Optical Sensing Apparatus Patents (Class 435/808)
  • Patent number: 6471916
    Abstract: A microarray scanning system for conducting microarray experiments on a planar substrate includes an excitation radiation source, a detection system, and a computational device, the planar substrate supporting a plurality of dilution marks containing a fluorophore and located on the substrate surface at predetermined distances from a fiduciual reference mark and/or a microarray.
    Type: Grant
    Filed: November 9, 1999
    Date of Patent: October 29, 2002
    Assignee: Packard Instrument Company
    Inventor: David Noblett
  • Publication number: 20020155592
    Abstract: A fluorescence detection system includes a photonic band gap structure. An internal surface of the photonic band gap structure defines a core region, and is coated with a film formed of conjugated polymer molecules. The core region is filled with a sample fluid or gas having a plurality of either chemical or biological analytes dispersed therein. An optical source generates excitation light directed to the sample fluid. In response, a binding event between a bacterium or chemical species in the fluid or gas and one or more of the conjugated polymer molecules generates a fluorescent signal whose wavelength falls within the photonic band gap. The fluorescent signal is guided through said core region by resonant reflections, and is guided onto a detector. A plurality of photonic band gap structures may be combined so as to form a biosensor array.
    Type: Application
    Filed: July 27, 2001
    Publication date: October 24, 2002
    Inventors: William P. Kelleher, Stephen P. Smith, Richard E. Stoner
  • Patent number: 6458547
    Abstract: Solid phase methods for the identification of an analyte in a biological medium, such as a body fluid, using bioluminescence are provided. A chip designed for performing the method and detecting the bioluminescence is also provided. Methods employing biomineralization for depositing silicon on a matrix support are also provided. A synthetic synapse is also provided.
    Type: Grant
    Filed: December 12, 1997
    Date of Patent: October 1, 2002
    Assignee: Prolume, Ltd.
    Inventors: Bruce J. Bryan, Stephen Gaalema, Randall B. Murphy
  • Patent number: 6458601
    Abstract: A test piece for use in biological analyses includes a plurality of different known specific binding substances disposed in predetermined positions on a substrate. The specific binding substances are disposed on a plurality of surfaces provided by the substrate and arranged in the direction of thickness of the substrate.
    Type: Grant
    Filed: May 16, 2000
    Date of Patent: October 1, 2002
    Assignee: Fuji Photo Film Co., Ltd.
    Inventor: Toshihito Kimura
  • Patent number: 6440748
    Abstract: The invention concerns a device and a method for carrying out fluorescence immunoassays, wherein from at least one light source light is directed onto a surface at one end of a light waveguide and with the light coupled into the light waveguide by evanescent field excitation at the surface of the light waveguide fluorescence of at least one labelling substance bound to a chemical or biochemical partner of a general receptor-ligand system is excited. The solution according to the invention is here to provide a possible way of carrying out fluorescence immunoassays with high accuracy of measurement at low cost and within a short time. To achieve this object, the fluorescent light is decoupled from the light waveguide and directed via an optical system onto an optical detector with which the intensity of the fluorescent light is measured.
    Type: Grant
    Filed: July 18, 2000
    Date of Patent: August 27, 2002
    Assignee: Institut für Chemo- und Biosensorik Münster E.V.
    Inventors: Andreas Katerkamp, Ulrich Kunz, Frank Grawe, Göran Key
  • Patent number: 6441898
    Abstract: In a test strip for the optical determination of the concentration of a substance in a liquid, especially for blood sugar determination, including a strip-shaped carrier with a reaction field, defined by opaque material on the carrier, containing a reagent carrying medium, which reagent carrying medium upon wetting with the fluid to be investigated changes in regard to its reflectivity or transmissivity, the carrier consists of an optically transparent material onto which a thin-layered carrying medium containing the reagent is applied.
