Involving Kinetic Measurement Of Antigen-antibody Reaction Patents (Class 436/517)
  • Patent number: 6132977
    Abstract: SNAP-25 (synaptosomal associated protein) is purified from cerebrospinal or amniotic fluid for immunoassay and quantitation. Quantitation of these proteins is useful in the diagnosis and monitoring of brain disorders and diseases such as schizophrenia and Alzheimer's.
    Type: Grant
    Filed: March 13, 1998
    Date of Patent: October 17, 2000
    Assignee: University of New Mexico
    Inventors: Peter M. Thompson, Nora Perrone-Bizzozero
  • Patent number: 6130037
    Abstract: A biosensor apparatus for detecting a binding event between a ligand and receptor. The apparatus includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having ligands attached to the exposed monolayer surface. Binding of a receptor to the monolayer-bound ligand, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer. In one embodiment, the monolayers have a coil-coil heterodimer embedded therein, one subunit of which is attached to the substrate, and the second of which carries the ligand at the monolayer surface.
    Type: Grant
    Filed: April 24, 1997
    Date of Patent: October 10, 2000
    Assignee: PENCE and McGill University
    Inventors: R. Bruce Lennox, Robert S. Hodges, Randall T. Irvin
  • Patent number: 6127120
    Abstract: The invention relates to the detection of target nucleic acids or nucleic acid units in a sample, by obtaining a SER(R)S spectrum for a SER(R)S-active complex containing, or derived directly from, the target. The complex includes at least a SER(R)S-active label, and optionally a target binding species containing a nucleic acid or nucleic acid unit. In this detection method, the concentration of the target present in the SER(R)S-active complex, or of the nucleic acid or unit contained in the target binding species in the SER(R)S-active complex, is no higher than 10.sup.-10 moles per liter. Additionally or alternatively, one or more of the following features may be used with the method: i) the introduction of a polyamine; ii) modification of the target, and/or of the nucleic acid or nucleic acid unit contained in the target binding species, in a manner that promotes or facilitates its chemi-sorption onto a SER(R)S-active surface; iii) inclusion of a chemi-sorptive functional group in the SER(R)S-active label.
    Type: Grant
    Filed: April 21, 1998
    Date of Patent: October 3, 2000
    Assignee: University of Strathclyde
    Inventors: Duncan Graham, Adrian Matthew Thornton Linacre, Callum Hugh Munro, William Ewan Smith, Nigel Dean Watson, Peter Cyril White
  • Patent number: 6121055
    Abstract: The invention provides methods for separating bound label from unbound label within an assay mixture, for predispensing assay reactants in self-contained assay vessels, as well as for detecting the presence and/or amount of an analyte within a fluid sample. In addition, a reusable detection vessel for use therein and with specific binding assays in general is disclosed. In the methods, generally an analyte within a sample is detected or measured by forming an assay mixture containing sample, analyte binding components and label, placing the assay mixture in contact with an immisable primary layer, subjecting the assay mixture to conditions that separate the analyte bound with binding components and label from unbound binding components and label, and subsequently detecting bound label.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: September 19, 2000
    Assignee: Roche Diagnostics Corporation
    Inventor: William R. Hargreaves
  • Patent number: 6103536
    Abstract: The present invention provides internally calibrated competitive assays for use on a solid support. Additionally, the invention provides a method of using such assays.
    Type: Grant
    Filed: May 1, 1998
    Date of Patent: August 15, 2000
    Assignee: Silver Lake Research Corporation
    Inventor: Mark S. Geisberg
  • Patent number: 6103537
    Abstract: The present invention concerns methods for masking inhomogeneity of a member of a specific binding pair (sbp) employed in a capillary electroseparation. The method comprises binding the sbp member to synthetic particles that become localized during capillary electroseparation. Also disclosed is one embodiment of the present invention, which is a method for conducting a capillary electroseparation specific binding assay. The method involves the electroseparation of a labeled first member of a specific binding pair that is bound in a complex from labeled first member that is not bound in the complex. The complex comprises the first member and a second member of a specific binding pair. A combination is provided comprising a sample suspected of containing an analyte, a labeled first member of a specific binding pair, and a second member of a specific binding pair under conditions for forming a complex between labeled first member and the second member.
    Type: Grant
    Filed: September 30, 1998
    Date of Patent: August 15, 2000
    Assignee: ACLARA Biosciences, Inc.
