Signal Modification Or Steric Inhibition Patents (Class 436/537)
  • Patent number: 5459045
    Abstract: A reagent for use in an immunoassay for measuring haptens, antigens or antibodies by means of a competitive binding method, which comprises a combination of an antibody and a labelled hapten or a labelled antigen or a combination of a hapten or an antigen and a labelled antibody, wherein the antibody and the labelled hapten or the labelled antigen in one combination or the hapten or the antigen and the labelled antibody in another combination are capable of undergoing reversible binding, and a device for use in an immunoassay wherein the reagent of the present invention is included in a single container.An immunoassay can be performed in a short time by the use of the immunoassay device of the present invention.
    Type: Grant
    Filed: November 10, 1993
    Date of Patent: October 17, 1995
    Assignee: Mochida Pharmaceutical Co., Ltd.
    Inventors: Hiroshi Sato, Tadakazu Yamauchi, Toshio Izako, Masahiro Nobuhara, Ei Mochida
  • Patent number: 5447846
    Abstract: An enzyme-labelled antibody adapted for use in a homogeneous immunoassay is provided. The enzyme-labelled antibody is a conjugate of an enzyme with two or more different monoclonal antibodies, each of the monoclonal antibodies being capable of specifically recognizing and binding to a different epitope of the same antigen. By using the enzyme-labelled antibody in the homogeneous enzyme immunoassay process, an analyte can be quantitatively analyzed at a higher sensitivity through a simple operation. Also provided is a dry immunoassay element comprising an immunological reaction layer containing the enzyme-labelled antibody. By the provision of such an immunoassay element, a further simplified quick analysis of an analyte is realized to give an accurate result.
    Type: Grant
    Filed: July 14, 1993
    Date of Patent: September 5, 1995
    Assignee: Fuji Photo Film C., Ltd.
    Inventors: Hiroshi Shinoki, Masashi Ogawa
  • 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: 5445972
    Abstract: A Raman label which, upon radiation, produces a detectable Raman scattering signal in a ligand-binding assay for an analyte in a test sample. A conjugate containing a Raman label attached to a specific binding member.
    Type: Grant
    Filed: July 22, 1993
    Date of Patent: August 29, 1995
    Assignee: Abbott Laboratories
    Inventors: Peter J. Tarcha, Thomas E. Rohr, Therese Cotton, Gary E. Winter
  • 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: 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: 5434052
    Abstract: Compounds are evaluated for their binding to naturally occurring receptors, by employing the natural ligand conjugated to an enzyme donor fragment of .beta.-galactosidase for competing with the sample compound for the natural acceptor binding site or in the absence of competition where the sample compound binds to an allosteric site. By adding the enzyme acceptor fragment of the .beta.-galactosidase and substrate, the binding affinity of the sample compound may be evaluated as a measure of agonist or antagonist capability.
    Type: Grant
    Filed: July 21, 1993
    Date of Patent: July 18, 1995
    Assignee: Microgenics Corporation
    Inventor: Pyare Khanna
  • Patent number: 5432101
    Abstract: The invention relates to macropolycyclic rare earth complexes, namely cryptates which are useful as fluorescent tracers.
    Type: Grant
    Filed: December 17, 1992
    Date of Patent: July 11, 1995
    Assignee: Compagnie Oris Industrie SA
    Inventors: Gerard Mathis, Jean-Marie Lehn
  • Patent number: 5415998
    Abstract: The invention concerns a method of homogeneous immunoassay of a ligand in a liquid test sample which comprises: a)incubating a mixture of (1) the liquid test sample; (1i) where the ligand under assay has only one epitope, a covalent conjugate of the ligand with any mono- or poly-epitope molecule having at least one epitope distinct from the epitope of the ligand; (2) a labile enzyme; (3) a first bispecific monoclonal antibody protecting the activity of the encyme through binding to a first epitope on the encyme and capable of binding the ligand under assay; and (4) a second bispecific monoclonal antibody capable of bonding said enzyme and a second distinct epitope on the ligand under assay or an epitope of the said covalent conjugate; whereby a quaternary immunocomplex is formed; b) after incubation, subjecting the mixture to conditions whereby any enzyme not present in such a quaternary immunocomplex is inactivated; and c) determining the amount of detectable encyme, the determination being related to the am
    Type: Grant
    Filed: August 7, 1991
    Date of Patent: May 16, 1995
    Assignee: Applied Research Systems ARS Holding N.V.