    Type: Grant
    Filed: February 25, 2000
    Date of Patent: August 27, 2002
    Inventor: Ernst Markart
  • Patent number: 6436651
    Abstract: The present invention provides an inexpensive and sensitive device and method for detecting and quantifying analytes present in a medium. The device comprises a metalized film upon which is printed a specific, predetermined pattern of analyte-specific receptors. Upon attachment of a target analyte to select areas of the plastic film upon which the receptor is printed, diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined, precise placement of the analyte. A diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device.
    Type: Grant
    Filed: February 11, 2000
    Date of Patent: August 20, 2002
    Assignee: Kimberly-Clark Worldwide, Inc.
    Inventors: Dennis S. Everhart, Mark L. Jones, Rosann Marie Kaylor
  • Patent number: 6426213
    Abstract: A sperm analysis system has a sperm sample carrier (20) and “reader” module. The sperm sample carrier includes: 1) a shank (24) defining a chamber (26) with an opening for ingress and egress of a sperm sample; a manually operated pump (28) for aspirating a sample of sperm into the chamber (26), and a plurality of distinct photon paths (34) intersecting and passing through the chamber (26). The module includes: a processor responsive to an actuation signal from an operator, a photon source, e.g.
    Type: Grant
    Filed: January 9, 2001
    Date of Patent: July 30, 2002
    Assignee: Progeny Systems, LLC
    Inventor: Henry L. Eisenson
  • Patent number: 6426231
    Abstract: This invention relates to an improved method and system for sensing of one or more analytes. A host molecule, which serves as an adapter/carrier, is used to facilitate interaction between the analyte and the sensor element. A detectable signal is produced reflecting the identity and concentration of analyte present.
    Type: Grant
    Filed: November 17, 1999
    Date of Patent: July 30, 2002
    Assignee: The Texas A&M University System
    Inventors: Hagan Bayley, Orit Braha, LiQun Gu
  • Patent number: 6413783
    Abstract: An assay apparatus includes a cell with a working electrode and a sonicating device structurally coupled to the cell for sonication the contents of the cell.
    Type: Grant
    Filed: September 18, 1997
    Date of Patent: July 2, 2002
    Assignee: Meso Scale Technologies, LLC
    Inventors: Jacob N. Wohlstadter, James Wilbur, George Sigal, Mark Martin, Alan Fischer, Larry R. Helms, Ramin Darvari
  • Patent number: 6399295
    Abstract: The present invention provides an inexpensive and sensitive system and method for detecting analytes present in a medium. The system comprises a diffraction enhancing element, such as functionalized microspheres, which are modified such that they are capable of binding with a target analyte. Additionally, the system comprises a polymer film, which may include a metal coating, upon which is printed a specific, predetermined pattern of a analyte-specific receptors. Finally, the system includes a wicking agent which permits the system to be a single step system which avoids the necessity of any additional rinsing steps. Upon attachment of a target analyte to select areas of the polymer film, either directly or with the diffraction enhancing element, diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined, precise placement of the analyte. A diffraction image, such as a hologram, is produced which can be easily seen with the eye or, optionally, with a sensing device.
    Type: Grant
    Filed: December 17, 1999
    Date of Patent: June 4, 2002
    Assignee: Kimberly-Clark Worldwide, Inc.
    Inventors: Rosann M. Kaylor, Abraham B. Choi, Chibueze Obinna Chidebelu-Eze, Michael Heinrich Herbert Grunze
  • Patent number: 6391653
    Abstract: A fluorescent fiber-optic biosensor system using ultrasonic concentration of particles and cells for the detection of Salmonella typhimurium. A biosensor test chamber serves as an ultrasonic standing-wave cell that allows microspheres or cells to be concentrated in parallel layers or in a column along the axis of the cell. A fiber probe along the axis delivers laser excitation to fluorescent-labeled antibodies of Salmonella and collects the fluorescent signal. The Salmonella-antibody complexes are moved acoustically to the axis of the cell, increasing the fluorescent signal. Alternatively, the Salmonella-labelled antibody complexes attach to unlabeled antibodies that have been immobilized on the surface of polystyrene microspheres. This entire structure can be manipulated acoustically and the increase in the fluorescent signal, which can be an order of magnitude, indicates the presence of Salmonella.