    Inventors: Edwin F. Ullman, Gregory B. Stauber
  • Patent number: 6044330
    Abstract: The present invention relates to a method for instrument determination of measured variable L(t) which changes with time, the intention being to determine the maximum value of L(t) in a region with a linear reaction profile, and the time as well as the duration of the reaction time window being variable with the linear region and depending on the nature of the reaction and the reaction conditions. Specifically, the present invention relates to the determination of protein concentrations with the aid of light scatter, which is produced by specific antibodies, in homogeneous solutions. In particular, the invention relates to reactions which take place slowly and have a largely linear profile over a relatively long time, the rate of formation of antigen-antibody complexes in the linear section of the reaction (V.sub.MaxLin) being determined as the measured variable.
    Type: Grant
    Filed: September 24, 1997
    Date of Patent: March 28, 2000
    Assignee: Dade Behring Marburg GmbH
    Inventor: Jurgen Patzke
  • Patent number: 6037185
    Abstract: A non-competitive method for the determination of analytes. Initially the analyte is bound to a specific binding partner, after which the unoccupied binding sites of the binding partner are inactivated. The bound analyte is then dissociated from the binding partner and replaced by a labeled marker, after which the bound labeled marker is determined. The signal from the bound labeled marker is directly proportional to the initial amount of analyte in the sample, which makes the present method more favorable than the competitive assays.
    Type: Grant
    Filed: July 8, 1998
    Date of Patent: March 14, 2000
    Assignees: Wallac Oy, Orion-yhtyma Oy
    Inventor: Petri Saviranta
  • Patent number: 6008057
    Abstract: Disclosed is a method of assaying, in assay apparatus, for at least the ligand intended to be used to assay analyte in a sample, with which analyte the ligand will specifically bind. The method provides a product in which a ligand is labeled with a detectable tag and is immobilized on an appropriate substrate. An assay is made to measure the immobilized, labeled ligand by detecting the tag labeling the latter. The product can then be used to assay for the analyte by contacting the latter so as to form a complex. The extent and rate of specific binding of the analyte in the complex is identifiable, either by competition assay or sandwich assay as a rate of change, so the relative proportions of analyte and ligand are readily determinable.
    Type: Grant
    Filed: March 17, 1995
    Date of Patent: December 28, 1999
    Assignee: Roche Diagnostics Corporation
    Inventors: Thomas R. Glass, Myron J. Block
  • Patent number: 5968479
    Abstract: A diagnostic marker containing (a) a detection system such as an antibody and (b) a fluorescent functional group that is bound to the detection system and represented by the following formula: ##STR1## wherein R.sup.1 and R.sup.2 independently represent hydrogen atom, an alkyl group or the like; R.sup.3 represents an alkyl group, a sulfonic acid-alkyl group or the like; X.sup.- represents an anion species, if required; Y represents a C.sub.1 -C.sub.10 alkylene group or a C.sub.1 -C.sub.10 alkylene group containing one or more atoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom. The diagnostic marker emits fluorescence having a wavelength of 780 nm or more when irradiated with near or far infrared rays, and thus useful for infrared endoscopic diagnosis or identification of a focus in surgical operation.
    Type: Grant
    Filed: September 17, 1997
    Date of Patent: October 19, 1999
    Assignee: Daiichi Pure Chemicals Co., Ltd.
    Inventors: Susumu Ito, Masayuki Nozawa, Masanobu Shiga, Kazumi Sasamoto, Kazuhiro Takesako, Hiroshi Takeuchi
  • Patent number: 5958715
    Abstract: Method of quantitative analysis of an enzyme linked immuno assay comprising the steps of forming an antigen--antibody complex between an antigen present in a sample to be tested and an enzyme labelled antibody and thereafter adding a substrate composition which can be converted into a differently colored product composition by the catalytic action of the enzyme. Quantification is achieved by measuring the time elapsed from addition of the substrate composition until a sudden color change discernible to the eye occurs. The measured time is then compared against a predetermined standard to determine the amount of antigen present in the sample.
    Type: Grant
    Filed: December 23, 1997
    Date of Patent: September 28, 1999
    Assignee: BRF International
    Inventor: Robert Edwin Muller
  • Patent number: 5932700
    Abstract: A novel cell growth-inhibiting protein is provided. The cell growth-inhibiting protein, obtainable from extract of human uterine endometrial carcinoma, has the amino acid sequence rich in hydrophobic residue at its N-terminal, has a molecular weight of about 68,000 dalton, and is considered to act as a paracrine growth-inhibiting factor in an organism.
