Antigen Or Antibody Attached To A Carrier Via Bridging Agent Patents (Class 436/532)
  • Patent number: 5550063
    Abstract: Method for producing an optical assay device having a substrate and one or more optical layers, an attachment layer and a receptive layer, including the step of spin coating an anti-reflective layer or an attachment layer.
    Type: Grant
    Filed: June 10, 1993
    Date of Patent: August 27, 1996
    Assignee: Biostar, Inc.
    Inventor: Gregory R. Bogart
  • Patent number: 5543332
    Abstract: Water soluble reagents are claimed, comprising a water-soluble polymeric carrier molecule having attached thereto more than one connecting moiety wherein the connecting moiety is derived from divinyl sulfone, and wherein each connecting moiety is attached to a reactive functional group on the polymeric molecule, and wherein the reagents are capable of reaction with a molecular species having a functional group which is reactive towards the terminal vinyl group of the more than one connecting moiety and the molecular species is selected from the group consisting of labelling species, marking species, and targeting species.
    Type: Grant
    Filed: November 8, 1991
    Date of Patent: August 6, 1996
    Assignee: Immunodex K/S
    Inventors: Allan O. F. Lihme, Thomas Boenisch
  • Patent number: 5541117
    Abstract: The invention concerns a method for the determination of the content of a particular haemoglobin derivative in a blood sample. In particular, the invention concerns a method for the determination of the content of haemoglobin derivatives such as glycated haemoglobin which require the separate determination of the total haemoglobin content and the determination of the haemoglobin derivative in order to determine the proportion of the derivatized haemoglobin in the blood as well as a suitable haemolysis reagent for this.
    Type: Grant
    Filed: March 4, 1993
    Date of Patent: July 30, 1996
    Assignee: Boehringer Mannheim GmbH
    Inventors: Johann Karl, Lorenz Kerscher, Erich Schneider
  • Patent number: 5540995
    Abstract: A granular polymer composite comprising polymeric granules having coated on a surface thereof a calcium phosphate compound, at least a part of the particles of the calcium phosphate compound penetrates into the polymeric granules. The composite has a high bonding strength between the polymeric granules as a matrix and a coating of the calcium phosphate compound and also can fully exhibit the functions of a calcium phosphate compound. Using the granular polymer composite, a diagnostic agent which comprises of an antigen or antibody is adsorbed and immobilized on the composite and is therefore useful in diagnostic tests utilizing an antigen-antibody reaction for a number of infectious diseases.
    Type: Grant
    Filed: October 5, 1994
    Date of Patent: July 30, 1996
    Assignee: Asahi Kogaku Kogyo Kabushiki Kaisha
    Inventors: Tadahiko Kitano, Mikio Nakayama, Tetsuro Ogawa, Tsuneo Hiraide
  • Patent number: 5532170
    Abstract: A method of preparing functionalized particles including (a) treating an activated substrate (CPG) with a bifunctional cross-linking agent containing a cleavable bond so as to immobilize the cross-linking agent, (b) conjugating an activated particle (P) with the immobilized cross-linking agent, and (c) cleaving the cleavable bond so as to separate the particle (P) from the substrate (CPG). The functionalized particles subsequently can be conjugated to biologically active molecules for use in assay methods.
    Type: Grant
    Filed: August 6, 1993
    Date of Patent: July 2, 1996
    Assignee: Fisons plc
    Inventors: Philip E. Buckle, Denise V. Pollard-Knight
  • Patent number: 5527901
    Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.
    Type: Grant
    Filed: December 22, 1993
    Date of Patent: June 18, 1996
    Assignee: Alberta Research Council
    Inventors: Robert M. Ratcliffe, Andre P. Venot, S. Zaheer Abbas
  • Patent number: 5527712
    Abstract: A substrate for surface-enhanced analytical procedures, such substrates prepared for use in specific procedures to detect specific binding partner molecules, and a method for making them. The substrate is a body having a substrate surface on which there are randomly spaced apart metal islands. A continuous layer of coupling agent coats the islands and any intervening substrate surface. First binding partner molecules are bonded to the coupling agent. These are specifically attractive to specified second partner molecules for an analytical procedure for detecting the presence of, and perhaps the concentration of second partner molecules, or in some procedures, of a specified third binding partner molecule which becomes bonded to the second binding partner molecule. The thickness of the coupling agent layer is selected to improve the sensitivity of a given analytical procedure for detecting or measuring the specific binding partner molecule.
