Antigen Or Antibody Entrapped Within The Carrier (e.g., Gel, Hollow Fiber, Etc.) Patents (Class 436/535)
  • Patent number: 5792669
    Abstract: The invention provides a fragment of C1q which is characterized in that a plurality of such fragments selectively binds immune complexes or aggregated immunoglobulins in the presence of monomeric immunoglobulin. The invention also provides a synthetic peptide comprising the sequence: ##STR1## or variants thereof capable of binding immunoglobulin. Like the C1q fragment, a plurality of the peptides can selectively bind immune complexes or aggregated immunoglobulins in the presence of monomeric immunoglobulin. As a result of this property, the fragments and peptides are well-adapted for removing immune complexes and aggregated immunoglobulins from fluids containing monomeric immunoglobulin, and for detecting or quantitating immune complexes in such fluids. The invention also provides a binding material for removing immune complexes or aggregated immunoglobulins from a fluid.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: August 11, 1998
    Assignee: Northwestern University
    Inventors: Michael A. Baumann, Byron E. Anderson
  • Patent number: 5783401
    Abstract: A device for detecting the presence of substances, particularly biological materials, contained in a liquid sample is formed of a series of layers of film materials. A first film has a cut-out which forms an upper reservoir for receiving the liquid sample. A first reagent is provided in the upper reservoir capable of reacting with a substance possibly contained in the liquid sample. A first membrane is situated at the base of the upper reservoir and is made of a material which is temporarily impermeable so that the liquid sample is temporarily retained in the upper reservoir in contact with the first reagent, but after awhile the membrane becomes permeable and allows the liquid to pass. A second film has a cut-out which forms a median reservoir positioned for receiving the liquid passing through the first membrane. A second reagent is provided in the median reservoir capable of reacting with a predetermined substance.
    Type: Grant
    Filed: July 1, 1994
    Date of Patent: July 21, 1998
    Assignee: Quidel Corporation
    Inventor: Jacques Toledano
  • Patent number: 5770462
    Abstract: An analytical apparatus comprises a biosensor device (3) which forms the base of a sample chamber. A stirrer (8) extends into the sample chamber and moves within the chamber so as to homogenize a sample contained within the chamber in contact with the biosensor (3). Movement of the stirrer (8) is preferably reciprocal movement along an axis perpendicular to the surface of the biosensor (3).
    Type: Grant
    Filed: February 20, 1996
    Date of Patent: June 23, 1998
    Assignee: Fisons plc
    Inventor: James Oscar Molloy
  • Patent number: 5770460
    Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: June 23, 1998
    Assignee: Quidel Corporation
    Inventors: Catherine Pawlak, Allan D. Pronovost, Keren Goins
  • Patent number: 5766552
    Abstract: Red blood cells are removed from whole blood or a fraction thereof by agglutinating whole blood with a mixture of a free agglutinating agent and nucleating particles having agglutinating agent intimately associated therewith to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma, which is substantially free of red blood cells, is further passed through a filter that optionally contains an additional agglutinating agent. Flow-delay additives may be provided to retain the fluid sample in contact with a reagent for a predetermined time.
    Type: Grant
    Filed: February 5, 1996
    Date of Patent: June 16, 1998
    Assignee: ActiMed Laboratories, Inc.
    Inventors: Sonal R. Doshi, John K. McGeehan, Wai Tak Law
  • Patent number: 5766961
    Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.
    Type: Grant
    Filed: November 23, 1993
    Date of Patent: June 16, 1998
    Assignee: Quidel Corporation
    Inventors: Catherine Pawlak, Allan D. Pronovost, Keren Goins
  • Patent number: 5750411
    Abstract: Disclosed is a method for determining the concentration of an analyte in a liquid test sample. The method involves the use of colloidal sized metal particles, which exhibit a spectral response in the agglomerated state which is detectably different than in their unagglomerated state, which bear specific binding partners for the analyte in question on their surface. The specific binding partner treated colloidal particles are combined in a buffered, aqueous medium with a destabilizer material capable of destabilizing the specific binding partner-colloidal particle conjugates thereby permitting the particles to agglomerate. Also included in the liquid medium is a polymer bearing multiple analyte or analyte analog molecules along its surface which serves to protect the specific binding partner coated metal particles from dissociation by the destabilizing agent.
