybrid mode, embodiments of the present invention provide a controlled slip mode to reduce driveline torque disturbances while improving efficiency. Torque converter 26 is controlled by controlling the bypass clutch 27 in slip mode, with the target torque ratio calculated as discussed below. The converter torque ratio is controlled by controlling bypass clutch apply pressure to adjust the delivered torque towards the desired torque, which may be based on the driver demand as indicated by the accelerator pedal, or in response to a system demand, such as when the motor cannot produce enough power due to the status of the battery. Controlling or managing the target torque ratio of the torque converter 26 compensates for the loss of the electrical motor torque due to the motor assisting in the quick rolling engine start event. While in the slip mode, the torque converter 26 damps the noise, vibration and harshness from engine start and power transition.
The process of control according to a representative embodiment is more clearly illustrated in FIG. 2 . The terminologies and equations to calculate a hybrid desired torque ratio and associated slip speed for a representative operating scenario are described below. For example, when the actuator 42 is depressed by a driver as more vehicle torque is demanded (see step 54 ), from electrical drive mode steady state shown at 50 with the locked torque converter at 52 , the powertrain controller 40 analyzes the drive demand and may request an engine rolling start as represented at 54 . Then the powertrain controller calculates the requested turbine torque in response to the drive demand, adjusting for the transmission inefficiency losses, as indicated in the following equation:
Tq_TurbineRequested = ( Tq_TransOutDemand + Tq_TransOutLoss ) GearRatio ( Gear ) - TransLossRatio 1 )
The torque converter is then operated in slip mode as shown at 56 to maintain a substantially constant turbine torque by controlling apply pressure of the bypass clutch to control the slip, speed ratio, and torque ratio of the torque converter as illustrated in the following equations. By hydraulic design, the torque converter torque ratio is associated with the speed ratio and the speed ratio or slip speed is controlled by modulation of the bypass clutch apply pressure. Therefore, by controlling the torque converter target slip, the torque converter torque ratio can be adjusted to maintain a substantially constant turbine torque while using the motor torque to assist with starting the engine.
[1] In one embodiment, a target slip speed, speed ratio, and torque ratio are determined according to the following equations:
Converter_TargetSlip = Spd_Impeller - Spd_turbine .
Converter_TargetSpdRatio = Spd_Turbine Spd_Impeller = Spd_Impeller - Converter_TargetSlip Spd_Impeller
Converter_TargetTqRatio = f TransConverterRatio ( Converter_TargetSpdRatio ) , 2 )
The desired impeller torque is directly related to the requested turbine torque and the torque converter torque ratio, in addition to transmission pumping inefficiency losses, as illustrated by the following equation:
Tq _Impeller Desired= Tq _TurbineRequested÷Converter_Target Tq Ratio+Tq_TransPumpLoss 3)
As one of ordinary skill in the art will recognize, during the rolling engine start, the delivered impeller torque is the delivered motor torque, which is offset by the amount of torque used to assist in the engine start, as illustrated by the following equation:
Tq _ImpellerDelivered= Tq _MotorDelivered− Tq _EngineStart_Assist 4)
After the completion of the rolling engine start, the delivered impeller torque is the sum of the delivered engine torque and the delivered motor torque, as illustrated by the following equation:
Tq _ImpellerDelivered= Tq _EngineDelivered+ Tq _MotorDelivered 5)
Through controlling the bypass clutch and slip speed to make the torque converter generate the target torque ratio, the delivered impeller torque should generate the desired turbine torque based on the torque ratio of the converter before, during, and after the rolling engine start as illustrated by the following equations:
Tq _ImpellerDelivered= Tq _Impeller Desired; therefore
Converter_Target Tq Ratio= Tq _TurbineRequested÷( Tq _ImpellerDelivered− Tq _TransPumpLoss) 6)
When the engine start is completed, the disconnect clutch 20 may be fully engaged or locked to frictionally or mechanically link the engine 14 with the motor 18 , the vehicle will drive in the hybrid drive mode combining engine and motor torque.
As such, various embodiments of the present invention control the bypass clutch 27 to operate the torque converter 26 in a controlled slip mode ( 56 ). Appropriate control of the bypass clutch to control slip to a target slip (target slip ratio) regulates the associated converter torque ratio which can be used to adjust the delivered torque towards the desired torque at the impeller and turbine. At the same time, the slipping torque converter 26 is a very good damping device to reduce the vibration and harshness from engine start and power transition. After the rolling engine start, the power source may change to the engine 14 as needed, or the combination of both the engine and the electrical motor. In order to improve the fuel economy, the controller will lock the torque converter ( 68 FIG. 2 ) once the demand has been met, as further economy may be realized by adjusting the engine torque and the motor torque contribution to the total powertrain torque.
While exemplary embodiments are described above, it is not intended that these embodiments describe all possible forms of the invention. Rather, the words used in the specification are words of description rather than limitation, and it is understood that various changes may be made without departing from the spirit and scope of the invention. Additionally, the features of various implementing embodiments may be combined to form further embodiments of the invention.
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A system and method for controlling a hybrid vehicle including a transmission having a torque converter with a bypass clutch include controlling the slip between the impeller and the turbine of the torque converter in slip mode operation to regulate the converter torque ratio and maintain substantially constant torque at the turbine. Controlled slip uses the hydrodynamic coupling of the torque converter to balance the desired and delivered torque while damping torque disturbances transmitted through the driveline to manage noise, vibration and harshness (NVH).
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FIELD OF THE INVENTION
[0001] The present invention relates to a downhole shut-in device for testing pressure variation in gas lift wells. These wells require high pressure gas injection in order to decrease the hydrostatic column weight, since without pressure power oil ceases flowing. Thus, this downhole shut-in device, object of the invention, is capable of testing pressure variation in gas lift wells. Currently it has no precedent in the national and international market. This invention is used in the area of field exploitation.
BACKGROUND OF THE INVENTION
[0002] According to the history of the country's hydrocarbon production, in recent years we have observed that oil production has been declining. To stop this we require development and/or improvement of current techniques specifically focused on oil extraction. Exploitation of mature fields or low pressure ones requires generating strategies to incorporate new technologies and design scenarios, planning, operation, maintenance, monitoring, control and optimization of production systems throughout the production life. Therefore, there is the need for the use of advanced technologies for the acquisition of downhole information. One technique for acquiring such information is the pressure variation testing.
[0003] Pressure variation tests are to generate and record pressure variation downhole of one or more wells for a period of time. These downhole pressure variations are generated by modifying injection or production conditions of the wells.
[0004] The purpose of testing pressure variations is to obtain characteristic information from the fluid-rock system (petrophysical properties of the reservoir). From the pressure variations recorded, we can obtain the dynamic characterization of the reservoir in order to establish the optimum exploitation system.
[0005] Techniques for generating pressure disturbance are based primarily on surface operations such as opening and /or closing the well, fluid injection, variation in throttle, etc. The echometer is the device that collects information in this type of operation. When performing these surface operations there arise technical-mechanic issues, undesired physical phenomena, impacts to surface facilities, among others. These problems affect the quality of information and cannot be filtered by the echometer, reducing then the reliability of the same. The shortcomings of the echometer are that production rigging must not present accessories that alter the behavior of the sound wave, and it is only applied in liquid wells.
[0006] Therefore, the Systems and Tools for Information Acquisition from Wells (SHAIP for its acronym in Spanish) group of the Instituto Mexicano del Petróleo (Mexican Petroleum Institute), set itself the task of developing a device that can generate pressure disturbances inside a gas injection well comprising the following characteristics: installation close to the producing reservoir; use in wells with gas present; diminishing or eliminating storage effects of the well with short times of interruption of production; not being affected by rigging accessories of production; and that the recorded information be reliable. Based on these characteristics, we obtain the downhole shut-in device for pressure variation testing in gas lift wells.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] In order to provide a clear and accurate description of the functionality of the downhole shut-in device of the present invention, reference is made to the accompanying figures.
[0008] FIG. 1 shows the general components of the downhole shut-in device for pressure variation testing in gas lift wells.
[0009] FIG. 2 shows the typical curve obtained by processing the information retrieved from the downhole shut-in device.
[0010] FIG. 3 shows the plotted results of the pressure variation test obtained in Well Coyotes 461 of PEMEX.
DETAILED DESCRIPTION OF THE INVENTION
[0011] Below is a detailed description of our invention, for which reference is made to the accompanying descriptive figures.
[0012] FIG. 1 shows the device, object of the invention, which is constituted by a retaining pressure check valve with variable opening ( 1 ), which permits passage of the flow in the reservoir; an anchoring system ( 2 ) that installs the device inside the production tubing, a sealing system ( 3 ) which serves to seal the wellbore; untethering system ( 4 ), to retrieve the device, a shock absorber ( 5 ), which has the function of dissipating the energy generated by shock and vibration in the device body, through all stages of the operation, which can damage the memory probe set pressure and temperature, and a jacket for the memory probes ( 6 ) to prevent loss of information because the operating conditions in the reservoir, avoiding also damages to probe circuitry. This downhole shut-in device for testing pressure variation in gas lift wells is placed downstream of the operation valve, just at the lower end of the production tubing, and is mainly used to generate pressure variations in gas lift wells through a pressure check valve with variable opening, which allows only the flow from below upwards of the closing equipment and opens when the differential pressure (lower initial pressure and higher flow pressure) is greater on magnitude than the calibration pressure of the valve after opening the well and injecting the gas for pneumatic pumping.
[0013] The present invention is based on the principle of downhole shut-in of oil producing wells that do not flow to the surface self-powered, but require the injection of gas to lighten the fluid column and thus enable the well to produce. At the beginning, only the fluids into the production tubing will be moved with pneumatic gas injection pumping until the differential pressure between the inferior initial pressure (P 1 initial) and the superior pressure due to flow (P 2 flow) is greater on magnitude than the calibration pressure of the valve (P 3 spring), the pressure check valve with variable opening ( FIG. 1 ) which will open and begin the drawdown pressure stage in downhole ( FIG. 2 ).
P 3 Spring<PInitial−P 2 Flow
[0014] After closing the well and stopping the pneumatic gas injection pumping, the downhole pressure will seek to achieve the pressure P 1 initial and the flow will increase to fulfill the following inequality for the check valve closure:
[0000] P 3 spring< P 1 flow− P 2 flow
[0015] Once the valve is closed, downhole pressure increment will start due to the reservoir response without the effects of the fluid stored in the well ( FIG. 2 ).
[0016] The present invention operates by downhole shut-in to minimize storage effect within the well and duration of the variation pressure tests.
Operation of the Parts Constituting the Invention
[0000]
1. Check Valve:
[0018] Non-return or check valve with variable opening that will isolate the bottom of the well as this area does not have a high enough pressure to overcome the pressure of the upper zone; it has a fluid homogeneous inlet and outlet according to the fluid composition, flow velocity and downhole pressure when well is flowing. At the top has a fishing neck, which is designed to work with JDC type pulling tool.
2. Anchorage System:
[0020] Bidirectional anchoring system comprises four lower jaws and three upper ones that allow the device to be placed on any free area of the production tubing. The system is activated by falling impacts.
3. Seal System:
[0022] This system comprises three seals made of high-strength polymer to the temperature and chemical attack. These seals insulate the top of the lower zone of the well to ensure the flow path through the interior of the device. Actuation occurs when the falling impacts activate the anchoring system, whereupon compression occurs on the seals, so that they reduce theft length and increase theft diameter.
4. Untethering System:
[0024] Untethering system comprises bolts made of high tensile strength but low shear strength. Its function is to maintain the anchorage of the tool until the time to be retrieved upon.
5. Shock Absorber:
[0026] The shock absorber has the function of dissipating the energy generated by shock and vibrations in the body of the device during all stages of the operation, which can damage the memory probe set. Its principle is based on the combination of the spring-damper.
6. Probes Jackets,
[0028] Produced in high strength steel, they will have the purpose of protecting memory probes from any impact effects occurring during development of the device operation.
EXAMPLES
Application in Well Coyotes 461 PEMEX.
[0029] The results obtained in the pressure variation test in Well Coyotes 461 made with the “downhole shut-in device for testing pressure variation in aft lift wells IMP” and high resolution memory probes at 955 m depth are presented. The shut-in period was carried out with downhole shut-in, allowing a clear definition of the response of a hydraulically fractured well and we were able to identify the different flow periods in a Reservoir-Hydraulic Fracture-Well system.
[0030] Well Coyotes-461 produces at an interval of 993 to 1040 m, that belongs to the body of sand Sim — 50, of Chicontepec formation. The well is located in the central part of the field Coyotes. It is located NW of Paleocanal Chicontepec within the study area called Sector 3.
[0031] Analysis determined that the well has a finite conductivity fracture with a length of 88 m, which represent 61% of the programmed (144 m) and a conductivity of 10.4×10 −3 Darcy/ft which is well below of estimated (2855 mD-ft) by Byron Jackson Company (BJ).
[0032] The well was producing with a rate of 16-20 bpd and a head pressure of 4-6 kg/cm2. Based on this, we asked the production area of Activo Cerro Azul, belonging to Poza Rica-Altamira, a portable separator installed to measure the volume of gas and liquid before closing the well, With the well closed, and using slickline the well was calibrated with a printing block of 2 5/16 going down “free” to 1060 m, subsequently the accessory “collar stop” was descended and anchored at 960 m.
[0033] Two pressure and temperature high resolution probes were programmed and the device of downhole shut-in was assembled with check valve and the two probes connected to their respective battery. The trial period took place after starting the pneumatic gas injection pumping, producing gas and liquid toward liquids dam and subsequently carry it to portable separator for measurement.
[0034] Once the probe was retrieved and pressure information obtained, we proceeded to perform the analysis. FIG. 3 shows the total time spent on the test of pressure variation (pressure trend, pressure increase curve and decrease curve). The buildup test shows a trend fairly good, almost perfect, without distortion or abnormalities during development. This is because the downhole shut-in was effective and there was no leakage through the seals and the interior of the check valve calibrated to ⅓ of downhole pressure. The literature mentions that the buildup curves are the most representative due to full control of the flow rate because the well is closed, so that the flow rate is zero as long as there are no leaks.
From This Test it was Concluded That:
[0035] A.) The drawdown pressure was successfully performed by the lightening of the hydrostatic column, through the gas injection through the annular space and the corresponding opening of the check valve calibrated previously
[0036] B) The shut-in downhole, which was conducted stopping the gas injection through the annular space and the corresponding closure of the precalibrated check valve. Through buildup test, which allowed reducing storage effects, it have gotten a clear definition of the response of a finite conductivity in a “Reservoir-hydraulic fracture-Well” system.
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The device is based on the principle of downhole shut-in of oil producing wells that do not flow to surface self-powered but require the injection of gas to lighten the fluid column and thus enable the well to produce. This downhole shut-in device comprises a check valve, an anchoring system, a seal system; an untethering system, a shock absorber and a sleeve for the protection of pressure and temperature memory probes.
The objective of the downhole shut-in device is to obtain characteristic information of the fluid-rock system from variations in the pressures recorded in order to obtain the dynamic characterization of the reservoir.
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This invention was made in the course of work under Contract No. 4-37067 between the Babcock and Wilcox Co. and the U.S. Department of Commerce. The Government is licensed under and, on the occurence of a condition precedent set out in the contract, shall acquire title to this application and any resulting patent.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to nuclear reactor pressure vessel supports and, more particularly, to a link and pin support system that provides primary vertical and lateral support without restricting thermally induced radial expansion and contraction of the vessel.
2. Summary of the Prior Art
Nuclear reactor pressure vessels must be supported by structures that can adequately restrain vessel movement and accommodate the static, dynamic, and thermal loads which occur during normal operating conditions, in addition to the most adverse combination of loadings which may be experienced during postulated accidents and seismic events.
Design of the support structure will naturally be interrelated with various aspects of the reactor including its size and application, e.g., ship propulsion or electric power generation.
A number of support systems have been used in the prior art.
Primary vertical support has often been achieved by the utilization of cylindrical or frustoconical support skirts attached or integrally formed at the bottom of the reactor vessel. The skirt construction also permits radial growth of the vessel due to temperature and pressure through bending of the skirt in the manner of a vertical beam on a foundation. The skirt's length is chosen so as to permit this bending to take place safely. When space does not allow sufficient skirt flexing length, a construction consisting of a partially longitudinally slotted skirt can be used. The slotted portion acts as a multitude of cantilevers, while the unslotted portion, under the imposition of the moments and forces transmitted by the cantilevered portion, behaves as a cylinder. The support skirts rest upon soleplates, pedestals or the like.
Radially extending brackets circumferentially spaced about the reactor vessel or rings attached to its external surface which bear upon the horizontal surfaces of an enclosing reactor containment structure have also been used to achieve primary vertical support. The radial brackets and rings additionally have accommodated radial thermal growth displacements by the provision of means enabling siding contact to exist between the vessel and the containment. The reactor vessel support flange has similarly been used as a support means which bears upon portions of the containment structure.
Reactor vessels have been designed, moreover, which utilize the main coolant flow nozzles to perform the support function. In these cases, the nozzles may be arranged to transmit loads to the walls of a surrounding containment well. Typically, pads formed at the underside of the nozzles bear upon and are supported by wear plates that are disposed on the containment well walls. Guide channels and lubricants may be employed to facilitate radial movement. Where the containment well walls are concrete structures, cooling means may be required between the wear plates and walls to assure that the walls are not subjected to the high temperature of the coolant flowing through the nozzles. Alternately, vertical columns have been connected between the nozzles and a support base within the containment structure. In this arrangement, the columns are designed to accommodate relative displacements between the vessel and containment structure by flexing, thereby eliminating the need for relative sliding movements and allowing the columns to be securely fixed to the reactor vessel.
Support of reactor vessels at the nozzles requires that the nozzle structure have sufficient strength to accommodate the primary loads. Since nozzle sizing is generally dependent upon process conditions and the reactor's power rating, use of the nozzles for primary support necessitates additional nozzle reinforcement, strengthening and the like, not otherwise required. Strengthening of the nozzles to the extent necessary to carry design loads can be prohibitively expensive or otherwise impractical, particularly in reactor applications such as for marine propulsion.
The use of support brackets, moreover, are not generally considered on shipboard where high horizontal and vertical loadings, as well as roll and pitch, are involved.
A support structure which does not require strengthening of the nozzles or support brackets and allows unrestricted radial thermal growth without the need for sliding, lubricated guide channels and cooled support structures is desirable.
SUMMARY OF THE INVENTION
According to the present invention, an improved arrangement for supporting a reactor vessel is presented. Link and pin supports restrain vertical, lateral and rotational movement of the reactor vessel without restricting thermal radial expansion and contraction. The support arrangement allows vertical thermal expansion at the lower end of the reactor.
The arrangement comprises a plurality of links and pins interconnected with lugs that are attached to the reactor vessel and with an exterior support. The primary vertical loads are carried by the links and pins. The links carry the lateral component of the various lateral loads in a direction parallel to the axes of the pins associated with the links.
In alternate embodiments, a pin and socket arrangement supplements the link and pin supports by assisting in the maintenance of vertical alignment of the vessel and providing additional lateral support.
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 specification. For a better understanding of the invention, its operating advantages and specific objects attained by its use, reference should be had to the accompanying drawings and descriptive matter in which there is illustrated and described a preferred embodiment of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevational view of a typical reactor pressure vessel supported in accordance with the invention.
FIG. 2 is a partial elevational view of the lower portion of a pressure vessel and depicts an alternate arrangement of a feature which supplements the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings, there is shown in FIG. 1 a nuclear reactor pressure vessel 10 disposed with its longitudinal axis 11 in a vertical plane. The pressure vessel 10 comprises a generally cylindrical shell 13 closed at its lower end, in the illustrated embodiment, by an integrally formed spherically-dished end closure 12. The upper end of the cylindrical shell 13 is joined to a thicker cylindrical shell ring 14. The shell ring 14 is provided with a main vessel flange 15 generally at its upper extremity. A removable closure head 17 is provided at the upper end of the pressure vessel 10. The closure head 17 is a spherical-dished head welded to a ring flange 16. The ring flange 16 of the flanged closure head 17 mates with the main vessel flange 15 and is secured thereto in a pressure tight relation by a plurality of studs (not shown).
Reactor coolant nozzles 20, 21, only two of which are shown for increased clarity, are formed in the shell ring 14 to provide fluid communication between the interior of the reactor and a reactor coolant system (not shown). The cylindrical shell ring 14 is generally formed thicker than the cylindrical shell 13 to provide inherent compensation for the nozzle apertures.
Radially projecting lugs 22 welded to the shell ring 14 are circumferentially spaced about the shell ring. Pin connectors 23 attach the lugs 22 to links 24. At room temperature, the links 24 extend generally parallel to the longitudinal axis of pressure vessel. The opposite ends of the links 24 are secured by similar pins 25 to a baseplate 26. The baseplate 26 is securely attached to a foundation 27 by bolts and nuts, welding or other means.
A plurality of radial brackets are welded to the cylindrical shell 13 at circumferentially spaced intervals, in an alternate embodiment of the invention. Each bracket 31 longitudinally and radially extends into a channel 32 that is supported by a foundation 34. A longitudinal clearance 33 exists between the bottom of bracket 31 and the opposing face of the channel 32.
The expression "lateral loads" as used herein, unless otherwise qualified, shall denote loads transmitted perpendicularly to the longitudinal axis 11 of the pressure vessel 10. Vertical loads are those loads transmitted in parallel with the longitudinal axis 11.
Thermal expansion and contraction of the pressure vessel will occur due to temperature changes resulting from changes in the reactor's operating conditions. Radial movements due to thermal expansion and contraction are accommodated by the pivoting action of the links 24 about the pins 25. Vertical movement due to thermal changes is unhindered at the lower end of the vessel. The vessel is free to expand and contract, radially and longitudinally, in the region of the radial brackets 31 due to the channel 32 and the clearance 33.
Alternatively, as is shown in FIG. 2, a longitudinally extending boss 42 is integrally attached at the lower end of a spherically-dished bottom end closure 41. The boss 42 extends into a socket 43 that is attached to a foundation 44.
Primary vertical support of the vessel is afforded by the links and pins. Vertical loads due to restrained translatory motion of the vessel are transmitted through the lugs, the links and the pins. Lateral loads due to restrained translatory motion of the vessel are transmitted through the lugs and links in directions parallel to the pin at each support.
The hinged pin and link support can be supplemented by radial bracket and channel, or boss and socket arrangements that provide additional lateral support at the cylindrical shell 13. These arrangements assure that the axial alignment of the vessel is maintained.
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A link and pin support system provides the primary vertical and lateral support for a nuclear reactor pressure vessel without restricting thermally induced radial and vertical expansion and contraction.
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This application is a continuation of application Ser. No. 735,689, filed May 20, 1985, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a sensor, especially an electrode structure in a field effect transistor type sensor.
2. Description of the Prior Art
A field effect transistor (hereinafter, referred to as FET) type sensor, which compries an FET device incorporated with a sensitive means exhibiting an electric variation of electrostatic capacity, electric conductivity, electrostatic potential, etc., due to a physical or chemical interaction with the physical quantity to be detected, detects the said physical quantity as a variation of the gate operation of the said FET device. Taking advantage of the high input impedance and the amplifying function of the FET device, such an FET type sensor can exhibit a high output, even though its size is extremely small, and thus is advantageous in actual use. For the incorporation of an FET device with a sensitive means, electrodes are required to be formed on a substrate containing silicon oxide or silicon nitride. Thus, for materials for the electrodes must tightly bind to silicon oxide and/or silicon nitride.
On the other hand, depending upon the kind of sensitive means required, the sensitive means is formed on the electrodes in an atmosphere at a high temperature and/or a high humidity. Thus, the electrode materials must be stable to such an atmosphere. Moreover, since the FET type sensor, which is designed to be used as a gas sensor, a moisture sensor, an ion sensor, a biological sensor, etc., is exposed to an atmosphere due to the necessity of an interaction between the atmosphere and the sensitive means, the electrode materials must be also stable to the atmosphere.
Although aluminium, etc., which is used as an under-gate electrode in the FET device, is excellent in binding to the gate insulating film such as silicon oxide, silicon nitride, etc. it is readily oxidized or corroded in a high temperature and/or high humidity atmosphere or in an external atmosphere. This, aluminium, etc., is not suitable for an electrode material to be used for sensors. On the other hand, noble metals, such as platinum, gold, silver, etc., are stable in a high temperature and high humidity atmosphere and in an external atmosphere, but are inferior in binding to silicon oxide, silicon nitride, etc., and thus are not suitable for electrode materials for FTt type sensors.
SUMMARY OF THE INVENTION
The sensor of this invention which overcomes the above-discussed disadvantages and other numerous drawbacks and defficiencies of the prior art, has an electrode structure which comprises a lamination of at least two layers composed of a titanium layer bound to an insulating grounding layer and a noble metal layer covering said titanium layer.
The electrode structure constitutes electrodes in a field effect transistor which is incorporated with a sensitive means. The noble metal layer is made of gold.
Thus, the invention described herein makes possible the objects of (1) providing a novel sensor having an electrode structure which is not corroded or damaged in a severe environment such as high temperature and high humidity; (2) providing a novel sensor having an electrode structure which is excellent in bonding to a grounding layer to ensure stable operation; (3) providing a novel sensor having an electrode structure which can be stably incorporated into the sensor structure; for instance, when the electrode structure is incorporated into the FET device, it is tightly bound to the gate insulating film such as silicon oxide, silicon nitride, etc., and is stable in an external atmosphere in which the sensitive means is formed and to which the resulting FET type sensor is exposed in the use thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
This invention may be better understood and its numerous objects and advantages will become apparent to those skilled in the art by reference to the accompanying drawings as follows:
FIG. 1 is a sectional front view showing an FET type moisture sensor according to this invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows an FET type moisture sensor as an embodiment of the FET type sensor according to this invention, which comprises an FET device 11 incorporated with a sensitive means 9.
The FET device 11 is a MOS-type n-channel FET in which an n-type source 2 and an n-type drain 3 are formed in a row by the diffusion of phosphorus into the surface of a p-type silicon substrate 1. The surface of the silicon substrate 1, is covered with a silicon dioxide insulating film 4 containing through-holes for the source 2 and the drain 3. The portion of the insulating film 4 which is formed on the silicon substrate 1 between the source 2 and the drain 3 forms a gate insulating film 100. A source electrode 5 and a drain electrode 6, each of which comes into contact with the source 2 and the drain 3 at one of their ends, are buried in the insulating film 4. The other ends of each of the source and the drain electrodes 5 and 6 are connected to an external circuit at the ends of the silicon substrate 1, respectively.
On the gate insulating film 100 of the insulating film 4, a titanium layer 7 having a thickness of 500 Å and a gold layer 8 having a thickness of 5000 Å are successively formed by a vacuum evaporation method. The titanium layer 7 and the gold layer 8 are patterned by a lift-off method to form an under-gate electrode. Lamination consisting of two layers of a titanium layer 7' and a gold layer 8' is diposed in a row on a portion of the insulating layer 4 other than the gate insulating film 100 in the same manner as the above-mentioned under-gate electrode, resulting in a bonding pad. The under-gate electrode 7, 8 and the bonding pad 7', 8' can be simultaneously formed by a lift-off method. A moisture sensitive means 9 is disposed in a manner to cover the under-gate electrode 7, 8 and to come into contact with an end of the bonding pad 7', 8'. The moisture sensitive means 9 is covered with a moisture permeable upper-front electrode 10, an end of which is extended at the side of the moisture sensitive means 9 to be connected to the bonding pad. The bonding pad is connected to a control circuit.
The moisture sensitive means 9 is made of polyvinylalcohol or cellulose acetate crystallized by a baking treatment, but is not limited thereto. An organic or inorganic solid electrolyte film, a metal oxide film such as an aluminium oxide film, etc., can be used therefor. The moisture permeable upper-front electrode 10 is made of a gold evaporation film having a thickness of about 100 Å , but is not limited thereto. The moisture sensitive means 9 is not limited to a moisture sensitive means, but may be a gas sensitive means, an ion sensitive means, another chemical substance sensitive means, a heat sensitive means, a light sensitive means, etc. As the FET device, a MIS-type FET can be used.
When an electric current flows from the source electrode 5 to the drain electrode 6, the current obtained in the drain electrode 6 varies depending upon a variation of the voltage in the under-gate electrode based on the characteristic of the FET device 11. The under-gate electrode is connected to the upper-front electrode 10 by the moisture sensitive means 9 and a given potential is applied to the upper-front electrode 10 through the bonding pad by the external control circuit. The impedance of the moisture sensitive means 9 varies with the humidity in the surrounding atmosphere, and thus the voltage in the undergate electrode 7, 8 varies with the impedance variation in the moisture sensitive means 9, resulting in a variation of the current in the drain electrode. By detecting the current, the humidity in the surrounding atmosphere can be determined.
Electric charges tend to be accumulated in the same direction in the moisture sensitive means 9 depending upon the operation period, causing non-uniform gate voltage which results in a decrease in measurement accuracy. In order to eliminate the problem, according to this embodiment, a refreshing potential is directly applied to the under-gate electrode by an external circuit to remove such accumulated electric charges from the moisture sensitive means 9.
As mentioned above, the under-gate electrode and the bonding pad are composed of a double layered structure of the titanium layers 7 and 7' and the gold layers 8 and 8'. The adhesion between each of the titanium layers 7 and 7' and the insulating layer 4 is excellent and moreover, the titanium layers 7 and 7' are coated with the gold layers 8 and 8', respectively, so that the electrode structure is stable in a high temperature and/or a high humidity atmosphere and in an external atmosphere. Instead of the gold layers 8 and 8', noble metal layers such as platinum, silver, etc., can be employed.
The electrode structure was subjected to a pressure cooker test at 120° C. for 96 hours under 2 atmospheres to accelerate deterioration thereof, but neither the separation of electrodes from the insulating film nor the variation of resistance values could be observed.
The above-mentioned electrode structure is not limited to the application to FET type sensors, but can be widely applied to grounding layer materials such as silicon oxide, silicon nitride, glass, ceramics, etc.
It is understood that various other modifications will be apparent to and can be readily made by those skilled in the art without departing from the scope and spirit of this invention. Accordingly, it is not intended that the scope of the claims appended hereto be limited to the description as set forth herein, but rather that the claims be construed as encompassing all the features of patentable novelty which reside in the present invention, including all features which would be treated as equivalents thereof by those skilled in the art to which this invention pertains.
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A sensor having an electrode structure which comprises a lamination of at least two layers composed of a titanium layer bound to an insulating grounding layer and a nobel metal layer covering said titanium layer.
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PRIORITY CLAIM
[0001] The present application claims priority to the U.S. Provisional Patent Application Serial No. 60/311,035 filed Aug. 9, 2001, Serial No. 60/336,437 filed Nov. 1, 2001, both of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to ellipsometric systems for measuring feature configurations on wafers. Particularly, the present invention relates to a compact ellipsometer having multiple measurement beams. The measurement beams operate alternately and in conjunction with a rotating stage such that linear stages for positioning the wafer may be operated within reduced travel ranges.
BACKGROUND OF THE INVENTION
[0003] Semiconductors are typically fabricated by depositing and etching a number of layers that are shaped and configured on the upper or top surface of a wafer. Controlling those fabrication steps and testing the wafer early during production helps to keep production costs low. An increasingly important technique for a non-destructive measurement of semiconductors is ellipsometry. In ellipsometry, a specifically configured probe light beam is directed to reflect off the wafer. The change in polarization state of the beam induced by the interaction with the wafer is monitored to provide information about the wafer.
[0004] Ellipsometers have been used extensively to monitor thin film parameters such as thickness, index of refraction and extinction coefficient. More recently, ellipsometers have been used to monitor the properties (critical dimensions) of small, repeating, periodic structures on wafers. These periodic structures are similar to a grating and the measured data can be subjected to a scatterometry analysis to derive information about the structure. Information of interest includes, but is not limited to, line width and spacing as well as sidewall profile.
[0005] Such periodic structures have distinct orientations. It has been found that the most useful information about such structures can be obtained if the probe beam of the ellipsometer is directed substantially perpendicular to the line structure.
[0006] As seen in FIG. 1, a typical wafer W will have multiple such periodic structures PS formed thereon. In some cases, all of the periodic structures will be oriented in the same direction (i.e. all lines parallel). In other cases, some of the structures will have lines running perpendicular to other structures.
[0007] A conventional, ellipsometer is typically provided with a stage for moving the wafer through full linear motions FX, FY as well as rotation about the central axis so that the probe beam PB can be directed to each of the periodic structures PS in the appropriate direction (usually perpendicular to the line structure). The linear motions FX, FY are about equal to the wafer diameter WD. The wafer W moved during the measurement consequently occupies a travel envelope LE that extends in the directions of each of the linear axes about twice the wafer diameter. The travel envelope LE determines the minimal footprint of an ellipsometer apparatus.
[0008] Recently, there has been a push to substantially reduce the size of ellipsometer apparatus. This effort is particularly directed to allowing an ellipsometer to be incorporated directly into a semiconductor processing tool. To achieve the desired miniaturization, stage system have been developed which reduce the total range of motion of the wafer, thereby reducing the travel envelope and consequently the footprint of the system (e.g. stages that implement a cylindrical coordinate system consisting of a linear and a rotational stage). The use of these stages has not significantly impeded the measurement of thin film parameters since such measurements are not effected by the direction in which the probe beam strikes the sample. However, such reduced motion stage systems have caused a problem with measuring periodic structures where the impinging direction of the probe beam PB has to correspond to a measurement relevant orientation of the periodic structure PS.
[0009] As shown in FIGS. 2A and 2B the wafer can be manipulated with the X- and Y-stages such that only one of the four quadrants of the sample is located at the intersection between the sample and the probing beam. To perform measurements within the other three quadrants of the sample, the rotating stage needs to move by multiples of 90°. To achieve perpendicular orientation of the periodic sample structures in these cases, a second probing beam perpendicular to the first one is necessary.
[0010] This difficulty can best be seen in FIGS. 2A and 2B. In FIG. 2A, the probe beam PB is shown striking periodic structure PSI perpendicular to the line structure. When the operator wishes to measure periodic structure PS 2 , the rotating stage is used to bring the sector of the wafer where that structure is located within the region which can be reached by the probe beam. As noted above, the stage travel in the X and Y directions is not sufficient to bring the structure PS 2 under the probe beam without a rotation. Unfortunately, and as seen in FIG. 2B, the result of this rotation is to orient the periodic structure PS 2 so that the probe beam impinges thereon in a direction parallel to the lines. As noted above, it has been found that most relevant information can be obtained when the beam strikes the structure perpendicular to the line structure.
[0011] Accordingly, it would be desirable to develop an ellipsometer system, which can utilize a reduced motion stage but also provides for optimal measurement of both thin film parameters and periodic structures.
SUMMARY OF THE INVENTION
[0012] In the present invention, a probe beam is selectively directed along two or more beam paths to provide two or more focused beams impinging in various impinging directions on a tested wafer. Two perpendicularly operating linear stages provide a travel area that is only a fraction of the wafer size. Combined with the linear stages is a rotating stage positioned with its axis of rotation perpendicular to the movement plane defined by the linear stages. The movement plane is preferably parallel to the top of the fixed wafer. The rotating stage rotates the fixed wafer within a rotation range such that a number of sectors of the wafer top are brought within range of the respective focal spot during consecutive sector measurement steps. During a sector measurement step, only the linear stages are operated to move the wafer along the focal spot.
[0013] The focused beams are positioned in a number and in an angular orientation to each other that corresponds to the number of angular orientations of patterns within the measurement sectors. In the preferred embodiment, where wafer patterns have one measurement relevant orientation, two focused beams are provided in perpendicular impinging directions relative to each other such that the pattern can be measured in all four quadrants while still maintaining a perpendicular orientation of the pattern relative to the plane of the probing beam. Since two focused beams are utilized, the rotating stage operates only to adjust the wafers global orientation prior to the sector measurement steps and to rotate the predetermined sectors within the travel area so that is accessible by the focal spots. In the preferred embodiment, four sectors are defined for measuring a wafer in four consecutive sector measurement steps. The linear ranges of the linear stages are about half the wafer diameter, which significantly reduces the travel envelope and consequently the footprint of the apparatus.
[0014] The goal of the subject invention could be achieved using two completely separate ellipsometers mounted on the same support system. In other words, two light sources, two sets of focusing and collecting optics, two sets of polarizers and analyzers and two separate detectors could be used. However, in the preferred embodiment, only a single light source and a single detector are used. This approach not only conserves space, but also reduces complexity as only one light source and one detector needs to be adjusted and characterized for the measurement.
[0015] Preferably, a broad band light source is used to generate a polychromatic probe beam. At some point before striking the sample, optics are provided for either splitting the beam along two paths or selectively directing the beam along a first or a second beam path. After reflection off the sample, optics are provided before the detector to either recombine the previously split beam portions or selectively combine the two beam paths into a single path. In the preferred embodiment, movable mirrors are used to create two beam paths rather than splitting the beam to maximize the light energy being used for the measurement.
[0016] The subject invention is not limited to any particular ellipsometer configuration. Those skilled in the art will be aware of many variants such as rotating polarizer (analyzer) or rotating compensator systems. The elements necessary to create the polarization state of the incoming probe beam and analyze the polarization state of the reflected beam can be located in the common path regions or in the separate path regions. If in the separate path regions, two sets of optical elements are needed as shown in the preferred embodiment illustrated herein.
[0017] In the illustrated embodiment, a broadband rotating compensator (waveplate retarder) system is shown. Such a system is disclosed in U.S. Pat. No. 5,973,787. A suitable rotating analyzer system is shown in U.S. Pat. No. 5,608,526. See also, U.S. Pat. No. 6,278,519. All of the above patents are incorporated herein by reference.
[0018] In the illustrated embodiment, a pair of movable mirrors are provided for controlling the beam propagation. In a first position, the mirrors are located out of the beam path and allow the beam to travel along a first beam path. In a second position, both mirrors are located within the beam path and cause the beam to travel along the second beam path. The moveable mirrors are specifically configured to provide high position accuracy and repeatability for a large number of switching cycles.
[0019] In the preferred embodiment, stepper motors that have a hollow shaft are utilized to rotate and control the waveplates. The stepper motors are placed such that the beam paths run through the hollow shaft of the stepper motors' axes of revolution. The hollow shaft assembly reduces significantly the space otherwise occupied by the mechanism for driving the waveplates contributing to a reduced footprint of the optical assembly. As a result, the optical assembly fits into the apparatus despite the increased number of individual optical components.
[0020] The combination of single light source and single detector in combination with reduced travel range, multiple alternate focused beams, hollow shaft waveplate assembly and moving mirrors provides for an ellipsometry apparatus that has a footprint smaller than the travel envelope LE for a given wafer size.
[0021] As noted above, the subject invention allows periodic structures to be measured from a preferred direction while using a reduced motion stage. It should also be noted that this system allows any measurement area to be measured from any direction. While it is generally true that maximum information may be obtained when measuring a periodic structure when the beam is directed perpendicular to the line structure, additional information may be obtained from measurements where the beam is also directed parallel to the line structure or even at a 45 degree angle with respect thereto. In cases where the measured structure is rather simple, this information alone might even be sufficient. The subject invention allows measurements from any desired direction. Such measurements could be used individually or combined in a regression analysis to more fully characterize the structure.
BRIEF DESCRIPTION OF THE FIGURES
[0022] [0022]FIG. 1 shows a simplified scheme of a prior art positioning system of an ellipsometer system where two linear stages move a wafer in ranges about equal the wafer diameter.
[0023] [0023]FIGS. 2A and 2B show simplified schemes of a prior art positioning system of an ellipsometer system where two linear stages move a wafer in ranges about half the wafer diameter. In such prior art positioning system the probe beam is limited to direction irrelevant reflectance measurements.
[0024] [0024]FIG. 3 shows a first perspective view of an exemplary apparatus according to the preferred embodiment of the present invention.
[0025] [0025]FIG. 4A shows a top view of the device of FIG. 3 as indicated in FIG. 3 by the arrow 17 . The device is shown with a light beam propagating along a first beam path.
[0026] [0026]FIG. 4B shows schematic and simplified the main contents of FIG. 4A for the purpose of general understanding.
[0027] [0027]FIG. 5A shows a top view of the device of FIG. 3 as indicated in FIG. 3 by the arrow 17 . The device is shown with the light beam propagating along a second beam path.
[0028] [0028]FIG. 5B shows schematic and simplified the main contents of FIG. 5A for the purpose of general understanding.
[0029] [0029]FIG. 6 shows a second perspective view of the device of FIG. 3 with the light beam propagating along the first beam path.
[0030] [0030]FIG. 7 shows the second perspective view of the device of FIG. 3 with the light beam propagating along the second beam path.
[0031] [0031]FIG. 8 shows the second perspective view with the device of FIG. 3 having a top portion removed. A travel envelope occupied by a work piece during the operational use of the device is illustrated. Also shown is a travel area provided by the travel ranges of the linear stages.
[0032] [0032]FIG. 9 shows the second perspective view with the device of FIG. 3 having the top portion removed. A first focused beam is illustrated impinging a first sensitive measurement area in a first impinging direction.
[0033] [0033]FIG. 10 shows the second perspective view with the device of FIG. 3 having the top portion removed. A second focused beam is illustrated impinging a second sensitive measurement area in a second impinging direction.
[0034] [0034]FIG. 11 is a perspective view of a hollow shaft stepper motor used to mount a rotating waveplate.
DETAILED DESCRIPTION
[0035] According to FIG. 3, an ellipsometric apparatus 1 of the preferred embodiment is configured in order to make directional reflectance (in this embodiment, ellipsometric) measurements on the top 9 (see FIGS. 4A, 5A, 6 - 10 ) of a wafer 2 . The ellipsometric apparatus includes a base 5 and a top portion 8 , which carries an optical assembly 12 . The optical assembly 12 includes two rotating waveplate assemblies 10 , 14 .
[0036] Directional reflectance measurements are measurements for which a certain impinging direction of a focused beam relative to structure 6 , 11 (see FIGS. 4 A- 10 ) needs to be maintained. The structures 6 , 11 may be patterns as they are well known to those skilled in the art. The structures 6 , 11 typically have a plurality of parallel lines in a grating-like configuration. The structures 6 , 11 may also be layer configurations and other features on the wafer top 9 with properties measurable by the known techniques of ellipsometry. For more detailed information on related ellipsometry techniques, see the patents cited above.
[0037] It is noted that for the purpose of general understanding, the elements illustrated in the figures are schematically shown without any claim for accuracy. Moreover, for the purpose of clarity, propagating beams are shown as solids.
[0038] The ellipsometric apparatus 1 has a base 5 on which a first linear stage 4 is assembled. On top of the first stage 4 is mounted a second linear stage 3 , which itself carries a rotating stage 7 . The first stage 4 may have a first travel range TX (see FIG. 8) along a first linear axis Al and the second stage 3 may have a second travel range TY (see FIG. 8) along a second linear axis A 2 perpendicular to axis Al. First stage 4 and second stage 3 are positioned and computer controlled operated such that the rotating stage 7 may be moved within the apparatus as shown by a travel area TA (see FIGS. 8 - 10 ).
[0039] The travel area TA is defined by the ranges TX, TY. The travel area TA is the area accessibly by focal spots 41 , 81 (see FIGS. 4 A- 7 , 9 , 10 ) by only operating the linear stages 3 , 4 . The travel area TA is a fictive and global entity introduced for the purpose general understanding. It can be imagined as being drawn by the focal spots 41 , 81 on an fictive element directly attached to the linear stage 3 while the linear stages 3 , 4 move within their travel ranges TX, TY.
[0040] The rotating stage 7 has a rotating range preferably of 360 degrees around an axis of revolution AR (see FIG. 8). The rotating stage 7 is fixed on the linear stage 3 such that any area of the concentrically supported wafer 2 may be brought within the travel area TA by rotating the wafer 2 via the rotating stage 7 .
[0041] In the preferred embodiment, the wafer 2 has a wafer diameter WD (see FIG. 8) that is about twice the amount of the ranges TX, TY. The first range TX defines together with the diameter WD a first envelope extension EX (see FIG. 8). The second range TY defines together with the diameter W 1 a second envelope extension EY (see FIG. 8). Extensions EX, EY define a travel envelope 90 (see FIG. 8).
[0042] Reflectance measurements are performed on essentially the whole wafer top 9 in a number of consecutive measurement steps where individual wafer sectors 91 - 94 (see FIGS. 9, 10) are brought within the travel area TA. Following the step of positioning one of the sectors 91 - 94 within the travel area TA, the wafer 2 is linearly moved by the stages 3 , 4 to bring predetermined test areas within the focal spots 41 , 81 . The focal spots are fixed and defined by the optical assembly 12 . A predetermined test area may be part of the structures 6 , 11 , which have different measurement relevant orientation on the wafer top 9 . Structures 6 , 11 are solely shown for the purpose of general understanding to exemplarily represent the dense arrayed patterns that are measured by the apparatus 1 . The structures 6 , 11 are direction sensitive measurement areas, which require a predetermined impinging direction in order to accomplish a reflectance measurement in accordance with known techniques of ellipsometry. A multitude of such direction sensitive measurement areas may be present on a wafer top 9 with varying angular fabrication orientation.
[0043] The apparatus top 8 is dimensioned in correspondence with the base 5 and may extend beyond the footprint of the base 5 for the purpose of providing secured access to supply and communication cables (not shown) as is clear to one skilled in the art. In the preferred embodiment, a common light source and a single final detector are utilized in order for the optical assembly 12 to fit within the apparatus top 8 together with eventual other functional elements like, for example a well known focusing unit and/or calibration unit (not shown). The apparatus top 8 is positioned in a gap height HG above the rotating stage 7 such that the rotating stage 7 is externally accessible for placing the wafer 2 on it.
[0044] In the preferred embodiment, the optical assembly 12 is configured to provide a first focused beam 40 (see FIGS. 3, 4A, 4 B, 6 , 9 ) and alternately a second focused beam 80 (see FIGS. 5A, 5B, 7 , 10 ) from an initial light beam 30 (see FIGS. 3 - 7 ). The first focused beam 40 provides a first focal spot 41 in a first impinging direction (see FIG. 9). The second focused beam 80 provides a second focal spot 81 in a second impinging direction (see FIG. 10). Impinging directions are the directions of center axes of the focused beams 40 , 80 .
[0045] A first moveable mirror 28 (see FIGS. 4 A- 7 ) alternately switches the initial light beam 30 between a first beam path and second beam path. According to FIG. 4A, 4B, the first beam path includes the initial section 31 up to a first lens unit 37 from which the first focused beam 40 propagates towards the first focal spot 41 . The first beam path further includes a first inclining path segment 46 from a parabolic mirror 45 to the mirror 33 and a path end segment 50 from the mirror 33 up to a parabolic mirror 56 .
[0046] According to FIGS. 5A and 5B, the second beam path includes the initial section 71 from a first moveable mirror 28 being in an in-position such that it redirects the initial light beam 30 up to a second lens unit 77 from which the second focused beam 80 propagates towards the second focal spot 81 . The second beam path further includes a second inclining path segment 86 from a parabolic mirror 85 to the mirror 73 and a path end segment 70 from the mirror 73 up to a second moveable mirror 54 . The second moveable mirror 54 is also in an in-position where it redirects the incoming light beam towards the parabolic mirror 56 . Light beams propagating along first or second beam path are both directed towards final optical elements, which prepare a terminating beam 60 to terminate on a single detector 61 .
[0047] The final optical elements include the parabolic mirror 56 together with mirrors 57 , a pin hole 58 and a holographic grating 59 , which prepare in a well known fashion the terminating beam 60 for impinging and terminating in the final detector 61 . In the preferred embodiment, the parabolic mirror 56 has a focus angle of 20° and a focal length of 100 mm, the holographic grating 59 is from Jobin Yvon, part number 543.02.190 and the final detector 61 is a CCD detector having 512 pixels, each corresponding to a different narrow wavelength bandwidth. The pin hole 58 includes a selectable element for changing the size of the pin hole so that the measurement spot size can be varied.
[0048] The scope of the invention includes embodiments in which other optical features well known for alternately redirecting an incoming light beam are used instead of the moveable mirrors 28 , 54 . The scope of the invention is also not limited by a specific mode by which the moveable mirrors 28 , 54 alternately redirect the incoming beams. For example, a configuration may be selected in which one of the moveable mirrors 28 , 54 is in an in-position while the other one is in an out-position where it does not interfere with a light beam. The scope of the invention is also not limited by a particular shape of geometry of the beam paths or by any particular number and/or configuration of additional optical elements like, for example, mirrors 34 , 74 .
[0049] According to FIG. 4A, a first structure 6 has a measurement relevant orientation on the wafer top 9 requiring a first impinging direction provided by the first focused beam 40 . In order to perform the reflectance measurement in accordance with the known techniques of ellipsometry, the first focused beam 40 impinges the structure 6 within the first focal spot 41 along the first impinging direction and initiates a first reflected beam 42 whose polarization state has been changed away from the focal spot 41 . The first focused beam 40 is provided by a first lens unit 37 and a first polarizer 35 , which focus and polarize the initial light beam 30 propagating along the first beam path. In the preferred embodiment, the first lens unit 37 is a triplet lens with f=69 mm and the polarizer 35 is a Rochon prism. A mirror 32 is spatially oriented to redirect the propagating beam from a horizontal beam plane towards the angulated oriented and lower positioned polarizer 35 and lens unit 37 . The beam plane is sufficiently high above the top 8 to give room for mechanical features used, for example, for positioning and fixating the optical elements on the top 8 .
[0050] The initial light beam 30 is provided by a light source, which may include but is not limited to a white light source 20 , a lens 21 , a UV light source 22 , an ellipsoid >mirror 23 , a source pinhole 24 and a parabolic mirror 25 . In the preferred embodiment, the white light source 20 is a tungsten light bulb, the UV light source 22 is a D2 UV-lamp, the ellipsoid mirror 23 has f=80 mm, and the parabolic mirror 25 has focus angle of 20° and f=50 mm.
[0051] To obtain an ellipsometric measurement with high accuracy, polarization detection needs to be performed on the reflected beams 42 , 82 (see also FIGS. 7, 10) with only a minimum number of additional reflections induced on the reflected beams 42 , 82 . Since the reflected beams 42 , 82 propagate conically away from the focal spots 41 , 81 , at least one optical element is used to collimate the reflected beams 42 , 82 . The collimating optic can be a lens, or as shown in the illustrated embodiment, parabolic mirrors 45 , 85 , which have in the preferred embodiment has a focus angle of 45° and f=59.51 mm.
[0052] In the present invention, polarization detection is performed by rotating the waveplate (under computer control) around an axis of revolution, which is parallel to the propagation direction of the beam passing through the waveplate with the beam centered on the rotation symmetry axis. In the present invention, the polarization detection is at a high level of accuracy by introducing two alternately operating rotating waveplate assemblies 10 , 14 such that each of the two reflected beams 42 is passed through one of the two rotating waveplates with only a single prior reflection induced by the parabolic mirrors 45 , 85 . The waveplate assemblies 10 , 14 include hollow shaft stepper motors with their rotor axes being collinear with a center axes of the reflected beams 42 , 82 , which propagate parallel along the inclining path segments 46 , 86 . The highly compact size of the waveplate assemblies 10 , 14 accomplished by the use of hollow shaft stepper motors contributes significantly to the reduced space consumption of the optical assembly 12 and its successful integration into the apparatus 1 despite the increased number of optical components compared to that of a conventional apparatus having only a single focused beam.
[0053] Referring back to FIG. 4A, 4B, a polarizer 47 is placed along each path segment after the first waveplate assembly 10 . In the preferred embodiment, the polarizer 47 is a Rochon prism. The spatially oriented mirror 33 reflects the incoming beam and directs it along the first beam path within the horizontal beam plane.
[0054] According to FIG. 5A, a second structure 11 has an orientation on the wafer top 9 requiring a second impinging direction provided by the second focused beam 80 . This orientation may be the result of the fact that the wafer is provided with structures having different measurement orientations in a single quadrant or the same measurement orientation in a neighboring quadrant. In the latter case, a structure with the same orientation on a neighboring quadrant of the wafer would need to be measured with the second SE path, since it would require a 90 degree stage rotation to get it into the area where it can be reached by the beam.
[0055] In order to perform the reflectance measurement, the second focused beam 80 impinges the second structure 11 within the second focal spot 81 along the second impinging direction and initiates a second reflected beam 82 that carries reflectance information away from the focal spot 81 . The second focused beam 80 is provided by a second lens unit 77 and a second polarizer 75 that focus and polarize the initial light beam 30 propagating along the path section 71 . In the preferred embodiment, the second lens unit 77 is similar to the first lens unit 37 and the second polarizer 75 is the similar to the first polarizer 35 . A mirror 72 is spatially oriented to redirect the propagating beam from a horizontal beam plane towards the angulated oriented and lower positioned polarizer 75 and lens unit 77 .
[0056] The second reflected beam 82 is reflected by the parabolic mirror 85 from which it propagates parallel along the second inclining path segment 86 . A polarizer 87 is placed after the second waveplate assembly 14 along the path segment 86 . In the preferred embodiment, polarizers 87 , 47 are similar. A mirror 73 is spatially oriented to direct the incoming beam along the second beam path within the horizontal beam plane.
[0057] The second moveable mirror 54 is in an in-position where it interferes with the beam traveling along the end section 70 . The second moveable mirror 54 reflects the beam again towards the parabolic mirror 56 and continues as described under FIG. 4A.
[0058] The perspective views of FIG. 6 and FIG. 7 illustrate the extent to which the compactness of the waveplate assemblies 10 , 14 contribute to the small scale of the optical assembly 12 especially in the proximity of the focal spots 41 , 81 . For the purpose of clarity, FIG. 6 shows the first beam path and FIG. 7 shows the second beam path. FIG. 6 illustrates the limited space available for the waveplate assembly 14 between the path segment 46 and the polarizer 87 . FIG. 7 illustrates the limited space available for the waveplate assembly 10 between the path segment 86 and the polarizer 47 .
[0059] Referring to FIG. 8, the travel envelope 90 primarily defines the footprint of the apparatus 1 and consequently the available space on the apparatus top 8 as already explained in the above. Where the apparatus 1 is configured for measuring a wafer 2 having a diameter WD of about 300 mm, the envelope extensions EX, EY are according to the above description about 450 mm in each direction. The travel envelope 90 preferably remains within the overall boundaries of the apparatus 1 thus primarily defining a width FY (see FIG. 3) and a depth FX (see FIG. 3) of the apparatus 1 . However to allow this instrument to be used in applications where smaller samples (e.g. 200 mm wafers) are used, while still requiring a minimal footprint, this instrument was designed minimizing the size of the optics plate 8 (FIG. 7) and allowing a 300 mm wafer to extend outside of the enclosure 5 (FIG. 7) in certain situations.
[0060] Other factors like, for example, structural requirements, additional space for cabling and other well known components of an ellipsometric apparatus are secondarily defining the footprint of the apparatus 1 . Other well known components may be part of the base 5 and/or the top 8 . Such components may be required, for example, for controlling, processing, calibrating and/or focusing during the operation of the apparatus 1 . Some of these components, like for example, a focusing unit and or a calibration unit may be placed on the top 8 , which may additionally reduce the space available for the optical assembly 12 .
[0061] The sectors 91 - 94 (FIG. 10) are predetermined and fictive areas on the wafer 2 , which can be accessed for measurement without rotating the wafer 2 . In the preferred embodiment and in accordance with the preferred travel ranges TX, TY, the sectors 91 - 94 are about one quarter of the wafer 2 . Hence, the wafer 2 has to be rotated four times in a case where all four sectors 91 - 94 are accessed for reflectance measurements.
[0062] Prior to performing a measurement, the wafer 2 is loaded on the rotating stage 7 by a wafer-loading tool like, for example, a robotic arm that holds the wafer 2 on its bottom surface via a vacuum fixture and releases the wafer 2 on the rotating stage 7 . The gap height HG is selected to provide sufficient space for loading and unloading of the wafer 2 even when a pin lifter assembly is used to raise the wafer to allow the robot arm to slip underneath and pick up the wafer. Due to eventual loading inaccuracies or other limitations in the loading cycle, the wafer 2 is typically globally reoriented such that the orientation of the structures 6 , 11 corresponds to impinging directions. The rotating stage 7 may be configured to perform such initial global orienting. In this regard, a flat or notch finding procedure may be performed followed by a mask alignment procedure using a pattern recognition system.
[0063] The optical geometry relevant in that context includes an angle of incidence IA and a focusing angle FA (see FIGS. 9, 10) of the focused beams 42 , 82 . In the preferred embodiment, the angle of incidence IA (in the Figures, defined with respect to the surface of the wafer) is about 25 degrees. The focusing angle FA or cone is between 1-6 degrees. The reflected beams 42 , 82 have a corresponding reflecting angle RA and a spreading angle SA.
[0064] As illustrated in FIGS. 6, 7, the sizes and positions of the lens units 37 , 77 and the parabolic mirrors 45 , 85 are influenced by the angles IA, FA, RA, SA in combination with the gap height HG. Sizes and positions of the lens units 37 , 77 and the parabolic mirrors 45 , 85 again define the available space for dimensioning and positioning the waveplate assemblies 10 , 14 . The use of hollow shaft stepper motors significantly assists in down scaling the waveplate assemblies 10 , 14 so that they are positioned along the inclining path segments 46 , 86 without interfering with the lens units 37 , 77 .
[0065] The waveplates are mounted in the hollow portions of the rotor shafts, and are concentrically fabricated relative to the rotor axes. The absence of separate waveplate bearings and a mechanical transmission system greatly simplifies the design and provides at the same time for a more accurate rotation control of the waveplates. Since the rotor bearing of the stepper motor is also the bearing for the waveplates, specific bearing tolerances and tolerances for concentricity of the hollow portion of the rotor shaft are defined to meet the precision demands of optical assembly 12 . In the preferred embodiment, linear actuator stepper motors from Eastern Air Devices were used.
[0066] [0066]FIG. 11 illustrates the optical mount 102 for the waveplate. Mount 102 supports stepper motor 106 having a rotating hollow shaft 108 therein. The waveplate is mounted to the end of the shaft 108 and is carried thereby. Reflected probe beam light ( 42 , 82 ) passes through the hollow shaft and waveplate and thereafter passes through the analyzer (polarizer) 47 . The output of a home sensor 110 provides feedback for the position of the hollow shaft.
[0067] Another factor for keeping the size of the optical assembly 12 to a minimum is to utilize a common light source and a single final detector 61 as described above. In order to direct the initial light beam 30 and the reflected beams carrying the reflectance information, the moveable mirrors 28 , 54 have to be switched into their in-position with highest accuracy over a high number of switching cycles. The movement and positioning of the moveable mirrors 28 , 54 are provided by actuator units 29 , 53 . In the preferred embodiment, the actuator units 29 , 53 linearly move the mirrors 28 , 54 . The actuator units 29 , 53 are computer controlled and pneumatically operated. They provide custom designed hardened steel guides to achieve position precision over a large number of switching cycles. The precision requirements for the mirrors 28 , 54 in their in-positions is 0.005° angular tolerance for 1 million switching cycles.
[0068] A measurement of a wafer 2 within the inventive apparatus may be performed by the following steps. In a first step, the wafer 2 is loaded, fixated and eventual globally reoriented. In a second step, the first sector 91 is rotated and brought within the test area TA. Then, one of the first or second focused beams ( 40 , 80 ) is activated to perform the desired measurements. Conceivably, all of the areas of interest within one sector could be measured by only one of the two beams. However, depending on the orientation of the structures and the type of measurement sought, it may be either necessary or desirable to use both beam (at different times) to measure all the features of interest in a given sector. For example, to gain further information about a periodic structure, two measurements might be made, one with beam 40 perpendicular to the periodic structure and a second with beam 80 parallel to the periodic structure.
[0069] Once the measurements of the first sector 91 are completed, the rotating stage 7 rotates the second sector 92 within the travel area TA so that measurements in this sector can be obtained. After all predetermined sectors 91 - 94 have been measured, the wafer 2 is unloaded from the apparatus 1 .
[0070] The output from the detector 61 is supplied to a processor for analysis. The type of analysis performed is based on the type of measurement as is well known to those skilled in the art. For example, thin film parameters of a multi-layer structure can be characterized from multi-wavelength reflectometric or ellipsometric data using a theoretical model and the Fresnel equations. Information about small periodic structures (critical dimensions) can be derived using a diffraction model including, for example, rigorous coupled wave theory. (See U.S. Pat. Nos. 5,867,276 and 5,963,329, both incorporated herein by reference.) The scope of the present invention includes embodiments, where the apparatus 1 is configured to make reflectance measurements on work pieces having features suitable to be measured with ellipsometric techniques as described in the above. Further more, the invention includes embodiments, where the work piece is non circular, and at least one of the ranges TX, TY is less than a parallel width of the fixed work piece.
[0071] In the preferred embodiment, two separate beam paths are provided within a single photodetector system as exemplarily illustrated by the final optical elements 56 , 57 , 58 , 59 and the final detector 61 . Nevertheless, the scope of the present invention includes embodiments in which two physically separate photodetector systems may be provided. In such embodiment, each of the two separate photodetector systems receives one of the two reflected beams 50 , 70 thus further reducing the number of optical elements in the path of the reflected beams 50 , 70 . No moveable mirror 54 is present is such embodiments. Also, the scope of the present invention includes embodiments, where two separate light sources as exemplarily illustrated by the elements 20 - 25 are provided. In such embodiments, no moveable mirror 28 is present.
[0072] Accordingly, the scope of the invention described in the specification above is set forth by the following claims and their legal equivalent:
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An ellipsometric apparatus provides two impinging focused probe beams directed to reflect off the sample along two mutually distinct and preferably substantially perpendicular directions. A rotating stage rotates sections of the wafer into the travel area defined by two linear axes of two perpendicularly oriented linear stages. As a result, an entire wafer is accessed for measurement with the linear stages having a travel range of only half the wafer diameter. The reduced linear travel results in a small travel envelope occupied by the wafer and consequently in a small footprint of the apparatus. The use of two perpendicularly directed probe beams permits measurement of periodic structures along a preferred direction while permitting the use of a reduced motion stage.
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BACKGROUND OF THE INVENTION
The present invention relates to improvements in grates for use in industrial furnaces or the like, and more particularly to improvements in grate bars which can be utilized in such grates. Still more particularly, the invention relates to improvements in grates of the type wherein the grate bars form rows or tiers of partly overlapping grate bars and at least some of the grate bars are movable longitudinally of the neighboring grate bars. Such grates are disclosed, for example, in U.S. Pat. Nos. 4,235,172, 4,240,402, 4,239,029 and 4,096,809 to which reference may be had, if necessary.
It is already known to utilize in a grate of the above outlined character elongated grate bars whose lateral surfaces are adjacent to or contact each other and which have marginal zones adjacent to the respective lateral surfaces and located outwardly of the downwardly extending ribs which are provided at the undersides of the fuel- and cinder-carrying top sections of the grate bars.
When the mobile grate bars of the grate perform a stirring action, relatively hard or very hard particles (especially particles of metal) are likely to penetrate into the clearances between the lateral surfaces of neighboring grate bars. Such particles are likely to jam and thereby increase the width of clearances between the respective grate bars with a host of undesirable consequences. Thus, the clearances of increased width allow larger quantities of so-called lower wind to penetrate from the underside of the grate into the layer of fuel on the grate to cause uneven combustion and uneven heating of the grate. This entails uneven cooling of the grate bars, especially of those grate bars which are hollow in order to establish paths for forced circulation of a cooling medium. Overheating of grate bars shortens their useful life and causes more pronounced wear. Still, further, a piece of metallic material, cinder or the like which has penetrated between the lateral surfaces of two neighboring grate bars is likely to prevent such grate bars from moving relative to each other which affects the quality of the heating operation and can result in serious damage to grate bars as well as to the equipment which imparts motion thereto.
OBJECTS AND SUMMARY OF THE INVENTION
An object of the invention is to provide a novel and improved grate wherein the likelihood of longer-lasting retention of solid particles between the lateral surfaces of neighboring grate bars is reduced or eliminated in a simple but efficient way.
Another object of the invention is to provide a grate wherein any foreign matter which happens to penetrate between the lateral surfaces of neighboring relatively movable grate bars is expelled immediately or within a surprisingly short interval of time.
A further object of the invention is to provide a grate bar wherein the likelihood of jamming of mobile grate bars is reduced in a novel and improved way.
An additional object of the invention is to provide a grate wherein those portions of grate bars which are adjacent to their lateral surfaces are configurated in a novel and improved way with a view to reduce the likelihood of jamming of mobile grate bars and/or of retention of solid matter between the lateral surfaces.
Still another object of the invention is to provide a grate which can be used with advantage in existing industrial furnaces as a superior substitute for heretofore known grates.
An additional object of the invention is to provide a grate wherein penetration of solid matter between the lateral surfaces of neighboring grate bars does not adversely influence the cooling of grate bars and/or the rate of flow of lower wind from the underside of the grate into the area above the upper sides of the grate bars.
A further object of the invention is to provide a novel and improved method of prolonging the useful life of relatively movable grate bars in a grate for industrial furnaces or the like.
Another object of the invention is to provide a novel and improved grate bar which can be used in a grate of the above outlined character.
One feature of the invention resides in the provision of a grate, particularly for use in industrial furnaces wherein successive rows of relatively movable grate bars partially overlap each other. The grate comprises a pair of neighboring elongated grate bars at least one of which is movable longitudinally with reference to the other grate bar. The grate bars have adjacent marginal zones including serrated undersides having alternating teeth and tooth spaces, as considered in the longitudinal direction of the respective grate bars. Each grate bar further comprises a top section having an upper side, an underside and a lateral surface adjacent to the other grate bar, and at least one rib extending downwardly from the underside of the top section and being spaced apart from the lateral surface. The marginal zones are disposed between the lateral surfaces and the ribs of the respective grate bars and constitute integral parts of the respective top sections. The alternating teeth and tooth spaces need not necessarily extend along the full length of each grate bar; for example, such teeth and tooth spaces can extend along those (selected) portions of the grate bars which are not continuously overlapped by the grate bars of the neighboring row or rows of grate bars.
The teeth of one of the marginal zones are preferably staggered with reference to the teeth of the other marginal zone, at least in one position of the one grate bar with reference to the other grate bar. It is presently preferred to configurate the marginal zones and to mount the grate bars in such a way that the teeth of the two marginal zones are staggered with reference to each other by distances equaling of approximating half the distance between the top lands of two neighboring teeth on a marginal zone. The one grate bar is reciprocable with reference to the other grate bar between first and second end positions and through a predetermined distance which is preferably half the distance between the top lands of two neighboring teeth on a marginal zone.
The angles between the planes of flanks on the teeth of the marginal zones and the planes of the upper sides of the respective top sections are preferably between 20 and 50 degrees, most preferably about 35 degrees. The distance between the deepmost portion of a tooth space and the upper side of the respective top section is preferably a small fraction of the distance between the top land of a tooth and the upper side of the respective top section; for example, the first distance can be between one third and one fourth of the second distance.
Another feature of the invention resides in the provision of an elongated longitudinally movable grate bar for use in the grates of industrial furnaces or the like. The grate bar comprises a top section having an upper side, a longitudinally extending lateral surface and an underside, and at least one rib extending downwardly from the underside of the top section and being spaced apart from the lateral surface. That portion of the underside of the top section which is disposed between the rib and the lateral surface has an undulate shape with alternating hills and valleys or teeth and tooth spaces, as considered in the longitudinal direction of the grate bar. As stated above, the flanks of teeth at the underside of the top section and the upper side of the top section preferably make angles of between 20 and 50 degrees, most preferably angles of approximately 35 degrees. As also mentioned above, the distance between the deepmost portion of any tooth space and the upper side of the top section is preferably a small fraction (preferably between one third and one fourth) of the distance between the top land of any of the teeth and the upper side of the top section of the grate bar.
The novel features which are considered as characteristic of the invention are set forth in particular in the appended claims. The improved grate itself, however, both as to its construction and the mode of assembling its grate bars, together with additional features and advantages thereof, will be best understood upon perusal of the following detailed description of certain specific embodiments with reference to the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a schematic plan view of a portion of a grate;
FIG. 2 is an enlarged fragmentary longitudinal vertical sectional view of a grate bar in the grate of FIG. 1 as seen in the direction of arrows from the line II--II; and
FIG. 3 is a fragmentary transverse vertical sectional view as seen in the direction of arrows from the line III--III of FIG. 2.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows schematically a row of neighboring elongated grate bars at least some of which are reciprocable with reference to the neighboring grate bars 1 in directions indicated by the double-headed arrow A. For example, the extent of movement of mobile grate bars 1' relative to the other grate bars 1 may be such that the mobile grate bars can move between the illustrated foremost positions and rear end positions in which their front and rear ends are flush with the respective ends of the neighboring (stationary) grate bars 1.
In accordance with a feature of the invention, those marginal portions or zones 3 of neighboring grate bars 1 and 1' which are immediately adjacent to each other have serrated or undulate undersides 2b' (see FIG. 3) including alternating hills and valleys or teeth (9) and tooth spaces (5), as considered in the longitudinal direction of the respective grate bars. FIGS. 2 and 3 show that each of the grate bars 1, 1' comprises a plate-like top section 2 having a flat or substantially flat upper side 2a which supports fuel and/or combustion products, a vertical or nearly vertical lateral surface 2c, and an underside 2b which includes the underside 2b' of the respective marginal zone 3. Each of the grate bars 1, 1' further comprises one or more ribs 4; the illustrated ribs 4 are inwardly spaced from the respective lateral surfaces 2c, they extend downwardly from the undersides 2b of the respective top sections 2, and they determine the inner boundaries of the respective marginal zones 3. The ribs 4 can be used to engage coupling devices in a manner as disclosed, for example, in the aforementioned U.S. Pat. No. 4,239,029.
The teeth 9 at the underside 2b' of one of the marginal zones 3 shown in FIGS. 2 and 3 are staggered relative to the teeth 9 at the underside of the adjacent marginal zone 3, as considered in the longitudinal direction of the grate bars 1 and 1', at least in one position of the mobile grate bar 1' with reference to the neighboring grate bar or grate bars 1. The tooth spaces 5 do not extend all the way to the upper sides 2a of the respective top sections 2, i.e., these tooth spaces are open only in a downward direction for the purpose of facilitating gravitational descent of any foreign matter (see the solid particle 11 in FIG. 2) as indicated by the arrow 10. These portions of the lateral surfaces 2c which are provided on the respective teeth 6 are denoted by the reference characters 2cc; the edges 8 bounding such portions 2cc of the lateral surfaces 2c can be said to constitute cutting or shearing edges which bring about rapid comminution of a foreign particle that has penetrated into the space or clearance between two neighboring lateral surfaces 2c when the grate bars 1' move relative to the grate bars 1. The flanks 7 of the teeth 9 preferably make relatively small acute angles alpha with the planes of the upper sides 2a of the respective top sections 2; for example, each angle alpha may be in the range of 20-50 degrees, most preferably exactly or close to 35 degrees. Such inclination of the tooth flanks 7 has been found to contribute significantly to the cutting or shearing action of the cutting edges 8 bounding the portions 2cc of or the entire lateral surfaces 2c on the top sections 2 of neighboring grate bars.
The distance between the deepmost portions 12 of tooth spaces 5 and the upper sides 2a of the respective top sections 2 is preferably a small fraction of the distance between such upper sides 2a and the top lands (actually bottom lands) 6 of the teeth 9. For example, the distance between a top land 6 and the upper side 2a of the respective top section 2 can be between three and four times the distance between the deepmost portion 12 of a tooth space 5 and the same upper side 2a. The cutting edges 8 of neighboring lateral surfaces 2c cooperate to promptly crush or flatten any solid particle 11 which happens to penetrate therebetween or, at the very least, to rapidly advance such particle into one of the tooth spaces 5 so that the particle can descend by gravity in the direction which is indicated by the arrow 10. The extent to which the cutting edges 8 of neighboring lateral surfaces 2c overlap when the grate bar 1' is in motion varies continuously, and this also contributes to the shearing, crushing, flattening and expelling action of the marginal zones 3 upon the particles 11 between the lateral surfaces 2c of two neighboring top sections 2. In other words, the volume or capacity of pockets which include pairs of neighboring tooth spaces 5 (one in the marginal zone 3 of a grate bar 1 and the other in the marginal zone 3 of the neighboring grate bar 1') varies continuously as a result of reciprocatory movements of the grate bar 1', and this also contributes to greater tendency of the marginal zones 3 to rapidly induce a foreign particle 11 to leave the clearance between the lateral surfaces 2c and descend to the bottom below the grate.
The reference character 13 denotes in FIG. 2 the distance between the top lands 6 of two neighboring teeth 9 on the marginal zone 3 of the grate bar 1 or 1'. Such distance is preferably approximately twice the length of strokes of the mobile grate bars 1'. In at least one position of the mobile grate bar 1', the relative positions of the two marginal zones 3 are such that the distance 13 is twice or approximately twice the distance between the top land 6 of a tooth 9 on the marginal zone 3 of the grate bar 1 and the top land 6 of the nearest tooth 9 on the marginal zone 3 of the adjacent grate bar 1'. Thus, in the just mentioned position of the mobile grate bar 1' with reference to the adjacent grate bar 1, the pitch (distance 13) of teeth 9 at the serrated undersides 2b' of the two marginal zones 3 is twice the extent to which the teeth 9 of the two marginal zones 3 are staggered relative to each other, as considered in the longitudinal direction of the grate bars. The arrangement may be such that the teeth 9 of the marginal zone 3 of the mobile grate bar 1' register with the teeth 9 of the other marginal zone 3 when the mobile grate bar 1' assumes its rear end position.
It is not necessary to provide teeth and tooth spaces along the full length of each marginal zone 3. For example, it is sufficient (at least in many instances) if the teeth 9 and tooth spaces 5 are provided on and in those portions of the undersides 2b' where the grate bars 1 and 1' of FIGS. 2 and 3 are not continuously overlapped by the grate bars in the adjoining row or row of the grate.
An important advantage of the improved grate and its grate bars is the ability of such parts to expel foreign matter with surprising ease and within surprisingly short intervals of time. The marginal zones 3 of neighboring grate bars 1 and 1' act not unlike the cooperating blades of a mower cutter bar by rapidly and predictably comminuting, flattening and/or expelling a foreign particle 11 into the nearest tooth space or spaces 5 for gravitational descent to a level below the undersides 2b' of the marginal zones 3. The inclination of flanks 7 relative to the upper sides 2a of the respective top sections 2 entails the development of forces which tend to move solid particles between the lateral surfaces 2c downwardly and out of the clearance between the marginal zones 3. The entrapped solid particles which are in the process of moving downwardly immediately enter the nearest tooth spaces 5 as soon as they descend to the level of such tooth spaces whereby the lateral stressing of solid particles is terminated and the particles are free to leave the grate by gravity. As mentioned above, the selection of angles alpha between 20 and 50 degrees, preferably approximately 35 degrees, has been found to further enhance the solids-expelling action of the marginal zones 3 when the grate bar 1' is in motion. The aforediscussed selection of the extent to which the teeth 9 on one of the marginal zones 3 are staggered relative to the teeth 9 on the other marginal zone also contributes to a more satisfactory and more predictable comminuting, flattening and/or expelling action of the marginal zones 3. The dimensions of pockets or niches which are defined by neighboring tooth spaces 5 of the two marginal zones 3 reach a maximum value when the teeth 9 of one marginal zone register with the teeth of the other marginal zone, i.e., when the mobile grate bar 1' assumes one of its end positions with reference to the stationary grate bar 1. It is evident that the improved marginal portions are just as effective if they are provided on grate bars each of which moves relative to the neighboring grate bar or if the invention is embodied in grates wherein the grate bars 1 move jointly back and forth and the grate bars 1' move with as well as relative to the moving grate bars 1.
The feature that the distance 13 is twice the maximum stroke of the mobile grate bar 1' and that the teeth 9 on one of the marginal zones 3 register with the teeth 5 of the other marginal zone in one end position of the mobile grate bar 1' is desirable and advantageous because this ensures more or less uniform wear upon the entire cutting edges 8 and full utilization of each and every portion of each of these cutting edges. Moreover, this invariably ensures that each and every solid particle which happens to penetrate between the neighboring lateral surfaces 2c is invariably entrained and moved downwardly when the grate bar 1' is in motion.
The feature that the distance between the deepmost portions 12 of the tooth spaces 5 and the upper sides 2a of the respective top sections 2 is a small fraction (normally between one third and one fourth) of the distance between the top land 6 of a tooth 9 and the upper side 2a is also desirable and advantageous because this ensures that a foreign particle 11 which has barely entered the clearance between two neighboring lateral surfaces 2c is compelled to reach the nearest tooth space or tooth spaces 5 after a relatively short downward movement from the upper sides 2a of the corresponding top sections 2.
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 and specific aspects of my contribution to the art and, therefore, such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the appended claims.
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A grate for use in industrial furnaces wherein rows of elongated grate bars partially overlap each other and the grate bars of each row include neighboring stationary and longitudinally movable grate bars. The undersides of the marginal zones of neighboring grate bars are undulate by exhibiting alternating teeth and tooth spaces which ensures rapid expulsion of solid particles which happen to penetrate between the lateral surfaces of neighboring grate bars when the movable grate bars reciprocate relative to the adjacent grate bars. The flanks of teeth at the undersides of the marginal zones make with the upper sides of the respective grate bars acute angles of between 20 and 50 degrees, and the thickness of each marginal zone above the deepmost portion of a tooth space is a small fraction of the thickness of the marginal zone above the top land of a tooth. The lateral surfaces of neighboring marginal zones define cutting edges which comminute the solid particles while the particles are in the process of descending toward the nearest tooth spaces so that they can leave the grate by gravity.
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BACKGROUND
1. Field of the Invention
This invention relates to laundry accessories and, more particularly, to novel systems, methods, and tools to keep socks matched during laundering.
2. Background Art
Laundry is a perennial activity in most households. Also, socks are historically difficult match. This is not simply because they sometimes look somewhat alike, but a greater problem. Typically, socks are a comparatively small article of clothing. They are often colored, sometimes is not. They often contain synthetic fabrics such as nylon, polyester, spandex, other elastic, and so forth. These and even natural fibers, such as wool, often generate static cling. This puts socks in the position of being captured by other articles placed in the laundry load with socks, whether “whites” or “colors.”
In colors will be found shirts, towels, and other comparatively larger objects. In whites may be found linens, towels, underclothing, and so forth. Static buildup during the drying process may cause small articles of clothing to cling to other articles, and not separate.
For example, towels or t-shirts may be withdrawn from a tumbling dryer and put in another basket for, or as part of, sorting. It is completely within the realm of contemplation that a towel may be folded with a sock clinging to the backside. Thus, the sock is not seen, does not produce a noticeable bulge, and is not found until the towel is removed from a linen closet for use.
Thus, by such modes and many others, socks may become separated from one another, and such as been the case forever. Unmatched socks are the bane of the laundry function in any household. Moreover, some socks are apparently never found. A lone sock may sit in a drawer waiting a mate for months or years. Thus, there exist common jokes about how gremlins reach into the washing process and remove one out of every two socks in a pair. Of course this is not true. However, such jokes illustrate the ubiquitous nature and severity of the frustration from the problem.
Thus, it would be an advance in the art to find a simple system and mechanism for binding two socks of a pair together reliably and releasing them readily on demand. It would be an advance in the art if this system and mechanism could function equally well in a wash cycle and a drying cycle. For example, dryers operate at comparatively very high temperatures over 250 degrees Fahrenheit (115 degrees C.) in order to vaporize water to evaporate out of the fabric of clothing being dried.
Meanwhile, agitation, detergents, and the water are problematic for metals. Thus, resistance to chemical attack, corrosion, and the like may be important for protection of the system and device. This may also be a concern so that socks are not stained by rust or other oxidation of metals.