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: June 18, 1996
    Assignee: Medifor Limited, an Irish Corporation
    Inventor: Timothy M. Sheehy
  • Patent number: 5527681
    Abstract: A synthetic strategy for the creation of large scale chemical diversity is claimed. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis of an array of polymers that are based on a target polymer. The array includes systematically substituted versions of the target polymer.
    Type: Grant
    Filed: November 5, 1992
    Date of Patent: June 18, 1996
    Assignee: Affymax Technologies N.V.
    Inventor: Christopher P. Holmes
  • Patent number: 5516703
    Abstract: A surface of specific reactivity is formed by adsorbing a modified block polymeric surfactant of the Pluronic-type, i.e., containing pendant poly(ethylene oxide) blocks attached at an end to poly(propylene oxide) center blocks and with specifically reactive groups at the unattached ends of the poly(ethylene oxide) blocks, upon a hydrophobic surface.
    Type: Grant
    Filed: August 20, 1993
    Date of Patent: May 14, 1996
    Assignee: The University of Utah
    Inventors: Karin M. E. Caldwell, Per J. E. Carlsson, Jenq-Thun Li
  • Patent number: 5514559
    Abstract: Novel conjugate of the general formulaA--L.sub.1 --L.sub.2 --Bwherein A and B are the substances to be coupled selected from the groups of haptens, proteins, polysaccharides, soluble polystyrenes, or peptides, L.sub.1 and L.sub.2 are trivalent linkers and L.sub.1 and L.sub.2 are bound via two thioether. They can be used in immunological assays and exhibit an improved storage stability.
    Type: Grant
    Filed: March 29, 1994
    Date of Patent: May 7, 1996
    Assignee: Boehringer Mannheim GmbH
    Inventors: Christine Markert-Hahn, Beatus Ofenloch-Haehnle, Eva Hoess, Erasmus Huber
  • Patent number: 5510270
    Abstract: A method for synthesizing and screening oligonucleotides on a solid substrate. The method provides for the irradiation of a first predefined region of a substrate comprising immobilized nucleotides on its surface, without irradiation of a second predefined region of the substrate. The irradiation step removes a protecting group from the immobilized nucleotides. The substrate is contacted with a first nucleotide to couple the nucleotide to the immobilized nucleotides in the first predefined region without coupling in the second predefined region. At least a part of the first predefined region and at least a part of the second predefined region are subjected to further irradiation. The substrate is contacted with a second nucleotide, which couples to the immobilized nucleotides in at least part of the first and at least part of the second predefined regions. By repeating these steps, an array of diverse oligonucleotides is formed on the substrate.
    Type: Grant
    Filed: September 30, 1992
    Date of Patent: April 23, 1996
    Assignee: Affymax Technologies N.V.
    Inventors: Stephen P. A. Fodor, Michael C. Pirrung, J. Leighton Read, Lubert Stryer
  • Patent number: 5501949
    Abstract: An immunoassay method for the detection or quantitation of an analyte suspected of being in a solution comprising: (a) combining said specimen, a first binding component, insoluble particles, and second binding component labelled with a signal generating material in a solid phase retention and separation apparatus having a sufficient pore size such that said particles are trapped within said filter yet permitting rapid passage of fluid therethrough in such a manner that an immunological reaction occurs if analyte is present in said specimen, resulting in the formation of an immunocomplex of insolublized first binding component:analyte:second labelled binding component on or within said filter means; (b) separating bound from unbound material; and (c) determining the presence and/or amount of signal produced which is correlative with the amount of analyte present in the solution.
    Type: Grant
    Filed: August 15, 1994
    Date of Patent: March 26, 1996
    Assignee: Murex Diagnostics Corporation
    Inventor: David L. Marshall
  • Patent number: 5494815
    Abstract: Biochemical substances, such as enzymes, are immobilized using an olefinic-unsaturated, epoxyfunctional polysiloxane. The polysiloxane is applied to a carrier material. The polysiloxane on the carrier is cross-linked by using high-energy radiation or a peroxide to form a polymer matrix. The polymer matrix is treated with an aqueous solution of a biochemical substance that reacts with epoxy groups and becomes immobilized. The polymer matrix is stabilized by the reaction of non-reacted epoxy groups with a compound containing an amino group, a carboxyl group or an amino group and a carboxyl group. The crosslinked polysiloxane can be hydrophilized after cross-linking and prior to immobilization of the biochemical substance by the reaction of a portion of the epoxy groups with a hydrophilic compound.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 27, 1996
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht, Helmut Formanek, Gerhard Wanner
  • Patent number: 5491083
    Abstract: Poly(fluoroalkyl) sugar reagents are prepared containing a sugar such as a monosaccharide or a disaccharide to which are bonded a plurality of fluoroalkyl anchor groups capable of attaching to a fluorocarbon surface, and either a reactive group capable of covalent coupling to a biomolecule such as an enzyme or a charged group to form an ion-exchanger or a non-ionic group to give a neutral fluorosurfactant. A spacer may be between the reactive group and the sugar. The poly(fluoroalkyl) sugar reagents are strongly adsorbed onto fluorocarbon surfaces to provide supports for such applications as separation and immobilization of biomolecules such as enzymes, carrying out heterogeneous diagnostic assays, and preparation of biosensors.