    Type: Grant
    Filed: June 3, 1996
    Date of Patent: May 12, 1998
    Assignee: Bayer Corporation
    Inventor: Ronald G. Sommer
  • Patent number: 5723345
    Abstract: The present invention provides a general purpose specific binding assay method which has the advantages of highly accurate and quick measurements which exclude the effects of various factors that decrease reliability of the measured values, such as non-specific reactants in test samples, assay conditions and inactivation and the like changes in the activity of reagents. The present invention is further drawn to a specific binding assay device suitable for the practice thereof.
    Type: Grant
    Filed: June 27, 1995
    Date of Patent: March 3, 1998
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Tadakazu Yamauchi, Hideyuki Terasawa
  • Patent number: 5711915
    Abstract: The present invention relates to an optical solid-phase biosensor for the detection of molecules which can be labelled with a fluorescent dye for the identification of substances in solution, for which there exists a biomolecule (receptor) which specifically recognises these and is chemically bonded to the uppermost layer of one or more layers of polyions on the surface of the sensor, by measurement of the Forster transfer between another dye molecule which is bonded in one of the uppermost layers of the sensor, and the said dye molecule.
    Type: Grant
    Filed: October 24, 1995
    Date of Patent: January 27, 1998
    Assignee: Bayer Aktiengesellschaft
    Inventors: Hans-Ulrich Siegmund, Ludger Heiliger, Boudewijn van Lent, Arno Becker
  • Patent number: 5683916
    Abstract: A method and apparatus for carrying out affinity purification of a ligate. The method comprising, (a) providing a ligate containing liquid to a first side of at least one porous hollow fiber membrane with a ligand immobilized thereto that binds and separates the ligate from the liquid, (b) withdrawing a first portion of the liquid from the first side of the porous hollow fiber membrane, (c) recirculating the first portion of liquid to the first side of the porous hollow fiber membrane, (d) repeating steps (a) to (c) until a majority of the liquid has flowed through the porous hollow fiber membrane, and (e) providing an elution solution to one side of the porous hollow fiber membrane under a pressure sufficient to cause the elution solution to flow into and through the membrane to effect disassociation of any ligate-ligand bonds wherein any ligate bound to the ligand is eluted with the elution solution.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: November 4, 1997
    Assignee: Hemasure Inc.
    Inventors: Randal A. Goffe, Stephen E. Zale, James L. O'Connor, Stephen B. Kessler
  • Patent number: 5660798
    Abstract: Red blood cells are removed from whole blood or a fraction thereof by contacting whole blood with a combination of an agglutinating agent and nucleating particles to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma which is substantially free of red blood cells is further passed through a filter that optionally contains an additional agglutinating agent. Flow-delay means may be provided to return the fluid sample in contact with a regard for a predetermined time.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: August 26, 1997
    Assignee: ActiMed Laboratories, Inc.
    Inventors: Sonal R. Doshi, John K. McGeehan, Wai Tak Law
  • Patent number: 5652149
    Abstract: An assay device for detecting the presence of analytes in an unknown sample includes a reaction system wherein resilient storage reservoirs containing reagents are fluidly connected to a track containing the sample. An actuation mechanism forces the reagent from each of the reservoirs into the track where the reagents mix together and with the sample. The mechanism produces a first flow rate and the mechanism is operable to reverse the pressure applied to the reservoirs to reverse the direction of flow of the fluids in the track for a predetermined period of time after which the flow is again reversed. The mechanism then reduces the force applied to allow a second flow rate less than the first flow rate so that reaction can occur whereby a determination may be made as to whether the target analyte is present in the sample.
    Type: Grant
    Filed: March 6, 1995
    Date of Patent: July 29, 1997
    Assignee: Westinghouse Electric Corporation
    Inventors: Daryl S. Mileaf, Noe E. Rodgriguez, II
  • Patent number: 5643764
    Abstract: A reagent such as a heat resistant enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated so the reagent is available for reaction. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.