    Type: Grant
    Filed: August 29, 1997
    Date of Patent: August 3, 1999
    Assignee: Suntory Limited
    Inventor: Atsushi Imai
  • Patent number: 5912182
    Abstract: A sample of liquid with suspended particles is contained in a tube and subjected to a standing wave ultrasound field transverse to the tube, the standing wave exhibiting a progressive change in pressure amplitude transverse to the tube, so that particles in suspension are displaced transversely of the tube to one or more predetermined regions; exposure of the sample to the standing wave is then terminated and the particles are allowed to settle, and inspected to determine whether they remain aggregated or whether they dissociate. The ultrasound field is produced by a transducer of tubular form encircling the tube. The invention may be used for agglutination of particles or cells via cross-bridging molecules in immuno-agglutination assays.
    Type: Grant
    Filed: September 8, 1997
    Date of Patent: June 15, 1999
    Assignee: University College Cardiff Consultants Limited
    Inventors: William Terence Coakley, Martin Alan Grundy, Werner Bolek
  • Patent number: 5898004
    Abstract: Novel sensor devices composed of a crystalline colloidal array (CCA) polymerized in a hydrogel are disclosed. The hydrogels are characterized as being capable of shrinking and swelling in response to specific stimuli applied thereto. As the hydrogels shrink or swell, the lattice structure of the CCA embedded therein changes, thereby changing the wavelength of light diffracted by the CCA. Thus by monitoring the change in diffracted wavelength, the concentration of a stimulus is determined. The gels can be modified to sense numerous different stimuli. The sensor devices are specific in that they are modified to react with only one species or family of species. These sensors have various applications in areas including, for example, environmental and chemical systems, chemomechanical systems, sensor devices and medical diagnostic tools. Various methods for making and using these devices are also disclosed.
    Type: Grant
    Filed: November 6, 1996
    Date of Patent: April 27, 1999
    Assignee: University of Pittsburgh of the Commonwealth System of Higher Education
    Inventors: Sanford A. Asher, John H. Holtz
  • Patent number: 5869261
    Abstract: When measurement by a 1 step sandwich method is performed, a signal corresponding to a quantity of labeled antibodies A is sampled, the labeled antibodies being constrained in the vicinity of a surface of an optical waveguide (D) by an antigen-antibody reaction. A differential value by time at the beginning of the measurement and a signal corresponding to an extent of an immunological reaction at a time at which the signal becomes nearly stable are obtained based upon the sampled signals. The extent of the immunological reaction is then uniquely determined based upon the differential value by time and the signal corresponding to the extent of the immunological reaction.
    Type: Grant
    Filed: August 30, 1995
    Date of Patent: February 9, 1999
    Assignee: Daikin Industries, Ltd.
    Inventor: Kaori Tosa
  • Patent number: 5856106
    Abstract: Disclosed are a composition and method for determining the levels of specific immune responsiveness to a glycoprotein in an individual being treated therewith by (i) contacting a body fluid sample obtained from the individual prior to glycoprotein treatment with glycoprotein that has been modified to have an oxidized carbohydrate portion; (ii) contacting a body fluid sample obtained from the individual subsequent to glycoprotein treatment with the glycoprotein that has been modified to have an oxidized carbohydrate portion; and (iii) observing the degree of difference in the specific immune response to the oxidized glycoprotein in the pre- and post-treatment samples.
    Type: Grant
    Filed: November 1, 1995
    Date of Patent: January 5, 1999
    Assignee: BioTransplant, Inc.
    Inventors: Michel G. Awwad, Sonny Abraham, Mary E. White-Scharf, James A. Hope
  • Patent number: 5851781
    Abstract: The present invention discloses novel immunogens, antibodies prepared from such immunogens, and labeled reagents useful in immunoassays for the detection and quantification of testosterone in a test sample. Also disclosed are immunoassays using these reagents and methods for synthesizing these reagents. The immunoassays are preferably microparticle enzyme immunoassays (MEIAs) and fluorescence polarization immunoassays (FPIAs). Further disclosed are novel starting materials for making the above novel immunogens and labeled reagents. Methods for making the novel immunogens and labeled reagents from the novel starting materials are also disclosed.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: December 22, 1998
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Yon-Yih Chen, John A. Walling, Bryan D. James, Sharon G. Artrip
  • Patent number: 5846738
    Abstract: A conjugate of at least two binding sites that bind specifically to the analyte-specific binding region of the receptor that is used for detection in a test, wherein the binding sites are linked by at least one soluble carrier substance and the conjugate is a product of a synthetic or recombinant production, dissolved in an aqueous solution in an exactly known amount is particularly suitable as a stable calibrator in a test for the detection of an analyte.