    Inventors: Franco Celada, Gyorgy Gorog
  • Patent number: 5413911
    Abstract: Method and reagents for determining a compound of interest present in a test sample also containing one or more interfering compounds having substantially similar chemical structures, and otherwise analytically indistinguishable from each other, employing a pretreatment reagent capable of selectively modifying the chemical structure of one of the compounds without significantly modifying or altering the chemical structure of the other one of the compounds.
    Type: Grant
    Filed: December 14, 1990
    Date of Patent: May 9, 1995
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Charles A. Harrington, Daryl E. Hartter, Robert E. Hruska
  • Patent number: 5407835
    Abstract: Immunoassay methods and reagents for the specific quantification of amitriptyline or nortriptyline in a test sample are disclosed employing antibodies prepared with amitriptyline or nortriptyline derivatives of the Formula III: ##STR1## wherein for amitriptyline, R is CH.sub.3, and for nortriptyline, R is H. The present invention also describes the synthesis of unique fluorescein tracers of the structure of Formula IV and Formula V: ##STR2## wherein for a specific amitriptyline immunoassay, W.sub.1 is a heteroatom linked to the aromatic ring at the 2 or 3 position, and for a specific nortriptyline immunoassay, W.sub.2 is two heteroatoms linked together and attached to the aromatic ring at the 2 or 3 position, and wherein Q is a detectable moiety, preferably fluorescein or a fluorescein derivative.
    Type: Grant
    Filed: July 24, 1992
    Date of Patent: April 18, 1995
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Donald Johnson, Daryl E. Hartter
  • Patent number: 5407834
    Abstract: The present invention is directed to a fluorescence polarization assay for phencyclidine and phencyclidine derivatives, to the various components needed for preparing and carrying out such an assay, and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them, and a reagent kit containing them. The tracers and the immunogens are made from substituted phencyclidine compounds. A fluorescein moiety is included in the tracer, while a poly(amino acid) forms a part of the immunogen. The assay is conducted by measuring the degree of polarization retention of plane polarized light that has been passed through a sample containing antiserum and tracer.
    Type: Grant
    Filed: April 27, 1992
    Date of Patent: April 18, 1995
    Assignee: Abbott Laboratories
    Inventors: Robert E. Dubler, Mary P. Frintner, Jonathan Grote, Gregg A. Hadley, David J. Hawksworth, Hal D. Hopkins, Daniel S. Nam, Frank S. Ungemach, Larry K. Wray
  • Patent number: 5399486
    Abstract: A disposable diagnostic unit is provided which employs a housing which provides for a sample port, and a channel which feeds the sample to an incubation area by means of capillary action. The incubation area is underneath an optically-clear window and comprises a lipid membrane which has optical properties, particularly fluorescent properties and usually a reagent. A reservoir at the end of the channel downstream from the incubation area receives the sample and waste washes, while on one side of the platform area is a reagent reservoir and on the other side a side waste reservoir, so that one can move the reagent from the reagent reservoir through the platform area into the waste reservoir. Various reagents may be contained within the unit and the necessary liquids added automatically by appropriate instrumentation, so as to have the assay carried out automatically, without technician involvement, providing an accurate and sensitive determination.
    Type: Grant
    Filed: February 18, 1993
    Date of Patent: March 21, 1995
    Assignee: Biocircuits Corporation
    Inventors: Cheryl A. Cathey, Henry L. Schwartz
  • Patent number: 5387527
    Abstract: A method for correcting for light scattering affects obtained from a sample to which a fluorophore has been added. In accordance with the invention, a sample to which a fluorophore has been added is irradiated with light in the adsorption band of the fluorophore such that the fluorophore emits light at a different intensity. By manipulating the pH of the sample, and obtaining both pre- and post-manipulation emission light intensity readings, the value of the reading attributed to "light scattering" can be determined, such that correction of an erroneous fluorescence reading can be obtained.