BRIEF SUMMARY OF THE INVENTION
In view of the foregoing, in accordance with the invention as embodied and broadly described herein, a method and apparatus are disclosed in one embodiment of the present invention as including the manufacture and use of a loop or apparatus having elastic properties. Here, the word “elastic” is used in the engineering sense. That is, elastic deflection or deformation is fully recoverable upon release of applied force or stress.
For example, a steel spring, certain types of polymeric materials, and the like may be stretched or compressed. Their stretch (elongation, strain) is proportional to the force or stress (weight, force, force per unit area) in an effectively linear relationship according to Hooke's Law. Hooke's Law states that force is equal to a constant characterizinag the material and its configuration, multiplied by the deflection. Of course, this is a linear relationship wherein deflection is proportional to force directly through the spring constant.
The apparatus may take on various configurations. For example, its cross section may vary from one sided (circular) to two sided (an elongate cross section terminating at each extremum at a comparatively zero distance), to three sided (triangular). Moreover, a four sided device (square, parallelogram, rhombus, rectangle, trapezoid, etc.), or the like is within contemplation. Moreover, five, six, eight, or some other number of sides may be considered.
The aspect ratio of thickness to width may vary. For example, a right circular cylinder may be one cross sectional representation of a segment of an apparatus. On the other hand, an oval cross section, a figure eight cross section, an ellipse, or the like may likewise be tractable. In fact, the cross sectional area and the cross sectional shape may be produced by extrusion, injection molding, or other process to be made in any number of shapes.
The band may also be extruded as a closed loop of any shape, and then sliced to form closed, narrow bands with their own cross sections representing the opening within the elastic apparatus.
The wall of such a band or apparatus may be of a thickness, length, and width to suit a user and supportable manufacturing processes. Also, the wall thickness will necessarily affect the stiffness or the spring constant governing performance of the apparatus. In some embodiments, the thickness may be comparatively smaller, with an inside diameter comparatively larger for the overall loop. Thus, the apparatus may stretch a greater or lesser distance. Material and dimensions may change how far it will stretch.
For example, a thicker wall will typically require more force to stretch the opening. A thinner wall will be easier to stretch. Likewise, the particular maximum deflection permissible in a specific elastomeric polymer may depend on its cross linking and its particular principal chemistry. Accordingly, some materials may stretch a mere ten to twenty percent of their initial circumference. Other materials may stretch literally one thousand percent of their initial circumference. Thus, maximum permissible deflection may be affected, as well as the stiffness or spring constant of the material itself or of a thicker or thinner cross section thereof.
This leads to the fact that a loop or apparatus in accordance with the invention may be used in a single pull and a single wrap around a pair of socks. In other embodiments, the loop may be sufficiently flexible, and have sufficient elongation that a loop may be placed around a pair of socks, twisted and then looped back over the pair again to provide two loops or two encircling of the pair of socks to bind them together.
Also, in certain embodiments, a tab or grip may be provided in one region of an apparatus. The loop, for example, may have a tab that extends radially outward. In other embodiments, the tab may actually extend axially upward or downward perpendicular to the plane representing the top and bottom surface of such a loop. In this way, fingers may obtain a good grip to place a loop on, or remove a loop from the socks.
The tab is perhaps more important after washing and drying of the socks. At this time, the socks may be fluffed up to their highest bulk. A tight constriction of the loop about the socks may render difficult placing a finger inside the loop or inside one turn of the loop in order to remove it from the socks. Thus, the tab provides a grip.
In certain embodiments, the grip is disposed in a particular shape, and may be provided in particular colors or shapes to indicate a logo, a message, a theme, a set, owner-selectable distinction, or the like. Likewise, words, such as instructions or other text, an image, or a logo may be built into the grip or tab used for handling, especially removal, of the apparatus.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing features of the present invention will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only typical embodiments of the invention and are, therefore, not to be considered limiting of its scope, the invention will be described with additional specificity and detail through use of the accompanying drawings in which:
FIG. 1 is a perspective view of one embodiment of an apparatus in accordance with the invention;
FIG. 2 is a cross-sectional view of various alternative cross sections of a loop apparatus in accordance with the invention;
FIG. 3 is a top plan view of the article of FIG. 1 ;
FIG. 4 is a front elevation view thereof, the rear elevation view being identical;
FIG. 5 is a right side elevation view thereof, which is identical to the left side elevation view thereof;
FIG. 6 is a top plan view of an alternative embodiment of a loop apparatus in accordance with the invention;
FIG. 7 is a front elevation view thereof, the rear elevation view being identical;
FIG. 8 is a right side elevation view thereof, the left side elevation view being identical thereto;
FIG. 9 is a perspective view thereof;
FIG. 10 is a prospective view of application of the apparatus in accordance with the invention, with the socks being absent for clarity;
FIG. 11 is a perspective view of an alternative embodiment of a loop apparatus in accordance with the invention;
FIG. 12 is a perspective view of various alternative embodiments for the tab of FIG. 11 ;
FIG. 13 a left side elevation view of an alternative embodiment of a loop apparatus in accordance with the invention, illustrating by exploded inset views, and various alternative cross sections;
FIG. 14 is a perspective view of one embodiment of a loop apparatus in accordance with the invention, being drawn around the pair of socks, twisted and drawn around the socks again to form a double loop or a double turn around the socks; and
FIG. 15 is a perspective view of a pair of socks in which a loop apparatus in accordance with the invention has been looped around a portion of the socks a single time to bind them together.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
It will be readily understood that the components of the present invention, as generally described and illustrated in the drawings herein, could be arranged and designed in a wide variety of different configurations. Thus, the following more detailed description of the embodiments of the system and method of the present invention, as represented in the drawings, is not intended to limit the scope of the invention, as claimed, but is merely representative of various embodiments of the invention. The illustrated embodiments of the invention will be best understood by reference to the drawings, wherein like parts are designated by like numerals throughout.
Referring to FIGS. 1 through 9 , while referring generally to FIGS. 1 through 15 , an apparatus 10 or loop 10 in accordance with the invention may be formed of a polymer, typically an elastomeric polymer having a suitable flexibility, spring constant, cross sectional area, and other dimensions to operate as an elastic band 10 . Typically, an apparatus 10 will be characterized by an outside diameter 12 or effective outside diameter 12 .
By effective diameter is meant the hydraulic diameter as understood in the engineering arts. A hydraulic diameter is four times the area enclosed divided by the wetted perimeter or the enclosed perimeter. Thus, a circle devolves to an actual physical diameter. An effective diameter or hydraulic diameter of a square is simply the length of one side.
Any other shape has a value of hydraulic diameter by the same relationship, which will be something calculated only because it may not actually exist anywhere. Slits and slots sometimes degenerate to simply the distance across the smaller dimension. Nevertheless, an effective diameter 12 may be calculated for any shape.
For example, the actual shape of the loop 10 or apparatus 10 may be any shape desired. For example, the shape of the outside diameter 12 is actually the outer surface 13 or defined by the outer surface 13 . Similarly, the inside diameter 14 , which is actually the effective internal diameter 14 , may be calculated according to the rules of hydraulic diameter. Likewise, the inner surface 15 describes or defines the actual perimeter giving rise to the effective inside diameter 14 . Accordingly, the thickness 16 need not be uniform. However, it has been found that a uniform thickness 16 is often the best to serve the need for a comparatively uniform deflection or strain.
Strain is actually a dimensionless deflection or stretch. By stretch is meant deflection in either direction, compression or tension. Thus, deflection is the general term, while stretch represents elongation under tensile load. Compression or shrinkage represents deflection under compressive load. The point here is that strain is a dimensionless number meaning the distance of deflection divided by the overall length dimension.
For example, a circle may have an amount of strain constituting a number of inches per inch of length of circumference or the number of centimeters per centimeter of overall length. Thus, it is proper to speak of deflection as distortion and change of dimension and strain as the normalized or nondimensionalized measurement of distance of strain per total distance.
Thus, for strain (normalized change of dimension) to be uniform about the entire circumference of an apparatus 10 , it is preferable that the thickness 16 as well as the top surface 17 a to bottom surface 17 b height 18 be uniform throughout. Even with a comparatively uniform thickness 16 , and a uniform height 18 , the circumference about the apparatus 10 may actually take on (be formed in) any shape.
Some examples are a star, a circle, a rectangle, an image shape, such as the head of a horse, the profile of an entire horse, the face of a cat, the entirety of a cat, the shape of a dog, the shape of any other animal pet, the shape of a particular vehicle style or design, and so forth. Thus, any of the conventional shapes of polygons, starts, circles, or images of live things or inanimate objects is a perspective profile to substitute for the “ring” 10 that is the apparatus 10 illustrated. One may thus consider the apparatus 10 to be defined by a wall 20 following any suitable shape and extending from an inner diameter 14 to an outer diameter 12 and having a height 18 .
As a practical matter, a method of manufacture may involve extruding the shape of the apparatus 10 . The extrusion constitutes the circumference thereof. Actually it includes both inner circumference and outer circumference. Generally, it is not necessarily a circular cross section. This may be done in a conventional extruder having a die shaped to the periphery or circumference, effectively, of the apparatus 10 . Extrusion may involve any of several suitable methods, but may benefit from a vertical extrusion of an elastomeric polymer.
Elastomeric polymers may include compositions of silicone, natural rubber, synthetic rubber, and substantially any elastomeric polymer. Silicone and other “high temperature” polymers are those having temperatures greater than would normally be melted by exposure to the hot air of a commercial or domestic clothes dryer. Silicone compositions are used in bakeware exposed to temperatures over 400 degrees Fahrenheit.
Thus, any such elastomeric material having the proper mechanical characteristics may serve. It requires a suitable spring constant, elongation, maximum stress at rupture, and so forth. Those properties are understood in engineering. Any material suitable and durable may serve as the elastomeric polymer from which the apparatus 10 may be formed.
Following extrusion, individual instances of the product 10 or apparatus 10 may be sliced or cut across the shape (cross section) at a periodicity equal to the height 18 . Thus, the height 18 may be adjusted to be comparatively shorter (thinner) or taller (thicker) as desired. There exist reasons to have the height 18 be comparatively low, even less than the wall thickness 16 in some instances. Total force required, ease of manipulation, and manufacturing are. In other instances it makes sense and provides a certain life expectancy and a different handling benefit of not “rolling up” to have the height 18 be comparatively longer than the wall thickness 16 , and sometimes several times larger (several multiples thereof). However such a loop 10 requires or admits to a single loop with no twisting or doubling up.
The shape of the apparatus 10 necessarily will have a cross section. Indeed, the cross section of the wall 20 itself, as well as the cross section of the gap 21 or space 21 in the center thereof may take on any suitable shape. The number of shapes possible is a digit too high to begin to consider even a small fraction of the possibilities. One may refer to FIG. 2 for the shapes of several polygons. These polygonal shapes may be the cross sections 22 of the wall 20 itself along the section A-A of FIG. 1 , as illustrated.
Nevertheless, each of these shapes of FIG. 2 also represents a possible shape for the interior surface 15 of the apparatus 10 . Thus, with the wall thickness minimized and represented only by a line, any of those shapes and more may represent the perimeter and outer of an apparatus 10 . Meanwhile, any of the other shapes of nature, plants, animals, houses, buildings, objects, tools, toys, vehicles, or the like may be the shape taken by the apparatus 10 when relaxed and unstretched.
A sheath 23 may be thought of as a decorative cover 23 . For example, an alternative mechanism for manufacturing an apparatus 10 in accordance with the invention may involve extrusion of the solid polymer in a cross section 22 illustrated. For example, a circular cross section 22 a , square cross section 22 b , triangular cross section 22 c , and trapezoidal cross section 22 d may represent the wall 20 of the apparatus 10 . Likewise, the rectangular cross section 22 e is a parallelogram 22 e . Meanwhile, the hexagon 22 f and octagon 22 g are not the limit. More sides are possible. Moreover, all of the shapes illustrated so far except a star are fully convex. They have no external concave surfaces. However, providing shapes of animals, plants, cars, other things, and so forth may involve the use of inside corners or concave corners on the outer perimeter of any of the walls 20 of an apparatus 10 .
Thus, virtually any cross section 22 may be molded or extruded. Extrusion provides a continuous process. Moreover, extruding a shape 22 or cross section 22 may be done as a linear and continuous process. To form an actual ring 10 , loop 10 , or the like as an apparatus 10 , one may bond cut ends of a stranded material to form the loop 10 . There will be some uneven stress across the cross section too, as a result. However, with a sufficiently soft elastomeric polymer, such a construction technique is totally tractable.
A sheath 23 is most easily applied to an open strand of a linear material having a cross section 22 . Thus, the decorative cover 23 may provide the entire decoration. In alternative embodiments, the decorative cover 23 may be augmented by having the ends thereof along with the ends of the internal wall 20 captured, bonded, cast, clipped, stapled, or otherwise captured in a grip or medallion that serves to close the loop 10 , as well as provide a material by which to grasp the apparatus 10 .
Referring to FIG. 10 , while continuing to refer generally to FIGS. 1 through 15 , an apparatus 10 may be used as a single loop 10 , or may be stretched and doubled back over itself. In the illustrated embodiment, the apparatus 10 may be placed around a pair of socks, drawn tight, and twisted as illustrated. The socks have been removed to illustrate the shape of the apparatus 10 . Nevertheless, in the center configuration of the apparatus 10 , stretching the apparatus 10 and twisting it to form two separate loops, serves to permit doubling up. Thus, ultimately, the apparatus 10 as in the configuration on the right demonstrates that the diameter has been diminished to about half. The overall stress or force has actually been doubled by two layers of the wall 20 . The cross-over 24 or twist 24 is necessary in order to form one complete loop 10 around the socks or the object to be tied. Another loop 10 is then stretched larger to fit over the same object in order to provide the double loop 10 illustrated as the consequence of such an operation.
It is worth noting that the thickness 16 and height 18 of the wall 20 cooperate along with the overall inside diameter 14 to determine the ease with which the apparatus 10 may be stretched about socks a first, second, or both number of times. The smaller the opening 21 or gap 21 enclosed by the wall 20 , the less space and therefore more constrictive hold will be imposed upon the grasped objects. The first loop 26 is typically made, and then all the slack or all the available tension drawn against it. Thereafter, a second loop 28 may follow the twist 24 , and enclose once again the same object.
The size, meaning here the thickness 16 , and height 18 , which are necessarily affected by the shape 22 or cross section 22 , will govern the stiffness or the resistance to stretching of the circumference or the diameters 12 , 14 of the loop apparatus 10 .
Referring to FIGS. 11 and 12 , while continuing to refer generally to FIGS. 1 through 15 , a tab 30 may act as a grip 30 for grasping and stretching the size of the apparatus 10 . For example, in applying the band 10 or apparatus 10 to an object or a bundle of objects to be gripped, one may insert fingers inside the space 21 encompassed by the wall 20 . However, following a laundering of the grasped objects, the loop 10 or apparatus 10 may be difficult to grasp.
Depending on how much tension was put in the wall 20 (where tension is a stress or force per unit cross sectional area), it may be quite unsatisfactory to reach a fingernail or finger underneath or inside the inner diameter 14 to pull against the inside surface 15 . Removing the apparatus 10 from a grasped bundle of articles may be done by rolling the apparatus 10 along the surface of the grasped objects.
It may be a more satisfactory mechanism to simply re-stretch one of the loops 26 , 28 by grasping the tab 30 , drawing it away from the grouped articles. Drawing enough slack may require moving it back and forth in a plane parallel to its upper and lower surfaces 17 a , 17 b . Once sufficient slack is drawn out of one of the loops 26 , 28 the other loop 28 , 26 may be drawn over the bundled articles. This effectively reduces multiple loops 26 , 28 to a single loop 10 .
In fact, depending on the particular dimensions it may be possible to loop more than just two loops 26 , 28 in the article 10 . Three, four, or more may be possible. Nevertheless, it has been found that one or two loops 26 , 28 will serve well and provide a sufficiently robust and long lived product 10 .
Referring to FIG. 12 , while continuing to refer generally to FIGS. 1 through 15 , the tab 30 may have any of a variety of shapes, and each may serve the purpose of decoration, information, or some other functionality. For example, the shape of the tab 30 may be somewhat arbitrarily defined. So long as it is of about sufficient surface area to be gripped well between the thumb and forefinger, it may serve its role to draw tension in the wall 20 of the apparatus 10 .
Some of the shapes illustrated are, for example, a simple semicircle or circle. Beginning at the top configuration and proceeding clockwise, a circle blended into the wall 20 may provide a tab 30 with an aperture in the middle, or simply a material of a different color. Similarly, proceeding clockwise a star or other recognizable shape or symbol may be used as the tab 30 . Meanwhile, an elongated or elliptical shape may provide space for a panel 32 receiving text 34 .
In each of the shapes of tabs 30 , the panel 32 serves as a frictional contact surface for the digits of a user. However, it may also serve the function of hosting text 34 . The shape may altered, such as the next (trapezoidal) shape. This may accommodate specific text or provide room for larger text farther from the wall 20 and smaller text closer thereto. Moving more of the material farther away from the wall 20 may provide less influence on the loop 10 by the change of cross sectional area in the tab 30 .
In other embodiments, the tab 30 may extend along a greater or lesser portion of the wall 20 . One will note that the trapezoidal shape is rounded at the corners. This may provide benefit in manufacturing. It may also provide reduction of stress concentrations at changes in cross section, such as between the tab 30 and the wall 20 . The rounded fillet area may provide additional life, and reduce the probability that such an interior corner might serve as a source of rupture for damage or failure over time.
Moving clockwise to the next inset, a shape of an object, such as the pair of socks shown in the same or different colors may be molded as the tab 30 . These may be extruded in different colors, or may be stamped in different shapes or with a boundary thus shown. As illustrated, this cross section may be altered to meet some other image desired for commercial identification, user classification, or a suggestion of use.
Of course, different shapes, such as a rectangular tab 30 in the next inset, or a modified circular tab 30 may also be relied upon. Thus, the various tabs 30 a , 30 b , 30 c , 30 d , 30 e , 30 f , 30 g , are but a sampling of the possible shapes that may be formed. In fact, in FIG. 11 , a somewhat rounded corner on a rectangular object is but a variation of the somewhat elongated but circular shape of the tab 30 g . Thus, any of a variety of shapes that are suitable for gripping, may extend a sufficient distance away from the wall 20 to support a good stiff tug or pull to stretch the ring 10 open. Any may well serve as a decorative, functional, or both types of elements for the tabs 30 .
Referring to FIG. 13 , while continuing to refer generally to FIGS. 1 through 15 , the tab 30 need not be shaped in any particular way or limited to any particular shape in the orthogonal direction. That is, the top plan view illustrated in the tabs 30 a through 30 g may have a constant thickness, or it may vary.
For example, beginning clockwise at the top, a tab 30 may have a rectangular aspect or rectangular shape that is either thinner, thicker, or the same thickness as the height 18 of the wall 20 of the loop 10 . In fact, any of the shapes of FIG. 13 may actually have uniform thickness in the direction into the page. Alternatively, any of the shapes of FIG. 13 may also be applied to any of the shapes in FIG. 12 . Since each is a cross section in a direction orthogonal to the other, they may be used in any combination.
Thus, the profile of the tab 30 h is simply extending at exactly the same thickness 18 of the main loop 10 . The shape of the tab 30 j extends at a varying thickness, tapering as it extends away from the apparatus 10 . Similarly, the tab 30 k provides for an image 36 such as a logo 36 . Just as a surface parallel to the top surface 17 a of the loop 10 may have a message, a surface orthogonal thereto may have a logo 36 , text 34 , or other emblem.
Meanwhile, the dimensions of the tab 30 m illustrate that the panel 32 may include text 34 that is much smaller. Of course, a matter of design choice and utility of the tab 30 may be overridden by design characterizations or desires, communication of information, and so forth. Thus, in general, the shapes in a direction axially 11 a , radially 11 b or circumferentially 11 c may include all possibilities.
For example, an axis 11 d extending radially but orthogonal to both the axial direction 11 a , and another radial direction 11 b , may define a three-dimensional, rectangular set of coordinates. However, as a practical matter, in the illustrated embodiments, a circular cross section of the shape may be defined by an axial direction 11 a and a radial direction 11 b , which may proceed in any direction orthogonal to the axial direction 11 a , as will be sufficient to define a position. Nevertheless, in a circumferential direction 11 c , it will typically be necessary to define a point by at least three axes out of the group of axes 11 a , 11 b , 11 c , 11 d.
Referring to FIGS. 14 and 15 , while continuing to refer generally to FIGS. 1 through 15 , a pair of socks 40 may be grasped with multiple turns as illustrated in FIG. 14 , or as a single loop about a pair or multiple pairs. Typically, the thickness 16 , height 18 , and material are all matters of design choice and engineering of molds, dies, and the like. Likewise, an outer diameter 12 , inner diameter 14 , and the overall constitution of film in the polymer selected may all be matters of personal choice, design choice, or engineering expediency.
Thus, it may be possible to use two or more turns in an apparatus 10 about one or more pairs of socks 40 . Similarly, the single loop 10 may be sufficient. However, it has been found that more turns with higher tension become more difficult to remove as tension equalizes during the rustle and bustle of the washing and drying processes. Thus, an apparatus 10 is adaptable to being used on one pair of socks 40 with a single loop 10 , or providing multiple turns 26 , 28 with a single pair 40 .
The size of any of the dimensions may be selected to provide a comfort level. It may even be provided in multiple sets of dimensions in order to provide a tough pull or more forceful requirement, a more modest or medium amount of pull, or a comparatively easy pull. Of course these gradations may be color coded, may be marked, such as with numbers or emblems on the tab 30 , and so forth.
The present invention may be embodied in other specific forms without departing from its purposes, functions, structures, or operational characteristics. The described embodiments are to be considered in all respects only as illustrative, and not restrictive. The scope of the invention is, therefore, indicated by the appended claims, rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
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A sock tie is used when laundering socks, in order to keep a pair together. Formed of a comparatively high temperature polymer, the elastomeric loop may be drawn around a pair of socks one or more times to bind them together. The tension in the loop need not be excessively high. The nearer to the center of the length of a pair of socks the loop is placed, the less tension is required, inasmuch as the socks themselves by their random motion will resist self removal of the band or loop. Logos, labels, text, instructions, images, colors and the like may be formed into tabs attached at one or more points about the circumference of a sock tie loop. The tab provides an ease of removal while also providing space for advertising, logos, instructions, or the like.
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This is a divisional application of Ser. No. 389,533, filed 8/20/73, now U.S. Pat No. 3,998,910 and a continuation-in-part of Ser. No. 143,225, now abandoned.
BACKGROUND OF THE INVENTION
This application is a continuation in part of copending application U.S. Ser. No. 143,225, filed May 13, 1971 and entitled "Process for the Polymerization and Copolymerization of Vinyl and Diene Compounds".
This invention relates to new polymeric and copolymeric compositions containing chemically bound tertiary amine nitrogen in the macromolecular structure and processes for their preparation.
The polymerization of unsaturated compounds in the presence of initiating system comprising diacyl peroxides and tertiary amines is known, for example, from U.S. Pat. Nos. 2,647,878 and 2,744,886. However, the starting amines and the products of the reaction of the amines with diacyl peroxide remain free and chemically unbound to the high molecular weight chains of the polymers produced, especially in the case of block or bead polymers. Consequently, the possible diffusion of the amines into the environment presents a serious obstacle in the application of polymers manufactured in this way in numerous areas of use, and particularly in such areas of use as sanitation and nutrition.
There exists, therefore, a need to provide polymeric compositions such as those mentioned above and processes for their preparation which do not exhibit the abovementioned disadvantages and, therefore, permit the use of such polymeric compositions in a wider variety of applications than heretofore employed. The present invention fulfills such a need.
SUMMARY OF THE INVENTION
In accordance with the invention there are provided unsaturated compounds at ambient temperature in the presence of an initiating system comprising an organic peroxide and a macromolecular compound containing at least one chemically bound tertiary amino group in a macromolecule. By macromolecular compounds, containing in its molecules at least one chemically bound tertiary amine group are meant synthetic and natural compounds with molecules, being formed partly by carbon atoms, where one of the basic, structural units is repeated at least three times. The tertiary amine groups may be built in the macromolecular compound molecule by different ways such as:
A. WHEN PREPARING THEM BY HOMOPOLYMERIZATION AND COPOLYMERIZATION OF ETHYLENICALY UNSATURATED MONOMERS SUCH AS: POLY(N,N-dimethylaminostyrene), poly(dimethylaminoethylmethacrylate), poly(dimethylaminoethylacrylate), poly(N-vinylpyrrolidone), poly(N-vinylcarbazol), poly(N-vinylmorpholine), poly(N,N-dimethylamine-styrene-co-styrene, poly-dimethylaminoethylacrylate-co-methylmethacrylate),
B. WHEN PREPARING THEM BY POLYREACTIONS (POLYADDITION, POLYCONDENSATION) OF LOW MOLECULAR COMPOUNDS WITH SUITABLE FUNCTIONAL GROUPS E.G. REACTION OF DI-GLYCIDYLETHER 2,2-BIS-(P-HYDROXYPHENYL)PROPANE WITH ANILINE DERIVATIVES/R. L. Bowen, H. Argentar, J. Dental Research 51, 473 (1972)/,
c. by polymer analogous reactions on natural and synthetic polymer such as: alkylation or alkylarylation of primary and secondary amine groups, bound to the polymer, by reduction of carbonyl groups in poly(N,N-dialkyl-acrylamide) or by dialkylaminomethylation of poly(2-alkyl-4-vinylphenol)/F. Danusso, P. Ferruti, Polymer 11, 88 (1970); P. Ferruti, A. Bertelli, Polymer 13, (4) 184 (1972)/.
DESCRIPTION OF PREFERRED EMBODIMENTS
According to the invention, the compositions comprise homopolymers and copolymers of unsaturated compounds of the formula ##STR1## wherein X can be the same or different and can be hydrogen, halogen, --CN, ##STR2## --CH 2 Y, --C 6 H 4 Y, --CY═CHY, ##STR3## and Y can be hydrogen, halogen, alkyl, hydroxyl, amino, N,N-dialkylamino, N,N-diarylamino, N-alkyl-N-arylamino, N,N-dialkylaminoaryl, N,N-diarylaminoalkyl, N,N-diarylaminoaryl, N-alkyl-N-arylaminoalkyl, N,N-dialkylaminoalkyl, --NHC 6 H 4 COOH and --O--C 6 H 4 COOH.
The polymers of this invention can be linear or branched and generally have an average degree of polymerization in a range of from about 5 to about 100,000 and more, indicative of average molecular weight in a range from about 500 to about 5 000 000 determined by the vapor-pressure or osmometric methods. The polymeric compositions can also be crosslinked with any known suitable crosslinking agents such as divinylbenzene, glycol methacrylate, and butadiene and the like. Moreover, depending on the character of the compounds or materials being polymerized, or on the ratio in the original polymerization mixture, the homopolymers or copolymers formed can be plastic, rubbery or hard and they may be used as adhesives, rubbers, lacquers, thermoplasts or thermosets.
When the tertiary amine nitrogen is already present in the starting unsaturated compound, homopolymers can be formed simply by polymerizing the polymerization components in the presence of a suitable peroxide. Where such is not the case, the macromolecular tertiary amine is provided as part of the initiating system and copolymers are thusly obtained.
In general, a wide variety of unsaturated compounds or materials having the above formula ##STR4## can be employed in carrying out the practice of this invention. Such compounds or materials include all known vinyl compounds and conjugated diene compounds. Exemplary but not limitative unsaturated compounds or materials suitable for use in this invention are vinyl compounds such as styrene and its derivatives, divinylbenzene, vinylchloride, vinylpyridine, N-vinylpyrrolidone, acrylic acid and its derivatives, vinylidene chloride, vinyl acetate and the like; conjugated diene compounds or materials such as chloroprene, butadiene, isoprene, 2,3-dichlorbutadiene and the like; vinyl and conjugated diene compounds or materials containing tertiary amine nitrogen such as p-dimethylaminostyrene, 2-dimethylaminoethyl acrylate, 2-dimethylaminoethyl methacrylate, N-vinylcarbazole and product of dialkylaminomethylation of poly(2-alkyl-4-vinylphenol) and the like. Moreover, compounds such as those set forth which are already polymerized and copolymerized can also be reacted in accordance with this invention to form more complex polymeric molecules.
The polymerizable materials or reactants employed in this invention can be utilized in all proportions or ratios with such other depending upon the desired properties and the use of the product. However, the most appropriate unsaturated compounds are those whose polymerization is not retarded by the tertiary amine nitrogen material employed.
The effect of a chosen macromolecular tertiary amine upon the polymerization of a particular unsaturated compound can be determined experimentally. Thus for example, poly(p-dimethylaminostyrene) retards the polymerization of vinyl acetate but initiates without retardation in the presence of benzoylperoxide the polymerization of styrene and methyl methacrylate.
Any macromolecular compound with chemically bound tertiary amino group can be used in carrying out the present invention.
Generally the peroxide employed is used in an amount ranging from about 0.01 percent to about 5.0 percent by weight, based on the monomer weight. It is preferable, however, to employ the peroxide in an amount of from about 0.2 to 0.3 percent to about 1.0 percent by weight, based on the monomer weight. The amount of amine is preferably chosen in such a manner that the molar number of tertiary amino groups equals approximately the molar number of peroxide groups in the amount of peroxide employed. However, the molar ratio between peroxide and amino groups can be used within the range 1:10 to 10:1. Moreover, the polymerization of some unsaturated compounds such as chloroprene occurs without the addition of peroxide, the reaction probably proceeding by initiation of the absorbed oxygen. These ranges also apply where polymeric materials are being further combined.
Peroxides which can be employed include the diacyl peroxides, diarylperoxides and dialkyl peroxides. However, because of their thermal stability, dibenzoylperoxide, dilauroylperoxide and di-tert-butylperoxide have been found to be particularly useful.
Where the substituents X and Y in the formula set forth above are of non-polar character, alcohols can be used as precipitating agents for the polymers and copolymers. On the other hand, where the substituents are polar, saturated aliphatic and alicyclic hydrocarbons are generally used as precipitating agents for the polymer.
The preparation of the new polymeric compositions of this invention broadly comprises mixing the unsaturated compound or compounds and the peroxide or peroxide tertiary amine initiating system and polymerizing the mixture at ambient temperatures, generally at about 25° C., until polymerization is complete. However, temperatures ranging from about 20° C. to about 30° C. are preferred and the upper limit may be as high as the decomposition temperature of the materials to be reacted and of the final reaction product. The polymeric material so formed can then be precipitated, depending upon whether it is polar or nonpolar in character, with a suitable precipitating agent as mentioned above.
The polymeric materials of this invention and the preparation thereof present many advantages, for example, the polymers contain chemically bound tertiary amine nitrogen and, therefore can be used in a wide variety of fields including the areas of sanitation and nutrition. Moreover, they are simple to prepare under relatively mild conditions on existing equipment and with readily available materials.
In order to illustrate the present invention more fully the following examples are set forth. It is to be understood that the examples are illustrative and not limitative. In the examples and the appended claims all parts, proportions and percentages are by weight unless otherwise stated.
EXAMPLE I
Solutions of 0.083 gram of benzoyl peroxide in 3 grams of styrene and 0.051 gram of poly(p-dimethylaminostyrene) in 3.2 grams of styrene were mixed together in glass ampoules having two arms and which had been previously flushed with nitrogen, sealed, and placed into a bath maintained at the constant temperature of 20° C. The mixture was thick and gelatinous after 1 hour and when precipitated with methanol formed a hard, slightly yellowish polymer. It had a number average molecular weight of 45 000 and was suitable for use as block or powder polystyrene.
EXAMPLE II
Solutions of 0.088 gram of benzoyl peroxide in 3 grams of chloroprene and 0.054 gram of poly(p-dimethylaminostyrene) in 4 grams of chloroprene were mixed and further worked up as in the case of Example I. The ampoule became considerably warm and the mixture turned into a rubber-like, pale brown polymer after several minutes which was crosslinked and insoluble in benzene and was suitable for use as vulcanized polychloroprene rubber.
EXAMPLE III
A solution consisting of 0.20 gram of lauroyl peroxide in 4.4 grams of methyl methacrylate was mixed with a solution containing 0.30 gram of a copolymer of methyl methacrylate and N,N-dimethylaminoethyl methacrylate in a glass dilatometer which was then placed in a bath having a constant temperature of 20° C. According to the volume and contraction of the mixture, the polymerization took place at a rate of 0.7% in an hour. The solid, colorless polymer was precipitated from the mixture with methanol and had a number average molecular weight of 62 000 and was suitable for use as a molding polymer.
EXAMPLE IV
A solution of 0.0067 gram of benzoyl peroxide in 0.5 gram of styrene was added to 0.5 gram of the powdery polystyrene and 0.0041 gram of poly(p-dimethylaminostyrene). The resulting mixture was mixed and kept in a test tube under a nitrogen blanket at the ambient room temperature of about 20° to 30° C. It became hard and slightly yellowish after 18 hours, had an average molecular weight of 46 000. The polymeric mixture is suitable for use as selfcuring monomer-polymer composition.
EXAMPLE V
A mixture of 0.3 gram of powdery polystyrene, 0.005 gram of poly(p-dimethylaminostyrene), 0.7 gram of chloroprene and 0.009 gram of benzoyl peroxide was blended together and kept under a nitrogen blanket in a sealed test tube at the room temperature of about 20° to 30° C. The polymer which was formed was tough and brownish colored after 18 hours. It was crosslinked and was suitable for use as modified vulcanized polychloroprene rubber.
EXAMPLE VI
A copolymer of styrene and p-dimethylaminostyrene (molecular ratio 50:1) in an amount of 0.5 gram was stirred into a solution of 0.0064 gram of benzoyl peroxide in 0.5 gram of methyl methacrylate and the mixture was kept in a sealed test tube which had previously been filled with nitrogen. The content of the test tube was hard and colorless after 20 hours of standing, the product had a number average molecular weight of 65 000 and was suitable for use as selfcuring dental materials.
EXAMPLE VII
A solution of 0.048 gram of lauroyl peroxide in 0.5 gram of styrene was blended with 0.5 gram of the copolymer of methyl methacrylate and N,N-dimethylaminoethyl acrylate (molecular ratio 40:1). The mixture was sealed in a test tube under a nitrogen blanket and the test tube was kept in a laboratory stand. The test tube was opened after 20 hours and the polymer formed was hard and cloudy, had a number average molecular weight of 84 000. The starting mixture is suitable for use as selfcuring monomer-polymer composition.
EXAMPLE VIII
A solution of 1 gram of copolymer of methyl methacrylate and N,N-dimethylaminoethyl acrylate (molecular ratio 40:1) in 15 grams of methyl methacrylate was mixed with a solution containing 0.058 gram of benzoyl peroxide in 3 grams of methyl methacrylate in an evacuated ampoule. The clear, flowable liquid turned to a syrup after 17 hours. The poly(methyl methacrylate) which was precipitated with methanol had an average molecular weight of 56 000.
EXAMPLE IX
To a solution of 0.2 gram of a copolymer of styrene and p-dimethylaminostyrene (molecular ratio 50:1) in 0.8 gram of cloroprene, 0.009 gram of benzoyl peroxide was added. Nitrogen was passed through the resulting mixture which was then kept in a sealed ampoule at room temperature, i.e. about 20° to 30° C. The mixture had the character of a gel after 18 hours and of a rubber-like polymer after 72 hours, and was crosslinked. The starting composition, as well as the monomer-polymer compositions in examples 2 and 5, is suitable to transform liquid monomer to solid vulcanized product.
EXAMPLE X
Solutions of 0.083 gram of benzoyl peroxide in 4 grams of styrene and of 0.050 gram of N,N-dimethyl-p-aminostyrene in 2.2 grams of styrene were mixed in a glass dilatometer. The dilatometer was placed in a bath with a controlled constant temperature of 25° C. According to the volume contraction of the mixture, the polymerization took place at a rate of 4.4% in an hour. The polymer at completion of the reaction was precipitated from the reaction mixture by addition of an excess of methanol, as a slightly yellowish powder, having an average molecular weight of 45 000.
EXAMPLE XI
Solutions of 0.083 gram of benzoyl peroxide in 4 grams of methylmethacrylate and 0.051 gram of N,N-dimethyl-p-aminostyrene in 2.5 grams of methyl methacrylate were mixed in a glass dilatometer at 25° C. The polymerization rate was 9.7% in an hour. The colorless powdery polymer formed at completion of the reaction was precipitated by methanol, had an average molecular weight of 85 000.
EXAMPLE XII
A mixture of solutions consisting of 0.081 gram of benzoyl peroxide in 4 grams of chloroprene and 0.049 gram of N,N-dimethyl-p-aminostyrene in 2.4 grams of chloroprene was polymerized at 20° C. at the rate of 6.6% of the monomer present in an hour. The plastic, brownish-red polymer was precipitated at completion of the reaction by addition of methanol. It was crosslinked and insoluble in benzene.
EXAMPLE XIII
Polymerization of a mixture consisting of 6.6 grams of styrene, 0.008 gram of benzoyl peroxide and 0.057 gram of N,N-dimethylaminoethyl methacrylate was carried out at 25° C. at a rate of 1.2% in an hour. The polymer on completion was precipitated with methanol and was fibrous and brownish, having an average molecular weight of 26 000.
EXAMPLE XIV
Polymerization of a mixture consisting of 6.45 grams of methyl methacrylate, 0.136 gram of lauroyl peroxide and 0.049 gram of N,N-dimethylaminoethyl acrylate was carried out at 25° C. at a rate of 1.4% in an hour. The polymer after completion of the reaction and after precipitation with methanol was tough and colorless.
EXAMPLE XV
A solution of 0.003 gram of N,N-dimethyl-p-aminostyrene in 0.4 gram of styrene was added to 0.6 gram of finely ground polystyrene and 0.005 gram of benzoyl peroxide powder. The sticky mixture was plasticized and then kept in a sealed test tube at room temperature of about 20° C. to 25° C. under an atmosphere of nitrogen. It became hard and brownish after 24 hours.
EXAMPLE XVI
A mixture of 0.3 gram of polystyrene, 0.009 gram of benzoyl peroxide, 0.7 gram of styrene and 0.006 gram of N,N-dimethyl-p-aminostyrene was blended and kept in a sealed test tube under nitrogen at room temperature of about 20° C. to 25° C. The originally sticky, syrupy blend was converted into a brownish gel within 18 hours.
EXAMPLE XVII
A mixture of 0.6 gram of poly(methyl methacrylate) with 0.005 gram of benzoyl peroxide, 0.4 gram of stytene and 0.003 gram of N,N-dimethyl-p-aminostyrene was plasticized and placed into a sealed test tube filled with nitrogen. The contents of the test tube were hard and colorless after being kept in a laboratory stand for 20 hours.
EXAMPLE XVIII
A mixture of 0.6 gram of polystyrene with 0.005 gram of benzoyl peroxide and 0.4 gram of methyl methacrylate with 0.003 gram of N,N-dimethylaminoethyl was plasticized and kept in a sealed test tube under nitrogen at room temperature of about 25° C. It became hard and colorless after 18 hours.
EXAMPLE XIX
The mixture as described in Example XVIII, but containing 0.008 gram of lauroyl peroxide instead of benzoyl peroxide became hard and colorless after being kept in a laboratory test tube for 18 hours. The starting composition as well as the compositions in examples 15, 17 and 18, is suitable for use as selfcuring monomer-polymer composition.
Similar materials such as those mentioned hereinbefore when processed according to the foregoing examples gave products of like properties.
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Monomeric conjugated or unconjugated organic compounds are polymerized in an initiator systems consisting of an organic peroxide and a macromolecular compound consisting of a polymer or copolymer of styrene or styrene derivative containing at least one tertiary amine group chemically bound by all its valences to carbon atoms in its macromolecule.
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TECHNICAL FIELD
[0001] The present invention relates generally to integrated circuits, and more specifically to lowering power consumption in integrated circuits during certain modes of operation.
BACKGROUND OF THE INVENTION
[0002] Many battery-powered portable electronic devices, such as laptop computers, Portable Digital Assistants, digital cameras, cell phones and the like, require memory devices that provide large storage capacity and low power consumption. One type of memory device that is well-suited to use in such portable devices is flash memory, which is a type of semiconductor memory that provides relatively large nonvolatile storage capacity for data. The nonvolatile nature of the storage means that the flash memory does not require power to retain the data, as will be appreciated by those skilled in the art.
[0003] A typical flash memory comprises a memory-cell array having an array of memory cells arranged in rows and columns and grouped into blocks. FIG. 1 illustrates a conventional flash memory cell 100 formed by a field effect transistor including a source 102 and drain 104 formed in a substrate 106 , with a channel 108 being defined between the source and drain. Each of the memory cells 100 further includes a control gate 110 and a floating gate 112 formed over the channel 108 and isolated from the channel and from each other by isolation layers 114 . In the memory-cell array, each memory cell 100 in a given row has its control gate 110 coupled to a corresponding word line WL and each memory cell in a given column has its drain 104 coupled to a corresponding bit line BL. The sources 102 of each memory cell 100 in a given block are coupled together to allow all cells in the block to be simultaneously erased, as will be appreciated by those skilled in the art.
[0004] The memory cell 100 is charged or programmed by applying appropriate voltages to the source 102 , drain 104 , and control gate 110 and thereby injecting electrons e − from the drain 104 and channel 108 through the isolation layer 114 and onto the floating gate 112 . Similarly, to erase the memory cell 100 , appropriate voltages are applied to the source 102 , drain 104 , and control gate 110 to remove electrons e − through the isolation layer 114 to the source 102 and channel 108 . The presence or absence of charge on the control gate 112 adjusts a threshold voltage of the memory cell 100 and in this way stores data in the memory cell. When charge is stored on the floating gate 112 , the memory cell 100 does not turn ON when an access voltage is applied through the word line WL to the control gate 110 , and when no charge is stored on the floating gate the cell turns ON in response to the access voltage. In this way, the memory cell 100 stores data having a first logic state when the cell turns ON and having a second logic state when the cells does not turn ON.
[0005] To reduce the power consumption and thereby extend the battery life in portable electronic devices, the flash memory typically operates in a low-power or standby mode when the memory is not being accessed. When a flash memory is operating in the standby mode, the memory will at some point be activated to commence data transfer operations in an active mode of operation. For example, in a portable device the flash memory may be operated in the standby mode when a key has not been pressed for a specified time, and be activated in response to a user pressing a key. The time required to switch from the standby mode to the active mode is ideally minimized so that a user does not experience a delay due to the flash memory changing modes of operation. Thus, the flash memory should be able to begin transferring data to and from the memory cells 100 as soon as possible after termination of the standby mode. In a conventional flash memory, a chip enable signal CE# is applied to the memory and places the memory in the standby and active modes when inactive high and active low, respectively. The “#” designates a signal as being active low, as will be appreciated by those skilled in the art.
[0006] Certain circuits within the flash memory continue operating during the standby mode to enable the flash memory to more quickly return to the active mode of operation. For example, as illustrated in FIG. 2, a conventional flash memory includes a charge pump 200 that generates a word line drive voltage VX that is used by row drivers 202 in activating corresponding word lines WL. Each row driver 202 is coupled to a respective word line WL 1 -N in the memory-cell array (not shown) and receives a corresponding decoded row address signal DRA 1 -N. When the DRA 1 -N signal indicates the corresponding row of memory cells 100 is to be activated, the row driver 202 applies the voltage VX to the word line WL 1 -N to thereby activate the row of memory cells 100 (not shown in FIG. 2) coupled to the word line. When the DRA 1 -N signal indicates the corresponding row of memory cells 100 is to be deactivated, the row driver 202 drives the corresponding word line WL 1 -N to ground to deactivate the row of memory cells 100 .
[0007] During the standby mode, the charge pump 200 continues generating the word line drive voltage VX so that the row drivers 202 can more quickly activate a selected word line WL when the flash memory is thereafter placed in the active mode. The faster the flash memory can activate a selected word line WL, the faster data can be read from the memory upon return to the active mode, and thus the faster a portable electronic device containing the memory can return to normal operation. As will be understood by those skilled in the art, a bandgap voltage reference 204 generates a bandgap voltage reference VBG that is supplied to the charge pump 200 , and the charge pump 200 utilizes the bandgap reference voltage VBG in generating the supply voltage VX, as will be understood by those skilled in the art. The bandgap voltage reference 204 is a popular analog circuit for generating the bandgap reference voltage VBG that is very stable as a function of temperature and as a function of variations in a supply voltage VCC supplied to the bandgap voltage reference. One skilled in the art will understand various circuits that can be utilized in forming the bandgap voltage reference 204 , charge pump 200 , and row drivers 202 , and thus, for the sake of brevity, the details of these components will not be discussed herein. Moreover, although the voltage reference 204 is described as being a bandgap voltage reference, other suitable voltage references may also be utilized, as will be understood by those skilled in the art.
[0008] In operation, the conventional bandgap voltage reference 204 consumes a relatively large current in generating the reference voltage VBG. As will be appreciated by those skilled in the art, the bandgap voltage reference 204 draws a relatively large current to enable the voltage reference to quickly charge the reference voltage VBG to its desired value and maintain the reference voltage in response to fluctuations in the supply voltage VCC. As a result, during the standby mode of operation the bandgap voltage reference 204 draws a relatively large current, which increases the power consumption of the flash memory containing the bandgap voltage reference and reduces the battery life of a portable device containing the memory. If a low-current bandgap voltage reference 204 were used, the bandgap reference voltage VBG will not have the required stability as a function of temperature and variations in the supply voltage VCC, and the bandgap voltage reference would take an undesirably long time to charge the voltage VBG to the desired value when the supply voltage VCC is initially supplied to the bandgap voltage reference.
[0009] There is a need for reducing the current consumption of a flash memory during a standby mode of operation while still providing a highly stable bandgap reference voltages to required circuits in the memory, and for minimizing the time required for the flash memory to switch from the standby to active mode of operation.
SUMMARY OF THE INVENTION
[0010] According to one aspect of the present invention, a voltage switching circuit includes an active voltage reference receiving a mode signal and operable responsive to the mode signal going active to generate a first reference voltage. The active voltage reference terminates generation of the first reference voltage responsive to the mode signal going inactive. A standby voltage reference generates a second reference voltage, and a multiplexer coupled to the active and standby voltage references applies the first and second reference voltages on an output responsive to a selection signal going active and inactive, respectively. A delay circuit is coupled to the multiplexer and receives the mode signal. The delay circuit drives the selection signal active a delay time after the mode signal goes active in response to the mode signal going active and drives the selection signal inactive without the delay time responsive to the mode signal going inactive.
[0011] According to another aspect of the present invention, a method of operating a memory includes generating a first reference voltage and detecting an active mode of operation of the memory. Upon detection of the active mode, commencing the charging of a node to develop a second reference voltage having a desired value on the node. The word line drive voltage is generated using the first reference voltage while the node is charging the second reference voltage to the desired value. The word line drive voltage is generated using the second reference voltage once the second reference voltage on the node has been charged to the desired value. A standby mode of operation of the memory is detected, and upon detection of the standby mode, the charging of the node is terminated and the word line drive voltage is generated using the first reference voltage.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] [0012]FIG. 1 is a simplified cross-sectional view of a conventional flash memory cell.
[0013] [0013]FIG. 2 is a schematic illustrating a conventional charge pump and bandgap voltage reference for generating a word line drive voltage used by a row driver in accessing data stored in the memory cell of FIG. 1.
[0014] [0014]FIG. 3 is a functional block diagram illustrating a voltage reference switching circuit including dual bandgap voltage references according to one embodiment of the present invention.
[0015] [0015]FIG. 4 is a functional block diagram of a flash memory including the voltage reference switching circuit of FIG. 3.
[0016] [0016]FIG. 5 is a functional block diagram illustrating a computer system including the flash memory of FIG. 4.
DETAILED DESCRIPTION OF THE INVENTION
[0017] [0017]FIG. 3 is a functional block diagram illustrating a voltage reference switching circuit 300 including an active bandgap voltage reference 302 for generating a bandgap reference voltage VBG during an active mode of operation of a flash memory (not shown) containing the switching circuit, and including a standby bandgap voltage reference 304 for generating the bandgap reference voltage during a standby mode of operation of the flash memory, as will be explained in more detail below. The active bandgap voltage reference 302 consumes a relatively large amount of power and operates only during the active mode, while the standby bandgap voltage reference 304 consumes a relatively small amount of power and operates during the standby mode. The switching circuit 300 reduces the power consumption of the flash memory during the standby mode, and also reduces a transition time of the flash memory in switching between the active and standby modes, as will described in more detail below.
[0018] In the following description, certain details are set forth to provide a sufficient understanding of the present invention, but one skilled in the art will appreciate that the invention may be practiced without these particular details. In other instances below, the operation of well known components have not been shown or described in detail to avoid unnecessarily obscuring the present invention.
[0019] The bandgap switching circuit 300 further includes a charge pump 306 that supplies a word line drive voltage VX to a plurality of row drivers 308 . The charge pump 306 and row drivers 308 operate in the same manner as the charge pump 200 and row drivers 202 of FIG. 2, and thus, for the sake of brevity, the operation of these components will not again be described in detail. In the bandgap switching circuit 300 , a multiplexer 310 receives a first bandgap voltage VBG 1 from the active bandgap voltage reference 302 and receives a second bandgap voltage reference VBG 2 from the standby bandgap voltage reference 304 . The multiplexer 310 applies either the VBG 1 or VBG 2 voltage to the charge pump 306 as the VBG voltage in response to a band gap selection signal SELBG generated by a delay circuit 312 , which generates the SELBG signal in response to an internal chip enable signal CEI#. In operation, when the CEI# signal goes active low, the delay circuit 312 drives the SELBG signal low after a time delay TD. When the CEI# signal goes in active high, the delay circuit 312 drives the SELBG signal high with a substantially no time delay. In response to the SELBG signal being low, the multiplexer 310 outputs the VBG 1 voltage as the VBG voltage applied to the charge pump 306 . In contrast, when the SELBG signal is high, the multiplexer 310 outputs the VBG 2 voltage as the VBG voltage applied to the charge pump 306 .
[0020] In the bandgap switching circuit 300 , the standby bandgap voltage reference 304 receives a supply voltage VCC directly, and generates the VBG 2 voltage from the supply voltage. The active bandgap voltage reference 302 does not receive the supply voltage VCC directly, but instead receives the supply voltage through a switch 314 that selectively couples the supply voltage to and isolates the supply voltage from the active bandgap voltage reference in response to the CEI# signal. When the CEI# signal is active low, the switch 314 supplies the supply voltage VCC to the active bandgap voltage reference 302 which, in turn, generates the VBG 1 voltage from the supply voltage. When the CEI# signal is inactive high, the switch 314 isolates the supply voltage VCC from the active bandgap voltage reference 302 to thereby turn OFF the active bandgap voltage reference.
[0021] In operation, the bandgap switching circuit 300 operates in an active mode and a standby mode in response to the CEI# signal being active low and inactive high, respectively. The active and standby modes of the bandgap switching circuit 300 correspond to the active and standby modes of operation of the flash memory containing the bandgap switching circuit. For the following description of the overall operation of the bandgap switching circuit 300 , assume the band gap switching circuit 300 is initially operating in the active mode, with the CEI# and SELBG signals being low. In response to the low CEI# signal, the switch 314 applies the supply voltage VCC to the active bandgap voltage reference 302 which, in turn, generates the VBG 1 voltage. The low SELBG signal also causes the multiplexer 310 to apply the VBG 1 voltage to the charge pump 306 as the VBG voltage. The charge pump 306 thereafter operates as previously described to generate the VX voltage using the applied VBG voltage, and applies the VX voltage to the row drivers 308 which operate as previously described to selectively apply the VX voltage on the word lines WL 1 -N responsive to the decoded row address signals DRA 1 -N. Note that during the active mode, the standby band gap voltage reference 304 generates the VBG 2 voltage although this voltage is not utilized (the multiplexer 310 isolates this voltage). The standby bandgap voltage reference 304 consumes a relatively small amount of power, however, as previously mentioned, and thus does not significantly increase the power consumption of the flash memory during the active mode.
[0022] When the CEI# signal goes inactive high, the bandgap switching circuit 300 commences operation in the standby mode. In response to the high CEI# signal, the switch 314 isolates the supply voltage VCC from the active bandgap voltage reference 302 , turning the active bandgap voltage reference OFF. Also in response to the CEI# signal going high, the delay circuit 312 drives the SELBG signal high, causing the multiplexer 310 to apply the VBG 2 voltage from the standby bandgap voltage reference 304 to the charge pump 306 as the VBG voltage. At this point, the relatively high-power active bandgap voltage reference 302 is turned OFF while the relatively low power standby bandgap voltage reference 304 supplies the VBG voltage to the charge pump 306 . In this way, the charge pump 306 utilizes the VBG voltage from the standby bandgap voltage reference 304 in generating the VX voltage during the standby mode of operation. The power consumption of the flash memory containing the bandgap switching circuit 300 is accordingly reduced since only the relatively low power standby bandgap voltage reference 304 operates during the standby mode.
[0023] When the CEI# signal goes low, the bandgap switching circuit 300 terminates operation in the standby mode and commences operation in the active mode. In response to the low CEI# signal, the switch 314 applies the supply voltage VCC to the active bandgap voltage reference 302 which, in turn, begins charging the VBG 1 voltage to its desired value. At this point, although the CEI# signal is active low, the delay circuit 312 continues driving the SELBG signal high and thus the multiplexer 310 continues providing the VBG voltage from the standby bandgap voltage reference 304 to the charge pump 306 . Recall, the delay circuit 312 does not drive the SELBG signal low until the delay time TD after the CEI# signal goes low. Thus, while the active bandgap voltage reference 302 is charging the VBG 1 voltage to the desired value during the delay time TD, the standby bandgap voltage reference 304 supplies the VBG voltage to the charge pump 306 . The charge pump 306 thus continues generating the VX voltage using the VBG voltage from the standby bandgap voltage reference 304 , allowing any of the row drivers 308 to activate the corresponding word line WL 1 -N using the VX voltage of the charge pump. As a result, if a data transfer command such as a read command is applied to the flash memory before expiration of the delay time TD, the selected row driver 308 can activate the corresponding word line WL 1 -N to access the addressed row of memory cells 100 (FIG. 1). This is true even though the active bandgap voltage reference 302 has not yet charged the VBG 1 voltage to the desired value. After expiration of the delay time TD, the delay circuit 312 drives the SELBG signal low causing the multiplexer 310 to apply the VBG voltage from the active bandgap voltage reference 302 to the charge pump 306 which thereafter operates as previously described in generating about VX voltage from the applied VBG voltage.
[0024] With the bandgap switching circuit 300 , several data transfer operations can occur before expiration of the delay time TD and thus prior to the active bandgap voltage reference 302 charging the VBG 1 voltage to the required value. For example, a typical flash memory may have a read cycle time on the order of 50 nanoseconds. A typical time required for the active bandgap voltage reference 302 to charge the VBG 1 voltage to the required value is 200-300 nanoseconds. Thus, during the delay time TD when the VBG 1 voltage is charging to the required value, several read cycles may occur with the charge pump 306 using the VBG 2 voltage from the standby voltage reference 304 in generating the VX voltage. The value of the VBG 2 voltage is subject to more variation than the VBG 1 voltage due to the inherent characteristics of the standby voltage reference 304 . Moreover, such variations in the VBG 2 voltage can cause variations in the value of the VX voltage generated by the charge pump 306 . If the VX voltage varies too much from its required value, problems in accessing row of memory cells 100 (FIG. 1) could arise, as will be understood by those skilled in the art. This is, in part, is why flash memories do not simply use a single low power but less accurate voltage reference like the standby voltage reference 304 . In the bandgap switching circuit 300 , however, the less accurate VBG 2 voltage from the standby reference voltage 304 is used at most for only several data transfer operations. This short duration for use of the VBG 2 voltage, which is less than the delay time TD, reduces the likelihood of any intolerable variations in the VX voltage generated using the VBG 2 voltage. Moreover, typically when the flash memory transitions from the standby mode to the active mode the first data transfer operation are read commands applied to read data from the memory. During read commands, the value of the VX voltage is less critical than during write or erase operations, as will be understood by those skilled in the art. Thus, the VBG 2 voltage will typically be used in generating the VX voltage only during read data transfers, which further lessens the likelihood of any intolerable variations in the VX voltage due to variations in the VBG 2 voltage.
[0025] The bandgap switching circuit 300 utilizes the dual bandgap voltage references 302 , 304 to reduce the power consumption of the flash memory containing the bandgap switching circuit, while at the same time keeping the transition time of the flash memory from the standby mode to the active mode relatively small. The power consumption is reduced by deactivating the relatively high power and high precision active bandgap voltage reference 302 during the standby mode and using the relatively low power standby bandgap voltage reference 304 . In this way, the charge pump 306 utilizes the VBG 2 voltage generated by the low power standby voltage reference 304 to maintain the VX voltage during the standby mode and the high power active voltage reference 302 is turned OFF. The less accurate VBG 2 voltage can be used during the standby mode since the actual value of the VX voltage the charge pump 306 generates using the VBG 2 voltage is less critical because the row drivers 308 are not actually applying the VX voltage to word lines WL 1 -N to access rows of memory cells 100 (FIG. 1).
[0026] The bandgap switching circuit 300 reduces the transition time of the corresponding flash memory from the standby to active mode through the use of the dual voltage references 302 , 304 . The standby bandgap voltage reference 304 generates the VBG 2 voltage while the active bandgap voltage reference 302 is charging the VBG 1 voltage. In this way, a processor or other device can apply data transfer commands to the flash memory relatively quickly after the memory is placed in the active mode, and the processor need not wait the relatively long time (200-300 nanoseconds as mentioned above) it takes the VBG 1 voltage to charge to its required value. Note that during the active mode, the standby band gap voltage reference 304 generates the VBG 2 voltage although the voltage is not being utilized. The standby bandgap voltage reference 304 consumes a relatively small amount of power, however, and thus does not significantly increase the power consumption of the flash memory during the active mode. One skilled in the art will understand various circuits that can be used in forming the components 302 - 314 in the bandgap switching circuit 300 of FIG. 3, and thus such circuits will not be described in detail herein.
[0027] In another embodiment of the bandgap switching circuit 300 , the VBG 2 voltage is used for a predetermined number of data transfer operations after commencement of the active mode, and in this way the VBG 2 voltage is used while the VBG 1 voltage is charging to its required value. In this embodiment, the delay circuit 312 would be replaced with a circuit that monitors commands applied to the memory and the mode of the memory, and develops the SELBG signal in response to the commands and mode. Another embodiment includes voltage monitoring circuitry in place of the delay circuit 312 . The voltage monitoring circuitry monitors the value of the VBG 1 voltage as it is charging, and when it reaches a predetermined value, applies the SELBG signal to the multiplexer 310 , causing the multiplexer to apply the VBG 1 voltage to the charge pump 306 .
[0028] [0028]FIG. 4 is a functional block diagram of a flash memory 400 including the bandgap switching circuit 300 of FIG. 3. The bandgap switching circuit 300 is shown contained in a program/erase charge pump voltage switch 464 , although the row drivers 308 (FIG. 3) would typically be contained in address decoders 440 a , 440 b , as will be appreciated by those skilled in the art. The operation of the program/erase charge pump voltage switch 464 and address decoders 440 a , 440 b will be discussed in more detail below. The flash memory 400 includes a command state machine (CSM) 404 that receives control signals including a reset/power-down signal RP#, a chip enable signal CE#, a write enable signal WE#, and an output enable signal OE#, where the “#” denotes a signal as being low true. An external processor (not shown) applies command codes on a data bus DQ 0 -DQ 15 and these command codes are applied through a data input buffer 416 to the CSM 404 . A command being applied to the flash memory 400 includes the control signals RP#, CE#, WE#, and OE# in combination with the command codes applied on the data bus DQ 0 -DQ 15 . The CSM 404 decodes the commands and acts as an interface between the external processor and an internal write state machine (WSM) 408 . When a specific command is issued to the CSM 404 , internal command signals are provided to the WSM 408 , which in turn, executes the appropriate process to generate the necessary timing signals to control the memory device 400 internally and accomplish the requested operation. In response to the RP# and/or CE# signals, the CSM 404 develops applies signals to the delay circuit 312 and switch 314 (see FIG. 3) to control the mode of operation of the bandgap switching circuit 300 . In one embodiment, when the CE# signal goes active low, the CSM 404 drives the CEI# signal low, placing the bandgap switching circuit 300 in the active mode of operation. When the CE# signal goes inactive high, the CSM 404 drives the CEI# signal inactive high, placing the bandgap switching circuit 300 in the standby mode of operation.
[0029] The CSM 404 also provides the internal command signals to an ID register 408 and a status register 410 , which store information regarding operations within the flash memory 400 . The external processor issues an appropriate command to the flash memory 400 to read the ID and status registers 408 , 410 and thereby monitor the progress of various operations within the flash memory 400 . The CE#, WE#, and OE# signals are also provided to input/output (I/O) logic 412 which, in response to these signals indicating a read or write command, enables a data input buffer 416 and a data output buffer 418 , respectively. The I/O logic 412 also enables an address input buffer 422 which, in turn, applies address signals on an address bus A 0 -A 19 to an address latch 424 . The address latch 424 latches the applied address signals A 0 -A 19 from the address input buffer 422 under control of the WSM 406 .
[0030] The address multiplexer 428 selects between the address signals provided by the address latch 424 and those provided by an address counter 432 . The address signals provided by the address multiplexer 428 are used by the address decoders 440 a , 44 b to access the memory cells of memory banks 444 a , 444 b that correspond to the address signals. A gating/sensing circuit 448 a , 448 b is coupled to each memory bank 444 a , 444 b for the purpose of programming and erase operations, as well as for read operations. An automatic power saving (APS) control circuit 449 receives address signals from the address input buffer 422 and also monitors the control signals RP#, CE#, OE#, and WE#. When none of these lines toggle within a time-out period, the APS control circuit 449 generates control signals to place the gating/sensing circuits 448 a , 448 b in a power-saving mode of operation.
[0031] During a read operation, data is sensed by the gating/sensing circuit 448 a , 448 b and amplified to sufficient voltage levels before being provided to an output multiplexer 450 . The read operation is completed when the WSM 406 instructs an output buffer 418 to latch data provided from the output multiplexer 450 which, in turn, applies the latched data over the data bus DQ 0 -DQ 15 to the external processor. The output multiplexer 450 can also select data from the ID and status registers 408 , 410 to be provided to the output buffer 418 when instructed to do so by the WSM 406 . During a program or write operation, the external processor supplies data on the data bus DQ 0 -DQ 15 and the I/O logic 412 commands the data input buffer 416 to provide the data to a data register 460 to be latched. The WSM 406 also issues commands to program/erase circuitry 464 which uses the address decoders 440 a , 440 b to access memory cells in the memory banks 444 a , 444 b . The program/erase circuitry 464 operates in combination with the address decoders 440 a , 440 b , data register 460 , and gating/sensing circuits 448 a , 448 b to carry out the process of injecting or removing electrons from the accessed memory cells to thereby store the data latched by the data register 460 in the accessed memory cells. The program/erase circuitry 464 also controls the erasure of blocks of memory cells in the memory banks 444 a , 444 b . To ensure that sufficient programming or erasing has been performed, a data comparator 470 is instructed by the WSM 406 to compare or verify the state of the programmed or erased memory cells to the data latched by the data register 460 .
[0032] The flash memory 400 operates in a standby power-savings mode when the RP# and CE# signals are both high, and operates in a reset deep power-down mode when the RP# signal goes active low. In response to the high CE# signal, the CSM 404 applies a high CEI# signal (FIG. 3) to the bandgap switching circuit 300 which, in turn, turns OFF the active bandgap voltage reference 302 (FIG. 3) as previously described, reducing the power consumption of the flash memory 400 .
[0033] It will be appreciated that the embodiment of the flash memory 400 illustrated in FIG. 5 has been provided by way of example and that the present invention is not limited thereto. Those of ordinary skill in the art have sufficient understanding to modify the previously described flash memory embodiment to implement other embodiments of the present invention. For example, although the bandgap switching circuit 300 is shown as being contained in the program/erase charge pump voltage switch 464 and the row decoders 308 (FIG. 3) indicated as being contained in the address decoders 440 a , 440 b , components of the bandgap switching circuit may be incorporated in other circuit blocks in the flash memory 400 . The particular arrangement of the bandgap switching circuit 300 is a matter of design preference. Moreover, although the bandgap switching circuit 300 is described as including the bandgap voltage references 302 , 304 , other types of voltage reference circuits can also be utilized, as will be understood by those skilled in the art. Although the bandgap switching circuit 300 has been described with reference to flash memories, the circuit and principles described herein may also be applied to other types of memories and integrated circuits.
[0034] [0034]FIG. 5 is a block diagram of a computer system 600 including computer circuitry 602 that contains the flash memory 400 of FIG. 4. The computer circuitry 602 performs various computing functions, such as executing specific software to perform specific calculations or tasks. In addition, the computer system 600 includes one or more input devices 604 , such as a keyboard or a mouse, coupled to the computer circuitry 602 to allow an operator to interface with the computer system. Typically, the computer system 600 also includes one or more output devices 606 coupled to the computer circuitry 602 , such output devices typically being a printer or video display. One or more data storage devices 608 are also typically coupled to the computer circuitry 602 to store data or retrieve data from external storage media (not shown). Examples of typical storage devices 608 include hard and floppy disks, tape cassettes, compact disc read-only memories (CDROMs), read-write CD ROMS (CD-RW), and digital video discs (DVDs). The computer system 600 also typically includes communications ports 610 such as a universal serial bus (USB) and/or an IEEE-1394 bus to provide for communications with other devices, such as desktop or laptop personal computers, a digital cameras, and digital camcorders. The computer circuitry 602 is typically coupled to the flash memory 400 through appropriate address, data, and control busses to provide for writing data to and reading data from the flash memory.
[0035] Even though various embodiments and advantages of the present invention have been set forth in the foregoing description, the above disclosure is illustrative only, and changes may be made in detail and yet remain within the broad aspects of the invention. Therefore, the present invention is to be limited only by the appended claims.
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A method of operating a memory includes generating a first reference voltage and detecting an active mode of operation of the memory. Upon detection of the active mode, commencing the charging of a node to develop a second reference voltage having a desired value on the node. The word line drive voltage is generated using the first reference voltage while the node is charging the second reference voltage to the desired value. The word line drive voltage is generated using the second reference voltage once the second reference voltage on the node has been charged to the desired value. A standby mode of operation of the memory is detected, and upon detection of the standby mode, the charging of the node is terminated and the word line drive voltage is generated using the first reference voltage.
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CROSS-REFERENCES TO RELATED APPLICATIONS
This application is a U.S. national stage application of International Application No. PCT/FI00/00843, filed Oct. 2, 2000, and claims priority on Finnish Application No. 19992133 filed Oct. 4, 1999, the disclosures of both of which applications are incorporated by reference herein.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
Not applicable.
BACKGROUND OF THE INVENTION
The present invention relates to a procedure for generating and maintaining turbulence in stock suspension flow conducted through a turbulence generator into the slice duct of the headbox and therefrom through the slice opening to the web former, in which procedure the stock suspension flow is with the aid of turbulence pipes divided into a number of superimposed layers, whereafter the effect of the elements creating and maintaining turbulence is directed thereupon.
The invention also relates to a turbulence generator of the headbox of a paper machine, comprising a number of overlapping turbulence pipes being arranged in rows and extending across the entire width of the headbox, through which pipes the stock suspension flow to be conducted from the headbox to the web former is arranged to flow and which turbulence pipes are provided with stepwise expansion of the flow cross-section area between the inlet and outlet of the pipe, and to which turbulence generator a plurality of headbox dividers or lamellae can moreover be connected, starting from between the pipe rows and extending to the slice duct of the headbox.
It is of vital importance, considering the quality of the paper/board being manufactured, to understand what kind of turbulence spectrum of stock suspension flow prevails in the slice duct of the headbox and in the subsequent web former. The turbulence generated with the aid of the turbulence generator in the stock suspension flow will decrease quite rapidly unless turbulence energy is continuously added in the flow. The formation of paper or board is best enhanced by small-scale vortices which efficiently disintergate fibre bundles. Large-scale vortices may even be detrimental considering the formation of paper. Owing to the properties of the turbulence, the small-scale vortices are first to reduce in the flow, whereby, for instance, the surface layer of the web on the Fourdrinier wire and the middle layer of the web on a gap former tend to be more flocculated than the other layers due to decreasing turbulence. A generally employed manner to increase turbulence energy in the flow by using the draw between the slice jet and the wire does not act in the area being dewatered last. In order to have more turbulence in said area, the draw is to be great. Hereby, the formation of the area dewatered first is easily deteriorated to the extent that the formation of the entire product can no longer be improved. A similar progress may also occur when endeavours are made in the web former to introduce turbulence energy into a stock suspension layer not yet dewatered, e.g. by means of loading lists through a layer already dewatered.
In a majority of the state-of-art turbulence generators, all turbulence pipes are mutually identical because the aim is to achieve homogeneous turbulence in different parts of the stock flow. Such turbulence generators make no difference between the bottom, surface and middle layers of the web. In web formation, said layers become, however, dewatered at different times. On the Fourdrinier wire, the surface layer is dewatered last and in the gap former the layer to be dewatered last is the middle layer.
In patent specification U.S. Pat. No. 5,124,002, a turbulence generator is disclosed in which the flow cross-section areas of the turbulence pipes in superimposed layers differ in size and shape, and advantageously, the mutual spaces between the pipes are also different. In this manner, a different microturbulence level can be generated in different layers of the stock suspension flow discharging from the turbulence generator into the slice duct, and such paper can be manufactured which is provided with different fibre orientations in superimposed layers. The flow cross-section area of each turbulence pipe remains the same from the first part of the pipe to the end thereof.
Such turbulence generators are also known in the art in which the flow cross-section area of the turbulence pipes is step-wise expanded at least at one spot between the inlet and the outlet of the pipe. In the turbulence generators known in the art, the expansion spots of the pipe are at equal distance from the outlet of the pipe in all pipes. One such prior art design is disclosed in U.S. Pat. No. 5,183,537.
SUMMARY OF THE INVENTION
The objective of the present invention is to develop a new procedure for generating and maintaining turbulence and a new kind of turbulence generator, with the aid of which a different turbulence can be generated in different layers of stock suspension flow flowing out of the headbox.
One more aim of the invention is to achieve an application in which the turbulence of the stock suspension layer dewatered last in the former after the headbox can be maintained closer to the optimal level during the formation than with currently used turbulence generators. Thus, the aim is a stock suspension flow in which the turbulence is “freshest”, and consequently, most lasting in the layers of the flow which stay “running” longest. When the impact of the factors generating turbulence in the flow ceases, the turbulence begins to slow down rapidly. The turbulence is the fresher the shorter length the flow has propagated after the generation of turbulence.
To achieve said objectives and those to be disclosed below, the procedure of the invention is characterized in that turbulence is generated in different layers of the flow in different phases of the flow by arranging the elements generating and maintaining turbulence at different distances from the slice opening of the headbox, so that a different turbulence prevails in different layers of the stock suspension flow.
Respectively, the turbulence generator of the invention is characterized in that the distance of the expansion spot of the turbulence pipes in superimposed pipe rows from the slice opening of the headbox and/or the distance of the tips of the trailing elements in association with the pipe rows from the slice opening of the headbox is different so that at the slice opening, the turbulence is different in different layers of the stock suspension flow.
In an advantageous embodiment of the invention, the expansion spots of individual turbulence pipes of a turbulence generator are so stepped that in the superimposed turbulence pipe rows, the expansion of the flow cross-section area is carried out at a different distance from the slice opening of the headbox. The later the phase is in which the cross-section area of a turbulence pipe expands, the fresher is the turbulence as the stock suspension flow discharges from the slice opening of the headbox onto the forming wire or into the gap between the forming wires. The expansion spots of the turbulence pipes acting on the layer of the stock suspension flow to be dewatered last are arranged to be last in the flow direction, that is, closest to the slice opening.
In addition to stepping the expansion spots, or instead of it, a different turbulence can be generated in different layers of the stock suspension flow by providing, after the turbulence pipes, trailing elements extending to the slice duct, which in superimposed flow layers extend to a different distance from the slice opening of the headbox. The trailing elements can be fixed in length or their lengths can be adjustable, as in U.S. Pat. No. 4,133,713. Alternatively, the fixing point of a trailing element in the longitudinal direction to the headbox can be adjustable, as in FI patent specification No. 88317. The purpose of the trailing elements is to keep different layers of the stock suspension flow separated as long as possible after a different turbulence has first been generated in the layers, for example, by stepping the expansion parts or by employing turbulence pipes differing in the flow cross-section area. The trailing elements maintain and strengthen the difference of turbulences prevailing between different layers. Alternatively, all trailing elements can be mutually of equal length, whereby various levels of turbulence prevailing in different layers can be achieved solely with the aid of structural differences of turbulence pipes.
The invention is described below more in detail, reference being made to the figures of the accompanying drawing, to which, however, the invention is not intended to be exclusively restricted.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 presents schematically a headbox provided with a turbulence generator of the invention, being particularly appropriate for use in connection with a gap former.
FIG. 2 presents a turbulence generator which is particularly appropriate for use in connection with a Fourdrinier or hybrid former.
FIG. 3 presents a turbulence generator according to a second embodiment of the invention particularly for a gap former.
FIG. 4 presents a turbulence generator appropriate for Fourdrinier and hybrid formers.
FIG. 5 presents a turbulence generator appropriate for a gap former, in which two advantageous embodiments of the invention are combined.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 presents in cross-section a simplified headbox 2 for a paper machine. Stock suspension is brought to the headbox 2 via a cross-direction stock inlet header 4 , wherefrom the flow is distributed into a number of distributor pipes 6 in machine direction. Subsequent to the distributor pipes 6 , the stock suspension flows through an equalization chamber 8 into the flow pipes 14 a 1 . . . 14 a 5 of the turbulence generator 10 , and further, into a wedgewise tapering slice duct 12 , wherefrom the stock suspension spray is discharged through a slice opening 13 to the web former.
The turbulence pipes 14 a 1 . . . 14 a 5 of the turbulence generator 10 are arranged in five superimposed rows R 1 . . . R 5 extending in cross machine direction across the entire width of the headbox 2 . Each individual turbulence pipe 14 a 1 . . . 14 a 5 comprises an initial section 15 relatively narrow in cross-section, expanding stepwise at point 16 into an end section 17 wider than the initial section 15 . Preferably, the initial section 15 of the pipe is circular in cross-section and also the end section 17 starts circular at the expansion 16 but ends rectangular on the side of the slice cone 12 , so that necks 18 are left between the superimposed turbulence pipes 14 a 1 . . . 14 a 5 . As known in the art, the cross-section of the latter part can also be different, such as triangle, square or polygon. The expansions 16 of the flow cross-section area in the turbulence pipes 14 a 1 . . . 14 a 5 cause a change of the flow rate in the stock suspension flowing through the turbulence generator 10 and an increase in the amount of turbulence.
Thus, each row R n of turbulence pipes comprises a plurality of parallel turbulence pipes 14 a n , these being mutually identical in said horizontal row R n . The subscript n refers to the order number 1 to 5 of the pipe, starting from the topmost pipe. The superimposed turbulence pipes 14 a 1 . . . 14 a 5 differ from one another in the respect that the expansion spot 16 of the flow duct 14 a n is in different pipe rows R 1 . . . R 5 placed at a different distance L n from the slice opening 13 of the headbox. Said distance L n reduces in the order L 1 =L 5 >L 2 =L 4 >L 3 .
The headbox as in FIG. 1 is intended for use in association with the gap former. When a web is dewatered between two wires, the middle layer thereof is dewatered last. In order to maintain a sufficient micro-turbulence level considering the achieving of uniform formation as long as possible also in the middle layer of the stock flow being dewatered last, the expansion points 16 in the centermost row of pipes R 3 are positioned closest to the outlet end of the turbulence generator 10 and the slice opening 13 of the headbox, respectively, in the topmost R 1 and the lowermost R 5 pipe row, the expansion points 16 are farthermost from the outlet end of the turbulence generator 10 .
FIG. 2 presents a turbulence generator 10 which is particularly appropriate for use in association with the web forming units starting with a Fourdrinier wire portion. The means comprises four superimposed rows R 1 . . . R 4 of turbulence pipes 14 b 1 . . . 14 b 4 . The expansion spots 16 of the turbulence pipes are in this instance stepped to grow in that the space L 4 between the expansion 16 and the slice opening 13 in the turbulence pipes 14 b 4 of the lowermost pipe row R 4 is greatest and in the topmost pipe row R 1 , the respective distance L 1 is smallest. The lowest layer of the stock suspension flow sprayed onto the Fourdrinier wire is filtered first and the topmost layer, last. To have the turbulence maintained longer in the upper stock suspension layer being dewatered last, the locations of the expansion 16 of the flow cross-section area are in the present embodiment stepped so that the expansions 16 in the lowermost pipe row R 4 closest to the level of the Fourdrinier wire are earlier in the flow direction and the pipe expansions 16 in the topmost pipe row R 1 farthermost from the Fourdrinier wire are last in the flow direction.
FIG. 3 shows a turbulence generator for a gap former according to another embodiment of the invention. In this instance, the stepped expansion 16 located between the narrow initial part 15 of the turbulence pipe 14 c 1 . . . 14 c 4 and the wide latter part 17 thereof is in all four superimposed rows R 1 . . . R 4 of turbulence pipes in the flow direction at one and same distance from the slice opening 13 of the headbox. Instead, the superimposed turbulence pipes 14 c 1 . . . 14 c 4 have different cross-sections so that the cross-section areas of the topmost and the lowermost turbulence pipes 14 c 1 and 14 c 3 are smaller than the cross-section areas of the two centermost turbulence pipes 14 c 2 and 14 c 3 . The greater the cross-section of the flow duct, the greater in dimension is the turbulence generated in the pipe. A turbulence of a greater dimension also slows down more slowly than a turbulence of a smaller dimension.
A turbulence generator as in FIG. 3 comprises further three trailing elements 20 a 1 . . . 20 a 3 fastened as extensions to necks 18 separating the three superimposed pipe rows R 1 . . . R 4 from each other, said elements extending to the slice cone 12 of the headbox. The purpose of the trailing elements 20 a 1 . . . 20 a 3 is to keep the stock suspension flows of turbulence of different magnitude, coming from turbulence pipes 14 c 1 . . . 14 c 4 , apart from each other and in addition, to generate and/or to maintain the turbulence of the flow. In the design of the invention, said three trailing elements 20 a 1 . . . 20 a 3 are different in length so that the topmost and the lowermost trailing elements 20 a 1 and 20 a 3 extend to the same distance s 1 =s 3 from the slice opening 13 of the headbox, and the middlemost trailing element 20 a 2 is shorter than the others, extending to distance s 2 .
The turbulence generator in FIG. 4 is intended for a Fourdrinier or hybrid former. As in FIG. 3, also in the present embodiment the cross-section areas of the turbulence pipes 14 d 1 . . . 14 d 3 arranged in three superimposed rows R 1 . . . R 3 are different so that the cross-section area in the lowermost pipe row 14 d 3 is smallest and the cross-section area in the topmost pipe row 14 d 1 , and hence, also the dimension of the turbulence generated in the flow, is greatest. The lengths of two trailing elements 20 b 1 and 20 b 2 fastened as continuations to pipe rows R 1 . . . R 3 are arranged so that the distance S 2 of the tip of the trailing element 20 b 2 from the slice opening 13 separating the two lowermost stock flows from each other is greater than the respective distance s 1 of the trailing element 20 b 1 separating the two topmost stock flows from each other.