    Type: Grant
    Filed: July 19, 2000
    Date of Patent: May 21, 2002
    Assignee: The Board of Governors for Higher Education, State of Rhode Island and Providence Plantations
    Inventors: Stephen V. Letcher, A. Garth Rand, Chonghua Zhou
  • Patent number: 6379915
    Abstract: A dry chemistry dye indicator composition provides improved shelf life, stable color indication end point and capability for a system at near normal pH. The novel dry chemistry dye indication system comprises 3-Methyl-6-(sodium sulfonate)-benzothiazolinone-(2)-hydrazone (MBTH-S). A preferred dye systems are based on the dye couple (MBTH-S) and 8-anilino-1-naphthalenesulfonate (ANS), and the dye couple MBTH-S and N-(3-sulfopropyl)analine. These dye indicator systems are used in conventional blood chemistry test strips and are particularly preferred for indication of glucose in blood.
    Type: Grant
    Filed: March 20, 2000
    Date of Patent: April 30, 2002
    Assignee: Amira Medical
    Inventors: Joel S. Douglas, Karen R. Drexler
  • Patent number: 6372485
    Abstract: A diagnostic microbiological testing system and method for microorganism identification (ID) and antimicrobial susceptibility determinations (AST). The system includes multiple-well test panels capable of performing ID and AST testing on the same test panel. Each test panel is inoculated with reagents, broth-suspended organisms, and placed into the instrument system. The instrument system includes a rotating carousel for incubation and indexing, multiple light sources each emitting different wavelength light, precision calorimetric and fluorometric detection, barcode test panel tracking and a control processor for making determinations based on measured test data. One light source includes a plurality of LEDs arranged in a linear array. Each of the LEDs' junction currents are controllable to produce a predetermined illumination profile.
    Type: Grant
    Filed: May 17, 2000
    Date of Patent: April 16, 2002
    Assignee: Becton Dickinson and Company
    Inventors: Alexander W. Clark, Paul Gladnick, Robert E. Armstrong, Nicholas Bachur, Klaus W. Berndt, Dwight Livingston
  • Patent number: 6340590
    Abstract: Thermal sterilization indicator process, apparatus and test indicator product which enable indication of microbial sterility achieved during a thermal sterilizer cycle by measuring visible light absorption due to chemical change in an encapsulated liquid indicator material, including measurements taken when a thermal sterilizer cycle is completed without a time delay requirement for spore growth, and in which the liquid indicator material includes a growth nutrient and microbes, so as to enable verification of achieved microbial sterility by measurement of the liquid indication subsequent to an incubation period following completion of the thermal sterilizer cycle.
    Type: Grant
    Filed: November 12, 1998
    Date of Patent: January 22, 2002
    Inventor: John R. Gillis
  • Patent number: 6340598
    Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide and optionally has multi-well features and improved evanescent field intensity. The preferred biosensor and assay method have the capture molecules immobilized to the waveguide surface by site-specific coupling chemistry. Additionally, the coatings used to immobilize the capture molecules provide reduced non-specific protein adsorption.
    Type: Grant
    Filed: December 8, 1998
    Date of Patent: January 22, 2002
    Assignee: University of Utah Research Foundation
    Inventors: James N. Herron, Douglas A. Christensen, Karin D. Caldwell, Vera Janatová, Shao-Chie Huang, Hsu-Kun Wang
  • Patent number: 6338960
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: January 15, 2002
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6331441
    Abstract: A method and apparatus for analyzing molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. The invention is also directed to a method and apparatus for constructing molecular arrays having a plurality of test sites. The invention allows for definitive high throughput analysis of multiple analytes in complex mixtures of sample substances. A combinatorial analysis process is described that results in the creation of an array of integrated chemical devices. These devices operate in parallel, each unit providing specific sets of data that, when taken as a whole, give a complete answer for a defined experiment. This approach is uniquely capable of rapidly providing a high density of information from limited amounts of sample in a cost-effective manner.
