Glass Or Silica Patents (Class 436/527)
  • Patent number: 6312960
    Abstract: The invention provides methods for preparing a reaction substrate for use as assay devices comprising parallel printing of arrays of biosites on reaction substrates, wherein each biosite comprises a single type of capture probe bound to the reaction substrate and the array of biosites is deposited on the reaction substrate by a capillary bundle printer device.
    Type: Grant
    Filed: December 22, 1998
    Date of Patent: November 6, 2001
    Assignee: Genometrix Genomics, Inc.
    Inventors: William J. Balch, Michael E. Hogan
  • Patent number: 6310110
    Abstract: A method of making a molecularly imprinted porous structure makes use of a surfactant analog of the molecule to be imprinted that has the imprint molecule portion serving as the surfactant headgroup. The surfactant analog is allowed to self-assemble in a mixture to create at least one supramolecular structure having exposed imprint groups. The imprinted porous structure is formed by adding reactive monomers to the mixture and allowing the monomers to polymerize, with the supramolecular structure serving as a template. The resulting solid structure has a shape that is complementary to the shape of the supramolecular structure and has cavities that are the mirror image of the imprint group. Similarly, molecularly imprinted particles may be made by using the surfactant to create a water-in-oil microemulsion wherein the imprint groups are exposed to the water phase.
    Type: Grant
    Filed: July 30, 1999
    Date of Patent: October 30, 2001
    Inventors: Michael A. Markowitz, Paul E. Schoen, Bruce P. Gaber, Banahalli R. Ratna, Paul R. Kust, David C. Turner, Douglas S. Clark, Jonathan S. Dordick
  • Patent number: 6306664
    Abstract: A method to produce arrays of compounds for concurrent testing is described. Two formats are described using porous rods or porous sheet materials. In one format, the compounds of the array are immobilized onto porous rod elements. In the second format, the compounds are immobilized as lines on a sheet of porous material. In both cases, a bundle is formed by radial compression of the rods or spiral wrapping of the sheet. A sheath is applied to the bundle, and arrays are cut as slabs. Each synthesis or application step to create an array element is used to fabricate multiple arrays. Relatively high-density arrays can be produced with current printing technologies. The method is particularly suited to mass production of arrays.
    Type: Grant
    Filed: June 21, 1999
    Date of Patent: October 23, 2001
    Assignee: Unitec Co., Ltd.
    Inventor: Don Stimpson
  • Patent number: 6306665
    Abstract: Microporous solid phase materials that are suitable for lateral flow and other assays for detecting the presence of analytes in test samples, that are stable under variations in humidity and, even after storage for extended periods of time, can form stable covalent bonds with molecules containing a free primary or secondary amine group or sulfhydryl group are described. The invention further concerns chemically derivatized solid phase materials, and conjugates comprising such materials. Examples of lateral flow devices for the quantitative or semi-quantitative determination of an analyte in a biological sample are described.
    Type: Grant
    Filed: October 13, 1999
    Date of Patent: October 23, 2001
    Assignee: A-Fem Medical Corporation
    Inventors: Robert Lee Buck, Huiying Wang, Timothy Patrick Hyatt, Paul Andrew Mueggler
  • Patent number: 6303290
    Abstract: The present invention provides a process for the encapsulation of biologically important proteins into transparent, porous silica matrices by an alcohol-free, aqueous, colloidal sol-gel process, and to the biological materials encapsulated thereby. The process is exemplified by studies involving encapsulated cytochrome c, catalase, myoglobin, and hemoglobin, although non-proteinaceous biomaterials, such as active DNA or RNA fragments, cells or even tissues, may also be encapsulated in accordance with the present methods. Conformation, and hence activity of the biomaterial, is successfully retained after encapsulation as demonstrated by optical characterization of the molecules, even after long-term storage. The retained conformation of the biomaterial is strongly correlated to both the rate of gelation and the subsequent drying speed of the encapsulatng matrix.
    Type: Grant
    Filed: September 13, 2000
    Date of Patent: October 16, 2001
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Dean-Mo Liu, I-Wei Chen
  • Patent number: 6300141
    Abstract: A diagnostic card device for use in detecting or quantitating an analyte present in a liquid sample, comprising a card substrate having a sample introduction region, a biosensor, and a sample-flow pathway communicating between the sample-introduction region and the biosensor, circuitry for generating an analyte-dependent electrical signal from the biosensor; and a signal-responsive element for recording such signal. In one embodiment, the biosensor includes a detection surface with surface-bound molecules of a first charged, coil-forming peptide capable of interacting with a second, oppositely charged coil-forming peptide to form a stable &agr;-helical coiled-coil heterodimer, where the binding of the second peptide to the first peptide, to form such heterodimer, is effective to measurably alter a signal generated by the biosensor. The sample-flow pathway contains diffusibly bound conjugate of the second coil-forming peptide and the analyte (or an analyte analog) and immobilized analyte-binding agent.