    Type: Grant
    Filed: June 26, 1992
    Date of Patent: February 7, 1995
    Assignee: Beckman Instruments, Inc.
    Inventor: James C. Sternberg
  • Patent number: 5356820
    Abstract: Disclosed is a substantially optically pure hapten, useful in an immunoassay for dextropropoxyphene and/or nordextropropoxyphene. The hapten corresponds to a specified structural formula (IX).Also disclosed is an immunogen derived from the hapten as well as an antibody raised in response to an immunogen derived from the hapten.Also disclosed is a fluorescent tracer derived from a substantially optically pure compound corresponding to the hapten, the tracer being useful in an immunoassay for dextropropoxyphene and/or nordextropropoxyphene.Also disclosed is an improved immunoassay for determining dextropropoxyphene and/or nordextropropoxyphene in a biological sample involving a step of contacting the sample with antibodies raised in response to the immunogen.
    Type: Grant
    Filed: May 12, 1993
    Date of Patent: October 18, 1994
    Assignee: Abbott Laboratories
    Inventors: Robert E. Dubler, Jonathan Grote, Donna R. Kuhn
  • Patent number: 5354693
    Abstract: A fluorescence polarization immunoassay (FPIA) for detecting the presence of one or more amphetamine-class analytes in a test sample is provided. The immunoassay uses competition between the analyte and a fluorescently labeled tracer for the binding site on an antibody specific for phenethylamine derivatives. The concentration of amphetamine-class analyte in the sample determines the amount of tracer that binds to the antibody. The amount of tracer-antibody complex formed can be quantitatively measured and is inversely proportional to the quantity of analyte in the test sample. The invention relates to tracers, to immunogens used to elicit antibodies for use as assay reagents, and to assay kits incorporating these tracers and assay reagents.
    Type: Grant
    Filed: June 29, 1993
    Date of Patent: October 11, 1994
    Assignee: Abbott Laboratories
    Inventors: Paul J. Brynes, Donald D. Johnson, Cynthia M. Molina, Charles A. Flentge, Patrick F. Jonas
  • Patent number: 5346832
    Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is chemically bonded to a suitable carrier molecule, which is also chemically bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.
    Type: Grant
    Filed: December 18, 1992
    Date of Patent: September 13, 1994
    Assignee: Ciba Corning Diagnostics Corp.
    Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
  • Patent number: 5344784
    Abstract: The invention relates to a device for use in optical methods of assay. The device comprises an optical structure comprising a dielectric substrate (2) and a thin film waveguide (5), between which is interposed a buffer layer (4). The waveguide carries a layer (10) of reagent suitable for a desired assay. The invention also relates to methods of using the device in an assay.
    Type: Grant
    Filed: May 21, 1991
    Date of Patent: September 6, 1994
    Assignee: Applied Research Systems ARS Holding N.V.
    Inventor: John W. Attridge
  • Patent number: 5342789
    Abstract: A method for quantifying glucose concentration in blood, body fluids, and other samples within, below and above the normal physiological range, which relies on non-radiative fluorescence resonance energy transfer, as well as devices useful in quantifying blood glucose concentration using the present method.
    Type: Grant
    Filed: December 14, 1989
    Date of Patent: August 30, 1994
    Assignee: Sensor Technologies, Inc.
    Inventors: William L. Chick, David E. Wolf, Richard A. Cardullo
  • Patent number: 5340750
    Abstract: Immunoassay methods and reagents for the specific quantification of imipramine or desipramine in a test sample are disclosed. The measurement of imipramine or desipramine is accomplished in a specific immunoassay employing antibodies prepared with imipramine or desipramine derivatives of the Formula III: ##STR1## wherein P is an immunogenic carrier material, X is two heteroatoms, Y is a linking group comprising from 1 to 6 carbon atoms and P is an immunogenic carrier material, and wherein for imipramine, R is CH.sub.3, and for desipramine, R is H.The present invention also describes the synthesis of unique labeled reagents of the structure of the Formula IV: ##STR2## wherein Z is a linking group comprising 1 to 4 carbon atoms and 0 to 2 heteroatoms and Q is a detectable moiety, preferably fluorescein or a fluorescein derivative, and wherein for imipramine, R.sub.1 is CH.sub.3, and for desipramine, R.sub.1 is H.