    Type: Grant
    Filed: December 21, 1998
    Date of Patent: December 18, 2001
    Assignee: Genometrix Genomics Incorporated
    Inventors: William J. Balch, Michael E. Hogan, Leopoldo G. Mendoza
  • Patent number: 6329194
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: December 11, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6329154
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: December 11, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6326213
    Abstract: A fluorescent fiber-optic biosensor system using ultrasonic concentration of particles and cells for the detection of Salmonella typhimurium. A biosensor test chamber serves as an ultrasonic standing-wave cell that allows microspheres or cells to be concentrated in parallel layers or in a column along the axis of the cell. A fiber probe along the axis delivers laser excitation to fluorescent-labeled antibodies of Salmonella and collects the fluorescent signal. The Salmonella-antibody complexes are moved acoustically to the axis of the cell, increasing the fluorescent signal. Alternatively, the Salmonella-labelled antibody complexes attach to unlabeled antibodies that have been immobilized on the surface of polystyrene microspheres. This entire structure can be manipulated acoustically and the increase in the fluorescent signal, which can be an order of magnitude, indicates the presence of Salmonella.
    Type: Grant
    Filed: February 9, 1998
    Date of Patent: December 4, 2001
    Assignee: The Boards of Govenors for Higher Education, State of Rhode Island and Providence Plantations
    Inventors: Stephen V. Letcher, A. Garth Rand, Chonghua Zhou
  • Patent number: 6326160
    Abstract: The invention relates generally to methods, systems, and devices for measuring the concentration of target analytes present in a biological system using a series of measurements obtained from a monitoring system and a Mixtures of Experts (MOE) algorithm. In one embodiment, the present invention describes a method for measuring blood glucose in a subject.
    Type: Grant
    Filed: September 27, 1999
    Date of Patent: December 4, 2001
    Assignee: Cygnus, Inc.
    Inventors: Timothy C. Dunn, Yalia Jayalakshmi, Ronald T. Kurnik, Matthew J. Lesho, Jonathan James Oliver, Russell O. Potts, Janet A. Tamada, Steven Richard Waterhouse, Charles W. Wei
  • Patent number: 6327410
    Abstract: A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.
    Type: Grant
    Filed: September 11, 1998
    Date of Patent: December 4, 2001
    Assignee: The Trustees of Tufts College
    Inventors: David R. Walt, Karri L. Michael
  • Patent number: 6323042
    Abstract: A displacement-type flow immunoassay is performed using a microcapillary passage. The inner wall of the microcapillary passage has immobilized thereon antibodies to the antigen of interest. Labeled antigen is immunologically bound to the immobilized antibodies. Sample antigen passing through the column displaces the labeled antigen. Downstream, the displaced labeled antigen is detected. The microcapillary format of the present invention enhances the sensitivity of the immunoassay over the sensitivity of displacement-type flow immunoassays performed in a column at similar flow rates.
    Type: Grant
    Filed: November 8, 1999
    Date of Patent: November 27, 2001
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventors: Upvan Narang, Paul R. Gauger, Frances S. Ligler
  • Patent number: 6316274
    Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.
    Type: Grant
    Filed: March 1, 2000
    Date of Patent: November 13, 2001
    Assignee: University of Utah Research Foundation
    Inventors: James N. Herron, Douglas A. Christensen, Hsu-Kun Wang, Karin Caldwell, Vera Janatová, Shao-Chie Huang
  • Publication number: 20010039005
    Abstract: The present invention relates to a method of screening for drug binding to serum proteins by: preparing at least two solutions each including a concentration of a serum protein and a concentration of a candidate drug, wherein the concentration of the candidate drug is different for each of the at least two solutions; exposing each of the at least two solutions to a light source; measuring fluorescent emission by the serum protein or a serum protein-candidate drug complex for each of the at least two solutions upon said exposing; and determining whether a change in fluorescence emission is measured for an increased concentration of the candidate drug, wherein the change in fluorescence emission indicates binding of the candidate drug to the serum protein. A kit useful for performing a fluorimetric screening of drug binding to serum proteins is also disclosed.