FIG. 5 presents a turbulence generator appropriate for a gap former, in which the technology of FIG. 1 and FIG. 3 is combined in an advantageous fashion. The expansion spots 16 in superimposed rows R 1 . . . R 5 of turbulence pipes 14 a 1 . . . 14 a 5 are so stepped that the centermost turbulence pipe 14 a 3 expands last in the flow direction and the two sidemost turbulence pipes 14 a 1 and 14 a 5 expand first in the flow direction. As extensions to the partitions 18 of the turbulence pipes 14 a 1 . . . 14 a 5 four trailing elements 20 c 1 . . . 20 c 4 are arranged, of which the distance s 2 =s 3 of the tips of two centermost trailing elements 20 c 2 and 20 c 3 is smaller than the respective distance s 1 =s 4 of the two trailing elements 20 c 1 and 20 c 4 closer to the edge.
Also several other modifications of the invention are conceivable within the scope of the claims presented below. For instance, the trailing elements separating superimposed flows from each other can be mutually of identical dimensions when a layered turbulence has been generated in the stock suspension flow already in the preceding turbulence pipes.
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In a paper machine headbox, a stock suspension flow passes through turbulence pipes (14 a n ) and is distributed into superimposed layers. Stepped expansion spots ( 16 ) of the flow cross-section area of the turbulence pipes ( 14 ) or the positions of trailing elements starting from between the pipe rows (R n ) and extending to the slice duct ( 12 ) of the headbox control the onset and level of turbulence in each layer. Turbulence is generated in different phases of the flow in different layers by arranging the expansion spots ( 16 ) and/or the trailing elements in superimposed layers to be located at different distances from the slice opening ( 13 ) of the headbox, whereby a different turbulence prevails at the slice opening ( 13 ) in different layers of the stock suspension flow.
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BACKGROUND OF THE INVENTION
The present invention relates to an improved method and apparatus for hanging off a coiled tubing (CT) velocity string in an existing production well.
It is well known that liquid loading in gas wells is a problem which results in decreased gas production and in some cases complete cessation of production, i.e., what is known as a "kill". The gas flowing characteristics of a well may be affected by the normal production from gas reservoirs of condensate or water naturally occurring in the formation. If these liquids are not carried to the surface by the gas they will eventually load up in the downhole tubing and cut off the flow of gas. This occurs when there is insufficient transport energy in the gas phase to overcome the head of liquid in the tubing.
By running a line of smaller diameter CT into the existing production tubing string, a reduction in the gas flow area will result in an increased gas flow velocity sufficient to overcome the critical production velocity (C.P.V.). Thus, there has been considerable interest in methods for more economically (both in terms of time and material costs) hanging off the CT in the existing production string, particularly without having to kill the well. (See Wesson and Shursen, "Coiled Tubing Velocity Strings Keep Wells Unloaded," p. 56-60, WORLD OIL (July 1989)).
Current hangoff methods normally involve the following steps:
a. Setting up necessary rigging;
b. Installing a CT hanger/packoff assembly on the existing production string;
c. Installing a pumpout plug into the end of the CT to allow the CT to be run into the well while it is flowing without gas or liquid entering the CT;
d. Running the CT to the desired depth;
e. Energizing the packoff in the hanger/packoff assembly;
f. Installing and setting slips on the CT;
g. Cutting off the excess and removing the CT above the cut;
h. Installing valves and other flow plumbing;
i. Connecting nitrogen source to CT and blowing out the plug in the downhole end of the CT.
j. Disconnecting nitrogen source and placing well on production through the CT velocity string.
Alternatively, if there is a need to initially blow out fluid in the production string, then the CT may be run into the string without the plug, but attached to a nitrogen source. After the nitrogen source is activated and the well fluids blown out, the CT must be retracted and the end plug placed in the CT. This is an extra step requiring additional time and cost.
As may be seen the current methods require the insertion of the downhole end plug which must be pumped out after the CT is run to the desired depth and cut off and this necessitates having a pumpout gas (nitrogen) and delivery system available on site. The method and apparatus of the present invention eliminates this costly and time-consuming step by allowing the operator to "hot tap" the CT which is loaded with gas or liquid after being inserted into the wellbore.
SUMMARY OF THE INVENTION
The present invention makes use of a unique hangoff head and cutter assembly which in combination enables the operator to run the CT into the wellbore through the existing production string without a plug and to subsequently cut off the excess CT without exposing the operator to the pressurized gas and fluid in the CT velocity string.
BRIEF DESCRIPTION OF THE DRAWINGS
In describing the invention in detail, reference is had to the accompanying drawings, forming a part of this specification, and wherein like numerals of reference indicate corresponding parts throughout the several views in which:
FIG. 1 illustrates a typical existing gas well head.
FIG. 2 illustrates the initial hangoff assembly of the present invention.
FIG. 3 illustrates the details of the hangoff head of the present invention.
FIG. 4 illustrates the CT run to the top of the master valve in the present invention.
FIG. 5 illustrates the step of running CT to the desired depth in the existing production tube in the present invention.
FIG. 6 illustrates the step of cleanout prior to hangoff in the present invention.
FIG. 7 illustrates the initial step in hangoff in the present invention.
FIG. 8 installation of slips in the present invention.
FIG. 9 illustrates the replacement of the cap and installation of the cutter assembly of the present invention.
FIG. 10 illustrates the cutter of the present invention advanced and the hydraulic packoff closed.
FIG. 11 illustrates in an alternative embodiment the cutter assembly of the present invention with the stem and cutter wheel withdrawn.
FIG. 12 illustrates the alternative embodiment of the cutter of the present invention advanced to contact the CT.
FIG. 13 illustrates the severing of the CT of the present invention.
FIG. 14 illustrates the retraction of the cutter of the present invention.
FIG. 15 illustrates the final removal of the CT and cutter assembly of the present invention.
FIG. 16 illustrates the final well head configuration with CT velocity string installed.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 illustrates a typical existing well head 10 (gas well) prior to the installation of the coiled tubing velocity string. Gas 12 is shown in these illustrations by use of dotted areas. Master valve 14 is open and gas 12 is shown in production tubing 16 up to valve 18 which is shown closed to an existing sales line 20. Large annulus valve 22 is shown closed.
In the method of the present invention, the well should be shut in for a period of time sufficient to achieve a maximum pressure buildup and, in addition, to minimize the fluid level. Soap sticks dropped into the well before shut-in have been found to aid in fluid removal up through the velocity string after its installation.
The initial hangoff assembly of the present invention is illustrated in FIG. 2. Master valve 14 is closed and the hangoff head 24 of the present invention has been installed between master valve 14 and sales valve 18. Further added to the piping as part of the hangoff assembly are side valve (or second line valve) 26, top valve 28, and hydraulic packoff valve 30.
A detailed illustration of hangoff head 24 is shown in FIG. 3. Body 30 is provided with a first threaded end 33 for connection to said master valve piping and outer grooves to receive and retain back pressure O-rings 34. O-rings 34 serve an important function in the present invention in that they provide a sealing function once the CT is severed and gas or fluid fills the hangoff assembly. Body 30 has a second upper end which is threaded to secure cap 50 to the body 30. Stripper rubber member 36 with O-ring 38 fits into the inner portion 42 of body 30. FIG. 3 also illustrates the snap ring 40, slip bowl 43, slips 44, split rubber packing 46, split steel ring 48, and cap 50. Cap 50 has a thread neck 52 for connection to the piping to second line valve 26. Thus, hangoff head 24 is unlike any known in the art. It is capable of handling pressures directed to either side of rubber packing 36 and is threaded on both ends 33 and 52.
Coiled tubing 54 is shown in FIG. 4 without a plug in its downhole end. CT 54 has been run down through open hydraulic packoff valve 30, through hangoff head 24, and through stripper rubber member 36. Thus, when master valve 14 is opened CT 54 is in fluid communication with the existing production tubing run and pressurized up through CT 54 to the coiled tubing unit (not shown). Gas 12 is sealed off from side valve 26 by the seals in hangoff head 24.
FIG. 5 illustrates that CT 54 has been run down through the existing production string 56 to the desired depth into the well tubing run producing gas and fluids 37 through the CT 54 to the coiled tubing unit (not shown). To clean out the well prior to hangoff of the velocity string, nitrogen, fluid, and air (or foam air) 39 may be pumped through CT 54 driving discharge fluids 41 through valve 18 as shown in FIG. 6. This step may be eliminated if cleanout is not desired or if cleanout equipment is not available at the well site.
Once hangoff is desired (the desired depth having been reached), cap 50 may be rotated to unscrew and elevate it as shown in FIG. 7. Valve 18 has been closed and fluid and gas 37 flow up CT 54. Slip bowl 42 is ready to receive and retain slips 44 as shown in FIG. 8. In FIG. 8 snap ring 40 is installed, slips 44 inserted with O-ring 43 and split rubber top packing 46 completing the packoff. When cap 50 is reverse rotated it is tightened onto body 32, the CT 54 is then held and suspended in the production string. Cap 50 is in sealing engagement with seals 34 in body member 32.
FIG. 9 illustrates the replacement of cap 50 and the installation of the cutter assembly 60. Side valve 26 now becomes the cutter valve through which cutter wheel 62 and stem 64 must pass as discussed below. The opening 27 in valve 26 is sufficient to allow cutter wheel 62 to twist as handle 66 is rotated to advance stem 64 toward CT 54.
As may be seen in FIG. 9, cutter housing 61 has seal grooves 29 for receiving and retaining seals (not shown) which seat against stem 64 in sealing engagement. In FIG. 10 cutter wheel 62 has been advanced to contact CT 54, and hydraulic packoff is closed to seal around CT 54. Cutter wheel 54 is forced into cutting engagement with CT 54 by securing stem 64 from rotating by holding its alignment nut 67 while turning handle 66. Internal threads on handle post 69 cooperate with threads on stem 64 to apply pressure to shoulder 71 on stem 64 to move it forward without twisting. Thus once cutter wheel 62 engages CT 54 and is aligned perpendicular to CT 54, cutter wheel 62 is not further twisted.
A more detailed illustration of an alternative cutter assembly 61 is shown in FIG. 11. Coupling 68 connects cutter assembly front end housing member 70 to cutter assembly back end housing member 72. Coupling 68 has left hand threads 74 on its front end for cooperation with threads on housing 70 and right hand threads 76 on its rear end for cooperation with threads on housing 72.
Cutter assembly front end member 70 is provided with seal grooves 78 for receiving and retaining seals (not shown in FIG. 11). The seals form a seal along cutter stem 64 as previously discussed with FIGS. 9 and 10 Rotation of stem 64 advances cutter wheel through valve 26 and into initial, perpendicular contact with CT 54. By rotating coupling 68 while holding stem 64 from rotation, cutter wheel 62 is forced into cutting engagement with CT 54 as is shown in FIG. 12 without any further twisting or misalignment. Seals 79 are shown in FIG. 12.
It must be understood that in both cases (FIGS. 10 and FIG. 12), the cutter wheel 62 is engaging a fully charged or "hot" CT run. The seals in the cutter assembly ensure that gas and fluid is not discharged to the environment when the cut into CT 54 is made. (The shading shown in FIGS. 11 and 12 is not intended to represent gas.)
In FIG. 13, cutter assembly 60 is rotated transverse of CT 54 and cutter wheel 62 presses into further cutting engagement to sever CT 54 by either turning handle 66 and securing alignment nut 67 (FIG. 10) or rotating coupling 68 while holding stem 64 from rotation (FIG. 12). Thus the entire hangoff assembly is charged with gas and fluid as a result of the rupture or severing of CT 54. Because hangoff head 24 including body 32 is constructed to take back pressure, the entire tap or cut is made safely. Hydraulic packoff 30 ensures that gas and fluid do not escape, while seals 79 in cutter assembly protect against gas leakage through cutter assembly 60, and back pressure O-ring 34 in head 24 prevents leakage through the hangoff.
Cutter stem 64 and wheel 62 are retracted in FIB. 14 and valve 26 is closed. Thus the "hot" tap is safely, quickly, and economically accomplished. Excess tube 55 may then be withdrawn through hydraulic packoff valve 30 and as tube 55 passes through top valve 28, valve 28 is closed (FIG. 15).
FIG. 16 illustrates the final well head configuration with the CT velocity string installed and gas flowing through valve 26 and sales line 80.
While the invention has been described in connection with a preferred embodiment, it is not intended to limit the invention to the particular form set forth, but, on the contrary, it is intended to cover alternatives, modifications, and equivalents, as may be included within the spirit and scope of the invention a defined by the appended claims.
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A method and apparatus for hanging off a coiled tubing velocity string in an existing, active gas production well. The method allows for the "hot" tapping into a charged coiled tubing run thereby eliminating the need for an end plug and blow out equipment on site. A sealed cutter assembly is connected to the hangoff assembly, the charged coiled tube is cut, and back pressure leakage is avoided by the use of a hangoff head which seals in two directions. The cutter assembly is removed and the coiled tubing velocity string is piped to a new sales line.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is based on, and claims priority from, Chinese Application Number 201320352419.4, filed Jun. 7, 2013, the disclosure of which is incorporated herein in its entirety.
TECHNICAL FIELD
[0002] The present disclosure relates generally to a pet product and, specifically, a collapsible storage bucket used for storing pet food.
BACKGROUND
[0003] With the development of society and the improvement of living standards, people are constantly in pursuit of the spiritual life, while enjoying the material life. Consequently, having pets is gradually becoming a popular custom. Since pets are occupying a higher position in people's lives, people are demanding an ever higher quality of life for their pets. Because more and more people are feeding their pets with pet food, the storage and transportation of the pet food has been problematic. While conventional storage buckets have appeared in the market, most of these buckets are made of a ceramic or a metal material. They are designed as a single unit which cannot be expanded, collapsed, or dismantled. Furthermore, these buckets are heavy, expensive for transportation, easily susceptible to damage, and take up large amounts of storage space. In response to these problems, there have been some improvements in the design of these buckets; however, none of the improvements are able to entirely remedy the above problems in conventional storage buckets.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] The present disclosure will be further described in conjunction with drawings and embodiments. Aspects of the present disclosure are to be understood from the following detailed description when read with the accompanying figures which are incorporated herein by reference.
[0005] FIG. 1 is a schematic perspective view of a collapsible storage bucket in accordance with an embodiment.
[0006] FIG. 2 is a schematic perspective view of a collapsible storage bucket with a lid, a bucket opening surround, and a chamber portion in accordance with an embodiment.
[0007] FIG. 3 is a schematic perspective view of a collapsible storage bucket with a chamber portion in a collapsed state in accordance with an embodiment.
DETAILED DESCRIPTION
[0008] An embodiment, as described in connection with FIGS. 1-3 , is a collapsible storage bucket 100 . The collapsible storage bucket 100 includes a chamber portion 200 , wherein the chamber portion includes an opening. Additionally, the collapsible storage bucket 100 includes a bucket opening surround 300 and a lid 400 . The bucket opening surround 300 is placed over the opening of the chamber portion 200 . The lid 400 is placed over the bucket opening surround 300 to cover the opening of the chamber portion 200 .
[0009] Chamber portion 200 , which is an enclosure that is collapsible, is made from a blow-molded material. The chamber portion 200 includes the opening, and a base 250 . The chamber portion 200 has a vertical height perpendicular to the base 250 . In some embodiments, the chamber portion 200 has sidewalls that are shaped like sidewalls of a spring. In some embodiments, the chamber portion 200 has sidewalls that are accordion pleated. In some embodiments, the chamber portion 200 has accordion pleats that are perpendicular to the vertical height. Several advantages are provided by one or more embodiments of the chamber portion including the following features: the chamber portion 200 is sturdy, durable, and easy to clean; the height is freely adjustable according to the amount of food stored; and the chamber portion is compressed to its smallest size, thereby reducing transportation costs, and making the storage more efficient, as illustrated in FIG. 3 .
[0010] Bucket opening surround 300 is placed over the opening of chamber portion 200 . In some embodiments, the bucket opening surround 300 is separate and detachable from the chamber portion 200 .
[0011] Lid 400 is placed over bucket opening surround 300 to cover the opening of chamber portion 200 . The lid 400 has a size which is commensurate with the bucket opening surround 300 such that the lid covers the entire opening. In some embodiments, the lid 400 is separate and detachable from the chamber portion 200 to form different entities. In some embodiments, the lid 400 is attached to the chamber portion 200 . In some embodiments, the lid 400 is made from a blow-molded material. Several advantages are provided by one or more embodiments of the lid 400 including the following features: ease of cleaning and assembly when the lid and the chamber portion 200 require cleaning.
[0012] In order to overcome the aforementioned shortcomings, one or more objects of one or more embodiments of the present disclosure are to provide a collapsible storage bucket. The collapsible storage bucket 100 is capable of being extended and collapsed. Thus, the collapsible storage bucket 100 is lightweight, compact, and efficient for transportation and storage. Additionally, the collapsible storage bucket 100 has a rational structure which is also aesthetically appealing in some embodiments.
[0013] In an aspect of one or more embodiments, a collapsible storage bucket includes a chamber portion that is collapsible, wherein the chamber portion includes an opening. Additionally, the collapsible storage bucket includes a bucket opening surround and a lid. The bucket opening surround is placed over the opening of the chamber portion. The lid is placed over the bucket opening surround to cover the opening of the chamber portion.
[0014] The chamber portion, which is collapsible, is made from a blow-molded material. The chamber portion includes the opening, and a base. The chamber portion has a vertical height perpendicular to the base. In some embodiments, the chamber portion has sidewalls that are shaped like sidewalls of a spring. In some embodiments, the chamber portion has sidewalls that are accordion pleated. In some embodiments, the chamber portion has accordion pleats that are perpendicular to the vertical height. In some embodiments, the chamber portion is used to store pet food. Several advantages are provided by one or more embodiments of the chamber portion including the following features: the chamber portion is sturdy, durable, and easy to clean; the height is freely adjusted according to the amount of food stored; and the chamber portion is compressed to its smallest size, thereby reducing transportation costs, and making the storage more efficient.
[0015] The bucket opening surround is placed over the opening of the chamber portion. In some embodiments, the bucket opening surround is separate and detachable from the chamber portion.
[0016] The lid is placed over the bucket opening surround to cover the opening of the chamber portion. In some embodiments, the lid is separate and detachable from the chamber portion to form different entities. In some embodiments, the lid is attached to the bucket opening surround. Several advantages are provided by one or more embodiments of the lid including the following features: ease of cleaning and assembly when the lid and the chamber portion require cleaning.
[0017] Several advantages are provided by one or more embodiments including the following features: the collapsible storage bucket has potential to be efficient with storage, while having a rational structure which is also aesthetically appealing in some embodiments; the chamber portion has a collapsible structure; the chamber portion is sturdy and durable; the collapsible storage bucket facilitates ease of use, storage, and transport.
[0018] The foregoing outlines features of several embodiments so that those skilled in the art may better understand the aspects of the present disclosure. Those skilled in the art should appreciate that they may readily use the present disclosure as a basis for designing or modifying other processes and structures for carrying out the same purposes and/or achieving the same advantages of the embodiments introduced herein. Those skilled in the art should also realize that such equivalent constructions do not depart from the spirit and scope of the present disclosure, and that they may make various changes, substitutions, and alterations herein without departing from the spirit and scope of the present disclosure.
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A collapsible storage bucket includes a chamber portion. The chamber portion further includes an opening. Additionally, the chamber portion is collapsible. The collapsible storage bucket further includes a bucket opening surround over the opening, where the bucket opening surround is detachable from the chamber portion. The collapsible storage bucket further includes a lid over the bucket opening surround, where the lid configured to cover an entirety of the opening. Additionally, the lid is detachable from the bucket opening surround.
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CROSS REFERENCE TO RELATED APPLICATION
The present application is a continuation-in-part of application Ser. No. 246,550, filed Mar. 23, 1981 now abandoned.
FIELD OF THE INVENTION
This invention is concerned with an improvement in apparatus for ripping or fracturing subsoils. It is particularly advantageous in sites where the ground surface is covered with debris which ordinarily interferes with ripping operations or where there are subterranean rocks or other obstructions.
BACKGROUND OF THE INVENTION
Soil rippers and related devices have found application in a number of areas. They are commonly used on construction sites for fracturing subsoils, particularly when these are underlaid by hardpans or are rocky. Rippers also find wide agricultural use where they are likewise employed for breaking up hardpan or other types of impermeable subsoils. Cable plows are a modified type of ripper which simultaneously create a deep, narrow trench and bury an electrical or other type of cable within the trench.
Agricultural ripping usually has a two-fold purpose in that it fractures subsoils to make them permeable to both plant roots and water. When these impermeable formations are close to the surface; the soil may be poorly drained yet have a tendency to dry out rapidly under droughty conditions. Fracturing of these impermeable soils by ripping creates an environment which can be more easily penetrated by roots. The rip lines themselves tend to act as moisture reservoirs.
One large-scale application of ripping is in reforestation of logged or otherwise unproductive forest lands. There is much land in the southeast and the southern part of mid-continent America in which forest soils are underlaid by shales or hardpans which lie close to the surface. Tree growth on such lands is less than optimum from the standpoints of both size and rate, even though other aspects of the environment are favorable. It has become a standard silvicultural practice in many areas to rip the sites before they are replanted with tree seedlings. Commonly, the seedlings will be planted directly in rip lines, which are located on a spacing considered optimum from the silvicultural standpoint. Depending on the nature of the soil and subsoil, the rips may be anywhere from 40 cm to 1 m in depth, or even greater.
Because of the strength of the substrate and the considerable depths to which it is being fractured, ripping is normally carried out using large tracked, crawler-type prime movers. The land itself is often rough and uneven and is typically covered with logging debris and stumps. All of these considerations work together to virtually exclude the use of smaller, lower powered prime movers.
A typical ripper comprises a frame carrying a tool bar, one or more ripping teeth mounted on the tool bar, and an actuating mechanism. This is rigidly bolted behind a crawler-type tractor. Most typically, because of the high amount of power required, not more than two ripper teeth will be used. The mechanisms used to control the position and attitude of the teeth are well known. These usully have either a radial-arm type control linkage or a parallel-arm type, with the latter type prevailing. Hybrid types are also reasonably common. These may be made with either compound radial linkages between the control mechanism and the ripper teeth, or a combination parallel-radial linkage. Examples of these types can be seen in the following patents.
Larson, U.S. Pat. No. 3,503,546 shows a hybrid linkage in which a lower cylinder serves to actuate a parallel-arm motion and an upper cylinder can be used to give a radial arm action. The two cylinders, which may be operated simultaneously, produce a form of motion on the ripper tooth which will be intermediate between the two types.
Mayo, et al, U.S. Pat. No. 3,295,612 shows a modified parallel-arm linkage, which, in effect, gives an arcuate entry of the tool into the ground, similar to a radial type.
The major difference between the parallel arm and the radial arm control linkages is in the mode of entry of the ripper tooth into the ground. The parallel arm control linkage causes essentially a straight line insertion of the tool into the ground in the same attitude it will have during operation. In radial-arm linkage, the tool tip describes a wide arc as it enters the ground. This type generally requires more power on entry because the ripper tooth typically has a less favorable angle and must sweep through the ground to assume an operating attitude. This deficiency is one of the reasons for the present higher popularity of parallel-arm type rippers.
One problem encountered in using rippers on debris-covered land is that they tend to act as rakes. Accumulated debris periodically will be discharged by withdrawing the teeth from the ground. Frequently the tractor operator must resort to maneuvers such as reversing his machine to clear this accumulated debris. In this regard, a radial arm action has an advantage over the parallel arm action in that it will clear debris more rapidly. This is a problem of no small consequence in ripping logged over forest land. It is common for the ripper operator to spend about 25% of his time in the field clearing accumulated debris. This wasted time is expensive because of the high capital cost of the prime mover and also because of the large amount of fuel and operator time that is used unproductively. Conventional rippers present other problems as well. Because they are located behind the prime mover, they tend to act as a rudder, which interferes with steering. When the tractor operator must make a sharp turn while ripping, he must overcome not only the forward resistance to the ripper teeth, but the newly introduced lateral component as well. Furthermore, as the prime mover rides over objects such as a stump or a log, there is a significant pitching action that is magnified by the distance between the tractor center of mass and the ripper teeth. At one point, this drives the ripper teeth much deeper than required into the ground, thus requiring substantially more power. At another point in travel the ripper teeth may be lifted completely from the ground, thus failing to do the job for which they are intended. The net result is an undesirable undulating rip depth.
The present invention has been successful in overcoming these problems by side mounting the rippers on a crawler-type prime mover approximately opposite the fore/aft center of mass.
While side mounted rippers have been proposed previously, they have never been made available commercially. Perhaps one reason is that they have not successfully addressed a major problem of resisting lateral thrust forces that act on the ripper teeth during operation. One instance in which these forces are very high is when a tooth tries to deflect around the edge of a large subterranean boulder. Ripper mechanisms that are not substantially mounted can literally be twisted off the vehicle.
One side-mounted ripping device known to Applicant is shown in Stedman et al., U.S. Pat. No. 4,152,991. This is a ballast ripper designed for breaking up compacted railroad bedding. It consists of two vertical shafts and appropriate bearings, with horizontal ripper elements working arcuately beneath the railroad ties. Both the prime mover and the ripper mechanism are significantly different from those in the present invention. It is hard to visualize the Stedman machine being useful for anything beyond the specific application for which it was designed.
U.S. Pat. No. 4,204,578, also to Stedman, shows a side-located ripper mechanism having a hybrid-type action. The ripper teeth and actuating means are mounted on "wing portions" comprising buttressed vertical faces welded on the outside of a U-shaped frame. This frame is located in the position normally occupied by a blade arm and blades.
McCauley, in U.S. Pat. No. 2,396,739, shows a bulldozer equipped with ripper teeth that function when the tractor moves backwards. Two of the teeth are mounted on the outside of the blade arms, immediately behind the blade.
U.S. Pat. Nos. 2,358,298, 2,737,868, 3,046,917, 3,092,187, and 3,387,665 all show side-mounted cultivators on light agricultural tractors. The patent to Rafferty, U.S. Pat. No. 2,743,655, shows mid-mounted plows which are essentially in line with the rear wheels of the vehicle.
Most of these devices are either light duty implements designed for tilling or cultivating surficial soil, or would not be suitable for subsoil ripping in many soils because of the side thrust problem.
SUMMARY OF THE INVENTION
This invention comprises an improved soil ripper. It is a device particularly well adapted for use on rough ground or on debris-covered sites. The improvement resides principally in the positioning of the ripper teeth and in the provision for resisting side or lateral thrust forces on the teeth. Typically, the ripper mechanisms would be within rigid frames which are mounted on a U-shaped frame which usually comprises the blade and blade arms of a blade-equipped crawler-type prime mover. The frames would contain means for holding a ripper tooth and control means to determine the position and attitude of the tooth. When in the ripping position, the teeth will be positioned outside the tracks and between the fore and aft axles of the prime mover, preferably approximately opposite the center of mass of the machine. The control means can be either a radial arm linkage, a parallel arm linkage, a compound radial arm linkage, a hybrid linkage, or some new combination of these. This side-mounted arrangement is advantageous from a number of standpoints. One principal advantage is that the improved construction does not tend to rake piles of debris, which must then be discharged from the mechanism. Instead, the crawler-tracks run over the debris, which is securely held down by the weight of the vehicle. Unless the debris is very large, it will simply be snapped off by the ripper teeth. On a prime mover of the size normally used in preparing forest land for replanting, the ripper teeth can readily break off small logs as large as 30 cm in diameter, or even greater. Roots and small stumps are dealt with in similar fashion. A further advantage is found in the much better maneuverability of the tractor. Because the ripper teeth are mounted on the side, they do not have the rudder action of a rear-mounted ripper. The equipment operator has thus gained for more rapid maneuverability when this is necessary. Finally, the ripper teeth do not have the tendency to move up and down in the ground as badly when the prime mover rides over an obstruction, because the lever arm between the obstruction and the ripper tooth has been significantly shortened. All of these advantages combine to permit a high ratio of useful operating time to debris cleaning time with attendant increase in field efficiency and a major saving in fuel consumption.
A major improvement in the present ripper is the provision for resisting torsional forces on the arm portions of the mounting frame. These forces can occur when a ripper tooth hits a subterranean or other object in a manner that tends to deflect it toward or away from the prime mover. On a side-mounted ripper, such forces can achieve magnitudes so great that the arm of the mounting frame can be severely rotated and permanently deformed, or even broken. In the present invention, torque rotation or resisting means associated with the ripper subframes are provided to resist rotation or twisting caused by these laterally acting forces. In one embodiment, the torque resisting means comprises a rigid arch which bridges the ripper subframes on opposite sides of the tractor. In another embodiment, the torque resisting means is a strut or struts acting between the ripper subframes and the tractor frame.
It is an object of the present invention to provide a soil ripper with many improved operating characteristics.
It is a further object to provide a soil ripper that has greater efficiency in debris-covered sites.
It is yet an object to provide a soil ripper that does not accumulate debris ahead of the ripper teeth.
It is another object to provide a soil ripper which has improved steering characteristics.
It is still another object to provide a soil ripper that has less tendency to cause uneven rips as the prime mover passes over obstacles.
It still is a further object to provide a side-mounted ripper that effectively resists lateral thrust forces acting on the ripper teeth.
These and other objects will become readily apparent on reading the following detailed description, accompanied by reference to the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a prior art ripper using a parallel arm-type control linkage.
FIG. 2 is a partial perspective of a prior art ripper using a radial arm-type control linkage.
FIG. 3 is a fragmentary side view, partially in section, of a prior art radial arm-type ripper.
FIG. 4 is a fragmentary side view, partially in section, of a prior art ripper having a parallel arm control linkage, further showing the tendency to accumulate debris.
FIGS. 5 and 6 are a side elevation views of one version of a ripper made by the teachings of the present invention.
FIG. 7 is a top plan view of the ripper shown in FIGS. 5 and 6.
FIG. 8 is a fragmentary rear elevation view, partially in cross section, showing details of one way of mounting a ripper subassembly to a blade arm.
FIG. 9 is a side elevation view of another version of the present invention shown in operation on debris-covered land.
FIG. 10 is a top view of the ripper shown in FIG. 9.
FIG. 11 is a fragmentary rear elevation view of the versions shown in FIGS. 9 and 10, showing detail of mounting a torque-resisting arch to the ripper subframe and further showing a cause of high lateral deflection forces.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 illustrates a conventional soil ripper using a parallel arm control linkage. Ripper assembly 2 is attached to a crawler-type tractor 4. The ripper consists of a base frame 6 carrying vertical frame members 8 and upstanding ears 10. The frame is attached to the prime mover by a series of heavy bolts 11. A lower parallel arm member 12 is pivotally attached to frame member 8 at 20, near the point of attachment of the ripper frame to the prime mover. An upper parallel arm member 14 is similarly pivotally attached to frame member 8 at 18. The vertical links 16 complete the parallelogram. These are pivotally attached to the upper parallel arms at 22 and to the lower arms at 24. A pair of main control hydraulic cylinders 26 are pivotally attached to frame ears 10 at their upper ends. The cylinder piston rods are likewise pivotally attached to lower frame members 12 at 27. The position of the piston rods in cylinders 26, acting through the parallel arm mechanism, controls the elevation of tool bar 28, which is rigidly attached to vertical members 16. The tool bar 28 contains mounting brackets 30, which hold heavy ripper teeth 32. These are typically equipped with wear-resistant forwardly raked tips 34.
This type of ripper also usually includes a pair of shock absorbers 36 and tooth attitude trimming cylinders 38.
Referring to FIG. 4, we see an example of a parallel arm ripper that has been operating an debris-covered ground. A mass of material 42 has accumulated ahead of the teeth 32 by their raking action during the formation of rip 40 in soil 41. Note that in a parallel arm ripper it is difficult to disengage debris of this type, because if the ripper teeth are raised there is a tendency to pinch the debris between the teeth and the frame rather than to clear it. In this situation, it is often necessary for the tractor operator to back up over the accumulated debris pile before it can be released. This causes a discontinuity in the rip line. However, of more significance, it is extremely wasteful of time and fuel. On many sites, clearing debris from the ripper teeth will account for about 25% of field operation hours.
FIGS. 2 and 3 show a typical prior art radial arm ripper. The ripper 52 is rigidly connected to a crawler-type tractor 54. The ripper is mounted on frame 56 and carries heavy longitudinal arms 58 pivotally attached to the frame, at a point not shown, behind the track of the prime mover. Frame 56 bears ears 60 mounted on a reinforcing member near its upper edge. These ears carry hydraulic cylinders 62 which are pivotally attached at 64. The piston rods of these cylinders are attached to longitudinal arms 58 at 66. The heavy longitudinal arms carry a tool bar 68. In turn, this holds two mounting brackets 70 which contain ripper teeth 72. These ripper teeth likewise have hardened tips 74. At the upper end of the teeth shock absorbers 76 tend to reduce heavy impact loads.
FIG. 3 shows teeth 72 forming rip 78 in soil 79. The alternate position version of FIG. 3 shows the action of the radial arm linkage as it is removed from the ground. This type of linkage will clear debris more efficiently than the parallel arm linkage. However, it has the disadvantage that on re-entry its attitude tends to be at an acute angle to the ground's surface, rather than essentially vertical. For this reason, re-entry to operating depth requires more power and is slower than is the case with a parallel arm ripper. Because of the essentially vertical attitude of the axis of the tooth at the time of entry, the tips of a parallel arm type tend to plow themselves quickly into operating depth with a minimum of additional force being required.
FIGS. 5 through 8 show one preferred version of the present invention. A crawler-type tractor 162 is equipped with side-mounted ripper assemblies 250. These are mounted on conventional blade arms 164, carrying a blade 166. The blade arms are attached to the tractor frame by a pivot or ball joint 165. Blade 166 is pivotally mounted to arms 164 at point 168. The attitude or vertical angle of the blade is controlled by a pair of main hydraulic cylinders 170. Hydraulic cylinders 172 serve as stabilizing struts and also act to give some control over horizontal angle of the blade. The blade and arms described in FIGS. 5 through 8 illustrate a common tilt-type blade arrangement. It is to be understood that the ripper assemblies may be mounted on any rigid, substantially U-shaped frame. In the illustrations, the crawler tracks 218, are seen running on a ground surface 212.
The ripper assemblies 250 comprise a frame, an operating or control arm bearing a ripper tooth, and a hydraulic cylinder for controlling tooth attitude. In the illustration shown, the frame comprises an inner or medial steel plate 252, on outer or lateral plate 254, and a steel web member 256 (FIG. 7), which unites the two plates into a rigid box structure, open to the rear. The ripper control arm 260 is a modified third-class lever. At one end it bears a chuck or tooth-holder 262, containing a ripper tooth 200. This tooth may optionally be equipped with a tip 202 to resist wear. Control arm 260 is pivotally mounted in the box frame at pivot point 264. Attitude of the tooth is controlled by a hydraulic cylinder 266, which operates between the box frame at pivot point 268 and the control arm at pivot point 270. Control cylinders 266 control both the entry and withdrawal of the ripper teeth from the ground, as well as the operating attitude.
An important element of the present embodiment of the invention is strut 274, best seen in FIG. 8. This strut is preferably a double ball-ended rod which is engaged in ball seat 276, attached to the inner wall 252 of the ripper frame assembly, and ball seat 278, attached to the tractor frame 163. This strut effectively stabilizes the ripper assemblies against lateral thrust forces, which may occur during operation of the unit. Another important feature of the present version is the manner in which it is mounted to the blade arms. In the most preferred version, this mounting comprises a pair of heavy hinges or clevis linkages 282,284. The combination of the hinged mounting to the blade arms with the double ball-ended strut allows full vertical freedom of movement of the blade arms 264 from a position in which blade 166 is engaged with the ground surface to a second position in which it is fully clear of the surface. The arrangement also is tolerant of side-to-side adjustment of the blade, as might be accomplished by secondary cylinders 172. This combination of hinged mounting with a lateral thrust transfer element gives great strength to the assembly, as well as great versatility during use.
It is typical of all versions of the present invention that the control cylinders will have an overload sensor. This serves as a safety device in case the tooth should hit a very large rock or other obstacle which could cause an overload. When such an occasion occurs, the overload sensor would typically activate cylinder 266 automatically to swing ripper tooth 200 out of the ground. In such a situation, the operator would normally manually control the reinsertion of the ripper tooth into the ground, although this could be done automatically as well. On sites where there are large subterranean rocks, it may be desirable not to drag them to the surface where they will become future obstacles. In many cases, without the overload sensors, the ripper would have sufficient power to raise these buried rocks. By judicious adjustment of the overload sensors, this situation can be avoided.
FIGS. 9 through 11 show another version of the present invention. The ripper assembly, generally shown at 160, is mounted on a conventional crawler-type tractor 162, as in the previous example. The ripper mechanism is again contained within a box frame, which would typically be a welded fabrication. In this example, it comprises rear plate 174, front plate 176, and end plate 175 to give a box construction which is open at its rearward end. The end plate 175 can be considered as wrapping around the entire forward end of the frame from top to bottom. The frame is mounted to blade arm 164 by bolts 178. In the construction shown, the entire ripper can be readily removed from the crawler-type prime mover simply by removing the four bolts 178 and by disconnecting the appropriate hydraulic lines. Ripper control arm 180 is pivotally mounted within the frame at 182. The main control hydraulic cylinder 184 is pivotally mounted within the frame at its forward end 186. The piston rod of this cylinder is likewise pivotally mounted to the control arm 180 at 188. The other end of the control arm carries ripper tooth holder 190 which is pivotally mounted at 192. In the version shown, a secondary hydraulic cylinder 194 is mounted between appropriate pivot points 198 on tooth holder 190 and 196 on control arm 180 to form a compound radial control system. The ripper tooth holding means 190 includes a housing which contains ripper tooth 200. This contains a two-piece hardened tip 202. The extension of the tooth can be controlled by the use of adjustment pins which operate through adjustment openings 204. A single-pin engages one of an appropriate series of holes, not shown, in the ripper tooth and is held in place by a retainer 205.
In certain very difficult soils, particularly those which may contain large subterranean boulders, occasioned very high lateral forces may act on the ripper teeth. In order to prevent distortion of the equipment, it is sometimes necessary to provide a torque-resisting means to counteract these lateral forces. In many cases, the frame formed by the blade arms 164 and the blade 166 will be adequate. However, this version of the invention carries a torque-resisting arch 206 which connects the upper portions of the ripper frames on either side of the vehicle. The upper portion of the frame carries flange 207 which engages a like flange 208 on the bottom of the arch. A boxed gusset 216 (FIG. 11) on the back of frame plate 174 gives added strength to the assembly. The flanges are rigidly united by a series of bolts 209.
FIG. 9 illustrates one version of the present device in the process of making a rip in soil which is covered with logging debris. In the partial cross-section shown, the rip 210 has been made by teeth 200 in soil 212. The surface of the soil is covered with branches and tree tops 214. This debris would tend to be raked and bunched by conventional rippers. As can be seen in FIG. 9, this material is firmly held down by the weight of the tractor 160 under tracks 218 at the time it is engaged by the ripper teeth. Unless the debris is very large, it will simply be snapped off and the ripper will be able to proceed along its intended path without interruption. With the large prime movers normally employed for ripping, hardwood or softwood debris will be readily broken.
In most cases, a simple radial linkage will provide adequate speed and power for re-entry of the ripper teeth. In this case, the secondary cylinder 194 can simply be replaced by a rigid strut, not shown. This, in effect, serves to rigidly mount tooth holder 190 on the end of control arm 180. Of course, a rigidly mounted modified fabrication or casting can also be used to achieve the same result accomplished by using the strut. Use of the single hydraulic control cylinder 184 considerably simplifies the hydraulic circuitry as well as reducing the cost of the unit.
FIG. 11 exemplifies one situation in which a high lateral thrust would be placed upon a ripper tooth. In this figure, tooth 200 is grazing a large, subterranean rock 230 in a manner that would tend to force the tooth outward. This laterally acting force is magnified by the lever arm present between the point of contact between tooth 200 and the rock and the pivot point 192 of control arm 180. These lateral forces can become very severe, and if provision is not made for resisting them, blade arm 164 could be severely twisted or even fractured. In the present example, lateral forces in either direction are resisted by arch 206.
Having thus described preferred embodiments of the present invention, it should be evident to one skilled in the art that many variations can be introduced that will still be within the spirit of the invention. It is the intention of the inventor that the invention should be limited only as defined in the attached claims.
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An improved subsoil ripping device is disclosed in which ripper teeth are mounted on the sides of a tracked, crawler-type prime mover approximately opposite the center of mass. The frames carrying the ripper mechanisms are most conveniently mounted on the arms of a conventional bulldozer blade. In order to increase resistance to lateral forces acting on the ripper teeth, the frames may be bridged by a rigid arch. Alternatively, they may be braced by a strut acting between the ripper assembly and the tractor frame. If this latter arrangement is used, the ripper assemblies are preferably hinged to the blade arms to permit full normal blade movement. A ripper made according to the present teaching is especially useful when operating on uneven or debris covered ground. It does not tend to rake up debris, and thus does not require time and fuel for clearing the teeth. Because of the location of the teeth, the prime mover is easier to steer and a rip of more uniform depth can be maintained.
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This Application claims priority based on my U.S. Provisional Patent Application No. 60/143,447, filed Jul. 13, 1999.
BACKGROUND OF THE INVENTION
This invention relates to the manufacture of large diameter III-V compound semiconductor wafers used to make semiconductor devices such as FETs (field effect transistors), HBTs (heterojunction bipolar transistors) and MMICs (monolithic microwave integrated circuits).
Among III-V semiconductor compounds, GaAs is most prominent. There has been more extensive device and IC development work and manufacturing infrastructure for GaAs than any other III-V compound semiconductor. Some GaAs devices are in direct competition against silicon devices for application in the commercial market. While much of the discussion below is directed to GaAs, it can also be applied to other III-V compound semiconductors because these other compounds have the same zencblende crystal structure, and have physical and chemical characteristics similar to GaAs.
GaAs, as well as other III-V semiconductor wafers, are much more fragile than silicon wafers. Thus, wafer breakage during device manufacturing is one of the cost disadvantages of GaAs devices and ICs compared to silicon. Another disadvantage of GaAs is that sizes of GaAs wafers available for manufacturing are far smaller than silicon wafers. Currently, the largest size of GaAs wafer available is increasing from 100 mm to 150 mm. However, this increase in wafer size exacerbates the wafer breakage problem.
The density of GaAs is 2.28 times that of silicon. Therefore, a GaAs wafer having a size comparable to a silicon wafer will have more than twice the weight of the silicon wafer. Because such GaAs wafers are more fragile than silicon wafers, and because such GaAs wafers are heavier than silicon wafers, most of the processing machinery originally designed to process silicon wafers may have to be modified if it is used to handle GaAs wafers. Such modifications are generally directed toward slowing the motion of wafers inside the equipment to minimize the likelihood of wafer breakage.
Because GaAs is much denser than silicon, increasing the GaAs thickness to enhance wafer strength is impractical. Further, because of the fracture mechanism of a GaAs single crystal wafer (as well as other III-V semiconductor wafers), making the wafer thicker does not always increase the strength of the wafer proportionally against breakage. This is because III-V semiconductor wafers cleave very easily along { 110 } crystal planes. The cleavage can be initiated from mechanical surface defects, such as scratches from wafer processing or intrinsic material flaws, such as micro voids. A small crack is first formed from these defects or flaws on one of the { 110 } planes which has the smallest cross section (i.e. one of the { 110 } planes perpendicular to the wafer surface). The crack then propagates along the { 110 } plane in response to repeated mechanical impacts and thermal cycling that wafer is subjected to during device processing. The wafer breaks apart when the crack along the { 110 } plane extends across the whole wafer. When that occurs, it occurs most often when the wafer is handled kinetically, e.g. transferring the wafer between cassettes or between a cassette and a machine. If the wafer breaks inside a machine, this not only destroys the wafer, but also may force the shut down of the machine.
After fabrication of devices such as FETs, HBTs and MMICs is done on front side of wafer (the so-called “front side process” in the industry), wafer backside processing follows. The first step of backside processing is wafer thinning by grinding followed by wet chemical etching on the backside of wafer. See, for example, R. E. Williams, “Modern GaAs Processing Methods”, published by Artech House in 1990; and Grupen-Shemansky, et al., “A Novel Wafer Thinning Process for GaAs or Si”, 1994 GaAs MANTECH Conference, pp. 167-170. Although a GaAs wafer is more fragile than silicon, a GaAs wafer needs to be thinned to about 0.1 mm or even 0.03 mm, compared to 0.2 mm to 0.3 mm typically used for silicon wafers. The main reason for such thin GaAs device wafers is that the thermal conductivity of GaAs is only ¼ that of silicon. Another reason is that a thin and precise semi-insulating GaAs substrate thickness is a result of design optimization for strip-line microwave transmission impedance of a MMIC.
A rigid wafer support and front side protection has been developed to aid in the GaAs wafer backside thinning process. See R. E Williams above and Norman, et al., “Substrate Mounting for Wafer Thinning or Substrate Removal, New Technique Factors”, 1992 GaAs Mantech, p. 19-22. To obtain sufficient accuracy in thickness and uniformity, great care is needed during the thinning process.
After wafers are thinned, there are three choices of backside processes before the wafer is scribed and separated into individual devices/ICs:
1. One can do no such additional backside processing if the device/IC will be attached to a metal carrier by an epoxy bond.
2. One can deposit metal on the wafer backside if the device/IC will be attached to a circuit by a solder bond.
3. One can etch small holes extending from the backside of the device/IC to the front side and then deposit metal in the holes to connect device ground (on the front side of the wafer) to the backside metal. This third backside process requires many steps including photo-resist spin and bake, an infrared (“IR”) contact mask to align a mask on one side of the wafer with structures on the other side of the wafer (see R. E. Williams as cited above), and reactive ion etching (“RIE”). To avoid processing these steps on thin and fragile GaAs, it has been proposed to move these processing steps to front side. See Furukawa et al “A Novel Fabrication Process of Surface Via-Holes for GaAs Power FETS”, Tech. Dig. 1998 GaAs IC Symposium, pp251-254, and Ishikawa et al., “A High-Power GaAs FET Having Buried Plated Heat Sink for High Performance MMICs”, IEEE Trans. Electron Devices, Vol. 41, No. 1, 1994, pp. 3-9.) However, this is at a tradeoff cost of requiring a precisely controlled etched hole depth. When using this process, one still cannot avoid the requirement of precise control during backside thinning.
In summary, GaAs wafers are more fragile than silicon. Therefore, the wafers must be handled with greater care. This makes backside processing more complex and difficult.
SUMMARY
A method for reducing the likelihood of a III-V compound semiconductor wafer breaking comprises the step of bonding first and second wafers together. Of importance, the { 110 } cleavage planes in the first wafer perpendicular to the surface of the first wafer are not aligned to any of the { 110 } planes in the second wafer perpendicular to the surface of second wafer. (The symbol { 110 } refers to a family of equivalent crystallographic planes. For example, the ( 110 ), ( 101 ), ( 011 ), ( 110 ), ( 110 ), etc. are all members of this family of planes.) The angle of misalignment between such { 110 } planes in two wafers is preferably the maximum allowed by the nature of the zencblende crystal in III-V compounds to maximize the benefit of misalignment in strengthening the bonded wafer to prevent cleavage.
In a preferred embodiment of bonding two wafers with same crystal surface orientation, e.g. a ( 100 ) orientation, every { 110 } plane in the first wafer perpendicular to the surface of the first wafer is misaligned by about a 45° angle with respect to any corresponding { 110 } plane in the second wafer.
In another embodiment, two wafers with different crystal surface orientations, e.g. an orientation of ( 100 ) for one wafer and ( 111 ) for the second wafer, are bonded together. The maximum effective misalignment between two ( 011 ) planes in the two wafers is 15°. Because the { 110 } planes perpendicular to the wafer surface in the two wafers are misaligned, cleavage along one { 110 } plane of one of the wafers will not propagate to the second wafer's { 110 } plane, and the bonded wafers will exhibit a reduced tendency to break.
The preferred bonding technique is high temperature (400 to 1000° C.) wafer fusion bonding to achieve mechanical strength against wafer separation. (Fusion bonding has been successfully achieved in GaAs, InAs, GaP, InP and epitaxial grown surface films of ternary and quaternary III-V compounds. See Okuno et al, “Direct Wafer Bonding of III-V Compound Semiconductors for Free-Material and free-Orientation Integration” IEEE J. of Quantum Electronics, Vol. 33, No, 6, 1997.) The first and second wafers can be any combination of two different III-V compound semiconductors, but are preferably made of the same III-V compound. Because of this, their coefficients of thermal expansion match, and thermal stress introduced into the wafers during processing should be minimized, which is advantageous during device and device processing.
Electronic devices, such as transistors and MMICs, are typically formed in semi-insulating material in the first wafer after bonding. Thereafter, the second wafer and part of the first wafer can be removed, first by mechanical grinding followed by chemical etching to reduce the wafers to the final device/IC substrate thickness. Unique to III-V semiconductor device fabrication, selective wet etching or dry etching is widely used in device manufacturing. The wafer fusion bond structure can be used to take the advantage of these selective etch properties in III-V semiconductors for a robust backside process. Since the second wafer provides mechanical support, the first wafer (the device wafer) is polished to device substrate thickness (e.g. 0.03 mm to 0.15 mm ) prior to front side device processing. During backside processing, the second wafer is selectively etched off by one of two techniques:
1. Select a material for the second wafer that can be selectively etched against the first wafer. In other words, the second wafer material has a substantially greater etch rate than the first wafer material. (This difference in etch rate can be accomplished, for example, by doping one of the wafers with an impurity, or using completely different wafer materials.)
2. Provide a thin (e.g., 30 to 100 nm) etch stop layer on the bonding surface of either the first or second wafers before wafer bonding. In one embodiment, this etch stop layer can be epitaxially grown on the bonding surface prior to bonding. Etching of the second wafer stops at etch stop layer. Then, the thin etch stop layer is etched off in a second selective etching step. The second bonded wafer and etch stop layer combined with the use of a selective etching process can be used advantageously to provide a high yield via hole process in front side of the wafer.
FIG. 1 illustrates first and second III-V semiconductor wafers bonded together in accordance with a first embodiment of my invention.
FIG. 2 illustrates first and second III-V semiconductor wafers bonded together in accordance with a second embodiment of my invention.
FIGS. 3A to 3 D illustrate the manufacturing of a transistor on a pair of bonded wafers in accordance with one embodiment of my invention.
FIGS. 4A to 4 D illustrate the manufacture of a transistor with a backside contact via hole on a pair of bonded wafers in accordance with another embodiment of my invention.
DETAILED DESCRIPTION
FIG. 1 illustrates a first ( 100 ) III-V semiconductor wafer 1 bonded to second ( 100 ) III-V semiconductor wafer 2 . Wafers 1 and 2 are typically GaAs, but other III-V semiconductor materials can be used as well. The ( 100 ) crystal directions of first and second wafers are shown by arrow 3 . Also shown in FIG. 1 are the directions of ( 011 ) crystal plane for wafer 1 (arrow 4 ) and ( 011 ) crystal plane (arrow 5 ). Arrows 6 and 7 show equivalent { 110 } crystal planes in ( 100 ) wafer 2 . These { 110 } planes are perpendicular to the surface of ( 100 ) wafers 1 and 2 . The angle between the planes represented by arrows 4 and 5 is 90°. Similarly, the angle between the planes represented by arrows 6 and 7 is 90° . Therefore, a maximum effective rotational misalignment between two sets of { 110 } planes in wafers 1 and 2 is 45°, i.e. one half of 90°.
An effective rotational misalignment φ is given because for any actual angle of rotation θ of wafer 1 with respect to wafer 2 , there can only be an effective rotational misalignment φ that is between 0 and 45°. This effective rotational misalignment φ repeats within each quadrant of rotation. Thus, if wafer 1 is rotated by an angle θ=40°, that produces the same effective rotational misalignment φ as if wafer 1 were rotated by an angle θ=50°. Because of the four-fold symmetry of { 110 } planes in ( 100 ) wafers, there are a total of eight equivalent angles of rotation θ for each effective rotational misalignment φ. These equivalent angles of rotation θ are θ=±φ+n90°, where n is any integer. For a given angular rotation θ of wafer 1 with respect to wafer 2 , the effective rotational misalignment φ equals abs(θ±n90°) for that integer n that produces a value of φ between 0 and 45°. (“abs” refers to the absolute value.) Another way of stating this relationship is that φ=θ modulus 90° if θ modulus 90° is less than or equal to 45°; otherwise, φ=90°−(θ modulus 90°). If wafer 1 is rotated by an angle θ that is an integral multiple of 90°, the effective rotational misalignment φ is zero.
FIG. 1 illustrates one of the maximum effective rotational misalignments of wafer 1 with respect to wafer 2 , i.e. misalignment by 45°. Specifically, wafer 1 (or arrow 4 ) is rotated clockwise with respect to wafer 2 (or arrow 6 ) by 45°.
In an alternate embodiment of my invention, two ( 111 ) wafers 1 and 2 are bonded together. The angle between any two of the ( 011 ), ( 101 ) and ( 110 ) cleavage planes (the { 110 } planes which are perpendicular to the ( 111 ) wafer surface) is 60° and the crystal symmetry is six fold. The maximum effective rotational misalignment, φ max is thus 30°. When bonding two ( 111 ) wafers together. The effective rotational misalignment, φ, is calculated by the equation φ=abs(θ±n60°) for that integer n which provides a value of φ between 0 and 30°. Another way of stating this relationship is that φ=θ modulus 60° if θ modulus 60° is less than or equal to 30°; otherwise, φ=60°−(θ modulus 60°). The equivalent angles of rotation θ for an effective rotational misalignment φ are θ=±φ+n60° where n is any integer. There are a total of twelve equivalent angles of rotation θ that can produce a given effective misalignment angle φ when bonding two ( 111 ) wafers.
FIG. 2 shows a second embodiment of my invention in which two wafers with different surfaces, ( 100 ) in wafer 1 ′ and ( 111 ) in wafer 2 ′, are bonded together. Directions of the ( 011 ) and ( 0 {overscore ( 1 )} 1 ) planes in wafer 1 ′ are represented by arrows 4 ′ and 5 ′, respectively. Directions of the ({overscore ( 1 )} 10 ), ({overscore ( 1 )} 01 ) and ( 0 {overscore ( 1 )} 1 ) planes in wafer 2 ′ are represented by arrows 8 , 9 and 10 , respectively. There is only one { 110 } cleavage plane from each wafer that can be aligned. If the ( 0 {overscore ( 1 )} 1 ) planes from wafer 1 ′ and wafer 2 ′ are aligned (0° of rotation between arrows 5 ′ and 10 ), the angle between the ( 011 ) plane (arrow 4 ′) in wafer 1 ′ and the ({overscore ( 1 )} 10 ) plane (arrow 8 ) and ({overscore ( 1 )} 01 ) plane (arrow 9 ) in wafer 2 ′ is 30°. Therefore, 30° rotation will align the ( 011 ) plane (arrow 4 ′) in wafer 1 ′ with either the ({overscore ( 1 )} 10 ) plane (arrow 8 ) or the ({overscore ( 1 )} 01 ) plane (arrow 9 ) in wafer 2 ′. 60° of rotation will align the ( 0 {overscore ( 1 )} 1 ) plane (arrow 5 ′) in wafer 1 ′ with either the ({overscore ( 1 )} 10 ) plane (arrow 8 ) or the ({overscore ( 1 )} 01 ) plane (arrow 9 ) in wafer 2 ′. The maximum effective rotational misalignment between ( 100 ) and ( 111 ) wafers 1 ′ and 2 ′, φ max , is thus 15°. The equivalent angles of rotation θ between wafers 1 ′ and 2 ′ for an effective rotational misalignment angle, φ, are θ=±φ+n30°, where n is any integer. For a given rotational angle θ, the effective rotational misalignment is φ=abs(θ±n30°) for that integer n that produces a value of φ between 0 and 15°. Another way of stating this relationship is that φ=θ modulus 30° if θ modulus 30° is less than or equal to 15°; otherwise, φ= 30°−(θ modulus 30°).
FIG. 2 illustrates one of the maximum effective rotational misalignments of wafer 1 with respect to wafer 2 , i.e. misalignment by 15°. Specifically, wafer 1 (or arrow 5 ′) is rotated clockwise with respect to wafer 2 (or arrow 10 ) by 15°.
Wafers 1 and 2 are preferably bonded together by thermal fusion at temperature between about 400 and 100° C. The technology of high temperature wafer fusion bonding is well established in manufacturing. Equipment for manufacturing can be purchased from Karl Suss, and Electronic Visions Co. Selection of a fusing temperature depends on the subsequent highest process temperature that the bonded wafers will be exposed to. For example, if wafer 1 will be subjected to ion implantation and an annealing process at a temperature of 700 to 850° C., the fusion temperature may be as high as 900° C. If wafer 1 will be used for epitaxial layer growth in a molecular beam epitaxial machine (e.g. a growth temperature of about 650° C.), a fusion temperature of 700° C. may suffice for bonding wafer 1 and 2 . (I prefer to ensure that the bonding temperature is greater than or equal to the highest processing temperature that wafers 1 and 2 are subsequently subjected to.)
Top wafer 1 is used for device fabrication using conventional GaAs IC manufacturing techniques. Typical materials for wafer 1 are ( 100 ) semi-insulating GaAs or InP. Bottom wafer 2 is provided first for mechanical strengthening purposes. The thickness of wafer 2 is in range of 0.3 to 0.6 mm. Wafer 2 is removed completely during the backside process. Alternatively, wafer 2 can be used to assist in the backside process as discussed below.
FIGS. 3A to 3 D show the use of bonded wafers to assist backside processing. In this embodiment, a p + conducting GaAs wafer 2 and a semi-insulating ( 100 ) GaAs wafer 1 are fusion bonded according to first or second embodiment (FIGS. 1 or 2 ). FIG. 3A shows that with wafer 2 supporting wafer 1 , wafer 1 is polished to a thickness T 1 (0.15 to 0.03 mm). This thickness is appropriate for forming devices in wafer 1 .
FIG. 3B shows that devices, such as FET 20 for example, are fabricated in wafer 1 during front side processing. (As shown in FIG. 3B, FET 20 comprises a source S, a drain D and a gate G.) During backside processing, wafer 2 is partially removed, first by mechanical means, such as backgrinding or lapping, for high removing rate. This can be done in a manner similar to that described by the Grupen-Shemansky or R. E. Williams references, described above. Thereafter, the remaining portion of wafer 2 is etched off using an anodic etching technique as shown in FIG. 3 C. This can be done using a technique as described by Nuese, et al., “Electrolytic Removal of P-Type GaAs Substrates from Thin, n-type Semiconductor Layers”, J. Electrochem. Soc. Vol. 117, No. 8, 1970, pp1094-1097.
FIG. 3D shows that an optional backside metallic layer 13 , such as Ti/Au, is deposited on the bottom side of wafer 2 . After deposition of layer 13 , wafer 1 is sawed or scribed and separated to individual devices or ICs.
FIGS. 4A to 4 D show a fourth embodiment of a bonded wafer assisting backside processing. During this processing, a via hole is provided. A thin (30 to 100 nm) etch stop layer 30 is sandwiched between ( 100 ) semi-insulating GaAs wafer 1 and any GaAs wafer 2 . (The wafers can be oriented in accordance with the first or second embodiments.) The etch stop layer 30 is III-V compound semiconductor alloy such as Al x Ga 1−x As (0.03<x<1) which, prior to wafer bonding, is epitaxially grown on one bonding surface using MBE or MOCVD technique. Alternatively, etch stop layer 30 can be grown by a liquid epitaxial technique using the following steps. A thin layer of Al is deposited, prior to wafer bonding, on one bonding surface of one of the wafers. Thereafter, the two wafers are bonded at a temperature much higher than the melting point of Al (660° C.) to dissolve part of the GaAs into the molten Al layer. Dissolved GaAs precipitates in a Al x Ga 1−x As alloy during wafer cooling and epitaxially grows on the GaAs surfaces. With wafer 2 supporting wafer 1 , wafer 1 is polished to a thickness T 1 (0.15 to 0.03 mm). (Thickness T 1 is appropriate for forming devices such as FETs, HBTs or ICs.) Devices such as FETs (e.g. FET 20 ) and ICs are fabricated in wafer 1 during front-side processing. Also during front-side processing, a via 32 is etched through wafer 1 . When etch stop layer 30 (at depth T 1 below the surface of wafer 1 ) is reached, the via hole etching process is stopped. Etch stop layer 30 ensures the etched via hole using selective etching stops at etch stop layer 30 . The etched via hole 32 is covered with a conductive layer such as thick Au 34 and connected to a device such as FET 20 , e.g. by the combination of sputtering or electroless plating followed by electroplating (see Furukawa et al cited above). During backside processing, wafer 2 is removed partially first by mechanical means, such as backgrinding or lapping, for a high removal rate. The remaining portion of wafer 2 is etched off with a selective wet etchant, which etches GaAs, but etches only a small amount of Al x Ga 1−x As (0.03<x<1) etch stop layer 30 . Etch stop layer 30 is then etched off with second selective etchant, which etches Al x Ga 1−x As (0.03<x<1) rapidly compared to GaAs. Results from these selective etches are shown in FIGS. 4A to 4 C.
Thereafter, a metallic layer 13 , such as Ti/Au, is deposited on the bottom side of wafer 2 as shown in FIG. 4 D. Then wafer is sawed or scribed and separated to individual device or IC chip. Of importance, a voltage such as ground can be applied to transistor 20 via the carrier that device or IC chip is mounted on and through the Ti/Au 13 and thick Au 34 .
In summary, bonding two wafers in the manner described above results in a stronger, more mechanically robust III-V semiconductor wafer than a single crystal wafer with same thickness. Further, bonding two wafers offers an opportunity to simplify III-V semiconductor backside processing by combining two materials different in etching characteristics or inserting a thin etch stop layer between two wafers. With a stronger bottom wafer (wafer 2 ) in support, it is easier to thin the top device wafer to an appropriate device substrate thickness prior to front side processing than thinning a device wafer from the backside after the expense of front-side fabrication has been incurred. Via hole processing can be moved from the backside to the front-side process. The selective etching stops via hole etching at the correct depth and permits one to selectively etch only the bottom wafer during backside processing in the manner as described above. This backside process is robust and results in a high yield manufacturing process. In contrast, without this novel structure and method, precise control during etching would be required to stop etching at the required depth and to remove right amount of backside material.
While the invention has been described with respect to specific embodiments, those skilled in the art will recognize that changes can be made in form and detail without departing from the spirit and scope of the invention. For example, the angle of rotational misalignment between two bonded wafers is preferably as close to the maximum effective rotational misalignment as practical to maximize the benefit of misalignment in strengthening the bonded wafer. However, strengthening wafers using rotational misalignment angles other than the maximum effective rotational misalignment angles also falls in the scope of this invention. Two different III-V semiconductors can be used in bonding. Examples of such materials include GaAs, GaP, GaSb, InP, InAs and InSb. A ternary Al x Ga 1−x As alloy etch stop layer is given because it can be grown easily on GaAs and a large number of selective etching chemistries are available. However, other ternary or quaternary alloy layer can be used as etch stops. Examples are In .x Ga x P for ternary, and In. y (Al .x Ga 1−x ) 1−y P for quaternary etch stop layers. Because the lattice constant of Ge is very close to GaAs, Ge is a good choice for an etch stop. Accordingly, all such changes come within the invention.
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A first III-V semiconductor wafer is bonded to a second III-V semiconductor wafer, e.g. by thermal fusion. The { 110 } crystal plane of the III-V semiconductor wafer is displaced angularly relative to the { 110 } crystal plane of the second III-V semiconductor wafer. Because of this, the tendency of the bonded wafer to break is reduced and many backside processes can be moved to front side and results in a robust device manufacturing process.
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REFERENCE TO RELATED APPLICATION
This application is a continuation of International Application No. PCT/EP97/00809 filed Feb. 19, 1997.
BACKGROUND OF THE INVENTION
This invention relates to multifunction display arrangements for motor vehicles which include an electronic display unit having a picture screen to display information in the form of signs and symbols and at least one control member within the driver's field of view in a part of the interior trim of the vehicle.
Increased traffic density and the desire of vehicle users for greater comfort have led to numerous electronic accessories in motor vehicles, such as guidance, warning, audio systems and mobile radios which provide large quantities of information and messages to be supplied to the operator. For presentation of such information, electronic display units, especially in the form of monitors or picture screens, which are increasingly coming into use, have the advantage that different data sets can be presented in time sequence at the same location. The reception of such a large quantity of information is necessary for the driver's operation of the vehicle but causes a diversion of the driver's attention from the road while reading the screen. For this reason, the duration of any such diversions must be kept as short as possible.
Various lighting conditions, incident light on the display screen and light or images reflected from the display screen may interfere seriously with reading of the displayed information. This results in a diversion of the vehicle driver's attention for time durations that are often unwarranted in terms of safety.
To reduce light reflection from picture screens or monitors, for example, U.S. Pat. No. 5,288,558 and German Offenlegungsschrifts Nos. 41 00 831 and 41 17 257 disclose the application of antireflection coatings either directly to the surface of a display screen or to a sheet of glass in front of it.
To provide a display in a motor vehicle, U.S. Pat. No. 4,521,078 further discloses arranging the display surface of the display screen at an angle between the display surface and the direction of the viewer's gaze which is different from 90° to prevent specular and other reflections, and presenting characters on the inclined display surface which are distorted in such a way that they are viewed without distortion by the user.
Further, to diminish specular reflection in the display surface of a display unit in a motor vehicle, German Offenlegungsschrift No. 44 25 204 discloses a covering glass for a display screen which is oriented so that, from a driver's average viewpoint, a portion of the instrument panel located in front of the display unit is reflected by the glass.
Because vehicle users have different stature and use different seat adjustments, however, such solutions do not always provide the desired result with every driver.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a multifunction display arrangement for a motor vehicle which overcomes disadvantages of the prior art.
Another object of the invention is to provide a multifunction display arrangement which, considering a vehicle user's individual ergonomy and the lighting conditions under which the vehicle is operated in each instance, is easily readable because the effects of light shining into the vehicle and/or specular and other reflections from light-colored interior surfaces can be avoided to a large extent or even eliminated completely.
These and other objects of the invention are attained by providing a multifunction display arrangement having a display screen which is supported for pivotal motion on at least two axes.
According to the invention, at least the electronic display unit of the multifunction display arrangement may be mounted in an aperture of the interior vehicle trim, pivotably on at least two axes, preferably a vertical and a horizontal axis, to improve readability.
This has the advantage that, beside permitting an optimal orientation of the display screen in relation to directly incident light, the display unit may be adjusted with respect to reflected light colored areas or surfaces in the motor vehicle to provide a viewing or reading direction which is convenient to the user.
In accordance with one embodiment of the invention, the electronic display screen is part of a structural unit which also contains a control member or members, in which case the entire unit may advantageously be pivotable on the two axes.
Preferably for design reasons the angle through which the electronic display unit is pivotable in the aperture of the interior trim is no more than about 10-20° on each axis.
The pivotal suspension of the electronic display screen or unit may be achieved in many different ways. Thus, in one embodiment, the display screen or unit is pivotable about a mounting constructed, for example, in the manner of a ball-and-socket joint. In this case, a socket member is provided in which a ball member, having the configuration of a partial or complete sphere, is rotatably held so that, upon pivoting of the display screen or unit about the joint, individual points of the picture screen surface follow a spherical motion path having a center of curvature which is located more or less at the center of symmetry of a picture screen surface of rectangular, oval or circular shape. For this purpose, according to another aspect of the invention, the center of rotation for the mount consisting of a socket element and a ball element is in the region of the surface of the multifunction display screen. For a display screen or unit mounted in a housing so that the picture screen surface is substantially flush with the front of the housing, the center of rotation is thus moved into the region of the screen. The center of rotation can be positioned to the front or rear of the screen, depending on the application, to the extent that the mobility of the display screen or unit as a whole is not unduly impaired. In the ideal case, however, the center of rotation is located exactly at the picture screen surface. The socket element and the ball element may be associated either with the movable display screen or unit or, at least indirectly, with the interior trim.
According to another embodiment, the display screen or display unit of the multifunction display arrangement is pivotable about a position which is essentially flush with the front of the housing in a mounting constructed, for example, in the manner of a telescoping ball-and-socket joint. For example, at least three socket elements are provided, in which ball elements in the form of partial or complete spheres at the ends of movable piston rods are rotatably held and are also displaceable lengthwise perpendicular to the normal position of the display screen so that, by appropriate pressure on the display screen or unit, the position can be adjusted to the direction of view of a user. Because the screen or unit is supported at several positions, individual adjustability to the needs of the user and to prevailing visibility and lighting conditions is possible.
It will be understood that the components of the ball-and-socket mountings may be reversed if desired, that is, the end portions of the piston rods may be in the form of socket elements, and the corresponding ball elements may be affixed to the rear of the display screen or unit. Reversing the components of the ball-and-socket mounting in this manner will not limit the mobility of the display screen or unit.
In an advantageous modification of this embodiment, coupling arrangements are provided to connect bearing mounts. Coupling of the bearing mounts may be accomplished by various mechanisms, for example mechanical linkages such as cables, hydraulic lines, electrical servo motors and the like. Because of the linkages of the bearing mounts, at least when coordinated in pairs, the axis of rotation of the display screen or unit is located at the midpoint of a line connecting the coupled bearing mounts, in other words a line parallel to the visible surface of the display screen or unit. An advantage of coupling the bearing mounts is that only pressure need be applied to adjust the display screen or unit. The distance over which piston rods acted upon by the applied pressure are moved into the housing is compensated by motion of the coupled bearings in the opposite direction. Thus an over-all motion of the display screen or unit to a position into the interior of the housing is prevented. Furthermore, no handles or gripping devices need be attached to the display screen or unit to effect a motion of a portion of the display screen or unit toward the user.
As one example, the coupling between bearing mounts may be effected by Bowden cables or the like. The use of commercially avialable Bowden cables or the like provides an economical, well-tried, dependable and easily replaced mechanism. Because of the built-in flexibility of these devices, their placement can be adapted to the requirements of the housing interior.
Further, by connecting the bearing mounts through fluid lines, hydraulic coupling can be effected and the hydraulic channels can be integrated to special advantage into the housing walls so that they require no space in the interior of the housing and the walls are not burdened by connections or holders. Also, the use of hydraulic couplings provides the possibility of intercoupling all the bearing locations and thus generating a center of rotation of the display screen or unit in the center of the area bounded by the end points of the bearing mounts.
It is also of advantage that, by suitable choice of viscosity of the hydraulic coupling, adjustable damping can be achieved. Thus, the display unit can be arranged so that it can only be pivoted slowly, avoiding any unintentional shifting of the display unit beyond a desired position. Furthermore, the damping effect of the hydraulic fluid prevents automatic restoration of the display unit to its normal position, so that a selected setting is maintained.
Pivoting of the display screen or unit by way of electrical signal detectors, signal emitters and servo elements advantageously assures that there need be no restriction as to placement of the conductors inside the housing. The conductors may either be integrated in the housing wall or laid along the wall. The use of servo elements permits a spatial separation of a control element and the display screen or unit, much like that of electrically operable window drives and outside mirrors. The control element may, for example, be mounted in the vicinity of the vehicle steering wheel so that a driver need not move a hand to the display unit while driving.
In another advantageous embodiment a multi-function display arrangement has a housing frame mounted in the interior vehicle trim and arranged to accommodate the movable mounting of the display unit. Such a multifunction display arrangement may be mounted as a complete module, for example, into an instrument panel or a central console. Alternatively, however, it is possible to configure the trim part as a housing for the display unit.
Because of the small structural depth of the display unit mount and its good angular adjustability, application of the invention to other information media is possible. Installation for example of one or more display screens or units in the backrest or headrest for the front seats to exhibit television programs or as a computer picture screen may be advantageously effected.
BRIEF DESCRIPTION OF THE DRAWINGS
Further objects and advantages of the invention will be apparent from a reading of the following description in conjunction with the accompanying drawings, in which:
FIG. 1 is a fragmentary view illustrating a portion of an instrument panel of a motor vehicle containing a representative embodiment of a display arrangement according to the invention, in particular a picture screen, pivoted on a vertical axis;
FIG. 2 is a view similar to FIG. 1 showing a portion of an instrument panel of a motor vehicle with a combined display screen and operating unit pivotable on a horizontal axis;
FIG. 3 is a perspective view showing a multifunction display arrangement as viewed by a vehicle user;
FIG. 4 is a sectional view of the multifunction display arrangement shown in FIG. 3, taken along the line IV—IV of FIG. 3;
FIG. 5 is a sectional view taken on the line V—V of FIG. 4;
FIG. 6 is a perspective view showing a housing for a multifunction display unit as viewed by a vehicle user;
FIG. 7 is a sectional view taken on the line VI—VI of FIG. 6; and
FIG. 8 is a schematic view showing a universal mount for an electronic display unit.
DESCRIPTION OF PREFERRED EMBODIMENTS
In the typical embodiment of the invention shown in FIG. 1, a portion of an instrument panel 1 of a motor vehicle is shown from the point of view of the driver's seat. A region 1 a of the instrument panel 1 facing the driver's seat includes a display element 3 in the form of a pointer instrument and a steering wheel 4 as well as a central console 1 b . A portion 2 of the central console accommodates a picture screen 5 of a multifunction display arrangement and includes an operating member 6 consisting of keys 6 a and a rotary switch 6 b arranged below the portion 2 . Using the keys 6 a , various accessories in the motor vehicle, such as a navigating instrument, audio instruments or a mobile radio, can be selected for operation. The rotary switch 6 b operates the particular accessories selected. An information display 5 a which is necessary for operation of the accessories is presented to the user on the picture screen.
In FIG. 1, the picture screen 5 has been turned on its vertical axis y toward the driver's seat to improve contrast. In this embodiment, this is accomplished by applying gentle pressure of the finger on the side of the picture screen frame facing the driver's seat. By this measure, for example, contrast on the surface of the picture screen can be improved if light is incident in the direction of the arrow r.
In the multifunction display arrangement illustrated in FIG. 2, the picture screen 5 is included in a display unit 7 together with the operating elements 6 , which again consist of keys 6 a and a rotary switch 6 b , the unit 7 being pivotably supported for motion in two axes x and y in the aperture 2 of the central console 1 b . The integration of the picture screen 5 and the operating members 6 in a display unit 7 enhances operability of the multifunction display arrangement since there is no danger that the operating members 6 may become invisible or difficult of access when the display unit containing the picture screen 5 is pivoted. In FIG. 2, the display unit 7 has been turned on its horizontal axis x by applying pressure at the bottom of the unit to minimize reflections due to light incident on the screen 5 through the windows, not shown, of the vehicle. Also, the unit 7 can be optimally adjusted in this way to be convenient to a user's direction of view.
FIG. 3 shows a multifunction display arrangement built into an instrument panel 1 , which is only partially illustrated. A display screen 5 is pivotable about axes x and y, singly or jointly, within a housing frame 9 . At the front 21 of the housing frame 9 , several operating members 6 are provided in a conventional manner. The complete multifunction display arrangement has the configuration of a drawer module, and includes tabs 10 and 11 of the type used for mounting of vehicle radios, to secure the display unit in a frame (not shown) which is associated with the instrument panel 1 . As shown in FIG. 4, similar tabs 12 and 13 are located on the opposite side of the housing frame 9 , which is not visible in FIG. 3 .
The internal structure of a representative embodiment of the multifunction display arrangement according to the invention is illustrated in FIG. 4 . As there shown, the housing frame 9 has a front portion 14 , a back wall 15 , and lateral function compartments 22 and 23 holding electronic components which are only schematically indicated. These components can be controlled by the operating members mounted in the front portion 14 . If desired the components may also be supplied with external control signals from remote sensors or by radio transmission. A transmission line 24 supplies the display unit with operating signals and is also capable of transmitting information signals from the electronic components to the display unit where they are displayed on the screen 5 .
In this embodiment a ball element 16 , in the form of a partial sphere, is supported for rotation about the axes x and y, singly or jointly, by a socket element 17 which is affixed to the back wall 15 by a pin 30 . The radius of curvature of the engaging surfaces of the ball and socket is chosen so that a center of rotation D is located in the region of the picture screen surface 25 . Thus, inside an opening 26 in the housing frame 9 , the display unit 5 can be pivoted in such a way that the inner walls of the function compartments 22 and 23 are not touched by the rotatable unit, even for relatively large angles of rotation. To provide a defined maximum limit to the angle of motion, guide shells 27 and 28 are provided which, as part of the supporting stand accommodating the display screen 5 , form a circular aperture 29 surrounding a pin 30 by which the ball 16 is affixed to the back wall 15 . In the maximum angular positions, the pin 30 affixed to the back wall 15 engages the edges of the aperture 29 in the socket element 17 . In an especially advantageous embodiment, the pin, ball and socket can be provided in a single subassembly made of parts which can be very economically produced by injection molding. If desired, the pin 30 and the socket element 17 may be integrated in one part, which is then attached to the back wall 15 by a screw or clip connection. It is also possible to provide an arrangement in which the inside walls of the function compartments 22 and 23 and the back wall 15 together form a spherical dish, optionally also in one piece, in which a supporting stand formed like a partial sphere is rotatably supported.
In a preferred embodiment, the ball element 16 is also an integral part of the supporting stand holding the display unit 5 . The support stand is here made like a drawer receptacle, having a push-in opening in a lateral region 31 . The display unit is pushed or placed into this opening and the, locked, for example by catches not shown in detail, engaging catch recesses. In this example, the bearing shells 27 and 28 are screwed to the support stand. However, mounting by clipping or plugging is also possible.
In a modification of the arrangement illustrated in FIG. 4, a socket element may be associated with the support stand of the display unit 5 . The ball element and the bearing shells enclosing the socket element may then be associated either with the back wall 15 , or with the inside walls of the side parts 22 and 23 , or with a bottom 32 or a cover of the housing frame 9 . The invention also includes embodiments in which the radius of the ball element is markedly smaller than the width of the picture screen, and the ball element is located directly behind the picture screen surface in a correspondingly small socket element.
In another embodiment, not illustrated, the entire display unit 5 is displaceable also in the z-direction, i.e., in a guide preferably designed in the manner of a mechanical flip-flop. In this way, the display unit 5 can be moved forwardly out of the housing frame 9 under especially extreme conditions of view. For this purpose, an outer frame of the display unit 5 may merely be subjected to an actuating pressure. Spring action then moves the complete display unit 5 with its mount out of the housing frame 9 . For the return motion likewise, a gentle pressure on the frame is sufficient. Such flip-flop constructions are known in a variety of modifications, for example in furniture or covers and flaps on electronic equipment, and therefore will not be described in detail here.
Another embodiment of a pivoting mechanism for the multifunction display arrangement is shown in FIGS. 6 and 7.
In FIG. 6, a housing arrangement, generally designated 9 , for a multifunction display with housing walls 20 , a housing front 19 and operating members 6 is shown, the housing arrangement 9 being represented in this view without a display unit 5 . Four bearing elements 18 a-d are mounted in a housing aperture 34 . These elements have connections 35 a - 35 d of spherical shape, set back behind the housing front 19 , for supporting a display unit 5 . In the housing 9 , two coupling lines 36 are disposed in the rear and along the inside housing walls, preferably in the corner regions, for coupling two pairs of bearing locations 18 a and 18 c , and 18 b and 18 d , respectively. The coupling lines 36 cross at the rear wall of the housing so that the pairs of bearing locations are connected diagonally, or crosswise. In a preferred embodiment, hydraulic fluid is provided as working medium. In other words, the coupling of the location pairs is hydraulic. The ends of the lines 36 are connected to the bearing elements 18 a-d , which constitute reservoirs and cylinders for the hydraulic fluid. The spherical connections 35 a-d for supporting the display unit are mounted on piston rods 37 a-d , respectively which extend perpendicular to the housing front 19 . By pressure on the display unit 5 , any angular setting within the pivotable range around the center of the display unit 5 can be reached.
