Carrier Is Water Suspendible Particles Patents (Class 436/534)
  • Patent number: 5466611
    Abstract: The invention relates to a latex agglutination method for the detection or determination of one partner of an antigen-antibody reaction, wherein, in order to suppress non-specific reactions, to, for example, Clq and rheumatoid factors the immunochemical reaction takes place in the presence of an immune complex which does not contain any antibody or antigen that is specific for one of the partners.
    Type: Grant
    Filed: January 28, 1993
    Date of Patent: November 14, 1995
    Assignee: Behringwerke Aktiengesellschaft
    Inventor: Tibor Toth
  • Patent number: 5466574
    Abstract: A magnetic separator for isolating magnetically-labeled substances of interest, such as immunological agents, from a non-magnetic test medium using a method of high gradient magnetic separation. The target substance is contacted with microscopic magnetic particles having a receptor for binding with the target substance. The test medium containing the magnetic particles is held in a non-magnetic container and placed into a gap within an arrangement of magnets for causing the magnetic particles to adhere to selected locations upon the interior wall of the container. The quantity of magnetic particles may be controlled to cause the magnetic particles collected upon the interior wall to form a monolayer. The magnets are arranged upon a yoke which may provide linear, surrounding multipolar, or partially surrounding multipolar configurations of magnetic pole faces about the gap.
    Type: Grant
    Filed: January 15, 1993
    Date of Patent: November 14, 1995
    Assignee: Immunivest Corporation
    Inventors: Paul A. Liberti, Yuzhou Wang, Weixin Tang, Brian P. Feeley, Dhanesh I. Gohel
  • Patent number: 5464777
    Abstract: A method for the determination of protein and creatinine in urine. An organic acid, in the form of its lithium salt, is dried onto a suitable substrate in the second reaction zone of a reaction vessel having a first reaction zone for the immunometric determination of the protein and a second reaction zone for the colorimetric determination of creatinine. After completion of the immunometric determination of the protein the dried organic salt is contacted with the urine containing creatinine resulting in solubilization of the organic acid salt as creatinine reactive reagent thereby facilitating the colorimetric determination of the creatinine.
    Type: Grant
    Filed: September 26, 1994
    Date of Patent: November 7, 1995
    Assignee: Miles Inc.
    Inventor: Kin-Fai Yip
  • Patent number: 5460979
    Abstract: A patient's health is diagnosed by centrifuging blood samples in a transparent tube, which tube contains one or more groups of particles such as lyposomes or plastic beads of different densities for each group. Each group of density-defined particles carries antigens or antibodies which are specific to a complement antigen or antibody which may be in the blood sample being tested, and which are indicative of the patient's health. A label-tagged antibody which is specific to all bound antibody/antigen couples is added to the blood sample so as to form labelled antibody+antigen-antibody complexes (AAAC) in the blood sample. Upon centrifugation, the complexed particles will settle out in different areas in the tube according to the respective density of the particles, and the degree of label emission of the particle layers can enable qualitative or quantitative analyses of the blood sample to be made.
    Type: Grant
    Filed: February 7, 1994
    Date of Patent: October 24, 1995
    Assignee: Becton Dickinson and Company
    Inventors: Robert A. Levine, Stephen C. Wardlaw, Leon W. M. M. Terstappen, Thomas J. Mercolino, Diether J. Recktenwald
  • Patent number: 5460940
    Abstract: Methods and cards for detecting an antigen or antibody in a fluid sample are disclosed. The fluid sample is added to a microreaction vessel containing a slurry suspension of inert particles and a binding partner to the antigen or antibody to be determined. The fluid sample is added to the micro reaction vessel, with one of the antigen and antibody binding partners being carrier bound. The vessel contents are centrifuged, to cause the binding partners to contact each other to form an optically detectable binding complex. The location of the optically detectable complex is observed to determine the presence of the antibody.