    Type: Grant
    Filed: March 2, 2000
    Date of Patent: October 9, 2001
    Assignee: Helix BioPharma Corporation
    Inventors: Donald Segal, Heman Chao, Wah Y. Wong, Jerry McElroy
  • Patent number: 6300140
    Abstract: A slide having a portion thereof provided with transparent adhesive which adheres to a test sample. The slide and adhesive may be transparent. Specific types of infection and particularly fungal infections can be detected in the test sample using immunotest-methods. In a special embodiment the adhesive slide is fashioned with a peripheral lip or well to contain a test sample and a reagent.
    Type: Grant
    Filed: July 7, 1999
    Date of Patent: October 9, 2001
    Assignee: Leonard Bloom
    Inventors: Howard N. Robinson, Francisco A. Tausk, Bruce S. Bochner, Neil F. Martin
  • Patent number: 6300082
    Abstract: A method and apparatus for measuring binding between a plurality of molecules of a biological receptor protein and a plurality of molecules of a type which binds to said biological receptor is presented. Apparatus utilizes a sensor possessing a waveguide to which have been attached in close proximity to its surface, features resembling molecules having binding affinity for said biological receptor. Light is injected into said waveguide so as to produce an evanescent field at its surface. Molecules of receptor protein are tagged with a tag belonging to that class of chemicals which alters a characteristic of light, when said light passes through said chemical tag. Apparatus utilizes a rapid means of monitoring the change in optical signal coming from the waveguide as binding proceeds between tagged receptor protein and the binding molecular feature of the waveguide. This allows direct measurement of binding and dissociation rates between the receptor and the binding feature of the waveguide.
    Type: Grant
    Filed: March 20, 1998
    Date of Patent: October 9, 2001
    Assignee: IA, Inc.
    Inventors: Judith L. Erb, James G. Downward, IV, John R. Erb-Downward, James L. Wittliff
  • Patent number: 6284459
    Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.
    Type: Grant
    Filed: September 5, 1996
    Date of Patent: September 4, 2001
    Assignee: Discovery Partners International
    Inventors: Michael P. Nova, Andrew E. Senyei, Xiao-Yi Xiao, Chanfeng Zhao, Hanan Potash
  • Patent number: 6284470
    Abstract: Methods are disclosed for using paramagnetic particles to concentrate or harvest cells. Methods are also disclosed for clearing a solution of disrupted biological material, such as a lysate of cells or a homogenate of mammalian tissue. Methods are also disclosed for using paramagnetic particles to isolate target nucleic acids, such as RNA or DNA, from a solution cleared of disrupted biological material using the same type or a different type of paramagnetic particle. Kits are also disclosed for use with the various methods of the present invention. Nucleic acids isolated according to the present methods and using the present kits are suitable for immediate use in downstream processing, without further purification.
    Type: Grant
    Filed: August 24, 2000
    Date of Patent: September 4, 2001
    Assignee: Promega Corporation
    Inventors: Rex M. Bitner, Craig E. Smith, Douglas H. White, Braeden L. Butler, Jacqui Sankbeil
  • Patent number: 6281004
    Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide and processed simultaneously with a tissue sample.
    Type: Grant
    Filed: April 14, 1999
    Date of Patent: August 28, 2001
    Assignee: Cytologix Corporation
    Inventors: Steven A. Bogen, Gail E. Radcliffe
  • Patent number: 6277628
    Abstract: The present invention provides a method and a composition for detecting the levels of a plurality of biomolecular probes in a sample. In particular, the invention relates to a hybridization composition for detecting the presence or levels of different polynucleotide sequences in a sample.
    Type: Grant
    Filed: October 2, 1998
    Date of Patent: August 21, 2001
    Assignee: Incyte Genomics, Inc.
    Inventors: Timothy W. Johann, Sang Chul Park
  • Patent number: 6277653
    Abstract: An optical assaying method and system having a movable sensor is described. In one aspect, the present invention is a sensing system having a rotating sensor disk coated with indicator dyes sensitized to a variety of substances. In this configuration the sensing system further includes a detector for sensing spectral changes in light received from one or more of the indicator dyes. In another aspect, the present invention is a sensing system having a surface plasmon resonance sensor disk having grooves extending radially from a center of the disk. In yet another aspect, the present invention is a sensing system including a diffraction anomaly sensor disk having a dielectric layer that varies in thickness. The present invention allows for construction of an inexpensive sensing system that is capable of easily detecting a variety of substances either in a sample or a surrounding environment.
    Type: Grant
    Filed: June 29, 1999
    Date of Patent: August 21, 2001
    Assignee: Imation Corp.