    Type: Grant
    Filed: October 5, 1994
    Date of Patent: February 13, 1996
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Rene Arentzen, Prabhakar K. Jadhav, Robert K. Kobos, Bruce E. Smart
  • Patent number: 5486479
    Abstract: The invention relates to immunoassay reagents that are both sensitive and specific and which require no sample pretreatment. The invention reagents are particularly useful for assaying digoxin concentrations in patient sera. More particularly, the invention relates to methods and kits comprising (A) an immunoreactant immobilized on a support; and, (B) a buffer agent comprising (i) a buffering agent, (ii) sodium chloride, (iii) choline chloride, (iv) a polysaccharide, (v) fatty-acid-free serum albumin, and (vi) a non-specific reaction suppressor of the formula: ##STR1## wherein X is --NH--(CO)--NH--, --NH--(CS)--NH--, or --N.dbd.C.dbd.N--, R.sub.1 and R.sub.2, which may be the same or different, are C.sub.1 -C.sub.5 linear or branched alkyl groups, or R.sub.1 and R.sub.2, together with nitrogen, is ##STR2## or the metho-p-toluenesulfonate salt thereof, Y, which may be the same or different, is any of H, OH and halogen,R.sub.3 is --NR.sub.1 R.sub.2, --NH.sub.
    Type: Grant
    Filed: May 2, 1994
    Date of Patent: January 23, 1996
    Assignee: Mitsubishi Chemical Corporation
    Inventors: Michio Ito, Satoshi Sugawa, Atsushi Yanagida
  • Patent number: 5474765
    Abstract: This invention discloses new targeted conjugates for the delivery of a compound, and particularly, a steroid, to vascular endothelial cells. The conjugates comprise two components, preferably linked by a selectively-hydrolyzable bond, such as an acid-labile bond or enzyme-sensitive bond. The first component, a polyanionic polymer, and preferably, a polysulphated polymer such as a heparin-derivative, specifically directs the conjugate to vascular endothelial cells. The second component is a selected agent, such as asteroid, which exerts a specific effect on the target cell following its release. In particular, the present invention provides novel conjugated angiogenesis inhibitors, for use in the treatment of pathogenic conditions including cancer, arthritis, and diabetic blindness.
    Type: Grant
    Filed: March 23, 1992
    Date of Patent: December 12, 1995
    Assignee: UT SW Medical CTR at Dallas
    Inventor: Philip E. Thorpe
  • Patent number: 5472883
    Abstract: A solid phase reagent is provided which comprises a carrier having a surface onto which functional groups containing a negative charge or a lone pair of electrons and/or free radicals containing a negative charge or a lone pair of electrons have been introduced and having .beta.2-glycoprotein I coated on the surface. Using this reagent, antibodies specific to antiphospholipid syndrome can be specifically assayed. Moreover, antibodies specific to antiphospholipid syndrome can be assayed differentially from antibodies specific to infectious diseases by using the solid phase reagent described above or a further modified solid phase reagent.
    Type: Grant
    Filed: October 5, 1993
    Date of Patent: December 5, 1995
    Assignees: Yamasa Corporation, Takao Koike
    Inventors: Eiji Matsuura, Yoshiko Igarashi, Hisato Nagae, Takao Koike
  • Patent number: 5466609
    Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.
    Type: Grant
    Filed: October 29, 1992
    Date of Patent: November 14, 1995
    Assignee: Coulter Corporation
    Inventors: Olavi Siiman, Alexander Burshteyn, Ravinder K. Gupta
  • Patent number: 5466610
    Abstract: Methods have been developed to produce novel compounds by covalently coupling thiazolidinedione insulin sensitivity enhancers (ISEs) to proteins. These novel compounds are well suited for producing antibodies, which are specific for thiazolidinedione ISEs and which are well suited for fluorescent immunoassays of thiazolidinedione and non-thiazolidinedione ISEs in buffers and biological tissues. Antibodies also are well suited for high-volume screening for immunologically related novel, non-thiazolidinedione and thiazolidinedione ISEs.