    Type: Grant
    Filed: January 4, 1995
    Date of Patent: October 24, 1995
    Assignee: Stiftung fur diagnostische Forschung
    Inventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
  • 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: 5451528
    Abstract: A method for modifiying a liquid assay reagent to provide prolonged homogeneity thereof, particularly where the liquid assay reagent comprises microparticles for performing a heterogeneous immunoassay, is provided wherein the addition of an inert material to a liquid assay reagent achieves neutral density to thereby prolong the homogeneity thereof for extended periods of time. A method for the automated agitation of assay reagents to maintain the homogeneity thereof with an automated, continuous and random access analytical instrument is also provided. The automated mixing is accomplished by a back and forth motion of a carousel onto which assay reagent containers or packs are mounted with asymmetric pauses which can be completed within a short period of time. The carousel acceleration, velocity, distance moved, and pause-asymmetry are optimized to provide rapid assay reagent resuspension without foaming or bubble formation.
    Type: Grant
    Filed: August 20, 1993
    Date of Patent: September 19, 1995
    Assignee: Abbott Laboratories
    Inventors: William J. Raymoure, Frederic L. Clark, Gibert Clift, Kendall B. Hendrick, William J. Kanewske, III, Peter A. Lagocki, Richard R. Martin, James E. Mitchell, Larry E. Moore, Charles D. Pennington, Edna S. Walker, B. Jane Smith, Apparao Tayi, James A. Vaught, David A. Yost
  • Patent number: 5445970
    Abstract: The present invention provides assay methods for performing binding assays, wherein the detectable label is a magnetically responsive material. Direct and indirect, competitive and sandwich assay formats are used to partition the magnetically attractable label between a solid phase and a fluid phase in proportion to the presence or amount of analyte in the test sample. The magnetic responsiveness of the magnetically attractable label in one or both phases results in the exertion of a force upon the label. By determining the extent of the force or influence of the force exerted upon the label, the amount of the analyte in the test sample is determined.
    Type: Grant
    Filed: December 1, 1994
    Date of Patent: August 29, 1995
    Assignee: Abbott Laboratories
    Inventor: Thomas E. Rohr
  • Patent number: 5445944
    Abstract: Methods and compositions are disclosed for determining a peroxidatively active substance (PAS). The methods comprise the step of detecting a fluorescent signal produced upon cleavage of a compound of the formula F-L-Q, wherein F is a fluorescer capable of producing the signal, Q is a quencher capable of quenching the signal when linked to F, and L is a bond, or a linking group having a bond, wherein the bond is capable of being cleaved by a reaction of the PAS with a substrate of the PAS and a hydrogen donor wherein the cleavage of the bond substantially reduces the quenching. The methods have application in a wide variety of systems including assays and improved assays for analytes. Also disclosed are kits for conducting the methods and improvements in accordance with the present invention.
    Type: Grant
    Filed: April 22, 1994
    Date of Patent: August 29, 1995
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Edwin F. Ullman
  • Patent number: 5445936
    Abstract: A novel non-competitive immunoassay technique has been developed which not only improves sensitivity, but also is convenient and less susceptible to interfering factors. It is compatible with existing instruments and is an assay that can be run in one test tube. The analyte is reacted with labeled specific binder, after which the mixture is reacted with (1) an insoluble material attached to an analyte derivative and (2) a solid phase carrying a binder. The solid phase is then separated, and the label attached to the solid phase is measured.
    Type: Grant
    Filed: September 15, 1993
    Date of Patent: August 29, 1995
    Assignee: Ciba Corning Diagnostics Corp.
    Inventors: Uri Piran, William J. Riordan, Laurie A. Livshin
  • Patent number: 5445971
    Abstract: The present invention provides devices for performing binding assays. Such devices comprise (i) a reaction vessel where unbound and immobilized magnetically-labeled reagent are produced in relation to the amount of said analyte in said test sample; (ii) a separation means for partitioning said immobilized magnetically-labeled reagent and said bound magnetically-labeled reagent; (iii) a magnetic field generator means for the application of a magnetic field to said magnetically-labeled reagent; and (iv) a measurement means to assess the effect of said magnetic field on said magnetically-labeled reagent as a measure of the presence or amount of said analyte in said test sample. The device provided by the instant invention can run, for example, direct indirect, competitive, inhibition and sandwich assay formats.