    Inventors: William A. Challener, Richard R. Ollmann
  • Patent number: 6274387
    Abstract: A novel magnetic carrier is provided which comprises particulate silica containing a magnetic material, having polyacrylamide on the surface thereof in an amount ranging from 0.3 to 5 mmol/g in terms of monomeric acrylamide. A process for producing the magnetic carrier is also provided in which the surface of particulate silica containing a magnetic material is treated with a coupling agent, and the treated particulate silica is reacted with acrylamide and/or polyacrylamide. The magnetic carrier is useful for extraction of nucleic acid. The magnetic carrier can be produced readily by controlling the shape, the particle diameter, and the pore diameter, and is excellent in strength and adsorption efficiency. The extraction of a nucleic acid can be automated by use of the magnetic carrier.
    Type: Grant
    Filed: December 28, 1998
    Date of Patent: August 14, 2001
    Assignee: Tosoh Corporation
    Inventors: Syoichi Yamauchi, Kiyoshi Kasai
  • Patent number: 6274385
    Abstract: The present invention relates to a process of coding and identifying individual members of a chemical combinatorial library synthesized on a plurality of solid supports which undergo mix and split synthesis. The process provides for tagging the solid supports with a coding identifier that is attached to the solid support and which can be decoded by infrared or raman spectroscopy when directly attached to the support.
    Type: Grant
    Filed: August 9, 1999
    Date of Patent: August 14, 2001
    Assignee: Abbott Laboratories
    Inventors: Jill Edie Hochlowski, Thomas J. Sowin, Daniel W. Norbeck, Anne-Laure Marie Grillot, Rolf E. Swenson
  • Patent number: 6274384
    Abstract: A system for detecting a specific substance or analyte of interest is provided that includes one or more sensing units and an instrument for analyzing the sensing units. Each sensing unit preferably includes a substrate, an attachment layer and at least one capture layer that includes a ligand layer. In one embodiment, the attachment layer is tripartite and includes a lower binding surface held to the substrate and an upper binding surface that holds the ligand layer, together with an insulating layer disposed between these two surfaces. The lower binding surface provides a durable and stable attachment to the substrate. The upper binding surface holds the ligand layer and does not jeopardize the integrity or viability thereof. The insulating layer prevents any unwanted interaction between the lower and upper binding surfaces. Each sensing unit is supported on a test piece received by the instrument. The instrument controllably positions the test piece using marks and/or codes on the test piece.
    Type: Grant
    Filed: July 6, 1999
    Date of Patent: August 14, 2001
    Assignee: Accelr8 Technology Corporation
    Inventors: Timothy W. Starzl, David W. Nunnery, MaryBeth Robinson, H. John Hanlin
  • Patent number: 6261776
    Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.
    Type: Grant
    Filed: April 15, 1999
    Date of Patent: July 17, 2001
    Assignee: Affymetrix, Inc.
    Inventors: Michael C. Pirrung, J. Leighton Read, Stephen P. A. Fodor, Lubert Stryer
  • Patent number: 6258607
    Abstract: An indirect agglutination immunoassay includes the steps of providing, in a container, an immunoassay system comprising a test sample containing a desired analyte, and a reagent composed of magnetic particles or magnetic-material containing particles containing iron therein, wherein the magnetic particles or magnetic-material containing particles have been sensitized to allow specific binding to the desired analyte, and have a particle size in the range of 1 to 5 &mgr;m, with the content of the iron being in the range of 8 to 20 wt. %, precipitating the magnetic particles or magnetic-material containing particles by the application of magnetic force, allowing the container to stand at an inclination, and detecting the presence or absence of an immune reaction from the absence or presence of slippage observed of the precipitated magnetic particles or magnetic-material containing particles on the bottom of the container.
    Type: Grant
    Filed: June 28, 1993
    Date of Patent: July 10, 2001
    Assignee: Fujirebio Inc.
    Inventors: Tomo Saito, Mikio Ikeda
  • Patent number: 6258552
    Abstract: A method for estimation of change in bone mineral density or a method for diagnosis of osteoporosis, comprising the step of measuring change in a concentration of soluble interleukin-6 receptor in a blood sample, by for example, sandwich assay or competition assay; and a kit for carrying out the methods, comprising: (1) an anti-sIL-6R antibody immobilized to a solid carrier, and (2) an anti-sIL-6R antibody bound to a detectable marker or capable of binding to a detectable marker.