    Type: Grant
    Filed: July 24, 1992
    Date of Patent: August 23, 1994
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Charles A. Harrington, Donald Johnson
  • Patent number: 5336622
    Abstract: A fluorescence polarization immunoassay for flecainide and tracers therefor are disclosed.
    Type: Grant
    Filed: April 11, 1989
    Date of Patent: August 9, 1994
    Assignee: Abbott Laboratories
    Inventor: Daniel F. Heiman
  • Patent number: 5332661
    Abstract: Immunoassay methods and reagents for the quantification of total doxepins (i.e., E-doxepin, Z-doxepin, E-desmethyldoxepin, and Z-desmethyldoxepin) in a test sample are disclosed. The quantification of total doxepins is accomplished in an immunoassay employing antibodies and labeled reagents prepared with doxepin derivatives of the Formula II: ##STR1## wherein Y--Z can be C.dbd.CH or N--CH.sub.2, R.sub.` is a linking group, R.sub.2 can be H or CH.sub.3, and Q can be a detectable moiety or an immunogenic carrier material. The antibody reagent comprises antibodies which are capable of binding to total doxepins and which are produced with one or more immunogens prepared from the doxepin derivative of Formula II, and the labeled reagent is also prepared from the doxepin derivative of Formula II.
    Type: Grant
    Filed: July 24, 1992
    Date of Patent: July 26, 1994
    Assignee: Abbott Laboratories
    Inventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Donald Johnson, Robert E. Hruska
  • 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: 5328828
    Abstract: The instant invention is directed toward an immunoassay which can determine the presence of amphetamines in a sample suspected of containing amphetamine and/or methamphetamine by employing at least two conjugates, each comprised of a functionally similar label bound to an amphetamine analog and a methamphetamine analog respectively and an antibody to amphetamine and an antibody to methamphetamine wherein at least one of the antibodies is a monoclonal antibody.
    Type: Grant
    Filed: July 20, 1992
    Date of Patent: July 12, 1994
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Mae W. Hu, Cheng-I Lin, Chen-jung Hsu, James V. Freeman, Marcel Pirio, Edwin F. Ullman
  • Patent number: 5316909
    Abstract: The invention relates to a method based on fluorescence, especially time-resolved fluorescence for quantitative assay of a bioaffinity reaction involving bioaffinity components. The method comprises the labelling of one or several of the bioaffinity components participating in the reaction with a lanthanide chelate, forming of a lanthanide chelate for a fluorescence measurement after the reaction, and measuring the fluorescence of the chelate. The lanthanide (Eu, Tb, Sm or Dy) is brought to a strongly fluorescent form before the fluorescence measurement by incorporating the lanthanide in an aggregated particle that comprises the lanthanide chelate and a chelate of a fluorescence-increasing ion (Y, Gd, Tb, Lu or La) to bring about a cofluorescence effect. An aliphatic or aromatic beta-diketone is used as the chelating compound in the aggregate.
    Type: Grant
    Filed: March 13, 1992
    Date of Patent: May 31, 1994
    Assignee: Wallac Oy
    Inventor: Yongyuan Xu
  • Patent number: 5314802
    Abstract: A substance having binding sites for at least two molecules may be detected within a sample. A molecule which can be recognized by the substance is labelled such that when at least two of the labelled molecules are bound the binding sites on the substance, the labels on the molecules electronically interact with each other and vary the wavelength dependance of their spectra. This variation in the spectra of the label can be detected. If the sample is suspected of containing the unlabelled form of a molecule, such as biotin or cocaine, a known amount of the above substance, along with a known amount of the corresponding labelled biotin or cocaine is added to the sample. In this instance, the amount of the suspect molecule in the sample is then determined by the extent to which the variation in the spectra of the label has been reduced. Alternatively, the present invention can be used to determine the binding characteristics of the substance within the sample.