    Type: Grant
    Filed: September 7, 1993
    Date of Patent: November 14, 1995
    Assignee: Eli Lilly and Company
    Inventors: Stuart W. Bright, Gerald Gold, Scott W. Sage, John R. Sportsman
  • Patent number: 5462867
    Abstract: A hydrophobic polymer such as polysulfone or polyethersulfone is modified to contain an increased number of functionalizable chain ends such as by treating with an alkali hydroxide to provide hydroxyl groups. A linker is covalently bonded to a chain end of the polymer and a macromolecule is covalently bonded to the linker. A ligand may be covalently bonded to the macromolecule. The macromolecule can be a natural polymer, a synthetic polymer or a biologically active species. The hydrophobic polymer is preferably in the form of a microporous membrane. By the use of a four-component dope composition, substantially isotropic microporous structures in the form of flat sheets or hollow fibers are produced. An improved spinnerette assembly is provided for the production of hollow fibers.
    Type: Grant
    Filed: February 2, 1994
    Date of Patent: October 31, 1995
    Assignee: Hemasure, Inc.
    Inventors: A. R. M. Azad, Randal A. Goffe
  • Patent number: 5459079
    Abstract: A support for biological molecules comprising a porous inorganic matrix and particles of a water-insoluble polymer, and a biologically active support comprising a porous inorganic matrix and particles of a water-insoluble polymer "sensitized" by biological molecules. The supports are prepared by bringing the matrix into contact with an aqueous dispersion of optionally "sensitized" polymer particles, and the use of such supports in biological application.
    Type: Grant
    Filed: March 7, 1994
    Date of Patent: October 17, 1995
    Assignee: Rhone-Poulenc Chimie
    Inventor: Bernard Vinot
  • Patent number: 5451508
    Abstract: For the determination of vitamin B12 a sample solution is incubated with at least two receptors R.sub.1 and R.sub.2 of which R.sub.1 mediates the binding to the solid phase and R.sub.2 is labelled, whereby a receptor is used as one of the receptors R.sub.1 or R.sub.2 which contains a monoclonal antibody capable of specific binding to B12 that has an affinity constant of at least 5.times.10.sup.9 l/mol and a receptor is used as the other receptor R.sub.1 or R.sub.2 which contains B12 or an analogue thereof, the two phases are separated and the label is measured in one of the two phases.
    Type: Grant
    Filed: October 15, 1993
    Date of Patent: September 19, 1995
    Assignee: Boehringer Mannheim GmbH
    Inventors: Nicholas R. Hoyle, Gunter Pappert, Michael Grol, Christa Hubner-Parajsz
  • Patent number: 5439829
    Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.
    Type: Grant
    Filed: January 24, 1992
    Date of Patent: August 8, 1995
    Assignees: Eli Lilly and Company, Hybritech Incorporated
    Inventors: Leslie D. Anderson, James A. Cook, Gary S. David, Susan M. Hochschwender, Mary S. Kasher, Michele C. Smith, Willem P. C. Stemmer
  • Patent number: 5437983
    Abstract: A method for carrying out a binding assay is described wherein a member of a specific binding pair (sbp) and a sample are combined with a matrix of non-porous beads in a liquid medium under conditions such that the beads bind to the sbp member. The liquid medium is removed from the beads by aspiration using an aspiration tube having one or more orifices each of a diameter smaller than the minimum diameter of the smallest bead thereby allowing removal of the liquid medium while prohibiting aspiration of the beads.
    Type: Grant
    Filed: February 1, 1993
    Date of Patent: August 1, 1995
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Richard P. Watts, Mary C. Ericson, Hrair Kirakossian, Chiu C. Chang
  • Patent number: 5436170
    Abstract: The present invention provides a membrane comprising a closely packed array of self-assembly amphiphilic molecules, and is characterized in that it incorporates plurality of ion channels, and/or at least a proportion of the self-assembling molecules comprise a receptor molecule conjugated with a supporting entity. The ion channel is selected from the group consisting of peptides capable of forming helices and aggregates thereof, coronands, cryptands, podands and combinations thereof. In the amphiphilic molecules comprising a receptor molecule conjugated with a supporting entity, the receptor molecule has a receptor site and is selected from the group consisting of immunoglobulins, antibodies, antibody fragments, dyes, enzymes and lectins. The supporting entity is selected from the group consisting of a lipid head group, a hydrocarbon chain(s), a cross-linkable molecule and a membrane protein. The supporting entity is attached to the receptor molecule at an end remote from the receptor site.