    Type: Grant
    Filed: February 20, 1996
    Date of Patent: July 10, 2001
    Assignee: Tosoh Corporation
    Inventors: Masataka Shiraki, Jui-Tung Chen, Ikuo Morita, Naoko Maruo
  • Patent number: 6255053
    Abstract: An assay plate for detecting the presence of a mobile reactant that binds to a immobilized reactant and the methods of making and using the same. An assay plate according to the present invention includes a substrate and at least one dried aliquot of the immobilized reactant, the immobilized reactant being bound to the surface of the substrate. The immobilized reactant binds the mobile reactant when a solution containing the mobile reactant is brought into contact with the immobilized reactant. The mobile and immobilized reactants may be any pair of biological compounds that have a specific affinity for one another For example the reactants may be nucleic acids or antibody-antigen pairs.
    Type: Grant
    Filed: June 21, 1999
    Date of Patent: July 3, 2001
    Assignee: Agilent Technologies Inc.
    Inventor: Kay Lichtenwalter
  • Patent number: 6251688
    Abstract: A method and apparatus for measuring binding between a plurality of molecules of a first type and a plurality of molecules of a second type is presented. Apparatus utilizes a sensor possessing a waveguide to which have been attached in close proximity to its surface, features resembling molecules of said first type. Light is injected into said waveguide so as to produce an evanescent field at its surface. Molecules of said second type are tagged with a tag belonging to that class of chemicals which alters a characteristic of light, when said light passes through said chemical tag. Apparatus utilizes a rapid means of monitoring the change in optical signal coming from said waveguide as binding proceeds between tagged molecules of type 2 and the feature resembling molecules of type 1 on said waveguide. This allows direct measurement of binding and dissociation rates between the two types of molecules.
    Type: Grant
    Filed: March 20, 1998
    Date of Patent: June 26, 2001
    Assignee: IA, Inc.
    Inventors: Judith L. Erb, James G. Downward, John R. Erb-Downward, Otho Ulrich
  • Patent number: 6248542
    Abstract: A device for detecting the presence of an antigen including (1) a cell having antibodies which are expressed on the surface of the cell and are specific for the antigen to be detected, where binding of the antigen to the antibodies results in an increase in calcium concentration in the cytosol of the cell, the cell further having a emitter molecule which, in response to the increased calcium concentration in the cytosol, emits a photon; (2) a liquid medium for receiving the antigen and in which the cell is immersed; and (3) an optical detector arranged for receiving the photon emitted from the cell.
    Type: Grant
    Filed: October 9, 1998
    Date of Patent: June 19, 2001
    Assignee: Massachusetts Institute of Technology
    Inventors: Todd H. Rider, Laura Smith
  • Patent number: 6248539
    Abstract: The measurement of the wavelength shifts in the reflectometric interference spectra of a porous semiconductor substrate such as silicon, make possible the highly sensitive detection, identification and quantification of small analyte molecules. The sensor of the subject invention is effective in detecting multiple layers of biomolecular interactions, termed “cascade sensing”, including sensitive detection of small molecule recognition events that take place relatively far from the semiconductor surface.
    Type: Grant
    Filed: October 30, 1997
    Date of Patent: June 19, 2001
    Assignees: The Scripps Research Institute, The Regents of the University of California at San Diego
    Inventors: M. Reza Ghadiri, Kianoush Motesharei, Shang-Yi Lin, Michael J. Sailor, Keiki-Pua S. Dancil
  • Patent number: 6245579
    Abstract: The invention relates to water-soluble polymeric thiosulfates, to a method for their preparation by polymer-analogous addition of tetrathionate to unsaturated polymers and to their application in surface coating.
    Type: Grant
    Filed: June 9, 1999
    Date of Patent: June 12, 2001
    Assignee: Universitat Karlsruhe
    Inventors: Gerhard Wenz, Denise Freitas Petri, Soo Whan Choi
  • Patent number: 6245578
    Abstract: An analytical apparatus comprises a biosensor device (3) which forms the base of a sample chamber. A stirrer (8) extends into the sample chamber and moves within the chamber so as to homogenize a sample contained within the chamber in contact with the biosensor (3). Movement of the stirrer (8) is preferably reciprocal movement along an axis perpendicular to the surface of the biosensor (3).
    Type: Grant
    Filed: February 23, 1998
    Date of Patent: June 12, 2001
    Assignee: Fisons PLC
    Inventor: James Oscar Molloy
  • Patent number: 6242267
    Abstract: An apparatus and method for rapidly analyzing samples for analytes of interest by an homogeneous immunofluorescence assay. The apparatus includes a sample test cartridge having a high control sample section, a low control sample section, and at least one test sample section. Each of these sections contain at least one pre-loaded reagent housed in a well within the cartridge wherein the low control sample section contains a known low amount of an analyte of interest and the high control sample section contains a known high amount of an analyte of interest. The cartridge includes a biosensor comprising a planar waveguide having first and second parallel plane surfaces and an edge extending between them, the edge having a receiving region for receiving a light beam.