    Type: Grant
    Filed: March 1, 1995
    Date of Patent: July 1, 1997
    Inventors: Kenneth M. Kosak, Matthew K. Kosak
  • Patent number: 5641865
    Abstract: An interaction system, including an antibody or, antibody fragment having functional capability, which comprises a surfactant-stabilized microheterogeneous dispersion of aqueous phase in a water-immiscible medium, said aqueous phase containing an amount of said antibody or said fragment in a functional state sufficient to effect the interaction; and methods for making and for using said system.
    Type: Grant
    Filed: January 28, 1994
    Date of Patent: June 24, 1997
    Assignee: IGEN, Inc.
    Inventors: Charles N. Durfor, Richard J. Bolin, Allen R. Schantz, II, Richard J. Massey
  • Patent number: 5641688
    Abstract: A method of separating bound labeled indicator from free labeled indicator in a layer of a test element for immunoassay. The method comprisesa) depositing sample containing a target immunoanalyte capable of binding to the labeled indicator or to an immobilized antibody in competition with the labeled indicator, onto an exterior surface of a test element in the presence of the labeled indicator andb) adding an amount of wash liquid to the exterior surface to form a pool of the liquid having a meniscus on the surface, the liquid penetrating the surface over an area bounded by a closed intersect edge formed between the pool meniscus and the surface, so that penetrating liquid can push free labeled indicator away from bound labeled indicator in a volume of the layer below the bounded area.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: June 24, 1997
    Assignee: Johnson & Johnson Clinical Diagnostics, Inc.
    Inventor: Merrit Nyles Jacobs
  • Patent number: 5641634
    Abstract: Disclosed are materials and methods for detecting biomolecules in samples employing transponders having memory elements associated with particle(s) used as a solid phase in art assay, and information pertinent to the assay is encoded on the transponder memory elements. A dedicated read/write device is used remotely to encode or remotely to read the information encoded on the transponder memory elements. The invention can be used in direct or competitive ELISA-type assays, or in multiplex assays for the simultaneous assay of several analytes.
    Type: Grant
    Filed: November 30, 1995
    Date of Patent: June 24, 1997
    Inventor: Wlodek Mandecki
  • Patent number: 5605662
    Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridization, antibody/antigen reaction, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micromachining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific microlocations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
    Type: Grant
    Filed: November 1, 1993
    Date of Patent: February 25, 1997
    Assignee: Nanogen, Inc.
    Inventors: Michael J. Heller, Eugene Tu
  • Patent number: 5587128
    Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide amplification reaction. The devices are provided with a substrate microfabricated to include a polynucleotide amplification reaction chamber, having at least one cross-sectional dimension of about 0.1 to 1000 .mu.m. The device also includes at least one port in fluid communication with the reaction chamber, for introducing a sample to the chamber, for venting the chamber when necessary, and, optionally, for removing products or waste material from the device. The reaction chamber may be provided with reagents required for amplification of a preselected polynucleotide. The device also may include means for thermally regulating the contents of the reaction chamber, to amplify a preselected polynucleotide. Preferably, the reaction chamber is fabricated with a high surface to volume ratio, to facilitate thermal regulation.
    Type: Grant
    Filed: November 14, 1994
    Date of Patent: December 24, 1996
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Peter Wilding, Larry J. Kricka
  • Patent number: 5565366
    Abstract: Methods for determining the presence of a ligand in a sample suspected to contain the ligand are provided, along with apparatus suitable for performing the methods. The methods depend upon a color visualization indicating the ligand's presence or absence in the sample. Preferred methods comprise contacting the sample with colored particles which bear on their surface a receptor specific for the ligand, passing the sample/particle mixture through a filter, and then analyzing the color of the filtrate. The presence of ligand in the sample is established where the color of the filtrate is substantially different from the color of the receptor-bearing particles.
    Type: Grant
    Filed: May 25, 1994
    Date of Patent: October 15, 1996
    Assignee: 501 Akers Research Corp.
    Inventor: Raymond F. Akers, Jr.
  • Patent number: 5563056
    Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.