    Type: Grant
    Filed: January 25, 1990
    Date of Patent: July 25, 1995
    Assignee: Commonwealth Scientific and Industrial Research Organization
    Inventors: Bruce A. Cornell, Vijoleta L. B. Braach-Maksvytis
  • Patent number: 5436147
    Abstract: Heterobifunctional crosslinking agents are synthesized that covalently link molecules such as enzymes, cells, proteins and nucleic acids to a plastic substrate. The agents contain a central ring structure having a hydrophobic hydrocarbon chain that binds to a plastic substrate and distal to the hydrophobic chain one or more hydrophilic chains terminating in a reactive group that covalently binds the molecule. Immobilized molecules are useful in diagnostic assays or bioreactors.
    Type: Grant
    Filed: June 16, 1993
    Date of Patent: July 25, 1995
    Assignee: Nucleic Assays Corporation
    Inventors: Randall K. Pegg, Mary S. Saunders
  • Patent number: 5427915
    Abstract: Apparatus and methods are provided for the detection of analytes. A polyunsaturated polymerized lipid layer is employed, which is anisotropic, has a member of a specific binding pair bound to an end of the lipids, and whose optical characteristics are modified upon complex formation between the specific binding pair member and its complementary member. By providing for polarized light, linear and/or circular, one can detect the presence of complex formation by the change in the optical characteristics of the film. Polarizers, analyzers, and wave plates are employed for providing for a light signal which can be analyzed and related to the presence of an analyte in a sample.
    Type: Grant
    Filed: August 9, 1993
    Date of Patent: June 27, 1995
    Assignee: Biocircuits Corporation
    Inventors: Hans O. Ribi, Todd A. Guion, Joseph R. Murdoch, John C. Scott, Victor Pan, Glenda L. Choate
  • Patent number: 5427739
    Abstract: Apparatus for performing immunoassays which is essentially self-contained, requiring only the introduction of a sample and, at appropriate times, washing solution. The apparatus (10) includes: a fluid container (12) having a central platform area with a reaction area (30) which can contain a reactive agent; a sample receiving chamber (22) having a sample conduit (24) located above the porous medium; at least one openable reagent container (46); a conduit (28) for directing reagents onto the porous medium; an opening member (50) attached to the upper unit and positioned to contact and open reagent containers sequentially, by incremental relative rotation of the upper and base units; and a window (34) for viewing the reaction area. The apparatus can also include a sampler member (58) in the nature of a tampon for assays involving samples taken from body cavities.
    Type: Grant
    Filed: July 15, 1994
    Date of Patent: June 27, 1995
    Assignee: Schering-Plough Healthcare Products, Inc.
    Inventors: Peter M. Meserol, Rita C. Prodell
  • Patent number: 5422239
    Abstract: Hybridomally produced monoclonal IgM antibodies having high affinity are useful for the immunoassay and purification of vital antigens.
    Type: Grant
    Filed: May 15, 1987
    Date of Patent: June 6, 1995
    Assignee: General Hospital Corporation
    Inventors: Jack R. Wands, Vincent R. Zurawski, Jr.
  • Patent number: 5413912
    Abstract: There is disclosed an antigenic peptide that comprises at least 15 amino acids having the sequence Ala Glu Pro Lys X Ala Glu Pro Lys X Ala Glu Pro Lys X, wherein X is Pro or Ser. This peptide is useful in an ELISA assay to detect antibodies specific to T. cruzi infection and Chagas disease. This peptide is further useful in a vaccine composition for immunizing an individual to prevent Chagas disease upon exposure to T. cruzi.
    Type: Grant
    Filed: December 17, 1993
    Date of Patent: May 9, 1995
    Inventor: Steven G. Reed
  • Patent number: 5412087
    Abstract: Substrates with surfaces comprising compounds with thiol functional groups protected with a photoremovable protecting group can be used to construct arrays of immobilized anti-ligands, such as oligonucleotide probes or other biological polymers. The arrays can be used in assays to detect the presence of complementary nucleic acids in a sample. Spatially addressed irradiation of predefined regions on the surface permits immobilization of oligonucleotides and other biological polymers at the activated regions on the surface. Cycles of irradiation on different regions of the surface and immobilization of different anti-ligands allow formation of an immobilized matrix of anti-ligands at defined sites on the surface. The immobilized matrix of anti-ligands permits simultaneous screenings of a liquid sample for ligands having high affinities for certain anti-ligands of the matrix.