    Type: Application
    Filed: January 23, 2001
    Publication date: November 8, 2001
    Inventors: Murali Ramanathan, Marilyn E. Morris
  • Patent number: 6312961
    Abstract: A biosensor comprises a waveguide into which light is coupled by a diffraction grating. The sample to be analyzed is placed on a reaction region in which a component of the immunological reaction is provided, for example antibodies or antigens. Fluorescence is excited on the surface of the waveguide because of the presence of a marker for example, a labelled antigen or antibody. Fluorescence is decoupled from the waveguide by the coupling diffraction grating or another diffraction grating. The waveguide is made of a material emitting light when it is excited by the marker excitation beam. This latter emission has a peak wavelength different from that of the emission radiation due to the marker used in the immunological reaction. Waveguide material fluorescence emission provides a reference during measurement.
    Type: Grant
    Filed: May 24, 1999
    Date of Patent: November 6, 2001
    Assignee: CSEM Centre Suisse D'Electronique et de Microtechnique SA
    Inventors: Guy Voirin, Rino Kunz
  • Patent number: 6303326
    Abstract: The present invention includes the characterization of the major salivary protein or enzyme of the corn earworm Helicoverpa zea for triggering resistance to bacterial blight and frogeye leafspot in soybeans and for triggering resistance to insects in tomatoes. The invention includes an enzyme or a novel protein secreted from the salivary glands of certain insects including the saliva of species belonging to the order Hymenoptera and Lepidoptera. The regurgitant of Helocoverpa zea obtained from the functional salivary glands contains a protein that possesses glucose oxidase activity. The amino acid sequence of the protein is unique and when the protein is applied to plants, it triggers disease and insect resistance systematically. The physical and kinetic attributes of the enzyme are a pH of 7.0, a pI of 4.4 and a molecular weight of 88 kd. The km and Vmax of the enzyme for glucose is 26.9 mmol and 26.7 &mgr;mol min−1 mg−1, respectively.
    Type: Grant
    Filed: December 3, 1998
    Date of Patent: October 16, 2001
    Assignee: University of Arkansas
    Inventors: Gary W. Felton, Mary C. Mathews, Jianlong Bi, John B. Murphy
  • 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: 6287791
    Abstract: This invention relates to an improved method for the multi-parameter analysis of cells from peripheral blood or bone marrow. The method uses a nucleic acid dye, at least two fluorescently labelled monoclonal antibodies and at least two light scatter parameters to differentiate and discriminate between and among different cells in the blood or bone marrow.
    Type: Grant
    Filed: May 6, 1994
    Date of Patent: September 11, 2001
    Assignee: Becton Dickinson and Company
    Inventors: Leon W M M Terstappen, Chia-Huei Chen
  • Patent number: 6287783
    Abstract: The present invention involves an optical assay device and method of use for the detection of an analyte of interest in a sample that conveniently allows control of the flow characteristics of the sample through the device without significant user intervention. The optical assay device includes a base having an absorbent material, and a member having an optically active test stack that is rotatably coupled to the base for rotation between a lowered position and a raised position. In the lowered position, the optically active test stack contacts the absorbent material for drawing the sample through the surface. In the raised position, the optically active test stack does not contact the absorbent material.
    Type: Grant
    Filed: March 18, 1999
    Date of Patent: September 11, 2001
    Assignee: Biostar, Inc.
    Inventors: James E. Maynard, Mark A. Crosby, Alan J. Fujii
  • Patent number: 6280960
    Abstract: Method and apparatus for the single particle detection of submicron structures such as biological molecules and viruses utilises and optically transparent substrate coated with a thin film of metal illuminated with an optical beam incident at or close to critical or SPR angle wherein part of the beam propagates along the metal surface defining a measurement zone from which submicron particles contained in a sample placed in contact with the metal film scatter light which can be detected in the far field by conventional photodetection systems. The apparatus can be configured in a flow cytometric of optical microscope configuration.
    Type: Grant
    Filed: May 13, 1999
    Date of Patent: August 28, 2001
    Inventor: Robert Carr
  • Patent number: 6277559
    Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.