    Type: Grant
    Filed: December 1, 1994
    Date of Patent: August 29, 1995
    Assignee: Abbott Laboratories
    Inventor: Thomas E. Rohr
  • Patent number: 5441894
    Abstract: An improved device is used for performing solid-phase chemiluminescent immunoassays. The device comprises a container having a fibrous matrix and a porous absorbent material. An improvement in the device is the use of light absorbing material as the absorbent material or as a light barrier between the fibrous matrix and the absorbent material. A second improvement comprises a fibrous matrix of binderless fiber matrix, such as glass fiber. The invention improves the direct measurement of the chemiluminescent signal from a solid surface by reducing background signal. The device is disposable and is suitable for manual use or for use with an apparatus having programmed instructions. The device is designed to be employed in a variety of solid-phase diagnostic assays such as sandwich or competitive binding assays. The device is also designed for use with microparticle capture or ion capture methods of separating the immunochemical reaction products.
    Type: Grant
    Filed: April 30, 1993
    Date of Patent: August 15, 1995
    Assignee: Abbott Laboratories
    Inventors: Carole L. Coleman, Kevin R. Genger, Hugh W. Graham, Charles F. Hanna, Omar S. Khalil, David C. Wender
  • Patent number: 5439830
    Abstract: In an immunoassay for determining the amount of a target substance in a sample using photothermal deflection spectroscopy to determine the amount of bound label, a sandwich procedure is used which comprises reacting the target substance with two antibodies or antigens, one labelled with a compound having photothermal deflection activity, and the other immobilized on a carrier capable of amplifying that photothermal conversion activity of the label.
    Type: Grant
    Filed: October 20, 1993
    Date of Patent: August 8, 1995
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Hajime Sakashita, Hiroshi Kishioka, Shohei Konishi, Tsuguo Swada, Takahiko Kitamori
  • 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: 5434088
    Abstract: A target substance is detected by a sandwich immunoassay using fine particle (A) having bound to it a fluorescer and an antibody reacting specifically with the target substance, and a fine particle (B) having bound to it a quencher and an antibody reacting specifically with the target substance, through a different antigenic determinant. Also disclosed is a competitive immunoassay having a fine particle (C) bound to it a fluorescer or a quencher, and an antibody reacting specifically with the target substance, a bound product (D) composed of the remainder of the fluorescer and the quencher, or a known amount of the target substance. Binding of the fluorescer and the quencher to the fine particle (A), (B) or (C) is affected so that the fluorescer and the quencher are covalently bound to a substance adsorbed on the fine particle.
    Type: Grant
    Filed: May 24, 1994
    Date of Patent: July 18, 1995
    Assignee: Tosoh Corporation
    Inventors: Kenji Ikeda, Kazuhisa Toyoda, Hideo Suzuki
  • Patent number: 5434051
    Abstract: An assay for photometrically detecting and/or quantitating the presence of an analyte in a sample in which the signal generated by a label associated with the analyte is photometrically detected in the presence of a suspended solid support.
    Type: Grant
    Filed: July 8, 1993
    Date of Patent: July 18, 1995
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: William J. Allard, David M. Obzansky, Hermant C. Vaidya
  • Patent number: 5432100
    Abstract: In a diagnostic apparatus system, a one piece porous substrate is provided in a container. The substrate serves both to extract an antigen in or on a top layer thereof with the remainder of the substrate serving as a reservoir. The pores in the top surface of the substrate are microscopic for entrapment of microspheres carrying antibodies. A target antigen in a test sample attaches to the antibodies when the test sample is poured through the top layer. The pores in all but the top layer of the substrate have a much greater pore size to comprise tile reservoir portion of the substrate.
    Type: Grant
    Filed: December 13, 1991
    Date of Patent: July 11, 1995
    Assignee: Porex Technologies Corp.
    Inventors: Michael W. Smith, Robert S. Pierce
  • Patent number: 5429951
    Abstract: In a known method of immunodiffusion, a sample containing a first agent such as an antigen is introduced into a well in a lamina of agarose gel containing a second agent such as a complementary antibody. The first agent diffuses through the gel and becomes releasably bound to the second agent and, when the concentrations of agents are optimal, the agents form an extended matrix incorporating light-scattering aggregates. The size of the visible matrix enables the concentration of one of the agents to be assessed when that of the other agent is known. Each aggregate comprises very large numbers of the molecules of the agents. The invention provides an improved method in which the second agent is attached to carrier means in the gel so that the carrier means constitutes part of the visible aggregations. The carrier means may constitute the gel itself and/or it may constitute particulate material such as polystyrene particles.