    Type: Grant
    Filed: April 24, 1992
    Date of Patent: May 2, 1995
    Assignee: Affymax Technologies N.V.
    Inventors: Glenn H. McGall, Stephen P. A. Fodor, Edward L. Sheldon
  • Patent number: 5405766
    Abstract: Enzymes and certain other bioactive substances are immobilized on solid substrates which have sufficient functional groups such as hydroxyl or carboxyl. The bioactive substances are linked to the substrates through spacer compounds having a long open alkyl chain with 7-18 carbon atoms and also through phospholipid intermediates. The spacer compound is chemically linked to the substrate. The phospholipid is covalently linked to the spacer compound. Immobilized bioactive substances of the invention exhibit a marked increase in activity and stability. In a preferred embodiment, immobilized enzymes having a high degree of resistance to thermal inactivation are prepared.
    Type: Grant
    Filed: March 25, 1993
    Date of Patent: April 11, 1995
    Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National Defence
    Inventors: Krishna M. R. Kallury, Michael Thompson, William E. Lee
  • Patent number: 5401636
    Abstract: An agglutination-based method for detecting and/or an analyte by allowing the agglutination reaction between the analyte, a carrier reagent, and an agglutinating agent to occur in the presence of a multivalent ligand.
    Type: Grant
    Filed: November 23, 1993
    Date of Patent: March 28, 1995
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Alan R. Craig
  • Patent number: 5401469
    Abstract: A reagent for biomaterials assay of (fluorescent dye).sub.n --avidin--a compound having a plurality of reactive groups--a biomaterial, or a reagent in which avidin is bound to a compound having a plurality of reactive groups through biotin in the above, a plastic fiber optics necessary for utilizing this, an assaying device having a sensing portion utilizing this fiber optics and an assaying method of biomaterials by use of this reagent and device. The assay method can be used for an immunoassay of biomaterials such as antigens, antibodies, and enzymes contained in extremely minute amounts in blood or body fluid for medical diagnosis, and improves the detectable sensitivity to a great extent.
    Type: Grant
    Filed: May 6, 1994
    Date of Patent: March 28, 1995
    Assignee: Ibiden Co., Ltd.
    Inventors: Takeshi Kobayashi, Hiroyuki Honda, Ken-ichi Shimada
  • Patent number: 5401628
    Abstract: A polypeptide linked to a solid matrix useful as a solid support of a diagnostic kit is disclosed. The polypeptide has the formula: X-Glu-Thr-Gly-Gln-Glu-Thr-Ala-Tyr-Phe-B-Leu-Lys-Leu-Ala-Gly-Arg-Trp-Pro-Va l-Lys-Z, wherein B is Ile or Leu, X is a chain of from 1 to 20 amino acid residues or an amino-terminal group and Z is a chain of from 1 to 20 amino acid residues or a carboxy-terminal group. The polypeptide immunologically mimics HIV endonuclease.
    Type: Grant
    Filed: July 19, 1993
    Date of Patent: March 28, 1995
    Assignee: Ortho Diagnostic Systems Inc.
    Inventor: Francesca Chiodi
  • Patent number: 5399501
    Abstract: A specific binding member such as an antigen or antibody is immobilized by covalent attachment to a solid phase such as a latex microparticle. The solid phase is reacted with a heterobifunctional or homobifunctional coupling agent to form a complex that is then reacted with a dithiol compound to form a thiolated solid phase. A specific binding member is reacted with the coupling agent to form a complex which is then reacted with the thiolated solid phase to link the specific binding member to the solid phase through thioethers. Alternatively, the dithiol compound may be reacted with the specific binding member/coupling agent complex to form a thiolated complex that is reacted with the solid phase/coupling agent complex. The coupling agent may contain a spacer. In another embodiment, the solid phase is reacted with a disulfide compound to form a complex and the complex is reacted with a reductant to form a thiolated solid phase which is reacted with a specific binding member/coupling agent complex.