    Type: Grant
    Filed: February 21, 2001
    Date of Patent: August 21, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Tomoko Takeshita, Jun Otomo
  • Patent number: 6277627
    Abstract: The present invention relates to a glucose biosensor comprising a genetically engineered Glucose Binding Protein (GBP). In a specific embodiment, the invention relates to a GBP engineered to include mutations that allow site specific introduction of environmentally sensitive reporter groups. The signal of these prosthetic groups changes linearly with the degree of glucose binding. Thus, the glucose sensor of the invention can be used, for example, for detection of glucose in blood or industrial fermentation processes.
    Type: Grant
    Filed: December 31, 1998
    Date of Patent: August 21, 2001
    Assignee: Duke University
    Inventor: Homme W. Hellinga
  • Patent number: 6277652
    Abstract: Disclosed is a colorimetric sensor comprising polydiacetylene membrane liposomes, a polydiacetylene membrane film or fine particles coated with a polydiacetylene membrane, in which the polydiacetylene membrane is incorporated with a protein having a reduced molecular weight low enough not to cause color change in the polydiacetylene membrane. The examples of the reduced-molecular-weight proteins include an antibody Fab′ fragment, an antigenic protein of molecular weight of 100,000 or less, and a peptide consisting of 3-20 amino acid residue, which undergo an antigen-antibody reaction with an antigen or antibody contained in a sample. As the reduced-molecular-weight protein is also employed a combination of single-stranded DNA of 100 bases or less which hybridizes with single-stranded DNA contained in a sample to form a double-stranded DNA, and an antibody which reacts with said double-stranded DNA but does not react with the single-stranded DNA contained in the sample.
    Type: Grant
    Filed: December 23, 1998
    Date of Patent: August 21, 2001
    Assignee: Hogy Medical Co., Ltd.
    Inventors: Yoshio Jo, Toshiki Inoue, Kouichi Takada
  • Patent number: 6277629
    Abstract: An apparatus (1) for measuring physiological parameters has a test chamber (2) having boundaries defined by a first semiconductor chip (3) and a second semiconductor chip (4), between which chips a seal (7) bordering the test chamber (2) is arranged as a distance spacer. The first semiconductor chip (3) has an active side, which faces the test chamber (2) and has planar sensors, on which biological cells (6) located in a nutrient medium can be adherently deposited in order to measure physiological parameters directly on the cells (6). The second semiconductor chip (4) has on an active side, facing the test chamber (2), at least one additional sensor to measure global physiological parameters. The semiconductor chips (3, 4) are held in the sealing position using a mounting (8) that grasps over them on the outer side. Outside of the test chamber (2) the semiconductor chips (3, 4) each have electric connection contacts, which contact with opposing contacts of the mounting.
    Type: Grant
    Filed: June 1, 2000
    Date of Patent: August 21, 2001
    Assignee: Micronas GmbH
    Inventors: Bernhard Wolf, Ulrich Sieben
  • Patent number: 6277654
    Abstract: Various types of templates are stored in a template storage section in accordance with various types of array chips varying in disposition of spot positions. In making an analysis in an analysis section, a template, on which ROIs are disposed at positions corresponding to the spot positions on the array chip used, is read out from the template storage section. This template is set onto images represented by labeled data, and a signal value at a position corresponding to the ROI on the template is detected and evaluated.
    Type: Grant
    Filed: March 30, 2000
    Date of Patent: August 21, 2001
    Assignee: Fuji Photo Film Co., Ltd.
    Inventor: Yasuhiro Tsutamori
  • 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: 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: 6268125
    Abstract: A surface plasmon resonance apparatus for detecting a soluble analyte (e.g. a protein) or a particulate analyte (e.g. a cell), the apparatus comprising: (a) a sensor block adapted to receive a sensor, said sensor, for example a sensor slide, having a metallised sensor surface capable of binding the analyte; (b) a light source capable of generating an evanescent wave at the sensor surface of a sensor slide on the sensor block; (c) a first detector capable of detecting light from the light source which is internally reflected from the sensor surface; and (d) a second detector (e.g. a video camera) capable of detecting light scattered or emitted from an analyte bound thereto. Optionally the apparatus further comprises a second light source for increasing the intensity of the light scattered or emitted from an analyte bound to the sensor surface, preferably this is sited to such as to minimise the amount of light transmitted therefrom which is detected by the first detector.