    Type: Grant
    Filed: February 27, 1995
    Date of Patent: October 8, 1996
    Assignee: BSI Corporation
    Inventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
  • Patent number: 5550044
    Abstract: Droplets of molten wax or waxy polymer containing a reagent are dropped onto the surface of liquid nitrogen, the droplets remain on the surface until solidified and the droplets are removed from the surface before they sink into the liquid nitrogen to provide beads containing the reagent. The reagent can be any material that can be entrapped in the beads and does not undergo excessive inactivation when the beads are melted by heating to release the reagent. Examples of reagents are heat resistant enzymes, enzyme substrates, metal salts, oligonucleotides, inclusion compounds, surfactants, emulsifiers, antioxidants, stabilizers, drugs, antibiotics, antibodies and antigens. An apparatus for producing the beads contains a plurality of channels through which liquid nitrogen flows from a reservoir. Each channel passes under a dispenser tip from which droplets are formed and released onto the surface of flowing liquid nitrogen.
    Type: Grant
    Filed: June 10, 1994
    Date of Patent: August 27, 1996
    Inventors: Kenneth M. Kosak, Matthew K. Kosak
  • Patent number: 5521101
    Abstract: A method of determining an analyte in the gaseous or vapour phase and in which a bioreceptor or biomimic is retained at an electrode. The bioreceptor or biomimic is preferably retained at a support at the electrode which comprises a solid or gel matrix of an electrolyte, especially organic salt electrolytes. Electrochemical detection of analytes in this way has several advantages over existing methods which rely on solution monitoring. For example gas sensors can be prepared for monitoring an analyte by the occurrence of a reaction with a bioreceptor or biomimic, in addition to monitoring the presence of toxins due to inhibition of the bioreceptor or biomimic reaction. Furthermore, the invention enables gas or vapour analyte monitoring with increased sensitivity and speed and greater stability of the sensors can be achieved. The invention also relates to novel media for carrying out bioelectrochemical reactions.
    Type: Grant
    Filed: August 26, 1993
    Date of Patent: May 28, 1996
    Assignee: Cranfield University
    Inventors: Selwayan Saini, Anthony P. F. Turner
  • Patent number: 5514598
    Abstract: Meconium State Pregnancy is diagnosed by analysis of prenatal maternal fluids for the presence of specific meconium antigens, including a specific meconium protein antigen of approximately 14 KD.
    Type: Grant
    Filed: November 30, 1993
    Date of Patent: May 7, 1996
    Inventor: Michael Doody
  • 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: 5413924
    Abstract: A reagent such as an enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.
    Type: Grant
    Filed: August 27, 1992
    Date of Patent: May 9, 1995
    Inventors: Kenneth M. Kosak, Matthew K. Kosak
  • Patent number: 5405618
    Abstract: A biomosaic polymer is provided. Biologically active materials are bound at surfaces of such polymers polymerized from emulsions containing hydrophobic polymerizable monomers, such biologically active materials, and surface active agents. The biomosaic polymers may be formed into membranes, films, beads, or other structures for a variety of assays, bioseparations, or catalyzed reactions and other uses. A single step polymerization of the emulsion provides significant retention of the biologically active material bound and congregated at surfaces of the polymer.
    Type: Grant
    Filed: November 5, 1992
    Date of Patent: April 11, 1995
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: Howard J. Buttery, Patrick L. Coleman, Dean S. Milbrath
  • Patent number: 5395754
    Abstract: The present invention is directed to a membrane-based immunoassay method for an analyte of interest having at least two sterically separate antigenic sites. The method comprises providing a reactive membrane having a calibration zone and a test zone, wherein the calibration zone is characterized by having a predetermined amount of the analyte of interest immobilized via a first antibody as a first specific binding pair to a solid phase, the immobilized first binding pair being covalently cross-linked such that any remaining binding sites on said first immobilized antibody are substantially incapable of further specifically binding to any additional analyte, but at least some of said analyte is capable of specifically binding to a preselected amount of a labelled second antibody.
    Type: Grant
    Filed: July 31, 1992
    Date of Patent: March 7, 1995
    Assignee: Hybritech Incorporated
    Inventors: Paul P. Lambotte, Robert C. Darter, Mark J. Sarno
  • Patent number: 5391478
    Abstract: This invention relates to an improved assay device and assay for detecting or quantitating the presence or absence of a substance in a sample. The device has multiple layers comprising a permeable layer (a) having a capture reagent attached to less than the entire membrane, a selectively permeable layer (b) which does not allow assay reagents to pass through (b) and an absorbent layer (c). Layer (b) is in communication with layers (a) and (c). Layer (b) has at least one hole extending therethrough and the hole or holes are directly below the capture reagent in layer (a). The area of the hole or the combined area of the holes is less than the area covered by the capture reagent. This invention also relates to a method of reducing background color development in an absorbent layer of an assay device.