The sectional representation in FIG. 7 shows the housing arrangement 9 of a multifunction display arrangement with a display unit 5 mounted therein. In this case the display unit comprises a frame 38 on the back 39 of the display to which the connections 35 a-d (only 35 c and 35 d are seen in the drawing) are coupled in the manner of ball-and-socket joints. On the back, socket elements 40 a-d (only 40 c and 40 d are visible in the drawing) are provided to receive the corresponding balls, permitting free rotary motion of the balls 35 a-d in the sockets. The piston rods 37 a-d (only 37 c and 37 d are seen in the drawing) are guided in the bearing devices 18 a-d (only 18 c and 18 d are seen in the drawing) so as to permit linear motion. The combination of linear and rotary motions provides adjustability of the display unit about the center of the display screen 5 .
It should be noted that the coupling of the bearing positions 18 may be hydraulic, electrical, cable or Bowden type, or by other mechanical linkage. The lines 36 either extend along the housing wall or, in embodiments not shown in the drawing, are integrated with the housing wall, or a combination of both. Advantageously, the bearing members 18 are coupled crosswise diagonally. In other embodiments the coupling may be in parallel pairs through a common system of lines or otherwise.
FIG. 8 shows another example of a pivotable mounting of the display unit 7 , using a universal gimbal mount suspension mechanism. The display unit 7 is mounted in an accessory housing 8 , in which the display unit is pivotable about a horizontal axis x. The accessory housing 8 is in turn pivotable about a vertical axis y in the aperture 2 in the central console 1 b , thereby providing pivotability of the unit 7 in both the horizontal and the vertical direction.
Although the invention has been described herein with reference to specific embodiments, many modifications and variations therein will readily occur to those skilled in the art. Accordingly, all such variations and modifications are included within the intended scope of the invention.
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A multipurpose display arrangement for a motor vehicle includes an electronic display device for displaying information and at least one control element. The multipurpose display arrangement is located in an aperture in the vehicle instrument panel in the visual range of the vehicle driver. In order to minimize reflections and dazzle on the display surface which are caused by the incident light and/or bright surfaces inside the vehicle, the electronic display device is mounted so as to be pivotable in at least two axes in the instrument panel aperture.
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RELATED APPLICATION
This is a continuation-in-part of Ser. No. 686,632, filed Dec.31, 1984 now abandoned which was a continuation of Ser. No. 527,060, filed Aug. 29, 1983, now abandoned.
BACKGROUND OF THE INVENTION
This invention concerns a method for protecting living organisms against ionizing radiation, and more particularly involves the administration of high molecular weight radiation protecting agents to living organisms to protect them against ionizing radiation.
In the early 1950s it was found that cysteamine and related aminoalkyl thiols could protect living organisms against ionizing radiation. In particular, when these substances were given to mice prior to exposure to x-rays, the substances reduced the lethal effect of the x-ray radiation. Since that time, searches have been underway to discover better radiation protecting agents. Prior to making the invention disclosed in the present application, the most promising agent was WR2721 (S-2(3-Aminopropylamino)-Ethyl-Phosphorothioic Acid), which breaks down in the body to an aminoalkyl thiol, and its effect is similar to that of cysteamine.
Radiation protecting agents are useful for treating people who are likely to be exposed to radiation including workers associated with atomic reactors, military personnel, and astronauts who may be exposed while in orbit to a sudden burst from a solar flare. Radiation protecting agents are also useful as adjuncts in the radiotherapy of cancer in which the radiation protecting agents will selectively protect normal tissue allowing the cancerous tissue to be destroyed by the radiation therapy. The radiation protecting agents, to date, however, have many shortcomings including high toxicity in humans and very limited degree of protection.
SUMMARY OF THE INVENTION
It is thus an object of the present invention to provide a method for protecting animals including humans against ionizing radiation by use of a class of high molecular weight radiation protecting agents.
It is also an object of the present invention to provide protection for animals including humans against ionizing radiation by the administration of radiation protecting agents comprising a polymer with the approximate formula H(OCH 2 CH 2 ) n OH, where n varies between 4 and 13.
It is a further object of the present invention to provide protection of animals including humans against ionizing radiation by the administration of radiation protecting agents including polyethylene glycol (molecular weight 400), polyvinylpyrrolidone (molecular weight 10,000), and polyethyleneglycolmonomethylether (molecular weight 400).
Other objects and advantages of the invention will become apparent upon reading the following detailed description.
DETAILED DESCRIPTION OF THE INVENTION
While the invention will be described in connection with a preferred embodiment and procedure, it will be understood that we do not intend to limit the invention to that embodiment or procedure. On the contrary, we intend to cover all alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.
We have discovered that a prototype for radiation protecting agents, which are especially useful in protecting animals including humans against ionizing radiation, is embodied in a polymer with the approximate formula H(OCH 2 CH 2 ) n OH, where n varies between 4 and 13. One such substance is known commercially as polyethylene glycol 400 (molecular weight 400) and has been in existence for a number of years.
Polyethylene glycols are known to interreact with living cells causing a stabilization of the cell membrane, thereby promoting cell fusion and protection of cells against freezing. It is this phenomenon that is thought to account for the effectiveness of polyethylene glycol as a radiation protecting agent when administered prior to radiation.
The effectiveness of polyethylene glycol 400 as a radiation protecting agent is experimentally evidenced by the following protocol. Groups of 12 ICR male mice of about 25 to 28 grams each were injected intraperitoneally with 0.15 ml of polyethylene glycol 400 dissolved in 0.15 ml of water. The 1:1 solution was used to lower the viscosity of the polyethylene glycol 400 and thereby facilitate injection with a syringe. The polyethylene glycol can be injected undiluted in mice without harm, and it can be injected in more dilute form limited by the volume of solution that can be accommodated by the volume of the mouse's body. Ten minutes later the mice were anesthetized with pentobarbital, and twenty minutes later were irradiated with 1,650 rads of 250 kV x-rays limited to the head and neck. Control ICR male mice were irradiated in the same manner without being pretreated with polyethylene glycol 400.
Following irradiation, the mice were checked daily for fifteen days, and were examined for weight gain, symptoms, general appearance, and death from either administration of the drug or the radiation. The group which was injected with polyethylene glycol 400 experienced 2 out of 12 and 2 out of 12 deaths in two separate experiments. The control group with no injection of polyethylene glycol 400 experienced 9 out of 12 and 11 out of 12 deaths respectively.
The difference in survival is highly significant. Based on prior experiments in which death rates were correlated with radiation doses, the effect of the polyethylene glycol 400 treatment is the same as that of reducing the amount of radiation administered to untreated control groups of mice.
Polyethylene glycol 400 even provides protection when administered intraperitoneally after irradiation. In two experiments in which polyethylene glycol 400 in a 1:1 solution in water was injected five minutes after irradiation, only 6 out of 12 and 7 out of 12 mice were dead after fifteen days as compared to 10 out of 12 and 11 out of 12 untreated control mice.
Based on the experimental results of post radiation treatment, we have concluded that the mechanism of action involved in post-radiation treatment is something other than free radical scavenging which would only occur if the radiation protecting agent was present during radiation exposure. While the precise mechanism of post-radiation treatment with polyethylene glycol 400 is not known, the mechanism is probably related to polyethylene glycol's interaction with cellular membranes.
While polyethylene glycol having a molecular weight of 400 is preferred, we have found that significant radiation protection is achieved with polyethylene glycol having a molecular weight between 200 and 600. We have also determined that effective dosages of poly- ethylene glycol 400 for mice ranges from 1.6 grams per kilogram to 6.4 grams per kilogram. Because polyethylene glycol 400 is much less toxic than cystamine, WR2721, or other previously used radiation protecting agents, the maximum effective dose of 6.4 grams per kilogram is well below the LD 50 for poly- ethylene glycol 400 of approximately 9 grams per kilogram when injected intraperitoneally in mice.
Based on our experiments we have discovered no beneficial results in mice from treatment administered twenty-four hours before or three hours after irradiation. Therefore we have concluded that treatment should be undertaken within a short a period of time of the radiation as practical.
We have also discovered that polyethyleneglycolmonomethylether of various molecular weights and polyvinylpyrrolidone of various molecular weights also display radiation protection properties.
While polyethyleneglycolmonomethylether having molecular weights between 200 and 600 is an effective radiation protecting agent, we prefer polyethyleneglycolmonomethylether having a molecular weight of 400.
In experiments with polyethyleneglycolmonomethylether (molecular weight 400) conducted on mice in accordance with the protocol set out above, polyethyleneglycolmonomethyl- ether was given at a dosage of 6.4 grams per kilogram prior to the radiation of the mice. At that dosage level of polyethyleneglycolmonomethylether, only 3 out of 11 deaths occurred as compared to the usual experimental results with polyethylene glycol 400 in which between 0 and 2 out of 12 deaths occur in similar experiments.
With respect to polyvinylpyrrolidone having a molecular weight of 10,000, similar experiments conducted with a dose level of 11 grams per kilogram injected intraperitoneally prior to radiation. The results after 15 days yielded 3 out of 12 deaths again compared to between 0 and 2 out of 12 deaths for polyethylene glycol 400.
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There is disclosed a method of protecting animals including humans against ionizing radiation by injecting the animals with a polymer having the approximate formula H(OCH 2 CH 2 ) n OH, where n varies between 4 and 13. Particularly, it is found that polyethylene glycol (molecular weight between 200 and 600), polyethyleneglycolmonoethylether (molecular weight between 200 and 600), and polyvinylpyrrolidone (molecular weight up to 10,000) when injected into standard experimental animals, such as mice, protects them from the lethal effect of ionizing radiation.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a Continuation-in-Part of and claims the benefit of the filing date under 35 USC §120 of patent application Ser. No. 14/490,510, filed Sep. 18, 2014, the contents of which are incorporated herein by reference.
STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT
(Not Applicable)
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to an adapter for extension tubes for use with an aerosol can, and more specifically, to an adapter configured to connect two extension tubes to allow engagement between the two extension tubes.
2. Description of the Related Art
Aerosol cans are well-known in the art and are extensively used to deliver a wide variety of products, including lubricants, paints, personal care products, food products, insulation and caulks, herbicides and insecticides, as well as compressed air for cleaning. In recent years, annual production of aerosol cans in the United States alone has surpassed 10 billion cans.
Aerosol cans generally include a can body defining an internal reservoir or chamber which stores a pressurized gas/liquid mixture to be dispensed through a spray nozzle connected to the can's dispensing mechanism, i.e., valve stem, orifice, etc. Aerosol cans are typically operated by depressing the spray nozzle to actuate dispensing of the contents stored within the internal reservoir. The spray nozzle may be specifically designed to control the spray pattern and droplet size of the fluid emitted from the aerosol can.
Some aerosolized products require precise control onto remote, hard to reach areas. Current methods of dispensing such products may employ a spray nozzle having an orifice sized to allow for insertion of an extension tube so that the point of disbursement is on the order of a few inches to several inches away from the spray nozzle (depending on the size of the extension tube).
Typically, the extension tubes are seated within a recess formed about the fluid dispensing orifice in the spray nozzle to connect the extension tubes to the spray nozzle and to facilitate fluid communication there between. Thus, as the spray nozzle emits the product, the product travels through the extension tube and is emitted out an end portion thereof.
A common deficiency associated with aerosol cans and extension tubes relates to the ability of an aerosol can with extension tube attached to reach areas that are not within reach of a single extension tube, or areas that do not allow the aerosol can to be maneuvered freely. Current solutions for reaching difficult to reach areas with aerosolized sprays require jury-rigging straws together with adhesive tape, glue or other means of attaching straws together. The user may attempt to connect two or more straws together, resulting in an inefficient delivery of aerosolized spray; adhesive tape is prone to failure because the pressurized substances travelling through the extension tubes can dislodge the tape, allowing the aerosol to escape before reaching its intended destination.
Accordingly there is a need in the art for a device which can improve the connection between extension tubes to mitigate unwanted disconnection between said extension tubes.
The present invention addresses this particular need, as will be discussed in more detail below.
BRIEF SUMMARY OF THE INVENTION
According to an aspect of the present invention, there is provided a removable adapter configured for use with two extension tubes. The adapter is configured to fit onto the distal end of an extension tube and to receive the proximal end of an extension tube to provide a more rigid and fluidly secure connection between the extension tubes.
According to one embodiment, the adapter includes an adapter body having a first surface, a second surface, and a side surface extending between the first and second surfaces. The first and second surfaces each have one opening that is configured with tolerances as to allow the adapter to squeeze/grip an extension tube. An inner channel extends from the first surface to the second surface; the center of the channel contains a constriction section that narrows the inner channel to a diameter substantially equal to the inner diameter of that of the extension tube, stopping the tube from crossing the center of the adapter, and creating a continuous and substantially uniform flow channel.
The inner channel of the adapter body may be configured to allow the extension tube to be inserted therein by a first force and to allow the extension tube to be removed by a second force equal to or greater than the first force. Along these lines, the adapter body may include a plurality of projections extending into the inner channel to facilitate the friction-tight engagement between the adapter body and the extension tube. The adapter body may additionally include a plurality of annular protrusions extending into the inner channel to facilitate the friction-tight engagement between the adapter body and the extension tube. The adapter body may further include a helical protrusion extending into the inner channel to facilitate friction-tight engagement between the adapter body and the extension tube.
The adapter body may be formed from a resilient material, such as rubber, plastic or the like to allow the inner channel to expand to increase the size of the opening. The material used should ideally have a hardness rating of 75 on the Shore A hardness scale. This level of hardness would allow for an expandable friction fit that is hard enough to prevent backwash of the aerosol; backflow could potentially blow the adapter off of a straw. The opening may then decrease in size, i.e., contract, around the extension tube to tightly engage the tube. It is contemplated that a suitable material may include ENFLEX®. However, the instant invention may include alternative materials suitable to achieve the functionality and purposes herein.
The present invention is best understood by reference to the following detailed description when read in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The features and advantages of the various embodiments disclosed herein will be better understood with respect to the following description and drawings in which like numbers refer to like parts throughout and in which:
FIG. 1 is a side view of an adapter for securely and fluidly connecting two extension tubes;
FIG. 2 is a view of one end of an adapter for securely and fluidly connecting two extension tubes;
FIG. 3A is a cross-sectional view of the adapter;
FIG. 3B is a cross sectional view of another embodiment of the adapter including uni-directional teeth formed within an inner channel;
FIG. 3C is a cross sectional view of another embodiment of the adapter including a plurality of annular protrusions formed within an inner channel;
FIG. 3D is a cross sectional view of a further embodiment of the adapter including a helical projection formed within an inner channel;
FIG. 3E is a cross sectional view of still another embodiment of the adapter including a gripping insert disposed within the inner channel; and,
FIGS. 4A-4J are top views of various embodiments of extension tubes configured for use with the adapter.
DETAILED DESCRIPTION OF THE INVENTION
The detailed description that follows is intended to describe the presently preferred embodiment of the invention, and is not intended to represent the only form in which the present invention may be constructed or utilized. The description sets forth the functions and sequences of steps for constructing and operating the invention. It is to be understood, however, that the same or equivalent functions and sequences may be accomplished by a variety of different embodiments and that they are also intended to be encompassed within the scope of the invention.
Referring now to FIG. 1 , there is shown an adapter 10 for securely connecting an extension tube 14 a to a second extension tube 14 b . The adapter 10 is configured to be easily connected to the first extension tube 14 a , and to allow the extension tube 14 a to fluidly connect the second extension tube 14 b . The adapter 10 is configured to frictionally engage the first extension tube 14 a and second extension tube 14 b to maintain the engagement and fluid connection between the first extension tube 14 a and the second extension tube 14 b during usage. In this regard, the adapter 10 prevents leakage between the first extension tube 14 a and second extension tube 14 b . The adapter 10 is also configured to allow for disassembly of the first extension tube 14 a from the second extension tube 14 b during nonuse of the adapter 10 .
Referring now specifically to FIGS. 1 and 2 , the adapter 10 includes an adapter body 24 having a first surface 26 extending generally across the adapter body 24 , and two side surfaces 30 . Those skilled in the art will appreciate that the surfaces 26 , 30 are not limited to planar surfaces, and that the surfaces 26 , 30 may be angled, slanted, curved, arcuate, etc. without departing from the spirit and scope of the present invention.
Now, referring specifically to FIGS. 2 and 3 a , an inner wall 40 extending from the side wall 30 to the inner recess 23 define an inner channel 42 . The inner channel 42 is sized and configured to allow the extension tube 14 to be insertable therein to engage with the spray nozzle 12 , as shown in FIG. 3 a . When an end portion of the extension tube 14 a is inserted within the inner channel 42 , the end of the extension tube 14 may seat within the recess 23 formed within the adapter 10 to fluidly connect the extension tube 14 a to the extension tube 14 b . Therefore, when the extension tube 14 a is connected to the adapter 10 fluid may be communicated from the first extension tube 14 a to the second extension tube 14 b.
The inner channel 42 is sized and configured to mitigate inadvertent removal of the extension tube 14 therefrom. According to one embodiment, the inner channel 42 frictionally engages the extension tube 14 to maintain the extension tube 14 in fluid connection with the spray nozzle 12 . In this regard, in order to remove the extension tube 14 from the spray nozzle 12 and adapter 10 , a force must be applied to the extension tube 14 to overcome the frictional engagement between the extension tube 14 and the adapter 10 .
The size of the inner channel 42 may expand during insertion of the extension tubes 14 a , 14 b and subsequently contract around the extension tubes 14 a , 14 b to tightly engage the extension tubes 14 a , 14 b . Thus, the diameter or other peripheral dimension of the inner channel 42 may be smaller than the corresponding dimension of the extension tubes 14 a , 14 b (i.e., the outer diameter), such that insertion of the extension tubes 14 a , 14 b causes the inner channel 42 to expand and impart a frictional force on the extension tubes 14 a , 14 b.
FIGS. 3B-3E show several side sectional views of various embodiments of the adapter body wherein the inner channel is configured to maintain engagement between the adapter body and the extension tube. Referring now specifically to FIG. 3B , there is shown an embodiment of the adapter 10 b wherein the second inner wall 40 b defines a plurality of unidirectional teeth 44 extending at an angle into the inner channel 42 toward the first inner wall 36 . The uni-directional teeth 44 make it easier to insert the extension tubes 14 a , 14 b into the inner channel 42 and more difficult to remove the extension tubes 14 a , 14 b from the inner channel 42 . Thus, a first force may be used to insert the extension tubes 14 a , 14 b into the inner channel 42 and a second force may be required to remove the extension tubes 14 a , 14 b from the inner channel 42 , wherein the second force is larger than the first force.
Referring now specifically to FIG. 3C , there is shown another embodiment of the adapter 10 c wherein the inner channel 42 is configured to maintain the first extension tube 14 a in fluid engagement with the second extension tube 14 b . In the embodiment shown in FIG. 3C , the second inner surface 40 c forms a plurality of concentric annular rings 46 which extend into the inner channel 42 . The rings 46 are configured to allow the extension tubes 14 a , 14 b to be inserted therein and to exert a frictional force on the extension tubes 14 a , 14 b to make it difficult to remove the extension tubes 14 a , 14 b . In this regard, the rings 46 define an opening having an inner diameter that is sized to receive the extension tubes 14 a , 14 b in friction tight engagement.
Referring now specifically to FIG. 3D , there is shown a different embodiment of the adapter 10 c , wherein the second inner surface 40 d forms a helical protrusion 48 extending into the inner channel 42 . The helical protrusion 48 provides a frictional force similar to the annular rings 46 or teeth 44 discussed above to “grip” the extension tubes 14 a , 14 b when the extension tubes 14 a , 14 b is inserted within the inner channel 42 . The helical protrusion 48 defines an opening which is sized to allow the extension tubes 14 a , 14 b to be inserted therein and to allow the helical protrusion 48 to frictionally engage the extension tubes 14 a , 14 b.
FIG. 3E shows still another embodiment of an adapter 10 e having a gripping insert 41 positioned within the inner channel 42 to enhance the gripping capability of the adapter 10 e . The adapter 10 e is designed to allow the gripping insert 41 to assume a nested configuration within the adapter 10 e . Along these lines, the inner channel 42 of the adapter 10 e defines a first recess 43 disposed at one end of the inner channel 42 and a second recess 45 disposed at the opposite end of the inner channel 42 . The gripping insert 41 includes a first flange 47 which fits within the first recess 43 and a second flange 49 that fits within the second recess 45 and a tubular body 51 that extends between the first and second flanges 47 , 49 and defines a gripping member channel 53 . The adapter 10 e is preferably formed from a resilient material which is deformable to allow the gripping insert 41 to be placed therein, yet assumes the depicted configuration when the gripping insert 41 is completely inserted within the adapter 10 e . When the gripping insert 41 is placed within the adapter 10 e , the gripping member channel 53 is preferably coaxially aligned with the inner channel 42 of the adapter 10 e , such that when the extension tubes 14 a , 14 b is inserted into the adapter 10 d , the extension tubes 14 a , 14 b pass through the gripping member channel 53 . The gripping insert 51 additionally includes a plurality of gripping members 55 extending into the gripping member channel 53 to “grip” or engage with the extension tubes 14 a , 14 b when the extension tubes 14 a , 14 b are inserted therein. In the exemplary embodiment, the gripping members 55 include teeth which extend into the gripping member channel 53 , although it is understood that the gripping member(s) 55 may define other shapes or configurations, such as a helical protrusion, annular protrusions, a reduced diameter, a grippable material, threads or other gripping elements known by those skilled in the art.
Referring now to FIGS. 4A-4J , there is shown several different embodiments of extension tubes which may be used in connection with the adapter body. Each extension tube defines a first end portion and an opposing second end portion and a middle portion extending between the first and second end portions. The extension tube may define several different configurations to facilitate disbursement of the pressurized fluid to hard to reach areas, such as around corners and in tight spaces. For instance, the extension tube may have a generally 90° bend, as is shown in FIG. 4A , or may be substantially linear. Furthermore, the extension tube may have two generally 90° bends, as is shown in FIGS. 4C and 4E . FIG. 4B shows an extension tube having a bend which is each less than 90°. It is additionally contemplated that the length of the extension tube may be altered without departing from the spirit and scope of the present invention.
It is contemplated that the extension tubes may be selectively inserted within the inner channel of the adapter body to connect the extension tube to another extension tube. Several different extension tubes may be sold as a kit, and may be selectively interchanged as needed.
It is contemplated that the extension tubes may be selectively inserted within the inner channel of the adapter body to connect the extension tube to the adapter body and the spray nozzle. Several different extension tubes may be sold as a kit, and may be selectively interchanged as needed.
Furthermore, it is also contemplated that the adapter and the extension tube(s) may be packaged as a kit for sale. The kit may include one or more configurations of the adapter (such as those shown in FIGS. 3A-3E ) as well as one or more configurations of the extension tube (such as those shown in FIGS. 4A-4J ). It is also contemplated that the kit may include one or more dampeners, as described above.
The above description is given by way of example, and not limitation. Given the above disclosure, one skilled in the art could devise variations that are within the scope and spirit of the invention disclosed herein. Further, the various features of the embodiments disclosed herein can be used alone, or in varying combinations with each other and are not intended to be limited to the specific combinations described herein. Thus, the scope of the claims is not to be limited by the illustrated embodiments.
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Provided is an adapter configured for use with an aerosol can spray nozzle and an extension tube. The adapter is configured to fit onto an extension tube and to receive a second extension tube to provide a more rigid and fluidly secure connection between the extension tubes. The adapter includes a portion for a first extension tube and a second extension tube portion. Each extension tube portion includes an inner channel extending therethrough, and is sized and configured to allow the extension tube to be insertable therein to create friction-tight engagement between the extension tube and the adapter.
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FIELD OF THE INVENTION
The invention relates generally to the field of lathe bed scanners having a rotating imaging drum for maintaining the positional relationship of donor elements and writing elements during the writing process, and having a focusing beam directed onto the writing element for permitting calibration of the writing laser beam. More particularly, the invention relates to such imaging drums having a laser-absorbent coating for substantially eliminating an undesirable, reflected laser beam originating from the focusing beam and reflected from the imaging drum which reflected beam causes the writing laser beam to produce artifacts on the writing element during writing.
BACKGROUND OF THE INVENTION
Color-proofing is the procedure used by the printing industry for creating representative images that replicate the appearance of printed images without the cost and time required to actually set up a high-speed, high-volume printing press to print an example of the images intended. One such color proofer is a lathe bed scanner which utilizes a thermal printer having half-tone capabilities. This printer is arranged to form an image on a thermal print medium, or writing element, in which a donor transfers a dye to the writing element upon a sufficient amount of thermal energy. This printer includes a plurality of writing diode lasers which can be individually modulated to supply energy to selected areas of the medium in accordance with an information signal for writing onto the writing element. A focusing laser beam is focused at the preceding position to which the writing laser beam is to write next (i.e., next printing location) for permitting adjustment of the focal point of the writing laser beam prior to its writing at the next printing location.
The writing element is supported on a rotatable imaging drum, and rests concentrically around the imaging drum with the ends of writing element positioned in a spaced apart relationship so that a portion of the imaging drum is not covered by the writing element, hereinafter referred to as the exposed portion of the imaging drum. A print-head includes one end of a fiber optic array having a plurality of optical fibers that are coupled to the writing diode lasers for transmitting the signals from the laser to the print head. The print-head with the fiber optic array is movable relative to the longitudinal axis of the drum. The dye is transferred to the writing element as the radiation, transferred from the diode lasers to the donor element by the optical fibers, is converted to thermal energy in the donor element.
The cylindrical-shaped imaging drum includes a hollowed-out interior portion and further includes a plurality of holes extending through its housing for permitting a vacuum to be applied from the interior of the drum to the receiver and writing elements for maintaining their position as the drum is rotated.
During the writing process, the print head emits the laser beam as it moves along the drum. The beam then passes through the donor element for causing the dye to transfer to the writing element.
Although the presently known and utilized scanner is satisfactory, it is not without drawbacks. The focusing laser beam is sometimes directed from the writing element, to the imaging drum and back to the writing element due to the fact that writing element does not cover the exposed portion of the imaging drum. This reflected beam causes the focusing of the writing laser beam to have transient oscillations which can create undesirable artifacts in the writing element.
Consequently, a need exists for improvements in the construction of the lathe bed scanner so as to overcome the above-described shortcomings.
SUMMARY OF THE INVENTION
The present invention is directed to overcoming one or more of the problems set forth above. Briefly summarized, according to one aspect of the present invention, the invention resides in an imaging processor for receiving a medium for processing. The processor comprises a print head for providing and for directing a writing laser beam. A laser source also disposed in the image processor for creating a focusing laser beam for ultimately permitting adjustment of the writing laser beam. An imaging receptacle receives the medium and is exposed to both the writing and focusing laser beams, and the focusing laser beam is periodically directed from the medium, to the imaging receptacle and back to the medium. A laser-absorbent coating is coated onto the imaging drum for absorbing the focusing laser beam that is received by the imaging receptacle for substantially eliminating transient oscillations in the writing laser beam.
It is an object of the present invention to coat the drum with a laser-absorbent coating so as to overcome the above-described drawbacks.
It is an advantage of the present invention to provide cost-efficient means for implementing the present invention.
It is a feature of the present invention to provide a laser-absorbent coating coated onto the imaging drum for absorbing the focusing laser beam that is received by the imaging drum for substantially eliminating transient oscillations in the writing laser beam.
The above and other objects of the present invention will become more apparent when taken in conjunction with the following description and drawings wherein identical reference numerals have been used, where possible, to designate identical elements that are common to the figures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view in vertical cross section of a lathe bed scanner of the present invention;
FIG. 2 is a perspective view of an imaging drum, laser writer and lead screw of the present invention; and
FIG. 3 is perspective view of the imaging drum of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1, there is illustrated a lathe bed scanner 10 of the present invention having a housing 15 for forming a protective cover. A movable, hinged door 20 is attached to a front portion of the housing 15 for permitting access to two media trays, a lower tray 30a and upper tray 30b, that are positioned in an interior portion of the housing 15 for supporting receiver material 40, typically paper, thereon. It is obvious to those skilled in the art that only one media tray 30 will dispense receiver material 40 out of its paper tray 30 for creating an image thereon; the alternate media tray 30 either holds an alternative type of paper or functions as backup. In this regard, the lower media tray 30a includes a cam 50a for lifting the paper 40 upwardly toward a rotatable, lower media roller 60a and, ultimately, toward a second rotatable, upper media roller 60b which, when both are rotated, permits the receiver material 40 to be pulled upwardly towards a media guide 70. The upper media tray 30b also includes a cam 50b for lifting the receiver material 40 toward the upper media roller 60b which directs it towards the media guide 70.
As illustrated by the phantom position, the movable media guide 70 directs the receiver material 40 under a pair of rollers 80 which engages the receiver material 40 for assisting the upper media roller 60b in directing it onto a staging tray 90. The media guide 70 is attached and hinged to the interior of the housing 15 at one end, and is uninhibited at its other end for permitting multiple positioning of the media guide 70. The media guide 70 then rotates its uninhibited end downwardly, as illustrated by the solid line, and the direction of rotation of the upper media roller 60b is reversed for forcing the receiver material 40 resting on the staging tray 90 back under the rollers 80, upwardly through an entrance passageway 100 and around a rotatable imaging drum 110.
Four rolls of donor material 120 (only one is shown) are connected to a carousel 130 in a lower portion of the housing 15, and each roll includes a donor material 120 of a different color, typically black, yellow, magenta and cyan. These donor materials are ultimately cut into sheets and passed to the imaging drum for forming a medium from which dyes imbedded therein are passed to the receiver material resting thereon, which process is described in detail herein below. In this regard, a drive mechanism 140 is attached to each roll 120, and includes three rollers 150 through which the donor material 120 of interest is rolled upwardly into a knife assembly 160. After the donor material 120 reaches a predetermined position, the rollers 150 cease driving the donor material 120 and two blades 170 positioned at the bottom portion of the knife assemble cut the donor material 120 into a sheet. The media rollers 60a and 60b and media guide 70 then pass the donor material 120 onto the drum 10 and in registration with the receiver material 40 using the same process as described above for passing the receiver material 40 onto the drum 110. The donor material 120 rests atop the receiver material 40 with a narrow gap between the two created by microbeads imbedded into the receiver material 40.
A laser assembly 180 includes twenty writing lasers 185 in its interior, and these lasers are connected via fiber optic cables 187 to a coupling head 190 and ultimately to a write head 200. The write head 200 creates thermal energy from the signal received from the lasers 185 causing the donor material 120 to pass its dye across the gap to the receiver material 40. The writing lasers 185 preferably emit a wavelength between 800 and 880 nm. The write head 200 is attached to a lead screw 210 via a nut (not shown in FIG. 1) for permitting it to move axially along the longitudinal axis of the drum 110 for writing data onto the receiver material 40.
A focusing laser assembly 205 is mounted to the print head 200 and includes a laser in its interior for providing a laser beam which will be used for assisting in focusing the writing lasers 185. A fiber optic cable 206 connects the focusing laser assembly 205 to the print head 200 out of which the beam is emitted. The focusing laser assembly 205 is selected to produce a second beam of light having a wavelength different from the wavelength of the writing beam and preferably outside the range of 800 nm-880 nm. Preferably, the focusing light source produces a beam of light having a predominant wavelength of 960 nm. It has been found that a focusing beam having a wavelength of 960 nm is substantially unabsorbed by all of the various donor dye materials 120. As a result, substantially all of the focusing beam of this wavelength will penetrate the donor material 120, regardless of the color dye employed, to be reflected from the reflective surface which is part of the receiver element 40. Inasmuch as this surface has been found to be much closer to the dye layer, where it is desirable to focus the writing beam, rather than the top surface of the donor layer 120, it is possible for both the writing beam and the focusing beam to be aimed at more nearly the same surface than is possible if the focusing beam is reflected from some other surface of the receiver element 40. As a result, the writing beam may have less depth of focus and consequently may have a greater numerical aperture which permits the transmission of greater writing power to the receiver element 40 than would be the case were the focusing beam and the writing beam to be focused at more widely separated surfaces.
For writing, the drum 110 rotates at a constant velocity, and the write head 200 begins at one end of the receiver material 40 and traverses the entire length of the receiver material 40 for completing the transfer process for the particular donor material resting on the receiver material 40. To maintain focus of the writing beam the focus laser assembly 205 emits beam of light which is reflected off from the reflective layer in the receiver element 40 back to the print head 200 and is monitored therein by the focus control circuit (not shown) to detect any change in the energy level of the focus beam. A change in energy level indicates a change in position of the reflective layer in the receiver material 40 which indicates a corresponding change in the position of the dye layer on the donor material 120. When a change is detected the focus control circuitry sends a signal to the focusing lens assembly (not shown) which adjusts the position of the focusing lens (not shown) thus maintaining focus of the writing beam. After the donor material 120 has completed its dye transfer, the donor material 120 is then transferred from the drum 110 and out of the housing 15 via a skive or ejection chute 210. The donor material eventually comes to rest on a donor material tray 212 for permitting removal by a user. The above-described process is then repeated for the other three rolls of donor material.
After all four sheets of donor material have transferred their dyes, the receiver material 40 is transported via a transport mechanism 220 through an entrance door 230 and into a dye binding assembly 240 where it rests against an exit door 250. The entrance door 230 is opened for permitting the receiver material 40 to enter into the dye binding assembly 240, and shuts once it comes to rest in the dye binding assembly 240. The dye binding assembly 240 heats the receiver material 40 for further binding the transferred dye on the receiver material 40 and for sealing the microbeads thereon. After heating, the exit door 250 is opened and the receiver material 40 with the image thereon passes out of the housing 15 and comes to rest against a stop 260.
Referring to FIG. 2, there is illustrated a perspective view of the imaging drum 110 and write head 200 of the lathe bed scanner 10. The imaging drum 110 is mounted for rotation about an axis (x) in a frame support 270. The write head 200 is movable with respect to the imaging drum 110, and is arranged to direct a beam of actinic light to the donor material 120 (shown in FIG. 1). The write head 200 contains therein a plurality of writing elements (not shown) which can be individually modulated by electronic signals from the laser diodes 185, which signals are representative of the shape and color of the original image, so that each dye is heated to cause volatilization only in those areas in which its presence is required on the receiver material 40 to reconstruct the color of the original object.
The write head 200 is mounted on a movable translator member 280 which, in turn, is supported for low friction slidable movement on bars 290 and 300. The bars 290 and 300 are sufficiently rigid so that they do not sag or distort between the mounting points at their ends and are arranged as parallel as possible with the axis (x) of the imaging drum 110. The upper bar 300 is arranged to locate the axis of the writing head 200 precisely on the axis (x) of the drum 110 with the axis of the writing head perpendicular to the drum axis (x). The upper bar 300 locates the translator member 280 in the vertical and the horizontal directions with respect to the axis of the drum 110. The lower bar 290 locates the translator member 280 only with respect to rotation of the translator about the bar 290 so that there is no over-constraint of the translator member 280 which might cause it to bind, chatter, or otherwise impart undesirable vibration to the writing head 200 during the generation of an image.
Referring to FIGS. 3, there is illustrated the imaging drum 110 having a cylindrical-shaped housing 305 partially and respectively enclosed on both ends by two plates 310. The housing 305 further includes a hollowed-out interior (annular shaped in vertical cross section) for permitting a vacuum to be applied from its interior portion. A plurality of holes 320 extend entirely through the housing 305 for permitting the vacuum to maintain the donor 120 and writing elements 40 thereon during rotation of the drum 110.
It is constructive to note that the receiver element 40 does not cover all of the vacuum imaging drum 110 so that a gap is formed between the lead edge 322 and trail edge 321 of the receiver element 40.
A black chrome coating 330 is applied on the housing 305 by using well known techniques such as electroplating, thermal spraying or physical vapor deposition. These black chrome coatings have a total reflectance of between 0-5% from 900 nm to 1000 nm which includes the focusing beam's wave length of 960 nm. When the focusing beam is exposed to the drum 110 due to the gap formed between the lead edge 322 and trail edge 321 of the receiver element 40, the coating 330 absorbs all or substantially all of the focusing beam that would otherwise reflect off the drum surface; if not absorbed, this reflected beam would cause the focusing of the writing laser beam to have transient oscillations which can create undesirable artifacts in the writing element.
The invention has been described with reference to a preferred embodiment. However, it will be appreciated that variations and modifications can be effected by a person of ordinary skill in the art without departing from the scope of the invention.
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An imaging processor for receiving a medium for processing, the processor comprises a print head for providing and for directing a writing laser beam. A laser source also disposed in the image processor for creating a focusing laser beam for ultimately permitting adjustment of the writing laser beam. An imaging receptacle receives the medium and is exposed to both the writing and focusing laser beams, and the writing laser beam is periodically directed from the medium, to the imaging receptacle and back to the medium. A laser-absorbent coating is coated onto the imaging drum for absorbing the focusing laser beam that is received by the imaging receptacle for substantially eliminating transient oscillations in the writing laser beam.
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BACKGROUND OF THE INVENTION
It is frequently desirable to reinforce rubber articles, for example, tires, conveyor belts, power transmission belts, timing belts, hoses, and the like products, by incorporating therein steel reinforcing elements. Pneumatic vehicle tires are often reinforced with cords prepared from brass coated steel filaments. Such tire cords are frequently composed of high carbon steel or high carbon steel coated with a thin layer of brass. Such a tire cord can be a monofilament, but normally is prepared from several filaments which are stranded together. In most instances, depending upon the type of tire being reinforced, the strands of filaments are further cabled to form the tire cord.
In order for rubber articles which are reinforced with steel wire elements to function effectively it is imperative that good adhesion between the rubber and the steel cord be maintained. Thus, generally steel wire reinforcement elements are coated with brass in order to facilitate rubber-metal adhesion.
It is generally agreed by those skilled in the art that adhesion of rubber to brass-plated steel wire is dependent upon a bond between the copper in the brass and sulfur in the rubber. When such brass coated steel reinforcing elements are present in the rubber composition during vulcanization, it is believed that bonds between the rubber and steel reinforcement gradually form due to a chemical reaction between the brass alloy and the rubber at the interface forming a bonding layer. The brass coating also serves an important function as a lubricant during final wet drawing of steel filaments.
Over the years various techniques have been employed for coating steel filaments with brass. For instance, alloy plating has been used to plate steel filaments with brass coatings. Such alloy plating procedures involve the electrodeposition of copper and zinc simultaneously to form a homogeneous brass alloy insitu from a plating solution containing chemically complexing species. This codeposition occurs because the complexing electrolyte provides a cathodic film in which the individual copper and zinc deposition potentials are virtually identical. Alloy plating is typically used to apply alpha-brass coatings containing about 70% copper and 30% zinc. Such coatings provide excellent draw performance and good initial adhesion. However, research in recent years has shown that long-term adhesion during the surface life of a tire depends on more than bulk coating chemistry. More specifically, the nature of the service oxide layer and the chemistry variation (gradient) across the total brass coating have proven to be important.
Sequential plating is a practical technique for applying brass alloys to steel filaments. In such a procedure a copper layer and a zinc layer are sequentially plated onto the steel filament by electrodeposition followed by a thermal diffusion step. For sequential brass plating, copper pyrophosphate and acid zinc sulfate plating solutions are usually employed. Iron-brass coatings can also be applied by sequential plating. Such a procedure for applying iron-brass to steel filaments and the benefits associated therewith are described in U.S. Pat. No. 4,446,198.
In the standard procedure for plating brass on to steel filaments, the steel filament is first optionally rinsed in hot water at a temperature of greater than about 60° C. The steel filament is then acid pickled in sulfuric acid or hydrochloric acid to remove oxide from the surface. After a water rinse, the filament is coated with copper in a copper pyrophosphate plating solution. The filament is given a negative charge so as to act as a cathode in the plating cell. Copper plates are utilized as the anode. Oxidation of the soluble copper anodes replenishes the electrolyte with copper ions. The copper ions are, of course, reduced at the surface of the steel filament cathode to the metallic state.
The copper plated steel filament is then rinsed and plated with zinc in a zinc plating cell. The copper plated filament is given a negative charge to act as the cathode in the zinc plating cell. A solution of acid zinc sulfate is in the zinc plating cell which is equipped with a soluble zinc anode. During the zinc plating operation, the soluble zinc anode is oxidized to replenish the electrolyte with zinc ions. The zinc ions are reduced at the surface of the copper coated steel filament which acts as a cathode to provide a zinc layer thereon. The acid zinc sulfate bath can also utilize insoluble anodes when accompanied with a suitable zinc ion replenishment system. The filament is then rinsed and heated to a temperature of greater than about 450° C. and preferably within the range of about 500° C. to 550° C. to permit the copper and zinc layers to diffuse thereby forming a brass coating. This is generally accomplished by induction or resistance heating. The filament is then cooled and washed in a dilute phosphoric acid bath at room temperature to remove oxide. The brass coated filament is then rinsed and air dried at a temperature of about 75° C. to about 150° C.
SUMMARY OF THE INVENTION
Standard copper plating cells utilized soluble copper anodes which replenish the electrolyte with copper ions. The amount of copper in such soluble anodes is diminished throughout the plating procedure. Ultimately, it becomes necessary to replace the soluble copper anode. This is an avoidable consequence of such procedures because the anode is the source of copper for plating onto the steel filament. Nevertheless, changing the soluble copper anode results in a significant amount of "down-time" in commercial operations. A significant quantity of copper from the anodes being replaced is relegated to scrap which is wasteful.
In practicing the process of the subject invention, an insoluble anode is utilized in the plating cell. This eliminates the need for replacing soluble copper anodes. This totally eliminates the down-time associated with changing soluble copper anodes in the plating cell. It also eliminates the scrap copper from old anodes which had been replaced. Practicing the subject invention also improves plating uniformity in a multi-wire line because there is a constant anode surface area.
The subject invention more specifically discloses a process for applying a copper layer to a steel filament which comprises:
(a) applying a negative charge to the steel filament and continuously passing the steel filament through a plating cell wherein the negatively charged steel filament is in contact with an aqueous copper pyrophosphate solution and wherein the aqueous copper pyrophosphate solution is in contact with a positively charged inert anode:
(b) providing the negatively charged steel filament with sufficient residence time in the pyrophosphate solution to plate the steel filament with the copper layer of the desired thickness:
(c) replenishing the concentration of copper in the copper pyrophosphate solution in the plating cell by circulating the copper pyrophosphate solution in the plating cell with copper ion replenished copper pyrophosphate solution from a replenishment cell, wherein the replenished copper pyrophosphate solution in the replenishment cell is in contact with at least one copper anode having a positive charge, wherein the replenished copper pyrophosphate solution is in contact with a conductive membrane such as a copolymer of tetrafluoroethylene and perfluoro-3,5-dioxa-4-methyl-7-octenesulfonic acid which separates the replenished copper pyrophosphate solution from a potassium hydroxide solution, wherein the potassium hydroxide solution is in contact with a negatively charged cathode:
(d) transferring a sufficient amount of the potassium hydroxide solution which is in contact with the negatively charged cathode which produces hydroxide ions to the copper pyrophosphate solution to replenish the hydroxide ions in the copper pyrophosphate solution which are consumed at the inert anode in the copper pyrophosphate solution in the plating cell: and
(e) adding a sufficient amount of water to the potassium hydroxide solution to replace the potassium hydroxide transferred to the copper pyrophosphate solution and water lost through reduction and evaporation.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a prospective, fragmentary, and diagramic view of the apparatus of this invention including the plating cell and the replenishment cell.
DETAILED DESCRIPTION OF THE INVENTION
By practicing the process of this invention, copper layers can be applied to steel filaments. The term "filaments" as used herein is meant to include cord, cable, strand, and wire as well as filaments. Thus, steel filaments, steel cords, steel cables, steel strands and steel wires can be coated by utilizing the technique of this invention. The process of this invention is, of course, also applicable to coating other types of platable articles with copper from a copper pyrophosphate solution.
The term "steel" as used in the present specification and claims refers to what is commonly known as carbon steel, which is also called high-carbon steel, ordinary steel, straight carbon steel, and plain carbon steel. An example of such a steel is American Iron and Steel Institute Grade 1070-high carbon steel (AISI 1070). Such steel owes its properties chiefly to the presence of carbon without substantial amounts of other alloying elements. U.S. Pat. No. 4,960,473 discloses some preferred steel alloys and an excellent process for manufacturing steel filaments which can be utilized in this invention. Brass is an alloy of copper and zinc which can contain other metals in varying lesser amounts. Alpha-brass which contains from about 60% to about 90% copper and from about 10% to about 40% zinc is generally used in coating filaments for reinforcing rubber articles. It is normally preferred for the brass to contain from about 62% to about 75% by weight copper and from about 25% to about 38% by weight zinc. Iron-brass alloys which contain 0.1 to 10 percent iron can also be employed. U.S. Pat. No. 4,446,198 discloses such iron-brass alloys and the benefits associated with using them to reinforce rubber articles, such as tires.
In practicing this invention, the steel filament is coated with a copper layer in a plating cell 10. A negative charge is applied to steel filament 11 as it is continuously passed through the plating cell. This negative charge can be applied to the steel filament by a negatively charged pulley 12 which is contact with steel filament 11. The plating cell walls 13 are typically comprised of a water impermeable plastic material, such as high density polyethylene or polypropylene. The steel filament 11 is in contact with an aqueous copper pyrophosphate solution 14 as it passes through the plating cell. The aqueous copper pyrophosphate solution 14 in the plating cell is also in contact with a positively charged inert anode 15. The inert anode 15 can be comprised of any material which will not be oxidized as a result of the plating procedure. Iridium oxide coated titanium electrodes, platinized titanium electrodes, and titanium suboxide (TiOx) electrodes (which are sold under the tradename Ebonex®) have proven to be a good choice for use as the inert anode 15. The inert anode can be comprised of any of the platinum metals, such as ruthenium, osmium, rhodium, iridium, palladium and platinum. The inert anode can also be comprised of an oxide of one or more of the platinum metals. The inert anode can also be a platinum metal oxide coated titanium electrode. The negatively charged pulley 12 and the positively charged inert anode 15 are charged from a direct current (DC) power source 16.
The copper pyrophosphate solution 14 in the plating cell will typically have a copper (Cu 2+ ) ion concentration of 22 to 38 grams/liter. The copper pyrophosphate solution will also typically have a pyrophosphate (P 2 O 7 ) ion concentration of 159 to 250 g/liter and will have a pyrophosphate ion to copper ion ratio which is within the range of about 6.5 to about 8. The pH of the pyrophosphate solution will be maintained within the range of 8.0 to about 9.3. It is preferred for the copper pyrophosphate solution to have a pH which is within the range of about 8.3 to about 8.7. The temperature of the copper pyrophosphate solution 14 in the plating cell will be maintained within the range of about 40° C. to 60° C. It is normally preferred for the temperature of copper pyrophosphate solution 14 in the plating cell to be maintained within the range of about 45° C. to 55° C. with temperatures within the range of about 48° C. to about 52° C. being most preferred. It is normally desirable to adjust the power source 16 so as to maintain a cathode current density which is within the range of about 4 to 20 A/dm 2 (amps per square decimeter). Lower current densities can be utilized but the rate of electrodeposition will be too slow for utilization in most commercial operations. Higher current densities can also be used with the risk of burnt deposits resulting. It is normally preferred to maintain a current density which is within the range of about 8 to about 15 A/dm 2 .
The electrodeposition procedure carried out in plating cell 10 results in Cu 2+ ions being reduced on the surface of the steel filament 11. This reaction can be depicted as:
Cu.sup.2+ +2e=Cu
simultaneously, hydroxide ions are oxidized at the surface of the inert anode according to the reaction:
4 OH.sup.- →O.sub.2 +2H.sub.2 O+4e
as can be seen, oxygen gas and water are generated at the inert anode.
The steel filament will be provided with a sufficient amount of residence time in the pyrophosphate solution 14 of the plating cell to allow for the electrodeposition of a copper layer of the desired thickness. The thickness of the copper layer depends on the starting wire diameter and the final drawn filament diameter, but will typically be within the range of about 0.5 microns to about 5 microns. It will be more common for a copper layer having a thickness which is within the range of about 1 micron to about 2 microns to be applied. The thickness of the copper layer can be controlled by adjusting the residence time or current density of the steel filament in the copper pyrophosphate solution 14 in the plating cell. The rate of electrodeposition of copper onto the steel filament will also be dependent upon the concentration of copper ions in the copper pyrophosphate solution and the cathode current density. Both of these variables can also be adjusted to attain a desired result.
As the electrodeposition proceeds, the level of copper ion in the copper pyrophosphate solution 14 in the plating cell diminishes. This is, of course, because the copper ions are being reduced onto the negatively charged steel filament as a copper layer. It is accordingly necessary to replenish the level of copper ions in the copper pyrophosphate solution 14 in the plating cell. This is accomplished by exchanging, circulating or mixing the copper pyrophosphate solution 14 in the plating cell which has a reduced level of copper ions with copper ion replenished pyrophosphate solution 21 which is generated in replenishment cell 20. This can be accomplished by simply pumping replenished pyrophosphate solution 21 from the replenishment cell through tube or piping equipped with a pumping mechanism 22. The replenished pyrophosphate solution flows from the replenishment cell to the plating cell in the direction of arrow 23. A corresponding amount of copper pyrophosphate solution 14 is conveyed from the plating cell to the replenishment cell through pumping mechanism 34. The copper pyrophosphate solution flows from the plating cell to the replenishment cell in the direction of arrow 35. In some cases it will be possible to orient the plating cell and the replenishment cell in a manner where it is not necessary to utilize mechanical motion to pump the replenished copper pyrophosphate solution from the replenishment cell or the copper pyrophosphate solution from the plating cell to the replenishment cell because gravity will supply all of the force necessary to convey the solution. It should also be noted that the plating cell and replenishment cell do not need to be in separate tanks.
The replenished copper pyrophosphate solution 21 in the replenishment cell 20 is in contact with at least one copper anode having a positive charge. It is generally convenient to utilize copper nuggets 24 as the anode for the replenishment cell. However, the copper anode can be of any geometric shape such as chips, rods, plates, wires, or scrap pieces of varying shapes. The copper nuggets 24 can be held in a titanium basket 25 or some other device which will hold the copper nuggets and which is inert. The copper nuggets are oxidized at the anode according to the reaction:
Cu→Cu.sup.2+ +2e
This reaction increases the amount of copper ions present in the replenished copper pyrophosphate solution. The copper nuggets are consumed during the operation of the replenishment cell. It is accordingly necessary to add copper nuggets to the titanium basket 25 from time to time during the operation of the replenishment cell to maintain an adequate level of copper nuggets for proper operation. This is an easy task because it is only necessary to drop the copper nuggets 24 into the titanium basket 25.
The replenished copper pyrophosphate solution 21 in the replenishment cell 20 is in contact with a conductive membrane 26 of a copolymer of tetrafluoroethane and perfluoro-3,5-dioxa-4-methyl-7-octene sulfonic acid. The conductive membrane is comprised of fluoropolymer chains having perfluorinated cation exchange sites chemically bound thereto. Such conductive membranes are sold by E. I. DuPont de Nemours & Company as Nafion® perfluorinated membranes. Nafion® 300 and 400 series perfluorinated membranes have excellent characteristics for the conductive membrane. Nafion® 324, 417, 423, and 430 perfluorinated membranes are all effective with Nafion® 324 and 430 perfluorinated membranes being preferred. The Nafion® 324, 417, and 423 perfluorinated membranes should be soaked in hot water for about 30 minutes before being used as the conductive membrane in the replenishment cell. The Nafion® 430 perfluorinated membrane should be soaked in a 2% solution of sodium hydroxide at room temperature for about 8 hours prior to being used.
The conductive membrane allows for the flow of electrical current. However, the conductive membrane 26 does not allow for copper ions or pyrophosphate ions to flow through it. Thus, the conductive membrane 26 keeps copper ions from migrating through it and being deposited onto the cathode 27. The conductive membrane 26 separates the replenished copper pyrophosphate solution 21 from a potassium hydroxide solution 28 which is in contact with the negatively charged cathode 27. The negative charge is provided to the cathode and the positive charge is provided to the copper anode by a second direct current power source 36. The cathode 27 can be comprised of virtually any conductive material. For instance, steel can be used as the negatively charged cathode 27. Hydrogen gas is generated at the cathode 27 according to the reaction:
2H.sup.+ +2e→H.sub.2
Even in commercial operations the amount of hydrogen generated is relatively small. Because only small amounts of hydrogen evolve, it can be allowed to simply escape into the atmosphere. However, it should be appreciated that hydrogen gas can be explosive and the use of open flame in the vicinity of the replenishment cell should be avoided.
As the replenishment cell operates, the concentration of hydroxide ions in the potassium hydroxide solution increases. Typically the potassium hydroxide concentration is not critical, but a concentration too low would increase the replenishment cell resistance and too high could cause membrane clogging and possible membrane degradation. The optimum range found is 50±5 g/l of potassium hydroxide. Further potassium cation was chosen to maintain commonality with the cation in the pyrophosphate bath. It should also be noted that other solutions can be utilized in the replenishment cell. On the other hand, hydroxide ions are consumed in the plating cell at the inert anode. More specifically, hydroxide ions are converted to oxygen gas and water at the inert anode 15 in the plating cell. For this reason, potassium hydroxide solution is transported around the conductive membrane 26 in the replenishment cell to the replenished pyrophosphate solution 21 in an amount sufficient to replenish the hydroxide ion consumed at the inert anode 15 in the plating cell 10. This can be accomplished by simply pumping the potassium hydroxide solution 28 into the replenished copper phosphate solution 21 at the appropriate rate by potassium hydroxide solution pumping mechanism 29 in the direction of arrow 30. In an alternative embodiment of this invention, the potassium hydroxide solution could be pumped or transported by some other means directly into the copper pyrophosphate solution 14 in plating cell 10. It should be noted that potassium ions can diffuse through the conductive membrane 26 to reenter the potassium hydroxide solution 28.
Water is consumed as a consequence of operating the plating cell 10 and the replenishment cell 20. For this reason water is added to the potassium hydroxide solution in the replenishment cell. A sufficient amount of water is added to replace the potassium hydroxide solution which is transferred to the plating cell, the water which is reduced to hydroxide ions and hydrogen gas, and the water which evaporates from the plating cell and the replenishment cell. Water is added to maintain a relatively constant level of potassium hydroxide solution 28 in the replenishment cell. This can be accomplished by directly adding water from an external water supply 31 with the flow of water being controlled by valve 32 which is operated by a float 33.
The present invention will be described in more detail in the following examples. These examples are merely for the purpose of illustration and are not to be regarded as limiting the scope of the invention or the manner in which it may be practiced. Unless specifically indicated otherwise, all parts and percentages are given by weight.
EXAMPLE
In this experiment, a steel wire was plated with copper using the process of this invention. A Nafion® 430 perfluorinated membrane was utilized as the conductive membrane in the replenishment cell. Copper nuggets were utilized as the copper anode in the replenishment cell.
The replenishment cell utilized a stainless steel cathode, an anode current density of less than 2A/dm 2 , a cathode current density of 1.4 A/dm 2 (assuming distribution over one face), a cathode voltage of -1.3V versus a standard hydrogen electrode, a membrane current density of 12A/dm 2 , a cell current of 24A, and a cell voltage of 4.2V.
The copper pyrophosphate solution in the plating cell contained about 25 g/l of copper ions, contained about 185 g/l of pyrophosphate ions, had a ratio of copper ions to pyrophosphate ions of about 7.4, was maintained at a temperature of about 50° C., was maintained at a pH of about 8.5, and was agitated. The potassium hydroxide solution in the replenishment cell contained about 50 g/l of potassium hydroxide and was maintained at a temperature of about 50° C.
The plating cell utilized an iridium oxide coated titanium mesh anode (15 g/m 2 coating weight), an anode current density of 1A/dm 2 (assuming distribution over one face), an anode voltage of 1.4V versus a standard hydrogen electrode, a cathode current density of 12A/dm 2 , a cell current of 26A, and a cell voltage of approximately 3.5V. Potassium hydroxide solution was transferred to the copper ion replenished copper pyrophosphate solution in the replenishment cell as needed to maintain the pH in the copper pyrophosphate solution in the plating cell and the potassium hydroxide concentration in the potassium hydroxide solution in the replenishment cell.
Steel wire was plated with copper to a thickness of 1±0.5 microns using this procedure. This unit was operated for over 140 hours with excellent results being realized.
It should be noted that a cell voltage of at least one volt should be applied at all times during which an insoluble iridium oxide coated titanium anode is immersed in copper pyrophosphate solution. If such a voltage is not applied, there is a risk of dissolution of the titanium substrate. For the same reason such anodes should be rinsed after being removed from the copper pyrophosphate solution.
While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the invention.
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Copper plating cells which utilize soluble copper anodes which replenish the electrolyte with copper ions are normally used for applying copper layers to steel filaments. The amount of copper in such soluble anodes is diminished throughout the plating procedure and ultimately such soluble copper anodes need to be replaced. It has been discovered that insoluble anodes can be utilized in such plating cells. Such a process for applying a copper layer to a steel filament comprises: (a) applying a negative charge to the steel filament which is in contact with an aqueous copper pyrophosphate solution, wherein the aqueous copper pyrophosphate solution is in contact with a positively charged inert anode; (b) allowing copper ions from the copper pyrophosphate solution to be reduced on the steel filament to form the copper layer; and (c) replenishing the concentration of copper ions in the copper pyrophosphate solution by applying a positive charge to a copper anode which is in contact with the copper pyrophosphate solution and applying a negative charge to a cathode which is in contact with a potassium hydroxide solution, wherein the copper pyrophosphate solution and the potassium hydroxide solution are separated by a conductive membrane which allows electrical current and potassium ions to flow through it without allowing copper ions or pyrophosphate ions to diffuse through it.
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BACKGROUND OF THE INVENTION
Hollow plastic extrusions in the form of tubing or those extrusions which are rectangular in cross section are used for a variety of purposes, but especially for fence rails. Common plastic material used for this purpose is vinyl. When fence rails made from such materials are put under a load at right angles to the fence rail between the ends of the fence rail, the rail can deflect a great deal.
BRIEF SUMMARY OF THE INVENTION
The purpose of this invention is to prevent such deflection of hollow plastic extruded members, especially those used as fence rails. The hollow extruded member is provided with end caps which have at least two pairs of oppositely disposed holes therein and at least two wires each extending through each of two sets of holes in each end cap and extending the interior length of the fence rail and are then joined together at the outside of one of the end caps and placed under tension when so joined.
It is therefore an object of this invention to provide a hollow plastic extrusion with suitable interior wire reinforcing so as to prevent unnecessary deflection in use. This, together with other objects of the invention, will become apparent from the following detailed description of the invention and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. A perspective view of an extruded plastic rectangular member with the two wires suitably connected together under tension.
FIG. 2. A side elevation of the extruded plastic rectangular member.
FIG. 3 . An end view of the end of the extruded plastic rectangular member in FIG. 1 where the wires are joined together.
FIG. 4. A section through FIG. 2 on the plane 4 — 4 .
FIG. 5 . An end view of the opposite end of the extruded plastic rectangular member.
FIG. 6. A side view in section of the extruded plastic rectangular member shown in FIG. 1 .
FIG. 7 . An extruded plastic member similar to that shown in FIG. 1 only circular in cross section.
FIG. 8. A section through FIG. 7 on the plane 8 — 8 .
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the drawings and in particular to FIG. 1, 10 is a typical fence rail provided with end caps 11 and 12 . Each of the end caps has holes near the comers thereof through which the wires are shown extending. The holes in end cap 12 are shown at 12 a , 12 b , 12 c and 12 d . The holes in end cap 11 are shown at 11 a , 11 b , 11 c and 11 d . (See FIG. 5 ).
One wire 13 extends through the two holes 11 a and 11 b in the end cap 11 (see FIG. 5 ), and through the corresponding two holes 12 a and 12 b in the end cap 12 and the two ends of wire 13 are joined together by connector 14 with the wire 13 under tension. Galvanized steel ⅛″ high tension wire has been found to be very satisfactory. Similarly, wire 15 is led through the holes 12 c and 12 d in end cap 12 and the corresponding holes 11 c and 11 d in end cap 11 and the two ends of wire 15 are joined together by connector 16 with the wire 15 under tension. Also shown in FIG. 2 are the wire 15 and the connector 16 .
Referring now to FIG. 5, it will be seen that the wire 15 extends through hole 11 c in the end cap 11 down along the back of the end cap 11 and back through the hole 11 d in the end cap 11 .
FIG. 3 shows the end cap 12 and the two ends of wire 13 and the two ends of wire 15 being joined together by connectors 14 and 16 respectively after having been placed under tension.
In FIG. 4, the wires 13 and 15 are shown traversing the interior length of the fence rail 10 adjacent the four interior comers of the fence rail 10 .
FIG. 5 is a view of the cap 11 and it will be seen that wire 13 enters through holes 11 a and 11 b in end cap 11 and the wire 15 enters the end cap 11 through holes 11 c and 11 d and then both wires return through the interior length of the fence rail 10 to the corresponding holes in end cap 12 .
FIG. 6 is a section of the fence rail 10 showing the wire 13 entering holes 11 a and 11 b in end cap 11 , traversing the length of the interior of the fence rail 10 and exiting end cap 12 through holes 12 a and 12 b and being held together under tension by connector 14 . Wire 15 is similarly positioned on the opposite side of fence rail 10 .
FIG. 7 shows a variation of the fence rail 10 , namely fence rail 10 a , which is circular in cross section and also provided with end caps provided with corresponding holes and wires 13 a and 15 a and connectors 14 a and 16 a functioning in the same fashion as is the case with the fence rail 10 shown in FIG. 1 . FIG. 8 is a sectional view of rail 10 a on the plane of 8 — 8 as shown in FIG. 7 with the two wires 13 a and 15 a shown running the interior length of the rail 10 a.
By constructing a hollow plastic member which is greater in length than in width with these internal wire supports under tension significant deflection of the member when a load is placed between the ends thereof is avoided and the member will return to within acceptable limits of its original position.
EXAMPLE
A standard 8 foot length of vinyl fence rail was supported at each end and a 500 lb. weight was placed on the fence rail at its center. The fence rail was distorted several feet and did not return to its original shape. An 8′ long length of vinyl fence rail made in accordance with the present invention was supported at each end and a 500 pound weight was placed at the center thereof. The fence rail was only distorted 5″ and when the weight was removed it recovered to within ½″ of its original position.
While this invention has been shown and described with respect to a detailed embodiment thereof, it will be understood by those skilled in the art that various changes in form and detail thereof may be made without departing from the scope of the claims of the invention.
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A hollow plastic member provided with end caps having holes therein through which wires can pass and be placed under tension so as to provide internal support for the member to reduce deflection of the member when a load is placed thereon and to return the member back within acceptable limits to its original position.
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FIELD OF THE INVENTION
This invention relates to extracting summaries of television (or audio) programming both during live broadcasting and post broadcasting. It is in one instance concerned with recipient controlled recovery of summaries of programming supplied via cable and xDSL access links. In another aspect it concerns back-and-forth intermingling of summaries and live/recorded programming under control of a recipient customer. It particularly concerns apparatus within a broadcast network and on customer premises to enable such extraction and presentation of summaries.
BACKGROUND OF THE INVENTION
Recording apparatus presently generally available permits a recipient of television and radio programming to record real-time programming (i.e., on VHS tapes) and replay it at a later time. The most ubiquitous example is the VCR, which allows recordation of live TV programming under recipient control for replay at a time of the recipient's choice. To record, the customer must select the time of the interval to be recorded.
There exist more sophisticated systems (Digital Video Recorders) which automatically record programming (via a digital cache/memory) and allow the user to selectively view portions of the recorded programming at a later time. An example of such a recording system is the ReplayTV digital video recorder and the TiVo Personal TV digital video recorder, which supply up to 30 hours of recording time. They provide features that surpass recording by monitoring listener preferences and by suggesting programming appropriate to these preferences. Recording may occur during live programming and if live viewing is interrupted the viewer may recover a delayed presentation of the programming at the end of the interruption interval.
These record/playback systems are however limited by failing to fully utilize network system capabilities. Summaries, for example, may be poorly defined or delimited resulting in loss of program material available to the user/viewer. Options available to the user are limited to manipulation of programming as received rather than using network and program provider resources to provide a broad spectrum of control.
SUMMARY OF THE INVENTION
Recipients who receive network programming are enabled, according to principles of the invention, to receive television/audio programming from a distribution network and view selected summaries of such programming as part of a network-based service. Identification and preparation of the summaries is at least in part a network-controlled process with recipient utilization of the features provided being under control of the recipient viewer. Features include recovery of audio, snapshots (stills) and full-motion video summaries extracted from program content. A summary in some instances may be a specially created overview, of a program created by a program source that is provided by a program source or provider. In some instances, segments may be created independent of the programming as a leader or overview in advance of the program or as an inducement to watch pre-stored programs.
Summaries are generally program segments extracted from complete programs and may include various combinations of audio, full-motion video, still pictures (i.e., selected frames), and other presentation modes either singly or in any desired arrangement. Accessing techniques may be by user control or system controlled selection based on user profiles. Direct user selections, may be made by a user for covering interruptions to user viewing. Network control allows greater selectively, to determine if program content is desired or to meet other user generated requests, which a summary may satisfy.
In an illustrative embodiment, the sources of programming generate and transmit summaries that include control information to permit a recipient to selectively choose and replay the summaries. In some embodiments a video summary server (VSS) is included in the network to perform summary/program storage and provide access functions. In another embodiment a set top box (STB) is included on recipient premises to receive program/summaries and perform some of the viewing control functions and store summaries.
The process of transmitting and generating summaries is based in part upon properties specified in the MPEG-2 (Moving Picture Experts Group) standards. MPEG-2 is a standard concerning signal encoding and real time transmission of video and audio program streams. The standards primary goal is bandwidth compression as well as combining and multiplexing. Packet headers under the standard include many features such as time stamps, typing of payloads and combining/multiplexing all of, which are useful in enabling the invention of applicants. MPEG-2 includes many features including information-carrying capability of a video stream. This permits the transmission of information by the program source that enables the features of the invention to be realized.
In one aspect the method of the invention processes programming to facilitate selection and delivery of summaries of the programming to recipients by providing the programming to the recipient via a program channel. Index markers are applied to the program to divide the programming into segments. Summary segments are generated containing information from corresponding programming segments and related to one another by corresponding index markers. Metadata files are created and associated with a summary channel and operate to delimit beginning and ending of segments in both programming and summary channels. Metadata includes the indexing information for facilitating links between programming segments and summary segments. A user/recipient selects a summary by activating a link between a programming segment and a summary segment by utilizing the metadata file included with the summary channel. The summary is transmitted to the recipient, via the summary channel.
In a particular embodiment the summary channels include metadata to implement/facilitate a linking back and forth between summary and program channels under command of a user. The MPEG-2 standards enable user data, in the form of metadata, to be included in a video sequence. This data delimits the beginning and end of segments in both summary and program channels. The standard further allows an elementary data stream to be included within a program stream. The elementary data stream is used to provide indexing used to implement video linking and interrupted viewing features.
In one aspect the relevant control is responsive to metadata supplied to define and identify summaries corresponding to particular programs. It defines start and end marks of both summaries and programs and the nature of the linking connections between summary and program. Such metadata is easily to integrate with the programming under the MPEG-2 standard.
The reviewing and selection functions include but are not limited to;
Supplying and viewing summaries of programs as a means of selection of programs to view in their entirety.
Providing recipient control to select related summaries and full program segments through summary-segment linkage marks.
Providing one-way and two-way video hyperlinks between programs and summaries.
Providing the viewing recipient with missing portions of interrupted program viewing.
Generating summaries during live programming for intermittent viewing.
Providing summaries permitting selective recipient recording of portions of a program.
DESCRIPTION OF THE DRAWING
FIGS. 1 through 6 are diagrammatic illustrations of modes of selections and presentations of summaries of video programming;
FIGS. 7 and 8 are schematics of a screen control menu presented to a viewer;
FIGS. 9 and 10 are schematics of video summary system components involving cable networks;
FIG. 11 is a schematic functionally illustrating a set top box (STB) with enhancements for enabling summary storage and retrieval;
FIG. 12 is a schematic of video summary system components added to a network having a xDSL access network;
FIG. 13 is a process diagram describing summarization of live television programming;
FIG. 14 is a flow chart describing a monitoring/control of video storage processes; and
FIGS. 15, 16 and 17 is a flow chart disclosing a control process permitting the exercise of summary selection and viewing by a recipient of programming.
DETAILED DESCRIPTION
Viewing of summaries of audio and video programming is available, according to the invention in many styles and formats. Summaries may be generated dynamically by a recipient viewer's requests or recalled from a central repository of summaries at user request. Various systems of generating, using and recalling summaries are illustrated in the program schematics of FIGS. 1 through 6. In the circumstances of FIG. 1 a program sequence is shown by the bar 101 showing the evolving of the program. As the program progresses the program's progress is marked by the markers P 1 , P 2 , P 3 , . . . These markers are related to corresponding markers shown in the Summary (audio) bar 102 and the Summary (video) bar 103 . As shown the program from 0 to P 1 may be shown as summary from 0 to S 1 . The subsequent portion from P 1 to P 2 may be bypassed and a subsequent portion of the program from P 2 to P 3 shown as summary from S 1 to S 2 . The summaries shown are full motion and all inclusive of materials within the marker interval covered and/or summarized.
In the illustrative summaries of FIG. 2, markers P 1 , P 2 , P 3 , . . . segment the program. An audio summary 201 is created resulting in audio summaries 0 to S 3 , and s# to S 5 . The video portion is reduced to snapshots or still pictures 203 with each still picture related to a particular program segment. The snapshot from position P 2 in the program is sued during the summary interval from S 1 to S 2 . The use of still images and full motion images may be interspersed as desired. This option is illustrated in FIG. 3 where the video summaries 303 , 304 , 305 , 306 and 307 comprise still images and full motion images of the basic programming 301 . Full motion images are interspersed with still images. An audio summary component 300 is also shown.
FIG. 4 illustrates an example of one-way video hyperlinks. A user beings by viewing a summary and selecting the link function during the summary segment 405 . Control passes to the beginning of the corresponding program segment 415 . When that program segment completes, control continues with the remaining program segments. Other summary segments are shown by way of illustration in FIG. 4 as segments 404 , 406 , 407 and 408 . Further, other program segments are also illustrated as program segments 414 , 416 , 417 and 418 .
One-way video hyperlinks can also pass control from a program segment to the beginning of the corresponding summary segment. When that summary segment completes, control continues with the remaining summary segments.
FIG. 5 illustrates the operation of two-way hyperlinks. A user begins by viewing the summary and selects the link function during the summary segment 505 . Control passes to the beginning of the corresponding program segment 515 . When that program segment completes, control automatically returns to the beginning of the next summary segment 506 . The user again selects the link function during summary segment 507 . Control passes to the beginning of the corresponding program segment 517 . When the program segment completes, control automatically returns to the beginning of the next summary segment 508 .
FIG. 5 further shows by way of illustration additional summary segment 504 and program segments 514 , 516 and 518 .
FIG. 6 also illustrates the operation of two-way hyperlinks. A user begins by viewing the program and selects the link function during the program segment 615 . Control passes to the beginning of the corresponding summary segment 605 . When that summary segment completes, control automatically returns to the beginning of the next program segment 616 . The user again selects the link function during program segment 617 . Control passes to the beginning of the corresponding summary segment 607 . When that summary segment completes, control automatically returns the beginning of the next program segment 618 .
FIG. 6 further illustrates segments such as summary segment 604 , 606 and 608 and program segment 614 .
The relationship between program and summary segments may be established and controlled through use of a metadata file or files. In the illustrative embodiment, metadata is used to identify program and summary segments. It also establishes the flags useful for two-way and one-way connecting links for use in changing from a program to a summary or vice versa. A one way link allows a user to switch from a summary segment to a corresponding program segment or switch from a program segment to a corresponding summary segment. A two-way link allows the user to view a summary segment and switch to a corresponding program segment with an automatic return to the next summary segment when the corresponding program segment completes. Two-way links also permit switching from a program segment to a corresponding summary segment with an automatic return to the next program segment.
The metadata file may also provide key words for each summary segment. Start and end positions for each summary segment may be established and correlated with start and stop positions for each program segment. Summary metadata may be expressed in XML (eXtensible Markup Language) or a suitable equivalent. XML is well known and need not be discussed in detail. An illustrative XML summary file may assume the following form, to select specific subject matter from, a program.
<summary>
<summary_id>726746425</summary_id>
<program_id>399868815</program_id>
<links>two-way</links>
<summary_segment>
<index>0<index>
<keywords>Federal Reserve, Interest Rates</keywords>
<start>0</start>
<end>1000</end>
<summary_segment>
.............
<program_segment>
<index>0<index>
<start>0</start>
<end>10000<end>
<program_segment>
..................
</summary>
etc.
The foregoing illustrative metadata file indicates that there is a summary of parts of a program relating to the federal reserve and interest rates. The metadata file is generated by the content provider. It permits the system to select the desired summary information if available. Transmission of the signal in accord with the MPEG-2 standard allows the interaction with the programming file by means of this metadata file.
The sections of this metadata file are now described. First the <summary> tag indicates the start of the file. Second the <summary id> tag provides a globally unique id for this summary. Third, the <program id> tag provides a globally unique id for the corresponding program. Fourth, the <links> tag indicates that the links between the program and summary segments operate as two-way links. Fifth, the <summary segment> tag indicates the start of a summary segment definition. One metadata file can define multiple summary segments. Sixth, the <program segment> tag indicates the start of a program segment definition. One metadata file can define multiple program segments.
Each <summary segment> contains four tags. The <index> tag assigns a unique index to that segment. The segments in a summary are assigned indexes that begin at zero and increase sequentially. The <keywords> tag associates several keywords with this summary segment. Software can use these keywords to identify segments that are most likely to be of interest to a particular viewer. The <start> tag indicates the position in the summary that marks the beginning of this segment. Position can be specified as a frame number. The <end> tag indicates the position in the summary that marks the end of this segment.
Each <program segment> contains three tags. The <index> tag assigns a unique index to that segment. The segments in a program are assigned indexes that begin at zero and increase sequentially. The <start> tag indicates the position in the program that marks the beginning of this segment. Position can be specified as a frame number. The <end> tag indicates the position in the program that marks the end of this segment.
Each summary is sequence of summary segments. The segments are contiguous and non-overlapping. Similarly, each program is a sequence of program segments. The segments are contiguous and non-overlapping.
A viewer exercises control, in one embodiment, by interaction with a set top box (STB) or with a video summary server (VSS) by means of an interactive menu such as illustrated in the screen display 702 of FIG. 7 . Here the list of summaries 704 in one example of the invention may be supplied over a channel used exclusively (i.e., an S channel) for this purpose. In the illustrative menu the view may select summaries related to the listed programs by entering the number associated with that summary in the summary id box 706 by a remote or other means. The menu 804 shown in the screen display 802 of FIG. 8 provides for summaries to recover material lost due to interrupted viewing of a program. Interrupted viewing occurs when a viewer is interrupted in his viewing (i.e. called away from the television receiver). If a viewer wishes to subsequently view a summary of missed programming content or view the current program, a selection may be entered by entering the appropriate control number in the option id box by a remote or other means. This process may be facilitated by use of a dedicated I channel.
The implementation is accomplished, in part, with an application of enhancements to various elements in the program delivery system. In the illustrative embodiments such enhancements are made to the set top box (STB) in a cable reception system or to a video summary server (VSS) in xDSL program delivery systems. These enhancements provide interface capabilities and information availability for program selection and the process of delivering summaries.
An illustrative system architecture for constructing and viewing program summaries is shown in the FIG. 9 . This system is adapted for Cable networks and as shown includes a television-broadcasting source 901 connected to a network POP (Point-of-Presence) 903 . POP herein is the physical equipment of a provider network at which the network terminates and which is connected to a recipient subscriber. A cable access link 905 connects POP 903 to an enhanced STB 907 located at customer premises 909 . STB 907 provides the television signals to the television receiver 911 . A server 913 maintains billing records.
A series of signals, for summary viewing, is diagrammed in the schematic of FIG. 10, showing the primary signal interfaces between the television-broadcasting source and the customer. The television-broadcasting source 901 provides program channels 1001 via the POP 903 to the STB 907 at the customer premises. The television channels are transmitted by various program providers to the POPs 903 and transmitted from the POPs to the STBs 907 at the customer's premises 909 .
Each program and summary is assigned a globally unique identifier. This information is transmitted to the VSSs and STBs by the program summary channel.
Each broadcaster maintains a schedule of programming, which is accessible to the STBs via IP unicasting 1002 through the POPs 903 . The customer may access programming-related descriptive material via the same IP channel. Separate digital summary channels 1003 are used to transmit program summaries from the broadcasters to the STB. The STB can receive and store these summaries from the broadcaster.
Charging data for the service provided is maintained by a billing system server 913 connected via channel link 1004 through the POP 903 to the STB 907 . Billing in the illustrative example may be by subscription, by transaction or other suitable arrangement.
An illustrative enhanced set top box (STB) 907 , for cable reception, is schematically shown in block form in the FIG. 11 . Program and summary channels from the broadcaster are applied to a bank of Audio/Video RF CATV Demodulators 1101 . The demodulators each recover a specific program or summary channel as directed by control of the software controller 1103 . Software controller 1103 includes stored programming that controls and coordinates operations of the various STB functions.
The recovered programming/summaries (streams) are applied to an MPEG-2 Decoder. MPEG-2 is a standard concerned with video and audio coding and processing other multimedia signals (e.g., packet streams). Decoder 1105 is designed in accord with this standard. MPEG processing, decoding of digital signals and design of a MPEG-2 system decoder is discussed in “Digital Video: An Introduction to MPEG-2 ” by B. G. Haskell et al 1997. This discussion of this book is incorporated herein by reference. This MPEG output stream is applied to a storage element 1107 for storing program and summary segments. Program storage may be by memory circuits, disk recordings or any suitable means compatible with the content stored.
Various stored material is selected under control of the software controller 1103 and transmitted to the digital to analog converter 1109 to place the program or summary in a suitable form for the home television receiver. The analog signal is coupled to the home television receiver, via the Audio/Video RF CATV Modulator 1111 , which converts the signals to NTSC (National Television Standards Committee) standards for application to the home television receiver.
The user/recipient exercises control of program summary selection by input to a user interface 1113 which commands are coupled to the software controller 1103 . Commands of the software controller 1103 are coupled to control the Modulator 1111 , the storage element 1107 and the Demodulator 1101 . A user Profile and Viewing history 1115 input is also connected the Software controller 1103 . Its input allows automatic selection of programming material to suit viewer desires and preferences. It may base these selections of stored demographic and prior selected subject matter. The software controller uses this information to self decide which summaries to store in order to effectively utilize the storage capacity of the storage medium 1107 . The user may transmit commands via the user interface 1113 to view or delete stored programs and summaries in the storage medium 1107 . Control by the user may be exercised by using dialog boxes that are displayed on the screen of the receiver. Examples of dialog displays are shown in the FIGS. 7 and 8. Various types of dialog boxes are discussed below in the description of the controlling flow process of the software controller. The user may communicate with the interface by a remote controller.
In systems utilizing xDSL, for video delivery (FIG. 12 ), the STB is replaced by a Video Summary Server (VSS) 1203 included in the DSL network. The programming is supplied to the user from the VSS 1203 , via a POP 1205 to a modem 1207 , via a xDSL Access Link 1211 , to the customer premises 1209 . The VSS 1203 has capabilities and processes similar to that of the STB and can autonomously decide which summaries to receive and store based on a user profile and past usage history stored in the VSS. A billing system 1213 is connected to the VSS via the POP 1205 . The VSS may be integrated within the POP if desired or be embodied as a separate unit within the network.
An important aspect of the process is monitoring the capability of the network storage elements to store the needed summaries. The process of FIG. 14 is intended to provide this capability. Starting at terminal block 1401 the controller and the storage medium it controls wait for input from the summary channels. The controller inquires, per decision block 1405 as to whether this summary should be stored based on user selection, user preferences, etc. If the summary is not to be stored the flow process returns to block 1403 and waits for further input from the summary channel.