    Type: Grant
    Filed: December 12, 1996
    Date of Patent: December 8, 1998
    Assignee: Boehringer Mannheim GmbH
    Inventors: Christoph Seidel, Peter Bialk, Herbert Von der Eltz
  • Patent number: 5834319
    Abstract: A method for determining the concentration of an analyte 6 in a liquid sample is described. The method uses a binding agent 2 capable of binding the analyte 6 and first and second developing agents 8, 12, the first developing agent 8 capable of binding to unoccupied binding sites on the binding agent 2 and having a first marker 10, the second developing agent 12 capable of binding to the bound analyte or to the occupied binding sites and having a second marker 14 different from the first. The concentration of the analyte is determined by measuring the signals from the markers on first and second developing agents 8, 12. Thus, the method combines the competitive and non-competitive methods of the prior art and preferably has the advantage of extending the working range and/or sensitivity of the assay. A kit for performing the assay is also disclosed.
    Type: Grant
    Filed: June 14, 1996
    Date of Patent: November 10, 1998
    Inventor: Roger P. Ekins
  • Patent number: 5814461
    Abstract: Method for the determination of an analyte in a volume of a fluid sample, in particular of anti-TSH receptor autoantibodies in a patient serum, in which one or more determination reagent(s) which contains or which containa) a predetermined amount of a binder (B) for the analyte (A) andb) a predetermined amount of a competitor (K) which is likewise bound by the binder (B), in such a way that the extent of its binding to the binder (B) is correlated with the simultaneous presence of the analyte (A) and/or its amount in the sample, the competitor (K) being labelled, or being capable of being labelled, with a label which permits its qualitative and/or quantitative determination, is or are added to the sample with the formation of a liquid reaction mixture, whereinc) the liquid reaction mixture is reacted simultaneously or subsequently with a solid phase to which a substance (Imm) for the selective immobilization of the amount of competitor (K) not bound to the binder (B) is bound, and optionally with a labelled r
    Type: Grant
    Filed: July 9, 1996
    Date of Patent: September 29, 1998
    Assignee: B.R.A.H.M.S. Diagnostica GmbH
    Inventors: Andreas Bergmann, Joachim Struck, Shaul Kornfeld
  • Patent number: 5807755
    Abstract: A method for determining the ambient concentrations of a plurality of analytes in a liquid sample of volume V liters, comprisesloading a plurality of different binding agents, each being capable of reversibly binding an analyte which is or may be present in the liquid sample and is specific for that analyte as compared to the other components of the liquid sample, onto a support means at a plurality of spaced apart locations such that each location has not more than 0.1 V/K, preferably less than 0.
    Type: Grant
    Filed: May 23, 1995
    Date of Patent: September 15, 1998
    Assignee: Multilyte Limited
    Inventor: Roger P. Ekins
  • Patent number: 5804390
    Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.
    Type: Grant
    Filed: February 24, 1997
    Date of Patent: September 8, 1998
    Assignee: Abbott Laboratories
    Inventors: Stephen W. Fesik, Philip J. Hajduk
  • Patent number: 5798448
    Abstract: The present invention provides nucleic acids encoding AL-1 protein, as well as AL-1 protein produced by recombinant DNA methods. Such AL-1 protein is useful in preparing antibodies and in diagnosing and treating various neuronal disorders.
    Type: Grant
    Filed: May 15, 1995
    Date of Patent: August 25, 1998
    Assignee: Genentech, Inc.
    Inventors: Ingrid W. Caras, John W. Winslow
  • Patent number: 5789262
    Abstract: The invention relates to the area of protein determinations in homogeneous solution by means of antigen-mediated precipitation by antibodies or using latex materials coated with antibodies and subsequent optical measurement of the precipitation reaction by a nephelometric or turbidimetric measurement.