    Type: Grant
    Filed: February 21, 1992
    Date of Patent: February 21, 1995
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Richard A. Greene, Patricia A. Kasila
  • Patent number: 5376551
    Abstract: Apparatus for studying the interaction of first and second molecules in a test solution containing fluorescently labeled molecules in addition to the first and second molecules, with the first molecules and the fluorescently labeled molecules being capable of binding with the second molecules. The apparatus comprises a flow channel having opposite, spaced apart walls, with at least one of the walls or a portion thereof being translucent or transparent. A porous matrix is retained in a fixed position between the walls of the flow channel and in direct contact with a translucent or transparent portion of the walls of the flow channel. A test solution flows through the flow channel and around the porous matrix so as to be in contact with the porous matrix.
    Type: Grant
    Filed: June 21, 1993
    Date of Patent: December 27, 1994
    Assignee: University of Utah Research Foundation
    Inventor: Doju Yoshikami
  • Patent number: 5352582
    Abstract: An apparatus detects a target reactant that binds to an immobilized reactant. The apparatus generates a holographic image at a predetermined location when the reactants are present and bound to one another. The immobilized reactant is bound to a support surface at selected locations. The locations are chosen such that a holographic plate is generated when the target reactant binds to the immobilized reactant. An associated method may be used to detect antibody-antigen reactions, the binding of two strands of nucleic acid, the binding of an enzyme to one of its substrates, and so on.
    Type: Grant
    Filed: October 28, 1993
    Date of Patent: October 4, 1994
    Assignee: Hewlett-Packard Company
    Inventors: Kay Lichtenwalter, Hewlett E. Melton, Jr.
  • Patent number: 5320725
    Abstract: An amperometric biosensor and method for the detection of hydrogen peroxide, NADH, or NADPH with high sensitivity includes an electrode having on its testing surface a three-dimensional redox polymer network in which peroxidase is immobilized.
    Type: Grant
    Filed: May 8, 1992
    Date of Patent: June 14, 1994
    Assignee: E. Heller & Company
    Inventors: Brian A. Gregg, Adam Heller
  • Patent number: 5320968
    Abstract: A method for assaying lipoprotein (a) in a liquid sample containing other lipoproteins, and a assay device for use in the method are disclosed. In the method, the liquid is contacted with a solid-support reagent containing lectin attached to a solid support, under conditions effective to bind of lipoprotein (a) to the support-bound lectin. After removing unbound lipoproteins, the amount of lipoprotein (a) bound to the support is assayed. In one embodiment, the method and assay device are designed for assaying cholesterol associated with lipoprotein (a).
    Type: Grant
    Filed: February 23, 1993
    Date of Patent: June 14, 1994
    Inventor: Leo J. Seman
  • Patent number: 5314642
    Abstract: An interaction system, including an antibody or, antibody fragment having functional capability, which comprises a surfactant-stabilized microheterogeneous dispersion of aqueous phase in a water-immiscible medium, said aqueous phase containing an amount of said antibody or said fragment in a functional state sufficient to effect the interaction; and methods for making and for using said system.
    Type: Grant
    Filed: August 31, 1992
    Date of Patent: May 24, 1994
    Assignee: IGEN, Inc.
    Inventors: Charles N. Durfor, Richard J. Bolin, Allen R. Schantz, II, Richard J. Massey
  • Patent number: 5310688
    Abstract: This invention relates to methods and apparatus for carrying out affinity separations of proteins under conditions optimized for recovering biologically active protein. The method utilizes a membrane-bound ligand first to capture and separate a ligate from a fluid mixture and subsequently to release said ligate in purified form. The present methods enhance the yield of active ligate recovered in the process. The invention has particular relevance to the recovery and purification of proteins from mixtures.
    Type: Grant
    Filed: March 23, 1993
    Date of Patent: May 10, 1994
    Assignee: Sepracor Inc.