    Type: Grant
    Filed: May 7, 1999
    Date of Patent: July 31, 2001
    Assignee: The Secretary of State for Defence in Her Brittanic Majesty's Government of the United Kingdom of Great Britain and Northern Ireland
    Inventor: Elaine A Perkins
  • Patent number: 6254830
    Abstract: A magnetic focusing immunosensor for the detection of pathogens comprising a laser, an exciting fiber and a collecting fiber, a fiber optic magnetic probe in communication with the collecting and exciting fibers and means for detecting, collecting and measuring fluorescent signals in communication with the collecting fiber. The probe and the collecting and exciting fibers are configured to focus paramagnetic microspheres attached to antigen/antibody/optically labeled complexes in a predetermined pattern in the field of view of the collecting fiber while blocking background interference.
    Type: Grant
    Filed: November 5, 1999
    Date of Patent: July 3, 2001
    Assignee: The Board of Governors for Higher Education, State of Rhode Island and Providence Plantations
    Inventors: Philip Pivarnik, He Cao, Stephen V. Letcher, A. Garth Rand
  • Patent number: 6251691
    Abstract: A method and apparatus for the manipulation of colloidal particles and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.
    Type: Grant
    Filed: October 26, 1998
    Date of Patent: June 26, 2001
    Assignee: Bioarray Solutions, LLC
    Inventor: Michael Seul
  • 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: 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: 6242207
    Abstract: A dry chemistry reagent matrix composition is provided containing a matrix material and a reagent composition containing 3-methyl-6(sulfonate salt)-benzothiazolinone-(2)-hydrazone (MBTH-S), N-ethyl-N-(3-sulfopropyl)aniline, and an oxidase enzyme or a peroxidase enzyme or a mixture thereof. The dry chemistry reagent matrix composition is useful in reagent test strips for determining the presence or concentration of an analyte in a fluid sample, such as blood.
    Type: Grant
    Filed: October 4, 1999
    Date of Patent: June 5, 2001
    Assignee: Amira Medical
    Inventors: Joel S. Douglas, Karen R. Drexler, John M. Gleisner, John H. Priest
  • 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: 6228652
    Abstract: A blood analyzing instrument includes a single transducer for simultaneously measuring the DC volume, RF conductivity, light scattering and fluorescence characteristics of blood cells passing through a cell-interrogation zone. Preferably, the transducer includes an electro-optical flow cell which defines a cell-interrogation zone having a square transverse cross-section measuring approximately 50×50 microns, and having a length, measured in the direction of cell flow, of approximately 65 microns.
    Type: Grant
    Filed: February 16, 1999
    Date of Patent: May 8, 2001
    Assignee: Coulter International Corp.
    Inventors: Carlos M. Rodriguez, Jose M. Cano, Barbara Carrillo, Kristie M. Gordon, Allan F. Horton, Ronald D. Paul, Mark A. Wells, James L. Wyatt
  • Patent number: 6225108
    Abstract: The invention relates to a microsensor for the measurement of the presence and the concentration of a primary medium, for example nitrate, in an environment where the microsensor is placed. The microsensor has a casing which surrounds a transducer and a reservoir containing nutrients. The transducer has a tip placed at a distance from the opening of the casing. Between the transducer tip and the opening is a reaction chamber with bacteria. The bacteria metabolises the primary medium (nitrate) into a secondary medium (nitrous oxide) which is detected by the transducer. The casing has a passage that stretches to the reservoir behind the transducer tip. Through the passage nutrients are fed to the bacteria whereby their activity can be maintained.
    Type: Grant
    Filed: May 7, 1999
    Date of Patent: May 1, 2001
    Inventors: Lars Hauer Larsen, Niels Peter Revsbech, Thomas Kjær