    Type: Grant
    Filed: April 9, 1992
    Date of Patent: May 24, 1994
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventor: David A. Kidwell
  • Patent number: 5310687
    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 low concentrations of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labeling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labeled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labeled substances are of particular use in homogeneous binding assays.
    Type: Grant
    Filed: November 4, 1991
    Date of Patent: May 10, 1994
    Assignee: Igen, Inc.
    Inventors: Allen J. Bard, George M. Whitesides
  • Patent number: 5302533
    Abstract: A method of increasing the light output from a chemiluminescent reaction of a dihydrophthalazinedione (DPD), and an oxidant, which comprises carrying out said reaction in the presence of at least one antibody, raised against an intermediate species of said chemiluminescent reaction.
    Type: Grant
    Filed: April 10, 1992
    Date of Patent: April 12, 1994
    Assignee: British Technology Group Limited
    Inventor: Larry J. Kricka
  • 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: 5284778
    Abstract: This invention provides a quantitative assay for determining the amount of a biologically active ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone present in a sample comprising contacting the sample with both the receptor to which the ligand naturally binds in order to effect its biologicaly activity and a monoclonal antibody directed to the ligand or to a complex of the ligand and the receptor so as to form a complex of the ligand bound to both the receptor, at the site to which the ligand naturally binds to the receptor, and the monoclonal antibody. In the complex so formed, either the receptor or the monoclonal antibody is labeled with a detectable marker and a determination is made of the amount of labeled receptor or of labeled monoclonal antibody bound to the ligand or the amount of labeled receptor or of labeled monoclonal antibody not bound to the ligand, or both such amounts.
    Type: Grant
    Filed: September 12, 1991
    Date of Patent: February 8, 1994
    Assignees: The Trustees of Columbia University in the City of New York, The University of Medicine & Dentistry of New Jersey
    Inventors: Robert E. Canfield, E. Glenn Armstrong, William R. Moyle, Gordon J. MacDonald, Donna M. Anderson
  • Patent number: 5279943
    Abstract: The present invention relates to a homogeneous process for the detection and/or determination of an analyte in a medium in which it may be present, by disclosing the reaction product of the analyte and a corresponding receptor, process consisting in: 1) adding to said medium a first reagent consisting of a receptor for the said analyte; 2) adding a second reagent consisting of at least one of the components of the reaction product of the analyte and at least one of its receptors; one of the two reagents being coupled with a luminescent compound and the other reagent possessing a heavy atom or units containing a heavy atom; 3) incubating the medium after addition of each reagent or after the addition of both reagents; 4) exciting the resulting medium and 5) measuring at equilibrium or during the kinetics, the signal emitted by the luminescent compound, said signal being modulated by the heavy atom effect.
    Type: Grant
    Filed: January 19, 1993
    Date of Patent: January 18, 1994
    Assignee: Compagnie Oris Industrie
    Inventors: Gerard Mathis, Thierry Davin
  • Patent number: 5278043
    Abstract: Energy-transfer systems which can be used, inter alia, for measuring distances within or between different molecules are described, comprising derivatives of lumazine and ruthenium, in particular derivatives of DNA or RNA sequences.
    Type: Grant
    Filed: January 22, 1991
    Date of Patent: January 11, 1994
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Wilhelm Bannwarth, Francis Muller
  • Patent number: 5264373
    Abstract: This disclosure related to a method and reagents for determining tetrahydrocannabinoids (THC) and THC metabolites in a biological fluid such as urine. In particular, this disclosure relates to a fluorescence polarization immunoassay procedure for determining the presence of THC and to a novel class of tracer compounds employed as reagents in such procedures. The procedure described also provides for novel wash reagent for a THC fluorescence polarization assay.