    Type: Grant
    Filed: July 3, 1996
    Date of Patent: August 4, 1998
    Assignee: Behring Diagnostics GmbH
    Inventor: Peter Tuengler
  • Patent number: 5759787
    Abstract: The invention provides novel methods and compositions for detecting kinase activity in solution, without the use of radioactivity. The methods marry the kinetic advantages of solution-based reaction with the efficiency and high-throughput adaptability of solid-phase wash and detection steps, yet is conveniently practiced in a single tube. The methods may be used to assay for kinase activity per se or, by controlling for the kinase activity, for modulators of kinase activity. The method is exemplified with a preferred chemiluminescent protein kinase assay using biotinylated substrate peptides captured on a streptavidin coated microtiter plate and monoclonal antibodies to detect their phosphorylation.
    Type: Grant
    Filed: August 26, 1996
    Date of Patent: June 2, 1998
    Assignee: Tularik Inc.
    Inventor: Berta Strulovici
  • Patent number: 5753518
    Abstract: A method of determining the affinity and kinetic properties of low molecular weight ligands for their interaction with a common receptor comprises the steps of immobilizing the receptor on a sensing structure, mixing in known proportions each ligand with a ligand analogue the response of which on the sensing structure is substantially higher than that of the low molecular weight ligands, contacting each mixture with the sensing structure and measuring the response, and comparing the response of each mixture with that of the ligand analogue alone, the distortion of the ligand analogue response being representative of the affinity and kinetic properties of the ligand.
    Type: Grant
    Filed: November 22, 1995
    Date of Patent: May 19, 1998
    Assignee: Pharmacia AB
    Inventor: Robert Karlsson
  • 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: 5750409
    Abstract: Pentacyclic derivatives having the general formulae (Ia), (Ib) and (Ic) ##STR1## denote: hydrogen, alkyl with 1 to 20 carbon atoms polyoxyhydrocarbyl, phenyl, phenylalkyl with 1 to 3 carbon atoms in the alkyl chain, wherein the alkyl residues or/and phenyl residues can be substituted by one or several hydroxy, halogen, sulfo, carboxy or alkoxycarbonyl groups in which alkoxy can have 1 to 4 carbon atoms;R.sup.7 denotes an alkyl group with 1 to 7 carbon atoms, substituted by at least one halogen, or denotes a carboxyalkyl group or a phenyl group which is substituted by a carboxy or alkoxycarbonyl group located at the o-position relative to the carbon atom bound to the pentacyclic ring system and by at least one halogen, wherein alkoxy can have 1 to 4 carbon atoms, or a carboxymethylene-oxy-alkyloxy group; the residues R.sup.14 and R.sup.
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: May 12, 1998
    Assignee: Boehringer Mannheim GmbH
    Inventors: Rupert Herrmann, Hans-Peter Josel, Karl-Heinz Drexhage, Jutta Arden-Jacob
  • Patent number: 5698401
    Abstract: The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.
    Type: Grant
    Filed: November 14, 1995
    Date of Patent: December 16, 1997
    Assignee: Abbott Laboratories
    Inventors: Stephen W. Fesik, Philip J. Hajduk
  • Patent number: 5688659
    Abstract: SLO peptide antigens are described. These peptide antigens are suitable for the determination of SLO antibodies, as immunogens for the production of antibodies against SLO and as vaccines for the production of vaccines against SLO.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: November 18, 1997
    Assignee: Boehringer Mannheim GmbH
    Inventors: Christoph Seidel, Geoffrey Burns, Wolf-Dieter Engel
  • Patent number: 5679581
    Abstract: There are provided a method and an apparatus for measuring an immunologically active material by physically or chemically immobilizing material immunologically active to a material to be measured of a specimen to the dehydrated solid fine particles, providing a desirable dispersion comprising said immunologically active material immobilized to said solid fine particles and said specimen in a liquid medium, reacting them to cause a reaction mixture in an agglutinated state and optically measuring said agglutinated state of the reaction mixture to thereby quantitatively determine the content of said material to be measured with an improved accuracy.
    Type: Grant
    Filed: January 13, 1995
    Date of Patent: October 21, 1997
    Assignee: Canon Kabushiki Kaisha
    Inventors: Takeshi Miyazaki, Kazumi Tanaka, Masanori Sakuranaga, Tadashi Okamoto
  • Patent number: 5665605
    Abstract: A sample of liquid with suspended particles is contained in a tube and subjected to a standing wave ultrasound field transverse to the tube, the standing wave exhibiting a progressive change in pressure amplitude transverse to the tube, so that particles in suspension are displaced transversely of the tube to one or more predetermined regions; exposure of the sample to the standing wave is then terminated and the particles are allowed to settle, and inspected to determine whether they remain aggregated or whether they dissociate. The ultrasound field is produced by a transducer of tubular form encircling the tube. The invention may be used for agglutination of particles or cells via cross-bridging molecules in immuno-agglutination assays.