If the summary is to be stored, the process inquires, as per decision block 1407 , if there is sufficient storage to store the summary. With sufficient storage the summary is stored and/or appended to an existing summary, as per block 1409 , with process flow returning to block 1403 .
If sufficient storage is not available, the summary is prioritized as per block 1411 as to whether it is desirable to the user and as per block 1413 is prioritized in relation to all other programs and summaries being processed. If the immediate summary is highly rated, preexisting summaries are deleted, as per block 1415 , to provide memory space for the new summary. The flow process proceeds to block 1409 instructing storage of the new summary.
One particular procedure of permitting interaction of a user with the system is presented as an illustrative embodiment, although many other processes may be used to enact the invention. A general understanding of this illustrative embodiment of user control may be obtained from the process disclosed in a flow chart disclosed in FIGS. 15, 16 and 17 . The process begins at the start terminal 2001 followed by user entry of a command as per block 2003 . The software controller categorizes the command, as per block 2005 , as a decision to change a channel or not change a channel. If the command is to change a channel to another program channel the flow of the process returns to the start of the process since this is a routine change of channel. If the command does not change the channel the process proceeds to a decision as specified by block 2007 , which inquires if the subscriber subscribes to the service, requested. If the user is not a subscriber to the service the flow process presents the user with a dialog box # 1 such as indicted by instruction box 2027 which presents a menu permitting the subscriber to enter a subscription to the service. The flow returns to the start of the flow process.
If the user is a subscriber, the process proceeds to a decision shown in the decision block 2009 to determine if the user wishes to change to a summary channel S. If the user wishes to change to a summary channel, the user is presented with a screen menu, as per box 2008 , similar to the box illustrated in the FIG. 7 presenting a listing of choices of readily available summaries for viewing. Subsequently the flow process returns to the start terminal.
If the user does not wish to be presented with a menu of existing summaries the process proceeds to decision block 2011 which inquires if the user wishes to change to an interrupt channel I to create a summary while the user is absent from the television receiver. If such a summary is desired the process proceeds to set P equal to a program channel number as per block 2033 and indicator II, as per box 2034 , is set to equal the index number associated with a current segment of the program being viewed. The interrupt-viewing screen (FIG. 8) is displayed as per block 2037 and the process returns to the start.
If no change to channel I is desired the next decision, as per block 2013 , determines if a particular channel Id is requested on the summary channel S. If a particular summary id is requested the summary is presented, as per instruction block 2038 and the process returns to the start. If no particular summary is requested, a decision, as per block 2015 , determines if there is a command to return to the channel P on the channel carrying the interrupted summary. If such a command has been issued the process returns the viewer to the program channel P, as per box 2016 . The process returns to start to await a new command.
If no return to the channel P is requested the viewer has a choice to view a summary of the missed content due to interruption as per the decision of block 2017 . If the missed content is to be viewed the index is set to I1 as per block 2045 and I2 is set to the current program segment, as per block 2047 . An inquiry is performed, as per decision block 2049 , as to whether the value I=I2 and if it is the process proceeds to instructions of block 2053 causing the program channel P to be transmitted to the viewer's television receiver and the flow returns to start. If I does not equal I2 the instructions of block 2051 set I=I+1 and the instructions of block 2052 transmit the I-th summary segment to the viewer's television receiver.
If the decision of block 2017 is not to view a summary of missed content a subsequent decision in block 2019 inquires if a link command has been issued (i.e., a link button, for example, has been actuated by the viewer). If not, flow returns to the start. If the link command has been actuated, an inquiry by block 2021 inquires if the stored summary is being transmitted. If stored summary is not being transmitted, flow proceeds to a subsequent inquiry of block 2023 to determine if a stored program is being transmitted. Again if a stored program is not being transmitted, an inquiry by block 2025 inquires if a live program is being transmitted and if not flow returns to start.
If the decision of block 2021 determines that a stored summary is being transmitted, a subsequent instruction of block 2057 sets I equal to the index of the current summary segment. An inquiry is initiated to determine if the I-th program segment is stored in the STB for cable reception or in the VSS for xDSL reception. If the segment is stored, as determined by block 2059 the flow process proceeds to instruction block 2119 . If the segment is not stored, an inquiry of block 2061 inquires if the program has been previously broadcast. If the program has been previously broadcast. a dialog box # 2 is transmitted to the viewer, as per box 2062 , which indicates to the viewer that the program has been previously broadcast but has not been recorded. If the program was not previously broadcast, an inquiry of block 2063 inquires if it is presently being broadcast. If it is being broadcast, the instructions of block 2071 switch the viewer to that program channel and the flow returns to start. If it is not being broadcast, a query of block 2073 asks if the program is schedule for future broadcast. If it is so scheduled, a dialog box # 3 is presented to the viewer, as per block 2075 , so indicating that the program is scheduled for future broadcast and makes an interactive offer to record it. If the program is not schedule for future broadcast, another dialog box # 4 is presented to the viewer, as per box 2076 , indicating that the program is not recorded and is not schedule for future broadcast. In both previous instances, the flow returns to start. The program schedule 1002 in FIG. 10 is used to obtain the information about the schedule of a particular program. This information includes the unique ids that identify the program and its summaries.
If the decision of block 2023 determines that the stored program is being transmitted, I is set equal to the index of the current program segment, as per box 2072 , and subsequent decision block 2077 presents the inquiry as to whether the I-th segment summary is stored in the STB or VSS. If it is not stored dialog box # 5 is transmitted to the viewer, as per box 2078 , to indicate that a summary is not stored for this program.
If the I-th summary segment is stored in the STB or VSS the I-th summary segment is sent to the viewer as instructed by block 2101 . Decision block 2103 inquires if this summary uses two way links. If two-way links are not used the remaining summary segments are transmitted as per block 2111 . As per subsequent instructions of block 2113 the entire summary is transmitted. The process subsequently returns to the start.
If the two-way links are being used the (I+1)-th program segment is transmitted to the user as per block 2105 followed by transmission of the remaining program segment as per block 2107 . Following this the entire program is transmitted, as per block 2019 , and the process returns to start.
A determination by decision block 2025 that a live program is being transmitted directs the flow process to block 2083 having the instruction to set I equal to the index of the current program segment. An inquiry of block 2085 inquires if the I-th summary is stored in the STB/VSS. If it is not stored the system transmits the dialog message # 6 , as per block 2086 , which indicates to the viewer that a summary is not stored for this program. If a summary is stored the I-th summary segment is transmitted to the viewer as indicated in the block 2089 . An inquiry of block 2091 determines if the summary uses two-way links. If two-way links are in use the user is switched to the program channel as per block 2095 and the process returns to start.
If two-way links are not in use the remaining summary segments are transmitted to the user as per block 2093 . The entire summary is transmitted as per block 2097 and the process returns to start.
If the decision block 2059 determines that an I-th program segment is stored in the STB/VSS the flow proceeds to block 2119 , as indicated above, whose instructions transmit the I-th program segment. The inquiry of subsequent decision block 2121 queries if the summary uses two-way links. If not the remaining program segments are transmitted to the viewer as per block 2125 and the entire program is transmitted as per block 2127 . If two-way links are in use the I-th summary segment is transmitted as per block 2123 and the remaining summary segments are also transmitted as per block 2129 resulting in transmission of the entire summary as per block 2131 . The process returns to start.
In the foregoing process the user is presented various dialog boxes on the television screen with which the user may interact or be provided with process-relevant information. These dialog boxes are listed to assist in understanding the above user process. Dialog Box # 1 informs the user that he/she has no subscription to the service. It provides interactive capability allowing the user to subscribe if desired. Dialog Box # 2 informs the user that the program desired has been previously broadcast but has not been recorded. Programs scheduled for future broadcast are announced by Dialog Box # 3 as well as providing an interactive capability to give the user the capability to record it. Dialog Box # 4 informs the user that a program previously broadcast and not recorded is not scheduled for future broadcast. The Dialog Box # 5 announces absence of summaries stored for the present program. This list of Dialog Boxes is intended to be exemplary and is not intended to limit the scope of the process features of the invention.
The proceeding process illustrates one illustrative method of user interaction with the system. Many departures from this scheme may be devised without departing from the spirit and scope of the invention.
A unique feature of the process is the allowance of summary generation during actual live event programming. The summarization process is schematically illustrated in FIG. 13 and involves the active monitoring of the program by an editor 1306 . The editor 1306 may be a live person or an apparatus programmed to perform the editing process. As shown, the Live program 1300 is recorded by camera and microphone 1301 and cast into a form (i.e., digital television signal) suitable for transmission by modulation and broadcast equipment 1302 . The program is transmitted by a program channel, via a POP, to an STB or VSS 1303 for application to a television receiver 1304 .
The broadcast program (i.e., digital television signal) is also coupled to a computer (i.e., PC, workstation, etc.) 1305 . The signal is buffered and displayed to allow an editor (i.e., live person), with appropriate editing software, to choose segments (i.e., program fragments) appropriate for creating a summary. These summaries, as well as associated metadata, are transmitted to the STB or VSS. the metadata in accord with MPEG-2 standards is transmitted as part of an elementary data stream associated with the program.
This method allows the generation of summaries almost simultaneously with the program itself, allowing a viewer to receive summaries only a few minutes subsequent to programming segments.
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A network-based device allows customers to receive television programming and to view summaries of the programming. A method of providing the summaries comprises: dividing a received program into program segments each identified by index marks, summarizing each program segment into summary segments identified by similar index marks, storing the summary segments and accessing the summary segments to supply the summary segments in lieu of program segments upon demand.
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Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 6 , 912 , 398 . The reissue application Ser. Nos. are 11 / 819 , 755 and 12 / 834 , 132 .
CROSS - REFERENCE TO RELATED APPLICATIONS
This application is a reissue application based on U.S. Pat. No. 6 , 912 , 398 , issued on Jun. 28 , 2005 (which issued from U.S. patent application Ser. No. 09 / 546 , 851 , filed on Apr. 10 , 2000 ).
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to information delivery systems. In particular, it relates to the delivery of information to an individual based on the individual's movements, and/or the individual's interests, and/or the time the individual is at a particular location, and/or the unique aspects of a particular location.
2. Background Art
While advertising has a substantial positive effect on any business, the cost of advertising can be a significant portion of the operating budget of any business. As a result, it is very important for any business operation to maximize the effectiveness of its advertisements. A primary disadvantage associated with conventional advertising and/or the delivery of noncommercial information is that it is unfocused such that it reaches a broad general audience rather than the smaller defined audience desired by the advertiser or other information provider.
Traditional advertising on the Internet uses hyperlinks in the form of banner ads. Companies using this type advertising have found that it has limited effectiveness because many individuals who visit Web sites ignore these banners, while the advertising companies pay for them regardless of whether the visitor clicks on their ads or not. It would be desirable to have a method of focusing advertisements on the most receptive individuals.
Another method of delivering advertisements for coupons to an individual using the Internet is through email. This is accomplished usually after someone visits a site, fills out an online form, and submits the form to be processed usually through a form handler. While this method may be effective for existing customers who may have loyalty to the advertising company, it can be ineffective for new customers because they may not take the time to enter any information. In addition, a substantial number of Internet users routinely discard advertising email, as a form of junk mail, without ever reading it. As a result, even if an advertiser identifies the potential customer and sends email, a substantial amount of that email will never be read. It would be desirable to have a system in which the likelihood of the potential customer reading the advertising communication would be relatively high.
Another problem associated with conventional Internet marketing is that due to the proliferation of Web sites, new companies engaging in e-commerce often find that they can only obtain Web addresses that are not the company's name, are not appropriate for the company, or do not seem to be the related to the goods or services sold by the company. The disadvantage of a poor Web address is that it increases the likelihood that the company will lose sales at their site since a potential visitor wouldn't think of such an unlikely address for the company, and often won't use a search engine to find the correct address. Ultimately, anything that makes it less convenient or harder for someone to link to a Web site will cost that company business. This inability to have a Web address that adequately reflects the company and/or its name is due to several factors and is one of many problems solved by the invention. Some of these factors are: 1) a limited number of characters are permitted for the Web address; 2) the high level of interest in the Internet has caused many entities to acquire rights in Web addresses which would better suit other companies and which are not used by the company that acquired them; 3) a company can acquire otherwise identical Web addresses which end in .com or .net and use both of those addresses to hyperlink to a single Web site, which further limits the number of available names; 4) there are many similar and confusing Web site addresses, for example Web addresses which are identical except for special characters such as dashes or underscores, which makes it harder to remember the Web site address; and 5) simply not remembering the Web site address. It would be desirable to have a method of using the Internet which is independent of the individual knowing the actual Internet Web site address.
Unfocused information is that information which is broadcasted to the general public in an indiscriminate manner. For example, a conventional television, radio, billboard, or print advertisement would be received by many individuals, most of whom would have no interest in the particular product or service in the advertisement. As a result, a significant portion of the cost associated with presenting a particular conventional advertisement is wasted since the advertisement is presented to the wrong individuals. It would be desirable to have an effective method of focusing advertising and distributing information to a well-defined set of individuals who represent the target group desired by the advertiser or information distributor.
Attempts to improve the effectiveness of advertising have involved the acquisition of information directly from individuals which describes their interests and resources. This can be done in one of several ways. For example, when an individual fills out a warranty card after a purchase, the warranty card typically contains numerous questions about the purchaser. These questions may inquire as to an individual's age, income, and interests. This demographic information may then be used to identify the most likely purchaser of a particular product or service. Once the group containing the most likely purchasers is identified, direct advertising can be presented to those purchasers. Hopefully this process will result in a greater percentage of purchasers for a given advertisement, which will in turn result in more effective use of the funds allocated to a business's advertising budget due to the resulting increase in sales.
The disadvantage associated with this type of marketing is that many types of economic activity are relevant to a particular individual depending on where that individual may be at a given time. For example, if an individual is an avid golfer, the computer may have this fact in its database. This would allow golf related advertisements from local merchants to be directed to the individual at the individual's residence etc. However, if the individual was traveling, local merchants in the area the individual was visiting would not be aware of the individual's presence and would have no reason to attempt to market their products to the visiting individual. It would be desirable for local merchants to have a method of contacting individuals visiting their locale at the time the individual was visiting such that the individual could take advantage of products and services provided by the local merchants.
With the advent of the Internet and e-commerce, the advantages and disadvantages of advertising have both increased. On the one hand, a small private or commercial entity is now able to reach a global market which was heretofore unavailable to any but the largest economic concerns. On the other band, there is no value for a small entity to have access to a global market when that entity may in fact only be able to provide particular goods or services in a limited geographic area. For example, a restaurant's clientele must be in the local area to take advantage of the restaurant's services. Further, if an individual is visiting the area of the local merchant, the individual may not have any knowledge of the local merchants' products and services. Due to this, not only do many local merchants not have an extensive out of area business due to e-commerce, they are also unable to take advantage of visitors to the area. It would be desirable to have a method of using the Internet to detect the presence of a visitor to a local area, and once the individual is detected, to allow the local merchants to advertise directly to the individual when the individual is in that area.
While addressing the basic desirability of advertising, the prior art has failed to provide a focused method of distributing information, either commercial advertising or other information, which is focused on a select target group of individuals, and can provide information to those individuals which is dependent on the time and/or the location that the individuals are in a given area
SUMMARY OF THE INVENTION
The present invention solves the foregoing problems by providing a system that provides focused advertising and/or other information to individuals based on the time and/or their location. The individuals carry a wireless identification device which can be identified as an individual passes through a specific geographic location. The identification information is then sent to a computer, such as a server on the Internet, which uses the identification information to access the individual's records. In addition, the location information is also uploaded to the server. A computer uses the ID and location information to select, from a list of information providers, those information providers which provide information content identifiable or correlated to a location and/or time, and is of interest to the individual.
The information can be forwarded to the individual by a variety of information channels. One channel uses conventional Internet email to deliver advertisements and other information to the individual's Internet mailbox. The email can be delivered to a conventional PC, a portable computer, a PDA (a personal digital assistant, well-known in the art), an intelligent wireless telephone or other suitable device.
The identification information can be stored in a card with an embedded RFID tag and its location determined by fixed interrogators. Alternatively, intelligent devices such as PDAs and wireless telephones can have embedded within them a GPS receiver which can provide precise position information and be transmitted directly to fixed interrogators or wireless telephone towers which will then relay that information to the computer. Another alternative embodiment uses multiple wireless telephone towers to detect wireless telephones that are not local to the area and to determine the position of the wireless telephone through triangulation techniques.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram which illustrates data flow between an individual and an advertiser or content provider system.
FIG. 2 is a diagram that illustrates an alternative embodiment of the invention in which the identification device is shown embedded in several different types of I/O devices.
FIG. 3 is a diagram that illustrates another alternative embodiment of the invention in which the identification device determines its own location from GPS satellite information and transfers that information to the advertising computer via the cellular telephone system and the Internet.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Prior to the discussion of the figures, a general overview of the features and advantages of the invention will be provided. The invention is directed to a method of providing focused information to individuals based on the time and/or the location of the individual in relation to a particular source of information or information provider. An information provider can be a merchant or advertiser, a public entity distributing information, or any other entity seeking to distribute information based on time and the location of an individual. This focused information can be very useful when used by local merchants attempting to reach visitors to the merchants geographical area, but it can be equally useful when marketing to local residents.
In general, this system can use personal preferences as a way to filter content from providers, but ordinarily position and/or time information determines which, not how much, data will be loaded or forwarded for an individual to see or use. In the event an individual desires to receive only certain types of information, then the individual can, via the system, update the filtering criteria. The system would filter out any information which the individual has indicated to be undesirable. This protects the user from receiving large quantities of unwanted information from a variety of advertisers or other sources. One way that the filtering preferences can be selected is via a form page in a Web site.
In addition to filtering under control of the individual, the system can also dynamically filter information before it is sent to the individual. This would be done to eliminate any redundant messages or hyperlinks that would otherwise be presented to the individual.
The system uses the Internet to deliver Web pages or other content through non-traditional push means. The information is directed to particular individuals when their presence is detected in a particular location. The information is distributed using conventional Internet email, or it can be distributed via an individual account designed to store accumulated content for display to the account member through wireless devices such as PDAs or intelligent wireless telephones interfacing with the Internet.
The system determines the presence of an individual through the use of an identification device, such as an RFID tag, intelligent wireless telephone, or other device such as a PDA, and based on the individual's identity and location and/or time they are at a location, the system selects information related to the location or time and pushes the information down through the available information channels to that individual. Once the system identifies the individual, it delivers information content, in whole or in part, via the Internet and through appropriate wired or wireless devices.
An example of how the invention is used is as follows: if an individual is carrying an identification device, such as an RFID tag in the individual's wallet, and the individual is passing by a particular store which has an interrogator, the interrogator in the store will read the identification information in the RFID tag and forward that information to a computer along with the location of the interrogator. The computer can then access any records related to the individual with the information from the RFID tag. The computer's records may indicate that the individual has preferences for a particular product or service. If the product or services are on sale, the computer can then notify the individual to allow the individual to take advantage of the sale or availability of the product. While older Internet communication methods, such as email, or pushing an icon to the customers desktop through conventional push technology can be used, the system can also notify the individual via alternative methods. For example, if the individual has a PDA, or an intelligent wireless telephone, the computer can immediately notify the individual by sending email or any other suitable message to the PDA or intelligent wireless telephone. Likewise, the information can also be made available to the individual at a specific Internet web site, say for example, through a user account. Alternatively, displays within the store can be synchronized with the individual such that as the individual passes by a specific location within the store, customized advertisements or information based on past user purchases or user preferences can be automatically downloaded to the monitors as the user passes by fixed interrogators within the store.
Interrogators can be self contained devices. However, their functions can also be implemented by computers having the necessary transmitter, receiver, and antenna.
A preferred embodiment of particular interest is one in which an RFID tag used as the identification device is embedded in a conventional credit card. This provides convenience to the individual because the individual does not have to carry anything additional beyond what the individual already carries. In addition, since credit cards are almost universally used, the placement of the identification device inside a credit card would achieve rapid penetration of the entire marketplace.
Referring to FIG. 1 , this figure illustrates the flow of information in a preferred embodiment of the invention. As shown in this figure, an individual 1 will be carrying identification device 3 . The identification device 3 should preferably be small enough to be carried conveniently in the individual's 1 wallet. For ease of illustration, the identification device 3 is shown in the individual's 1 pocket 2 . In the preferred embodiment, the identification device 3 would be an RFID tag with a unique ID number associated with that individual 1 . RFID tags and interrogator techniques are well-known in the art. As a matter of convenience, the RFID tag may be encased in a plastic card similar to a credit card for the purpose of allowing it to be conveniently stored in the individual's 1 wallet along with the individual's 1 credit cards.
Those skilled in the art will realize that an extremely effective way of using the identification device 3 is not to put it in a stand-alone container, but rather to embed it inside an actual credit card. This eliminates the need for the individual to carry anything extra, it ensures that the individual will be careful not to lose it, and it ensures that wide market penetration will be achieved by the system.
As the individual 1 travels from one location to another, the individual 1 may pass by an interrogator 4 (for the purpose of this discussion, an interrogator may also be referred to as an information retrieval or writing or loading device). In the preferred embodiment, a series of interrogators 4 would be located in various locations to allow an individual 1 to be monitored over a wide geographic area. It may also be possible, particularly to reduce costs, to use a switching scheme where only one interrogator's 4 transmission is relayed to different antennas at a physical or “brick and mortar” store. The switching can be prompted by a passive IR interrogator or can just be sequentially fired. This reduces the number of interrogators 4 which are needed. As the individual 1 passes the interrogator's 4 antenna, the interrogator 4 would awaken or energize the identification device 3 and the identification device 3 would respond to the interrogator 4 by modulating unique identification information to the interrogator 4 via returned RF. Interrogator 4 and RFID technology are well-known in the art. In addition to the RFID tags used by the interrogators 4 , other technologies, such as phase shifting detection (Doppler) and signal strength (amplitude) detection can also be used to determine location.
Those skilled in the art will recognize that while a commonly available RFID system is used in this embodiment, any suitable wireless technology can be used, such as near field (magnetic or “H” field) tags similar to those used as antitheft devices in stores, infrared devices, smart cards, bar codes, magnetic strips, ultrasonic transducers, etc. In addition, hybrid technologies can also be used. For example, GPS chip sets can be used in combination with an RFID tag. An on-board clock and timing circuit can be used to record locale at regular time intervals. The RFID tag can send this information when energized by an interrogator 4 . These hybrid technologies allow merchants or information gatherers to monitor movement of an individual through a given geographic area, for example, a store. This provides the observer with information which may be useful in monitoring traffic, placing advertising, etc.
Of course, some of these devices will require conscious action on the part of (he individual 1 to activate. In the preferred embodiment, a read-only RFID transponder is embedded in the card. However, it is also possible to use a read/write RFID transponder to allow the information in the identification device 3 to be altered. Likewise, while only one RFID transponder is needed to implement the system, multiple RFID transponders can be placed in the identification device 3 to allow the identification device 3 to be used in other countries such that the same identification device 3 can comply with government regulations in more than one country. In this case, each RFID transponder would operate in a different frequency or in a different frequency band. Likewise, multiple transponders may be used with different frequencies to provide redundancy which will avoid lost detections due to missed transmissions, and also provide improved performance by allowing the interrogator 4 to select the strongest incoming signal.
The interrogator 4 reads the ID information in the identification device 3 and transmits the individual's 1 ID information, in combination with location information to an advertiser system 7 via the Internet 6 . The advertiser system 7 , as discussed herein, is the system which gathers information from advertisers and other information providers, and which controls the downloading of that information to the individual. The advertising system 7 also collects preference selection information from the individual 1 and uses it to filter the information which is downloaded to the individual 1 . The connections between the interrogator 4 , the Internet 6 , and the advertiser system 7 can be any convenient technology, such as land line modem, cellular modem, hardwired connection (cable network, DSL, etc.). Once the advertiser system 7 receives the ID information from the individual 1 , the advertiser system 7 then uses the ID information to access the individual's 1 records in the advertiser system 7 . Based on the individual's 1 records, the advertiser system 7 knows that the individual 1 is more likely to be receptive to an advertisement or communication from one or more content providers related to the location and/or time that individual was at the location. The advertising system 7 will then select appropriate information and transmit that information to the individual 1 via predetermined information channels.
Those skilled in the art will recognize that the interrogator 4 may be a dedicated device which executes a single function. Likewise, it may also be implemented by being attached to a conventional PC.
For example, the advertising system 7 may forward email 8 to the individual 1 via the Internet. This is a conventional method of sending email 8 which does have a drawback in that it may not be received until the individual 1 checks incoming email 8 . The advertising system 7 may also decide to send communications to the individual 1 via more recently developed devices such as a PDA 9 . The advantage of the PDA 9 is that it can be carried by the individual 1 , which makes the incoming communication immediately available. If the PDA 9 is equipped with a cellular modem, the PDA 9 can receive a message or be used to access email immediately. A PC 10 , either desktop or portable, can also be used to receive messages from the advertising system 7 . When a PC 10 is used, alternatives to email can also be used. For example, the individual's 1 account can be accessed or a button in the browser bar can be “clicked” to view hyperlinks and advertisements. Also, the final delivery stage of content delivery can be through “traditional” push means. Alternatively, some data can be forwarded to the individual 1 via audio technology. In that situation, the individual 1 would specify that the text information is to be converted to audio via a text to speech program that would play the information to the individual 1 via an audio output device, such as the intelligent wireless telephone 11 .
In another alternative preferred embodiment, intelligent wireless telephones 11 can be used to receive the information. Intelligent wireless telephones 11 have been developed with a display screen suitable for displaying messages. These devices have built-in intelligence features that exceed the basic telephone technology. For example, they can have small processors and Web browsers which will allow them to surf the Web, to receive e-mail, etc. These devices are also commonly referred to as being Web enabled. One advantage of using an intelligent wireless telephone 11 is that the advertising system 7 can use the Internet to contact the intelligent wireless telephone 11 or directly dial the intelligent wireless telephone 11 without using the Internet. The individual 1 would be immediately notified of the incoming message when the intelligent wireless telephone 11 rings.
In addition to the conventional methods of receiving data, an identification device 3 reader can also be attached to the individual's 1 computer to read the information provided by the RFID device in the identification device 3 . In this configuration, when the individual 1 activates the individual's 1 computer, the identification device 3 is waived in front of the reader, the reader automatically notifies the advertising system 7 via the Internet, and the information is downloaded to the individual 1 or interfacing device (i.e.: PC, laptop, PDA, etc.).
Another advantage of the invention is that it allows an individual who does not own a PC to be able to take advantage of the information provided by the invention As discussed above, one alternative embodiment provides the ability to attach an interrogator 4 to a PC which may be owned by a merchant or some other entity, such as a library. If the individual 1 uses the merchant's or library's PC, the individual 1 would wave the identification device 3 in front of the interrogator 4 . This would notify the advertising system 7 of the presence of the individual 1 at that PC, and the advertising system 7 would then proceed with downloading information to the individual 1 .
In the preferred embodiment, an individual 1 would provide demographic and reference information which would be stored in the individual's record in the advertising system 7 computer. This information would be related to the identification information on the identification device 3 so that the advertising system would be able to evaluate potential information which is most appropriate to the particular individual 1 .
FIG. 2 illustrates an alternative preferred embodiment in which the identification information can be stored in alternative devices rather than the identification device 3 discussed above. In particular, in the event that the PDA 9 , the PC 10 , or an intelligent wireless telephone 11 is used, the identification device 3 can be integrated with either the PDA 9 , the PC 10 , or the intelligent wireless telephone 11 . This would eliminate the need for the individual 1 to carry the identification device 3 .
The only requirement for output devices used by the individual 1 to receive information is that they must have Internet access (with the exception of the intelligent wireless telephone 11 ).
The ability of the invention to determine where an individual 1 is at a given time allows a merchant or other information provider to focus its advertising on individuals 1 who have a probability of interest in a particular advertisement or information content. This is possible because the individual's 1 record on the advertising system 7 will contain demographic information that indicates to merchants whether there is a probability of interest. Likewise, the time the individual 1 is detected can be an important factor in advertising. For example, an advertiser who manages a restaurant may have a strong interest in immediately notifying nearby individuals 1 during the lunch or dinner hours. Alternatively, advertisements for restaurants would not be sent to the individual 1 after the restaurant is closed. Yet another example would be a business which advertises using billboards, bus stops, magazines stands, etc. These advertisements can be correlated to a specific location in between two or more specific dates. When someone is at this location at a particular time, the system can determine which advertisements were seen by that individual.
Shown in this figure is an interrogator 4 attached to an antenna 12 . For ease of illustration, the antenna 12 is shown as a separate device, but it may just as easily be an integrated component of the interrogator 4 . When the advertising system 7 has selected a the appropriate advertisements and/or information for the individual 1 , it then transmits that information to the interrogator 4 via the Internet 6 . The information is then transmitted via a hardwired link to a display or audible device (using speech software) or via wireless link to any of the interfacing devices such as the PDA 9 , computer 10 , or the intelligent wireless telephone 11 .
Those skilled in the art will recognize that while the interrogator 4 can be a read-only device that only forwards identifying information to the advertising computer 7 , the interrogator 4 can also be designed as shown in this figure to have read/write capability. Read/write capability provides increased functionality since it allows immediate transfer of data via the same data path used to collect the identifying information.
In FIG. 3 , another alternative preferred embodiment is illustrated. This embodiment eliminates the need for an interrogator 4 . It uses pre-existing GPS satellite position information and existing cellular phone systems. In addition. for ease of illustration, an intelligent wireless telephone 11 is shown in (his figure. While one particular technology is used for illustrative purposes, those skilled in the art will recognize that any suitable wireless technology can be used. In addition, those skilled in the art will realize that a device such as a PDA 9 equipped with a wireless modem can also function similar to the intelligent wireless telephone 11 .
Those skilled in the art will recognize that GPS is only one of a number of commercially available positioning systems. For example, Omega, Decca, Tacan, JTIDS, Loran, Relnav and PLRS are known navigation systems. However, GPS is preferred because of its accuracy, global availability, and low-cost.
In the shown figure, the individual 1 carries an intelligent wireless telephone 11 . The intelligent wireless telephone 11 has an integrated GPS receiver (GPS receivers are well-known in the art) which receives GPS satellite position information from GPS satellites 13 . The intelligent wireless telephone 11 determines its exact location based on the GPS data. The GPS data enables the computation of position, including longitude, latitude, and altitude data which identifies a precise geographic location. This data would preferably be passed to the advertising system 7 . As the individual 1 moves through a cellular telephone node area, the intelligent wireless telephone 11 communicates with the cellular telephone tower 14 on a periodic basis. At this time, the intelligent wireless telephone 11 transmits its GPS location data to the cellular telephone tower 14 . The intelligent wireless telephone 11 may also transmit its identification information to the cellular telephone tower 14 at this time. However, this identification information may also be omitted since the telephone number is unique to the individual 1 , and therefore the advertising system 7 can determine who the individual 1 is without receiving identification information other than the telephone number.
The information received from the individual 1 at the cellular telephone tower 14 is communicated to a data processing station IS connected to the cellular telephone tower 14 . In turn the data processing station 15 transmits the individual's 1 identifying information and location information to the advertising system 7 via the Internet 6 . Once the individual 1 is detected, the advertising system 7 can then directly download the appropriate data corresponding to the advertiser in that location to the intelligent wireless telephone 11 via the cellular telephone network using the data processing station 15 and the cellular telephone tower 14 .
An alternative preferred embodiment uses a GPS “slave” which is attached to an on-board “master” that commands the GPS slave to output location information at preset times. Using this information, the intelligent wireless telephone 11 transmits in batch quantities, all advertiser locations within an area close to the GPS computed location when requested by the master. The intelligent wireless telephone 11 has incorporated within it a scaled-down version of an Internet 6 Web browser. Information from advertisers and/or information providers in the requested location is downloaded to the intelligent wireless telephone 11 via the Internet 6 and cellular network.
As the individual 1 eventually travels by each location, the individual's 1 movement can be logged. This logged information can be used to measure the effectiveness of the advertising and to determine if the individual 1 has actually visited any of the advertiser sites. The advertiser sites may be any site which provides information to the individual 1 , which may include not only stores that provide products or services, but also other physical locations, such as billboards which only provide information or advertisements.
The foregoing embodiments have been discussed in terms of conventional advertiser sites with fixed locations. However, the invention is not limited to this scenario. For example, “mobile stores” or “advertisements” can have affixed a GPS/phone to report its location at any instant in time. This enables the “mobile store” or “ad” location information to be compared to an individual's 1 intelligent wireless telephone 11 location information. When a match occurs, the system functions the same as if the mobile store or ad were at fixed locations and only the individual 1 was mobile. This is a similar situation to that in which a merchant “walks” an area. When a merchant walks an area, the merchant defines the geographic area to which the merchant's information is to be distributed. Mobile stores or advertisements function in the same manner. As the mobile store or advertisement moves through an area, it dynamically updates the area to which its information applies, and any individual 1 who happens to be close enough to be identified will receive information related to the mobile store or advertisement.
Another advantage of the invention is that it can be used for social as well as commercial activity. For example, a “Buddy” system can be implemented whereby individuals can be alerted when friends are in the area, such as when two or more individuals are detected in a shopping mall. The system can notify each of the individuals so that they can have the opportunity to meet. This feature can be implemented as part of the individual's preference which the individual sets into the system. Preferably, this feature can be dynamically modified so that an individual can turn the feature on or off at will by updating preferences.
Another preferred embodiment allows the advertising system to synchronize with online radio and television broadcasts. A number of Internet Web sites currently provide radio and programming broadcast from various locations. If an individual is online and connected to one of those Web sites, the advertisements presented through the Web site can be monitored and synchronized with the other information presented to the individual. The individual would also initialize this feature through the individual's preferences set by the individual with the system. Likewise, this same method can be implemented in conjunction with local cable providers or satellite television by communication with the converter box, determining the channel the box is tuned to, and then using this information, referencing a commercial programming schedule stored in the advertiser system 7 . The information retrieved should be time stamped to know if the channel being watched is being watched when an advertisement is due to run. A URL or Web page can then be loaded to the user's account using the system outlined.
All identification information received from identification devices 3 can either be transmitted to the computer or server via the Internet at the end of the day or transmitted immediately via the intelligent wireless telephone 11 through the Internet as they are being received. Likewise, identification information received from a predetermined number of identification devices 3 can be stored and then bulk transferred to the computer of the advertising system 7 at predetermined times or levels.
When an interrogator 4 is used, a custom application program might be needed.
This application would reside on a platform which would collect and send the data from the interrogator 4 , using commonly known protocols such as FTP, to the advertising system 7 where the time, location, and individual identification information would be used to transmit select information to a specified individual 1 .
In an alternative embodiment, when a conventional fixed location business initiates use of the system, the merchant, rather than relying on a relational database of atlas information, may use an identification device 3 to “walk,” plot and record the locations of interest to the merchant. As the merchant walks through an area, the locations the merchant's walked in define the perimeter of the area which the merchant has an interest in. Once the walk is complete, the system will associate the area within this perimeter with the merchant. This alternative embodiment allows the merchant to customize locations covered by the system to the merchant's choice. For ease of discussion, the identification device 3 , when used by the Merchant to walk an area, may also be referred to as an information provider identification device.
The foregoing discussion has centered on conventional Internet based systems where telephone land lines are extensively used. However, those skilled in the art will recognize that alternative communications links can be used in the situation where an individual is in a remote location. In particular, communications systems which use it cellular phone/PCMCIA modem hybrid connections can overcome the lack of land telephone lines. This is useful in remote locales where identification devices 3 can be read, but not sent via conventional telephone land lines.
That alternative method of establishing the location of an individual 1 is to register their physical, street, or mailing address through an atlas database reference established coordinates that are triggered via GPS or other suitable scheme to then initiate data or advertisement delivery.
While the invention has been described with respect to a preferred embodiment thereof, it will be understood by those skilled in the art that various changes in detail may be made therein without departing from the spirit, scope, and teaching of the invention. For example, the device carried by the individual which communicates information may be any suitable technology, the type of device used by the individual to receive information from the advertising system may also vary. Accordingly, the invention herein disclosed is to be limited only as specified in the following claims.
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A time/location information delivery system that provides focused advertising and/or other information to individuals based on the time and their location. A wireless identification device is carried by an individual and can be read from or written to when the individual passes by interrogators in a specific geographic location. The detectors read ID information embedded in the wireless identification device. A computer uses the ID and location information to select, from a list of information providers, those information providers which provide information content identifiable or correlated to a location and/or time, and is of interest to the individual. The information content can be forwarded to the individual by a variety of information channels. One channel uses conventional Internet email to deliver advertisements and other information to the individual's Internet mailbox. The email can be delivered to a conventional PC, a portable computer, a PDA, an intelligent telephone, pager or other suitable device. For ease of discussion, a pager and a PDA will be referred to collectively as a PDA. The wireless identification device can be an RFID tag embedded in a card, or even a wireless telephone. The RFID tag is read or written to by fixed interrogators and the location of the wireless telephone is detected by triangulating information from cell towers or by embedding the GPS receiver in the wireless telephone thereby providing the location information directly from the telephone. Of course, other nearly identical location determination means, such as quadrangulation could also be used. The location determination can be performed through similar means with other devices such as PDAs, laptops, pagers, etc.
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FIELD OF INVENTION
[0001] The invention relates to methods of delivery of care, specifically, to the organization and administration of care across multiple disciplines for streamlined assistance of residents along the continuum of geriatric care in an assisted living setting. These methods of delivery of care utilize kits and a system for assistance in the administration of the methods. The methods of delivery of care also include provisions for assisted living dementia and assisted living palliative care units.
BACKGROUND OF THE INVENTION
[0002] Aged individuals who are in relatively good health and no longer capable of living on their own have found refuge in assisted living/residential care facilities. These facilities provide residential settings with living amenities intended to facilitate a semi-independent lifestyle for the elderly. While the services provided by these facilities vary, many provide laundry, food, and cleaning services in addition to some low level medical care. Individuals benefit from these organized residential settings; however, in almost all cases, residents experience a decline in health due to the natural progression of aging. Currently, residents who are in ill-health are almost always transferred to other facilities such as skilled nursing facilities, nursing homes, and hospitals. The transfer can be temporary or permanent and may depend upon the health of the resident in addition to their ability to pay for treatment. Oftentimes, elderly residents are shuttled between facilities. The transfer and constant shifting is very disorienting for the transferees and it often further complicates health issues. The shifting is also detrimental to care in that it abrogates any streamlined therapy; for example, medication administration may be confused, diagnoses can be lost, and health setbacks are almost always the result.
[0003] Further complicating the issue is the payment associated with care. Insurance coverage is generally only available to patients in skilled nursing facilities, nursing homes, and hospitals. The administration of care to residents in a traditional assisted living or residential care facility is generally not covered by healthcare insurance (including long-term care insurance) and does not qualify as a medical writeoff for tax purposes. Traditional assisted living models up until now have been considered a third party “carve out” by the insurance industry and the U.S. government; therefore, residents, their families, and their estates have had no other options except to pay all associated costs themselves. It is possible that under traditional assisted living and residential facility models, third party payors do not provide assisted living coverage and medical tax relief for residents, families, and their estates because residents who develop complex medical problems, experience functional decline, suffer significant dementia, or confront end-of-life issues cannot be adequately cared for. As a result, the ability of the residents and their families to privately pay has been the predominant mechanism for assisted living facilities to receive revenue. Accordingly, there is a need for the delivery of augmented assisted living care and the creation of a new niche of improved care to facilitate entrance of the third party payor industry into assisted living and residential care arenas.
[0004] Up until now, transfer is generally required for residents experiencing health issues, even if staying in a residential care facility would be better for the resident. Assisted living facilities lack adequate medical care or treatment services that are comprehensive and cohesive between different caregivers and staff. The lack of comprehensive treatment is evidenced by, among other things, the lack of available care around the clock, 24 hours a day, 7 days a week, and unavailable care by on-site physician health care workers, nurses, or medical specialists. Some facilities have no medical staff on-site, while others have medical care staff available for a few hours a day. The lack of cohesiveness is evidenced in many situations, for example, where a primary care physician or an on-site medical caregiver is not aware of the medications prescribed to the resident by a cardiologist, urologist, psychologist, or other specialist.
[0005] The residential care setting is generally beneficial to the aged; however, there remains a disconnect in the scope of services provided and the facilitation of care. These shortcomings are detrimental to the health of residents, thereby complicating the benefits intended by residential care.
[0006] There remain several obstacles to providing an organized, cohesive, and comprehensive environment for living that enhances, not hinders, the unavoidable declining health of residents. For example, there exists a need to bridge the gap between traditional assisted living or residential care and the more highly regulated skilled nursing facilities and nursing home care. Many assisted living and residential care facilities lack the ability to handle more medically complex patients resulting in a transfer to alternate facilities and the inevitable disorientation of the individuals and fragmentation of their care. Oftentimes, transfer uproots a resident's family unit. Moreover, traditional assisted living facilities lack the ability to care for many of these aging patients with the “graying of America” demographically as they develop dementia and require complex care in locked wards. As frail residents inevitably decline over time, traditional assisted living facilities are not medically equipped to provide seamless, on-site palliative and end-of-life hospice care. Thus, there is a need for assisted living and residential care facilities to maintain medical centers on-site or closely related to the facility that are staffed with medical doctors and mid-level practitioners such as nurse practitioners and physician's assistants, as well as medical students, physician's assistant students, and/or nurse practitioner students, in order to deliver care along the geriatric health continuum. There is a further need for staff of the medical center to work closely with many other individuals in the delivery of care, including primary care house staff employed by the facility.
[0007] Oftentimes, residents need specialized services that are not provided by a general practitioner, for example, services of specialists such as cardiologists, urologists, psychologists, dentists, podiatrists, ophthalmologists, and physical therapists. Residents also need services of ombudspersons to assist with insurance issues, wound care nurses to assist with wound-related nursing care, activities directors to provide entertainment and mental stimulation, and chaplains to fulfill spiritual needs. The numerous disciplines interacting with the elderly residents are often unaware of the attention or care provided by other caregivers at the facility and/or caregivers in the community. An overlap of care, a lapse of care, or conflicting care can be extremely detrimental to the health and well-being of the elderly residents. Accordingly, there is a further need to organize the many practitioners and staff that come in contact with residents with the core unit of caregivers in the facility, that is, an on-site medical doctor who may also be an on-site medical director and/or on-site mid-level practitioners such as physician's assistants and nurse practitioners. There is an additional need to deliver care to elderly residents in an assisted living facility whereby the care administered is covered by insurance.
[0008] In addition to this organization of care, the certification of on-site caregivers and staff is crucial to the quality of care. While it is beneficial to have many individuals involved with the residents, it is crucial for these individuals to be properly licensed and/or certified to do their jobs. Accordingly, there is a need to ensure that all parties have the proper certifications.
[0009] With several individuals contributing to the overall care of a resident, there exists a need for these individuals to be aware of and to follow specific protocols and procedures for delivery of care. These protocols and procedures may include how to address the resident; the extent of the service to be rendered; and how to create, store, and maintain records concerning the resident to ensure one cohesive set of resident records and to ensure compliance with applicable laws. Accordingly, there is a need to integrate protocols and procedures within the framework of a comprehensive and cohesive care unit.
[0010] Therefore, there remains a significant need in the art for improved methods and tools for the delivery and administration of care in an assisted living or residential care setting.
SUMMARY OF THE INVENTION
[0011] The present invention relates to a methods and tools for the delivery and administration of cohesive and comprehensive care. In one embodiment the delivery of care is for residents of an assisted living facility along the continuum of geriatric care. In another embodiment, the method defines components for the delivery of care and their organization. Components for care may include caregivers in multiple disciplines having unique relationships with one another and with the residents, and further includes a medical center, and dementia and palliative care units within, on the premises of, or near the assisted care facility. In another embodiment, the method and its related protocols and procedures is implemented in a kit for dissemination to all facilities offering residential care or assisted living services to achieve streamlined, efficient delivery and administration of care to its aging residents. In yet another embodiment, the kit includes certification and licensing requirements for caregivers and a method of tracking these requirements. In another embodiment, the method is integrated into a system capable of adoption by residential care or assisted living facilities to achieve streamlined, efficient delivery and administration of care to its aging residents.
DETAILED DESCRIPTION OF THE INVENTION
[0012] Unless defined otherwise, the terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. One skilled in the art will recognize many methods, kits, procedures, protocols and systems similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods, kits, procedures, protocols and systems described. For purposes of the present invention, the following terms are defined below.
[0013] “Assisted living facility,” “residential care facility,” and “assisted living residential care facility,” are used interchangeably and generally refer to those facilities providing a residential unit and services to the elderly. These facilities may also include “assisted living dementia units,” and “assisted living hospice and palliative care units.” A third party assisted living facility or a residential care facility means a facility at an alternate location or one run by a different entity.
[0014] “Medical center” is a central medical unit or hub for residents to receive a high level of medical care. The medical center is preferably located on-site or close to the residential care facility. It may be located in a separate office within the facility, may be a roving unit that attends to residents wherever they are located, or may be located in a separate office close to the facility, preferably within walking distance and/or within 100 yards of the facility. Location notwithstanding, the medical center may be operated as a separate legal entity from the assisted living facility.
[0015] “Medical center staff” is one or more individual making up the medical center that is a central medical unit or hub for delivering the high level of medical care to residents. The medical center staff is preferably comprised of at least one physician who may also be a certified medical director and one or more nurse practitioner or physician's assistant.
[0016] “Facility caregiver” is an individual employed by the facility or an individual who has a relationship with the facility as an independent contractor who interacts with the residents.
[0017] “Third party caregiver” is an individual not employed by the facility or under a contractual relationship with the facility who interacts with the residents.
[0018] “Physician medical director” is preferably a member of the medical center staff and may see residents for medical treatment. The physician medical director may also be employed by the assisted living facility or may be in a contractual arrangement with the assisted living facility, and may serve as an administrative and community liaison for the facility. The physician medical director is certified as a medical doctor and preferably as a medical director.
[0019] “Corporate medical director” is preferably a facility caregiver, and may function as a top level medical director focusing on administration of one or more assisted living facility, preferably serving at a regional administrative level, to ensure that medical directors at multiple assisted living facilities are addressing administrative issues consistently and to further ensure that the medical directors are focusing care and compliance with professional standards and industry norms. The corporate medical director is preferably a certified medical director.
[0020] “Medical student” is an individual currently studying to become a medical doctor and may be a member of the medical center staff.
[0021] “Nurse practitioner” is preferably a member of the medical center staff. The nurse practitioner may also be employed by the assisted living facility or may be in a contractual arrangement with the assisted living facility. The nurse practitioner provides mid-level practitioner support for the residents and serves as a liaison to the nurses serving at the residential care facility.
[0022] “Corporate nurse practitioner” is preferably a facility caregiver, and may function as a top level nurse practitioner focusing on administration of nurse practitioners offering services at one or more assisted living facility, preferably serving at a regional administrative level, to ensure that nurse practitioners at multiple assisted living facilities are addressing administrative issues consistently and to further ensure that the nurse practitioners are focusing care and compliance with professional standards and industry norms.
[0023] “Nurse practitioner student” is an individual currently studying to become a nurse practitioner and may be a member of the medical center staff.
[0024] “Physicians assistant” is preferably a member of the medical center staff. The physician's assistant may also be employed by the assisted living facility or may be in a contractual arrangement with the assisted living facility. The physician's assistant provides mid-level practitioner support for the residents and serves as a liaison to the nurses serving at the residential care facility.
[0025] “Corporate physicians assistant” is a facility caregiver, and may function as a top level physicians assistant focusing on administration of physicians assistants offering services at one or more assisted living facility, preferably serving at a regional administrative level, to ensure that physicians assistants at multiple assisted living facilities are addressing administrative issues consistently and to further ensure that the physicians assistants are focusing care and compliance with professional standards and industry norms.
[0026] “Physicians assistant student” is an individual currently studying to become a physicians assistant and may be a member of the medical center staff.
[0027] “Nurse” means a registered nurse, and may be a nurse with a particular specialty or title such as a director of nursing, wellness nurse, or wound-care nurse. The nurse is preferably a facility caregiver but may be a third party caregiver who administers nursing care to the residents. The nurse may also be employed by the medical center.
[0028] “Facility executive director” is a facility administrator who engages in day-to-day administration and management of the residential care facility.
[0029] “Dementia-care director” is preferably a facility caregiver but may be a third party caregiver who assists in the understanding and education of the community, facility staff, and family members in the association with elderly residents.
[0030] “Activities director” is preferably a facility caregiver but may be a third party caregiver who assists in organization of activities, games, programs, and outings for the elderly residents.
[0031] “Ombudsman” can be a facility caregiver, a third party caregiver and/or an individual associated with the state that assists residents and family members with complex insurance coverage and general grievances.
[0032] “Chaplain” is preferably a facility caregiver or a third party caregiver who assists in the spiritual needs of residents, family and community.
[0033] “Clinical pharmacist” is preferably a third party caregiver who works closely with prescribing professionals such as members of the medical center staff and the facility caregivers authorized to administer drugs in the proper dosing, administration, and tracking of drugs given to residents. The clinical pharmacist may be affiliated with a fulfillment pharmacy charged with medication oversight, on-site support, medication-medication interaction reporting, auditing, and pharmacy training.
[0034] “Gero-psychiatrist” is preferably a third party caregiver or facility caregiver who is available to meet with residents to address psychological, social, or other issues arising in the life of a resident. The gero-psychiatrist may prescribe medication.
[0035] “Physical therapist” is preferably a third party caregiver or facility caregiver who works with residents to restore motion, strength, functionality and ultimately independence to perform daily tasks in residents who need physical therapy services.
[0036] “Occupational therapist” is preferably a third party caregiver or facility caregiver who works with residents to restore motion, strength, functionality and ultimately independence to perform daily tasks in residents who need occupational therapy services.
[0037] “Speech Therapist” is preferably a third party caregiver or facility caregiver who works with residents to assess, diagnose, treat, and help to prevent speech, language, cognitive-communication, voice, swallowing, fluency, and other related disorders.
[0038] “Psychologist” is preferably a third party caregiver or facility caregiver who is available to meet with residents to address psychological, social, or other issues arising in the life of a resident.
[0039] “Licensed Clinical Social Worker” and “Nurse Case Managers” are preferably a third party caregiver or facility caregiver with a specialty in counseling, including grief, bereavement, family counseling, and adjustment, and knowledge and matchmaking with community resources.
[0040] “Podiatrist” is preferably a third party caregiver or facility caregiver with a specialty in podiatry, particularly useful to the treatment of some elderly residents.
[0041] “Respiratory therapist” is preferably a third party caregiver or facility caregiver with a specialty in respiratory therapy, particularly useful to the treatment of some elderly residents to provide respiratory care and enhance respiratory function.
[0042] “Dentist” is preferably a third party caregiver or facility caregiver with a specialty in dentistry, particularly useful to the treatment of some elderly residents.
[0043] “Ophthalmologist/optometrist” is preferably a third party caregiver or facility caregiver with a specialty in eye care, particularly useful to the treatment of some elderly residents.
[0044] “Medical technicians” are preferably facility caregivers and/or employed by the medical center, with the requisite licensures or certification to assist elderly residents in their specialty field.
[0045] “Care managers” are preferably facility caregivers and/or employed by the medical center, that serve as an additional liaison for the residents in their overall care. The care managers should be easily available to residents and should be resourceful and capable of fielding requests of the residents to the proper professional or entity.
[0046] “Third party payor” may be an insurance company, including a provider of healthcare insurance and/or long-term care insurance.
[0047] The invention is based on an improvement to the current method of assisted living organization and delivery of care whereby the delivery of assisted living care is medicalized. The invention includes a medical center at the residential care facility comprising medical center staff that administer a high level of medical care to residents. The medical center is preferably located within the residential care facility; for example, in an office or as a roving unit. The medical center may also be located close to the residential care facility preferably within walking distance or within one hundred yards of the facility. In one embodiment the medical center staff is comprised of one or more on-site physician medical director and one or more nurse practitioner and physician's assistant and optionally one or more rotating geriatric student such as a medical student, physicians assistant student, or nurse practitioner student, for administering a high level of medical care to the residents of the assisted living residential care facility. In another embodiment, the physician medical director serves as the administrative and community liaison for the facility. The medical center staff is integrated with a plurality of members of an interdisciplinary team, wherein the team comprises one or more facility caregiver and third party caregiver for administering care to residents. The facility caregiver and third party caregiver are from multiple disciplines. For example, a facility caregiver may be an executive director, corporate medical director, corporate physicians assistant, corporate nurse practitioner, nurse, director of nursing, wound care nurse, wellness nurse, physical therapist, respiratory therapist, dietician, dementia care director, activities director, ombudsman, chaplain, clinical pharmacist, gero-psychiatrist, psychologist, occupational therapist, speech therapist, licensed clinical social worker, ophthalmologist, podiatrist, dentist, medical assistant, or care manager. A third party caregiver may be a nurse, physical therapist, respiratory therapist, dietician, dementia care director, activities director, ombudsman, chaplain, clinical pharmacist, gero-psychiatrist, psychologist, podiatrist, dentist, occupational therapist, speech therapist, licensed clinical social worker, ophthalmologist, medical assistant, or care manager. The interdisciplinary team provides care and comes into contact with the residents that are also treated by the medical center staff.
[0048] Integration of the medical center staff with the interdisciplinary team means that the medical center staff is in communication with the interdisciplinary team regarding any care administered to a resident or contact made with a resident. Communication may be weekly or daily basis, or may occur after any care or contact is made with a resident. The integration of the medical center staff with the interdisciplinary team ensures that care of residents is comprehensive and cohesive, and is based upon the most up-to-date information about the resident; for example, information of high medical importance such as the type of medications prescribed to a resident or information concerning the resident's daily activities may be communicated to the medical center staff. The exchange of information concerning the residents is always in accordance with the law, especially in accordance with laws protecting the privacy of residents. The inventive geriatric assisted living care method, kit, and system, and the resulting integration of medical center staff with the interdisciplinary team also ensures infection control, quality assurance, safety of medical center staff and facility caregivers, up-to-date information on accidents and incidents, and decreases in medical errors.
[0049] Using the inventive geriatric assisted living care method, kit, or system, the physician or mid-level practitioner on-site patient encounter is now billed to Medicare (and/or other third party payor) utilizing a traditionally covered out-patient office visit code, rather than the poorly covered and poorly reimbursed house call or domiciliary codes utilized by traditional off-site practitioners heretofore.
[0050] The care delivery capabilities of the medical center extend to bringing in innovative healthcare, home care, mobile, and outpatient technologies on-site for diagnostics, therapeutics, screening, and wellness for facility employees, residents, and their families and friends (including, health fairs). For example, “CLIA Waived” finger stick lab tests (Glucose, Hemoglobin AIC, AST, ALT, Prothrombin Time/INR, CBC, Basic Metabolic Panel, and others), dipstick urinalysis testing, pulse oximetry (rest and exercise), nocturnal sleep oxygen saturation studies, electrocardiograms (EKG), Holter Monitor, spirometry testing, Bone Densitometry, Indirect Calorimetry are performed and read on-site. Innovative ultrasound technologies are not only routinely employed to look at organs like the heart, kidneys, liver/gall bladder, pancreas, bladder, and great vessels, but are also utilized to determine peripheral vessel and carotid vascular blood flow as well as non-invasive fluid balance determinations. Fluid-balance determinations include the determination of whether a resident is “wet” and over-hydrated or “dry” and under-hydrated. These additional determinations become additional “vital signs,” including: pulse oximetry, indirect calorimetry/Body Mass Index (BMI), and non-invasive ultrasound determinations of fluid status (including determinations of congestive heart failure). Accordingly, these additional vital sign determinations become more standardized and additionally serve to augment care at this level on-site, much like the pain assessment protocol on a scale of 1 to 10 has become recognized as the “5 th vital sign.” Other innovative technologies, including skin breakdown, fall and aspiration prevention and precautions, and incontinence devices, which likewise provide earlier detection of urinary tract infections, provide earlier warning, and provide enhanced detection for the facility and it's staff, giving residents and their families heightened safety, an improved quality of life, more awareness and assurance for high level of care while residing on-site. The facility reaps additional benefits from having employees and residents that are more apt to be monitored, educated, healthy, and health conscious, particularly as health savings accounts become more popular and incentives for healthy lifestyle approaches become fostered by businesses as well as third parties.
[0051] In one embodiment of the inventive geriatric assisted living care method, kit, and system, a whole new niche and level of care is created within the assisted living setting by bridging the gap between assisted living and nursing home/skilled nursing facility. Due to the “medicalization” of traditional assisted living facilities with the inventive geriatric assisted living care method, kit, and system, traditional long-term care insurance of healthcare insurance may now cover medically complex residents who may now continue to be housed and cared for on-site at a higher level of care.
[0052] In another embodiment, the services administered by the medical center staff are available 24 hours a day, 7 days a week by access to the medical center staff via in-person communication, communication via telephone, communication via pager, communication via voice mail, and communication via fax.
[0053] The medical center staff can also contribute to the education of the facility caregivers, third party caregivers, residents, family members of residents, and community by coordinating on-site health fairs, on-site lab testing stations, wellness lectures, vaccine promotion and implementation programs, and vaccine updates for residents, facility caregivers, and integrated third party caregivers.
[0054] The organization of the medical center staff as an educational service provider may also include the coordination of satellite assisted living and residential care clinical teaching sites, thereby extending geriatric, hospice and palliative care medical training and research. Such teaching sites may include affiliations with educational institutions such as universities and medical centers. Lectures can be provided on geriatric and aging topics; for example, the biology of aging, fall prevention and fractures, osteoporosis prevention, and proper hydration, physiology of aging, geriatric sexuality, principles of geriatrics and gerontology, physical rehabilitation, geriatric syndromes, neuropsychiatry, aging and the various organ systems, immobility, failure to thrive and frailty, psychotropic medication management, urinary tract infections, agitation and psychosis, antibiotics, unexplained weight loss, proper diets, diabetes mellitus management, role of exercise, pressure ulcers, skin and wound care, stress reduction, obesity, wellness and healthcare maintenance and screening, emergency responses including “911” responses, management of diarrhea and constipation, sleep-related breathing disorders and insomnia, resident's rights, dementia, delirium, depression, pain management, cardiac medications, gastrointestinal medications, role of hospice and palliative medicine and end-of-life care, role of vaccination programs, infection control measures, and signs of elder abuse.
[0055] The medical center staff can also coordinate and ensure certification and recertification by offering programs to facility caregivers, scheduling programs, or notifying caregivers of relevant programs. For example, care managers may be offered, scheduled for, or notified of a program to be certified or recertified to administer medication, manage incontinence, or detect urinary tract infections.
[0056] The medical center staff further assists in the creation of procedures and protocols including, but not limited to procedures and protocols for treating residents, and maintaining, storing, creating and retrieving records regarding residents. Such procedures and protocols can be stored electronically or on paper. The medical center staff further assists in tracking certification and licensing requirements and whether such requirements are met by the individuals in the medical center staff and any members of the interdisciplinary team that are employed by the facility or who have engaged with the facility as an independent contractor. The organization of medical center staff for the administration of a broad level of medical care to residents may also provide for a cost-efficient method of treatment for residents wherein long-term care insurance or other healthcare insurance coverage and/or medical tax breaks are now available for payment of all or a portion of the medical care administered by the medical center staff.
[0057] In one embodiment of the inventive method of the delivery of care, the medical center staff, including the physician medical director and mid-level practitioner, such as a nurse practitioner and/or physician's assistant, lead interdisciplinary on-site teams. For example, this team leader model:
1. Provides medical decision input and support to one or more of the following individuals such as the facility executive director, the wellness nurse director, the dementia director, the corporate medical director, the corporate physicians assistant, the corporate nurse practitioner, and the governing body of the facility; 2. Provides leadership of a clinical interdisciplinary team on a weekly basis and administrative team meetings on a monthly basis with facility caregivers; 3. Implements resident care policies and procedures; 4. Coordinates medical care and treatment, including policies and directives regarding attending physicians; 5. Assists in developing systems so that all necessary medical services provided to residents are adequate and appropriate; 6. Consults regarding the facility's quality assurance process for the assurance of quality medical and medically-related care; 7. Advises the facility administration including the facility executive director, the corporate medical director, the corporate physicians assistant, the corporate nurse practitioner, and the facility governing body of current medical issues affecting residents of the community; 8. Provides 24 hour per day “on-call” availability and medical response to urgent or emergent facility needs; 9. Participates in the development and presentation of educational programs and health fairs for residents, families, and the public (including training and re-training modules for staff); 10. Participates in employee health, welfare, and safety of employees (including on-site wellness physicals, Purified Protein Derivative (PPD) testing, and vaccination programs); 11. Helps articulate the facility's mission to the community and represent the facility in the community; 12. Provides medical leadership for geriatric research and development, clinical training, preventive medicine (including wellness principles), and medical information in the assisted living setting; 13. Participates in establishing policies and procedures for assuring that the rights of individual residents are respected and enhanced (including reducing physical and chemical restraints); 14. Reviews the medication administration record (MAR) of residents in the community and participates in quarterly meetings with the clinical pharmacist, a pharmacy liaison from the fulfillment pharmacy group; 15. Provides admission or updated Mini Mental Status (MMSE) Testing, Geriatric Depression Screening, Geriatric Suicidal Ideation Inventory, Acquired Involuntary Movement System (AIMS) Testing, and admission or annual Residential Care Facility Forms (RCFE's) as needed; and 16. Provides on-site Health Insurance Portability and Accountability Act (HIPAA) and Occupational Safety and Health Administration (OSHA) compliance manuals and officers.
[0074] With the medical center staff serving as an educational hub by extending geriatric on-site training to physician's assistant students, nurse practitioner students, medical students, and facility caregivers, a campus-like atmosphere is created which fosters additional social networking through computer/internet involvement, resident participation in local college courses, and promotion of social activities and enhanced community and support-group building. This assists in the overall care of the residents as it provides for exposure and interaction with the greater community, in contrast to the often isolating setting of an assisted living facility. Residents are less isolated and are stimulated by the positive interaction with others.
[0075] In another embodiment, the method of delivering care includes the administration of care by the medical center staff to facility caregivers. The administration of care to facility caregivers may include, but is not limited, to conducting employee physicals, administering vaccines, and addressing work injuries. The overall care of residents is thus enhanced as the health of their caregivers is monitored and improved.
[0076] The invention may also include a kit for organizing comprehensive care to residents of an assisted living facility that includes an organizational chart of the staff of a medical center located within or affiliated with the residential care facility. The medical center may be on-site or in close proximity to the residential care facility. Preferably, the medical center is on-site. The medical center staff may include a physician medical director and one or more physician's assistant or nurse practitioner. The medical center staff may also include one or more medical student, physicians assistant student, or nurse practitioner student. The medical center staff may further include a medical assistant. The kit may also include an organizational chart detailing the relationship of the medical center staff with an interdisciplinary team of facility caregivers and third party caregivers. The relationship is one where the medical center staff is in communication with the interdisciplinary team of facility caregivers and third party caregivers such that they are all integrated and working together in the delivery of care. Two or more written procedures for directing the medical care offered by the medical center are also included. For example, the written procedures may include a procedure for the first time the medical center staff examines a resident, a procedure for subsequent examinations, a procedure for general management of the medical center, and a procedure for scheduling appointments. A sample procedure for scheduling appointments is one that has six steps comprising:
1. Nurse, such as a wellness nurse, keeps appointment book to make appointments when doctor is not at facility. 2. New patients are all scheduled for one-hour appointments. 3. Nurse distributes new patient packets to patients and/or family members who need a physician. 4. Returning patients are scheduled for 30 minutes. 5. Employee physicals are scheduled for 30 minutes. 6. When office hours are in session, the medical assistant will make follow-up appointments.
[0083] Another sample procedure may outline the duties of a medical assistant:
1. Get mail out of mail box. 2. Get appointment book from nurse, such as a wellness nurse, and make sure all patient medication lists are given to you for the patient's being seen that day (the wellness nurse does this for you—if not you may photocopy them yourself); staple the medication lists and put in prescription section of patient's chart. 3. Make copy from appointment book and distribute to relevant on-site medical staff. 4. Pull charts for patient's being seen that day. 5. Attach a “superbill” template to the front of the patient's chart and put the patient's name and date on the bill. 6. Place a “progress note” template in the progress note section in the chart and put each patient's name and date on it unless they are a **NEW patient, in this use the “complete progress note” template (three pages). 7. On the backside of progress note divider, write “see medication list” and today's date. 8. Open mail and put on desk for review by the physician's assistant or nurse practitioner and the physician medical director. 9. Get all necessary paperwork ready in chart depending upon reason for visit (i.e. lab work, x-rays, hospital notes, consultation referral notes and/or other relevant templates). 10. Make copies when needed for file folders and for the nurse practitioner, the physician's assistant, and/or the physician medical director.
[0094] The kit may also include one or more written procedure for hosting health fairs or wellness lectures. These fairs promote the transmission of health information to residents. The kit may further include one or more written procedures for hosting lab technicians at the residential care facility. Such visits offer an easy way for residents to receive lab work. The kit may further include one or more written procedure for hosting vaccine implementation programs. These programs aid in the direct promotion of vaccine education and timely administration. The kit may also include one or more written procedure for coordinating satellite assisted living facility clinical teaching sites. The kit may further include one or more written procedure for tracking certification and licensure of the medical center staff and the facility caregivers. The kit may also include one or more written procedure for administering care to facility caregivers, including but not limited to conducting employee physicals, administering vaccines, and addressing work injuries.
[0095] The invention may also include a system for organizing care provided to residents of an assisted living facility comprising the ability to store personal and medical data pertaining to a resident, the ability of the medical center staff to access and update the data, and the ability of the facility caregivers and third party caregivers to access the data, wherein the data of the resident is the most up-to-date data available and access by the medical center staff, facility caregiver, or third party caregiver allows it to offer care based upon this comprehensive set of up-to-date information. Accessibility of information is in accordance with applicable laws such that the privacy of the resident is lawfully maintained. The information is also stored and transmitted in accordance with HIPAA. Storage and access of the data may be via a computer system. Access may be via a computer on a computer network. Storage may be via a server. The server is capable of receiving information from each of the medical center staff, facility caregiver, and third party caregiver; for example, information regarding incidents related to health and safety of the residents, whereby the server receives, transmits, and retains information input. The medical center staff and authorized facility caregivers and third party caregivers can then access the information to facilitate the administration of care, and the monitoring, and management of the facility and residents. Employee Health and Safety including accidents and incidents are likewise overseen, monitored, and tracked. The system may further include proprietary geriatric templates, including, but not limited to, progress notes, comprehensive wellness exams, geriatric depression screening, MMSE's, and AIMS Testing. These templates provide a standardized mechanism for the input of care information. The standardization of information provides for more efficient care whereby information is easy to read, input, and extract.
[0096] The system may include the ability of the medical center staff to track certification and licensure of the medical center staff and the facility caregivers. The system may also include the ability of the medical center staff to offer educational programs to one or more third party assisted living facility.
[0097] Implementation of the inventive, method, kit, and/or system provides treatment of aging residents on-site at a higher level of care in the assisted living setting throughout the continuum of their lives, even when the spectrum of inevitable progressive functional and/or cognitive decline occurs with aging with the concomitant loss of key instrumental activities of daily (“IADL's”) and activities of daily living (“ADL's”). While residing within the assisted living or residential care facility implementing the inventive method, kit, and/or system, aging residents who develop resultant medical complexity, functional decline, progressive dementia, and life-limiting illness (requiring palliative or end-of-life care), can continue to be well cared for on-site. Moreover, as a byproduct of the inventive enhanced on-site assisted living and residential care, with earlier, timely interventions becoming the “norm,” costly and disruptive transfers to emergency rooms and acute hospitalizations can also be avoided.
[0098] Third party payors, who heretofore have been “carved out” of the assisted living arena, may now participate in this new inventive paradigm of enhanced geriatric assisted living care through the extension of long-term care policies, healthcare coverage, and/or medical tax breaks for residents in a medically augmented assisted living environment. Geriatric training is likewise extended and enhanced utilizing the inventive geriatric assisted living method, kit, and/or system, wherein the medical center is an educational hub facilitating training of the next generation of geriatric primary care physicians, physicians assistants, nurse practitioners, and nursing students. This training according to one embodiment of the invention advantageously serves to develop professional expertise in an area projected to have a significant shortfall of capable professionals.
[0099] The aforementioned embodiments further provide more cost-efficient, streamlined and integrated care at an assisted living residential care facility level. The methods, kit, and system provide for higher acuity care for medically complex facility residents. Implementation of the methods, kit, and system allow for residents to stay at the facility, lessening transfer to other skilled nursing facilities, nursing homes, or hospitals; thereby achieving a better outcome of care, decreased disorientation, and decreased medication error.
[0100] Implementation of the methods, kit and system may also decrease risk associated with running a facility, allowing aging residents to remain on-site as they are cared for throughout the continuum of their care, which now may include inevitable medical complexity, progressive dementia, and life-limiting illness requiring hospice and palliative care.
[0101] While the description above refers to particular embodiments of the present invention, it should be readily apparent to people of ordinary skill in the art that a number of modifications may be made without departing from the spirit thereof. The presently disclosed embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
BRIEF DESCRIPTION OF THE FIGURES
[0102] FIG. 1 is chart showing the organization and integration of the medical center staff with the facility caregiver and the third party caregiver in accordance with an embodiment of the present invention.
[0103] FIG. 2 is a chart showing storage of medical and personal data and templates, and the ability to access and update the data and templates by various individuals in accordance with an embodiment of the present invention.
[0104] FIG. 3 is a chart of a sample kit in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0105] The invention is a method, system, and kit for the delivery and administration of cohesive and comprehensive care to residents of an assisted living facility.
[0106] In one embodiment, as depicted in FIG. 1 , the medical center staff 20 is intimately connected with a facility caregiver 40 and an integrated third party caregiver 60 . The medical center staff 20 serves as the center of an resident's care meaning that it is in contact with one or more facility caregiver 40 and third party caregiver 60 to ensure that the delivery of care to a resident is streamlined, comprehensive, and cohesive. Organizing the medical center staff 20 as the hub of care serves to deliver the most comprehensive and cohesive care to a resident.
[0107] As depicted in FIG. 2 , the medical and personal data is stored in a central location 80 , preferably on a server. Geriatric templates may also be stored in a central location 80 , preferably on a server. The data 80 is accessible and updateable by the medical center staff 20 , the facility caregivers 40 , and the third party caregivers 60 .
[0108] As depicted in FIG. 3 , one embodiment of a kit 100 of the present invention is shown containing an organizational chart of the medical center staff of a medical center associated with the assisted living facility, and preferably located within the facility for providing medical care to residents, an organizational chart of the medical center staff and their integration with an interdisciplinary team of one or more facility caregiver and third party caregiver for providing comprehensive care, including medical and social care to residents, and two procedures for directing medical care offered by the medical center.
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The present invention relates to methods and tools for the delivery and administration of care to residents of an assisted living facility. The health of elderly residents almost always declines after moving to an assisted living facility, and up until now, a high level of medical care and the integration of care with multiple caregivers was not provided to the residents. Care administered according to the method of the invention is cohesive and comprehensive, and includes a high level of medical care for acutely ill residents. In one aspect of the invention, the method defines components for the delivery of care and their organization. In another aspect of the invention, the method and its related protocols and procedures is implemented in a kit for dissemination to all facilities offering residential care or assisted living services to achieve efficient delivery and administration of care to residents. In yet another aspect of the invention the method is integrated into a system capable of adoption by residential care or assisted living facilities to achieve streamlined, efficient delivery of care to its residents.
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This application is a continuation, of application Ser. No. 775,525, filed Sept. 13, 1985 now abandoned.
BACKGROUND OF THE INVENTION
The invention relates to a circular knitting machine for the production of knit goods having combed-in fibers with a preselected fiber density comprising a rotatable needle cylinder having needles with needles hooks, a means for driving the needle cylinder during knitting cyles, and a card which has means for feeding fibers, a comb-in zone through which the needles pass for contactless reception of fibers, and a teasing cylinder rotating at high speed which picks up the fibers from the feeding means and yields them to the comb-in zone.
In methods and circular knitting machines of this kind (U.S. Pat. Nos. 4,458,506 and 4,546,622) the fibers, in contrast to conventional methods and circular knitting machines (U.S. Pat. No. 3,709.002) are combed contactlessly into the needle hooks, the term "contactlessly" meaning that the needle hooks do not pass through teasing hooks. The transfer of the fibers to the comb-in zone is performed as in circular knitting machines with conventional combs under conditions synchronous with the rotation of the needle cylinder. The term, "synchronous conditions", is to be understood to mean that, at any constant rotatory speed of the needle cylinder, the fibers are always delivered to the comb-in zone at a preselected, constant amount of fibers per unit time, so as to produce goods having a preselected, constant fiber density. On the other hand, the amount of fiber fed to the comb-in zone changes synchronously in the case of changes in the needle cylinder rotatory speed, in order that, in the event of reductions or increases in the needle cylinder rotatory speed, correspondingly less or more fibers will be delivered to the comb-in zone, thereby assuring that the preselected fiber density will be achieved at any rotatory speed of the needle cylinder, i.e., especially during the execution of start and stop cycles. If the feed of fiber to the teasing cylinder is by means of feed rolls, for example, "synchronous conditions" means that the feed rolls and the needle cylinder are driven from a single, main drive through gears, belts, rollers or the like, so that the ratio of their rotatory speeds is the same at all rotatory speeds of the needle cylinder, and that, independently thereof, the teasing cylinder is driven always at the same high rotatory speed at all needle cylinder speeds.
Experiments on such circular knitting machines with contactless fiber feed have surprisingly shown that, during those phases in which the needle cylinder is subjected to abrupt changes of rotatory speed, such as is the case especially during the start and stop cycles and during "tip" operation, undesirable deviations from the preselected fiber density can result, which lead to thick and thin areas in the finished knit goods. "Thick and thin areas" in this connection refers to those points in the finished goods at which the fiber density is lower or higher than the preselected fiber density. The length of the thick and thin areas appears to be dependent upon a number of factors, such as the length of time for which the needle cylinder is stopped, the fiber length or the titer of the fibers.
The invention is therefore addressed to the problem of improving the circular knitting machine of the kind defined such that thick and thin areas will be largely avoided. In particular, those thick and thin areas are to be avoided such as are observed after the needle cylinder has been stopped.
The knitting machine of this invention is characterized by first protective means which can be actuated for preventing fibers from being fed to the needles, by second protective means which can be actuated for preventing fibers from being removed from the needles, and by actuating means for actuating said first and second protective means such that the preselected fiber density of the knit fabric is substantially maintained constant also when the needle cylinder is stopped and again started between successive knitting cycles.
The invention brings with it the advantage that, when the needle cylinder is stopped, those fiber tufts are retained which have already been inserted into needles, but remain with the needles in the comb-in zone for the duration of the stoppage. Since these fiber tufts are in opened needle hooks, their density might become accidentally either increased or decreased, and this is effectively prevented by the protective device of the invention. In accordance with the invention, therefore, retention of the fiber tufts means that, during the stoppages of the needle cylinder, no additional fibers are fed to and no fibers are removed from the needles in the comb-in zone. Thus it is possible to prevent a number of the thick and thin areas which can be observed when the protective device is lacking.
Additional advantageous features of the invention will be found in th subordinate claims.
The invention will now be further explained in conjunction with the appended drawing of a preferred embodiment.
SUMMARY DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic longitudinal cross section taken through a circular knitting machine according to the invention,
FIGS. 2 and 3 are longitudinal sections taken through the area surrounding the comb-in zone of the knitting machine of FIG. 1, on an enlarged scale and in two different positions,
FIG. 4 is a perspective diagrammatic representation on a larger scale of the area surrounding the comb-in zone of the circular knitting machine of FIG. 1, and
FIG. 5 is the block circuit diagram of a control system for the circular knitting machine of FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENT
In FIG. 1, U.S. Pat. Nos. 4,458,506 and 4,546,622, a circular knitting machine for the production of high-pile knit goods 1 contains a rotatable needle cylinder 2 in which vertically displaceable knitting needles 3 with hooks 4 are mounted, which are moved up and down in the area of at least one knitting system by means of stationary cam parts 5a and 5b, for the purpose of producing a base knit fabric from the yarns that are not shown. The fibers are loosened up and combed into the knit fabric by means of at least one comb 6, which consists, for example, of a feed system consisting, for example, of two feed cylinders 7a and 7b for feeding a condensed sliver or fiber band 8, a teasing cylinder 10 intended to break up the fiber band 8 into individual fibers 9, and a comb-in zone 11 through which the knitting needles 3 and their hooks 4 pass in order to pick up the fibers 9.
The teasing cylinder 10, which can rotate in the direction of an arrow P, is covered on its circumference with a clothing 13 bearing outwardly projecting hooks 14. The teasing cylinder 10 is driven at a substantially greater circumferential speed than the feed cylinders 7, and therefore pulls the fiber band 8 apart in single fibers 9.
To prevent the fibers picked up by the teasing hooks 14 from being flung back out of the hooks, despite the great effective centrifugal forces acting on them due to the high speed of the loosening cylinder 10, the comb 6 has a shroud 15, which is preferably a part of a fully enclosed casing 20 surrounding the teasing cylinder 10 and the comb-in zone 11, and is situated opposite the outer circumference of the teasing cylinder 10, and contains an entry 16 for the fiber band 8 fed by the feed cylinders 7 and an exit opening 17 through which the fibers 9 can be fed into the comb-in zone 11. The shroud 15 then defines the outside of a teasing and accelerating section 18 beginning directly at the entry opening 16 and indicated by an arrow, within which the shroud 15 is at a small, but otherwise constant distance of, for example, less than one millimeter, from the tops of the teasing hooks 14 of the teasing cylinder 10, so that the fibers cannot come off the teasing hooks 14. The teasing and accelerating section 18 is then followed, in the direction of rotation of the teasing cylinder, by a teasing section 19 indicated by an arrow, which ends at the exit opening 17 and is at a distance from the tips of the teasing hooks 14 which gradually increases in the direction of rotation to a value of, for example, several millimeters. Therefore, the fibers 9 can be loosened in this section 19 by the centrifugal force, entrained tangentially in the air stream produced by rotation of the teasing cylinder, and combed into the knitting needles lifted by the cam parts 5 in the comb-in zone, without coming in contact with the teasing hooks 14.
With the teasing cylinder 10 there is associated a drive independent of the conventional needle cylinder drive, in the form of a motor 33 which drives the teasing cylinder 10 at a speed that is constant at all knitting machine speeds, or can be adapted to a certain extent to the momentary knitting machine speeds and/or the properties of the fibers involved. The motor 33 can be a reversible-pole motor having at least two rotatory speeds.
In known circular knitting machines of this kind (U.S. Pat. Nos. 4,458,506 and 4,546,622), the feed cylinders 7 are driven synchronously with the needle cylinder rotatory speed. According to the invention, however, a drive 34 is provided--a motor for example--which is connected on the one hand by a gear 35 to the crown gear of the needle cylinder 2, and on the other hand by additional gears 36, a shaft 37 and a belt drive 38 to one input of a differential gearing 39. Another input of this differential gearing 39 is connected by another belt drive 40 to the output shaft of a servo motor 41. On the output shaft of the differential gearing 39 there is fastened a belt pulley 42 which is connected by a belt 43 to another belt pulley 44 on whose shaft there is fastened a worm 45. This worm is engaged in the usual manner with a worm gear which is mounted on one of the shafts of the feed cylinder 7 and serves to drive the latter. On the basis of the drive just described, it is possible to drive the feed cylinders 7 either synchronously with the needle cylinder if the servomotor 41 is stopped, or, if motor 34 is stopped, synchronously with the rotatory speed of the servomotor 41, or, if both motors 34 and 41 are running, the feed cylinders can be driven at a resultant speed. If the servo motor 41 is a reversible motor, the feed cylinders can be driven either at a greater or at a lower rotatory speed than the momentary rotatory speed that can be produced through the gears 35, 36 and 38 and is synchronous with the needle cylinder speed, since the differential gearing will add or subtract the two input speeds depending on the direction of rotation of the servo motor 41. The differential gearing thus constitutes a means for the interruption and restoration of synchronism between the feed means and the needle cylinder.