    Inventors: Stephen E. Zale, Clark K. Colton
  • Patent number: 5283186
    Abstract: A porous carrier containing an immobilized biologically active material is prepared in which a relatively large amount of an enzyme or an antibody has been immobilized in a manner that produces a low diffusion resistance toward reagents and products. The porous carrier is produced by fixing enzymes or antibodies within internal micropores of the carrier and mechanically compressing the carrier to a final thickness which is in the range of about 0.20 to 0.80 times the uncompressed carrier thickness. The compressed carrier may have a density about 1.25 to about 5.0 times the density of the carrier before compressing. Surprisingly, the compressed carrier exhibits less diffusion resistance to specific reagents and products than would an uncompressed carrier. A preferred porous carrier is a semi-permeable membrane made from synthetic polymers, such as polyvinylidine difluoride.
    Type: Grant
    Filed: December 31, 1991
    Date of Patent: February 1, 1994
    Assignee: Abbott Laboratories
    Inventors: David D. Cunningham, Kenneth S. Johnson
  • Patent number: 5283066
    Abstract: Disclosed is a method of stimulating an immune response by using a hapten. Haptens are adhered onto a solid phase support to form a complex. This complex can stimulate an immune response of an animal and the animal's lymphocytes. The solid phase supports usable in the method preferably are membranes, latex particles or microparticle beads of hydrophilic cellulose mixed ester, nitrocellulose, cellulose acetate, nylon, polyvinylidone, vinylbenzyl chloromethyl styrene, polyacrolein, a ahydrophobic, polytetrafluoroethylene, polystyrene and silica gel.
    Type: Grant
    Filed: February 19, 1992
    Date of Patent: February 1, 1994
    Assignee: Development Center for Biotechnology
    Inventors: Jiuan J. Liu, Chun-Chieh Wang, Yuang-Ling Hwang, Tong H. Chang
  • Patent number: 5252494
    Abstract: An improved fiber optic sensor, sensing apparatus, and methods for making optical detections are provided. The fiber optic sensor employs a fiber optic strand to convey light energy, an immobilized polymeric reaction matrix, and at least one controlled release polymeric carrier within said reaction matrix comprising a controlled release polymer material and a releasable reagent formulation able to react with the analyte of interest. The optic sensors and sensor construction have been demonstrated to be both functionally useful and long serving in duration.
    Type: Grant
    Filed: March 30, 1992
    Date of Patent: October 12, 1993
    Assignee: Trustees of Tufts College
    Inventor: David R. Walt
  • Patent number: 5250443
    Abstract: A multilayer diagnostic assay element wherein glyoxyl agarose, an aldehyde group - derivatized agarose, is utilized in one or more layers of the element. In a preferred embodiment the glyoxyl agarose is used to immobilize biological species such as a protein in a layer of the element.
    Type: Grant
    Filed: February 12, 1992
    Date of Patent: October 5, 1993
    Assignee: PB Diagnostic Systems, Inc.
    Inventors: Edward P. Lindholm, Ernest J. Yamartino, Jr.
  • Patent number: 5243040
    Abstract: Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and individual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.
    Type: Grant
    Filed: November 4, 1991
    Date of Patent: September 7, 1993
    Assignee: Creative BioMolecules
    Inventors: James S. Huston, Lynn Baird, Charles Cohen, Hermann Oppermann
  • Patent number: 5225332
    Abstract: A process for manipulation of liquid microdroplets is disclosed. The process involves formation of microdroplets such that physical forces based on particular interactions of the microdroplets with a surrounding non-aqueous fluid results can be used to alter the position of the microdroplets.
    Type: Grant
    Filed: April 22, 1988
    Date of Patent: July 6, 1993
    Assignee: Massachusetts Institute of Technology
    Inventors: James C. Weaver, Julian Joseph
  • Patent number: 5212063
    Abstract: The present invention provides a process for the detection of analytes in body fluids containing free biotin by immunoassay with the use of biotin conjugates for the labelling, immobilization or complexing of immunological reagents, wherein the biotin present in free form is removed from the immunological reaction by incubating the sample solution with polymer particles consisting of a core and a covering which, as core, contain a polymer which has a plurality of binding sites for biotin and, as covering, at least one layer of protein, peptide, carbohydrate or co-polymer of carbohydrate and amino acids, the layer thickness of the covering being so adjusted that the coating is permeable for the free biotin but not for the biotin conjugate.