    Type: Grant
    Filed: September 18, 1998
    Date of Patent: June 5, 2001
    Assignee: University of Utah Research Foundation
    Inventors: James N. Herron, Douglas A. Christensen, Scott D. Miles
  • Patent number: 6242262
    Abstract: A method for isolating an active catalyst from a library of compounds that are potential catalysts is disclosed. The method involves providing a library which comprises a plurality of discrete solid supports, each solid support having a different organic compound bound thereto; and providing a reaction solution in a reaction vessel, the reaction solution containing the reactant or reactants necessary for a chemical reaction to occur in the presence of a catalyst for that reaction. The library and the reaction solution are then combined in the reaction vessel, and then one of the discrete solid supports is detected that is characterized by a temperature change in said solution greater than the temperature change of a plurality of other of said discrete solid supports in said solution. The detected solid support carries an active catalyst for the chemical reaction. Continuous flow apparatus for carrying out the method is also disclosed.
    Type: Grant
    Filed: October 24, 1997
    Date of Patent: June 5, 2001
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: James P. Morken, Steven J. Taylor
  • Patent number: 6238931
    Abstract: Particles and methods for the detection or visualization of analytes using fluorescence energy transfer. Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed.
    Type: Grant
    Filed: July 12, 1994
    Date of Patent: May 29, 2001
    Assignee: Biosite Diagnostics, Inc.
    Inventors: Kenneth F. Buechler, Joseph Barry Noar, Lema Tadesse
  • Patent number: 6235464
    Abstract: A method for immunoassay of a viral antigen is performed on a membrane precoated with an inert protein. Nonimmunological capture of antigen takes place by absorption onto the coated membrane. Captured antigen binds to a tracer which includes a label conjugated to a specific antibody, the inert protein concomitantly inhibiting nonspecific binding of tracer. The label may be an enzyme which converts a substrate to a detectable product or converts a blocked inhibitor to an inhibitor whereby a second enzyme is inhibited from converting a substrate to a product. The invention includes a kit of materials for performing an assay in accordance with the method of the invention.
    Type: Grant
    Filed: October 20, 1994
    Date of Patent: May 22, 2001
    Inventors: Glenn L. Henderson, Randal A. Hoke, Anne C. Hopkins, Daniel A. McLaurin
  • Patent number: 6235541
    Abstract: Substrates are patterned with antibodies attached thereto at discrete locations from which absorption resistant coating is removed by selectively controlled mechanical scribing contact to avoid chemical removal so as to decrease fabrication costs and increase fabrication speed.
    Type: Grant
    Filed: May 6, 1999
    Date of Patent: May 22, 2001
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventor: Robert A. Brizzolara
  • Patent number: 6235488
    Abstract: A mass biosensor uses an intermediate avidin layer to facilitate binding of a biotinylated antibody to a measurement surface of the biosensor. The avidin layer can be added by the manufacturer of the biosensor, while the biotinylated layer can be added by the user. This two-phase method of chemically modifying the measurement surface significantly reduces the user time required to customize the measurement surface to render it capable of binding selected compounds. An organosilane coupling agent attached to the surface provides sites to which avidin is bound. Avidin acts as a universal receptor of biotinylated compounds with specific binding affinities. Biotinylated antibodies or other biotinylated compounds are added and bind to the immobilized avidin. Surface adsorption is reduced by washing the modified surface with biotin to block potential sites of weak bond formation, electrostatic and hydrophobic interactions.
    Type: Grant
    Filed: April 29, 1992
    Date of Patent: May 22, 2001
    Assignee: Agilent Technologies, Inc.
    Inventors: May Tom-Moy, Carl Alan Myerholtz
  • Patent number: 6218194
    Abstract: A method for monitoring the interaction of molecular species utilizes a sensor device comprising a substrate (1) with a waveguide (2) formed on the surface thereof. A grating (3) is formed in one of the surfaces of the waveguide (2). A beam of light (6) is incident on the grating (3) and the angle of incidence at which maximum reflection occurs is monitored. A first molecular species is immobilized on the waveguide (2). Changes in the angular position of the reflection maximum provide an indication of interaction of the first molecular species with a second molecular species contained in a sample brought into contact with the sensor device.
    Type: Grant
    Filed: October 12, 1999
    Date of Patent: April 17, 2001
    Assignee: Thermo Fast UK Limited
    Inventors: Nikolai Mikhailovich Lyndin, Vladimir Alexandrovich Sychugov, Alexander Valentinovich Tishchenko, Boris Alexandrovich Usievich
  • Patent number: 6214560
    Abstract: Method for specific detection of one or more analytes in a sample. The method includes specifically associating any one or more analytes in the sample with a scattered-light detectable particle, illuminating any particle associated with the analytes with light under conditions which produce scattered light from the particle and in which light scattered from one or more particles can be detected by a human eye with less than 500 times magnification and without electronic amplification. The method also includes detecting the light scattered by any such particles under those conditions as a measure of the presence of the analytes.