    Type: Grant
    Filed: March 16, 1992
    Date of Patent: March 21, 1995
    Assignee: Abbott Laboratories
    Inventors: Mark R. Pope, Kevin M. Knigge
  • Patent number: 5397695
    Abstract: Useful materials for diagnostic tests, affinity chromatography, enzymatic reactions and immunoassays are prepared by covalently attaching reactive compounds containing reactive amino or sulfhydryl groups to polymeric particles having pendant carboxyl groups on the outer surfaces. Such reactive compounds include biologically reactive species, such as enzymes, polypeptides and proteins. This attachment is carried out using carbamoylonium compounds which react with the carboxyl groups to form intermediate reactive groups which then react with the amino or sulfhydryl groups to form a covalent linkage between particle and reactive compound. A kit comprises polymeric particles having carboxyl groups on the outer surfaces, and a carbamoylonium compound.
    Type: Grant
    Filed: June 29, 1989
    Date of Patent: March 14, 1995
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Susan J. Danielson, Pranab Bagchi, Patricia M. Scensny
  • Patent number: 5393527
    Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.
    Type: Grant
    Filed: January 4, 1993
    Date of Patent: February 28, 1995
    Assignee: Becton, Dickinson and Company
    Inventors: Adrien Malick, Hans H. Feindt
  • Patent number: 5389533
    Abstract: Biochemical substances such as enzymes are immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5389534
    Abstract: A biosensor is prepared having a selective detection system containing a biochemical substance such as an enzyme immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5389523
    Abstract: A method of immunoanalysis combines immobilized immunochemistry with the technique of flow injection analysis, and employs microscopic spherical structures called liposomes, or lipid vesicles, as carriers of detectable reagents. Liposomes are modified on their surface with analytical reagents, and carry in their internal volume a very large number of fluorescent or electroactive molecules. Aspects of this embodiment of the invention include the chemistry for covalent immobilization of antibody fragments in a specified orientation, the use of liposomes in a flow injection analysis system, and the combination of automated sampling and analysis with reusable immunoreactants. Another aspect of the invention involves the non-covalent binding of liposomes to a receptor for use in a homogeneous assay. In another aspect of the invention the intensity of scattered light is quantitated as a measure of liposome aggregation in response to a concentration-dependent immunospecific reaction.
    Type: Grant
    Filed: July 23, 1992
    Date of Patent: February 14, 1995
    Assignee: The United States of Americas, as represented by the Secretary of Commerce
    Inventors: Anne L. Plant, Laurie Locascio-Brown, Richard A. Durst
  • Patent number: 5384254
    Abstract: Poly(fluoroalkyl) sugar reagents are prepared containing a sugar such as a monosaccharide or a disaccharide to which are bonded a plurality of fluoroalkyl anchor groups capable of attaching to a fluorocarbon surface, and either a reactive group capable of covalent coupling to a biomolecule such as an enzyme or a charged group to form an ion-exchanger or a non-ionic group to give a neutral fluorosurfactant. A spacer may be between the reactive group and the sugar. The poly(fluoroalkyl) sugar reagents are strongly adsorbed onto fluorocarbon surfaces to provide supports for such applications as separation and immobilization of biomolecules such as enzymes, carrying out heterogeneous diagnostic assays, and preparation of biosensors.
    Type: Grant
    Filed: May 20, 1993
    Date of Patent: January 24, 1995
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Rene Arentzen, Prabhakar K. Jadhav, Robert K. Kobos, Bruce E. Smart
  • Patent number: 5384261
    Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.
    Type: Grant
    Filed: November 22, 1991
    Date of Patent: January 24, 1995
    Assignee: Affymax Technologies N.V.
    Inventors: James L. Winkler, Stephen P. A. Fodor, Christopher J. Buchko, Debra A. Ross, Lois Aldwin
  • Patent number: 5380658
    Abstract: A phosphazene polymer carrier is prepared that has functional groups capable of binding a biologically active substance such as an enzyme or antibody and groups which are non-reactive and hydrophilic. A bifunctional aldehyde is reacted with primary amino groups of a shaped phosphazene polymer to form side chains having aldehyde groups, an amino group-containing compound is reacted with a portion of the aldehyde groups to produce the groups that are non-reactive and hydrophilic, and aldehyde groups not reacted are capable of binding a biologically active substance. The phosphazene polymer may be crosslinked prior to reacting with the bifunctional aldehyde.
    Type: Grant
    Filed: September 16, 1993
    Date of Patent: January 10, 1995
    Assignee: Teijin Limited
    Inventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
  • Patent number: 5380825
    Abstract: This invention relates to a method for the immunoassay of AZT (3'-azido-3'-deoxythymidine), also known as zidovudine, in biological fluids such as serum, semen, plasma and urine, as well as other body fluids. The invention also includes (1) various novel analogs of AZT useful in preparing immunogens for antibodies to AZT and in preparing labeled AZT, (2) immunogens for antibodies to AZT, (3) monoclonal and polyclonal antibodies to AZT, (4) labeled AZT analogs and (5) diagnostic test kits for the immunoassay.