According to FIGS. 2 and 3, the casing 20 has in the area adjacent the needle backs a fixed fiber guiding plate 47 whose end at the comb-in zone 11 is of streamlined shape. The fiber guiding plate 47 is disposed such that, in back of the needles 3, and between it and an imaginary cylindrical surface 47 in which the tips of the teasing hooks 14 move, a wedge-shaped gap 49 is formed (U.S. Pat. No. 4,546,622). Furthermore, in back of the fiber guiding plate 47, in the direction of rotation of the teasing cylinder 10, there is provided an ejection flap 50 which is articulated on a pivot pin 51 on the fiber guiding plate 47 and is preferably a part of the latter. The other end of the ejection flap 50 adjoins, along a sloping junction, a fixed casing part 52, the components 47, 50 and 52 extending preferably at least over the width of the teasing cylinder. The ejection flap 50 has a lug 53 which is joined to an actuator 55 which consists, for example, of a solenoid coil with a plunger 54 which can be extended and retracted and is linked to the lug 53. This actuator 55 is disposed laterally beside the teasing cylinder 10 and is pivoted on a pivot pin 56 on a stationary machine part. In the disengaged position, e.g., when the plunger 54 is retracted, the fiber guiding plate 47 and the closed ejection flap 50 form a substantially continuous fiber guiding surface (FIG. 2) which prevents fibers from being thrown off the teasing hooks 14 and produces a combing out and orientation of the fiber tufts which have already been laid into the needles but are still in the comb-in zone 11. If, however, the plunger 54 is pushed out of the solenoid 55 by means of an electrical signal, the rear end of the ejection flap 50 is rocked in the manner shown in FIG. 3 radially away from the teasing cylinder 10 to the working position. This results in the formation of an ejection opening 58 virtually tangential to the circumference of the teasing cylinder 10, and any fibers that are still on the teasing hooks 14 are released by the centrifugal forces and then are, for example, aspirated by a central aspirating system.
Preferably ahead of the needles 3, in the direction of rotation of the teasing cylinder 10, there is disposed in accordance with the invention a blocking means 60 for blocking the needle hooks 4 that are in the comb-in zone 11. This blocking means 60 serves to block off the open needle hooks 4 if necessary, so that they will not pick up any more fibers. In accordance with FIGS. 1 to 3, the blocking means 60 is a thin, e.g., 0.15 mm thick, plate extending preferably at least over the width of the teasing cylinder 10 and guided displaceably in a slotted guide 61 which is provided in a wall portion 62 (FIGS. 2 to 4) surrounding the teasing cylinder. The slotted guide 61 runs from one exit end 63 of the wall portion 62 situated ahead of the comb-in zone in the teasing cylinder's direction of rotation, substantially tangentially to the teasing cylinder 10, and toward a gap 64, which is defined on the one hand by the upper ends of the needle hooks 4 raised to receive fibers, and on the other hand by the cylindrical surface 48, and whose width is slightly greater than the thickness of the blocking means 60. The end of the blocking means 60 protruding from the exit end 63 is linked to one end of a rocking arm 65 which is pivoted in its central portion at 66 and is linked at its other end to an actuator 68 which consists, for example, of a solenoid having a plunger 67 linked to the rocking arm 65, and is pivotally mounted on a fixed part 69 of the machine. By feeding an operating signal to the actuator 68, the blocking means 60 can therefore be moved either to the disengaged position shown in FIG. 2 in which it releases the gap 64 and is withdrawn far into the slotted guides 61, or it can be moved to its working position as shown in FIG. 3. In this working position, the end of the blocking means 60 associated with the needles extends both through the slot 64 and also through the wedge-shaped gap 49 that follows in the direction of rotation of the teasing cylinder. Due to the fact that the blocking means 60 extends through the slot 64, the open needle hooks 4 are blocked such that, ahead of the comb-in zone 11, fibers released from the card teasing hooks 14 are not combed into the needle hooks 4. Since the blocking plate extends into the wedge-shaped gap 49, however, the fiber tufts 57 combed into the needle hooks are protected against the teasing hooks 14 regardless of the fiber length selected in the individual case, and therefore they cannot be attacked by the teasing hooks and pulled out of the needle hooks. The blocking means 60 is thus a component of a protective means for preserving the fiber tufts 57 combed into the needles 3 situated in the comb-in zone. At the same time the section covering the needle hooks and the section covering the fiber tufts 57, of the blocking means 60, could also be separated from one another and connected to different actuating means. Also, the rocking arm 65 is shown much shorter than it would be, and actually it is about as long as is necessary to achieve the desired length of movement of the blocking element 60.
FIG. 5 shows a control apparatus for the circular knitting machine described in conjunction with FIGS. 1 to 4. It contains a power supply 71 which provides current to all electronic and electromagnetic components, especially a controller 72 for the servo motor 41 and a controller 73 for the drive 34 of the circular knitting machine, and is also connected to a main switch 74. The controller 72 for the servo motor has an input connected to the power supply 71 and an output connected to the servo motor. Another input is connected to a starter switch 75, a switch 76 being inserted into the line running to the latter, which can be brought by an actuator 77 from its normal, closed position to an open position. Another input of the controller 72 is connected to two switches 78 and 79 which are in series. Switch 78 can be brought by an actuator 80 from its normal, closed position to an open position, while switch 79 can be brought by an actuator 81 from its normal, open position to a closed position. An additional input of the controller 72 is connected to the moving contact of a switch 82 which can be turned to any of three solid contacts which are connected each with a potentiometer 83. The other terminals of this potentiometer 83 are connected to three fixed contacts of an additional switch 84, which also has a contact that can be moved to one of the three fixed contacts. The switches 82 and 84 and the potentiometer 83 form a preselection circuit and serve to provide the controller 72 with, for example, three individually selectable rotatory speeds for the rotation of the servo motor 41 in the forward direction. Another input of the controller 72 is finally connected by a line 85 to the moving contact 86 of a switch whose three fixed contacts are connected by potentiometer 87 to three fixed contacts of a switch 88 such that, with the switches 86 and 88 and the potentiometers 87, three individually presettable rotatory speeds, for example, can be selected for the servo motor 41 when it runs in the reverse direction.
The starter switch 75 is connected by an adjustable timer 89 to the fixed contact of a switch 90. The moving contact of this switch 90 is connected to the controller 73 for the motor 34 of the needle cylinder. This motor 34 has an indicator in the form of a tachometer generator 91 which, in the usual manner, consists of a dynamo which provides at its output a voltage which is proportional to the rotatory speed of the motor 34. The output of a reference standard 92 is connected to an additional input of the controller 73. The reference standard 92 contains an ordinary amplifier 93 to whose one input a potentiometer 94 is connected and whose output is connected to the moving contact of a switch 95 whose two fixed contacts are connected each through a resistance 96-97 to the input of an additional amplifier 98.
The output of the tachometer generator 91 is connected to the input of a comparator 100 to whose output is connected an actuator, 101 which serves to shift the moving contact of switch 95 from the one to the other fixed contact of this switch.
The controller furthermore contains a manually operated stop switch 102 and, if necessary, at least one automatically operating stop switch 103, for example in the form of a shutoff commonly used in circular knitting machines, which is tripped in the event of thread breakage, needle breakage or the like. The two switches 102 and 103 are connected to an actuator 104 which serves to shift the normally closed switch 90 to an open position. The actuator 81 is connected to the output of a comparator 105 whose input is connected to the output of the tachometer generator 91. Otherwise, the free terminals of switches 75, 84, 88, and 102 and 103 of the potentiometer 94 are connected to the power supply or to some other appropriate source of current or voltage.
Lastly, the controller of FIG. 5 has two additional comparators 106 and 107. The output of comparator 106 is connected on the one hand to one input of each of the actuators 55 and 68 and on the other hand to the actuator 77 of switch 76, while the comparator 107 is connected on the one hand with an additional input of each of actuators 55 and 68 and on the other hand to the actuator 80 of switch 78. The inputs of the comparators 106 and 107 are connected to the output of the tachometer generator 91.
The switches 76, 78, 79, 90 and 95 and their associated actuators 77, 80, 81, 101 and 104 can consist of purely electronic components, but also they can be electromechanical components, e.g., reed contacts operated by relays.
In the control system described, the following adjustments are possible:
Depending on the type of fiber to be used, which can vary in regard to fiber length, titer or the like, first the ganged pairs of switches 82-84 and 86-88 can be set such that the servo motor 41, whether turning forward or backward, will run at a rotatory speed determined according to the type of fiber. The rotatory speeds required in each case are to be determined in preliminary tests with the fibers to be used, and if necessary can be recorded in tables. Experiments have shown that, in most practical cases, three different rotatory speeds forward and three in reverse will suffice, and that these speeds can be associated with fiber lengths up to 25 mm, between 25 and 40 mm, and 40 to 80 mm of length. This gives the advantage that the potentiometers 83 and 87 can be set one time, and, when the type of fiber changes, only switch pairs 82-84 and 86-88 will need to be changed. Furthermore, the timer 89 can be adjusted to the time desired in the particular case. The timer 89 determines how long a time the servo motor 41 is to be energized before turning on the motor 34 of the knitting machine. Here, again, the adjustment can be determined on the basis of the type of fiber and recorded in tables. It would also be possible to provide several fixed timers, each associated with one type of fiber. It is desirable, however, to adjust the timer to a sufficiently long period of time to permit a sufficiently long preliminary feed by the servo motor 41 for all of the types of fibers that are involved. An additional adjustment is offered by the potentiometer 94 which is associated with the reference standard 92. The reference standard 92 establishes through the controller 73 the accelerations with which the speed of the needle cylinder is to be increased during start-up, and on the other hand it establishes the maximum rotatory speed, i.e., the production speed which the needle cylinder is to reach. The production speed can be adjusted with the potentiometer 94. Lastly, it is possible to set the rotatory speed of the motor 33 driving the teasing cylinder 10, through an additional potentiometer not shown, or through a switch.
The control system described operates as follows:
By operating the main switch 74, first the motor 33 driving the teasing cylinder 10 and the power supply are turned on to supply power to the control system. By means of an interlock, which is not shown, provision can be made such that operation of the starter switch 75 will not be possible until the teasing cylinder has reached its nominal rotatory speed. The blocking means 60 and the ejection flap 50 are during this time in the working position represented in FIG. 3, while the needle cylinder 2 is stopped and the different switches assume the positions seen in FIG. 5. The result is that, in the area of the entrance opening 16, the teasing cylinder 10 teases out the part of the condensed sliver 8 that extends into the range of action of the teasing hooks 14. The fibers pulled out of the sliver in this manner are accelerated out of the teasing hooks 14 in the area of the releasing section 19, but, on account of the extended blocking means 60, are unable to enter into the needle hooks 4. Consequently, these fibers are transported on over the needlehooks and then ejected through the open ejection flap 50. At the same time, the blocking means 60 prevents fiber tufts 57, which have already been laid into the needle hooks in a preceding knitting action, from being pulled out of the needle hooks by the suction of the teasing cylinder 10 or by the interference of the teasing hooks. The fiber tufts 57 already laid in the needles that are in the comb-in zone therefore are retained, so that thick and thin areas are prevented when the needle cylinder starts up.
After the teasing cylinder 10 has reached its nominal speed, the starter switch 75 is closed, thereby delivering power through the closed switch 76 and the controller 72 to the servo motor 41 to make the latter run in the forward direction at a speed depending on the position of the switch pair 82-84 and the potentiometer 83. As a result, the feed rolls 7 are set in rotation and the portion of the fiber sliver partially torn apart by the teasing cylinder 10 is replaced at the entry 16. Thus, a higher rate of feed of fibers than the synchronous rate is fed to the comb-in zone 11, because in conventional high-pile knitting machines the feed cylinders are at rest as long as the needle cylinder is at rest. This process, which is known as forefeeding the fibers and is intended for the prevention of thin areas caused by start-up, likewise takes place when the needle cylinder is stopped, and lasts until the timer 89 emits a signal. When this signal appears, the sliver or sheet of fibers situated on the teasing cylinder 10 is again built up to the extent that is necessary for the knitting procedure that follows.
The signal from the timer 89 runs through the switch 90 and the controller 73 to start the motor 34 driving the needle cylinder, preferably with an initial, comparatively great start-up acceleration established by the reference standard 92. This start-up acceleration results when the moving contact of switch 95 is connected to the resistance 97 which, with the capacitor 99, forms an RC circuit and results in a voltage rise at the output of the amplifier 98 corresponding to the first section of the U/t curve represented in a block 108 of the reference standard 92. The needle cylinder thus begins to rotate, and the tachometer generator 91 delivers a voltage proportional to the momentary speed of the motor 34, which is fed to the comparators 106 and 100 which were activated in the start-up cycle. When this voltage attains a relatively low value detected by the comparator 106, the comparator 106 emits a signal which is delivered to the actuator 77 which then opens the switch 76 thus turning off the servo motor 41. At the same time the output signal from the comparator 106 is delivered to the actuators 55 and 68, thereby shifting the ejection flap 50 and the blocking means 60 to the disengaged position seen in FIG. 2. As a result of the shutting off of the servo motor 41, the feed cylinders 7 are then driven at a speed determined only by the motor 34, i.e., a speed synchronous with the needle cylinder speed. The displacement of the ejection flap 50 and of the blocking means 60, however, brings it about that the needle hooks 4 are now released and the ejection opening 58 is closed, so that all of the fibers fed by the teasing cylinder 10 are placed in the needles 3. The synchronous rotation of the feed cylinders 7 now assures that the necessary amount of fibers will be fed. The voltage at which the comparator 106 emits its signal is best selected such that, when the needle cylinder is started, the lowest possible number of needles will enter the comb-in zone before the blocking mean 60 is withdrawn, so as to prevent failure of delivery of fibers to a plurality of adjacent needles. In practical use, the voltage of the tachometer generator 91 can be selected at such a low level that no more than one needle will pass through the comb-in zone without picking up fibers.
The rotatory speed of the needle cylinder now increases with the acceleration preset by the reference standard 92. It can happen that some thin areas will occur in the goods on start-up, which are apparently due to the fact that, if excessively great accelerations occur, the synchronous rotatory speed of the feed cylinders 7 is not sufficient. To prevent such thin areas a changeover to a lower acceleration rate will be made at a needle cylinder speed to be determined by experiment. This is accomplished as follows: when the voltage of the tachometer generator 91 reaches a certain level, corresponding for example to the voltage a in block 108, the comparator 100 will emit a signal and thus by means of actuator 101 will shift the moving contact of switch 95. Consequently, the needle cylinder will then be accelerated at a second, lower rate until it has reached its preset production speed and is maintained at this speed by the controller 73. The lower speed is established in this case by the RC circuit formed by the resistor 96 and the capacitor 99.
If the knitting machine is to be shut off, either the stop switch 102 or the stop switch 103 is operated automatically. When this happens, the comparators 105 and 107 which were inactive during the start cycle are activated and at the same time the two comparators 106 and 100 which were active during the start cycle are rendered inactive. Furthermore, a signal is delivered to the actuator 104 causing it to open the switch 90, thus shutting off the motor 34 and at the same time actuating a magnetic brake to stop the needle cylinder.
The needle cylinder is then braked according to the amount of braking power applied, while the teasing cylinder 10 continues to run at an unchanged speed so that fibers are fed into all needles running through the comb-in zone until the needle cylinder comes to a full stop. Since the feed cylinders 7 are also braked during the stop cycle, the wire hooks 14 in the teasing cylinder 10 now tear a higher percentage of fibers from the fiber sliver projecting into the entry opening 16 than is necessary for the attainment of a uniform knit fabric. The thickened areas thus caused are avoided in accordance with the invention in that, upon the attainment of a preselected needle cylinder speed, the feed cylinders are rotated more slowly than the synchronous speed in order thereby to compensate the oversupply of fibers produced by the teasing cylinder. To this end, the comparator 105 is set to a preselected voltage, so that, upon the attainment of this voltage at the output of the tachometer generator 91, it will emit a signal which will operate the actuator 81 to close switch 79 and thus turn on the servo motor 41, through line 85 and the controller 72, in the reverse direction at a speed predetermined by the setting of the switch pairs 86-88 and the potentiometer 87. Thus the rate of fiber feed in the area of the comb-in zone 11 is reduced to such a level that thick areas in the fabric caused by the shutoff cycle are prevented. The rotatory speed at which the servo motor 41 is to be turned on must be determined by experiment. It can also happen that the servo motor must be turned on when the switches 102 and 103 are actuated, in which case the comparator 105 is to be set to a value just below the production speed or it is to be turned on directly by the switches 102 and 103.
To avoid thick areas from forming in the start cycle, the comparator 107 puts out a signal shortly before the needle cylinder stops; this signal is delivered on the one hand to the actuators 55 and 68 and on the other hand it turns off the servo motor through the actuator 80 and the switch 78 which it opens, so that, when the needle cylinder comes to a stop, the feed cylinders will stop also. The feeding of the output signal to the actuators 55 and 68 has the result of shifting the ejection flap 50 and the blocking means 60 back to their working position shown in FIG. 3, and therefore fibers which might be fed by the still rotating teasing cylinder 10 while the needle cylinder is stopped are not introduced in the needles 3, which are also stopped, but are removed through the ejection opening 58. Thus no more fibers are introduced even into those needles 3 which enter the comb-in zone just before the needle cylinder stops than corresponds to the desired fiber density. At the same time the output voltage of the tachometer generator 91 at which the comparator 107 emits its signal can be selected so as to be so low that only one more needle enters the comb-in zone after the blocking means has been moved forward. Furthermore, provision is made through the output signal of the comparator 107 so that all switches will then reassume the positions shown in FIG. 5.
The invention is not limited to the described embodiment, which can be modified in many ways. For example, it is possible to provide, instead of the blocking means 60, a covering flap suspended pivotally from the side walls of the shroud 15 and bearing at its end adjacent the needles 3 a plate which, when the covering flap turns, is introduced into a gap 109 (FIG. 3) between the shroud 15 and the front sides of the needles for the purpose of blocking their open hooks 4. This covering flap could also be controlled by a solenoid actuator. Instead of the fiber guide plate 47 containing the pivoted ejection valve 50, a fiber guide plate consisting of one piece and displaceable radially and, if desired, also circumferentially of the teasing cylinder 10, can be provided, or a pivoting fiber guide plate simultaneously forming the ejection flap. Such a fiber guide plate would have the advantage that, between the blocking means 60 in its active position and the end of the fiber plate associated with it, a sufficiently wide air aspirating gap could be formed, which would improve the air flow needed for the ejection of fibers. Furthermore, it is possible to provide, instead of the solenoids 55 and 56, other actuating means, e.g., hydraulic or pneumatic cylinder-and-piston systems. The ejection flap 50 can be disposed at a point between the entry opening 16 and the comb-in zone 11 in the direction of rotation of the teasing cylinder 10, and it can be connected, if desired, to an aspirator. In this manner shut-down thickenings can be prevented without requiring a blocking means for the needles, because all of the fibers entering the hooks 14 of the teasing cylinder 10 while the needle cylinder is stopped would be removed through the ejection opening before reaching the comb in zone 11. Furthermore, the pivoting ejection flap 50 can be replaced by a sliding fiber guide plate, which offers advantages especially with regard to access to the parts of the card situated in back of the needles. The over-proportional braking of the feed cylinders 7 performed by means of the servo motor 41 could also be accomplished by means of a remote-controlled clutch (DE-OS No. 21 15 721) by temporarily disengaging this clutch during the stop cycles or withdrawing it pulse-wise, in order thereby to interrupt at least momentarily the synchronous running of the feeding cylinders.
As seen in FIG. 5, it is possible with a small number of different, preset speeds of the servo motor 41 to prevent any and all thick and thin areas. There is also the possibility of replacing the preselecting means formed by the switch pairs 82-84 and 86-88 and potentiometers 83 and 87, with programmed preselecting means which constantly change the speeds of the servo motors on the basis of a predetermined schedule, e.g., a curve, individually attuned to the type of fiber used in the individual case. Accordingly, all of the rest of the circuit elements can be adapted individually to the type of fiber. Provision can furthermore be made for momentarily interrupting the synchronism between the feed means and the needle cylinder, not only in the starting and stopping cycles, but also in the event of any other abrupt speed changes. A momentary interruption of the synchronism can also be brought about by varying the distance between the feed means, e.g., the two feed cylinders 7, and the teasing cylinder 10, or by varying the rotatory speed of the teasing cylinder 10, because the synchronism between the feeding of fibers to the teasing cylinder and the fiber transfer to the comb-in zone resulting in the required fiber density is also affected by these factors.
Those parts of the guard means which serve for the prevention of the disengagement of fiber tufts already held on the needles can also be modified. It is mentioned only by way of example that, to this end, (a) the teasing cylinder could be stopped upon every stop and restart and then started up again or at least it could be braked down, (b) the conditions of flow in back of the comb-in zone could be arranged such that the fiber tufts cannot come in contact with the tips of the teasing hooks 14 when the needle cylinder is stopped, (c) the distance between the teasing cylinder and the needles and/or the fiber guide plate could be increased while the needle cylinder is stopped, (d) teasing hooks could be used which, when the needle cylinder is stopped, are retracted into the teasing cylinder 10, and (e) compressed air or a vacuum could be produced by using teasing cylinders or fiber guide surfaces having screen-like surfaces, in order to keep the fiber tufts away from the card hooks 14.
The above-described controller can accordingly also be used in creep rate operation or for so-called tip operation, in which the needle cylinder is turned each time only briefly by a few needle spaces. In order even here to assure the preselected fiber density it can be necessary to further reduce the speed of the teasing cylinder or the feed rate of the fibers to the teasing cylinder or to sustain the synchronism in the operation of braking down.
Instead of the feed means represented, feed means can be provided which have at least one feed cylinder and a fiber guide plate associated with it (U.S. Pat. No. 3,968,662).
The invention has just been described in conjunction with the example of a single knitting system of a circular knitting machine. In circular knitting machines with a plurality of system, the described card 6 can be associated with each system. At the same time it is possible to drive a plurality of teasing cylinders with a single motor. Also, the term circular knitting machines is to include circular hosiery machines.
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The invention relates to a circular knitting machine for the production of knit goods with combed-in fibers, having a rotatable, needle-bearing needle cylinder and a card which has a means for feeding the fibers, a comb-in zone through which the needles pass for the purpose of contactlessly receiving the fibers, and a teasing cylinder rotating at high speed which takes the fibers from the feed means and yields them to the comb-in zone. To prevent thin areas or thick areas from being produced in the finished goods on account of the contactless fiber loading, the circular knitting machine has a protective device (60) which becomes active in the still state of the needle cylinder for the purpose of retaining the already combed-in fiber tufts (57) in the needles (3) which are in the comb-in zone in the still state of the needle cylinder.
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BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention generally relates to flextensional piezoelectric transformers and actuators, and more particularly, to a method of manufacturing a flextensional multi-layer piezoelectric transformer/actuator by cofiring the ceramic composition with the electrode forming metallization.
2. Description of the Prior Art
Wound-type electromagnetic transformers have been used for generating high voltage in internal power circuits of devices such as televisions or in charging devices of copier machines which require high voltage. Such electromagnetic transformers take the form of a conductor wound onto a core made of a magnetic substance. Because a large number of turns of the conductor are required to realize a high transformation ratio, electromagnetic transformers that are effective, yet at the same time compact and slim in shape are extremely difficult to produce.
To remedy this problem, piezoelectric transformers utilizing the piezoelectric effect have been provided in the prior art. In contrast to the general electromagnetic transformer, the piezoelectric ceramic transformer has a number of advantages. The size of a piezoelectric transformer can be made smaller than electromagnetic transformers of comparable transformation ratio. Piezoelectric transformers can be made nonflammable, and they produce no electromagnetically induced noise.
Materials exhibiting piezoelectric and electrostrictive properties develop a polarized electric field when placed under stress or strain. Conversely, they undergo dimensional changes in an applied electric field. The dimensional change (i.e., expansion or contraction) of a piezoelectric or electrostrictive material is a function of the applied electric field.
The ceramic bodies employed in prior piezoelectric transformers take various forms and configurations, including rings, flat slabs and the like. A typical example of a prior piezoelectric transformer is illustrated in FIG. 1 . This type of piezoelectric transformer is commonly referred to as a “Rosen-type” piezoelectric transformer. The basic Rosen-type piezoelectric transformer was disclosed in U.S. Pat. No. 2,830,274 to Rosen, and numerous variations of this basic apparatus are well known in the prior art. The typical Rosen-type piezoelectric transformer comprises a flat ceramic slab 10 which is appreciably longer than it is wide and substantially wider than thick. As shown in FIG. 1, a piezoelectric body 10 is employed having some portions polarized differently from others. In the case of FIG. 1, the piezoelectric body 10 is in the form of a flat slab which is considerably wider than it is thick, and having greater length than width. A substantial portion of the slab 10 , the portion 12 to the right of the center of the slab is polarized longitudinally, whereas the remainder of the slab is polarized transversely to the plane of the face of the slab. In this case the remainder of the slab is actually divided into two portions, one portion 14 being polarized transversely in one direction, and the remainder of the left half of the slab, the portion 16 also being polarized transversely but in the direction opposite to the direction of polarization in the portion 14 .
In order that electrical voltages may be related to mechanical stress in the slab 10 , electrodes are provided. If desired, there may be a common electrode 18 , shown as grounded. For the primary connection and for relating voltage at opposite faces of the transversely polarized portion 14 of the slab 10 , there is an electrode 20 opposite the common electrode 18 . For relating voltages to stress generated in the longitudinal direction of the slab 10 , there is a secondary or high-voltage electrode 22 cooperating with the common electrode 18 . The electrode 22 is shown as connected to a terminal 24 of an output load 26 grounded at its opposite end.
In the arrangement illustrated in FIG. 1, a voltage applied between the electrodes 18 and 20 is stepped up to a high voltage between the electrodes 18 and 22 for supplying the load 26 at a much higher voltage than that applied between the electrodes 18 and 20 .
A problem with prior piezoelectric transformers is that they are difficult to manufacture because individual ceramic elements must be “poled” at least twice each, and the direction of the poles must be different from each other.
Another problem with prior piezoelectric transformers is that they are difficult to manufacture because it is necessary to apply electrodes not only to the major faces of the ceramic element, but also to at least one of the minor faces of the ceramic element.
Another problem with prior piezoelectric transformers is that they are difficult to manufacture because, in order to electrically connect the transformer to an electric circuit, it is necessary to attach (i.e. by soldering or otherwise) electrical conductors (e.g. wires) to electrodes on the major faces of the ceramic element as well as on at least one minor face of the ceramic element.
Another problem with prior piezoelectric transformers is that the voltage output of the device is limited by the ability of the ceramic element to undergo deformation without cracking or structurally failing. It is therefore desirable to provide a piezoelectric transformer which is adapted to deform under high voltage conditions without damaging the ceramic element of the device.
Piezoelectric and electrostrictive devices (generally called “electroactive” devices herein) are also commonly used as drivers, or “actuators,” due to their propensity to deform under applied electric fields. When used as an actuator, it is frequently desirable that the electroactive device be constructed so as to generate relatively large deformations and/or forces from the electrical input. Prior electroactive devices include flextensional transducers which are composite structures composed of a piezoelectric ceramic element and a metallic shell, stressed plastic, fiberglass, or similar structures. The actuator movement of conventional flextensional devices commonly occurs as a result of expansion in the piezoelectric material which mechanically couples to an amplified contraction of the device in the transverse direction. By coupling two or more electroactive devices, the deformation of one “actuator” can cause the deformation of the adjacent coupled actuator.
Another type of transformer, which is disclosed in co-pending patent application Ser. No. 08/864,029 takes advantage of both the electrical properties of electroactive devices as well as the mechanical “actuator” properties. As disclosed in my copending patent application, a piezoelectric transformer can be made by mechanically bonding electroactive devices to each other such that an input voltage is transformed into mechanical movement, which is translated through the mechanical bond to the adjacent electroactive device, which generates an output voltage.
One embodiment of the type of piezoelectric transformer disclosed in my co-pending patent application is illustrated in FIG. 2 . This transformer 1 is manufactured by stacking two ceramic wafers 30 and 48 between three preferably metallic layers 36 , 42 and 54 , bonding them together with four adhesive layers 34 , 40 , 44 and 52 , and simultaneously heating the stack to a temperature above the melting point of the adhesive materials, such as LaRC-SI™ developed by NASA Langley Research Center. The adhesive used is a very strong adhesive and has a coefficient of thermal contraction which is greater than that of most ceramics (and, in particular, is greater than that of the materials of the two ceramic wafers 30 and 48 ). The adhesive is used to apply a bond between the respective metallic layers 36 , 42 and 54 and the ceramic wafers 30 and 46 and the bond is sufficient to transfer longitudinal stresses between adjacent layers of the transformer 1 .
After the entire stack of laminate layers have been heated to a temperature above the melting point of the adhesive materials, the entire stack of laminate layers is then permitted to cool to ambient temperature. As the temperature of the laminate layers falls below the melting temperature of the adhesive materials, the four adhesive layers 34 , 40 , 44 and 52 solidify, bonding them to the adjacent metallic layers 36 , 42 and 54 . During the cooling process the ceramic wafers 30 and 42 become compressively stressed along their longitudinal axes due to the relatively higher coefficients of thermal contraction of the materials of construction of the metallic layers 36 , 42 and 54 . By compressive stressing the two ceramic members 30 and 42 , the ceramic members 30 and 42 are less susceptible to damage (i.e. cracking and breaking).
A piezoelectric transformer constructed in accordance with the preceding description comprises a pair of piezoelectric ceramic wafers 30 , and 42 which are intimately bonded to each other (albeit separated by laminated adhesive 34 , 40 , 44 and 52 and metallic layers 36 , 42 and 54 ) along one of each of their major faces. The metallic layers 36 , 42 and 54 and the four adhesive layers 34 , 40 , 44 and 52 are longer than the two ceramic wafers 30 and 42 and, accordingly, protrude beyond the ends of the ceramic members 30 and 42 . Electric terminals 56 , 58 and 60 are connected (e.g. by wire and solder, or other common means) to an exposed surface of the metallic layers 36 , 42 and 54 respectively.
Referring again to FIG. 2 : When a primary (i.e. input) voltage V 1 is applied across terminals 58 and 60 connected to the electrodes 32 and 38 of the first ceramic wafer 30 , the first ceramic wafer 30 will piezoelectrically generate an extensional stress commensurate with the magnitude of the input voltage V 1 , the piezoelectric properties of the wafer 30 material, the size and geometry of the wafer 30 material, and the elasticity of the other materials of the other laminate layers (i.e. the ceramic wafer 48 , the three pre-stress layers 36 , 42 and 54 , and the four adhesive layers 34 , 40 , 44 and 52 ) which are bonded to the first wafer 30 . The extensional stress which is generated by the input voltage Vi causes the first ceramic wafer 30 to be longitudinally strained, (for example as indicated by arrow 64 ).
Because the first ceramic wafer 30 is securely bonded to the second ceramic wafer 48 (i.e. by adhesive layers 40 and 44 ), any longitudinal strain 64 of the first ceramic wafer 30 will result in a longitudinal strain (of the same magnitude and direction) in the second ceramic wafer 48 (as indicated by arrow 65 ). The longitudinal strain 65 of the second piezoelectric ceramic wafer 48 generates a voltage potential V 2 across the two electroplated surfaces 46 and 50 of the second ceramic wafer 48 . The electric terminals 58 and 56 may be electrically connected to corresponding electroplated surfaces 46 and 50 of the second ceramic wafer 48 . The magnitude of the piezoelectrically generated voltage V 2 between the two electrodes 46 and 50 of the second ceramic wafer 48 depends upon the piezoelectric properties of the wafer 48 material, the size, geometry and poling of the wafer 48 material.
Thus, by applying a first voltage V 1 across the electroplated 32 and 38 major surfaces of the first ceramic wafer 30 , the first ceramic wafer 30 is caused to longitudinally strain 64 , which, in turn, causes the second ceramic wafer 48 to longitudinally strain 65 a like amount, which, in turn produces a second voltage potential V 2 between the electroplated 46 and 50 major surfaces of the second ceramic wafer 48 .
The ratio of the first voltage V 1 to the second voltage V 2 is a function of the piezoelectric properties of the wafer 30 s and 48 , the size and geometry of the wafers 30 and 48 material, the elasticity of the other materials of the other laminate layers (i.e. the ceramic wafers 30 and 48 , the three pre-stress layers 36 , 42 and 54 , and the four adhesive layers 34 , 40 , 44 and 52 ), and the poling characteristics of the two ceramic wafers 30 and 48 .
In the one embodiment of the invention disclosed in my co-pending patent application, the facing electroplated surfaces 38 and 46 of the first ceramic wafer 30 and second ceramic wafer 48 , respectively, are electrically connected to a common electric terminal 58 . In alternative embodiments of the transformer (not shown) the corresponding facing electroplated surfaces 38 and 46 of two ceramic wafers 30 and 48 are electrically insulated from each other, (for example by a dielectric adhesive layer), and connected to corresponding terminals. In this modified embodiment of the transformer the two piezoelectric ceramic wafers 30 and 48 are completely electrically isolated from each other. A transformer constructed in accordance with this modification of the invention may be used in an electric circuit to electrically protect electrical components “downstream” from the transformer from damage from high current discontinuities “upstream” of the transformer.
Although, this type of piezoelectric transformer is simpler to manufacture than prior art Rosen transformers, it is still somewhat difficult to manufacture because the necessity of adhering electrodes between the ceramic wafers and to the major faces of the ceramic wafers.
Another problem with such methods of manufacturing piezoelectric transformers is that it is difficult to maintain complete electrical contact over the entire major face of the ceramic wafer, because of the presence of multiple adhesive layers between the ceramic and metallic layers.
Another problem with piezoelectric transformers manufactured by such a process is that the adhesive bond between the metallic layer and ceramic layer may not be uniform, and the adhesive may delaminate or detach due to deformation of the ceramic layer.
Another problem is that the presence of multiple adhesive layers between the metallic and ceramic layers makes miniaturization of piezoelectric transformers more difficult using such methods of manufacturing.
Another problem with piezoelectric transformers manufactured by such a process is that the multiple adhesive and metallic layers between ceramic layers dampen the motion of the first ceramic layer and limit the translation of motion from the first ceramic layer to the adjacent ceramic layer.
SUMMARY OF THE INVENTION
The term piezoelectric transformer is here applied to an electrical energy-transfer device employing the piezoelectric properties of co-joined materials to achieve the transformation of voltage or current or impedance. It is an object of the invention to provide a piezoelectric transformer which, in a preferred embodiment is not only capable of substantial transformation ratios, but in which relatively high power may be transferred in relation to the size of the unit.
Accordingly, it is a primary object of the present invention to provide a piezoelectric transformer which may be easily and inexpensively produced.
It is another object of the present invention to provide a device of the character described which is capable of producing high voltages and which may safely be used in high voltage circuits.
It is another object of the present invention to provide a piezoelectric transformer of the character described comprising a pair of ceramic elements, each exhibiting piezoelectric properties, which are in physical (mechanical) communication with each other such that deformation of one ceramic element results in corresponding deformation of the other ceramic element.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is easy to manufacture because it is sufficient to pole each ceramic element only once, and wherein the direction of poling for each ceramic element is constant over its entire mass.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is easy to manufacture because it is sufficient have electrodes only on the major faces of the ceramic elements, and which do not require application of electrodes to minor faces of the ceramic elements.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is easy to manufacture because it is sufficient to apply electrodes only to two parallel faces of the ceramic elements.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is easy to connect or install in an electric circuit, because it is sufficient to attach (i.e. by soldering or otherwise) electrical conductors (e.g. wires) only to electrodes on the major faces of the ceramic element.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is adapted to deform under high voltage conditions without damaging the ceramic element of the device.
It is another object of the present invention to provide a piezoelectric transformer of the character described which is operable over wide input and output frequency bandwidths.
It is another object of the present invention to provide a piezoelectric transformer of the character described which electrically isolates the voltage and current at the input to the device from the voltage and current at the output of the device.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the translation of motion from one ceramic layer to another ceramic layer is not dampened by an interposed adhesive layer.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the translation of motion from one ceramic layer to another ceramic layer is not substantially dampened by an interposed metallic layer.
It is another object of the present invention to provide a piezoelectric transformer of the character described which may be constructed without the use of adhesives.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization adheres well to adjacent ceramic layers.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization has similar mechanical characteristics to the adjacent ceramic layers.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization has thermal expansion characteristics similar to a ceramic.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization has desirable electrical characteristics for use in a piezoelectric transformer.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization is less expensive than conventional metallization (electrode) materials used in piezoelectric transformers.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the formation of piezoelectric ceramic layers occurs simultaneously with the bonding of electrodes (metallization) to the ceramic layer.
It is another object of the present invention to provide a piezoelectric transformer of the character described in which the metallization has desirable thermal and oxidation characteristics for use in a cofired piezoelectric transformer.
Further objects and advantages of the invention will become apparent from a consideration of the drawings and ensuing description thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view showing the construction of a Rosen-type piezoelectric transformer of the prior art;
FIG. 2 is a perspective view showing the construction of a piezoelectric transformer using adhesives for bonding adjacent laminate layers;
FIG. 3 is a flow diagram showing the steps of the cofiring process for producing a piezoelectric transformer in accordance with the preferred embodiment of the present invention;
FIG. 4 is a perspective view showing a piezoelectric transformer constructed in accordance with the preferred embodiment of the present invention;
FIG. 5 is a perspective view of a modified embodiment of the invention; and
FIG. 6 is a perspective view of a modified embodiment of the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
With reference directed toward the appended drawings, a piezoelectric transformer/actuator (generally designated by the reference numeral 2 ) manufactured embodying the principles and concepts of the present invention will be described.
As will be described more fully herein below, a piezoelectric transformer/actuator 2 is manufactured, in part, by first mixing a ceramic powder with a binder (step 100 ); forming green ceramic shapes (step 102 ); applying electrode materials (steps 104 and 114 ); and cofiring the composite structure (steps 106 , 108 , 110 and 112 ).
Referring to FIG. 3 : FIG. 3 is a flow diagram showing the steps in the preferred embodiment of the present invention, with individual steps denoted by three-digit reference indicia. The first step in the preferred embodiment of the present invention is to mix 100 a ceramic powder with an appropriate amount of a binder. This mixture of a powder and binder forms a sinterable ceramic composition which can produce an electrical ceramic upon firing the mixture.
A variety of electrical ceramic materials exist, such as might be or are used in electroactive devices (for example, lead titanate, PbTiO3; lead zirconate titanate, “PZT”; lanthanum doped PZT, “PLZT”; barium titanate, BaTiO3; lithium niobate, LiNbO3; bismuth titanate, Bi4Ti3O12; Aluminum Nitride, AlN; and yttrium barium copper oxide, YBa2Cu3O7. Other electrical ceramics include piezoelectric crystals which are grown, such as lithium gallium oxide, β-LiGa02; lithium aluminum oxide, LiA102; lithium tantalate; LiTaO3; and calcium pyroniobate, Ca2Nb207. Other electrical ceramics include those which are based on the above listed ceramics doped with small amounts of other materials to alter their electrical and/or mechanical properties
Production of sinterable ceramic compositions is known in the art. For example, lead zirconate titanate (PZT) is an often used ceramic for piezoelectric applications. Optimum material properties are obtained in the production of PZT when the titanium/zirconium ratio is exactly matched at least in the range of a few thousandths, with respect to the morphotropic phase boundary, when the titanium and zirconium atoms in the ceramic are uniformly distributed over the grains, as well as in the individual grains, and when the sintering temperature for the piezoceramic is as low as possible. The latter condition achieves stable and reproducible conditions by minimizing the evaporation of the lead oxide content from the ceramic during the sintering. These demands can only be met when extremely fine, chemically uniform and pure-phase PZT powders having a suitable stoichiometry are used for shaping the green compacts, which can subsequently be sintered at low temperature.
Numerous methods are known for producing PZT powders having the required properties. For example, powders can be produced chemically by co-precipitation, spraying reaction or sol-gel processes. These powders already contain all cations including lead. An optimally low sintering temperature is usually achieved by controlling the fineness of the particles.
A mixed oxide method is often used for practically producing a piezoceramic in commercial quantities. In this method, a mixture of lead oxide (PbO) dopant oxides, titanium dioxide (TiO2) and especially finely particulate zirconium oxide (ZrO2) is ground, dried and, typically, convened (calcined) into PZT powder at approximately 900 deg. C. Due to the different reaction behavior of TiO2 and ZrO2 with PbO, however, PZT powder particles arise having a Ti/Zr ratio from PbTiO3 (No zirconium) through PbZrO3 (No titanium) which is significantly scattered around a desired value. The powder must therefore be ground and mixed a second time. The homogeneity of the titanium/zirconium ratio which can be achieved by diffusion and grain growth in the sintering of this known powder during compression is limited by the sintering temperature, by particle size, as well as by the heterogeneity of the powder. The optimum piezoelectric material values of the sintered ceramic, or the optimum composition of the sintered ceramic with respect to the morphotropic phase boundary, are empirically set for each process on site, and may be possibly re-adjusted by a fine variation of the oxide mixture with respect to the Ti/Zr ratio. A reproducible production of PZT piezoceramics is thus possible by means of above mentioned processes.
Referring again to FIG. 3, in the first steps of the preferred embodiment of the present invention, a ceramic powder is combined 100 with an organic binder and pressed 102 into “green” shapes. The organic binding material used in the present process bonds the particles of ceramic powder together and enables formation of the required shape with desired solids content (i.e., ratio of ceramic powder to binding material). The organic binding material pyrolyzes, i.e. thermally decomposes, at an elevated temperature ranging generally from about 50 deg. C to below about 800 deg. C, and preferably from about 100 deg. C to about 500 deg. C. In non-oxidizing atmospheres, the binding material decomposes to elemental carbon and gaseous product of decomposition which vaporizes away. In an oxidizing atmosphere, the binding material decomposes to a gaseous oxidized product which vaporizes away.
The organic binding material is a thermoplastic material with a composition which can vary widely and which is well known in the art. Besides an organic polymeric binder it can include an organic plasticizer to impart flexibility to a green shape. The amount of plasticizer can vary widely depending largely on the particular binder used and the flexibility desired, but typically, it ranges up to about 50% by weight of the total organic content. The organic binding material may also be soluble in a volatile solvent.
Representative of useful organic binders are polyvinyl acetates, polyamides, polyvinyl acrylates, polymethacrylates, polyvinyl alcohols, polyvinyl butyrals, and polystyrenes. Representative of useful plasticizers are dioctyl phthalate, dibutyl phthalate, polyethylene glycol and glycerol trioleate. ordinarily, the organic binder has a molecular weight at least sufficient to make it retain its shape at room temperature and generally such a molecular weight ranges from about 20,000 to about 80,000.
The particular amount of organic binding material used in forming the mixture is determinable empirically and depends largely on the amount and distribution of solids desired in the resulting green shape. Generally, the organic binding material ranges from about 10% by volume to about 50% by volume of the solids content of the mixture in the green shape, and preferably constitutes about 15% to 25% by volume of the sinterable ceramic composition.
An oxidizing agent may be used when the green shape is to be sintered in a non-oxidizing atmosphere. The oxidizing agent should be used at least in an amount sufficient to react with the total amount of elemental carbon produced by pyrolysis of the organic binding material. For example, the actual amount of elemental carbon introduced by pyrolysis of the organic binding material can be determined by pyrolyzing the organic material alone under the same conditions used in the present cofiring and determining weight loss. Generally, the oxidizing agent ranges from about 0.5% by weight to about 5% by weight, and frequently from about 1% by weight to about 3% by weight, of the sinterable ceramic composition.
In carrying out the present process, the sinterable ceramic composition and organic binding material are admixed 100 to form a uniform or at least a substantially uniform mixture or suspension which is formed 102 into a sheet or other shape of desired thickness and solids content. A number of conventional techniques can be used to form the mixture 100 and resulting green shape 102 . Generally, the components are milled in an organic solvent in which the organic material is soluble or at least partially soluble to produce a castable mixture or suspension. Examples of suitable solvents are methyl ethyl ketone, toluene and alcohol. The mixture or suspension is then formed 102 into a sheet of desired thickness in a conventional manner, such as by doctor blading, or cast 102 into a desired shape by injection molding, extrusion, or pressing, and preferably hot pressing. The cast shape is then dried to evaporate the solvent therefrom to produce 102 the final green shape.
The particle size of the solids content of the mixture or suspension can vary widely depending largely on the particular substrate to be formed and is determinable empirically. The thickness of the present green shape can vary widely depending largely on its particular application. Generally, however, its thickness ranges from about 0.1 mm to about 10 mm. Preferably, the present green shape is of uniform or at least of substantially uniform thickness from about 1 mm to 6 mm.
In the present invention the green shape which is formed 102 , consists preferably of disk shaped wafers. Preferably two wafers are formed 102 , each wafer having two major opposing faces. The diameter of the wafer is generally greater than the thickness of the wafer and is generally at least four times the wafer's thickness. The wafers may be of equal or unequal thickness, depending on the final properties desired from the piezoelectric transformer. The wafers may be of unequal or preferably equal diameter. The wafers may also be made of dissimilar or preferably the same type of electrical ceramic materials. The green shape may also be of other shapes than disk-like wafers, such as in the shape of rectangular slabs.
The next step is to apply 104 metallization material to the green shapes. Metallization should be applied 104 to a major face of a green shape, and preferably to one face of each wafer. Metallization material is a metallization-forming material, i.e. during cofiring it forms the electrically conductive metal phase on the ceramic wafer. Generally, the metallization material is in the form of a paste or ink of the metal particles suspended in organic binder and solvent. Frequently, the metallization material also contains some glass frit or it may be mixed with some of the powder which formed the ceramic wafer. The glass or ceramic powder aid in the adherence of the metal to the ceramic wafer. Generally, the metal particles range in size from about 0.1 micron to about 20 microns and preferably from 2 to 5 microns.
The metallization material is a metal whose particles can be sintered together to produce a continuous electrically conductive phase during sintering 110 of the sinterable ceramic composition. Desirable metallization materials are materials that exhibit compatible thermal and mechanical properties with the electroactive ceramic. In particular, it is desirable to have a metallization material whose coefficient of linear expansion is close to that of the final sintered ceramic. Metallization that has a coefficient of linear expansion comparable to the final sintered ceramic is less likely to fracture or delaminate from the bonded ceramic.
Furthermore, the metal must be solid during sintering 110 to prevent migration of the metallization material into the ceramic during sintering 110 . Therefore, it is desirable that the metallization material have a high melting point, specifically, a melting point higher than the highest sintering temperature (usually around 1300 deg. C) of the ceramic. Metals which have lower melting points, such as aluminum (660 deg. C) and silver (962 deg. C), are thus not appropriate as metallization materials for electrical ceramics that require sintering temperatures above their melting points.
The properties of electroactive ceramics are typically optimized by heat treatments (sintering) at high temperatures (for example, 500 deg. C to 1300 deg. C). Many electrical ceramics, such as ceramic oxides require sintering in an oxidizing atmosphere. Many materials commonly used as electrodes are not suitable for use under high temperature and oxidizing conditions. The electrode material also should not deleteriously react with the ceramic substrate or the sintering atmosphere. As examples, aluminum electrodes would melt or react with the electrical ceramic oxide material; and silicides and polysilicon either react with the electrical ceramic at the higher temperatures or are oxidized at the surface in contact with the electrical ceramic oxide.
Moreover, if the oxide of an electrode metal has a high resistivity, reaction of the metallization material with the electrical ceramic oxide will create an interfacial dielectric layer of oxidized electrode material between the electrode and the electrical ceramic oxide. This may give rise to a capacitor in series with the electrical ceramic oxide, reducing the voltage drop experienced across the electrical ceramic oxide. Thus it is desirable that the metallization material not lose its conductivity due to reaction with oxygen or other ambients in the atmosphere or in the abutting ceramic layers. In the application of electroceramics as transformers, efficiency and the power factor are reduced as a result this loss.
Noble metals (e.g. platinum, palladium, and gold) may be used as electrode materials for multilayer piezoelectric devices. These noble metals have high melting points and are resistant to oxidation which helps to eliminate the problems associated with interfacial dielectric layers composed of the oxides of the electrode materials. Thus noble metals may be used as metallization for both oxide and non-oxide electroceramics.
Some other metals that are conductive are the platinum group metals (PGMs include Ruthenium, Rhodium, Iridium and Osmium). PGMs also form oxides that are conductive. Other conductive oxides of metals are Indium oxide and indium-tin oxide. These metals may be used as electrode materials for multilayer piezoelectric devices because they have high melting points, and because their oxides are conductive, they are resistant to the problems associated with interfacial dielectric layers composed of the oxides of the electrode materials. Thus, PGMs and their oxides may be used as conductors for both oxide and non-oxide electroceramics.
Some other metals readily oxidize in air at higher temperatures, forming nonconductive layers and thus are not suited to use as electrodes in oxide-containing electroceramics cofired in air. Among the metals that readily oxidize in air are zinc, copper and aluminum and particularly refractory metals (i.e., Tungsten @ 190 deg. C., Molybdenum @ 395 deg. C., Tantalum/Columbium @ 425 C.). Thus these metals are not appropriate as conductors for piezoelectric transformers cofired in an oxidizing atmosphere. These refractory metals however are desirable from the standpoint that they have good conductivity, high melting points, and a coefficient of linear expansion similar to that of final sintered electroceramics. The refractory metals may be used where the sintering atmosphere is slightly oxidizing with respect to the organic binder, but not oxidizing with respect to the metallization material, such as a hydrogen atmosphere with a high water vapor content.
The oxides of these metals may be appropriate in an alternate embodiment of the invention as intermediate dielectric layers located between the conductive layers in an oxide ceramic transformer. The refractory metals remain good conductors for non-oxide electrical ceramics, and in particular, the refractory metals have the advantages of having a high melting point and a coefficient of linear expansion similar to electroceramics.
The metallization material can be contacted 104 with the green shapes by a number of conventional techniques. These methods include Chemical Vapor Deposition (CVD), sputtering, and printing. Generally, the metallization is deposited or printed onto the electroceramic, and preferably it is screen printed thereon.
The shapes are then stacked 106 together, i.e. superimposed on each other, generally forming a sandwich. The stack can be laminated under a pressure and temperature determinable largely by its particular composition, but usually lower than about 100 deg. C., to form a laminated composite structure which is then cofired 108 and 110 . The term cofiring encompasses the application of heat 108 and 110 to the composite structure in a two part process. In the first part of the process, the temperature of the composite structure is raised 108 in order to cause the organic binder to burn off. In the second part of the cofiring process the temperature is again raised 110 in order to sinter the metallization and the ceramic. The final cofired structure is a sintered structure comprised of a sintered ceramic substrate and an adherent electrically conductive phase of metal or metal oxide between the ceramic layers.
The present cofiring process is carried out in an atmosphere in which the ceramic substrate and metal are inert or substantially inert, i.e. an atmosphere or vacuum which has no significant deleterious effect thereon. Specifically, for non-oxide ceramics, the atmosphere or vacuum should be nonoxidizing with respect to the metallization and the ceramic substrate. Representative of a useful atmosphere is dissociated ammonia, nitrogen, hydrogen, a noble gas and mixtures thereof. Preferably, a reducing atmosphere containing at least about 1% by volume of hydrogen, and more preferably at least about 5% by volume of hydrogen, is used to insure maintenance of sufficiently low oxygen partial pressure. Preferably, the atmosphere is at ambient pressure.
For oxide containing electroceramics, the sintering atmosphere is non-reducing, and is preferably air. However, where the metallization material oxidizes at higher temperatures, a slightly oxidizing atmosphere of up to 20 percent hydrogen in nitrogen with water vapor may be used (hydrogen to water ratio should be around 2.5). Preferably, the atmosphere is at ambient pressure.
Generally, during binder burn off 108 , in the firing temperature range up to about 500deg. C., a slower heating rate is desirable because of the larger amount of gas generated at these temperatures by the decomposition of the organic binding material. Typically, the heating rate for a sample of less than about 6 mm thickness can range from about 1 deg. C. per minute to about 8 deg. C. per minute up to 500 deg. C.
For non-oxide electrical ceramics, at a cofiring temperature of less than about 800 deg. C., the pyrolysis of the organic material is completed leaving a residue of elemental carbon. Generally, the amount of elemental carbon produced by pyrolysis is at least about 0.05% by volume, and usually at least about 0.4% by volume, of the substrate. When the cofiring temperature is increased 108 to a range of from about 800 deg. C. to about 1200 deg. C., but below the temperature at which closed porosity is initiated in the non-oxide ceramic substrate, the oxidizing agent reacts with the elemental carbon producing carbonaceous gases which vaporize away through the open porosity of the substrate thereby removing the elemental carbon from the substrate.
After the binder has burnt off 108 , the cofiring temperature is then increased 110 to the sintering temperature. The sintering temperature is that temperature at which the ceramic substrate densifies to produce a ceramic substrate having a decreased porosity. In the present cofiring, the rate of heating is determinable empirically and depends largely on the thickness of the sample and on furnace characteristics. After binder burnoff 108 , the rate at which the cofiring temperature is increased is about 200 deg. C. per hour.
The sintering temperature can vary widely depending largely on the particular ceramic composition, but generally it is above 800 deg. C. and usually ranges from about 900 deg. C. to about 1300 deg. C. For example, when firing PZT, upon reaching a sintering temperature from about 1240 deg. C. to 1300 deg. C., that temperature should be maintained for 1 to 8 hours. Below this temperature optimum density will not be achieved and above this temperature lead loss may become excessive and some melting may occur. The final porosity should be less than about 10% by volume, preferably less than about 5% by volume, and more preferably, less than about 1% by volume of the substrate.
During sintering 110 , the ceramic composition is liquid-phase sintered producing a ceramic substrate of desired density, and the metal particles are sintered together producing a continuous electrically conductive phase. During sintering 110 , a portion of the liquid phase which enables sintering of the ceramic migrates into the interstices between the sintering metal particles by capillarity resulting in a phase, usually a glassy phase, intermingled with the continuous phase of metal which aids in the adherence of the metal phase to the ceramic layers.
In order to produce a sufficiently densified ceramic, the composite structure must be sintered 110 in an appropriate atmosphere in order to enhance densification. For oxide based electrical ceramics, such as PZT, the sintering atmosphere should be substantially pure oxygen, although a positive oxygen pressure is unnecessary. A convenient way to achieve this atmosphere is to introduce pure oxygen into the open end of a tube furnace at a flow rate of about 150 cubic centimeters per minute. Sintering 110 should be carried out from 1240 deg. C. to 1300 deg. C. for 1 to 8 hours, below which optimum density will not be achieved and above which lead loss may become excessive and some melting may occur. It is preferred to sinter 110 at a temperature from 1280 deg. C. to 1300 deg. C. for 2 to 4 hours in order to achieve optimum density.
During sintering 110 , precautions should be exercised to avoid excessive lead loss by volatilization as such lead loss may be significant in shifting the composition outside the range in which optimum piezoelectric properties have been observed. For example, covering the pressed part with powder of the same composition, adding a compensatory excess of lead to the starting composition, carrying out sintering 110 in a sealed container, or a combination of one or more of these steps are appropriate precautions.
Upon completion of the cofiring 110 , the resulting structure is allowed to cool 112 , preferably to ambient temperature. The rate of cooling 112 can vary, but it should have no significant deleterious effect on the structure, i.e., should not cause thermal shock or cracking. Preferably, it is furnace cooled 112 to ambient temperature. The final ceramic should have a porosity of less than about 10% by volume, preferably less than about 5% by volume, more preferably less than 1% by volume, and most preferably, pore-free, i.e., fully dense.
Upon completion of the cofiring 110 , and more preferably upon completion of cooling 112 the sintered ceramic, exterior electrodes 76 and 78 may be applied 114 . The exterior electrodes 76 and 78 are deposited on the exterior faces of the ceramic wafers 70 and 72 . Because these exterior electrodes 76 and 78 do not undergo the cofiring process 108 and 110 , they are not required to withstand oxidation at high temperatures. Thus these electrodes 76 and 78 may be made of any conventional electrode material such as aluminum or silver. These exterior electrodes 76 and 78 may be applied 114 by any conventional means such as by sputtering, CVD, thin foil adhesion, or preferably by electroplating the exterior faces of the sintered ceramic. Optionally, the electrode materials 76 and 78 may be deposited 104 on both faces of the green ceramic and cofired 108 and 110 with the green shape to produce both the interior 74 and exterior electrodes 76 and 78 .
Upon completion of applying 114 the external electrodes, the sintered ceramic is then polarized 116 , preferably in the thickness direction (i.e. normal to the major faces transformer). Polarization should occur simultaneously to both ceramic layers 70 and 72 rather than one at a time, because dimensional shrinkage of a ceramic layer 70 due to the polarizing electric field may delaminate one ceramic layer 70 from the other ceramic layer 72 . Polarizing 116 may be accomplished by placing the sintered ceramic on a grounded, metallic, surface and contacting it with an electrically charged metal brush (not shown). Polarization 116 of the device should occur with the device submerged in oil, such as peanut oil or silicone oil, to prevent arcing across the electrodes under a high intensity electric field. The temperature of the ceramic should also come into equilibrium with the temperature of the oil (about 80 deg. C to 120 deg. C) to prevent damage to the ceramic. As the sintered ceramic comes into contact with the metal brush, the metal brush is electrically charged by a power supply, and the bottom facing exterior electrode 78 on the sintered ceramic is electrically conducted to the (grounded) surface, and the brush electrically conducts to the upward facing exterior electrode 76 of the sintered ceramic. The high voltage charge of the metal brush (e.g. 12 to 15 Kilovolts/cm) polarizes 116 the ceramic layers 70 and 72 of the sintered ceramic transformer 2 . To prevent arcing as the electrode 76 comes into close proximity with the metal brush, the power supply is only turned on after the electrode 76 establishes contact with the metal brush. This method of polarizing 116 produces two ceramic layers 70 and 72 polarized 116 in the same direction (i.e., 70 +/−, 72 +/−). It may be desirable to polarize the ceramic layers 70 and 72 in different directions with respect to each other (i.e., 70 +/−, 72 −/+). For polarizing 116 in this manner, the center electrode 74 is grounded and metal brushes contact the outer electrodes 76 and 78 .
A piezoelectric transformer 2 constructed in accordance with the preceding description comprises a pair of piezoelectric ceramic wafers 70 and 72 which are intimately bonded to each other along one of each of their major faces by an internal electrode 74 formed by the metallization layer 74 . Electric terminals 80 , 82 and 84 are connected (e.g. by wire and solder, or other common means) to an exposed surface of the electrodes 76 , 78 and 74 respectively.
Referring to FIG. 4 : When a primary (i.e. input) voltage V 1 is applied across terminals 82 and 84 connected to the electrodes 78 and 74 of the first ceramic wafer 72 , the first ceramic wafer 72 will piezoelectrically generate an extensional stress commensurate with the magnitude of the input voltage V 1 , the piezoelectric properties of the wafer 72 material, the size and geometry of the wafer 72 material, and the elasticity of the electrodes 78 and 74 which are bonded to the first wafer 72 . The extensional stress which is generated by the input voltage V 1 causes the first ceramic wafer 72 to be radially strained.
Because the first ceramic wafer 72 is securely bonded to the second ceramic wafer 70 (i.e., by internal electrode 74 ), any radial strain (and bending) of the first ceramic wafer 72 will result in a radial strain (of the same magnitude and direction) in the second ceramic wafer 70 . The radial strain (and bending) of the second piezoelectric ceramic wafer 70 generates a voltage potential V 2 across the two electrodes 74 and 76 of the second ceramic wafer 70 . The electric terminals 84 and 80 may be electrically connected to corresponding electrodes 74 and 76 of the second ceramic wafer 70 . The magnitude of the piezoelectrically generated voltage V 2 between the two electrodes 74 and 76 of the second ceramic wafer 70 depends upon the piezoelectric properties of the wafer 70 material, the size, geometry and poling of the wafer 70 material.
Thus, by applying a first voltage V 1 across the electrodes 78 and 74 of the first ceramic wafer 72 , the first ceramic wafer 72 is caused to radially strain, which, in turn, causes the second ceramic wafer 70 to radially strain a like amount, which, in turn produces a second voltage potential V 2 between the electrodes 74 and 76 of the second ceramic wafer 70 .
The ratio of the first voltage V 1 to the second voltage V 2 is a function of the piezoelectric properties of the wafer 70 and 72 , the size and geometry of the wafers 70 and 72 material, the elasticity of the other materials of the other laminate layers (i.e., internal electrode 74 and external electrodes 76 and 78 ) and the poling characteristics of the two ceramic wafers 70 and 72 .
As shown in FIG. 4, in the preferred embodiment of the invention, in the piezoelectric transformer 2 , the facing surfaces of the first ceramic wafer 72 and second ceramic wafer 70 , respectively, are electrically connected to a common electric terminal 84 connected to the metallization 74 layer.
Referring now to FIG. 5 : In an alternative embodiment of the transformer 3 , the corresponding facing metallized 74 surfaces of two ceramic wafers 70 and 72 are electrically insulated from each other, (for example by a dielectric layer 67 such as another ceramic), and connected to corresponding terminals. In this embodiment of a piezoelectric transformer 3 , the facing surfaces of the first ceramic wafer 72 and second ceramic wafer 70 , respectively, each have an internal electrode 74 (which are separated by the dielectric layer 67 ). Each internal electrode 74 is electrically connected to a common electric terminal 84 at the exposed surface of the internal electrode 74 . A piezoelectric transformer 3 constructed in accordance with this modification of the invention may be used in an electric circuit to electrically protect electrical components “downstream” from the transformer 3 from damage from high current discontinuities “upstream” of the transformer 3 .
Referring now to FIG. 6 : In an alternative embodiment of the transformer 4 , the corresponding facing metallized 74 surfaces of two ceramic wafers 70 and 72 are electrically insulated from each other, (for example by a dielectric layer 67 ), and connected to different corresponding terminals. In this embodiment of a piezoelectric transformer 4 , the facing surfaces of the first ceramic wafer 72 and second ceramic wafer 70 , respectively, each have an internal electrode 74 (which are separated by the dielectric layer 67 ). Each internal electrode 74 is electrically connected to a separate electric terminal 86 and 88 at the exposed surface of the internal electrode 74 . In this embodiment of the transformer 4 , the two piezoelectric ceramic wafers 70 and 72 are completely electrically isolated from each other. A transformer 4 constructed in accordance with this modification of the invention may be used in an electric circuit to electrically protect electrical components “downstream” from the transformer 4 from damage from high current discontinuities “upstream” of the transformer 4 .
While the above description contains many specificities, these should not be construed as limitations on the scope of the invention, but rather as an exemplification of one preferred embodiment thereof. Many other variations are possible, for example:
The two ceramic wafers 70 and 72 may be constructed of either similar or dissimilar piezoelectric materials which may either have identical or dissimilar piezoelectric coefficients;
The two ceramic wafers 70 and 72 may either be of equal or unequal thicknesses;
The ceramic wafers need not be disk shaped but may also be of a rectangular or other shape;
The ceramic wafers need not be flat but may be curved or dome shaped;
There may be more than two ceramic wafers;
Metallization may be used on more than one face of a ceramic wafer and can be used for both internal and external electrodes;
Metallization may be applied on only one or both facing surfaces of ceramic wafers;
Electrical connections need not be made solely on the exposed surface of the internal electrode but may be connected with through holes or vias;
External electrodes may by applied by any metal deposition technique including using an adhesive to attach one or both external electrodes;
The green ceramic wafers may be formed by any technique for making green shapes including doctor blading, extrusion, injection molding, casting, pressing, hot pressing or the like;
Sintering/cofiring may be conducted in an oven, a crucible, on a plate, in an autoclave, by conductive heating in a hot press or the like manner of heating;
Sintering/cofiring may be conducted in a reducing, oxidizing or neutral atmosphere depending on the desired reaction of the atmosphere with the ceramic or the metallization material;
Sintering/cofiring need not be conducted in a vacuum, or at a atmospheric pressure, but may be conducted at any pressure;
Binder burn-off and sintering the ceramic/metallization may be conducted in different atmospheres, at different pressures and by different heating mechanisms;
Accordingly, the scope of the invention should be determined not by the embodiment illustrated, but by the appended claims and their legal equivalents.
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A method for manufacturing a cofired multi-layer piezoelectric transformer device includes forming first and second green shapes of a sinterable ceramic composition and applying metallization layer therebetween. Upon cofiring, the composite structure comprises first and second electroactive members bonded together by a conductive layer therebetween. External electrodes are applied and the electroactive members are polarized in a thickness direction, between their two major faces. The first and second electroactive members are arranged such that deformation of one electroactive member results in corresponding deformation of the other electroactive member. The device provides substantial transformation ratios in which relatively high power may be transferred in relation to the size of the unit, operability over wide input and output frequency bandwidths, and electrical isolation of the input voltage and current from the output voltage and current.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 14/092,685 filed on Nov. 27, 2013 which claims the benefit of U.S. Provisional Application Ser. No. 61/731,948 filed Nov. 30, 2012, the contents of which are hereby incorporated by reference herein.
BACKGROUND
[0002] Wireless receive/transmit units (WRTUs) such as cellular phones have been used primarily to receive voice calls and carry voice traffic and text (SMS) messages. Today, however, users use WRTUs to access information while on the go from a variety of different sources, such as the World Wide Web, application stores, and corporate resources. Advanced WRTUs (which use operating systems such as Apple's iOS, Android, and other advanced operating systems) require significant wireless network resources because of the large data traffic they generate. Some of the data-intensive tasks that may be performed on advanced WRTUs include web surfing, receiving and displaying web pages written in HTML5, downloading applications, downloading mapping elements and other geographic data, streaming of audio and video content, and video conferencing. Additionally, corporate users seek to have secure communication to their corporate networks.
[0003] Many WRTUs have the capability to support multiple air interfaces. For example, some WRTUs implement one or more “cellular” mobile technologies such as, but not limited to, UTMS, GSM, Edge, IS-95, super-WiFi, WCDMA, TD-SCDMA, HSPDA, HSUDA, HSPA+, CDMA2000, IEEE 802.16 (Wimax), LTE, 3G, 4G, TD-LTE, and also implement “local” wireless technology such as Bluetooth, and Wireless Local Area Network (WLAN) technologies (such as those in the IEEE 802.11× family protocols, including 802.11a/b/g/n/af/ac).
[0004] Wireless access points (also referred to as “hot spots,” “WiFi hot spots”, APs, or WAPs) that are based on technologies in the IEEE 802.11 family have become more and more prevalent in businesses and homes. Operators and consumers alike seek to leverage these wireless access points to manage their traffic and provide communication services with adequate and predictable quality of service (QOS). Operators are actively looking at using those wireless systems to offload traffic. This is often done along with the deployment of traditional wireless standards femto-cells.
[0005] The re-farming of analog TV bands in the 700 MHz band has created new opportunities for wireless technology dubbed as “White Space”. WRTUs may use this spectrum provided they do not interfere with other devices using the same spectrum. Unlike Wireless LANs, checking on the availability of the spectrum is required on a regular basis. This may be done, among others, by mapping the location of a WRTU against a geo-location database or by using a WRTU-born sensor to detect the presence of transmitters (such as by but not limited to microphones). Sensor-based management solutions impact WRTU battery life, as they must constantly verify a status of the spectrum.
[0006] Wynn and Fraser teach in U.S. patent application Ser. No. 12/240,969 about creating network profiles (basically characteristics) for discovered wireless networks and the management of the attributes of these profiles over time, allowing the management of attributes. It is limited to being predicated solely on the network profile and does not take in account the functional and economic nature of the wireless network being considered. This “one size fits all” method suffers from supporting business models and operations of networks that are differentiated by ancillary economic or social components.
[0007] Wynn and Fraser further teach in U.S. patent application Ser. No. 11/823,698 about sharing information about network profiles between users. It allows, under user control, the sharing of the network profile to one or more other users. While this facilitates the discovery of the network, it does not allow for collaborations between users.
[0008] Wireless networks in the past have been perceived from the narrow perspective of network operators where matters such as delay, throughput, and coverage are the attributes that matter regardless of the nature of the network underlying the deployment not as a semantically set commerce transaction enabler or marketplace.
[0009] While considering models used in e-commerce and social networking, one must, however, be mindful that models that apply to one type of activity (such as purchases) do not apply to other domains (such as networking). Group incentives for commerce such as sites like Groupon or Living Social rely on having a minimum number of consumers interested in a specific offer before making it effective. Some social purchasing sites create an incentive for sharing more information about offers by offering a pyramid like incentive (get three friends to sign on and get an offer for free or reduced price). This type of offer management is appropriate when considering commercial activities. It is however not conducive to network management activities.
[0010] Business applications such as electronic commerce (“e-commerce”) applications, Customer Relationship Management (“CRM”) applications, Human Resource Management (HRM) applications, bidding and auction sites, and electronic catalogs are pervasive. A single merchant, business, or seller may operate such business applications. They may be accessed through broadband wired and wireless means, using among others smartphones, tablets, and personal computers. Such business applications may also be, as an example, centrally controlled or hosted to create an online marketplace. This marketplace can include numerous merchants, businesses, or sellers. They may not been integrated or coupled with the nature of the network they are being accessed with.
SUMMARY
[0011] The subject matter described herein relates to wireless network discovery, management, the enabling of services, and economic exchanges in a cooperative manner by one or more federated sets of consumers, one or more access point providers, and one or more wireless service providers. Described herein are methods and apparatus for the discovery, classification, and management of wireless networks. The methods and apparatuses described herein may leverage two complementary elements impacting the performance of wireless LANs: (1) organization and management of the wireless access points (hot spots) from an ontology perspective, and (2) organization of mobile devices as a federation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] A more detailed understanding may be had from the following description, given by way of example in conjunction with the accompanying drawings wherein:
[0013] FIG. 1 shows a flow chart of an example process for creating and managing a federation of WRTUs;
[0014] FIG. 2 shows an example of ontology managed wireless LAN hot spots system; and
[0015] FIG. 3 is a block diagram of a WRTU that may be used to implement features described herein; and
[0016] FIG. 4 is a block diagram of a server computer that may be used to implement features described herein.
DETAILED DESCRIPTION
[0017] As used herein, wireless receive/transmit unit (WRTU) includes but is not limited to a wireless phone, a smartphone, a tablet, a personal computer, a Universal Serial Bus (USB) modem, a PCMCIA modem, a telemetry modem, a test modem, a user equipment (UE), a station (STA), a mobile station (MS), a subscriber terminal, a mobile terminal, and/or any other type of device capable of communicating in a wireless environment.
[0018] As used herein, wireless access point (WAP) includes but is not limited to an access point (AP), a hot spot, or a WiFi hot spot.
[0019] As used herein, the term “connected” means that elements within the system are connected physically or functionally (via, for example, a remote connection). A connection may be temporary or permanent. As a non-limiting example, a remote connection may be through a localized Radio Frequency (RF) link. Alternatively or additionally, a connection may be a wired connection through a dedicated network and/or via the Internet.
[0020] The words “a” and “one,” as used herein, are defined as including one or more of the referenced items unless specifically stated otherwise. The phrase “at least one” followed by a list of two or more items, such as “A, B, or C,” means any individual one of A, B or C as well as any combination thereof. Further, as used herein, the singular forms “a,” “an,” and “the” include plural referents unless expressly and unequivocally limited to one referent. For example, while examples are provided above wherein a single instance of a credit/credential management system (CCMS) is referred to, it may be understood that the features described herein in a single CCMS may be implemented across multiple CCMS.
[0021] Value as used herein means a good, a service, or a pecuniary interest including cash, check, credit, and conditional credit.
[0022] Transaction as used herein means an exchange involving at least two parties. A purchase is a transaction. A subscription is a specific purchase and is thus a transaction. The exchange of information about a wireless network is a transaction. Receipt of an incentive offer (such as the act of downloading an incentive offer, banking a social network “like” or the act of rendering an offer on a terminal or cellphone), presentment of incentive offer at a retailer or online, redemption of an incentive offer, rating of one more or component and participation in a consumer survey are transactions.
[0023] Purchase as used herein means a transaction in which cash, check, charge, or credit is exchanged for one or more goods and services.
[0024] Transaction incentive as used herein means an offer for a certain value in exchange for entering into a specified transaction.
[0025] Purchase incentive as used herein means an incentive wherein the specified transaction for which the incentive is offered is a purchase.
[0026] Incentive as used herein means the certain value associated with entering into a transaction specified in a transaction incentive.
[0027] Incentive terms and transaction incentive terms as used herein each mean the specifications of the transaction into which someone must enter to be entitled to the incentive associated with the transaction incentive.
[0028] Purchase incentive terms as used herein mean the specifications of the purchase into which someone must enter to be entitled to the incentive associated with the purchase incentive.
[0029] Coupons as used herein are certificates with one or more purchase incentive terms consumers present at the time of purchase.
[0030] Queries from database to database system as used herein may be done directly (through say XML or JSON queries). They may also be done using proxy servers and/or caching/fetching systems. It is understood that architectures with these types of intermediate systems are covered by the example embodiments described herein.
[0031] Classification and managements of wireless access points using taxonomies and ontologies are both described herein.
[0032] Described herein are methods and apparatus for the management of Wireless LANs, which build on two key elements: 1) the classification of wireless networks using a commercial-social centric ontology and 2) the organization of WRTUs into WRTU federations.
[0033] Ontology may be defined as the exact description of things and their relationships. Ontologies have become important elements of the web standards, especially in terms of the semantic web. OWL (Web Ontology Language released in 2004 by W3C) is the primary Web Ontology Language. It is used extensively in science classifications and market-specific e-commerce applications.
[0034] The ontology of wireless networks as used in the methods and apparatuses described herein goes beyond the physical (for instance, located at XX and YY), logical (for instance IP address 192.156.184.5), and functional (for instance, 802.11ac WiFi capable of supporting video streaming) description of wireless networks. The ontology of the methods and apparatuses described herein allows the introduction of relations between classes of wireless networks (e.g. disjoint vs. continuous coverage), cardinality (e.g. “exactly one”), equality (e.g. it may allow WiFi-camera), and characteristics of properties (e.g. hot spot moves on the schedule of the German Train System). This goes beyond taxonomies that are solely hierarchical categorizations or classifications of entities within a domain.
[0035] Ontology may also be defined as the set of all possible characteristics of the entities in a domain, and taxonomy may simply be a grouping of subsets of the domain based on common characteristics that have been chosen for the particular taxonomy.
[0036] A WRTU federation may be defined as a loosely coupled affiliation of WRTUs whose users adhere to certain standards of social behavior and/or standards of commerce. The WRTU federation may provide a mechanism for trust among those users with respect to certain operations for the users within the federation. For example, a federation partner may act as a proxy for another partner. Other partners within the same federation may rely on the user's identity provider for primary management of the user's authentication credentials or virtual private network parameters. It may further be envisioned that participants in the federation may continue to independently manage and operate their WRTUs with minimal change required to participate in the federation. A WRTU may belong to one of more federations. WRTU federations may be organized around locations (or sets of locations, such as the wireless hot spots around Piccadilly Circus), activities (travelling on the same airlines or the same train line), or commerce (lovers of the same brands of coffee).
[0037] Communications between elements of the WRTU Federation may be peer to peer, one to one, or group wide (multicast).
[0038] An Ontology Library (OLB) may used to provide collective information for the access point ontology. The OLB may be implemented in a management server. A Federation Database (FDB) may be used to manage the federation of WRTUs, and may also be implemented in a management server. The two database systems may communicate through a network, such as but not limited to the Internet. This OLB may be used to create a series of profiles that are downloaded to one or more members of one or more federations as requested by the FDB. The FDB may be connected to one or more social network gateways (such as Twitter, Facebook) through an API. This allows the integration of preferences into the activities.
[0039] FIG. 1 shows a flow chart of an example method for creating and managing a federation of WRTUs 100 in accordance with a first embodiment, which may be used in combination with any of the other embodiments described herein. The process shown in FIG. 1 may be initiated, for example, when a WRTU transmits a request to create a federation that may be received by the FDB. The FDB may then begin the federation creation process by transmitting a request for a federated community identification (FCI) from the OLB management server 101 . The FDB may then receive the FCI from the OLB management server 102 . The FDB may then store the FCI in its database 103 . The FDB may then proceed to manage the federation of WRTUs based on the FCI 104 .
[0040] The FDB may also request and receive a management policy object (MPO), which may be used with the FCI to create the federation, and the FDB may then manage the federation based on the FCI and MPO. An MPO may enable one or more transactions to be performed based in part on a defined ontology. MPOs may for example be encoded in one or more digital objects (DO), which may be transmitted to one or more WRTUs within the coverage area of a WAP or within the federation. The DOs may also be transmitted to the WRTUs in the federation based on their FCI. DOs may be taken from sources including but not limited to the following a virtual private network (VPN) profile, economic incentives, and/or transaction incentives.
[0041] FIG. 2 shows an example network architecture 200 in which method of the first embodiment described herein may be implemented. The architecture of FIG. 2 includes one more Wireless Local Area Network (WLAN) access points (WAPs) 201 a , 201 b , 201 c , and 201 d , which are managed by one or more RADIUS servers 202 . These WAPs may provide specific areas of coverage 203 a , 203 b , 203 c , and 205 with various QoS and cost of use. The architecture of FIG. 2 also includes an ontology library 206 including concept 209 . The management server and the business model attribute library 208 may be connected via the Internet 207 . Also connected to the Internet 207 are at least one or more WRTUs 214 , 216 , 217 , and 218 . The FCI may be implemented in management server 210 .
[0042] As shown in FIG. 2 , some of the WRTUs such as WRTU 214 may receive coverage only via a WLAN. Some WRTUs such as WRTU 216 may have only cellular coverage. Other WRTUs such as WRTU 217 may have coverage in both cellular and WLAN networks. Other WRTUs may have coverage from two independently controlled WLANs.
[0043] FIG. 3 is a block diagram of an example WRTU 300 that may be used to implement the features or methods described herein. The WRTU may include one or more transmitter, receivers, or transceivers 301 , a processor 302 , a memory device 303 , a data storage device 304 , and a display device 305 . These components may be connected via a system bus in the WRTU, and/or via other appropriate interfaces within the WRTU.
[0044] The memory device 303 may be or include a device such as a Dynamic Random Access Memory (D-RAM), Static RAM (S-RAM), or other RAM or a flash memory. The data storage device 304 may be or include a hard disk, a solid-state disk (SSD), or any other type of device for persistent data storage.
[0045] The one or more transceivers 301 may implement various radio access technologies, including any combination of the radio access technologies mentioned herein, including but not limited to UTMS, GSM, Edge, IS-95, WCDMA, TD-SCDMA, HSPDA, HSUDA, HSPA+, CDMA2000, IEEE 802.16 (WiMAX), LTE, 3G, 4G, TD-LTE, Bluetooth, Wireless Local Area Network (WLAN) technology, and 802.11× technology (including 802.11a/b/g/n).
[0046] The display device 305 may be a Liquid Crystal Display (LCD) or Organic Light-Emitting Diode (OLED) display device, or any other appropriate type of display device. The display may be a touchscreen display, which may be based on one or more technologies such as resistive touchscreen technology, surface acoustic wave technology, surface capacitive technology, projected capacitive technology, and/or any other appropriate touchscreen technology.