    Type: Grant
    Filed: September 8, 1994
    Date of Patent: September 9, 1997
    Assignee: University College Cardiff Consultants Limited
    Inventors: William Terence Coakley, Martin Alan Grundy, Werner Bolex
  • Patent number: 5585241
    Abstract: A method for the flow cytometric assay of an analyte using monodisperse particles carrying a specific binding partner, the analyte and binding partner being selected from the group consisting of (a) antigen and specific antibody, (b) hormone and hormone receptor, (c) hapten and antihapten, (d) polynucleotide and polynucleotide binding protein, (e) biotin and avidin or streptavidin, (f) enzyme and enzyme cofactor and (g) lectin and specific carbohydrate, and the method comprising the steps of adding to the aqueous sample a predetermined amount of particles and a predeterminded amount of a labelled ligand having affinity for the analyte or the binding partner and detecting and quantifying the resulting labelled ligand-carrying particles by a flow cytometer, the method using a pair of different particle types which are distinguishable from each other by the flow cytometer and which respectively carry binding partners having the same specificity but different binding affinity for the analyte and independently but
    Type: Grant
    Filed: June 1, 1995
    Date of Patent: December 17, 1996
    Assignee: Sinvent A/S
    Inventor: Tore Lindmo
  • Patent number: 5583055
    Abstract: An initial rate photometric immunoassay method useful for detecting and quantifying analytes in various physiological fluids is disclosed. The method is carried out by combining in a liquid medium an undiluted sample of analyte-containing physiological fluid, such as serum, and an excess of an anti-analyte antibody. A substantially constant initial rate of increase of the liquid medium's turbidity, due to the resulting immunoprecipitation reaction, is measured in real time and compared to a calibration curve prepared from known analyte concentrations to detect and quantify the analyte. Detection and quantification of numerous analytes including, haptens, drugs and proteins, in a wide variety of physiological fluids can be rapidly carried out by the present method.
    Type: Grant
    Filed: September 6, 1994
    Date of Patent: December 10, 1996
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, Elizabeth K. Kearns
  • Patent number: 5571682
    Abstract: A method for reducing interferent bias such as hemoglobin bias in immunoassays using dried slide test elements featuring peroxidase and leuco dye as the labeling mechanism.
    Type: Grant
    Filed: December 22, 1994
    Date of Patent: November 5, 1996
    Assignee: Johnson & Johnson Clinical Diagnostics, Inc.
    Inventors: Merrit N. Jacobs, Paul A. Kildal-Brandt, Thomas C. Arter
  • Patent number: 5534441
    Abstract: There are provided a method and an apparatus for measuring an immunologically active material by physically or chemically immobilizing a material being immunologically active to a material to be measured of a specimen onto dehydrated solid fine particles, providing a desired dispersed body of said immunologically active material immobilized onto said solid fine particles in a dispersing medium, adding the specimen to said dispersed body while stirring to react the specimen with the immunologically active material, thereby causing a reaction mixture in an agglutinated state and optically measuring said agglutinated state of the reaction mixture to thereby quantitatively determine the content of the material to be measured with an improved accuracy.
    Type: Grant
    Filed: January 13, 1995
    Date of Patent: July 9, 1996
    Assignee: Canon Kabushiki Kaisha
    Inventors: Takeshi Miyazaki, Kazumi Tanaka, Masanori Sakuranaga, Tadashi Okamoto
  • Patent number: 5527710
    Abstract: The rate of a biomolecular reaction, such as an enzymatic reaction or an affinity binding reaction, is measured using electrochemiluminescence ("ECL"). The reaction is conducted in an electrochemical cell with a mixture of reagents including a luminophore which will relate the concentration of a reactant, a reaction partner or the reaction product of a reaction partner to the ECL intensity. The reaction partner is a reagent which reacts with the reactant and which participates with the luminophore (or its reaction product participates with the luminophore) to cause the emission of ECL. The ECL intensity is modulated with a series of electrical pulses which are applied to the mixture of reagents at a preselected potential and for preselected intervals of time and duration. The ECL intensity is measured at the same intervals to provide a timed series of values (P).
    Type: Grant
    Filed: December 2, 1994
    Date of Patent: June 18, 1996
    Assignee: IGEN, Inc.