    Type: Grant
    Filed: October 9, 1991
    Date of Patent: July 4, 1995
    Inventor: Arthur R. Bradwell
  • Patent number: 5429803
    Abstract: A biological fluid collection container comprising a cup member, a lid assembly removably mounted to the cup member having a housing with a downwardly extending cylindrical skirt, a luer lock with a throughgoing bore extending from one side of the lid housing. A hollow tube extends from the other side of the lid housing adjacent the luer lock and is axially aligned with the throughgoing bore of the luer lock. The hollow tube is provided with a plurality of throughgoing holes leading into its lumen along its surface to provide for a sampling along various liquid level layers of the biological fluid specimen collected in the cup member so that when the biological fluid specimen is removed from the cup member a representative sampling is obtained.
    Type: Grant
    Filed: April 18, 1991
    Date of Patent: July 4, 1995
    Assignee: LaMina, Inc.
    Inventor: Raouf A. Guirguis
  • Patent number: 5427913
    Abstract: The invention provides a method for determining platelet function in a mammal comprising providing platelets from the mammal, contacting the platelets in suspension with at least one immobilised ECM protein or an effective fragment or analog thereof while applying to the platelets an effective mechanical stimulus for an effective period of time and determining the platelet activation produced.The invention also provides a method for detecting a bleeding disorder in a human. Further, the invention provides a method for monitoring the efficacy of pharmacological agents affecting platelet function in vivo.
    Type: Grant
    Filed: December 3, 1992
    Date of Patent: June 27, 1995
    Assignee: Alberta Cancer Board
    Inventors: Andrew R. E. Shaw, Michael W. Stewart
  • Patent number: 5427959
    Abstract: On a slab-like board formed of a transparent material is closely attached a wedge-shaped transparent cover member provided with a recess in a central inner portion, thereby to form a clearance. The height of the clearance between the recess and the board is configured to decrease continuously or in steps. When an immunological active substance such as a monoclonal antibody is caused to sensitize carrier particles F, and a reagent having the carrier particles F dispersed into a liquid medium mainly composed of the water is mixed with a specimen, the reaction will occur in which the flocculate is formed from plural carrier particles. When this reaction liquid is poured into the clearance through the opening, the reaction liquid penetrates in the direction having a narrower vertical spacing due to surface tension. A single carrier particle unflocculated can move deep within the recess because it is small in diameter, but the flocculate G is trapped on its way and can not move because of its size.
    Type: Grant
    Filed: October 1, 1991
    Date of Patent: June 27, 1995
    Assignee: Canon Kabushiki Kaisha
    Inventors: Matsuomi Nishimura, Kazumi Tanaka, Takeshi Miyazaki, Hidehito Takayama, Toshikazu Ohnishi
  • Patent number: 5420042
    Abstract: Method for the analytical determination of the concentration of a component of a medical sample, in which a reaction of the sample with reagents leads to a time-dependent change S(t) in a measured quantity S and the concentration C correlates according to an evaluation curve C(X) with an input variable X derived from S(t), in which the calibration curve is ambiguous for at least a portion of the possible X values. In order to assign an input variable X to one of the sub-sections and thereby to obtain an unambiguous correlation to a particular concentration C, a training run and an analysis run are performed. In the training run, a discrimination algorithm is performed at least once, in which a discriminator set is generated from measurements of S(t), a score is generated in each case from the latter with a multivariate statistical technique and it is checked whether the scores can be divided into separate subsets, in which the concentrations are correctly assigned to the sub-sections of the calibration curve.
    Type: Grant
    Filed: June 29, 1993
    Date of Patent: May 30, 1995
    Assignee: Boehringer Mannheim GmbH
    Inventors: Rainer Schafer, Christoph Berding, Fridl Lang, Wilheim Kleider, Peter Wolf
  • Patent number: 5418140
    Abstract: A method for rapid identification of Vibrio parahaemolyticus in a sample containing suspect colonies which includes the steps of:(i) coating latex particles with a solution of antibodies or antisera against outer membrane proteins of V. parahaemolyticus at an appropriate concentration to obtain a latex reagent, and(ii) mixing the sample with the latex reagent obtained in the (i) under conditions appropriate to complete agglutination; and a kit for accomplishing the method are disclosed.