    Type: Grant
    Filed: April 18, 1997
    Date of Patent: April 10, 2001
    Assignee: Genicon Sciences Corporation
    Inventors: Juan Yguerabide, Evangelina E. Yguerabide, David E. Kohne, Jeffrey T. Jackson
  • Patent number: 6214541
    Abstract: The present invention relates to a method of detecting specific antibodies directed against HPV proteins in body fluids, comprising the following steps: (I) incubating a native carrier material-bound HPV protein with body fluids, and (II) reacting specific antibodies (a) bound to the HPV protein with labeled antibodies (b) directed against antibodies (a) or with unlabeled antibodies (b) and the latter with labeled antibodies (c) directed against antibodies (b). Furthermore, this invention concerns a kit usable for this purpose.
    Type: Grant
    Filed: March 9, 1998
    Date of Patent: April 10, 2001
    Assignee: Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts
    Inventors: Hanswalter Zentgraf, Manfred Frey, Iris Velhagen, Regina Martens, Wolfgang Meschede, Michael Pawlita, Joris Braspenning, Masimo Tommasino
  • Patent number: 6210910
    Abstract: A biosensor, sensor array, sensing method and sensing apparatus are provided in which individual cells or randomly mixed populations of cells, having unique response characteristics to chemical and biological materials, are deployed in a plurality of microwells formed at the distal end of individual fibers within a fiber optic array. The biosensor array utilizes an optically interrogatable encoding scheme for determining the identity and location of each cell type in the array and provides for simultaneous measurements of large numbers of individual cell responses to target analytes. The sensing method utilizes the unique ability of cell populations to respond to biologically significant compounds in a characteristic and detectable manner. The biosensor array and measurement method may be employed in the study of biologically active materials, in situ environmental monitoring, monitoring of a variety of bioprocesses, and for high throughput screening of large combinatorial chemical libraries.
    Type: Grant
    Filed: March 2, 1998
    Date of Patent: April 3, 2001
    Assignee: Trustees of Tufts College
    Inventors: David R. Walt, Laura Taylor
  • Patent number: 6210908
    Abstract: Novel activated peptides and conjugates thereof, useful in diagnostic assays and therapeutics, and processes for the preparation thereof are disclosed.
    Type: Grant
    Filed: September 2, 1999
    Date of Patent: April 3, 2001
    Assignee: Dade Behring Marburg GmbH
    Inventors: Michael E. Annunziato, Paul S. Palumbo
  • Patent number: 6210906
    Abstract: The present invention provides monoclonal antibodies specific for kringle 5 of apo(a) and hybridomas secreting such antibodies. The invention also relates to assay methods for directly measuring concentrations of lipoprotein(a) [Lp(a)] in a plasma sample. In one embodiment, the method involves the specific capture of Lp(a) from a plasma sample with a monoclonal antibody developed against kringle 5 of apo(a), which is non-cross-reactive with plasminogen and kringle 4 of apo(a). The quantity of the Lp(a) present in the sample is then measured by detecting the amount of Lp(a)-anti-kringle 5 complex that has formed in the reaction. Alternatively, the Lp(a) may be captured non-specifically and then detected with the monoclonal antibody specific for kringle 5 of apo(a). The invention also provides competitive assays using the above-mentioned kringle 5 specific monoclonal antibodies.
    Type: Grant
    Filed: January 20, 1999
    Date of Patent: April 3, 2001
    Assignee: Abbott Laboratories
    Inventors: Samar K. Kundu, Robert N. Ziemann
  • Patent number: 6207464
    Abstract: Boron complexes of certain bis-heterocyclic compounds are provided. The complexes resemble monomethine cyanines and are useful for imparting fluorescent properties to materials by covalent and noncovalent association. The compounds have the following general formula: wherein the dotted lines Z1 and Z2 represent the atoms necessary to complete a structure selected from the group consisting of one ring, two fused rings, and three fused rings, each said ring having five or six atoms, and each said ring comprising carbon atoms and, optionally, no more than two atoms selected from oxygen, nitrogen and sulfur, and R1 through R5 represent various atoms or groups and M is Cl or F.
    Type: Grant
    Filed: August 28, 1998
    Date of Patent: March 27, 2001
    Assignee: Carnegie Mellon University
    Inventors: Bhalchandra M. Karandikar, Alan S. Waggoner, Ratnakar B. Mujumdar
  • Patent number: 6207398
    Abstract: The present invention provides novel cyclosporine C (CsC) derivatives having improved protein conjugatibility and hydrolytic stability. The present invention further provides a CsC derivative conjugated to a carrier, e.g., a solid support. Preferably, the solid support is a latex or magnetic particle.