    Inventors: Laurette Nacamulli, Jonathan K. Leland, Stephanie A. Hayes
  • Patent number: 5491095
    Abstract: A system and method of determining absence or presence of an illicit substance in a flowing mixture of requisite reagents by agglutination or lack thereof. A plurality of photodetectors are positioned over an illuminated read area oblique to a path of the flowing mixture. Signal samples of each of the detectors are processed individually. Successive samples are processed over a period time to detect differences or edges between relatively clear liquid and relatively opaque clusters in the flowing mixture. The illicit substance is determined in accordance with the number of variations in signal samples for a predetermined number of detectors.
    Type: Grant
    Filed: May 26, 1993
    Date of Patent: February 13, 1996
    Assignee: Westinghouse Electric Corp.
    Inventors: Stephen Bepko, Donald M. McIver, Francis J. Kaisler
  • Patent number: 5453356
    Abstract: A chemical moiety is disclosed which comprises a chemical, biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organometallic compounds. Methods are disclosed for detecting very small amounts of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labelling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labelled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labelled substances are of particular use in homogeneous binding assays.
    Type: Grant
    Filed: November 30, 1993
    Date of Patent: September 26, 1995
    Assignee: Igen, Inc.
    Inventors: Allen J. Bard, George M. Whitesides
  • Patent number: 5447440
    Abstract: The present invention relates to an apparatus for conducting a variety of assays that are responsive to a change in the viscosity of a sample fluid and relates to methods of conducting such assays. In particular, the present invention is related to the use of a cartridge for conducting one or more coagulation assays or, conversely, fibrinolysis assays. The disclosed device enjoys simplicity and is adaptable to the point-of-care clinical diagnostic area, including use in accident sites, emergency rooms, surgery or intensive care units.
    Type: Grant
    Filed: October 28, 1993
    Date of Patent: September 5, 1995
    Assignee: I-Stat Corporation
    Inventors: Graham Davis, Imants R. Lauks, Michael P. Zelin
  • Patent number: 5431793
    Abstract: A method useful for determining the content of a first hemoglobin in a blood sample which also contains other forms of hemoglobin is based on capillary electrophoresis. In the method, a specific binding partner to the first form of hemoglobin is added to the sample, and the sample is then subjected to capillary electrophoresis. The method is particularly suited for the determination of the percentage of Hb A.sub.1c in a blood sample using anti-Hb A.sub.1c antibody.
    Type: Grant
    Filed: July 29, 1994
    Date of Patent: July 11, 1995
    Assignee: Beckman Instruments, Inc.
    Inventors: Hann-Ping Wang, Zara Safarian
  • Patent number: 5432099
    Abstract: A method for determining the ambient concentrations of a plurality of analytes in a liquid sample of volume V liters, comprisesloading a plurality of different binding agents, each being capable of binding specifically and reversibly an analyte of interest onto a support means at a plurality of spaced apart locations such that not more than 0.
    Type: Grant
    Filed: December 1, 1992
    Date of Patent: July 11, 1995
    Assignee: Multilyte Limited
    Inventor: Roger P. Ekins
  • Patent number: 5422281
    Abstract: A novel bidentate conjugate has two different chemical moieties, or bidentate members, attached through an adequate spacer moiety. Each bidentate member acts as a small molecule ligand and is capable of specifically binding to a different macromolecular substance. The bidentate members are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected so that both bidentate members can simultaneously bind to their respective specific binding partners. Where the specific binding partners are multivalent, large complexes can be formed. The formation of these complexes can be inhibited by the presence of an unconjugated monovalent bidentate member, such as free analyte from a test sample. The bidentate is of particular use in turbidimetric or nephelometric inhibition immunoassay procedures.
    Type: Grant
    Filed: July 31, 1992
    Date of Patent: June 6, 1995
    Assignee: Beckman Instruments, Inc.
    Inventors: Paul C. Harris, Chan S. Oh
  • 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: 5376249
    Abstract: Disclosed are methods and apparatus for determining the presence of one or more analytes in a sample, wherein the presence of a complex of an analyte and an analyte-specific binding moiety is detected at a location in an elongate pH gradient corresponding to a predetermined isoelectric point of the complex in the gradient. An electric field applied across the elongate pH gradient prior to the detection of the complex transports the complex to the location in the pH gradient corresponding to the predetermined isoelectric point. The analyte-specific binding moiety preferably is provided with a detectable label such as a fluorescent label. A parameter, e.g., fluorescence intensity, indicative of the amount of the complex at the location in the pH gradient corresponding to the predetermined isoelectric point may be determined to quantitate the analyte.