    Type: Grant
    Filed: May 9, 1990
    Date of Patent: May 18, 1993
    Assignee: Boehringer Mannheim GmbH
    Inventors: Beatus Ofenloch-Hahnle, Michael Berger, Arno Deger
  • Patent number: 5200315
    Abstract: Biologically active reactive are prepared from particles of copolymers having polyoxyalkylene side chains, each of which side chains has a molecular weight of at least about 88. The reagents are prepared by covalently attaching biologically active substances, for example antibodies, to the particles, directly or indirectly through reactive groups on the particle surface. These reagents are used to advantage in analytical elements and methods for the detection of specific binding ligands (such as immunological species) and immunoassays, and in purification methods as affinity chromatography reagents. Adsorption of undesirable proteins on the particles of the reagents was considerably reduced because of the specific composition of the particles.
    Type: Grant
    Filed: July 25, 1990
    Date of Patent: April 6, 1993
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Marsha B. Oenick
  • Patent number: 5190858
    Abstract: The present invention provides a monoclonal antibody which specifically forms a complex with TGF.alpha. in formalin-fixed, paraffin-embedded tissue sections which has an affinity of a least 10.sup.7, and which is directed to the epitope to which monoclonal antibody 213-4.4 (ATCC No. HB9992) is directed. The invention further provides the above-described monoclonal antibody wherein the epitope consists essentially of amino acids 34-43 of TGF.alpha..Additionally, the invention concerns the monoclonal antibody 213-4.4 (ATCC No. HB9992).The invention also provides a method of detecting TGF.alpha. in tissue sections of a tissue in which normal tissue is characterized by the absence of TGF.alpha. and neoplastic tissue is characterized by the presence of TGF.alpha. in a subset of such neoplastic tissue which comprises contacting the tissue sections with an antibody directed to an epitope on TGF.alpha.
    Type: Grant
    Filed: February 1, 1989
    Date of Patent: March 2, 1993
    Assignee: Oncogene Science, Inc.
    Inventors: John M. Sorvillo, David M. Valenzuela, Frederick H. Reynolds, Jr.
  • Patent number: 5182216
    Abstract: In a simultaneous marking specific binding assay for an analyte is a liquid sample, such as urine during pregnancy or fertile period test, wherein the liquid sample is simultaneously incubated with a first specific binding reagent immobilized on a solid phase carrier surface and with a second specific binding reagent dissolved or dispersed in the liquid sample and which bears a label by means of which the result of the assay can be determined, the improvement that prior to the incubation the second specific binding reagent is contained within a layer (2a) of readily soluble or dispersible solid material superimposed on the solid phase carrier surface (2a) on which the first specific binding reagent is immobilized.
    Type: Grant
    Filed: November 22, 1988
    Date of Patent: January 26, 1993
    Assignee: Unilever Patent Holdings B.V.
    Inventors: Richard A. Clayton, Philip Porter
  • Patent number: 5177021
    Abstract: A dipping element for immunoassay or quantitative analysis of an immunoreactive analyte is disclosed having a first matrix having a carrier therein containing an immobilized antibody capable of an immunochemical reaction with a sample antigen. The immobilized antibody is not released into the aqueous liquid sample upon contact. The element further comprises a second matrix which contains labelled antigen which does dissolve in the aqueous liquid sample upon contact. On dipping, the marker-labelled antigen reacts with the immobilized antibody in competition with the antigen-antibody reaction between the analyte antigen and the immobilized antibody. if the analyte is an antibody, then the second matrix contains a marker labelled antibody and the first matrix contains an immobilized antigen. Methods for the quantitative analysis of an analyte antigen or antibody are also disclosed.
    Type: Grant
    Filed: March 16, 1987
    Date of Patent: January 5, 1993
    Assignee: Fuji Photo Film Co., Ltd.