    Type: Grant
    Filed: August 10, 1993
    Date of Patent: May 23, 1995
    Assignee: Food Industry Research and Development Institute
    Inventors: Tsung C. Chang, Hui C. Chen
  • Patent number: 5416001
    Abstract: A method for detecting an analyte is disclosed in which the analyte is brought into contact with at least one receptor which is bound to or can be bound to a solid phase. In order to avoid unspecific interferences the addition of a glycosidic surfactant is proposed.
    Type: Grant
    Filed: June 25, 1993
    Date of Patent: May 16, 1995
    Assignee: Boehringer Mannheim GmbH
    Inventors: Peter Sluka, Rainer Wehner
  • 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: 5405784
    Abstract: The invention provides a method capable of determining the presence or absence of each of a plurality of different ligands in a specimen. The specimen is contacted with a predetermined number of different homogeneous populations of fluorescence beads having one or more predetermined antiligands affixed to their surface. The specimen and bead mixture is analyzed using a means having a single parameter for measuring the fluorescence per ligand to determine the number of nonagglutinated beads, the number of agglutinated beads, the number of bead aggregates, and for each aggregate, the number of beads it comprises. This information is used to correlate the presence or absence in the specimen of each of the different ligands analyzed for. The method of the invention thus provides for the simultaneous determination of a predetermined number of ligands in a specimen using only a single bead contacting step.
    Type: Grant
    Filed: February 25, 1993
    Date of Patent: April 11, 1995
    Assignee: Chemunex
    Inventor: Michel Van Hoegaerden
  • Patent number: 5403721
    Abstract: There is disclosed an improved method for testing for the presence of a particular microorganism or group of microorganisms characterized by a particular enzyme. The method uses a dye-forming substrate throughout a polymer matrix or on the surface of a solid support member that forms a colored precipitate when cleaved by the enzyme. The precipitate is concentrated to the polymer matrix and/or solid support member to create a visible reaction product, wherein the amount of dye-forming substrate needed is independent of the sample size. The present invention further comprises an enzyme indicator device comprising a dye-forming substrate throughout a polymer system or on the surface of a solid support member.
    Type: Grant
    Filed: April 21, 1993
    Date of Patent: April 4, 1995
    Assignee: BioControl Systems, Inc.
    Inventors: N. Robert Ward, Jr., John P. DesRosier, Elliott D. Marshall, III, Judith Ford, Nancy J. S. Mallinak
  • Patent number: 5401633
    Abstract: A biologically active reagent is prepared by reacting a biologically active substance covalently to a polymeric particle having pendant aldehyde groups. Such groups are provided by a polymerizable monomer represented by the structure: ##STR1## wherein Ar is arylene, R and R.sup.1 are independently hydrogen, halo or lower alkyl, R.sup.2 and R.sup.3 are independently alkylene of 1 to 4 carbon atoms in the chain, R.sup.4 is arylene, m is 0 or 1, and n is an integer of 1 to 4. These reagents can be used in a variety of specific binding and affinity purification methods, and in both solution assays and dry analytical elements.
    Type: Grant
    Filed: October 1, 1992
    Date of Patent: March 28, 1995
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Ignazio S. Ponticello, Susan J. Danielson
  • 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: 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: 5389521
    Abstract: The invention is a method for detecting pathogenic bacteria by specific binding of the bacteria to GalNAc.beta.1-4Gal sequences found in fucosyl-asialo GM1, asialo GM1 and asialo GM2. An agglutination reaction is disclosed comprising contacting a culture suspected of containing the bacteria with a suspension of a purified carbohydrate compound bound to an insoluble carrier and detecting the presence of perceptible agglutination of the carrier as an indication of the presence of the bacteria. Bacteria which can be detected using the claimed method include Pseudomonas, Haemophilus, Staphylococcus, Klebsiella and Streptococcus pneumoniae.