    Type: Grant
    Filed: June 17, 1991
    Date of Patent: January 10, 1995
    Assignee: Sigma Chemical Company
    Inventors: Kenneth J. Stenglein, Dennis M. Murray
  • Patent number: 5374516
    Abstract: Reagents have been prepared from water-insoluble polymeric particles to which are covalently attached avidin, biotin or an avidin or biotin derivative. The polymeric particles comprise a polymer on at least the outer surface which is derived from at least one ethylenically unsaturated monomer having a reactive activated 2-substituted ethylsulfonyl, vinylsulfonyl or active halogen atom. Covalent attachment of avidin, biotin or an avidin or biotin derivative is effected either directly or indirectly through these reactive groups. The resulting reagent is useful in analytical elements and various analytical methods including agglutination and sandwich assays. The immobilized avidin, biotin or derivative can be used to complex with the corresponding biotin or avidin molecule which may be conjugated to a compound of biological interest.
    Type: Grant
    Filed: February 24, 1989
    Date of Patent: December 20, 1994
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Brent A. Burdick, Susan J. Danielson, Harold C. Warren, III, Brian A. Snyder, Gregory J. McClune, Annie L. Wu
  • Patent number: 5372930
    Abstract: A sensor for ultra-low concentration chemical recognition comprises a force transducer, a tip coupled to this force transducer, and a substrate positioned for force interaction with the force transducer tip, where the substrate and tip are chemically modified with antigens, antibodies, nucleic acids, or chelating agents so that there is a specific force interaction between the tip and the substrate in the presence of the target species, and a measurably different force interaction in the absence of the target species.
    Type: Grant
    Filed: September 16, 1992
    Date of Patent: December 13, 1994
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventors: Richard J. Colton, David A. Kidwell
  • Patent number: 5369012
    Abstract: A portion of an organic polymer article such as a membrane is made hydrophilic by exposing a hydrophobic surface of the article to a depth of about 50 to about 5000 angstroms to atomic oxygen or hydroxyl radicals at a temperature below 100.degree. C., preferably below 40.degree. C., to form a hydrophilic uniform surface layer of hydrophilic hydroxyl groups. The atomic oxygen and hydroxyl radicals are generated by a flowing afterglow microwave discharge, and the surface is outside of a plasma produced by the discharge. A membrane having both hydrophilic and hydrophobic surfaces can be used in an immunoassay by adhering antibodies to the hydrophobic surface. In another embodiment, the membrane is used in cell culturing where cells adhere to the hydrophilic surface. Prior to adhering cells, the hydrophilic surface may be grafted with a compatibilizing compound.
    Type: Grant
    Filed: March 26, 1992
    Date of Patent: November 29, 1994
    Assignee: The United States of America as represented by the Administrator of the National Aeronautics and Space Administration
    Inventors: Steven L. Koontz, Glenn F. Spaulding
  • Patent number: 5366864
    Abstract: A buffered aqueous composition is useful simultaneously as a wash solution and a dye-providing composition in specific binding assays involving enzyme-labeled specific binding reagents. The wash composition includes a dye-providing composition, a buffer and an organic solvent having a certain molecular weight and water-solubility. Another useful composition includes a particulate substrate having avidin attached thereto, and a peroxidase reducing agent. Either composition can be provided in a diagnostic test kit, and can be used to detect a specific binding ligand in assays.
    Type: Grant
    Filed: September 30, 1992
    Date of Patent: November 22, 1994
    Assignee: Eastman Kodak Company
    Inventors: Gregory J. McClune, Karen L. Findling
  • Patent number: 5364591
    Abstract: There are described a device and method for doing confined reactions such as PCR amplification and detection, wherein solids (e.g., beads) used to obtain separation between bound and "free" label reagents, are transferred from region to region, specifically through a wash liquid so as to wash off the "free" label reagent from the solids. Separate chambers have dividers that are overcome by piercing or by liquification, to create passageways for the transfer of the solids. The passageways remain contained within the device.
    Type: Grant
    Filed: June 1, 1992
    Date of Patent: November 15, 1994
    Assignee: Eastman Kodak Company
    Inventors: Nancy F. Green, Thomas J. Cummins, Fred T. Oakes