    Type: Grant
    Filed: August 11, 1999
    Date of Patent: March 27, 2001
    Assignee: Dade Behring Inc.
    Inventor: Chengrong Wang
  • Patent number: 6205263
    Abstract: Distributed fiber optic chemical and physical sensors provide a relatively highly uniform response over the length of the fiber by, for example, varying such properties as the core/cladding index of refraction ratio to compensate for the non-linearity in sensitivity due to the loss of higher order modes in multi-mode fibers. The variation of the ratio changes the absorption coefficient of the fiber and can be used to compensate for any non-linearity in response. Other techniques for compensation also are disclosed.
    Type: Grant
    Filed: June 16, 1999
    Date of Patent: March 20, 2001
    Assignee: Intelligent Optical Systems
    Inventors: Robert A. Lieberman, Claudio O. Egalon
  • Patent number: 6200820
    Abstract: Disclosed are an optical flow particle apparatus and method for conducting a particle light scatter-based immunoassay for simultaneously measuring the presence or amount of one or more analytes in a fluid sample which involves the use of a reagent set for each analyte including first binding molecule-coated monodisperse microspheres and second binding molecule-coated colloidal particles in which at least one of the first or second binding molecules specifically binds a respective one of the analytes. In the case where more than one analytes are detected, each monodisperse microperse microsphere of a particular reagent set has a light scatter signal resolvable from that of microspheres of any other reagent set. Changes determined in the distributions of the measured light scatter signals for individual microspheres of each of the particular reagent sets are indicative of the presence or amount of the respective analyte(s) in the sample.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: March 13, 2001
    Assignee: Sienna Biotech, Inc.
    Inventors: W. Peter Hansen, Michael Cennerazzo, Carl Theodore Edens, Manish Kochar
  • Patent number: 6194552
    Abstract: The antitope of an antibody is masked with a masking agent, followed by immobilization on a support. The masking agent is then eluted to produce an improved immunosorbent, which is capable of binding more than double the amount of an antigen than existing immunosorbents having the same antibody bound at the same density. Preferably, the masking agent is an antigen or other compound having an epitope for which the antitope of the bound antibody has an avidity. In a preferred embodiment, greater than 30% of the bound antibodies maintain the same vicinity as when unbound for specific antigen or hapten molecules. Preferably, the support is formed of any conventional immunosorbent support material which allows the bound and unbound antibody to maintain an avidity for the same compounds or antigens.
    Type: Grant
    Filed: August 19, 1994
    Date of Patent: February 27, 2001
    Assignee: Center for Innovative Technology
    Inventors: William H. Velander, Carolyn Orthner
  • Patent number: 6194223
    Abstract: A method for the detection of an analyte is described which is characterized in that the binding of the analyte to a solid phase is determined by the independent analysis of the signals from a plasmon resonance measurement and a fluorescence measurement.
    Type: Grant
    Filed: April 13, 1998
    Date of Patent: February 27, 2001
    Assignee: Roche Diagnostics GmbH
    Inventors: Rupert Herrmann, Peter Sluka, Wolfgang Knoll, Thorstein Liebermann
  • Patent number: 6180378
    Abstract: Immobilized bioactive protein compositions are prepared containing a bioactive protein such as an enzyme intercalated into galleries of a phyllosilicate, and a crosslinking compound crosslinking the phyllosilicate and the bioactive protein. The phyllosilicate may contain sodium or alkylammonium ions and be montmorillonite. The protein may be lipoxygenase, and crosslinking compounds include tetramethyl orthosilicate, tetraethoxy silicate, propyltrimethoxy silicate, polydimethylortho silicate and methyltrimethoxy silicate. The composition is prepared by delaminating a sodium-saturated phyllosilicate, mixing a bioactive protein with the delaminated phyllosilicate and crosslinking with a crosslinking compound. After crosslinking, the composition may be vacuum dried and ground.
    Type: Grant
    Filed: January 29, 1999
    Date of Patent: January 30, 2001
    Assignee: The United States of America as represented by the Secretary of Agriculture
    Inventors: Siyuan Shen, An-Fei Hsu, Thomas A. Foglia, Shu-I Tu
  • Patent number: 6169194
    Abstract: Oligonucleotides and other biomolecules are immobilized in high density on solid substrates through covalent forces using either a permanent thioether bond, or a chemoselectively reversible disulfide bond to a surface thiol. Substrates which have hydroxyl groups on their surfaces can be first silanized with a trichlorosilane containing 2-20 carbon atoms in its hydrocarbon backbone, terminating in a protected thiol group. The oligonucleotides or other biomolecules are first connected to a tether consisting of a hydrocarbon or polyether chain of 2-20 units in length which terminates in a thiol group. This thiol may be further modified with a halobenzylic-bifunctional water soluble reagent which allows the conjugate to be immobilized onto the surface thiol group by a permanent thioether bond. Alternatively, the oligonucleotide-tether-thiol group can be converted to a pyridyldisulfide functionality which attaches to the surface thiol by a chemoselectively reversible disulfide bond.