    Type: Grant
    Filed: November 25, 1992
    Date of Patent: December 27, 1994
    Assignee: PerSeptive Biosystems, Inc.
    Inventors: Noubar B. Afeyan, Fred E. Regnier
  • Patent number: 5371021
    Abstract: An initial rate photometric immunoassay method useful for detecting and quantifying analytes in various physiological fluids is disclosed. The method is carried out by combining in a liquid medium an undiluted sample of analyte-containing physiological fluid, such as serum, and an excess of an anti-analyte antibody. A substantially constant initial rate of increase of the liquid medium's turbidity, due to the resulting immunoprecipitation reaction, is measured in real time and compared to a calibration curve prepared from known analyte concentrations to detect and quantify the analyte. Detection and quantification of numerous analytes including, haptens, drugs and proteins, in a wide variety of physiological fluids can be rapidly carried out by the present method.
    Type: Grant
    Filed: July 17, 1992
    Date of Patent: December 6, 1994
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, Elizabeth K. Kearne
  • Patent number: 5366858
    Abstract: The present invention provides a method of detecting microorganisms, comprising the step of converting physical forms of microorganisms by antigen-antibody reaction and successively measuring the information that shows the physical forms of the converted data, and the step of comparing a statistical pattern of the values thus measured and a reference statistical pattern of a control subjected to no antigen-antibody reaction, thus detecting the microorganisms of interest. A change in both patterns, i.e., no correspondence thereof, enables recognition of the presence of the microorganisms of interest.
    Type: Grant
    Filed: September 18, 1992
    Date of Patent: November 22, 1994
    Assignees: Canon Kabushiki Kaisha, Meiji Seika Kaisha
    Inventors: Naohisa Koizumi, Shokichi Nakajima, Naoki Yuguchi, Kazumi Tanaka
  • Patent number: 5344534
    Abstract: A kinetic reaction mixture is sampled continuously for determining the effect of a specific agent on the population density of a bio-organic molecule of interest as a function of time. A reaction sample containing the molecule of interest is processed through a high performance liquid chromatography column which produces longitudinal separation of a specific bio-organic molecule of interest. A continuous stream of longitudinally separated bio-organic molecules having a specific property of interest is delivered as a flowing stream into longitudinally separated sample receiving apertures formed in the face of a gel slab. Movement of the delivery nozzle and separation of the sample receiving apertures cause sample batches of reaction products to be deposited within separate channels, with the number of receiving channels corresponding generally with the number of discrete sample time intervals.
    Type: Grant
    Filed: March 5, 1993
    Date of Patent: September 6, 1994
    Inventor: Robert S. Danziger
  • Patent number: 5254460
    Abstract: A new ligand binding assay is based upon measurements of relaxation rates of the solvent, which are obtained with a magnetic resonance (MR) spectrometer. It is termed a solvent mediated relaxation assay system (SMRAS). SMRAS is based on the observation that the enhancement of proton relaxation rates produced by a magnetic material can be modulated by the binding of various analytes to a magnetic material. Hence the relaxation rate of the solvent can be interpreted to give information on the concentration of an analyte.
    Type: Grant
    Filed: May 3, 1991
    Date of Patent: October 19, 1993
    Assignee: Advanced Magnetics, Inc.
    Inventors: Lee Josephson, Edward T. Menz, Ernest V. Groman
  • Patent number: 5252492
    Abstract: A method disclosed for studying the interaction in solution of two molecules of the type such as a ligand and a receptor that are capable of reacting or binding with each other. The method comprises preparing an aliquot of a solution containing the first of the molecules. The second of the molecules is then added to the aliquot. A fluorescently labeled molecule is added to the aliquot, wherein the fluorescently labeled molecule is also capable of reacting or binding with the second of the molecules. A porous matrix that is optically transparent is immersed into the aliquot containing the two molecules being studied and the fluorescently labeled molecule, wherein the second molecule and any fluorescently labeled molecule bound thereto is sterically hindered from permeating the porous, optically transparent matrix, while any unbound fluorescently labeled molecule permeates the matrix.
    Type: Grant
    Filed: March 12, 1991
    Date of Patent: October 12, 1993
    Assignee: University of Utah Research Foundation
    Inventor: Doju Yoshikami