[0047] The WRTU of FIG. 3 may be configured to perform any feature or features or methods described herein as performed by a WRTU. Alternatively or additionally, the memory device 303 and/or the data storage device 304 in the WRTU may store instructions which, when executed by the processor 302 in the WRTU (in conjunction with the other components in the WRTU such as the one or more transceivers 301 , memory device 303 , display device 305 , and/or data storage device 304 ), may cause the WRTU to perform any feature or combination of features described herein as performed by a WRTU.
[0048] FIG. 4 is a block diagram of a server computer 400 that may be used to implement any of the features or methods described herein. The server computer includes one or more network interfaces 401 , a processor 402 , a memory device 403 , and a data storage device 404 . These components may be connected via a system bus in the server computer, and/or via other appropriate interfaces within the server computer.
[0049] The memory device 403 may be or include a device such as a Dynamic Random Access Memory (D-RAM), Static RAM (S-RAM), or other RAM or a flash memory. The data storage device may be or include a hard disk, a solid-state disk (SSD), or any other type of electronic device for persistent data storage.
[0050] The one or more network interfaces 401 may be or include one or more wired and/or wireless transceivers, and/or may implement various wired and/or wireless data communication technologies, including any combination of the radio access technologies mentioned herein. Alternatively or additionally, the one or more network interfaces may implement technologies such as IEEE 802.3 and/or Digital Subscriber Line (DSL) technology.
[0051] The server computer of FIG. 4 may be configured to perform any feature or method or combination of features or methods described herein as performed by a server computer, and/or any feature or combination of features described herein as performed by an AAME, AS, and/or WS. Alternatively or additionally, the memory device 403 and/or the data storage device 404 in the server computer may store instructions which, when executed by the processor 402 in the server computer (in conjunction with the other components in the server computer such as the one or more network interfaces 401 , memory device 403 , and/or data storage device 404 ), may cause the server computer to perform any feature or combination of features described herein as performed by an AAME, AS, and/or WS.
[0052] In another embodiment a federation of WAPs may be managed by an FDB or OLB management server in a federation of WAPs to integrate wireless connectivity management and business applications. For example, a request to create a federation may be received from a WAP, and a record may be created for the WAP in an OLB management server. WAP descriptions may then be stored as concepts of a device ontology in the OLB management server. WAP operational parameter descriptions may be stored as concepts of a performance ontology in the OLB management server. Then the device and performance ontologies based on the descriptions may be used to identify operations supported by the WAP and to store the identified operations in the OLB management server. These descriptions may include but are not limited to being associated with device specifications and/or performance parameters. The concepts may include but are not limited to mobile, mobile affixed on train, mobile affixed on airplane, mobile affixed on public transit, mobile affixed on airplane located in specific airport, mobile in common commercial area, private, commercial, business, governmental, NGO, humanitarian, and military. The OLB management server may then be scanned for WAP entries and a federation may be created based on the concepts in the OLB management server.
[0053] Alternatively or additionally, a collection of WAPs may be managed by obtaining business model attributes (BMAs) based on the location of a WAP. Specific BMAs may be extracted from the available BMAs based on geographic location. The BMAs may then be matched with concepts in an OLB management server according to geographic location, and the WAP may then be assigned incentive or transaction terms defined in the OLB management server based on the matched BMAs. The BMAs may include but is not limited to: permanent free access, free access for loyal customers, rental access, trade access, credit for access, and relay access. The OLB management server may then be scanned for WAP entries and a federation may be created based on the concepts in the OLB.
[0054] In another embodiment, a federated WRTU may expect coverage in a specific area. If the WRTU does not get coverage, it may record that absence into memory and transmit this information at a later time (for example in a another hot spot) or by using the broad area cellular network.
[0055] In another embodiment, the OLB management server may interface with one or more external servers associated with services to which consumers whose own federated WRTUs subscribe to or use. Unlike systems that cluster WAPs based on topology or geography, this embodiment may allow rules for access to networks and services within this network to be expressed at the semantic level and thus adapt a natural language processing or domain specific from the World Wide Web. This may allow for rich service descriptions. One example may be to associate knowledge that a consumer is at a specific train station, to prompt him for a destination (or integrate with a travel site such as tripit.com), to determine the one or many destinations the user might be going to, and to download the appropriate configuration information into the WRTU either at the station or during transit. This may be accomplished by having domain specific knowledge and a way to express and leverage that knowledge. Because the knowledge about hotspots is ontological in nature, it may be readily adapted for new information (such as a breakdown of specific spots) and new services.
[0056] Capturing the real time nature of that knowledge may be included in yet another embodiment. In this embodiment, the FDB may assign specific elements for monitoring the performance of one or more hot spots to a subset of federated WRTUs, effectively spreading the sensing and reporting load over a wide range. Whenever the FDB detects (many detection algorithms may be used including but not limited to location based probing, time based probing, or interfacing to a RADIUS server) a federated WRTU in a specific hot spot, the FDB may determine what sensing algorithm(s) (or parameters) to send to said WRTU for implementation. The FDB may also send different parameters to other members of the WRTU federation. One use of this embodiment may be mapping the throughput at a specific hot spot controlled by a WAP. If only one member of the WRTU federation is using the hot spot, throughput measurements may be done and reported at a predetermined frequency, such as every 10 minutes. This may be done because this hot spot is considered to be lightly loaded and thus unlikely to be throughput challenged. If ten members of the WRTU federation are using the same hot spot, however, the throughput may be reduced and require more reporting (not necessarily more probing by each member). The effective measurement rate may be changed to once every minute by distributing probing among WRTUs. If for example, twenty members of the WRTU federation use the same spot, the measurement rate may be changed to once every five minutes to preserve battery life.
[0057] In another embodiment, the FDB may manage a policy for sharing information about hot spots and the commerce supported by the hot spots. This may allow WRTUs that are members of a federation to benefit from others in the federation and thus create an incentive to increase and energize said federation. In this embodiment, whenever a member of the federation receives for example a series of VPN configurations or an electronic coupon, other members of the same federation (filtered based on their locations and preferences) may receive the same item. This may insure a group discovery of new hotspots and new commercial offers. In another embodiment, WRTUs may have the ability to forward those items to members of the federation. In another embodiment, WRTUs may have the ability to forward a subset of those items to non-members of the federation.
[0058] In yet another embodiment, the OLB may interface with one or more ecommerce web sites, enabling the integration of commercial incentives and economic incentives with wireless access. This integration may enable the owner of a WAP to offset the cost of providing network access for his consumers and providing an instantaneous linkage between access to wireless services and other economic activities. This linkage may be bidirectional wireless access to commercial incentives as well as commercial incentives to wireless access. An example of such integration may be, but is not limited to, for example a coffee shop that permits access to the WAP if something is purchased). Whenever a federated WRTU comes into the coverage area, a configuration message indicating this linkage may be displayed on the WRTU. When the WRTU owner accepts the offer, access to the wireless network (or a subset of wireless network capabilities) may be downloaded along with the automated economic transaction (in this case the purchase of a cup of coffee).
[0059] It should be understood that the features described herein are not limited to the particular embodiments disclosed, but is are to cover all modifications which are within the spirit and scope of the described features, as defined by the appended claims, the above description, and/or as shown in the attached drawings.
[0060] Although features and elements are described above in particular combinations, one of ordinary skill in the art will appreciate that each feature or element can be used alone or in any combination with the other features and elements. Although the solutions described herein consider 802.11 specific protocols, it is understood that the solutions described herein are not restricted to this scenario and are applicable to other wireless systems as well. In addition, the methods described herein may be implemented in a computer program, software, or firmware incorporated in a computer-readable medium for execution by a computer or processor. Examples of computer-readable media include electronic signals (transmitted over wired or wireless connections) and computer-readable storage media. Examples of computer-readable storage media include, but are not limited to, a read only memory (ROM), a random access memory (RAM), a register, cache memory, semiconductor memory devices, magnetic media such as internal hard disks and removable disks, magneto-optical media, and optical media such as CD-ROM disks, and digital versatile disks (DVDs). A processor in association with software may be used to implement a radio frequency transceiver for use in a WRTU, UE, terminal, base station, RNC, or any host computer.
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The subject matter described herein relates to wireless network discovery, management, the enabling of services, and economic exchanges in a cooperative manner by one or more federated sets of consumers, one or more access point providers, and one or more wireless service providers. Described herein are methods and apparatus for the discovery, classification, and management of wireless networks. The methods and apparatuses described herein may leverage two complementary elements impacting the performance of wireless LANs: (1) organization and management of the wireless access points (hot spots) from an ontology perspective, and (2) organization of mobile devices as a federation.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention lies within the field of eye shields/eye protectors, specifically those intended for infants requiring phototherapy treatment.
2. Description of Prior Art
Phototherapy treatment of infants require that as much skin area be exposed to the light rays as possible in order that the treatment have maximum effectiveness in counteracting the illness, specifically physiologic jaundice or hyperbilirubinemia. These is no known prior art which incompasses all the features desirable to protect the infant's eyes, i.e., maximum eye protection with minimum skin area coverage, ease of installation on and removal from the infant's head, and low cost.
Presently, nurses attending such infants use gauze pads over the infant's eyes. The gauze is secured with surgical tape placed over the gauze and adhesively secured to the infant's temples.
Inherent disadvantages of this prior art are (1) the quality and quantity of gauze used is susceptible to human judgement, (2) the frequent and necessary changing and removal of gauze injures the infant's skin as the tape is pulled from the temple and (3) the high cost of said prior art.
SUMMARY AND OBJECTS OF THE INVENTION
The invention is a preformed eye shield for infants which covers a minimum amount of skin area. The shield has the general shape of typical eye shields and is made of sterilized flexible material having a soft, nap like fiberous surface. Adhesive tabs, consisting of the hook side of Velcro with pressure sensitive adhesive on the back side thereof, are attached to the infants temples by the use of the adhesive back side. The shield is secured to the infant by the use of temple elements which are singularly attached to the tabs as Velcro hook and loop fastening means.
It is a primary object of the invention to have an eye shield which is of minimum size so as to cover the least possible skin area of an infant under phototherapy treatment.
It is a further object of the invention to provide such an eye shield which will not injure the infant upon removal of same.
Additionally, it is an object of the invention to have a low cost, disposable eye shield which is not susceptible to human error and/or judgement.
It is also an object of the invention to overcome those objections to prior art enumerated above.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates the eye shield in a plan view.
FIG. 2 illustrates the eye shield as worn by an infant.
FIG. 3 illustrates a modification to the eye shield in a plan view.
FIG. 4 is a detail of the adhesive tabs.
DESCRIPTION OF THE PREFERRED EMBODIMENT
While the preferred embodiment is illustrated and described below, it is to be understood that variations will be apparent to those skilled in the art without departing from the principles of the invention. Accordingly, the invention is not to be limited to the specific form as described and illustrated but rather is to be limited only by a literal interpretation of the claims appended herein.
FIG. 1 illustrates the invention, a one piece Infant Eye Shield 1 consisting of an eye piece 10 of two generally oval shaped protective areas 2 which are joined together by a bridge area 3. Said protective areas 2 are sized to cover the infant's eye and the area immediately surrounding the eye, approximately 3/4 inch by 1 inch in size. Said bridge area 3 fits over the infant's nose.
Radiating outwardly from each protective area 2 is a temple element 4 of a general triangular shape terminating at its apex in an element end 5.
Removably attached to the skin side of each said end 5 is an adhesive tab 6. The materials used for said tab 6 and temple elements 4 below are used in combination to form a VELCRO type fastener as known in the art. This type of fastener consists of two material forms; one having a multiplicity of small hooks on its surface and known as the `hook portion`, and the other having a soft nap-like, fiberous material with a multiplicity of small thread-like loops on its surface and known as the `loop portion`. The joining or pressing together of these surfaces causes said hooks to engage said loops, whereby the surfaces are securely fastened together. The surfaces are seperable by manually peeling one material away from the other. Said tab 6 is detailed in FIG. 4 and consists of the hook portion 7 of a Velcro fastener on one side thereof and self sticking adhesive 8 on the opposite side thereof, the latter side designated as the skin side 9 and the former designated as the outer side of said tab 6. An easily removable piece of waxed paper 13 covers said adhesive 8 during storage and manufacturing to prevent the drying out and/or contamination of the adhesive 8 prior to use. The ends 5, as described below, act as the loop side of a Velcro fastener.
The material used in the shield 1 is sterilized cloth having a soft nap like fiberous material resembling the loop portion of a Velcro fastening means. The major consideration for the material is that it be light proof, (a maximum of 3% light transmissability), from the phototherapy light, thereby insuring protection to the infant's eyes. The material may be multiple layers to insure the light proof requirement. The nap and hook portion 7 is selected so that the ratio of peel strength to shear strength is less than unity. This ratio insures that the shield 1 can easily be peeled from said tab 6 when desired while maintaining a high resistance to being pulled off as the infant turns his head against the bed clothing.
The adhesive 8 selected has a higher peel strength than that of the Velcro fastening device. This insures that when peeling said shield 1 from said tab 6, the tab 6 remains attached to the infant. Additionally, the adhesive 8 has sufficient shear capability to secure the shield 1 to the infant while its peel strength is such that the tab 6 is easily peeled from the infants skin without injury thereto. It's this unique combination of peel vs shear strength between the adhesive 8, hook portion 7, and nap like material which insures the inventions safety and useability.
Placement of said shield 1 on the infant is illustrated in FIG. 2 and described below. The nurse removes the waxed paper 13 from said tabs 6 and gently but firmly attaches the tab 6 skin side to the temple areas of the infant. The shield 1 is then centered over the infant's eyes. Said ends 5 are then attached to the tabs 6 via the hook portion 7 such that the shield 1 is snug but not uncomfortably tight on the infant. Said end 5 is to lie wholly on said tab 6 and not extend over thereof. This insures that an extended end 5 is not caught and rolled off (peeled) a tab 6 as an infant rolls his head (and said end 5) against the bed clothing.
FIG. 3 is a plan view of a modified eye shield 1a which differs only in that it's not one piece construction but requires separate temple elements 4a to be securely attached to the outer ends of said protective areas 2. Said elements 4a are similar in form, fit and function as to said elements 4 and require the use of said tabs 6 as described above. The attachment of said elements 4a to said areas 2 is by sewing.
The advantage of said shield 1a is the possibility of using different materials for said elements 4a and said areas 2, 3. In all instances the elements 4a will be of the same soft nap like material described above wherein said areas 2, 3 are constructed of less expensive gauze like material which is also light proof. An additional material for said areas 2, 3 is plastic film 11 which is specifically coated to be light proof. Additionally, combinations of said film 11 and gauze like material can be used for said areas 2, 3 by simply attaching or stitching 12 the combinations together as illustrated in FIG. 3.
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The invention is an Infant Eye Shield specifically used to protect the eyes of premature and full term infants requiring phototherapy treatment. The shield is constructed to be of the absolute minimum size to expose the greatest amount of skin area to the light rays. It is adhesively attached to the infant for ease of removal without injury to the sensitive skin. The shield is intended to be reuseable but its low cost permits disposable use.
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PRIORITY DATA
[0001] This application claims the benefit of U.S. Provisional Application No. 61/171,151 filed Apr. 21, 2009, said application hereby incorporated by reference in its entirety.
U.S. GOVERNMENT GRANT
[0002] Research leading to the inventions described herein was conducted under a grant from NIH: 5R37DK049108.
BACKGROUND OF THE INVENTION
[0003] Iron occurs in oxidation states from −2 to +6 depending on both pH and the nature of the ligating groups surrounding the metal [Bergeron, R. J.; Brittenham, G. M. The Development of Iron Chelators for Clinical Use . CRC: Boca Raton, Fla., 1994]. It is these dependencies that nature has exploited so effectively in enlisting the metal as a central component in a myriad of redox processes [Bergeron, R. J.; McManis, J. S.; Wiegand, J.; Weimar, W. R. A Search for Clinically Effective Iron Chelators. In Iron Chelators: New Development Strategies , Badman, D. G.; Bergeron, R. J.; Brittenham, G. M., Eds. Saratoga: Ponte Vedra Beach, Fla., 2000; pp 253-292]. In fact, life without iron is virtually nonexistent [Crichton, R. R. Inorganic Biochemistry of Iron Metabolism . J. Wiley & Sons: Chichester, UK, 2001]. However, while the metal composes some 5% of the earth's crust, it is nevertheless difficult for living systems to access. In the biosphere, iron exists largely as Fe (III), in a variety of water insoluble forms, at pH 7. The concentration of free Fe(III) under these conditions is ≈1.4×10 −9 M [Chipperfield, J. R.; Ratledge, C. Salicylate Is Not a Bacterial Siderophore: A Theoretical Study. BioMetals 2000, 13, 165-168], somewhat lower than that required to support most life forms. In the presence of phosphate ions in culture media and potential animal hosts, the free Fe(III) concentration in solution drops even further, by a factor of 10.
[0004] Both prokaryotes and eukaryotes have overcome the problem of iron accessibility by developing iron-binding ligands and associated transport systems [Bernier, G.; Girijavallabhan, V.; Murray, A.; Niyaz, N.; Ding, P.; Miller, M. J.; Malouin, F. Desketoneoenactin-Siderophore Conjugates for Candida: Evidence of Iron Transport-Dependent Species Selectivity. Antimicrob. Agents Chemother. 2005, 49, 241-248; Walz, A. J.; Mollmann, U.; Miller, M. J. Synthesis and Studies of Catechol-Containing Mycobactin S and T Analogs. Org. Biomol. Chem. 2007, 5, 1621-1628; Yuan, W. M.; Gentil, G. D.; Budde, A. D.; Leong, S. A. Characterization of the Ustilago maydis sid2 Gene, Encoding a Multidomain Peptide Synthetase in the Ferrichrome Biosynthetic Gene Cluster. J. Bacteriol. 2001, 183, 4040-4051; Byers, B. R.; Arceneaux, J. E. Microbial Iron Transport: Iron Acquisition by Pathogenic Microorganisms. Met. Ions Biol. Syst. 1998, 35, 37-66; Kalinowski, D. S.; Richardson, D. R. The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer. Pharmacol Rev. 2005, 57, 547-583; Bergeron, R. J. Iron: A Controlling Nutrient in Proliferative Procsses. Trends Biochem. Sci. 1986, 11, 133-136; Theil, E. C.; Huynh, B. H. Ferritin Mineralization: Ferroxidation and Beyond. J. Inorg. Biochem. 1997, 67, 30 and Ponka, P.; Beaumont, C.; Richardson, D. R. Function and Regulation of Transferrin and Ferritin. Semin. Hematol. 1998, 35, 35-54]. Prokaryotes produce a group of iron chelators or siderophores (generally low-molecular weight, iron-specific ligands) that they secrete into the environment. These ligands often present with very large formation constants (e.g., 10 48 M −1 ) [Bergeron, R. J.; McManis, J. S. Synthesis of Catecholamide and Hydroxamate Siderophores. In CRC Handbook of Microbial Iron Chelates , Winkelmann, G., Ed. CRC: Boca Raton, 1991; pp 271-307] and can effectively remove the metal from other donor arrays. The resulting metal complex, a ferrisiderophore, is then taken up by microorganisms [Ratledge, C.; Dover, L. G. Iron Metabolism in Pathogenic Bacteria. Annu. Rev. Microbiol. 2000, 54, 881-941; Nicholson, M. L.; Beall, B. Disruption of tonB in Bordetella bronchiseptica and Bordetella pertussis Prevents Utilization of Ferric Siderophores, Haemin, and Haemoglobin as Iron Sources. Microbiology 1999, 145, 2453-2461 and Occhino, D. A.; Wyckoff, E. E.; Hernderson, D. P.; Wrona, T. J.; Payne, S. M. Vibrio cholerae Iron Transport: Haem Transport Genes Are Linked to One of Two Sets of tonB, exbB, exbD Genes. Mol. Microbiol. 1998, 29, 1493-1507], most often beginning with binding to an outer membrane receptor [Stojiljkovic, I.; Srinivasan, N. Neisseria meningitidis tonB, exbB, and exbD Genes: Ton-Dependent Utilization of Protein-Bound Iron in Neisseriae. J. Bacteriol. 1997, 179, 805-812]. This is followed by shuttling the iron complex through the periplasm and finally, to the cytoplasm, where the iron is freed up. These ferrisiderophore transporters are energy-dependent, often exploiting the tonB system [Griffiths, E.; Williams, P. H. The Iron - Uptake Systems of Pathogenic Bacteria, Fungi, and Protozoa. 2 ed.; John Wiley & Sons: Chichester, UK, 1999; Ochsner, U. A.; Johnson, Z.; Vasil, M. L. Genetics and Regulation of Two Distinct Haem-Uptake Systems, phu and has, in Pseudomonas aeruginosa. Microbiology 2000, 146, 185-198 and Stoebner, J. A.; Payne, S. M. Iron-Regulated Hemolysin Production and Utilization of Heme and Hemoglobin by Vibrio cholerae. Infect. Immun. 1988, 56, 2891-2895]. In most instances, the desferrisiderophore is released to further gather iron.
[0005] There have now been over 500 different siderophores identified [Drechsel, H.; Winkelmann, G. Iron Chelation and Siderophores. In Transition Metals in Microbial Metabolism , Winkelmann, G., Carrano, C. J., Eds. Harwood Acad.: Amsterdam, the Netherlands, 1997; pp 1-9; Neilands, J. B. Siderophores: Structure and Function of Microbial Iron Transport Compounds. J Biol. Chem. 1995, 270, 26723-26726; Telford, J. R.; Raymond, K. N. Siderophores. In Comprehensive Supramolecular Chemistry , Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vogtle, F., Lehn, J-M., Eds. Elsevier Sci.: Oxford, UK, 1996; Vol. 1, pp 245-266; Winkelmann, G. CRC Handbook of Microbial Iron Chelates . CRC: Boca Raton, Fla., 1991 and Winkelmann, G.; Drechsel, H. Microbial Siderophores. Biotechnology. 2 ed.; Verlag Chem.: Weinheim, Germany, 1997; Vol. 7]. While there are certainly exceptions, the two main classes of natural product iron chelators are hydroxamates [Bergeron, R. J.; Phanstiel, O., IV. The Total Synthesis of Nannochelin: A Novel Cinnamoyl Hydroxamate-Containing Siderophore. J. Org. Chem. 1992, 57, 7140-7143; Bergeron, R. J.; McManis, J. S. Synthesis and Biological Activity of Hydroxamate-Based Iron Chelators. In The Development of Iron Chelators for Clinical Use , Bergeron, R. J.; Brittenham, G. M., Eds. CRC: Boca Raton, 1994; pp 237-273; Bergeron, R. J.; McGovern, K. A.; Channing, M. A.; Burton, P. S. Synthesis of N 4 -Acylated N 1 ,N 8 -Bis(Acyl)Spermidines: An Approach to the Synthesis of Siderophores. J. Org. Chem. 1980, 45, 1589-1592; Bergeron, R. J.; Kline, S. J. Short Synthesis of Parabactin. J. Am. Chem. Soc. 1982, 104, 4489-4492; Bergeron, R. J.; McManis, J. S.; Dionis, J. B.; Garlich, J. R. An Efficient Total Synthesis of Agrobactin and Its Gallium(III) Chelate. J Org. Chem. 1985, 50, 2780-2782 and Bergeron, R. J.; Garlich, J. R.; McManis, J. S. Total Synthesis of Vibriobactin. Tetrahedron 1985, 41, 507-510], such as desferrioxamine (1) and catecholamides [Bergeron, R. J.; Pegram, J. J. An Efficient Total Synthesis of Desferrioxamine. J. Org. Chem. 1988, 53, 3131-3134; Bergeron, R. J.; McManis, J. S. The Total Synthesis of Desferrioxamines E and G. Tetrahedron 1990, 46, 5881-5888; Bergeron, R. J. Synthesis and Solution Structures of Microbial Siderophores. Chem. Rev. 1984, 84, 587-602; Bergeron, R. J.; McManis, J. S. Total Synthesis of Bisucaberin. Tetrahedron 1989, 45, 4939-4944 and Bergeron, R. J.; McManis, J. S.; Perumal, P. T.; Algee, S. E. The Total Synthesis of Alcaligin. J. Org. Chem. 1991, 56, 5560-5563], including vulnibactin (2) and vibriobactin (3) ( FIG. 1 ). Some microorganisms can, in fact, utilize more than one type and/or class of siderophores [Kim, C.-M.; Park, Y.-J.; Shin, S.-H. A Widespread Desferrioxamine-Mediated Iron-Uptake System in Vibrio vulnificus. J. Infect. Dis. 2007, 196, 1537-1545].
[0006] Iron acquisition becomes somewhat more problematic for microorganisms in an in vivo situation (e.g., in humans). Pathogens have additional iron acquisition hurdles to overcome beyond low metal solubility. Animals, for example, have an iron-withholding system: proteinaceous iron chelators that make iron acquisition difficult for microorganisms. There is little of the free metal available in animals. It is generally bound to heme (iron-containing enzymes) by transferrin, (an iron shuttle protein) or stored in ferritin. In each instance, iron is not easily accessible to microorganisms.
[0007] The opportunistic microorganism Vibrio vulnificans nicely illustrates how pathogens can overcome host iron-withholding [Stoebner, J. A.; Butterton, J. R.; Calderwood, S. B.; Payne, S. M. Identification of the Vibriobactin Receptor of Vibrio cholerae. J. Bacteriol. 1992, 174, 3270-3274]. The siderophore produced by Vibrio vulnificans , vulnibactin (2) ( FIG. 1 ), cannot remove iron from transferrin, the ever-present iron shuttle protein in plasma, in spite of the fact 2 binds iron more tightly than transferrin. The chelator cannot access transferrin iron, as it is bound within the protein.
[0008] To solve this problem, the microorganism secretes a protease, which cleaves transferrin, thus releasing iron. The metal is then sequestered by 2, and the ferrisiderophore is taken up via an intermembrane receptor, viuA [Butterton, J. R.; Stoebner, J. A.; Payne, S. M.; Calderwood, S. B. Cloning, Sequencing, and Transcriptional Regulation of vuuA, the Gene Encoding the Ferric Vibriobactin Receptor of Vibrio cholerae. J. Bacteriol. 1992, 174, 3729-3738; Simpson, L. M.; Oliver, J. D. Siderophore Production by Vibrio vulnificus. Infect. Immun. 1983, 41, 644-649 and Okujo, N.; Akiyama, T.; Miyoshi, S.; Shinoda, S.; Yamamoto, S. Involvement of Vulnibactin and Exocellular Protease in Utilization of Transferrin- and Lactoferrin- Bound Iron by Vibrio vulnificus. Microbiol. Immunol. 1996, 40, 595-598].
[0009] In fact, Vibrio vulnificans mutants without the vulnibactin transporter have reduced pathogenicity in mice [Webster, A. C. D.; Litwin, C. M. Cloning and Characterization of vuuA, a Gene Encoding the Vibrio vulnificus Ferric Vulnibactin Receptor. Infect. Immun. 2000, 68, 526-534]. This uptake apparatus has been shown to have significant homology with the Vibrio cholerae receptor. However, while it seems clear from studies with genetically altered microorganisms that shutting down the siderophore iron-uptake system can slow growth and reduce pathogenicity, microorganisms can still access iron via other mechanisms [Henderson, D. P.; Payne, S. M. Vibrio cholerae Iron Transport Systems: Roles of Heme and Siderophore Iron Transport in Virulence and Identification of a Gene Associated with Multiple Iron Transport Systems. Infect. Immun. 1994, 62, 5120-5125; Litwin, C. M.; Rayback, T. W.; Skinner, J. Role of Catechol Siderophore in Vibrio vulnificus Virulence. Infect. Immun. 1996, 64, 2834-2838 and Stelma, G. N.; Reyes, A. L.; Peeler, J. T.; Johnson, C. H.; Spaulding, P. L. Virulence Characteristics of Clinical and Environmental Isolates of Vibrio vulnificus. Appl. Environ. Microbiol. 1992, 58, 2776-2782]. For example, Vibrio cholerae can utilize transferrin and heme as iron sources. The issue then becomes how useful a target the siderophore transport apparatus is in antimicrobial design strategies.
[0010] Miller has, in a series of classic studies, employed siderophores and the corresponding transporters as vectors for the delivery of antibiotics [Miller, M. J.; Malouin, F. Siderophore-Mediated Drug Delivery: The Design, Synthesis, and Study of Siderophore-Antibiotic and Antifungal Conjugates. In The Development of Iron Chelators for Clinical Use , Bergeron, R. J.; Brittenham, G. M., Eds. CRC: Boca Raton, 1994; pp 275-306]. Alternatively, Esteve-Gassent was able to demonstrate that a vaccine developed to treat eels infected with Vibrio vulnificus serovar E. contained antigens to the putative receptor for vulnibactin. Esteve-Gassent point out that the antibody could be blocking siderophore uptake, could trigger classical complement activation, or “mark bacteria for opsonophagocytosis.” [Esteve-Gassent, M. D.; Amaro, C. Immunogenic Antigens of the Eel Pathogen Vibrio vulnificus Serovar E. Fish Shellfish Immunol. 2004, 17, 277-291].
SUMMARY OF THE INVENTION
[0011] One embodiment of the invention relates to an immunogenic composition comprising a siderophore covalently linked to a pharmaceutically acceptable carrier molecule wherein the antigenicity of the siderophore moiety is sufficient to stimulate an immunologic response to the siderophore on a surface of a microorganism at the siderophore transporter level when the composition is circulating in the bloodstream of a human or non-human animal.
[0012] Another embodiment of the invention concerns a bacterial vaccine suitable for administration to a human or non-human animal comprising the above-described composition and a pharmaceutically acceptable carrier.
[0013] An additional embodiment of the invention comprises a method for immunizing a human or non-human animal against infection by at least one strain of bacteria, comprising administering to the animal a sufficient amount of the above-described vaccine to enhance the immune system thereof to infection; i.e., by stimulating the production of antibodies to at least one siderophore-siderophore receptor protein-complex of at least one strain of bacteria when the vaccine is circulating in the bloodstream of a human or non-human animal.
[0014] Still another embodiment of the invention relates to an article of manufacture comprising a package and, contained therein, at least one separately packaged dosage amount of the above-described immunogenic composition sufficient to stimulate production of antibodies to at least one siderophore-siderophore receptor protein-complex of at least one strain of bacteria when the composition is circulating in the bloodstream of a human or non-human animal, wherein the package is associated with instructions for administering the dosage amount to a human or non-human animal.
[0015] A further embodiment of the invention comprises an article of manufacture comprising a package and, contained in the package, at least one separately packaged dosage amount of the above-described vaccine sufficient to stimulate production of antibodies to at least one siderophore receptor protein of at least one strain of bacteria when said vaccine is circulating in the bloodstream of a human or non-human animal, wherein said package is associated with instructions for administering said dosage amount to a human or non-human animal.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIGS. 1 , 2 and 5 depict structural formulas of various compounds identified in the application.
[0017] FIGS. 3 and 4 depicts competitive binding ELISA for compounds of the invention
[0018] FIGS. 6-8 depict reaction schemes for synthesizing representative compounds of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The present invention is predicated on the discovery that siderophores, as well their iron complexes, where affixed to pharmaceutically acceptable large carrier molecules, exhibit sufficient antigenicity to induce antibodies to microbial outer membrane ferrisiderophore complexes, thereby rendering them useful for immunogenic applications such as, for example, the formulation of bacterial vaccines.
[0020] The invention is illustrated by reference to the following specific, working examples. It will be understood by those skilled in the art that the invention is not strictly limited to the illustrative examples, but rather, is inclusive of variations and extrapolations therefrom which are determinable by one skilled in the art, based on the teachings herein.
[0021] A VIB analogue, presenting with a thiol tether, 1-(2,3-dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraazatetradecane, was synthesized ( FIGS. 2 , 6 ).
[0022] The key step in the synthesis of the vibriobactin thiol is the assembly of 1,36-bis(2,3-dihydroxybenzoyl)-15,22-dioxo-18,19-dithia-1,5,9,14,23,28,32,36-octaaza-5,9,28,32-tetrakis(L-threonyl)hexatriacontane tetrakis(trifluoroacetate) ( FIGS. 8 , 25 ). The threonyl units were condensed with ethyl 2,3-dihydroxybenzimidate to generate the corresponding tetrakis(oxazoline). The resulting vibriobactin disulfide analogue was reduced to the vibriobactin thiol, and linked to both maleimide-activated ovalbumin (OVA) and bovine serum albumin (BSA).
[0023] When mice were immunized with the resulting OVA-VIB conjugate, a selective and unequivocal antigenic response to the VIB hapten was observed. The BSA-VIB conjugate was used initially for the detection of murine serum polyclonal antibodies, and ultimately IgG vibriobactin-specific monoclonal antibodies. The results are consistent with the concept that isolated adducts of siderophores covalently linked to their bacterial outer membrane receptor proteins represent credible targets for vaccine development.
[0024] There is now significant literature that supports the fact that many microorganisms present with outer membrane receptors for the binding and internalization of their ferrisiderophore complexes. It is not unreasonable, therefore to theorize that on binding to the microbial receptors, the iron siderophore complex is at least initially exposed. If sufficiently antigenic, this “ferrisiderophore face” represents a significant target in vaccine development. The antigenicity of a ferrisiderophore fixed to a large carrier molecule was determined. It was found to be very antigenic, meriting the assembly of ferrisiderophores with functionality that allow for covalent linkage to the transporter and isolation of the adduct or linking the ferrisiderophore to a C-terminal polypeptide fragment of the outer membrane receptor protein as potential vaccines. Optionally, protein adducts such as OVA- or BSA-ferrisiderophores or siderophore conjugates may be employed as vaccines.
[0025] Sufficient antigenicity of a ferrisiderophore bound to a large carrier molecule to function as a vaccine requires addressing specific issues: 1) assembling a carrier siderophore conjugate, i.e., a protein carrier conjugate, 2) raising antibodies to the conjugate in animals, and 3) assessing the antigenicity of the protein siderophore and its iron complex.
Antigen Design Concept.
[0026] The examples herein focus on the generation of antibodies against vibriobactin-carrier complexes (3, VIB). The hexacoordinate iron chelator, vibriobactin, is a siderophore, responsible for iron utilization in Vibrio cholerae [Griffiths, G. L.; Sigel, S. P.; Payne, S. M.; Neilands, J. B. Vibriobactin, a Siderophore from Vibrio cholerae. J. Biol. Chem. 1984, 259, 383-385 and Payne, S. M.; Finkelstein, R. A. Siderophore Production by Vibrio cholerae. Infect. Immun. 1978, 20, 310-311]; however, it will be understood by those skilled in the art that the invention is equally susceptible to using any suitable siderophore; e.g., enterobactin, aureochelin, petrobactin, vulnibactin and the like.
[0027] Vibriobactin (3, VIB) is attractive for two reasons: Vibrio cholerae represents an important pathological target [Crosa, J. H. Signal Transduction and Transcriptional and Posttranscriptional Control of Iron-Regulated Genes in Bacteria. Microbiol. Mol. Biol. Rev. 1997, 61; Crosa, J. H. Molecular Genetics of Iron Transport as a Component of Bacterial Virulence. In Iron and Infection: Molecular, Physiological, and Clinical Aspects, 2 ed.; Bullen, J. J.; Griffiths, E., Eds. John Wiley & Sons: Chichester, UK, 1999; pp 255-288 and Litwin, C. M.; Calderwood, S. B. Role of Iron in Regulation of Virulence Genes. Clin. Microbiol. Rev. 1993, 6, 137-149], and critical information about vibriobactin chemistry had been established in earlier studies. Accordingly, an ovalbumin (OVA) vibriobactin protein conjugate (4, OVA-VIB) was investigated as an antigen.
[0028] A fundamental issue is to append a tether to vibriobactin ( FIGS. 2 , 6 ), which would allow for fixing the ligand to a carrier protein, in this case, both OVA and bovine serum albumin (BSA). This demanded a synthetic approach very different from the assembly of vibriobactin itself. The OVA-VIB conjugate (4) would be used as an antigen to raise antibodies in mice, and the BSA-VIB conjugate (5) would be utilized in an enzyme-linked immunosorbent assay (ELISA), first for the detection of serum polyclonal antibodies, and finally, vibriobactin-specific IgG monoclonal antibodies. Thus, choosing the appropriate activated tether for the vibriobactin protein conjugate was the first hurdle. While a number of different tethers were considered (e.g., acyl, halo, thiol), previous experience with hypusine antibody generation [Bergeron, R. J.; Weimar, W. R.; Müller, R.; Zimmerman, C. O.; McCosar, B. H.; Yao, H.; Smith, R. E. Synthesis of Reagents for the Construction of Hypusine and Deoxyhypusine Peptides and Their Application as Peptidic Antigens. J. Med. Chem. 1998, 41, 3888-3900] encouraged pursuit of a thiol-containing tether. The final ligand would be 1-(2,3-dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraRzatetradecane (6), or vibriobactin thiol ( FIG. 2 ).
[0029] A catechol protecting group other than methyl, that is, one that could be removed concurrently with the BOC functionality while leaving the disulfide intact, was required. Thus, 2,3-dihydroxybenzoic acid (18) was converted to its trianion with NaH in DMF and treated with excess 4-methoxybenzyl bromide to make ester 19 in 62% yield. Hydrolysis of 19 with NaOH (aqueous) in dioxane produced 2,3-bis(4-methoxybenzyloxy)benzoic acid (20) in 90% recrystallized yield (Scheme 1: Synthesis of 20 a . a Reagents: (a) 60% NaH, 4-methoxybenzyl bromide (3.5 equivalents), DMF, 62%; (b) 2N NaOH, dioxane, 90%). Activation of an equivalent of carboxylic acid 20 with CDI and stirring with N 12 -(phthaloyl)thermospermine (12) in CH 2 Cl 2 and NEt 3 afforded diamine 21 in 57% yield ( FIG. 6 ).
[0030] The secondary amines of 21 were acylated with the active ester of N-(BOC)-L-threonine as before to generate tetraamine derivative 22 in 60% yield. The phthalimide protecting group of 22 was removed in 90% yield with hydrazine hydrate in EtOH at room temperature, yielding intermediate 23, two equivalents of which were joined utilizing 3,3′-dithiodipropionic acid (CDI in CH 2 Cl 2 ), resulting in disulfide 24 in 60% yield. The threonyl carbamates and the 4-methoxybenzyl ethers [Fletcher, S.; Gunnings, P. T. Mild, Efficient and Rapid O-Benzylation of the Ortho-Substituted Phenols with Trifluoroacetic Acid. Tetrahedron Lett. 2008, 49, 4817-4819] of 24 were simultaneously cleaved, using TFA in anisole and CH 2 Cl 2 ; Sephadex LH-20 purification resulted in a 60% yield of disulfide 25, a tetrakis(TFA) salt. The threonyl moieties of 25 were next condensed with excess ethyl 2,3-dihydroxybenzimidate in refluxing EtOH to produce tetrakis(oxazoline) disulfide 26 in 20% yield. Finally, disulfide iron chelator 26 was cleaved to the free thiol 6 in 60% yield, utilizing H 2 (3 atm) over Pd black in CH 3 OH under iron-free conditions ( FIG. 7 ).
[0000] Functionalization of Vibriobactin Thiol (6) with OVA and BSA Protein Carriers.
[0031] Vibriobactin thiol (6), freshly generated from disulfide 26 ( FIG. 7 ), was incubated with a maleimide-activated OVA (27) or BSA (28) protein carrier for 8 h., resulting in Michael adduct OVA-VIB (4) or BSA-VIB (5), respectively (Scheme 2: Synthesis of vibriobactin thiol 6 a . a Reagents: (a) 20, CDI, CH 2 Cl 2 , NEt 3 , 57%; (b) N-tert-butoxycarbonyl-L-threonine N-hydroxysuccinimide ester (2.5 equivalents), DMF, 60%; (c) hydrazine hydrate, EtOH, 90%; (d) 3,3′-dithiopropionic acid, CDI, CH 2 Cl 2 , NEt 3 , 60%; (e) TFA, anisole, CH 2 Cl 2 , 0°→rt, 2 h, 60%; (f) ethyl 2,3-dihydroxybenzimidate, EtOH, reflux, 36 h, 20%; (g) H 2 , 3 atm, Pd black, EtOH, 1 d, 60%).
[0032] Unreacted maleimide was capped by conjugating it further with cysteine for 8 h. Both 4 and 5 were purified on a dextran desalting column. Positive fractions, as determined by the optical density (OD) at 280 nm, were analyzed for protein concentration using a Coomassie assay [Pierce. Coomassie Plus-the Better Bradford™ Assay Kit. Product No. 23236. In Rockford, Ill.]. Functionalities 29 and 30 were also generated ( FIG. 8 ); 30 was used as a negative control in evaluating the capacity of 6 as an antigenic determinant when bound to BSA.
Iron Complexes of 4, 27, 3 and 26.
[0033] Protein desferrivibriobactin-OVA complex 4 was converted to the corresponding ferric siderophore complex 31 by mixing the conjugate with excess ferric nitrilotriacetate in phosphate buffer for 2 h. At this point, desferrioxamine (1) ( FIG. 1 ) was added to complex excess iron. The mixture was then purified on a G-25 Sepharose column. The same ferration procedure, including purification, was carried out on the maleimide-activated OVA (27), producing ferric protein complex 32. The iron content of the purified ferrivibriobactin protein adduct (31), the iron-treated maleimide protein (32), and the elution buffer were determined by inductively coupled plasma mass spectroscopy (ICP-MS). The background iron, elution buffer iron, and maleimide protein iron were subtracted from the iron content associated with the ferrivibriobactin OVA complex (31). From this measurement, and assuming that Fe(III) and vibriobactin form a 1:1 complex, the coupling efficiency of OVA maleimide (27) to 6 was 30%.
[0034] Vibriobactin (3) and vibriobactin disulfide (26) iron(III) complexes, 33 and 34 respectively, which were to be evaluated as potential antigens, were prepared by using iron(III) acetylacetonate (2.0 equivalents) in Tris HCl buffer, pH 7.4. The resulting suspension was separated on a small C-18 column eluting with EtOH (aqueous). Colored fractions were pooled and lyophilized.
Development of Murine Monoclonal Antibodies Against Vibriobactin.
[0035] The procedures were similar to those of Kao and Klein [Kao, K.-J.; Klein, P. A. A Monoclonal Antibody-Based Enzyme-Linked Immunosorbent Assay for Quantitation of Plasma Thrombospondin. Am. J. Clin. Pathol. 1986, 86, 317-323] and Simrell, et al [Simrell, C. R.; Klein, P. A. Antibody Responses of Tumor-Bearing Mice to Their Own Tumors Captured and Perpetuated as Hybridomas. J. Immunol. 1979, 123, 2386-2394]. Briefly, the OVA-VIB conjugate (4) was used as an antigen to raise antibodies in mice. Antigenic response was determined via an ELISA. Once an adequate IgG response was observed, an immunized mouse was given a final, prefusion booster of the antigen without adjuvant. The mouse was euthanized four days later and antibody-forming cells from the animal's spleen were fused to tumor cells grown in culture. The resulting hybridomas were screened for antibody production; antibody-producing hybridomas were cloned. Monoclonal antibodies were then produced and purified.
Polyclonal Antibody Response.
[0036] Two mice (M1 and M2) were immunized with 4. The immune response (serum titer) of these animals and non-immunized mice (normal mouse sera, NMS) was determined via ELISA for polyclonal antibodies against the following potential antigens: a) BSA-VIB conjugate (5), b) BSA-cysteine conjugate (30), c) vibriobactin thiol (6), d) vibriobactin disulfide (26), e) vibriobactin disulfide iron complex (34), f) vibriobactin (3), and g) vibriobactin iron complex (33). Twenty-three days after the second immunization, the serum from the mouse immunized with a higher dose of OVA-VIB (M2) seemed more active against the BSA-VIB antigen than M1, with a higher p-nitrophenol OD at 405 nm at all dilutions (Table 1). However, by day 56, there was little difference in the reactivity of serum from M1 vs. M2. At this time, even after a 25,600-fold dilution, the serum titers of the immunized mice against BSA-VIB were over nine times greater than that of the NMS (Table 1).
[0037] The mouse sera also contained polyclonal antibodies against BSA-cysteine that were nearly as active as antibodies against BSA-VIB (Table 1). Since cysteine was used to cap unreacted maleimide sites in the synthesis of 4, this was expected. As will be discussed below, this was not an issue for the purified monoclonal antibodies. It was still possible to select for antibodies specific against the OVA-VIB conjugate. The mouse sera did not react against any of the other antigens, c-g. This could have been attributed to a simple lack of activity in the case of antigens c-g, or the nature of the ELISA itself. Antigens c-g are relatively low molecular weight, moderately water-soluble ligands. These compounds may not have adhered to the ELISA wells, or they may have been removed during the washing steps. In order to settle this issue, a series of competitive binding ELISAs were performed.
Competitive Binding ELISA.
[0038] In the competitive binding ELISA, sera from immunized mice or non-immunized mice were first incubated with potential antigens f-g, or with OVA-VIB, at antigen concentrations ranging from 0-250 μg/mL. If an antigen is an effective competitor, it will bind to the antibody during this initial incubation, leaving less antibody available to bind to a second antigen coated on the ELISA plate. This “competition” will be reflected in lower p-nitrophenol optical density values.
[0039] The OVA-VIB antigen was found to be an effective competitor at all concentrations tested ( FIG. 3 , Table 2) (FIG. 3 —Competitive binding ELISA of diluted polyclonal sera (1:10,000) from mice immunized with the OVA-VIB conjugate (4)). Animal M1 (A) was immunized with 4 twice s.c. at 50 μg/injection, while mouse M2 (B) was immunized with 4 twice s.c. at 100 μg/injection. The sera were incubated with varying concentrations of the OVA-VIB antigen, prior to being tested via ELISA against the BSA-VIB antigen. The dotted line indicates the amount of OVA-VIB (˜0.05 μg/mL) needed to reduce the optical density of the p-nitrophenol product to 50% of that of the sera not incubated with any OVA-VIB. The closed circles indicate the optical density of unconjugated OVA (10 μg/mL).
[0040] The smaller antigens, f-g, were not effective competitors (data not shown), verifying the necessity for a large carrier molecule in order for the antibody to recognize vibriobactin. Unconjugated OVA was not an effective competitor. The p-nitrophenol optical density of serum incubated with OVA against the BSA-VIB antigen was 92% greater than serum first incubated with OVA-VIB at the same concentration ( FIG. 3 ). It is clear that the antibody “recognizes” the siderophore on the protein carrier.
Cell Fusion—Hybridoma Formation.
[0041] Four months after the second immunization, mouse M2 was given a prefusion booster of 4. Fusion was done following the method of Simrell, et al., except that the myeloma cell line used was Sp2/0. In short, spleen cells were fused with Sp2/0 cells such that the ratio of spleen cells to Sp2/0 cells was 7:1. After incubating for 11 days, the supernatants from the resulting hybridomas were tested via ELISA against the BSA-VIB antigen. The hybridomas that gave the strongest ELISA signal were further cultured for 7 days. Their supernatants were tested again via ELISA against BSA-VIB, BSA-VIB-iron, and BSA-cysteine. The class of antibody (IgG or IgM) was also determined. The twelve most active hybridomas that were BSA-VIB and BSA-VIB-iron positive and BSA-cysteine negative are shown in Table 3. One hybridoma, 2D6, was IgM-positive; the remaining eleven hybridomas were IgG-positive (Table 3). Two of the most promising IgG-positive hybridomas, 5A6 and 2F10, were cloned.
Cloning of Antibody-Producing Hybridomas.
[0042] Cells from the 5A6 and 2F10 hybridomas were diluted to a concentration of one or two cells per well. After incubating for four days, the plates were scanned microscopically and were scored for single colony and multiple colony wells. Ten days after seeding, supernatant from the wells that contained cells underwent screening via ELISA against BSA-VIB. Supernatants from the single colony wells of 5A6 were not very active against BSA-VIB (data not shown). Because of this, the four most BSA-VIB positive multiple colony wells of 5A6 were pooled, diluted, and replated as single cells. Ten days later, supernatants from the resulting clones were tested by an ELISA against BSA-VIB. The ten single colony wells with the strongest ELISA positives (primary) against BSA-VIB are shown in Table 4. After incubating for an additional 5 days, the supernatants were tested again (secondary) via ELISA against BSA-VIB, BSA-VIB-iron and BSA-cysteine. All ten clones were highly active against BSA-VIB and BSA-VIB-iron and showed little activity towards BSA-cysteine (Table 4). A positive BSA-VIB and BSA-VIB-iron response and a negligible BSA-cysteine response were a clear indication that the antigenic determinants of the antibody were associated with the vibriobactin segment of the BSA-VIB conjugate, and not to BSA itself.
[0043] Recloning of the 2F10 hybridoma was unnecessary: 2F10-1A9 and 2F10-2A3 were highly active against BSA-VIB and BSA-VIB-iron and poorly responsive to BSA-cysteine (Table 5). These two clones, as well as two clones from 5A6 (5A6-2D5 and 5A6-1G8), were selected for further evaluation. The clone supernatants were assayed for the class of antibody, IgG or IgM, and were shown to be IgG-positive (Table 5). Multiple stocks from each cell line were frozen. 5A6-1G8 and 2F10-2A3 were tested for mycoplasma contamination and were found to be negative. Additional monoclonal antibodies (mAb) derived from 5A6-2D5 and 2F10-1A9 were produced and purified.
Competitive Binding ELISA Studies: Determination of the Sensitivity of the Purified Monoclonal Antibodies.
[0044] Competitive binding ELISA studies using the purified mAb were conducted. The mAb were first incubated with varying concentrations of the OVA-VIB antigen, from 0-250 μg/mL, prior to being transferred to an ELISA plate that had been coated with the BSA-VIB antigen. The OVA-VIB antigen was found to be an effective competitor at all concentrations tested ( FIG. 4 , Table 6) ( FIG. 4 : Competitive binding ELISA of purified mAb from 5A6-2D5 (A) and 2F10-1A9 (B). The mAb (0.11 μg protein/mL) were incubated with varying concentrations of the OVA-VIB antigen, prior to being tested via ELISA against the BSA-VIB antigen. The dotted line indicates the amount of OVA-VIB (˜0.05-0.06 μg/mL) needed to reduce the optical density of the p-nitrophenol product to 50% of that of the mAb not incubated with any OVA-VIB. The closed circles indicate the optical density of unconjugated OVA (10 μg/mL).)
[0045] Unconjugated OVA was not an effective competitor. The p-nitrophenol optical density of the mAb initially incubated with OVA against the BSA-VIB antigen were approximately 90% greater than those of the mAb first incubated with OVA-VIB at the same concentration (Table 6). It is clear that the antibody “recognizes” the siderophore on the protein carrier.
Antigenic Determinants.
[0046] One of the observations that stands out with the data from the antibody-containing hybridoma supernatants is the lack of difference in reactivity between BSA-VIB and the corresponding BSA-VIB-iron complex (Table 3, Table 5). There are profound differences in structure between vibriobactin and its iron complex. The 1:1 vibriobactin iron complex would have all of the donor groups, (e.g., aromatic hydroxyls and oxazoline nitrogen) folded into the metal. Catecholamides such as vibriobactin bind iron very tightly, with formation constants of nearly 10 48 M −1 . This means that, because of the ubiquitous nature of iron, the OVA-VIB- and BSA-VIB-iron complexes were probably formed in vitro. In fact, it is likely that antibodies in animals are being formed against the OVA-VIB iron complex.
[0047] To support this idea, bile duct-cannulated rats were given vibriobactin (3) subcutaneously (s.c.) at a dose of 75 μmol/kg. The rodents' bile and urine were collected for 48 h to determine if vibriobactin sequestered and promoted the excretion of iron. The iron content of the bile and urine were determined using atomic absorption spectroscopy. This model has been used for many years to evaluate the efficiency with which iron chelators promote the excretion of iron from animals [Bergeron, R. J.; Streiff, R. R.; Creary, E. A.; Daniels, R. D., Jr.; King, W.; Luchetta, G.; Wiegand, J.; Moerker, T.; Peter, H. H. A Comparative Study of the Iron-Clearing Properties of Desferrithiocin Analogues with Desferrioxamine B in a Cebus Monkey Model. Blood 1993, 81, 2166-2173 and Bergeron, R. J.; Streiff, R. R.; Wiegand, J.; Vinson, J. R. T.; Luchetta, G.; Evans, K. M.; Peter, H.; Jenny, H.-B. A Comparative Evaluation of Iron Clearance Models. Ann. N.Y. Acad. Sci. 1990, 612, 378-393]. Vibriobactin was indeed found to sequester iron in vivo. Compound 3 forms a tight 1:1 iron complex with Fe(III). Rats given 75 μmol/kg of 3 would be expected to clear 75 μg-atoms/kg of iron if the binding and clearance were 100% efficient. However, the iron clearing efficiency of 3 in the rats, i.e., the actual amount of iron cleared by the ligand vs. the theoretical iron clearance, was only 4.3±1.1%. This implied that up to 95% of the free ligand remains, or is cleared uncomplexed. In the bile duct-cannulated rats this, of course, all unfolds in a matter of hours. However, in the mouse immunization experiments, the OVA-VIB conjugate had weeks to become saturated with iron; the most important issue is the iron to ligand ratio. Assuming that 3.23 μg-atoms of iron/kg is available for chelation, in a 25 g mouse 1.45×10 −9 moles of iron is available. The mice were effectively given 0.33×10 −9 (M1) or 0.66×10 −9 (M2) moles of vibriobactin conjugated to OVA. In view of the protracted exposure of the ligand to iron, it is difficult to imagine that all of the vibriobactin bound to OVA would not also be iron-bound.
[0048] It will be understood by those skilled in the art that various methodologies for assembling antigens that would allow for the assessment of the antigenic properties of vibriobactin fixed to large carrier molecules, e.g., OVA and BSA may be employed in the practice of the invention. In the examples herein, a thiol analogue was chosen, 1-(2,3-dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraazatetradecane (6), or vibriobactin thiol ( FIG. 2 ). Other tethers such as amines, carboxylic acids, halides, tosylates, alkylating agents and the like may also be used.
[0049] In the synthesis approach, a catechol protecting group was employed in 2,3-bis(4-methoxybenzyloxy)benzoic acid (20). This could be removed concurrently with the BOC functionality of the key intermediate 24 to produce 25, while leaving the requisite disulfide intact. The threonyl moieties of 25 were next condensed with excess ethyl 2,3-dihydroxybenzimidate. Finally, disulfide iron chelator 26 was cleaved to the vibriobactin thiol (6), utilizing H 2 (3 atm) over Pd black in CH 3 OH under iron-free conditions. The thiol (6) was then incubated with a maleimide-activated OVA (27) or BSA (28) protein carrier, resulting in Michael adduct OVA-VIB (4) or BSA-VIB (5), respectively. The OVA-VIB conjugate was mixed with an adjuvant and was successfully used as an antigen to raise antibodies in mice, and the BSA-VIB conjugate was used in an ELISA, first for the detection of serum polyclonal antibodies, and ultimately vibriobactin-specific IgG monoclonal antibodies.
[0050] These results are consistent with the idea that siderophores, such as vibriobactin, present with strong antigenic determinants when fixed to a large carrier molecule. The data are in keeping with the idea that covalently linking siderophore analogues to the bacterial outer membrane receptors represents a target for vaccine development. When isolated and injected into animals these siderophore “outer membrane receptor” adducts induce antibody formation, selecting for the ferrisiderophore face. Animals immunized with, for example, the ferrivibriobactin outer membrane adduct and then exposed to Vibrio cholerae would clear the microorganism by complement activation and opsonophagocytosis.
[0051] Alternatively, the appropriate siderophore could be affixed to a C-terminal polypeptide fragment of the siderophore outer membrane receptor protein. These C-terminal fragments have already been identified for a number of siderophore outer membrane receptor proteins. The siderophore/polypeptide fragment complex or the siderophore affixed to a large peptide such as OVA or BSA may also be employed as vaccines.
EXAMPLES
Biological Materials and Methods.
[0052] The animal-related protocols were approved by the University of Florida Institutional Animal Care and Use Committee. Two female Balb/c ByJ mice (6-7 weeks old) were purchased from The Jackson Laboratory (Bar Harbor, Me.). TiterMax Adjuvant was obtained from Sigma (St. Louis, Mo.). ELISA plates (MaxiSorp) were purchased from Nalge Nunc International Co. (Naperville, Ill.). An automatic microplate washer (Model EL404, Bio-Tek Instruments, Inc., Winooski, Vt.) and microplate reader (Spectromax Plus 384, Molecular Devices, Union City, Calif.) were utilized. The rabbit anti-mouse IgG (whole molecule), goat anti-mouse IgG (γ-chain specific) and goat anti-mouse IgM (μ-chain specific) antibodies were purchased from Sigma (St. Louis, Mo.). Dulbecco's Modified Eagle's Medium (HyClone) was obtained from Theromo Fisher Scientific (Waltham, Mass.). Hybridoma plates were incubated in a Forma Scientific Incubator, Model 3154 (Marietta, Ga.). A MycoAlert Kit (Lonza, Allendale, N.J.) was used to assess potential mycoplasma contamination. Monoclonal antibodies were produced using hybridoma production media, BD Cell Mab Medium, Quantum Yield, (BD Biosciences, San Jose, Calif.) supplemented with 10% low IgG fetal bovine serum (HyClone, Theromo Fisher Scientific, Waltham, Mass.) in CELLine CL 350 flasks (Sartorius Stedim, New York, N.Y.). Amicon Ultra-15 centrifugal filters with a 30 kDa cut-off were obtained from Millipore (Billerica, Mass.). Male Sprague-Dawley rats (400-450 g) were procured from Harlan Sprague-Dawley (Indianapolis, Ind.). Cremophor RH-40 was provided by BASF (Parsippany, N.J.). An atomic absorption spectrometer, Perkin-Elmer model 5100 PC (Norwalk, Conn.), was used to determine the iron content of the rat bile and urine samples.
Monoclonal Antibody Production: Immunization.
[0053] To produce antibodies to small molecules in animals, conjugation to larger carrier proteins (e.g., OVA or BSA) is generally required. The vibriobactin thiol (6) was conjugated with OVA using a linker (27) to prepare the OVA-VIB conjugate (4), which was mixed with an adjuvant and used as an antigen to immunize two mice. One mouse (M1) received 50 μg of 4 per s.c. injection and the other mouse (M2) received 100 μg of 4 per s.c. injection. The mice were given a second immunization of 4 at the same doses four weeks later.
Non-Competitive Binding ELISA Procedure.
[0054] The method followed the approach of Kao and Klein. Briefly, the assay involved coating a potential antigen (50 μL/well) on the ELISA plates, utilizing solutions of antigens ranging in concentration from 1-40 μg/mL. The antigens: a) BSA-VIB conjugate (5), b) BSA-cysteine conjugate (30), c) vibriobactin thiol (6), d) vibriobactin disulfide (26), e) vibriobactin disulfide iron complex (34), f) vibriobactin (3), and g) vibriobactin iron complex (33) were diluted in blocking buffer (1% BSA in PBS with 0.02% azide). Normal mouse sera (NMS) or medium served as negative controls. Polyclonal serum from an immunized mouse (M2) in a 1:1,000 dilution or hybridoma supernatant (Table 4, Table 5) were used as positive controls.
[0055] The plates were allowed to incubate overnight at 4° C. An ELISA wash buffer (EWB) containing PBS with 0.02% azide and 0.5% Tween-20 was used to wash the plates. The plates were washed 4 times (300 μL/wash) using an automatic microplate washer. The wells were then blocked with 1% BSA in PBS with 0.2% azide for 1 h at room temperature and washed again. Fifty microliters of diluted polyclonal mouse serum (1:200-1:25,600), undiluted hybridoma supernatant, or purified mAb (0.11 μg protein/mL) were added to each well. The plates for this and each subsequent step of the ELISA were incubated with gentle agitation for 1 h at room temperature. The plates were then washed 4 times as above and rabbit anti-mouse IgG (whole molecule), conjugated to alkaline phosphatase, was added (50 μL/well); the IgG antibody was diluted (1:1000) in BSA-blocking buffer. The plates were washed 4 times as above and p-nitrophenyl phosphate at a concentration of 1.0 mg/mL, 100 μL/well was added. The plates were read using an ELISA plate reader at 405 nm, tracking the absorbance (OD) of the yellow water-soluble product, p-nitrophenol. A positive response was considered a test well with a p-nitrophenol OD value three times greater than that of the negative control.
[0056] The class of antibody (IgG or IgM) of the hybridoma supernatant (Table 3) or the clone supernatant (Table 5) was determined by an ELISA, replacing the rabbit anti-mouse IgG (whole molecule) with goat anti-mouse IgG (y-chain specific) or goat anti-mouse IgM (p-chain specific) at a dilution of 1:4,000 (50 μL/well).
Competitive Binding ELISA Procedure.
[0057] Competitive binding ELISAs were performed on 1) serum from immunized mice that contained polyclonal antibodies, and 2) purified mAb derived from the cloning of 5A6-2D5 and 2F10-1A9. Medium was used as a negative control, while unconjugated OVA (10 μg/mL, 50 μL/well) served as a positive control for the competitive binding ELISA of the polyclonal serum (Table 2) and purified mAb (Table 6). Two types of plates were utilized: a conical bottom polypropylene plate was used for the incubation of the antibody-antigen mixture, whereas a 96-well MaxiSorp plate was used for the ELISA.
[0058] In brief, the polypropylene incubation plate was blocked with 300 μL of blocking buffer (1% BSA in PBS with 0.02% azide) and was allowed to incubate overnight at 4° C. The following day, the blocking buffer was removed (flicked) from the plate, and the plate was blotted on a paper towel. A 96-well ELISA plate was coated with the BSA-VIB antigen (10 μg/mL, 50 μL/well) that had been diluted in PBS with 0.02% azide. After incubating overnight at 4° C., the plate was washed 4 times (300 μL/wash) as described above, blocked with 300 μL of blocking buffer for 1 h, and washed again.
[0059] The OVA-VIB antigen was diluted in blocking buffer in micro centrifuge tubes at antigen concentrations ranging from 0-250 μg/mL. The diluted antigens (50 μL/well) were transferred from the micro centrifuge tubes to the polypropylene incubation plate that had been blocked and washed. Fifty microliters of the diluted polyclonal mouse serum (1:10,000 dilution) or mAb (0.11 μg protein/mL) were added to the incubation plate wells containing the diluted OVA-VIB antigen. The polypropylene plate was then incubated on a rocking platform for 2 h at room temperature, allowing time for the antigen-antibody complexes to form.
[0060] A portion of the antigen/antibody mixture (50 μL) was transferred from the polypropylene incubation plate to the BSA-VIB-coated ELISA plate that had been blocked and washed. The ELISA plate was incubated with gentle agitation for 1 h at room temperature and was washed 4 times with the EWB. Rabbit anti-mouse IgG antibodies conjugated to alkaline phosphatase were added (50 μL/well); the IgG antibody was diluted (1:1000) in 1% BSA-blocking buffer. After 1 h, the ELISA plate was washed four times with the EWB to remove any unreacted IgG antibodies. p-Nitrophenyl phosphate substrate (1.0 mg/mL, 100 μL/well) was added. The ELISA plate was allowed to incubate with gentle agitation for 1 h at room temperature and was read at 405 nm, tracking the OD of the yellow water-soluble product, p-nitrophenol. A positive response was considered a test well with a p-nitrophenol OD value three times greater than the negative control.
Cell Fusion—Hybridoma Formation.
[0061] Four months after the second immunization, four days before fusion, a mouse (M2) was given a prefusion booster of 100 μg of 4 without adjuvant. This final immunization was given intraperitoneally (i.p.) On the day of fusion, the mouse was anesthetized, exsanguinated and euthanized. The spleen was removed and washed with Dulbecco's Modified Eagle's Medium to remove the antibody-forming cells. The medium was supplemegted with 10% equine serum and 1× antibiotic-antimycotic (per mL: 100 I.U. penicillin, 0.10 mg streptomycin, 0.25 μg amphotericin B and 50 μg gentamycin). The fusion was performed by the procedures described in Simrell, et al., except that the myeloma cell line used was Sp2/0 (a murine myeloma aminopterin-resistant cell line with a defect in purine metabolism). Spleen cells were mixed with myeloma cells at a 7:1 ratio. The fusion was performed with 50% polyethylene glycol 1500 followed by a controlled dilution with media. A centrifugation step (1500-1800 rpm for 8 minutes) was performed to pellet the fused cells. The pellet was resuspended in Dulbecco's Modified Eagle's Medium-high glucose, supplemented with 20% equine serum, 25% Sp2/0 myeloma conditioned medium and 1× hypoxanthine, aminopterin, thymidine (HAT) and was seeded in five 96-well plates at 2.8×10 5 cells per well. The plates were incubated at 37° C., with a CO 2 concentration of 7%.
[0062] Eleven days post-fusion, supernatants from the resulting HAT-resistant hybridomas were subjected to a primary ELISA screening to detect if the cells were secreting antibodies against BSA-VIB. Cells from fifty-one wells that were positive in the primary screening against BSA-VIB were transferred to three 24-well plates and further incubated. The supernatant was assessed again one week later in a secondary ELISA screening against BSA-VIB, BSA-VIB-iron, and BSA-cysteine (Table 3). The hybridomas that were BSA-VIB and BSA-VIB-iron positive and BSA-cysteine negative were further tested as described above to determine the class of antibody, IgG or IgM (Table 3).
Cloning of Antibody-producing Hybridomas.
[0063] Two of the most promising hybridomas, 5A6 and 2F10, were cloned. Cells from the hybridomas were diluted to a concentration of one or two cells per well and were seeded in eight 96-well plates (four plates each for 5A6 and 2F10) over a feeder layer of irradiated 3T3 mouse fibroblasts. After incubating for four days, the plates were scanned microscopically and were scored for single colony and multiple colony wells. For the 5A6 cell line, 96 single colony wells and 60 multiple colony wells were found, whereas the 2F10 cell line presented 120 single colony wells and 47 multiple colony wells. Ten days after seeding, the supernatants from all 323 wells that contained cells underwent screening via ELISA against BSA-VIB.
[0064] Supernatant from the single colony wells of 5A6 were not very active against BSA-VIB. Because of this, the four most BSA-VIB positive multiple colony wells of 5A6 were pooled, diluted, and replated as single cells in four 96-well plates. Ten days after this recloning, the ten single colony wells with the strongest ELISA positives (primary) against BSA-VIB were chosen (Table 4) and cultured in a 24-well plate. After incubating for an additional 5 days, the supernatant was tested again (secondary) via ELISA against BSA-VIB, BSA-VIB-iron and BSA-cysteine. All ten clones were highly active against BSA-VIB and BSA-VIB-iron and showed little activity towards BSA-cysteine (Table 4).
[0065] Recloning of the 2F10 hybridoma was unnecessary. The ten single colony wells with the strongest ELISA response against BSA-VIB from the four 96-well plates were transferred to a 24-well plate. After incubating for an additional 5 days, the supernatants were tested against BSA-VIB, BSA-VIB-iron and BSA-cysteine. Two clones (2F10-1A9 and 2F10-2A3), as well as two clones from 5A6 (5A6-2D5 and 5A6-1G8), were chosen for further evaluation. All four sets of clones were BSA-VIB and BSA-VIB-iron positive, poorly responsive to BSA-cysteine, and IgG-positive (Table 5). Multiple stocks from each of the four cell lines were frozen. 5A6-1G8 and 2F10-2A3 were tested for mycoplasma contamination and were found to be negative. Additional monoclonal antibodies derived from 5A6-2D5 and 2F10-1A9 were produced and purified.
Production and Purification of Monoclonal Antibodies.
[0066] 5A6-2D5 or 2F10-1A9 cloned hybridoma cells were grown in hybridoma production media supplemented with 10% low IgG fetal bovine serum in CELLine CL 350 flasks. The flasks were incubated at 37° C., with a CO 2 concentration of 7%. One harvest per week was taken for three weeks. The cells were centrifuged at 2,000 rpm for 15 min and the resulting supernatant was collected and purified by circulating through a 5 mL Protein G Sepharose 4B column. The supernatant recirculated through the column for 90 min (˜23 passes). The column was then rinsed with PBS (70-150 mL). The antibodies were eluted using 0.1 M glycine, pH 2.8. Ten fractions of 3 mL each were collected. The eluted fractions Were neutralized with 2.0 M Tris, pH 9.0. Absorbance was measured at 280 nm. Fractions with the highest absorbance readings were pooled, desalted, and concentrated using Amicon Ultra-15 centrifugal filters with a 30 kDa cut-off. The concentrated, purified monoclonal antibodies were recovered in a final volume of 0.6 mL in PBS. The protein concentration of the purified mAb were measured spectrophotometrically at 280 nm. Most animalian antibodies (i.e., immunoglobulins) have protein extinction coefficients (ε percent ) in the range of 12 to 15 [Thermo Fisher Scientific. Extinction Coefficients. http://www.piercenet.com/files/TR0006dh5-Extinction-coefficients.pdf]. The final protein concentration of the purified IgG antibody was estimated assuming a protein extinction coefficient of 14. For an IgG antibody with a molecular weight of approximately 150,000, this corresponds to a molar extinction coefficient (ε) of 210,000 M −1 cm −1 .
Iron Clearance in Non-Iron-Overloaded, Bile-Duct Cannulated Rats.
[0067] Four rats were subjected to bile duct-cannulation as previously described. The rats were given 3 s.c. at a dose of 75 μmol/kg. The drug was solubilized in 40% Cremophor RH-40/water. Bile samples were collected from the rats at 3 h intervals for 48 h. The urine samples were taken at 24 h intervals. Sample collection and handling are as previously described. The iron content of the bile and urine were assessed by atomic absorption spectroscopy. Iron clearing efficiency was calculated as set forth elsewhere [Bergeron, R. J.; Wiegand, J.; McManis, J. S.; McCosar, B. H.; Weimar, W. R.; Brittenham, G. M.; Smith, R. E. Effects of C-4 Stereochemistry and C-4′ Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues. J. Med. Chem. 1999, 42, 2432-2440]. The theoretical iron output of the chelator was generated on the basis of a 1:1 vibriobactin:iron complex.
[0068] Reagents were purchased from Aldrich Chemical Co. (Milwaukee, Wis.), and Fisher Optima-grade solvents were routinely used and DMF was distilled. Organic extracts were dried with sodium sulfate and then filtered. Distilled solvents and glassware that had been presoaked in 3N HCl for 15 min were employed in reactions involving chelators. Silica gel 70-230 from Fisher Scientific was utilized for column chromatography, and silica gel 40-63 from SiliCycle, Inc. (Quebec City, Quebec, Canada) was used for flash column chromatography. Sephadex LH-20 was obtained from Amersham Biosciences (Piscataway, N.J.). An ICP-MS X 0675, manufactured by Thermo Electron Corporation (England), was used for the determination of the iron content of selected solutions/compounds. Derivatized OVA or BSA protein containing maleimide moieties were obtained from Pierce (Rockford, Ill.). NMR spectra were obtained at 400 MHz ( 1 H) or 100 MHz ( 13 C) on a Varian Mercury-400BB. Chemical shifts (δ) for 1 H spectra are given in parts per million downfield from tetramethylsilane for organic solvents (CDCl 3 not indicated) or sodium 3-(trimethylsilyl)propionate-2,2,3,3-d 4 for D 2 O. Chemical shifts (δ) for 13 C spectra are given in parts per million referenced to 1,4-dioxane (δ 67.19) in D 2 O or to the residual solvent resonance in CDCl 3 (δ 77.16). Coupling constants (J) are in hertz. The base peaks are reported for the ESI-FTICR mass spectra. Elemental analyses were performed by Atlantic Microlabs (Norcross, Ga.).
OVA-VIB (4) and BSA-VIB (5).
[0069] Derivatized proteins 27 [Pierce. Imject® Maleimide Activated BSA and OVA Kit Instructions. Product No. 77112, 77113. In Rockford, Ill.] or 28 [Pierce. Imject® Maleimide Activated BSA and OVA Kit Instructions. Product No. 77112, 77113. In Rockford, Ill.] (2 mg each) were dissolved in 100 μL of the conjugation buffer and incubated with a freshly prepared solution of 6 (2 mg in 200 μL of 50% aqueous DMSO) for 8 h. Unreacted maleimide was capped by conjugating it further with cysteine (2 mg in 50 μL degassed water) for 8 h. After incubation, 4 and 5 respectively were purified on a dextran desalting column (5 mL), eluting with 30% DMSO/purification buffer. Fractions (0.5 mL) were collected and the OD was measured at 280 nm. Positive fractions of each conjugate were pooled, and the protein concentration of each conjugate was estimated by a Coomassie assay.
1-(2,3-Dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraazatetradecane (6)
[0070] Palladium black (127 mg) was added to a solution of 26 (0.231 g, 0.133 mmol) in anhydrous degassed EtOH (5 mL), and the mixture was stirred under H 2 at 45 psi for 24 h. After filtration through Celite and washing the solids with degassed EtOH (2×5 mL), the filtrate was concentrated in vacuo to afford 0.137 g (60%) of 6 as a brown solid: 1 H NMR δ 1.35-1.75 (m,10H), 1.8-2.2 (m, 4H), 2.47-2.59 (m, 2H), 2.82-2.91 (m, 2H), 3.02-3.91 (m, 12H), 4.72-5.0 (m, 2H), 5.21-5.36 (m, 2H), 6.58-6.77 (m, 3H), 6.84-7.2 (m, 3H), 7.24-7.8 (m, 3H); HRMS m/z calcd for C 42 H 53 N 6 O 12 S, 865.338 (M+H); found, 865.3466.
N 1 -(4-Hydroxybutyl)-N 1 ,N 4 ,N 7 -tris(tert-butoxycarbonyl)norspermidine (9)
[0071] 4-Chloro-1-butanol (16.5 g, 0.150 mol) was introduced to a mixture of 7 (39.4 g, 0.300 mol), KI (2.475 g, 15.0 mmol), and K 2 CO 3 (10.5 g, 75.0 mmol) in 1-butanol (375 mL). The mixture was stirred at 125° C. for 24 h, slowly cooled to room temperature, filtered and concentrated under vacuum to afford 8 as a viscous oil, which was dissolved in 50% aqueous THF (500 mL). Di-tent-butyl dicarbonate (130.8 g, 0.600 mol) in THF (100 mL) was added with continuous stirring. After 16 h, volatiles were removed, and the residue was dissolved in H 2 O (300 mL) and extracted with EtOAc (200 mL, 3×100 mL). The combined organic layers were washed with 0.5 M citric acid (100 mL), H 2 O (100 mL) and saturated NaCl (100 mL) and were concentrated under reduced pressure. Column chromatography using 49:49:2 hexanes/EtOAc/CH 3 OH provided 31.73 g (42%) of 9 as a viscous colorless oil. 1 H NMR δ 1.44, 1.45, and 1.46 (3 s, 27H), 1.5-1.8 (m, 9H), 3.02-3.34 (m, 10H), 3.67 (t, 2H, J=5.9), 4.78 and 5.27 (2 br s, 1H); 13 C NMR δ 25.20, 27.84, 28.57, 28.60, 28.61, 29.82, 37.72, 44.10, 45.01, 47.01, 62.57, 79.57, 155.75, 156.16, 174.84; HRMS m/z calcd for C 25 H 50 N 3 O 7 , 504.3648 (M+H); found, 504.3640. Anal. (C 25 H 49 N 3 O 7 ) C, H, N.
N 1 -[4-(Tosyloxy)butyl]-N 1 ,N 4 ,N 7 -tris(tert-butoxycarbonyl)norspermidine (10)
[0072] N 1 -[4-(Tosyloxy)butyl]-N 1 ,N 4 ,N 7 -tris(tert-butoxycarbonyl)norspermidine was prepared; calcd for C 32 H 56 N 3 O 9 S, 657.3659 (M+H), found, 657.3672. Anal. (C 32 H 55 N 3 O 9 S) C, H, N.
N 1 -[4-(Phthalimido)butyl]-N 1 ,N 4 ,N 7 -tris(tert-butoxycarbonyl)norspermidine (11)
[0073] Potassium phthalimide (1.138 g, 6.15 mmol) was added to 10 (2.70 g, 4.10 mmol) in DMF (50 mL), and the reaction mixture was heated at 90° C. for 48 h. Solvent was removed in vacuo, and the residue was treated with H 2 O (50 mL) and extracted with CHCl 3 (3×50 mL). The combined organic phase was washed with saturated NaCl and concentrated under reduced pressure. Column chromatography with 4:1 CHCl 3 /EtOAc generated 1.84 g (71%) of 11. 1 H NMR δ 1.43-1.45 (3 s, 27H), 1.52-1.76 (m, 8H), 306-3.29 (m, 10H), 3.71 (t, 3H, J=6.8), 7.70-7.73 (m, 2H), 7.83-7.87 (m, 2H); 13 C NMR δ 25.98, 27.46, 28.48, 29.49, 37.40, 37.60, 43.71, 44.87, 46.52, 78.88, 79.43, 79.65, 123.25, 123.41, 132.10, 133.99, 134.11, 155.45, 156.03, 168.41. HRMS m/z calcd for C 33 H 53 N 4 O 8 , 633.3858 (M+H); found, 633.3920. Anal. (C 33 H 52 N 4 O 8 ) C, H, N.
N 1 -[4-(Phthalimido)butyl]norspermidine Tris(trifluoroacetate) (12)
[0074] TFA (25 mL) was added to 11 (3.46 g, 5.47 mmol) in CH 2 Cl 2 (25 mL) with ice bath cooling, and the solution was stirred for 1 h at 0° C. and 1 h at room temperature. After removal of volatiles in vacuo, the residue was treated with toluene and dried by high vacuum to give 3.69 g (quantitative) of 12 as a white solid: 1 H NMR (D 2 O) δ 1.72-1.75 (m, 4H), 2.05-2.15 (m, 4H), 3.08-3.19 (m, 10H), 3.71 (t, 3H, J=6.4) 7.81-7.87 (m, 4H); 13 C NMR δ (D 2 O) 23.24, 23.56, 24.37, 25.47, 37.10, 37.53, 44.90, 45.20, 45.29, 47.79, 123.91, 131.71, 135.37, 171.17; HRMS m/z calcd for C 18 H 29 N 4 O 2 333.2285, (M+H, free amine); found, 333.2324. Anal. (C 24 H 31 F 9 N 4 O 2 .1.5 H 2 O) C, H, N.
N 1 -(2,3-Dimethoxybenzoyl)-N 7 -[4-(phthalimido)butyl]norspermidine (13)
[0075] CDI (0.563 g, 3.48 mmol) was added to a solution of 2,3-dimethoxybenzoic acid (0.633 g, 3.48 mmol) in CH 2 Cl 2 (5 mL). After stirring for 1 h, the solution was cooled to 0° C. and was added to a suspension of 12 (2.82 g, 4.18 mmol) and NEt 3 (2.46 g, 24.4 mmol) in CH 2 Cl 2 (30 mL). The reaction mixture was stirred for 15 h at room temperature, diluted with CH 2 Cl 2 (100 mL), and washed with 8% NaHCO 3 (50 mL). The organic phase was concentrated in vacuo, and the residue was subjected to flash chromatography eluting with 5% concentrated NH 4 OH/MeOH to afford 1.20 g (70%) of 13 as a colorless oil: 1 H NMR δ 1.48-1.57 (m, 2H), 1.62-1.85 (m, 6H), 2.61-2.73 (m, 8H), 3.53 (q, 2H, J=6.0), 3.70 (t, 2H, J=7.6), 3.88 (s, 3H), 3.89 (s, 3H), 7.03 (dd, 1H, J=8.0, 1.6), 7.14 (t, 1H, J=8.0), 7.64 (dd, 1H, J=8.0, 1.6), 7.69-7.71 (m, 2H), 7.82-7.84 (m, 2H), 8.15 (br, 1H, J=7.2); HRMS m/z calcd for C 27 H 37 N 4 O 5 , 497.2765 (M+H); found, 497.2671. Anal. (C 27 H 36 N 4 O 5 ) C, H, N.