    Type: Grant
    Filed: October 16, 1997
    Date of Patent: January 2, 2001
    Inventors: Michael Thompson, Mark E. McGovern
  • Patent number: 6159749
    Abstract: An apparatus and method for chemical and biological analysis, the apparatus having an optical trapping means to manipulate the reaction substrate, and a measurement means. The optical trapping means is essentially a laser source capable of emitting a beam of suitable wavelength (e.g., Nd:YAG laser). The beam impinges upon a dielectric microparticle (e.g., a 5 micron polystyrene bead which serves as a reaction substrate), and the bead is thus confined at the focus of the laser beam by a radial component of the gradient force. Once "trapped," the bead can be moved, either by moving the beam focus, or by moving the reaction chamber. In this manner, the bead can be transferred among separate reaction wells connected by microchannels to permit reactions with the reagent affixed to the bead, and the reagents contained in the individual wells.
    Type: Grant
    Filed: July 21, 1998
    Date of Patent: December 12, 2000
    Assignee: Beckman Coulter, Inc.
    Inventor: Yagang Liu
  • Patent number: 6153440
    Abstract: The present invention provides methods for the simultaneous measurement of triiodothyronine (T.sub.3) and thyroxine (T.sub.4) in biological fluids such as serum by direct equilibrium dialysis and immunoassay. Specifically, the method comprises dialyzing the serum sample to equilibrium in a physiological buffer system so that the free T.sub.3 and the free T.sub.4 are separated from T.sub.3 and T.sub.4 bound to serum proteins. The method further comprises combining a measured quantity of the dialyzed serum sample having free T.sub.3 and free T.sub.4 with reagents comprising a measured quantity of T.sub.3 labelled with a detectable marker and a measured quantity of T.sub.4 labelled with a detectable marker; an anti-T.sub.3 antibody of sufficient specificity and in sufficient quantity to bind a measurable quantity of the free T.sub.3, and an anti-T.sub.4 antibody of sufficient specificity and in sufficient quantity to bind a measurable quantity of the free T.sub.4.
    Type: Grant
    Filed: September 23, 1998
    Date of Patent: November 28, 2000
    Assignee: The Regents of the University of California
    Inventor: Inder J. Chopra
  • Patent number: 6154706
    Abstract: An apparatus for predicting a residual hormone concentration in a patient after a removal of a portion of the patient's glandular tissue which secretes the hormone, includes an input device constructed to receive a plurality of measured hormone concentrations corresponding to a plurality of human fluid samples taken from a patient at a plurality of sample times, respectively; and further includes a computer processor configured to iteratively calculate a residual hormone concentration. In accordance with one feature of the present invention, the computer processor is configured to generate data denoting a residual amount of glandular tissue that will remain in the patient after the removal of the portion of the patient's glandular tissue; and the apparatus further comprises an output device constructed to output the generated data denoting the residual amount of glandular tissue.
    Type: Grant
    Filed: April 9, 1999
    Date of Patent: November 28, 2000
    Inventors: Alan T. Remaley, Mark Ruddel, Phillip C. Miller
  • Patent number: 6150147
    Abstract: The present invention provides modified methods and apparatus for the preparation of arrays of material wherein each array includes a preselected collection of polymers, small molecules or inorganic materials associated with a surface of a substrate. The methods of the invention provide for modifications to general apparatus, flow cell geometries and solutions used in array fabrication.
    Type: Grant
    Filed: February 6, 1998
    Date of Patent: November 21, 2000
    Assignee: Affymetrix, Inc.
    Inventors: Martin J. Goldberg, Mel Yamamoto, Glenn H. McGall, Steven J. Woodman, Eric Spence, Lisa T. Kajisa
  • Patent number: 6143576
    Abstract: The assay devices, assay systems and device components of this invention comprise at least two opposing surfaces disposed a capillary distance apart, at least one of which is capable of immobilizing at least one target ligand or a conjugate in an amount related to the presence or amount of target ligand in the sample from a fluid sample in a zone for controlled fluid movement to, through or away the zone. The inventive device components may be incorporated into conventional assay devices with membranes or may be used in the inventive membrane-less devices herein described and claimed. These components include, flow control elements, measurement elements, time gates, elements for the elimination of pipetting steps, and generally, elements for the controlled flow, timing, delivery, incubation, separation, washing and other steps of the assay process.
    Type: Grant
    Filed: March 3, 1997
    Date of Patent: November 7, 2000
    Assignee: Biosite Diagnostics, Inc.
    Inventor: Kenneth F. Buechler