    Type: Grant
    Filed: September 1, 1992
    Date of Patent: November 23, 1993
    Assignee: Abbott Laboratories
    Inventors: Nai-Yi Wang, Robert E. Dubler, Frank S. Ungemach, Roland L. Walters, Susan A. Thacker
  • Patent number: 5262333
    Abstract: This disclosure relates to a method and reagents for determining amphetamine and d-methamphetamine in a biological fluid, such as urine. In particular, this disclosure relates to improvements in a fluorescence polarization immunoassay procedure for determining the presence of amphetamine and d-methamphetamine in a single assay and to a novel class of tracer compounds employed as reagents in such procedures. The procedure described includes pretreatment of the biological sample to eliminate cross reactants such as .beta.-hydroxyphenethylamine by preincubating the sample solely with an aqueous periodate solution having a pH from about 4.0 to about 7.5 without adjustment to an alkaline pH, and contacting the sample with riboflavin binding protein to reduce interference from fluorescent components in the sample. The procedure also maintains the cross reactivity of the immunoassay for tyramine at about 0.4% and for 1-methamphetamine below about 5.
    Type: Grant
    Filed: June 12, 1992
    Date of Patent: November 16, 1993
    Assignee: Abbott Laboratories
    Inventors: Daniel F. Heiman, Sharon A. Johnson, Hsiang-Yun Y. Hu
  • Patent number: 5254477
    Abstract: A variety of conjugated compositions and methods for the detection of an analyte of interest in a fluid sample is provided which relies upon an intramolecular energy transfer between a conjugated fluorophore and a chromophoric light-absorbing ligand for qualitative and quantitative results. The detection methods preferably employ fiber optic sensors in combination with analyte-insensitive fluorophores and analyte-sensitive absorber ligands in conjugated form. The methods and compositions rely upon the ability of the absorbing ligands to absorb energy which is transferred non-radiatively by the fluorophore when in an excited state.
    Type: Grant
    Filed: September 19, 1991
    Date of Patent: October 19, 1993
    Assignee: Trustees of Tufts College
    Inventor: David R. Walt
  • 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
  • Patent number: 5244785
    Abstract: A method for detecting the presence of a high-molecular-weight analyte, which uses a variation on complementation assays, comprising (1) providing an enzyme donor (ED)complex comprising ED coupled to an analyte-specific binding molecule, wherein the ED complex retains measurable complementation activity such that active .beta.-galactosidase is formed in the presence of an enzyme acceptor (EA); (2) contacting the ED complex and EA in the presence of a sample suspected of containing a high-molecular-weight analyte that reacts specifically with the analyte-specific binding molecule; and (3) relating the presence of the analyte in the sample to the formation of active .beta.-galactosidase enzyme.
    Type: Grant
    Filed: February 1, 1991
    Date of Patent: September 14, 1993
    Assignee: Microgenics Corporation
    Inventors: Rueyming Loor, Jeff Shindelman, Pyare L. Khanna
  • Patent number: 5229302
    Abstract: A fluorescence immunoassay method is described in which the presence or absence of antigen is measured within one minute by measuring a variation in fluorescence emitted from an antibody. The method comprises reaction between a pseudo-antigen obtained by chemical combination of an antigen and a fluorescent quencher and an antibody by which fluorescence to be emitted from the antibody is quenched by the action of the quencher combined. When an analyte is added to a solution of the combination, the pseudo-antigen is replaced by an antigen if the analyte contains the antigen, so that the fluorescence increases in intensity. This intensity is measured and compared with the initially measured intensity to detect the presence of the antigen. The method does not make use of the action of antigen on antibody with respect to the fluorescence of the antibody and is applicable to all antigens.
    Type: Grant
    Filed: February 3, 1992
    Date of Patent: July 20, 1993
    Assignee: Matsushita Electric Industrial Co., Ltd.
    Inventors: Jinsei Miyazaki, Noboru Motoyama, Tadayasu Mitsumata
  • Patent number: 5225516
    Abstract: The invention provides a polymer comprising a chain of detectable units joined together by linker arms.The detectable units may be, for example, antigenic or form part of a fluorescent or chemiluminescent or chromogenic or enzyme signal system.The polymer may find an application in the assay of an analyte which is a member of a specific binding pair.The invention also provides a labelled reagent in which the reagent is a member of a specific binding pair and the label is a polymer in accordance with the invention. The invention further provides an assay involving the use of a labelled reagent in accordance with the invention. Also the invention provides a kit for performing an assay, which kit includes a supply of a labelled reagent in accordance with the invention.
    Type: Grant
    Filed: November 21, 1990
    Date of Patent: July 6, 1993
    Assignee: The General Electric Company, p.l.c.