    Inventor: Asaji Kondo
  • Patent number: 5160701
    Abstract: A novel material and device useful in solid-phase binding assays to determine the presence or amount of an analyte in a test sample, particularly antigens, antibodies, or other ligands or DNA segments. The material and device comprises a reaction site having procedural controls and an analyte binding area capable of being simultaneously contacted by the sample and reagent used in the performance of the assay. The procedural controls and analyte binding areas operate to provide readable results as to the presence or absence of analyte and simultaneously verify the assay procedure and therefore the assay result.
    Type: Grant
    Filed: April 15, 1991
    Date of Patent: November 3, 1992
    Assignee: Abbott Laboratories
    Inventors: William E. Brown, III, Sarah E. Safford, John M. Clemens
  • Patent number: 5149622
    Abstract: A novel material and device useful in solid-phase binding assays to determine the presence or amount of an analyte in a test sample, particularly antigens or antibodies, is disclosed. The material comprises a porous matrix of fibers and a plurality of substantially spherical, solid particles having an average diameter of from about 0.1 to about 5 microns. The particles are retained and immobilized upon the fibers of the matrix. Preferably, the particles have on their surfaces a substance capable of reaction with the analyte in the sample, and the average diameter of the particles is less than the average pore size of the matrix. The device, in a preferred embodiment, comprises a substantially planar layer of the described material.
    Type: Grant
    Filed: May 21, 1990
    Date of Patent: September 22, 1992
    Assignee: Abbott Laboratories
    Inventors: William E. Brown, John M. Clemens, Sharon M. Devereaux, John G. Hofler, Kevin M. Knigge, Sarah E. Safford
  • Patent number: 5143714
    Abstract: A test/control procedure and material is provided to facilitate standardization of immunostaining techniques and the assessment of their results. Pellets of an absorbent gel such as agar gel are caused to adsorb individual specific concentrations of an antigen of interest. The adsorbed antigens are confined to the individual pellets as by fixation or by enclosure in a diffusion-inhibiting barrier, and the pellets are installed in individual wells in a block of the gel in a manner to become integrated therein. The block may then be subjected to the same preparative routines as a tissue sample, sectioned and mounted like the sample, and then subjected to immunostaining by the same routine as the sample sections to provide a valid basis for assessment of the stained sample sections by comparison with the stained gel block sections. A gel block of suitable configuration is also disclosed.
    Type: Grant
    Filed: May 31, 1989
    Date of Patent: September 1, 1992
    Assignee: Shandon Scientific Limited
    Inventors: Raymond F. Cosgrove, Terence P. Male, Graeme M. Smalley
  • Patent number: 5141850
    Abstract: An immunoassay method comprising applying an aqueous solution containing the analyte antigen to one end of a multi-zoned test strip device such that the solution moves along the strip by capillary action. The zones are arranged so that the solution (a) first contacts and reconstitutes dry, diffusible labelled component comprising colloidal gold conjugated to an antibody specific for said analyte antigen and then (b) contacts and reconstitutes dry, diffusible biotinylated second antibody specific for said analyte antigen such that a diffusible, dispersed sandwich reaction product forms. The reaction product diffuses along the strip with the solution and into a zone containing capture component consisting of a latex and avidin complex which avidin collects the reaction product by means of reaction with its biotin moiety. Thus, gold particles are collected and concentrated in the detection zone for visual determination.
    Type: Grant
    Filed: February 7, 1990
    Date of Patent: August 25, 1992
    Assignee: Hygeia Sciences, Inc.
    Inventors: Francis X. Cole, Eric C. Sigillo, Paul C. MacDonnell, Nancy J. Cicia
  • Patent number: 5137804
    Abstract: This invention relates to an improved assay device and assay for detecting or quantitating the presence or absence of a substance in a sample. The device has multiple layers comprising a permeable layer (a) having a capture reagent attached to less than the entire membrane, a selectively permeable layer (b) which does not allow assay reagents to pass through (b) and an absorbent layer (c). Layer (b) is in communication with layers (a) and (c). Layer (b) has at least one hole extending therethrough and the hole or holes are directly below the capture reagent in layer (a). The area of the hole or the combined area of the holes is less than the area covered by the capture reagent. This invention also relates to a method of reducing background color development in an absorbent layer of an assay device.
    Type: Grant
    Filed: May 10, 1988
    Date of Patent: August 11, 1992
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Richard A. Greene, Patricia A. Kasila