    Type: Grant
    Filed: January 13, 1993
    Date of Patent: February 14, 1995
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Howard C. Krivan, Victor Ginsburg, David D. Roberts
  • Patent number: 5385847
    Abstract: Disclosed is a method for the determination of urinary protein and creatinine in a single reaction vessel using a continuous process. The method involves adjusting the pH to a level suitable for carrying out an immuno assay for the protein and making such a determination by an immuno agglutination technique. Raising the pH to a level suitable for determining the creatinine quickly dissipates the cloudiness caused by the agglutination reaction, so that the creatinine determination can be carried out without delay.
    Type: Grant
    Filed: December 2, 1993
    Date of Patent: January 31, 1995
    Assignee: Miles Inc.
    Inventors: Kin F. Yip, Amy H. Chu, Brenda Tudor
  • 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: 5374531
    Abstract: Methods and test kits are provided for the quantitative or qualitative determination of selected analytes, e.g., cell subsets in a mixed cell population, using a particulate separation reagent and a particulate detection reagent. The invention enables cell monitoring of AIDS patients in a efficient and reliable manner.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: December 20, 1994
    Assignee: Zynaxis, Inc.
    Inventor: Bruce D. Jensen
  • Patent number: 5372948
    Abstract: Disclosed are a method and device for performing sequential analytical reactions involving a first dry reagent and a second dry reagent comprised of two or more components having different rates of solubilization. The invention enables one to fully solubilize the components of the second reagent before they are brought into contact with each other to thereby avoid interference with the reaction kinetics which result when one or both of the components are not fully dissolved prior to their being brought into contact. The invention is especially useful in conjunction with immunoassay formats involving latex bound antibodies and polymeric agglutinators.
    Type: Grant
    Filed: March 17, 1993
    Date of Patent: December 13, 1994
    Assignee: Miles Inc.
    Inventor: Kin F. Yip
  • Patent number: 5370993
    Abstract: Compounds and methods are disclosed for reversibly aggregating particles suspended in a liquid medium. The method comprises combining the liquid medium containing the particles with a polyionic polymer capable of aggregating the particles under conditions suitable for such aggregation. Thereafter, the particles are contacted with a chemical reagent capable of cleaving the polyionic polymer under conditions sufficient to reverse the aggregation. Optionally, magnetic particles are added to the liquid medium in the present method under conditions for non-specific binding and the medium including the aggregates is subjected to a magnetic field gradient to separate the aggregates from the medium. The compounds of the present invention are polyions. The aggregation of the particles is reversible upon contact with chemical agents which cleave at least some of the bonds within the polyionic polymer.
    Type: Grant
    Filed: May 12, 1992
    Date of Patent: December 6, 1994
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Thomas L. Tarnowski, Cheng-I Lin, Edwin F. Ullman
  • Patent number: 5369037
    Abstract: A particle agglutination-based, stable kinetic method for simultaneously determining the concentrations of multiple analytes in a single fluid sample with the addition of a single reagent, that entails the use of a novel high resolution sheath flow cell, a novel optical flow particle analyzer (FPA), and unidirectional low angle forward light scattering from multiply-sized or refractive indexed, differently coated particles and their aggregates.
    Type: Grant
    Filed: August 30, 1993
    Date of Patent: November 29, 1994
    Assignee: Sienna Biotech, Inc.
    Inventor: W. Peter Hansen
  • Patent number: 5369036
    Abstract: A process for assaying at least one analyte uses a tracer which includes multiple detectable substances. A tracer composition includes at least one ligand labeled with a particulate label, the particulate label containing at least one detectable substance. Two or more detectable substances in the assay may be in the same particulate label or in different particulate labels conjugated to different ligands.
    Type: Grant
    Filed: July 2, 1992
    Date of Patent: November 29, 1994
    Assignee: Becton, Dickinson and Company
    Inventors: Thomas J. Mercolino, Joanne H. Hasskamp, Edward C. McFarland
  • 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
  • Patent number: 5342790
    Abstract: A patient's health is diagnosed by centrifuging blood samples in a transparent tube, which tube contains one or more groups of particles such as lyposomes or plastic beads of different densities for each group. Each group of density-defined particles carries antigens or antibodies which are specific to a complement antigen or antibody which may be in the blood sample being tested, and which are indicative of the patient's health. A label-tagged antibody which is specific to all bound antibody/antigen couples is added to the blood sample so as to form labeled antibody+antigen-antibody complexes (AAAC) in the blood sample. Upon centrifugation, the complexed particles will settle out in different areas in the tube according to the respective density of the particles, and the degree of label emission of the particle layers can enable qualitative or quantitative analyses of the blood sample to be made.