N 4 ,N 7 -Bis[(N-tert-butoxycarbonyl-L-threonyl]-N 1 -(2,3-dimethoxybenzoyl)-N 7 -[4-(phthalimido)butylinorspermidine (14)
[0076] A solution of freshly prepared N-tert-butoxycarbonyl-L-threonine N-hydroxysuccinimide ester (4.17 g, 13.2 mmol) in DMF (20 mL) was added to a solution of 13 (2.2 g, 4.4 mmol) in DMF (20 mL). After stirring for 72 h, the solvent was removed under vacuum and the residue was taken up in CHCl 3 (50 mL). The organic layer was washed with 5% NaHCO 3 (3×50 mL), H 2 O (50 mL), and saturated NaCl (50 mL) and was concentrated in vacuo. Flash chromatography eluting with 10% EtOH/EtOAc furnished 2.17 g (55%) of 14 as a white foam: 1 H NMR δ 1.14-1.22 (m, 6H), 1.38-1.46 (m, 18H), 1.54-2.02 (m, 8H), 2.90-3.61 (m, 10H), 3.68-3.76 (m, 2H), 3.89 (s, 3H), 3.91 (s, 3H), 3.98-4.14 (m, 2H), 5.44-5.68 (m, 2H), 7.04 (d, 1H, J=8.4), 7.14 (d, 1H, J=8.0), 7.62-7.67 (m, 1H), 7.70-7.72 (m, 2H), 7.84-7.86 (m, 2H); HRMS m/z calcd for C 45 H 67 N 6 O 13 , 899.4767 (M+H); found, 899.4783. Anal. (C 45 H 66 N 6 O 13 ) C, H, N.
N 4 ,N 8 -Bis[(N-tert-butoxycarbonyl-L-threonyl]-N 1 -(2,3-dimethoxybenzoyl)-thermospermine (15)
[0077] Hydrazine hydrate (5 mL) was added to a solution of 14 (0.350 g, 0.389 mmol) in EtOH (10 mL), and the reaction mixture was stirred at room temperature for 16 h. Solid was filtered, and the filtrate was concentrated in vacuo. The residue was taken up in 1N NaOH (10 mL) and extracted with CHCl 3 (3×10 mL), and organic extracts were concentrated. Flash chromatography eluting with 1% concentrated NH 4 OH/MeOH gave 195 mg (65%) of 15 as a viscous solid: 1 H NMR δ 1.14-1.22 (m, 6H), 1.38-1.46 (m, 18H), 1.54-2.02 (m, 8H), 2.68-2.76 (m, 2H), 2.90-3.61 (m, 10H), 3.89 (s, 3H), 3.91-3.94 (m, 3H), 3.98-4.14 (m, 2H), 4.44-4.62 (m, 2H), 5.46-5.64 (m, 2H), 7.04 (d, 1H, J=8.4), 7.14 (t, 1H, J=8.0), 7.62-7.67 (m, 1H); HRMS m/z calcd for C 37 H 65 N 6 O 11 , 769.4713 (M+H); found, 769.4709. Anal (C 37 H 64 N 6 O 11 ) C, H, N.
1,36-Bis(2,3-dimethoxybenzoyl)-15,22-dioxo-18,19-dithia-1,5,9,14,23,28,32,36-octaaza-5,9,28,32-tetrakis[(N-tert-butoxycarbonyl-L-threonyl]hexatriacontane (16)
[0078] CDI (0.10 g, 0.65 mmol) was added to a solution of 3,3′-dithiopropionic acid (0.06 g, 0.32 mmol) in CH 2 Cl 2 (2 mL). After stirring for 2 h, a solution of 15 (0.60 g, 0.78 mmol) in CH 2 Cl 2 (5 mL) was added to the reaction mixture. The solution was stirred for 15 h at room temperature and was diluted with CH 2 Cl 2 (25 mL). The organic layer was washed with 1N NaOH (15 mL) and saturated NaCl (15 mL) and was concentrated in vacuo. Flash chromatography using 15% EtOH/CHCl 3 generated 218 mg (40%) of 16 as a pale-brown solid: 1 H NMR δ 1.10-1.25 (m, 12H), 1.29-1.50 (m, 36H), 1.52-2.05 (m, 16H), 2.50-2.65 (m, 4H), 2.90-3.08 (m, 4H), 3.09 -3.60 (m, 24H), 3.85-3.98 (m, 12H), 3.99-4.60 (m, 8H), 5.40-5.65 (m, 4H), 6.98-7.15 (m, 2H), 7.18-7.20 (m, 2H), 7.60-7.69 (m, 2H); HRMS m/z calcd for C 80 H 135 N 12 O 24 S 2 , 1711.9155 (M+H); found, 1711.9170.
1-(2,3-Dihydroxybenzoyl)-5,9-bis[(N-tert-butoxycarbonyl-L-threonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraDzatetradecane Dihydrobromide (17)
[0079] Boron tribromide in CH 2 Cl 2 (1 M, 7.56 mL, 7.56 mmol) was added to a mixture of 16 (340 mg, 0.199 mmol) in CH 2 Cl 2 (20 mL) at −78° C., and after stirring for 1 h, the reaction mixture was warmed to room temperature and was stirred for 15 h. The reaction mixture was quenched cautiously at 0° C. with H 2 O (10 mL) and was stirred for 2 h. The aqueous layer was extracted with CH 2 Cl 2 (20 mL) and was concentrated in vacuo, and the residue was subjected to a Sephadex LH-20 column eluting with 40% EtOH/toluene to give 115 mg (73%) of 17 as a white solid: 1 H NMR δ 1.15-1.25 (m, 6H), 1.46-2.01 (m, 8H), 2.56-2.63 (m, 2H), 2.94-3.00 (m, 2H), 3.03-3.68 (m, 12H), 4.04-4.20 (m, 2H), 4.24-4.39 (m, 2H), 6.83 (t, 1H, J=8.4), 7.15 (d, 1H, J=8.0), 7.30 (d, 1H, J=7.6); HRMS m/z calcd for C 28 H 49 N 6 O 8 S, 629.3333 (M+H, free amine); found, 629.3329. Anal. (C 28 H 50 Br 2 N 6 O 8 S.H 2 O) C, H, N.
4-Methoxybenzyl2,3-Bis(4-methoxybenzyloxy)benzoate (19)
[0080] Sodium hydride (60%, 4.69 g, 0.117 mol) was added in portions to 18 (5.47 g, 35.5 mmol) in DMF (150 mL) with ice bath cooling, and the mixture was stirred at 0° C. for 45 min and at room temperature for 1 h. A solution of 4-methoxybenzyl bromide (25.0 g, 0.124 mol) in DMF (50 mL) was added to the reaction mixture over 30 min. After stirring for 20 h, quenching with H 2 O (30 mL) at 0° C. was performed, and solvents were removed under high vacuum. The concentrate was dissolved in EtOAc (200 mL), which was washed with H 2 O (100 mL) and saturated NaCl (100 mL); solvent was removed in vacuo. Flash chromatography, eluting with 5:1 hexanes/EtOAc, gave 11.33 g (62%) of 19 as a white solid, mp 108° C.: 1 H NMR δ 3.77 (s, 3H), 3.79 (s, 3H), 3.81 (s, 3H), 4.95 (s, 2H), 5.03 (s, 2H), 5.25 (s, 2H), 6.76 (d, 2H, J=8.8), 6.86 (d, 2H, J=8.8), 6.89 (d, 2H, J=8.4), 7.04 (t, 2H, J=7.8), 7.11 (dd, 2H, J=8.0, 2.0), 7.18 (d, 2H, J=8.8), 7.33-7.36 (m, 4H); 13 C NMR δ 55.32, 55.37, 55.40, 66.81, 71.20, 75.31, 112.97, 113.61, 114.02, 118.16, 123.93, 127.08, 128.19, 128.75, 129.51, 129.73, 130.31, 130.41, 148.43, 152.95, 159.43, 159.62, 159.70, 166.44; HRMS m/z calcd for C 31 H 30 NaO 7 , 537.1889 (M+Na); found, 537.1884.
2 , 3 -Bis(4-methoxybenzyloxy)benzoic Acid (20)
[0081] A solution of 19 (8.60 g, 16.71 mmol) in dioxane (84 mL) and 2N NaOH (42 mL) was stirred for 24 h at room temperature. The reaction mixture was concentrated in vacuo. The residue was stirred with H 2 O (100 mL) and then acidified to pH 2 with 1N HCl. The white solid was filtered, washed with hexane, and was recrystallised from EtOAc/hexanes to generate 5.93 g (90%) of 20 as a white crystalline solid, mp 129° C.: 1 H NMR δ 3.8 (s, 3H), 3.85 (s, 3H), 5.12 (s, 2H), 5.20 (s, 2H), 6.83 (d, 2H, J=8.8), 6.96 (d, 2H, J=9.2), 7.18 (t, 2H, J=8.0), 7.22-7.27 (m, 2H), 7.41 (d, 2H, J=8.4), 7.73 (dd, 1H, J=1.2, 8.0); 13 C NMR δ 55.36, 55.37, 55.44, 55.46, 71.42, 114.26, 119.12, 123.04, 124.37, 125.00, 126.87, 128.02, 129.73, 131.21, 147.17, 151.45, 159.94, 160.44, 165.45; HRMS m/z calcd for C 23 H 22 NaO 6 , 417.1332 (M+Na); found, 417.1332.
N 1 -[2,3-Bis(4-methoxybenzyloxy)benzoyl]-N 7 -[4-(phthalimido)-butyl]norspermidine (21)
[0082] CDI (0.239 g, 1.48 mmol) was added to a solution of 20 (0.583 g, 1.48 mmol) in CH 2 Cl 2 (2 mL). After stirring for 1 h, the solution was cooled to 0° C. and added to a suspension of 12 (1.0 g, 1.48 mmol) and NEt 3 (1.05 g, 10.4 mmol) in CH 2 Cl 2 (2 mL) at 0° C. The solution was stirred for 15 h at room temperature and was diluted with CH 2 Cl 2 (50 mL). The reaction mixture was washed with 8% NaHCO 3 (25 mL) and was concentrated. Flash chromatography eluting with 5% concentrated NH 4 OH/MeOH afforded 597 mg (57%) of 21 as a colorless oil: 1 H NMR δ 1.48-1.72 (m, 8H), 2.52-2.63 (m, 8H), 3.36 (q, 2H, J=6.0), 3.69 (t, 2H, J=7.2), 3.80 (s, 3H), 3.84 (s, 3H), 4.98 (s, 2H), 5.07 (s, 2H), 6.83 (d, 2H, J=8.8), 6.93 (d, 2H, J=8.4), 7.13 (d, 2H, J=4.8), 7.23 (m, 3H), 7.4 (d, 2H, J=8.4), 7.68-7.7 (m, 2H), 7.81-7.83 (m, 2H), 8.12 (t, 1H, J=7.2); HRMS m/z calcd for C 41 H 49 N 4 O 7 , 709.3596 (M+H); found, 709.3611. Anal. (C 41 H 48 N 4 O 7 ) C, H, N.
N 4 ,N 7 -Bis[(N-tert-butoxycarbonyl-L-threonyll-N 1 -[2,3-bis(4-methoxybenzyl-oxy)benzoyl]-N 7 -(phthalimido)butylJnorspermidine (22)
[0083] A solution of freshly prepared N-tert-butoxycarbonyl-L-threonine N-hydroxysuccinimide ester (1.12 g, 3.54 mmol) in DMF (10 mL) was added to a solution of 21 (1.0 g, 1.41 mmol) in DMF (10 mL). After stirring for 72 h at 40° C., the solvent was removed under vacuum, and the residue was taken up in CHCl 3 (50 mL). The organic layer was washed with aqueous 5% NaHCO 3 (3×50 mL), H 2 O (50 mL), saturated NaCl (50 mL) and was concentrated in vacuo. Flash chromatography eluting with 10% EtOH/EtOAc afforded 0.945 g (60%) of 22 as a white foam: 1 H NMR δ 1.14-1.21 (m, 6H), 1.37-1.49 (m, 18H), 1.52-1.8 (m, 8H), 3.10-3.60 (m, 10H), 3.68-3.74 (m, 2H), 3.79-3.81 (m, 3H), 3.84 (s, 3H), 3.97-4.11 (m, 2H), 4.32-4.60 (m, 2H), 502 (s, 2H), 5.07 (s, 2H), 5.44-5.62 (m, 2H) 6.82-6.86 (m, 2H), 6.93 (d, 2H, J=8.4), 7.11-7.13 (m, 2H), 7.22-7.26 (m, 3H), 7.39 (d, 2H, J=8.4), 7.69-7.72 (m, 2H), 7.81-7.85 (m, 2H), 8.02 (br s, 1H); HRMS m/z calcd for C 59 H 79 N 6 O 15 , 1111.5598 (M+H); found, 1111.5650. Anal. (C 59 H 78 N 6 O 15 ) C, H, N.
N 4 ,N 8 -Bis[(N-tert-butoxycarbonyl-L-threonyl]-N 1 -[2,3 -bis(4-methoxybenzyloxy)-benzoyl]thermospermine (23)
[0084] Hydrazine hydrate (5 mL) was added to a solution of 22 (250 mg, 0.225 mmol) in EtOH (10 mL), and reaction mixture was stirred at room temperature for 16 h. Solid was filtered, and the filtrate was concentrated under high vacuum. The residue was taken up in 1N NaOH (10 mL) and extracted with CHCl 3 (3×10 mL), and organic extracts were concentrated. Flash chromatography eluting with 1% concentrated NH 4 OH/MeOH afforded 198 mg (90%) of 23 as a white solid: 1 H NMR δ 1.11-1.22 (m, 6H), 1.37-1.43 (m, 18H), 1.58-2.02 (m, 8H), 2.71 (q, 2H, J=6.0), 2.90-3.60 (m, 10H), 3.80-8.81 (m, 3H), 3.84 (s, 3H), 3.98-4.14 (m, 2H), 4.30-4.60 (m, 2H), 5.00-5.08 (m, 4H), 5.42-5.65 (m, 2H), 6.82-6.86 (m, 2H), 6.93 (d, 2H, J=8.4), 7.13-7.19 (m, 2H), 7.22-7.26 (m, 3H), 7.4 (d, 2H, J=8.4); HRMS m/z calcd for C 51 H 77 N 6 O 13 , 981.5543 (M+H); found, 981.5589. Anal. (C 51 H 76 N 6 O 13 ) C, H, N.
1,36-Bis [2,3-bis(4-methoxybenzyloxy)benzoyl]-15,22-dioxo-18,19-dithia-1,5,9,14,23,28,32,36-octaaza-5,9,28,32-tetrakis[(N-tert-butoxycarbonyl-L-threonyl]hexatriacontane (24)
[0085] CDI (0.063 g, 0.372 mmol) was added to a solution of 3,3′-dithiopropionic acid (0.039 g, 0.186 mmol) in CH 2 Cl 2 (2 mL). After stirring for 2 h, the solution of 23 (0.550 g, 0.56 mmol) in CH 2 Cl 2 (5 mL) was added followed by NEt 3 (0.025 g, 0.25 mmol). The solution was stirred for 15 h at room temperature and was diluted with CH 2 Cl 2 (25 mL) was added. The organic layer was washed with 8% NaHCO 3 (20 mL) and saturated NaCl (20 mL) and concentrated in vacuo. Flash chromatography using 8% CH 3 OH/CHCl 3 generated 238 mg (60%) of 24 as a pale-brown solid: 1 H NMR δ 1.10-1.23 (m, 12H), 1.25-1.47 (m, 36H), 1.48-2.00 (m, 16H), 2.52-2.70 (m, 4H), 2.80-3.01 (m, 4H), 307-3.55 (m, 24H), 3.80-3.81(m, 6H), 3.83 (s, 6H), 3.95-4.17 (m, 4H), 4.27-4.62 (m, 4H), 5.01-5.04 (m, 4H), 5.07 (2 s, 4H), 5.42-5.65 (m, 4H), 6.82-6.86 (m, 4H), 6.93 (2 d, 4H, J=8.4), 7.12-7.18 (m, 4H), 7.22-7.27 (m, 6H), 7.4 (d, 4H, J=8.4); HRMS m/z calcd for C 108 H 159 N 12 O 28 S 2 2137.0859 (M+H), found 2137.0867. Anal. (C 108 H 158 N 12 O 28 S 2 ) C, H, N.
1,36-Bis(2,3-dihydroxybenzoyl)-15,22-dioxo-18,19-dithia-1,5,9,14,23,28,32,36-octaaza-5,9,28,32-tetrakis(L-threonyl)hexatriacontane Tetrakis(trifluoroacetate) (25)
[0086] TFA (25 mL) was added to a mixture of 24 (1.16 g, 0.547 mmol) and anisole (5 mL) in CH 2 Cl 2 (25 mL) with ice bath cooling, and the solution was stirred for 1 h at 0° C. and 1 h at room temperature. After removal of volatiles in vacuo, the concentrate was subjected to a Sephadex LH-20 column, eluting with 40% EtOH/toluene to give 0.54 g of 25 (60%) as a white solid: 1 H NMR δ 1.24-1.30 (m, 12H), 1.34-1.60 (m, 8H), 1.74-2.21 (m, 8H), 2.57-2.66 (m, 4H), 2.84-2.93 (m, 4H), 3.0-3.64 (m, 24H), 4.04-4.20 (m, 4H), 4.24-4.38 (m, 4H), 6.80-6.86 (m, 2H), 7.03-7.07 (m, 2H), 7.18-7.21 (m, 2H); HRMS m/z calcd for C 56 H 95 N 12 O 16 S 2 , 1255.6425 (M+H, free amine); found, 1255.6417. Anal. (C 64 H 98 F 12 N 12 O 24 S 2 .2.5H 2 O) C, H, N.
1,36-Bis(2,3-dihydroxybenzoyl)-15,22-dioxo-18,19-dithia-1,5,9,14,23,28,32,36-octaaza-5,9,28,32-tetrakis[[(4S,5R)-2-(2,3 -dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]hexatriacontane (26)
[0087] Ethyl 2,3-dihydroxybenzimidate 30 (0.231 g, 1.27 mmol) was added to a solution of 25 (0.35 g, 0.21 mmol) in anhydrous EtOH (15 mL). The mixture was heated at reflux under N 2 for 36 h and was concentrated in vacuo. Column chromatography on Sephadex LH-20, eluting with 15% EtOH/toluene afforded 0.072 g (20%) of 26 as a gray solid: 1 H NMR δ 1.35-1.75 (m, 20H), 1.8-2.2 (m, 8H), 2.47-2.59 (m, 4H), 2.82-2.91 (m, 4H), 3.02-3.91 (m, 24H), 4.72-5.0 (m, 4H), 5.21-5.36 (m, 4H), 6.58-6.77 (m, 6H), 6.84-7.2 (m, 6H), 7.8-7.24 (m, 6H); HRMS m/z calcd for C 84 H 103 N 12 O 24 S 2 , 1728.6669 (M+H); found, 1728.7344. Anal. (C 84 H 102 N 12 O 24 S 2 ) C, H, N.
BSA-Cysteine Conjugate (30)
[0088] Maleimide-activated protein 28 (2 mg in 100 μL buffer) and cysteine (2 mg in 200 μL of degassed water) were incubated for 8 h at room temperature. After incubation, 30 was purified on a dextran desalting column, eluting with a purification buffer. Fractions (0.5 mL) were collected and the OD was measured at 280 nm. Positive fractions were pooled and protein concentration was estimated by Coomassie assay.
Iron Complex of OVA-VIB Protein Conjugate (31)
[0089] A 1-mL solution of 4 (1.685 mg/mL) was incubated at pH 7.4 with 500 μL of FeNTA (1 mM) at room temperature. After incubating 2 h, excess desferrioxamine (1) was added and the mixture again incubated for 2 h. The incubated mixture was subjected to a G-25 Sepharose column, using 30% DMSO/phosphate buffer as an eluting solvent. Fractions (0.5 mL) were collected and the first colored band (fractions 3-6) was eluted; the OD was checked at 280 nm. Protein-containing fractions were pooled (4 mL) and subjected to ICP-MS for estimation of iron content.
Iron Complex of Vibriobactin (33)
[0090] Compound 3 (10 mg, 0.0142 mmol) in EtOAc (3 mL) was added to Fe(acac) 3 (14.7 mg, 0.0255 mmol) in EtOAc (3 mL). The mixture was shaken with 5 mL of 0.1 M Tris HCl buffer, pH 7.4. The aqueous layer became a deep wine/purple color in 5-10 min. The layers were separated and the aqueous layer was washed with EtOAc (3×5 mL). The aqueous layer was concentrated on high vacuum and subjected to C-18 reversed phase column eluting with 40% aqueous EtOH. Purple-colored fractions were combined and lyophilized to give 8.5 mg of 33 as a purple-colored solid.
Iron Complex of Vibriobactin Disulfide (34)
[0091] Compound 26 (50 mg, 0.029 mmol) was dissolved in EtOAc (2 mL) and added to a solution of Fe(acac) 3 (28.4 mg, 0.052 mmol) in EtOAc (2 mL). The mixture was shaken well with 5 mL of Tris HCl buffer (0.1 M, pH 7.4). After 10 min, the suspension was collected at the junction of the aqueous layer and the EtOAc layer. The layers were separated and the suspension was washed with Et
[0092] OAc (5 mL). A small C-18 column was pre-washed with Tris buffer and 50% aqueous EtOH. The iron complex was purified, eluting with 40% aqueous EtOH, then 30% aqueous EtOH. The purple-colored fractions (2 mL each) were collected. The fractions were pooled together and lyophilized to give 36 mg of 34 as a dark purple-colored solid.
[0093] Elemental analytical data for synthesized compounds is available via the Internet at http://pubs.acs.org.
[0000]
TABLE 1
ELISA Determination of Reactivity of Polyclonal Antibodies
(Serum Titer) Against BSA-VIB and BSA-cysteine.
Optical Density at 405 nm a
M1
M2
NMS
BSA-
BSA-
BSA-
Serum
BSA-VIB
cysteine
BSA-VIB
cysteine
BSA-VIB
cysteine
Dilution
23 d
56 d
56 d
23 d
56 d
56 d
23 d
56 d
56 d
1:200
3.192
3.675
3.464
3.381
3.647
3.496
0.111
0.111
0.087
1:400
3.295
3.749
3.340
3.370
3.692
3.496
0.106
0.095
0.077
1:800
2.986
3.708
2.787
3.148
3.664
3.359
0.113
0.107
0.074
1:1,600
2.230
3.586
1.676
2.867
3.637
2.975
0.087
0.087
0.072
1:3,200
1.370
3.535
0.883
2.188
3.486
2.025
0.109
0.096
0.076
1:6,400
0.905
2.919
0.447
1.255
2.724
1.270
0.179
0.100
0.072
1:12,800
0.476
1.756
0.254
0.809
1.718
0.736
0.106
0.095
0.080
1:25,600
0.296
0.830
0.167
0.431
1.012
0.379
0.100
0.091
0.094
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. M1 was immunized with the OVA-VIB conjugate twice s.c. at a dose of 50 μg/immunization; M2 was immunized with the conjugate twice s.c. at 100 μg/immunization. Sera were obtained 23 d and 56 d after the second immunization. Normal mouse sera (NMS) served as a negative control.
[0000]
TABLE 2
Competitive Binding ELISA of Serum from
Immunized Mice and Non-immunized Mice.
OVA-VIB
BSA-VIB Antigen:
Antigen Conc.
Optical Density at 405 nm a
(μg/mL)
M1
M2
NMS
0
1.147
1.800
0.113
0.08
0.486
0.926
0.109
0.4
0.250
0.581
0.108
2
0.135
0.243
0.105
10
0.114
0.137
0.108
50
0.106
0.113
0.108
250
0.108
0.109
0.111
Medium
0.048
0.044
0.045
OVA
1.152
1.655
0.113
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. Sera from immunized mice (M1 and M2) and normal mice (NMS), diluted 1:10,000, were incubated with the OVA-VIB antigen for 2 h at room temperature. A portion of this mixture was then transferred to an ELISA plate that had been coated with the BSA-VIB antigen, 10 μg/mL. Medium was used as a negative control; unconjugated OVA (10 μg/mL) served as a positive control.
[0000]
TABLE 3
Reactivity of Antibody-containing Hybridoma Supernatants Against
BSA-VIB and Other Antigens as Measured by an ELISA.
Optical Density at 405 nm a
Optical Density at 405 nm a
BSA-
BSA-VIB-
BSA-
IgG
IgM
Hybridoma
VIB
iron
cysteine
(γ-chain)
(μ-chain)
1H8
3.662
3.040
0.100
0.608
0.091
2C11
3.564
3.427
0.246
3.652
0.432
2D6
2.481
2.340
0.157
0.825
3.083
2F5
3.173
2.832
0.180
3.530
0.120
2F10
2.830
2.903
0.161
2.331
0.085
3F11
3.331
3.449
0.217
3.537
0.133
3H9
2.824
3.663
0.486
3.808
0.389
4A5
1.979
2.022
0.196
2.491
0.084
4A7
3.154
2.962
0.555
3.532
0.094
4G3
2.399
2.130
0.170
3.500
0.097
5A6
3.359
3.488
0.390
2.889
0.090
5D8
4.000
4.000
0.548
4.000
0.120
Medium
0.093
0.101
0.107
0.103
0.106
M2 (PC)
3.350
3.443
1.002
3.438
0.386
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. Medium served as a negative control; immune mouse serum (M2) in a 1:1,000 dilution was used as a positive control (PC). Hybridoma culture supernatants were undiluted and were screened for antigenic activity 18 days post fusion. Rabbit anti-mouse IgG (whole molecule), at a dilution of 1:1,000, was used to assess the reactivity of the BSA-containing antigens. The class of antibody (IgG or IgM) was determined by the use of goat anti-mouse IgG (γ-chain specific) or goat anti-mouse IgM (μ-chain specific) at a dilution of 1:4,000.
[0000]
TABLE 4
Recloning of 5A6 Pooled Multiple Colony Wells: ELISA Screening
of Supernatants from Resulting Single Colony Wells Against
BSA-VIB, BSA-VIB-iron, and BSA-cysteine.
BSA-VIB
Optical Density
BSA-VIB-iron
BSA-cysteine
at 405 nm a
Optical Density
Optical Density
Clone
Primary
Secondary
at 405 nm a
at 405 nm a
1G2
4.000
3.472
3.492
0.721
1G8
4.000
3.558
3.444
0.807
2D5
3.408
3.575
3.579
0.689
2F4
3.382
3.522
3.586
0.831
2G4
3.436
3.548
3.587
1.075
3B9
3.395
3.473
3.418
1.130
3E9
3.395
3.420
3.386
0.604
3G8
3.457
3.479
3.549
0.929
4B5
3.421
3.503
3.534
0.636
4B7
3.419
3.503
3.563
0.862
Medium
0.235
0.125
0.127
0.099
5A6 (PC)
3.359
3.488
3.488
0.667
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. Medium was used as a negative control; supernatant from the pooled multiple colony wells from 5A6 served as a positive control (PC). Hybridoma clone culture supernatants were undiluted and were assessed for activity against BSA-VIB 10 days after recloning (primary). The hybridomas were incubated for an additional 5 days, and the supernatants were screened again (secondary). Activity against BSA-VIB-iron and BSA-cysteine were determined 15 days after recloning.
[0000]
TABLE 5
Reactivity of 5A6 and 2F10 Clone Supernatant Against
BSA-VIB and Other Antigens as Measured by an ELISA.
Optical Density at 405 nm a
Optical Density at 405 nm a
BSA-
BSA-VIB-
BSA-
IgG
IgM
Clone
VIB
iron
cysteine
(γ-chain)
(μ-chain)
5A6-1G8
3.613
3.565
0.663
3.610
0.220
5A6-2D5
3.576
3.443
0.792
2.825
0.460
5A6 (PC)
3.359
3.488
0.667
3.659
0.250
2F10-1A9
3.410
3.335
0.413
3.522
0.413
2F10-2A3
2.675
2.656
0.300
2.825
0.460
2F10 (PC)
2.347
2.185
0.362
2.729
0.301
Medium
0.172
0.155
0.166
0.192
0.315
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. Hybridoma clone culture supernatants were undiluted. Medium served as a negative control; supernatant from the pooled multiple colony wells from 5A6, and supernatant from the 2F10 uncloned parent hybridoma, served as positive controls (PC). Rabbit anti-mouse IgG (whole molecule), at a dilution of 1:1,000, was used to assess the reactivity of the BSA-containing antigens. The class of antibody (IgG or IgM) was determined by the use of goat anti-mouse IgG (γ-chain specific) or goat anti-mouse IgM (μ-chain specific) at a dilution of 1:4,000.
[0000]
TABLE 6
Competitive Binding ELISA of Purified Monoclonal Antibodies
Derived From Clones of 5A6-2D5 and 2F10-1A9.
BSA-VIB Antigen:
OVA-VIB
Optical Density at 405 nm a
Antigen Conc.
5A6-2D5
2F10-1A9
(μg/mL)
(Purified mAb)
(Purified mAb)
0
2.132
3.572
0.08
0.669
0.889
0.4
0.483
0.879
2
0.189
0.497
10
0.145
0.137
50
0.113
0.109
250
0.093
0.095
Medium
0.092
0.090
OVA
2.190
3.214
a The optical density of the p-nitrophenol product was determined 1 h after the addition of the p-nitrophenyl phosphate substrate. Purified monoclonal antibodies (mAb) were incubated with the OVA-VIB antigen for 2 h at room temperature. A portion of this mixture was then transferred to an ELISA plate that had been coated with the BSA-VIB antigen, 10 μg/mL. Medium was used as a negative control; unconjugated OVA (10 μg/mL) served as a positive control.
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An immunogenic composition comprising a siderophore covalently linked to a pharmaceutically acceptable carrier molecule wherein the antigenicity of the siderophore moiety is sufficient to stimulate an immuno-logic response to the siderophore when the composition is circulating in the bloodstream of a human or non-human animal and vaccine.
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[0001] This is a continuation-in-part application based on co-pending non-provisional application U.S. Ser. No. 10/306614 filed Nov. 26, 2002, the disclosure of which is incorporated by reference.
FIELD OF THE INVENTION
[0002] The invention generally relates to fluorescent nanoparticles and more specifically to silica-based fluorescent nanoparticles of less than 30 nm with covalently attached organic dyes.
BACKGROUND OF THE INVENTION
[0003] Fluorescent nanoparticles have tremendous promise as indicators and photon sources of biotechnological and information applications such as biological imaging, sensor technology, microarrays, and optical computing. These applications require size-controlled, monodisperse, bright nanoparticles that can be specifically conjugated to biological macromolecules or arranged in higher-order structures.
[0004] Two general approaches have emerged in recent years for synthesizing highly fluorescent, water-soluble nanoparticles for use in a range of demanding biological and analytical applications. In the first approach, the nanoparticulate material itself is fluorescent (such as semiconductor nanocrystals or metal nanocrystals). In the second, the fluorescent nanoparticles are based on the incorporation of organic dye molecules. Given the vast diversity of organic dye molecules and the exquisite sensitivity of these dye molecules to their local environment, the latter approach raises the possibility of developing nanoparticles with a broad range of precisely controlled fluorescence characteristics.
[0005] Based on the work of Stöber et al., silica nanoparticles with an embedded dye have been synthesized in a range of sizes, colors, and architectures. In all previous reports of photophysical properties, the dye which is covalently bound inside the silica particle is observed to be quenched in comparison to the free dye. However, in the case of poly(organosiloxane) microgels in which the dye is non-covalently attached and loaded through diffusion, a slight increase in fluorescence efficiency is observed. For other materials, for example polystyrene microspheres, the quantum efficiency of the embedded dye is the same or less than the free dye. The quenching of fluorescence is usually attributed to either intraparticle energy transfer or non-radiative decay into the silica matrix. Both of these pathways are likely influenced by the local dye environment within the particle, suggesting that precise control of the architecture within the particle might ameliorate quenching or even lead to fluorescence enhancement.
[0006] There is still a need for highly fluorescent nanoparticles less than 30 nm with covalently attached organic dyes.
SUMMARY OF THE INVENTION
[0007] The invention relates to a class of silica nanoparticles in which the architecture within the silica particle has marked, controlled effects on the radiative properties of the constituent dye.
[0008] The invention provides a fluorescent monodisperse silica nanoparticle comprising fluorophore center core and a silica shell wherein the radiative properties of the nanoparticle are dependent upon the chemistry (composition) of the core and presence of the silica shell. In one aspect of the invention, the core-shell architecture provides an enhancement in fluorescence quantum efficiency. The invention generally provides control of photophysical properties of dye molecules encapsulated within silica particles with sizes down to 30 nm and below. This control is accomplished through changes in silica chemistry and particle architecture on the nanometer size scale and results in significant brightness enhancement compared to free dye.
[0009] In another aspect of the invention, the core-shell architecture provides the ability to control the photostability properties of the nanoparticle.
[0010] The quantum efficiency increase provided by the invention is due to both an increase in the radiative rate and a decrease in the non-radiative rate, with the latter effect being the most variable between architectures. The changes in non-radiative rate correlate well to differences in rotational mobility of the dye within the particle.
[0011] In one embodiment of the invention, the fluorescent monodisperse nanoparticle includes a core-shell architecture wherein the core comprises a compact core surrounded by a silica shell. In another embodiment of the invention, the fluorescent monodisperse nanoparticle includes a core-shell architecture wherein the core comprises an expanded core surrounded by a silica shell. In yet another embodiment of the invention, the fluorescent monodisperse nanoparticle includes a core-shell architecture wherein the core comprises a homogenous particle with dyes sparsely embedded within surrounded by a silica shell. In still another embodiment of the invention, the fluorescent monodisperse homogenous nanoparticle is not surrounded by a silica shell.
[0012] The invention provides a method of making a fluorescent monodisperse nanoparticle with a compact core architecture by mixing a fluorescent compound and an organo-silane compound to form a dye precursor, mixing the resulting dye precursor with an aqueous solution to form a compact fluorescent core, and mixing the resulting compact core with a silica precursor to form a silica shell on the compact core, to provide the fluorescent monodisperse nanoparticle.
[0013] The invention also provides a method of making a fluorescent monodisperse nanoparticle with an expanded core architecture by mixing a fluorescent compound and an organo-silane compound to form a dye precursor, co-condensing the resulting dye precursor with a silica precursor to form an expanded fluorescent core, and mixing the resulting expanded core with a silica precursor to form a silica shell on the expanded core, to provide the fluorescent monodisperse nanoparticle.
[0014] The invention provides a method of making a fluorescent monodisperse homogenous nanoparticle by mixing a fluorescent compound and an organo-silane compound to form a dye precursor and co-condensing the resulting dye precursor with a silica precursor to form a homogenous fluorescent monodisperse nanoparticle.
[0015] These and other features of the invention are set forth in the description of the invention which follows.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1A -C illustrates a schematic of different silica nanoparticle architectures designated as compact core-shell nanoparticle ( 1 A), expanded core-shell nanoparticle ( 1 B), and the homogenous nanoparticle ( 1 C). The silica shell in the compact and expanded core-shell architecture comprises silica without any dye molecules. The homogenous nanoparticle comprises a composite of silica and dye in a matrix.
[0017] FIG. 2A -C illustrates fluorescence correlation spectroscopy of nanoparticles and synthetic intermediates.
[0018] FIG. 2D -F illustrates the brightness (counts/particles/second) values for the synthesis stages of the compact core-shell architecture, expanded core-shell architecture and the homogenous architecture based on excitation value of 1.2 mW at 900 nm.
[0019] FIG. 3 illustrates the steady-state spectroscopy curves showing the quantum efficiency enhancement achieved by the core-shell architecture. FIGS. 3 A-C illustrate the absorbance and fluorescence of the compact core-shell nanoparticle ( 3 A), expanded core-shell nanoparticle ( 3 B) and homogenous nanoparticle ( 3 C). The absorbance values are in units of optical density. The fluorescence is scaled relative to the organic dye used, TRITC. FIGS. 3 D-F illustrate the comparison between absorbance and excitation for the compact core-shell nanoparticle ( 3 D), expanded core-shell nanoparticle ( 3 E), and homogenous particle ( 3 F).
[0020] FIG. 4 illustrates the time-resolved fluorescence of nanoparticles.
[0021] FIG. 4A illustrates the normalized fluorescence decay of a homogenous nanoparticle, expanded core-shell nanoparticle, compact core-shell nanoparticle and the TRITC dye. FIG. 4B illustrates the fluorescence anisotropy of an expanded core-shell nanoparticle, a compact core-shell nanoparticle, a homogenous nanoparticle, and the TRITC dye. FIG. 4C illustrates the normalized fluorescence anisotropy of the nanoparticle curves shown in FIG. 4B . Average fit values for the fluorescence lifetime (τ f ) and rotational lifetime (θ) are compiled in Table III.
DETAILED DESCRIPTION OF THE INVENTION
[0022] The fluorescent nanoparticles of the present invention include a core comprising a fluorescent silane compound and a silica shell on the core. The core of the nanoparticle can comprise, for example, the reaction product of a reactive fluorescent compound and a co-reactive organo-silane compound, and the shell can comprise, for example, the reaction product of a silica forming compound. The silica forming compound can produce, for example, one or more layers of silica, such as from 1 to about 20 layers, and various desirable shell characteristics, such as shell layer thickness, the ratio of the shell thickness to the core thickness or diameter, silica shell surface coverage of the core, porosity and carrying capacity of the silica shell, and like considerations.
[0023] The synthesis of the fluorescent monodisperse core-shell nanoparticles is based on a two-step process. First, the organic dye molecules, tetramethylrhodamine isothiocynate (TRITC), are covalently conjugated to a silica precursor and condensed to form a dye-rich core. Second, the silica gel monomers are added to form a denser silica network around the fluorescent core material, providing shielding from solvent interactions that can be detrimental to photostability. By first forming a dye-rich core enables the incorporation of various classes of fluorophores which cover the entire UV-Vis absorption and emission spectrum.
[0024] The amount of reagents used in the synthesis of the different core-shell architectures in terms of dye placement, i.e. compact core, expanded core, and homogenous, have been kept identical to generate precise structure property correlations. However, the order in which the reagents are reacted that resulted in the forming the core-shell architecture varies. Therefore, the chemical environment around the dye molecules in each architecture is different with respect to the silica matrix density and presence of organic moieties which has significant effects on the photophysical particle properties.
[0025] For the synthesis of the compact core-shell nanoparticle, the dye precursor was added to a reaction vessel that contains appropriate amounts of ammonia, water and solvent and allowed to react overnight. The dye precursor was synthesized by addition reaction between TRITC and 3-aminopropyltriethoxysilane in molar ratio of 1:50, in exclusion of moisture. After the synthesis of the dye-rich compact core was completed, tetraethylorthosilicate (TEOS) was subsequently added to grow the silica shell that surrounded the core.
[0026] The synthesis of the expanded core-shell nanoparticle was accomplished by co-condensing TEOS with the aforementioned dye precursor and allow the mixture to react overnight. After the synthesis of the expanded core was completed, additional TEOS was added to grow the silica shell that surrounded the core.
[0027] The synthesis of the homogenous nanoparticles was accomplished by co-condensing all the reagents, the dye precursor and TEOS, at the same time and allow the mixture to react overnight.
[0028] The FCS curves and monoexponential fits shown in FIG. 2A -C illustrate the monodispersity requirement for each architecture in an aqueous solution. The FCS curve further provides two independent parameters: the diffusion coefficient and the absolute concentration. The diffusion coefficient is directly related to the hydrodynamic radius, and the absolute concentration allows quantification of the particle brightness.
[0029] FCS curves for each nanoparticle and its respective intermediate are shown in FIG. 2A -C. As shown in FIG. 2A , the diffusion coefficient of the core (D=0.098 μm 2 /ms) for the compact core-shell architecture, is about half that of free TRITC dye (D=0.21 μm 2 /ms). The complete nanoparticle is about ten times bigger, as shown in FIG. 2A (D=0.014 μm 2 /ms). A similar relationship between the free TRITC dye, expanded core-shell architecture and complete nanoparticle is shown in FIG. 2B . The diffusion coefficient of the core in the expanded core-shell architecture is 0.075 μm 2 /ms compared to a diffusion coefficient value of the free dye TRITC (D=0.21 μm 2 /ms). For the homogenous nanoparticle, there is no intermediate core structure, so FIG. 2C illustrates the diffusion coefficient of the homogenous nanoparticle (D=0.015 μm 2 /ms) relative to the free TRITC dye.
[0030] FIG. 2D -E illustrates the brightness of each architecture and synthesis intermediates. For the syntheses which proceed with a core intermediate, the core is always dimmer than the free dye, despite the fact that multiple dyes are presumably present in the core. The brightness of the complete nanoparticle is always significantly greater than free dye and/or core intermediate. Furthermore, the brightness varies for the different architectures despite their same particle size and same absolute amounts of precursor materials.
[0031] The fluorescent nanoparticles of the invention include an organic dye, TRITC, which demonstrates quantum efficiency enhancement effects in its luminescent properties. When the fluorescent nanoparticles of the invention are illuminated with a primary energy source, a secondary emission of energy occurs at a frequency corresponding to band gap of the organic dye used in the nanoparticle.
[0032] The number of TRITC equivalents per particle can be determined through a combination of FCS and absorbance measurements, in which the absolute concentration is determined from FCS and the relative absorbance is measured with respect to TRITC in solution, as shown in FIG. 3A -C. Dilute solutions were used (about 50 nM) in FIG. 3A -C so that a sample could be measured by both FCS and absorbance. The number of TRITC equivalents per particle, calculated using an extinction coefficient of 42,105 M −1 cm −1 at 514.5 nm are shown in Table II. Similarly, the relative intensities of the nanoparticle fluorescence and nanoparticle absorbance give the quantum efficiency enhancement over free TRITC, as shown in Table II.
[0033] For the compact core-shell and expanded core-shell nanoparticles, the number of TRITC equivalents per particle is indistinguishable at 8.6. However, the expanded core-shell nanoparticle shows a three-fold quantum efficiency enhancement compared to the free TRITC dye, while the compact core-shell exhibits only a two-fold quantum efficiency enhancement compared to the free TRITC dye, as shown in FIG. 3A , B and Table II. The largest quantum efficiency enhancement was observed with the homogenous nanoparticle, which has on average 2.3 TRITC equivalents per particle, as shown in FIG. 3C and Table II.
[0034] The ability to control the photophysical properties through the nanoparticle chemistry and architecture enables both the development of the next generation fluorescent probes and the study of fluorescent properties that might be inaccessible in solution.
[0035] The fluorescence lifetime of the particles is shown in FIG. 4 A . Each lifetime, including free TRITC, is multiexponential and the average lifetime values are compiled in Table III. The lifetime of TRITC (τ ƒ =2.1 ns) is in good agreement with the literature value in water. The lifetime increases from the compact core-shell (1.8 ns) to the expanded core-shell (2.9 ns) to the homogeneous particle (3.2 ns) ( FIG. 4A ). The compact-core shell has a lifetime which is less than free dye, although the dominant contribution to this lifetime is a fast component ( FIG. 4A ). From this lifetime data alone, one might conclude that the dye is quenched inside the compact core-shell particle, but the steady state measurements suggest otherwise. The combination of fluorescence lifetime and quantum efficiency allow for a unique determination of the radiative and non-radiative rate constants, tabulated in both normalized and absolute form in Table III. The enhancement of the radiative rate is constant across the different architectures and is 2.2 fold greater than free TRITC. However, the non-radiative rate varies across architectures from a relatively high value for the compact core-shell nanoparticles to a value almost 3 fold less for the homogeneous particles.
[0036] The rotational anisotropy of the particles again shows complicated, multiexponential behavior ( FIG. 4B , C), and we restrict ourselves at present to the average rotational time constant (Table III, θ). As expected, the rotation of the dye inside the particle is hampered by the silica matrix, leading to longer rotation times than free dye ( FIG. 4B ). In fact, the anisotropy curves do not decay to zero on the timescale of the measurement, in contrast to the coumarin control (note that there is also some residual anisotropy of free TRITC). However, there is still a remarkable degree of rotational mobility, even inside the tightly packed core of the nanoparticle. The time scales of rotation are too fast to be overall rotation of the entire 30 nm nanoparticle and too slow to be depolarization due to energy transfer. Furthermore, the amplitude of the curve (r(0)) is near the theoretical amplitude for two-photon anisotropy (r(0)=0.57), suggesting that there is not the fast depolarization usually associated with energy transfer.
[0037] It is therefore likely that the decay in anisotropy is due to hindered rotation of the dye molecules within the silica matrix. The scaled anisotropy for each architecture is shown in FIG. 4C . The compact core-shell nanoparticle has the fastest, least hindered rotation ( FIG. 4C ), followed by the expanded core-shell particle ( FIG. 4C ), and finally the homogeneous nanoparticle ( FIG. 4C ). This rotation time has a monotonic, inverse dependence on the non-radiative rate constant (Table III), suggesting that the confined mobility in the silica nanoparticle is responsible for suppression of non-radiative decay.
[0000] Nanoparticle Synthesis Materials
[0038] Absolute ethanol (Aldrich), Tetrahydrofuran (Aldrich), Ammonium hydroxide (Fluka, 28%), Tetraethoxysilane (Aldrich, 98%), 3-Aminopropyltriethoxysilane (Aldrich, 99%), 3-Mercaptopropyltriethoxysilane (Gelest, 99%), Tetramethylrhodamine-5-(and -6-)-isothiocyanate*mixed isomers*(TRITC) (Molecular Probes, 88%), Alexa Fluor® 488 C 5 Meleimide (Molecular Probes, 97%), Alexa Flour® 488 carboxylic acid, and succinimidyl ester (Molecular Probes, ≧50%).
[0000] Preparation of Core (Fluorescent Seed) Nanoparticles Generally
[0039] Amounts of water, ammonia and solvent were measured in graduated cylinders. Fluorescent seed particle synthesis was carried out in 1 L Erlenmeyer flasks and stirred with magnetic TEFLON® coated stir bars at about 600 rpm. De-ionized water and ammonia solution were added to ethanol and stirred. About 2 nL of the reactive dye precursor in either ethanol or THF containing about 425 micromolar APTS, was added to the reaction vessel. Depending on the desired architecture, the resulting mixture was stirred from 1 to 12 hours at room temperature with the reaction vessel covered with aluminum foil to minimize exposure to light to afford a fluorescent seed particle mixture. Tetrahydrofuran (THF) and absolute ethanol (EtOH) were distilled under nitrogen. Organic dyes were brought to room temperature from storage temperatures of about −20° C., and then placed in a glove box.
[0000] Preparation of the Silica Shell on the Core (Fluorescent Seed) Particles Generally
[0040] The silica shell coating and growth step was performed in the above mentioned fluorescent seed particle reaction mixture with regular addition of solvent, such as ethanol, methanol, or isopropanol, to prevent drastic changes in solution ionic strength while the silica forming monomer tetraethoxysilane (TEOS) was added. This prevents particle aggregation during synthesis, which can broaden the particle size distribution.
[0000] Characterization of Fluorescence Nano-Particles
[0041] The particle size and particle size distribution of the resulting fluorescent nanoparticles were characterized by electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS).
[0042] Fluorescence Correlation Spectroscopy—All FCS measurements were done on a custom FCS microscope based on two-photon excitation. The instrument consists of a Ti:sapphire oscillator with ˜100 fs pulsewidth and 80 MHz rep. rate pumped by an Ar+ ion laser (Spectra Physics, Palo Alto, Calif.). The beam was positioned with a Bio-Rad MRC 600 confocal scan box (Hercules, Calif.) coupled to a Zeiss Axiovert 35 inverted microscope. Excitation light was focused with Zeiss 63X C-Apochromat water immersion objective (N.A.=1.2), and emission was collected through the same objective. The fluorescence was separated from the excitation with a 670 DCLP dichroic and passed through a HQ575/150 emission filter to a GaAsP photon-counting PMT. The resulting photocurrent was digitally autocorrelated with an ALV 6010 multiple tau autocorrelator.
The autocorrelation function G(τ) is defined as:
G ( τ ) = < ∂ F ( 0 ) ∂ F ( τ ) > < F ( τ ) > 2 ( 1 )
where F(τ) is the fluorescence obtained from the volume at delay time τ, brackets denote ensemble averages, and δF(τ)=F(τ)−<F(τ)>. The fitting function is the standard function for one-component, three-dimensional diffusion:
G ( τ ) = 1 N ( 1 + 4 D τ w xy 2 ) - 1 ( 1 + 4 D τ w x 2 ) - 1 / 2 ( 2 )
where w zy and w z are the lateral and axial dimensions of the two-photon focal volume, respectively; N is the number of diffusing species in the focal volume; D is the diffusion coefficient. All FCS measurements were carried out with an excitation wavelength of 900 nm. At this wavelength, the lateral dimension was determined to be 0.248 micro meters and the axial dimension was determined to be 0.640 micro meters. The concentration calibration was determined from standard samples of rhodamine green to be 1.43 nM/particle (i.e. N=1 corresponds to 1.43 nM).
Photobleaching—For photobleaching experiments, 30 μL of sample was illuminated continuously in a 3 mm pathlength quartz cuvette (Starna). The excitation was the 514 nm laser line from an argon laser with a power of 5 W and a spot size of 1.5 cm. The samples were prepared with similar absorbance at the excitation wavelength of 514 nm.
Fluorescence is collected at right angle to the excitation through an HQ605/90 emission filter and recorded with a bialkali PMT (HCC125-02, Hamamatsu).
[0043] The following examples are presented for the purposes of illustration only and are not limiting the invention.
EXAMPLE 1
[0044] TABLE I Hydrodynamic radii of nanoparticles and nanoparticle cores. Core Core/shell radius (nm) radius (nm) Nanoparticle (SD) (SD) Compact core/shell 2.2 (0.3) 15 (1.2) Expanded 2.9 (0.3) 17 (1.4) core/shell Homogeneous — 15 (1.1)
The hydrodynamic radii calculated at 21° C. are tabulated in Table I. Each nanoparticle curve fits with a single diffusion coefficient and the hydrodynamic sizes are equal within the error of the measurement (r=15, 17 nm). For the core intermediates, the expanded core is slightly larger (r=2.9 nm) than the compact core (r=2.2 nm).
EXAMPLE 2
[0045]
TABLE II
Brightness of nanoparticles
TRITC
QE
Brightness
Counts/
Sample
equivalents
enhancement
factor
particle
TRITC
1.0
1.0
1.0
1.0
Compact
8.6
2.0
18.
14.
core/shell
Expanded
8.7
3.1
27.
22.
core/shell
Homogeneous
2.3
3.3
7.5
6.0
[0046] The amplitude of the autocorrelation provides the number of the diffusing species and the average count rate is a measure of the photons collected from the optically defined focal volume. From this data, the count rate per molecule for each diffusing species can be obtained, which is a direct measure of the brightness of a probe.
[0047] The overall enhancement of brightness of the particle over free dye is the product of the number of TRITC equivalents inside the nanoparticle and the relative quantum efficiency enhancement of the dye, as shown in Table II, brightness factor. However, given the uncertainty in the determination of TRITC equivalents, it is necessary to have an additional, independent measure of brightness for comparison, such as the counts per particle measured from FCS (Table II, counts/particle). The brightness factor is similar to the independent brightness determination from FCS (Table II, comparing last two columns), and the trend for brightness over the different architectures is the same by both methods. The brightness factor consistently overestimates the values measured by FCS, possibly due to the error in the determination of dye equivalents.
[0048] The enhancement of the quantum efficiency can be due, in general, to an increase in the radiative rate (k r ), a decrease in the non-radiative rate (k nr ), or both. The relative contributions of these factors are related to the fluorescence lifetime (τ ƒ ) and the quantum efficiency (φ) by:
τ f = 1 k r + k nr ( 1 ) ϕ = k r h r + k nr ( 2 )
EXAMPLE 3
[0049]
TABLE III
Time-resolved parameters for silica nanoparticles
<lifetime>
k r
k r
k nr
k nr
<θ>
Sample
ns
φ
ns −1
(normalized)
ns −1
(normalized)
ns
TRITC
2.1
0.15
0.072
1.0
0.41
1.0
0.21
Compact core-shell
1.8
0.30
0.17
2.3
0.39
0.95
0.40
Expanded core-shell
2.9
0.47
0.16
2.2
0.18
0.45
3.2
Homogeneous
3.2
0.50
0.16
2.2
0.16
0.39
6.7
[0050] All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.
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The invention generally relates to fluorescent nanoparticles and more specifically to silica-based fluorescent nanoparticles of less than 30 nm with covalently attached organic dyes. The invention provides a fluorescent monodisperse silica nanoparticle comprising fluorophore center core and a silica shell wherein the radiative properties of the nanoparticle are dependent upon the chemistry (composition) of the core and presence of the silica shell. In one aspect of the invention, the core-shell architecture provides an enhancement in fluorescence quantum efficiency. The invention generally provides control of photophysical properties of dye molecules encapsulated within silica particles with sizes down to 30 nm and below. This control is accomplished through changes in silica chemistry and particle architecture on the nanometer size scale and results in significant brightness enhancement compared to free dye.
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BACKGROUND OF THE INVENTION
The invention is directed to a method for the preparation of highly elastic foams of reduced compression hardness having urethane groups by the reaction of polyethers having a molecular weight of 400 to 10,000 and containing at least two hydroxyl groups with polyisocyanates in the presence of cross-linking agents, catalysts and water and optionally in the presence of emulsifiers, stabilizers, organic blowing agents and further auxiliaries and additives.
Flexible polyurethane foams are used to a large extent in upholstered furniture and automobile industries. For the different uses and the different qualities desired therefor, it is necessary to be able to vary the apparent density and primarily also the compression hardness over a wide range.
Inorganic and organic fillers have already been used for preparing foams with increased compression hardness. The compression hardness can also be increased by polymerization reactions of the polyols used for foaming.
Compression hardness is lowered by the use of physical blowing agents, such as fluorocarbons or methylene chloride. The use of these materials is contrary to the endeavor, for environmental reasons, to limit the use of fluorocarbons as much as possible. The same is true for methylene chloride, which is physiologically not safe.
In formulations in which inert fillers are used in order to obtain other foam properties instead of an increase in hardness, according to the state of the art, the use of physical blowing agents is even indispensable when flexible foams are to be obtained. For example, considerable amounts of melamine or aluminum hydroxide are used in order to manufacture upholstered furniture and mattresses of high flame resistance on the basis of highly elastic, so-called HR foams. The increase in compression hardness, which is associated therewith, cannot be accepted for reasons of comfort, so that physical blowing agents must be used in considerable amounts.
The addition of compounds which contain at least one polyoxyalkylene group and at least one anionic group to formulations for the production of polyurethane foams is known from the art.
For example, the use of a mixture of polyoxyalkylene alkyl ether sulfate and a polyoxyethylene/polyoxypropylene polymer as emulsifier and dispersing agent for the manufacture of flexible polyester urethane foams is described in CS patent 253,786.
The use of anionic surfactants as foam stabilizers for the preparation of flexible polyester polyurethane foams is known from the German Offenlegungsschrift 11 78 595.
The use of nonylphenol polyoxyethylene ether sulfates as foam stabilizers for the preparation of rigid polyurethane or polyisocyanurate foams can be inferred from U.S. Pat. No. 4,751,251.
Japanese patent 56/152 826 discloses the use of carboxymethylated polyether polyols as trimerizing catalysts for the preparation of rigid polyisocyanurate foams. Derivatives of aminated, alkoxylated aliphatic alcohols with sulfonate or carboxylate groups as trimerization catalysts for forming rigid polyisocyanurate foams is disclosed in the U.S. Pat. No. 4,235,811.
However, the use of such anionic surfactants for the preparation of highly elastic, so-called high resilient polyurethane foams cannot be inferred from the state of the art; nor is the use known of such surfactants for the preparation of polyurethane foams of reduced compression hardness.
SUMMARY OF THE INVENTION
An object of the invention is to provide a method for the preparation of foams within a wide range of apparent densities using technically simple means, wherein the foams have a low compression hardness at the given apparent density.
Another object of the invention is to provide a method for the preparation of foams within a wide range of apparent densities, wherein the use of fluorocarbons is limited as much as possible.
These and other objects are attained by the invention described below.
Surprisingly it has been discovered that the objects of the invention can be accomplished by carrying out the reaction of the polyurethane-forming agents in the presence of a compound Y which contains at least one polyoxyalkylene group and at least one anionic group in the molecule, in an amount of 0.01 to 5% by weight, based on the polyol.
DESCRIPTION OF THE INVENTION
According to the invention, the structure of compound Y is variable over a wide range and need only fulfill the condition that it has at least one polyoxyalkylene group and at least one anionic group in the molecule.
As compound Y, preferably a compound of the following formula is used ##STR1## wherein R 1 is a hydrogen or an m-valent alkyl, aryl or alkylaryl group and the alkyl group in each case has 1 to 22 carbon atoms,
R 2 is the same or different in the polymeric molecule and represents a hydrogen, methyl or ethyl group,
A is an inorganic or organic anionic group,
M is a cation, which has a positive charge, which corresponds to the negative charge of the anion,
m has a value of 1 to 8, but is 1 when R 1 is hydrogen and
x has an average value of 1 to 100.
As an alkyl group, the R 1 group has 1 to 22 carbon atoms. The alkyl group is preferably linear and has, in particular, 1 to 8 carbon atoms. As the aryl group, the phenyl group, which is optionally substituted, is preferred. Examples of alkylaryl groups are the octylphenyl, nonylphenyl and dodecylphenyl groups.
A is an inorganic or organic group. Examples of such groups are --SO 3 , --CH 2 CH 2 --SO 3 , --(CH 2 ) 3 --SO 3 , --CH 2 --CH(CH 3 )--CH 2 --SO 3 , --CH 2 --CH(OH)--CH 2 --SO 3 , --CH 2 --CH(OH)--CH 2 --S 2 O 3 , --Z--COO-- (Z=a divalent, optionally substituted hydrocarbon group), --CO--Z--COO--, PO 3 , PO 2 , --(CH 2 ) n --PO 3 , --(CH 2 ) n --PO 2 (n=1, 2, 3 or 4).
The cation M preferably is an alkali, alkaline earth, Mn, Fe, Co, Ni, Cu, Zn, Al, NH 4 , alkylammonium or hydroxyalkylammonium ion. The alkyl group of the alkylammonium ion has 1 to 4 carbon atoms and the alkyl group of the hydroxyalkyl group has 2 to 4 carbon atoms.
Compounds of formula I may be obtained by the well known addition reaction between alkylene oxides and compounds containing active hydrogen atoms and the subsequent introduction of the anionic group. Alcohols in particular come into consideration as compounds having active hydrogens. Literature references, appropriate for the synthesis of anionic compounds, may be found in the Tensid-Taschenbuch (Surfactant Handbook), published by Carl Hanser Verlag, 1981, pages 85 to 167, and in Ullmann's Encyclopadie der technischen Chemie (Encyclopedia of Industrial Chemistry), published by Verlag Chemie, 1982, 4th edition, volume 22, pages 468 to 469.
Examples of suitable compounds are: (the symbols Y1, Y2, etc. serve to identify the products in the examples and the Tables)
A=--SO 3 ; polyalkylene sulfates such as
CH.sub.3 --(CH.sub.2 --).sub.11 (OCH.sub.2 --CH.sub.2 --).sub.2 O--SO.sub.3.sup.- Na.sup.+ Y 1 ##STR2## A=--CH.sub.2 CH.sub.2 --SO.sub.3 : polyoxyalkylene sulfonates such as
H--(OCH.sub.2 --CH.sub.2 --).sub.15 O--CH.sub.2 CH.sub.2 --SO.sub.3.sup.- Na.sup.+
Na.sup.+ SO.sub.3.sup.- --CH.sub.2 CH.sub.2 --O--(CH.sub.2 CH.sub.2 --O--).sub.6 (CH.sub.2 --).sub.4 (O--CH.sub.2 --CH.sub.2).sub.6 O--CH.sub.2 CH.sub.2 --SO.sub.3.sup.- Na.sup.+ Y 3
A=--(CH 2 --) 3 SO 3 , --CH 2 --CH(CH 3 )--CH 2 --SO 3 : polyoxyalkylenepropyl or polyoxyalkylene-2-methylpropyl sulfonates such as
H--(OCH.sub.2 --CH.sub.2 --).sub.10 (OCH.sub.2 --CH(CH.sub.3)--).sub.8 O--(CH.sub.2 --).sub.3 SO.sub.3.sup.- K.sup.+ Y 4
H--(OCH.sub.2 --CH.sub.2 --).sub.30 (OCH.sub.2 --CH(C.sub.2 H.sub.5)--).sub.5 O--(CH.sub.2 --).sub.3 SO.sub.3.sup.- NH.sub.4.sup.+Y 5
GL--[(OCH.sub.2 --CH.sub.2 --).sub.10 (OCH.sub.2 --CH(CH.sub.3)--).sub.12 O--CH.sub.2 --CH(CH.sub.3)--CH.sub.2 --SO.sub.3.sup.- Na.sup.+ ].sub.3Y 6
(GL=the ##STR3## group derived from glycerine) A=--CH 2 --CH(OH)--CH 2 --SO 3 : polyoxyalkylenehydroxypropyl sulfonates such as:
CH.sub.3 --(CH.sub.2 --).sub.3 (OCH.sub.2 --CH.sub.2 --).sub.4 O--CH.sub.2 --CH(OH)--CH.sub.2 --SO.sub.3.sup.- Na.sup.+
SR--[(OCH.sub.2 --CH.sub.2 --).sub.4 (OCH.sub.2 --CH(CH.sub.3)--).sub.4 O--CH.sub.2 --CH(OH)--CH.sub.2 --SO.sub.3.sup.- Na.sup.+ ].sub.6Y 7
(SR=the ##STR4## group derived from sorbitol) A=--CH 2 --CH(OH)--CH 2 --S 2 O 3 : polyoxyalkylenehydroxypropyl thiosulfates (Bunte salts) such as
[CH.sub.3 --(OCH.sub.2 CH(CH.sub.3 --).sub.8 O--CH.sub.2 --CH(OH)--CH.sub.2 --S.sub.2 O.sub.3.sup.- ].sub.2 Mg.sup.2+ Y 8
CH.sub.3 --(OCH.sub.2 --CH.sub.2 --).sub.12 O--CH.sub.2 --CH(OH)--CH.sub.2 --S.sub.2 O.sub.3.sup.- K.sup.+
A=--Z--COO polyoxyalkylene alkyl ether carboxylates such as
Na.sup.+- OOC--CH.sub.2 --O--(CH.sub.2 --CH.sub.2 --CH.sub.2 O--).sub.4 CH.sub.2 CH.sub.2 --(OCH.sub.2 --CH.sub.2 --).sub.4 O--CH.sub.2 --COO.sup.- Na.sup.+
C.sub.9 H.sub.19 --Ph--(OCH.sub.2 --CH.sub.2 --).sub.8 O--CH.sub.2 CH.sub.2 --COO.sup.- NH.sub.4.sup.+ Y 9
CH.sub.3 --(OCH.sub.2 --CH.sub.2 --).sub.6 (OCH.sub.2 --CH(CH.sub.3)--).sub.4 O--CH.sub.2 --Ph--CO.sup.- Na.sup.+
A=--CO--Z--COO: half ester carboxylates of polyoxyalkylenes such as
[CH.sub.3 --(CH.sub.2 --).sub.7 (OCH.sub.2 --CH.sub.2 --).sub.8 O--CO--CH═CH--COO.sup.- ].sub.2 Ca.sup.2+ Y 10 ##STR5## A=--PO.sub.3 : polyoxyalkylene phosphates (mono- and diesters) such as
CH.sub.3 --(CH.sub.2 --).sub.11 (OCH.sub.2 --CH.sub.2 --).sub.7 O--PO.sub.3.sup.2- 2Na.sup.+ Y 12
[C.sub.9 H.sub.19 --Ph--(OCH.sub.2 --CH.sub.2 --).sub.9 O--].sub.2 PO.sub.2.sup.- K.sup.+
A=--PO 2 : polyoxyalkylene phosphites such as
Ph--CH.sub.2 --(OCH.sub.2 --CH.sub.2 --).sub.24 O--PO.sub.2.sup.- Na.sup.+
CH.sub.3 --(CH.sub.2 --).sub.17 (OCH.sub.2 --CH.sub.2 --).sub.30 (OCH.sub.2 --CH(CH.sub.3)--).sub.6 O--PO.sub.2.sup.- Na.sup.+ Y 13
A=--(CH 2 --) n PO 3 : polyoxyalkylene phosphonates such as
CH.sub.3 --(OCH.sub.2 --CH.sub.2 --).sub.8 (OCH.sub.2 --CH(C.sub.2 H.sub.5)--).sub.30 O--(CH.sub.2 --).sub.2 PO.sub.3.sup.2- Mg.sup.2+Y 14
C.sub.4 H.sub.9 --Ph--(OCH.sub.2 --CH.sub.2 --).sub.15 O--(CH.sub.2 --).sub.4 PO.sub.3.sup.2- 2K.sup.+
A=--(CH 2 --) n PO 2 : polyoxyalkylene phosphinates such as
CH.sub.3 --(OCH.sub.2 --CH(CH.sub.3)--).sub.60 O--CH.sub.2 PO.sub.2.sup.2- 2Na.sup.+
CH.sub.3 --(CH.sub.2 --).sub.7 (OCH.sub.2 --CH.sub.2).sub.10 O--(CH.sub.2 --).sub.2 PO.sub.2.sup.2- 2NH.sub.4.sup.+ Y 15
Furthermore, compounds of the following formula ##STR6## wherein R 1 , R 2 , M and x have the meaning already given and o, p and q are the same or different and in each case have values from 0 to 7, with the proviso that the sum of o+p+q is at least equal to 3, are preferably used as compound Y.
These compounds can be obtained by alkoxylation of sulfonated alkene diols. Examples of suitable diols are 2-butene-1,4-diol, 1-butene-3,4-diol, isobutene-1,3-diol and 2-methyl-2-butene-1,4-diol. The sulfonation is carried out by the addition of compounds of formula HSO 3 M to the double bond of the diol.
Examples of suitable compounds are: ##STR7##
A further group of compounds Y, the use of which is preferred, corresponds to the general formula ##STR8## wherein R 1 , R 2 , M, m and x have the meaning already given, R 3 is a hydrogen, alkyl, aryl or alkylaryl group and the alkyl groups have 1 to 22 carbon atoms, R 4 is a hydrogen or methyl group and y is equal to m or a multiple of m.
The synthesis of compounds III is described in the German patent 36 33 421. It is accomplished by the addition reaction of alkylene oxides and allyl and/or methallyl glycidyl ethers with monohydric or multihydric alcohols and the addition of HSO 3 M to the olefinic double bond. Examples of suitable compounds are: ##STR9## (BR=the group --(CH 2 --) 4 derived from butane-1,4-diol)
Further preferable compounds Y correspond to the general formula
R.sup.5 --CH.sub.2 O--(CH.sub.2 --CH(R.sup.2)--O--).sub.X CH.sub.2 --CH(R.sup.4)--CH.sub.2 --SO.sub.3.sup.- M.sup.+ IV
wherein R 2 , R 4 , x and M have the meaning already given, and R 5 represents the HO--CH 2 --CH(OH)-- or OH--CH 2 --C(CH 2 OH)(R 6 )-- group, and in which R 6 is a methyl, ethyl or propyl group.
Such compounds are described in the European patent 0 158 053. They can be obtained by the allylation of ketalized 1,2- or 1,3 polyether diols, followed by deketalization and sulfonation with HSO 3 M. It is also possible to sulfonate first and to carry out the ketalization in a second step. Examples of such compounds are: ##STR10##
It is furthermore possible to use advantageously in the inventive method compounds Y which correspond to the following formula: ##STR11## wherein R 1 , R 2 , M, x and m have the meaning already given, R 7 is a divalent alkyl group with 1 to 22 carbon atoms, a divalent aryl or alkylaryl group or a group having the formula --CO--CH 2 --.
The half-esters of sulfosuccinic acid (R 7 =--CO--CH 2 --) can be obtained by the sulfonation of the half-ester of maleic acid. The α-sulfoalkyl polyoxyalkylene ether carboxylates can be obtained by the sulfonation of the corresponding alkyl polyoxyalkylene ether carboxylates.
Examples of these compounds are: ##STR12## (GL=the ##STR13## group derived from glycerin) ##STR14##
Finally, the following compounds also are preferred as compounds Y ##STR15## wherein R 1 , R 2 , R 7 , M, x and m have the meaning already given, R 8 has the meaning of R 1 or represents the R 1 --(O--CH 2 --CH(R 2 )--) x group.
The sulfosuccinic diesters can be obtained by the sulfonation of maleic diesters (R7=--CO--CH 2 --) and the α-sulfoalkyl polyoxyalkylene ether esters can be obtained by the sulfonation of the appropriate alkyl polyoxyalkylene ether esters.
Examples of such compounds are: ##STR16##
The preparation of HR block and molded foams is known and is described, for example, in "Flexible Polyurethane Foams, Chemistry and Technology," Applied Science Publishers, 1982, pages 133 to 139 and 158 to 173. Further information can be obtained from the "Kunststoff-Handbuch" (Plastic Handbook), vol. 7, published by Carl Hanser Verlag, 1983. According to these references, highly elastic foams are obtained by the combination of high molecular weight, highly active, polyether polyols, with as high a primary OH end group content as possible, and polyfunctional isocyanates in the presence of suitable cross-linking agents.
In German patents 25 07 161 and 26 03 498, the preparation is described of highly elastic foams from highly reactive polyether polyols, which are built up exclusively from alkylene oxides, and diisocyanates with addition of crystalline cross linking agents, which are insoluble or only slightly soluble in the polyether polyol at room temperature. However, it is also in keeping with the state of the art to use polyether polyols which contain organic fillers, such as the so-called polymer, PHD or PIPA polyols, which can be prepared in the form of sedimentation-resistant dispersions by the reaction of organic monomers in the polyether polyol. For this reaction, alkanolamines and/or higher functional alcohols are usually used as cross linking agents.
The inventive method and the properties of the foams prepared by this method are described in even greater detail by means of the following examples.
For these examples, the following products are used and the following product names are employed:
polyol A: conventional, commercial, highly reactive HR polyol with predominantly primary OH end groups. The OH number is approximately 36.
polyol B: conventional, commercial, highly reactive HR polyol, which contains a sedimentation-resistant polyurea dispersion as filler (a so-called PHD polyol). The OH number is approximately 28.
polyol C: conventional, commercial highly reactive HR polyol, which contains a sedimentation-resistant dispersion of a copolymer based on styrene and acrylonitrile (so-called polymer polyol). The OH number is approximately 30.
polyol D: the HR polyol of German patent 31 03 757, which contains a sedimentation-resistant polyurethane dispersion (through an in situ reaction of an isocyanate with an alkanolamine in a polyol of type A) (so-called PIPA polyol)
DEOA: N,N-diethanolamine
Ortegol®204: conventional, commercial cross-linking agent of German patents 25 07 161 and 26 03 498
TEGOAMINE®BDE: 70% solution of bis(2-dimethylaminoethyl) ether in dipropylene glycol
TEGOAMINE®33: 33% solution of triethylenediamine in dipropylene glycol
Kosmos®29: tin(II) octoate
Kosmos®19: dibutyl tin(IV) dilaurate
Tegostab®B 8681: conventional, commercial foam stabilizer for the preparation of HR block and molded foams
melamine: conventional, commercial melamine, with an average particle size of 20 μm
F 11: trichlorofluoromethane
Desmodur®T 80: conventional commercial toluylene diisocyanate, characterized by an isomer ratio (2,4- to 2,6-) of 80:20
compound Y of the invention
The foam is prepared according to the so-called hand foaming method. For this method, all the components, with the exception of the isocyanate and, if necessary, the physical blowing agent, are prestirred for 60 seconds at 1,000 rpm. The isocyanate and, if necessary, the blowing agent are added subsequently and stirring is continued for a further 7 seconds at 2,500 rpm. The liquid mixture is then added to an open container having the dimensions of 30 cm×30 cm×30 cm, so that the foam can rise freely.
The bulk density and the compression hardness of the foam are determined after a 72-hour storage under standard atmospheric conditions, that is, at 23°±1° C. and 50±2% relative humidity. The compression hardness is determined by the method of DIN 53 577 at 40% compression.
TABLE 1__________________________________________________________________________Formulations(Data in % by Weight)__________________________________________________________________________ Formulation 1 2 3 4 5 6 7 8 9 10__________________________________________________________________________Polyol A 100 100 100 100 100 100 100 100 100 100Polyol B -- -- -- -- -- -- -- -- -- --Polyol C -- -- -- -- -- -- -- -- -- --Polyol D -- -- -- -- -- -- -- -- --Water (total) 2.5 3.0 3.5 4.0 2.5 2.5 3.0 3.0 2.5 3.0DEOA 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5Ortegol ®204 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0Kosmos ®29 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Kosmos ®19 -- -- -- -- -- -- -- -- -- --TEGOAMINE ®BDE 0.12 0.10 0.08 0.06 0.12 0.12 0.10 0.10 0.12 0.10TEGOAMINE ®33 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4Tegostab ®B 8681 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0F 11 -- -- -- -- 5 10 5 10 -- --Melamine 25 25 25 25 25 25 25 25 25 25Desmodur ®T 80 35.1 39.9 44.7 49.6 35.1 35.1 39.9 39.9 35.1 39.9Inventive Compound (Y) -- -- -- -- -- -- -- -- 1.0 1.0__________________________________________________________________________ Formulation 11 12 13 14 15 16 17 18 19 20__________________________________________________________________________Polyol A 100 100 100 100 100 -- -- -- -- --Polyol B -- -- -- -- -- 100 100 100 100 100Polyol C -- -- -- -- -- -- -- -- -- --Polyol D -- -- -- -- -- -- -- -- -- --Water (total) 3.5 4.0 3.5 3.0 3.5 3.0 3.5 3.0 4.0 3.0DEOA 0.5 0.5 0.5 0.5 0.5 1.0 1.0 1.0 1.0 0.5Ortegol ®204 3.0 3.0 3.0 3.0 3.0 -- -- -- -- 3.0Kosmos ®29 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15Kosmos ®19 -- -- -- -- -- -- -- -- -- --TEGOAMINE ®BDE 0.08 0.06 0.05 0.1 0.1 0.05 0.05 0.05 0.03 0.05TEGOAMINE ®33 0.4 0.4 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3Tegostab ®B 8681 1.0 1.0 0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8F 11 -- -- -- 5 -- -- 5 -- -- --Melamine 25 25 -- -- -- 25 25 25 25 25Desmodur ®T 80 44.7 49.6 44.7 39.9 44.7 36.4 41.1 36.4 46.1 36.4Inventive Compound (Y) 1.0 1.0 -- -- 1.0 -- -- 1.5 1.5 1.5__________________________________________________________________________ Formulation 21 22 23 24 25 26 27 28 29 30__________________________________________________________________________Polyol A -- -- -- -- -- -- 100 100 100 100Polyol B -- -- -- -- -- -- -- -- -- --Polyol C 100 100 100 100 -- -- -- -- -- --Polyol D -- -- -- -- 100 100 -- -- -- --Water (total) 3.0 3.5 3.0 4.0 3.0 3.0 3.5 3.5 3.5 3.5DEOA 1.0 1.0 1.0 1.0 0.13 0.13 0.5 0.5 0.5 0.5Ortegol ®204 -- -- -- -- -- -- 3.0 3.0 3.0 3.0Kosmos ®29 -- -- -- -- -- -- 0.15 0.15 0.15 0.15Kosmos ®19 0.1 0.1 0.1 0.1 0.05 0.05 -- -- -- --TEGOAMINE ®BDE 0.5 0.5 0.5 0.03 0.12 0.12 0.08 0.08 0.08 0.08TEGOAMINE ®33 0.15 0.15 0.15 0.15 -- -- 0.4 0.4 0.4 0.4Tegostab ®B 8681 1.0 1.0 1.0 1.0 0.4 0.4 1.0 1.0 1.0 1.0F 11 -- 5 -- -- -- -- -- -- -- --Melamine 25 25 25 25 25 25 25 25 25 25Desmodur ®T 80 35.7 41.0 35.7 46.4 39.4 39.4 44.7 44.7 44.7 44.7Inventive Compound (Y) -- -- 1.5 1.5 -- 1.5 1.0 3.0 5.0 *__________________________________________________________________________ ##STR17##
TABLE 2______________________________________Foamings Formulation According to Compound Y CompressionExample Table 1 (See Above Density HardnessNumber Number Description) (kg/m.sup.3) (kPa)______________________________________ 1 1 -- 43.6 3.1 2 2 -- 37.0 2.9 3 3 -- 32.1 2.7 4 4 -- 29.2 2.7 5 5 -- 37.1 2.4 6 6 -- 31.8 1.8 7 7 -- 31.6 2.3 8 8 -- 28.9 1.8 9 9 Y1 44.8 2.710 9 Y2 44.6 2.311 9 Y3 44.0 2.512 9 Y4 44.3 2.213 9 Y5 44.5 2.614 9 Y6 43.7 2.315 10 Y7 37.0 2.116 10 Y8 37.3 2.217 10 Y9 37.6 2.618 10 Y10 37.1 2.019 10 Y11 37.1 2.320 10 Y12 37.4 2.221 10 Y13 36.9 2.522 10 Y14 37.3 2.623 10 Y15 37.6 2.224 11 Y16 33.2 1.925 11 Y17 32.8 1.826 11 Y18 32.5 2.227 11 Y19 32.7 1.828 11 Y20 32.4 2.129 11 Y21 32.6 2.330 12 Y22 29.4 2.531 12 Y23 29.2 2.332 12 Y24 29.0 1.733 12 Y25 29.6 2.334 13 -- 25.6 1.635 14 -- 26.0 1.136 15 Y4 25.7 1.137 16 -- 35.8 2.638 17 -- 27.8 2.139 18 Y4 36.4 2.040 19 Y4 27.2 2.041 20 Y4 36.2 2.042 21 -- 35.8 3.143 22 -- 27.5 2.544 23 Y10 36.0 1.945 24 Y10 27.8 2.046 25 -- 34.8 4.447 26 Y19 35.0 3.548 27 Y20 33.2 2.049 28 Y20 33.4 1.750 29 Y20 33.1 1.551 30 * 32.1 2.7______________________________________ ##STR18##
Comparison of Examples 9 to 33 (Formulations 9 to 12) with Examples 1 to 4 (Formulations 1 to 4) shows that when the inventive compound Y is used, a significant reduction in the compression hardness is possible over a wide range of specific gravities. This reduction in compression hardness is tantamount to the replacement of physical blowing agents such as Frigen 11 (Examples 5 to 8, Formulations 5 to 8). Examples 34 to 36 (Formulations 13 to 15) confirm that even in foams which do not contain any inert fillers, such as melamine, addition of the compound Y in accordance with the invention results in a reduction of the compression hardness.
Examples 37 to 47 (Formulations 16 to 26) show that the inventive method is not limited to filled polyols of the A type, but can also be used in combination with PHD, polymer and PIPA polyols, which are commercially available.
The concentration of Y, based on 100% by weight of polyol, can be varied over a wide range, in order to arrive at foams of different compression hardness (Examples 48 to 50, Formulations 27 to 29).
Example 51 (Formulation 30) shows that compounds which do not contain any polyoxyalkylene groups cannot bring about a reduction in the compression hardness, despite the presence of the anionic group in the molecule. On the other hand, the desired result is obtained (Example 10, Formulation 9) in the presence of the polyalkylene group (compound Y2).
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A method for the preparation of highly elastic foams of reduced compression hardness and having urethane groups is disclosed, in which the reaction of the polyurethane-forming materials is carried in the presence of 0.01 to 5% by weight, based on the polyol, of a compound, which has at least one polyoxyalkylene group and at least one anionic group in the molecule. The use of fluorocarbons to decrease the compression hardness can reduced appreciably by the use of this compound.
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