    Inventor: Ramadan A. Abuknesha
  • Patent number: 5206179
    Abstract: A methodology is presented which relates in general to fluorescence polarization immunoassays (FPIA) and modifications of current processes wherein detection and quantification of several commonly abused or therapeutic drugs in a single biological fluid sample are determined utilizing manual or current software or related equipment to allow the sequential and simultaneous performance of more than one FPIA assay. The methodology involves combining the reagents either separately or pre-mixed, for multiple assays in a single reagent package, these reagents being used to assay quantitative amounts of each of the assay analytes in a sequential step manner. The assay being performed by mixing the sample with a combination reagent and then initiating a specific reaction for each of the separate analytes by sequentially adding a specific reagent, i.e.
    Type: Grant
    Filed: March 25, 1991
    Date of Patent: April 27, 1993
    Assignee: Abbott Laboratories
    Inventor: Jack F. Ramsey
  • Patent number: 5206143
    Abstract: Methods for distinguishing multiple subpopulations of biological particles in a single sample based upon quantitative differences in the fluorescence intensity attributable to one or two fluorochromes with which the biological particles are labelled. The method is used with flow cytometric particle counting techniques to count and sort and biological particles such as the formed elements of blood and other tissue cells. Also disclosed are reagents containing fluorochrome-conjugated antibodies used in the methods.
    Type: Grant
    Filed: January 6, 1992
    Date of Patent: April 27, 1993
    Assignee: SmithKline Beecham Corporation
    Inventors: Paul K. Horan, Sue E. Slezak
  • Patent number: 5202270
    Abstract: The present invention is directed to a fluorescence polarization assay for benzoyl ecgonine and substituted benzoyl ecgonine compounds in biological fluids, and to a method of making reagents therefor. Specifically, tracers, immunogens and antibodies are disclosed. The tracers and the immunogens are made from substituted benzoyl ecgonine compounds. A fluorescein moiety is included in the tracer, while a poly(amino acid) forms a part of the immunogen. The assay is conducted by measuring the degree of polarization retention of plane polarized light that has been passed through a sample containing antiserum and tracer.
    Type: Grant
    Filed: August 30, 1990
    Date of Patent: April 13, 1993
    Assignee: Abbott Laboratories
    Inventors: Frank S. Ungemach, Daniel S. Nam, Oliver H. Meek
  • Patent number: 5198367
    Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is covalently bonded to a suitable carrier molecule, which is also covalently bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.
    Type: Grant
    Filed: June 9, 1989
    Date of Patent: March 30, 1993
    Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
  • Patent number: 5190857
    Abstract: A luminescence measuring system is provided for detecting luminescence at extremely low concentrations of luminescing moieties. The method employs alternating radiation at a plurality of loci of an inhomogenous solution, where the radiant power is maintained constant, and the irradiated volumes of pairs of loci are systematically varied. With the probability being very low that the same luminescence signal will be obtained in the two or more measurements, by comparing the measurements, one can detect a low luminescence signal in the presence of relatively high noise levels. Various techniques are described for modulating the irradiance and detecting changes in signal.
    Type: Grant
    Filed: June 5, 1991
    Date of Patent: March 2, 1993
    Assignee: Acrogen, Inc.
    Inventors: Fritz S. Allen, Carlos Bustamante, Thomas M. Niemczyk, Burton P. Dorman
  • Patent number: 5187106
    Abstract: A fluorescence decay time method and apparatus directly measuring the time decay function resulting from a plurality of fluorescing bodies, including background, and analytically determines the presence and concentration of the fluorescing bodies homogeneously and simultaneously is disclosed.The fluorescently labelled reaction product of a target ligand, such as an antigen, with a binding molecule for the ligand, such as an antibody, exhibits a fluorescent decay time curve which bears a direct straight line relationship to the concentration of the target antigen, in that the value for fluorescent intensity at time zero for the decay time curve is a measure of said concentration.The time zero intensity is proportional to the concentration of the target ligand in the unknown sample which can then be compared to the concentrations from a standard curve.
    Type: Grant
    Filed: August 30, 1984
    Date of Patent: February 16, 1993
    Assignee: Orbit Medical Systems, Inc.