    Type: Grant
    Filed: October 30, 1992
    Date of Patent: August 30, 1994
    Assignee: Becton Dickinson and Company
    Inventors: Robert A. Levine, Stephen C. Wardlaw, Leon W. M. M. Terstappen, Thomas J. Mercolino, Diether J. Recktenwald
  • Patent number: 5338689
    Abstract: A method of detecting target antibodies or antigens by reaction with specific binding partners thereto is disclosed. One of the target or the binding partner is bound to a carrier, and the other is unbound. The complex between the target and the binding partner, with one being carrier-bound, forms an optically detectable binding complex. A microreaction vessel having an upper portion, a transition portion and a lower portion is utilized, wherein the upper portion has a greater diameter or width than the lower portion, and the transition portion is situated between the upper portion and the lower portion, and is funnel shaped. The microreaction vessel contains a slurry or suspension of inert particles, and unbound target or binding partner thereto. A solution of the carrier bound target or binding partner thereto is added to the vessel, which is then centrifuged to produce an optical determination of the target.
    Type: Grant
    Filed: October 30, 1992
    Date of Patent: August 16, 1994
    Assignee: Stiftung fur diagnostische Forschung
    Inventors: Lapierre Yves, Dieter Josef, Jean Adam, Susanne Greber-Widmer
  • Patent number: 5338661
    Abstract: The present invention provides a human monoclonal antibody (C-OU1) which specifically binds a human adenocarcinoma tumor-associated antigen with an apparent molecular weight of about 43 kD and an isoelectric point of about 5.4-6.2. Screening assays using the antibody are also disclosed.
    Type: Grant
    Filed: September 29, 1989
    Date of Patent: August 16, 1994
    Inventors: Jens C. Jensenius, Per Borup-Christensen, Karin Erb
  • Patent number: 5336621
    Abstract: Divalent hapten derivatives wherein two hapten moieties are connected by means of a bifunctional spacer wherein the derivative has the formulaA--X--Awhere A is a bonded hapten moiety and X is a bifunctional spacer having the formula(B).sub.m --Y--(CH.sub.2).sub.n --Z--(CH.sub.2).sub.n --Y--(B).sub.mwhere m is independently 0 or 1, B is (CH.sub.2).sub.n', wherein n' is an integer from 1 to 4, or CO(CH.sub.2).sub.n", wherein n" is an integer from 2 or 4; Y is independently --CONH--, --NHCO--, --OOC, --COO--, --O--, --S--, or --NR--, wherein R is hydrogen or alkyl; n is an integer from 1 to 10; and Z is an organic moiety containing at least one hydrophilic atom, useful for the determination of haptens by immunochemical techniques are disclosed.
    Type: Grant
    Filed: June 27, 1988
    Date of Patent: August 9, 1994
    Assignee: Hoechst Celanese Corporation
    Inventors: Kathleen J. Primes, Gerald F. Sigler, Gerd Grenner, Wolfgang Kapmeyer
  • Patent number: 5332662
    Abstract: Methods and compositions are disclosed for determining a peroxidatively active substance (PAS). The methods comprise the step of detecting a fluorescent signal produced upon cleavage of a compound of the formula F-L-Q, wherein F is a fluorester capable of producing the signal, Q is a quencher capable of quenching the signal when linked to F, and L is a bond, or a linking group having a bond, wherein the bond is capable of being cleaved by a reaction of the PAS with a substrate of the PAS and a hydrogen donor wherein the cleavage of the bond substantially reduces the quenching. The methods have application in a wide variety of systems including assays and improved assays for analytes. Also disclosed are kits for conducting the methods and improvements in accordance with the present invention.
    Type: Grant
    Filed: July 31, 1992
    Date of Patent: July 26, 1994
    Assignee: Syntex (U.S.A.) Inc.
    Inventor: Edwin F. Ullman
  • Patent number: 5308749
    Abstract: Biologically active reagents are prepared from particles of copolymers having highly active succinimid groups. The reagents are prepared by covalently attaching biologically active substances, for example antibodies, to the particles, directly or indirectly through amide groups by displacement of highly active succinimid groups on the particle surface. These reagents are used to advantage in analytical elements, methods for the detection of specific binding ligands (such as immunological species) and immunoassays, and in purification methods such as affinity chromatography.
    Type: Grant
    Filed: January 25, 1991
    Date of Patent: May 3, 1994
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Ignazio S. Ponticello, Susan J. Danielson, Marsha D. B. Oenick
  • Patent number: 5302512
    Abstract: The invention includes an agglutinant complex which is useful for the investigation of the antigens present on erythrocytes, and which results from affinity couplings between nonagglutinant IgG type antibodies specific for the antigen to be identified, a protein capable of binding to at least two sites on the Fc part of antibodies and an anti-immunoglobulin antibody or its fragments.
    Type: Grant
    Filed: May 4, 1992
    Date of Patent: April 12, 1994
    Assignee: Pasteur Sanofi Diagnostics
    Inventor: Michel Pernelle
  • Patent number: 5296355
    Abstract: A method for assaying an immunologically active substance based on the antigen-antibody reaction in a liquid phase, and a reagent for use in the method are disclosed. This method comprises adding a reagent containing a compound represented by the general formulaR.sup.1 O---[(CH.sub.2 CH.sub.2 O).sub.m (AO).sub.n ]--R.sup.2(wherein R.sup.1 and R.sup.2 each represents a hydrogen atom or a hydrocarbyl group containing 1 to 5 carbon atoms, AO represents an oxyalkylene group containing 3 to 4 carbon atoms, m and n represent the number of oxyethylene groups and that of oxyalkylene groups, respectively, with said oxyethylene groups and oxyalkylene groups forming a random copolycondensate and having a molecular weight of 1000 to 20000, and the ratio of m/n being 60/40 to 90/10).
    Type: Grant
    Filed: June 12, 1991
    Date of Patent: March 22, 1994
    Assignee: Hoeschst Aktiengesellschaft
    Inventors: Shoichi Shutoh, Akinori Suginaka, Mikio Akita
  • Patent number: 5290707
    Abstract: A microorganism detection system provides initial warning, confirmation of dentity, and recognition of pathogenic factors in microorganisms from environmental samples. The method and apparatus of the invention uses different sized antibody coated microspheres which react with unknown antigens, are sized by electronic volume sizing, and are sorted by size. The sized particles are quantitated in addition to being sized. The microsphere sizes indicate the presence of specific microorganism groups.The samples can be further analyzed using fluorescent microspheres which agglutinate with the sized microspheres. The presence of specific microorganisms is indicated by a change in the fluorescence of the sample.
    Type: Grant
    Filed: November 25, 1991
    Date of Patent: March 1, 1994
    Assignee: The United States of America as represented by the Secretary of the Army
    Inventor: Sheila J. Wood
  • Patent number: 5288610
    Abstract: A detecting reagent for an antiplatelet antibody, comprises a carrier particle, and a platelet antigen component immobilized on a surface of the carrier particle. The reagent particles do not agglutinate with each other, contrary to the platelets subjected to natural agglutination, probably because the platelet membrane antigen component immobilized on the carrier particle is solubilized in advance.
    Type: Grant
    Filed: April 12, 1990
    Date of Patent: February 22, 1994
    Assignee: Olympus Optical Co., Ltd.
    Inventors: Yoichi Shibata, Naohiro Ozawa
  • Patent number: 5286452
    Abstract: A particle agglutination-based, stable kinetic method for simultaneously determining the concentrations of multiple analytes in a single fluid sample with the addition of a single reagent, that entails the use of a novel high resolution sheath flow cell, a novel optical flow particle analyzer (FPA), and unidirectional low angle forward light scattering from multiply-sized or refractive indexed, differently coated particles and their aggregates. Also disclosed are two embodiments of an instrument specifically designed to carry out the method of the invention.
    Type: Grant
    Filed: May 15, 1992
    Date of Patent: February 15, 1994
    Assignee: Sienna Biotech, Inc.
    Inventor: W. Peter Hansen