    Inventors: Robert W. Fritzsche, Kenneth J. Schlager
  • Patent number: 5173406
    Abstract: A liposome immunoassay comprising the steps of reacting an analyte antigen, a liposome bearing antibody comprising a first antibody to the analyte antigen and a liposome encapsulating a marker therein linked to the antibody, and a second antibody to the analyte antigen to form an antigen-antibody complex, releasing the marker from the liposome in an amount depending on an amount of the analyte antigen in the presence of a complement, and measuring the released marker to determine the analyte antigen, characterized in using a third antibody capable of binding directly or indirectly to the second antibody and having an ability to activate the complement; andA kit for liposome immunoassay comprising at least one of; (1) an liposome bearing antibody comprising a first antibody to an analyte antigen and liposome encapsulating a marker therein linked to the antibody; (2) a second antibody to the analyte antigen; (3) a third antibody capable of binding directly or indirectly to the second antibody and having an abil
    Type: Grant
    Filed: January 5, 1989
    Date of Patent: December 22, 1992
    Assignee: Teijin Limited
    Inventors: Kenji Hosoda, Hideaki Suzuki, Tatsuji Yasuda
  • Patent number: 5173434
    Abstract: A process to determine the concentration of any substance in a colorimetric, turbidimetric or nephelometric reaction using a fluorometric detector to measure fluorescence intensity. In particular, a change in color can be monitored by observing the measurement of fluorescence intensity of a fluorophore in an inert matrix. The absorption spectrum of the chromophore may overlap the excitation and/or emission spectrum of the fluorophore, thereby allowing the change in fluorescence to be related to the intensity of color in the reaction and thus related to the quantity of the substance of interest.
    Type: Grant
    Filed: November 5, 1990
    Date of Patent: December 22, 1992
    Assignee: Baxter Diagnostics Inc.
    Inventors: Roger J. Morris, Shoshana Bascomb, Carolyn S. Olson
  • Patent number: 5168057
    Abstract: A trifunctional conjugate is provided having three chemical moieties, attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical mouths sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule.
    Type: Grant
    Filed: September 30, 1991
    Date of Patent: December 1, 1992
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, James C. Sternberg
  • Patent number: 5162218
    Abstract: Polypeptide compositions are provided having a binding site specific for a particular target ligand and further having an active functionality proximate the binding site. The active functionality may be a reporter molecule, in which case the polypeptide compositions are useful in performing assays for the target ligand. Alternatively, the active functionality may be a chemotherapeutic agent, in which case the polypeptide compositions are useful for therapeutic treatment of various diseased states. A novel method for preparing such polypeptides having active functionalities proximate their binding site comprises combining the polypeptide specific for the target ligand with an affinity label including ligand having a reactive group attached thereto. The reactive group is then covalently attached to an amino acid side chain proximate the binding site and cleaved from the substrate. The substrate is eluted, leaving a moiety of the reactive group covalently attached to the polypeptide.
    Type: Grant
    Filed: June 10, 1991
    Date of Patent: November 10, 1992
    Assignee: The Regents of the University of California
    Inventor: Peter Schultz
  • Patent number: 5145772
    Abstract: Water soluble naturally-occurring and synthetic enhancer substances, generally macromolecular in nature, for example globular proteins that include hydrophobic regions such as bovine serum albumin, and polymeric quaternary ammonium salts such as poly(vinylbenzyltrimethylammonium chloride), which have the ability to inhibit light-emitting fluorophores resulting from the decomposition of chemiluminescent compounds from releasing energy through non-light emitting pathways, are disclosed as permitting the stabilization, and hence increasing the light intensity, of such light-emitting fluorophores in aqueous media as compared to the intensity of the light emitted by the same quantities of such fluorophores in aqueous media in the absence of such enhancer substances. Any chemiluminescent enzymatically cleavable 1,2-dioxetane, for example 3-(2'-spiroadamantane)-4-methoxy-(3"-phosphoryloxy)phenyl-1,2-dioxetane disodium salt, can be used.
    Type: Grant
    Filed: September 30, 1991
    Date of Patent: September 8, 1992