Optical Sensing Apparatus Patents (Class 435/808)
  • 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: 6207369
    Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces for use in diagnostics. The invention provides for electrochemiluminescence methods for detecting or measuring an analyte of interest. It also provides for novel electrodes for ECL assays. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use multiply specific testing procedures.
    Type: Grant
    Filed: September 17, 1996
    Date of Patent: March 27, 2001
    Assignee: Meso Scale Technologies, LLC
    Inventors: Jacob N. Wohlstadter, James Wilbur, George Sigal, Mark Martin, Liang-Hong Guo, Alan Fischer, Jon Leland, Mark A. Billadeau
  • Patent number: 6197576
    Abstract: An instrument to detect the presence of live microorganisms is described. The instrument is capable of providing simultaneous optical readings of multiple test vials containing different samples. Spectral variations due to metabolic activity of microorganisms are continuously recorded. An automated calibration scheme compensates for the parametric differences among the test vial locations.
    Type: Grant
    Filed: May 24, 1999
    Date of Patent: March 6, 2001
    Inventor: Gideon Eden
  • 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: 6165729
    Abstract: Electrochemiluminescent assay methods for determining an analyte of interest, which methods include forming one or more compositions which include, in the aggregate, (a) a sample to be tested for the analyte of interest, (b) a component capable of specifically binding with the analyte, (c) a label reagent which, when oxidized, is capable of electrochemiluminescence, (d) an amine which, when oxidized, forms a reducing agent, and (e) an electrolyte solution; subjecting such a composition containing the sample to conditions sufficient for specific binding to occur between the analyte of interest, if present, and one or more of the other components in the composition; thereafter, a composition containing the label reagent and amine, and reflecting the outcome of applying the aforementioned binding conditions, is exposed to conditions, such that both the label reagent and the amine are oxidized, the amine forms a reducing agent which interacts with the label reagent, electrochemiluminescence occurs, and the lumine
    Type: Grant
    Filed: April 15, 1994
    Date of Patent: December 26, 2000
    Assignee: Hyperion Catalysis International, Inc.
    Inventors: Jonathan Kent Leland, Michael Joseph Powell
  • Patent number: 6161437
    Abstract: The present invention is directed to a combined SAW sensor and a SPR sensor for evaluating an analyte, as well as a novel method for evaluating an analyte by utilizing a surface acoustic wave (SAW) sensor to determine the mass of the analyte and utilizing a surface plasmon resonance (SPR) sensor to determine the permittivity of the analyte. In accordance with one aspect of the invention, an apparatus is provided for evaluating an analyte. In one embodiment, the apparatus includes a piezoelectric substrate, a SAW sensor disposed on the substrate, and a SPR sensor disposed on the substrate in close proximity to the SAW sensor. In another embodiment, the apparatus more broadly includes a SAW sensor and a SPR sensor coupled to the surface acoustic wave sensor. In a preferred embodiment, the apparatus the SAW sensor includes two interdigital transducers and a chemically sensitive film interposed between the two interdigital transducers.
    Type: Grant
    Filed: April 9, 1999
    Date of Patent: December 19, 2000
    Assignee: Georgia Tech Research Corporation
    Inventors: Kevin F. Brennan, William Daniel Hunt
  • Patent number: 6150114
    Abstract: A method for determining the amount of an antiplatelet compound in a subject being treated with the compound which comprises calculating the ACT number of the subject's blood containing a reagent which immunoreacts with the antiplatelet compound and comparing the figure to a standardized concentration figure. In subjects concurrently being treated with heparin and antiplatelet compounds, the method can be practiced without additional heparin added to the blood sample. The invention also provides reagents which immunoreact with antiplatelet compounds and kits comprising immunoreactive reagents.
    Type: Grant
    Filed: May 15, 1997
    Date of Patent: November 21, 2000
    Assignee: G. D. Searle & Co.
    Inventors: Larry P. Feigen, Christopher P. Carron, Neal F. Haas, Debra M. Meyer, Jimmy D. Page, Jodi A. Pegg
  • Patent number: 6144448
    Abstract: A fluorescence detecting apparatus which allows highly precise measurement of fluorescence even with minute sample amounts, which has a strong responsiveness to temperature variations, which allows simultaneous measurement of a plurality of samples, and wherein the light source and the container holder, and the container holder and the fluorescence detector, are each optically connected by optical fibers; and the optical fibers are connected to the container holder in such a manner that the sample in the container is excited for fluorescence from below the sample container held by the container holder, and that they may receive the fluorescent light which is emitted by the sample from below the sample container.
    Type: Grant
    Filed: October 30, 1996
    Date of Patent: November 7, 2000
    Assignee: Tosoh Corporation
    Inventor: Yasutami Mitoma
  • Patent number: 6140045
    Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces which are electronically excited for use in electrochemiluminescence based tests. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use in flat panel displays and multiply specific testing procedures.
    Type: Grant
    Filed: March 6, 1997
    Date of Patent: October 31, 2000
    Assignee: Meso Scale Technologies
    Inventors: Jacob Wohlstadter, James Wilbur, George Sigal, Mark Martin, Liang-Hong Guo, Alan Fischer, Jon Leland
  • Patent number: 6136611
    Abstract: An optical assay apparatus is described which includes a light source module and an optical sensing element coupled by an interrogation module. The light source module produces light having propagation angles ranging from a lower, non-zero limit. This is accomplished by including an obscuration which blocks low propagation angle light. The sensing element includes a reflector portion and an sensing fiber portion. The reflector portion receives, as incident light, the light produced by the light source module and produces, as reflected light, light having an approximately constant propagation angle, preferably just less than the critical angle of the sensing fiber. The sensing element also includes a lens position which collimates signal recovery light collected by the sensing fiber. The interrogation module includes a window containing a light source optical fiber that transmits light from the light source module to the sensing element.
    Type: Grant
    Filed: July 31, 1997
    Date of Patent: October 24, 2000
    Assignee: Research International, Inc.
    Inventors: Elric W. Saaski, Charles C. Jung
  • Patent number: 6133021
    Abstract: A bioreactor system of probing toxic materials using microorganisms comprises two reactors. A first-step reactor serves as a microorganism reservoir in which the microorganisms are continuously cultured in a constant phase and a second-step reactor, provided with fiber optics, offers a place in which the microorganisms meet the toxic materials for the first time. Since the microorganisms are so genetically recombinant as to luminesce upon reaction with toxic materials, light is generated in the second-step reactor and, then, transmitted along the fiber optics to a luminometer where the change in the intensity of the light is monitored over time. The microorganisms can be stably provided from the reservoir, so that it is possible to continuously monitor the light intensity and thus, to trace the pollution of the toxic materials. The toxic materials may come from any of the sources including rivers, waste water, sewage, agricultural and industrial water, household water, tap water, atomic power plants, etc.
    Type: Grant
    Filed: December 15, 1998
    Date of Patent: October 17, 2000
    Assignee: Kwangju Institute of Science and Technology
    Inventors: Man Bock Gu, Joong Hyun Kim
  • Patent number: 6120734
    Abstract: A system for assaying a fluid sample, typically employing a fluorescent tag, the system comprising a lens capable of focussing both excitation and fluorescent radiation, a fluid-flow conducting conduit being provided in the lens extending transversely of the optical axis of and through the focal region of the latter. One or more mechanical screens are disposed adjacent to the focal region in the conduit to arrest passage of beads as a function of bead diameter. The beads, precoated with at least a moiety of a ligand/conjugate complex, e.g. a specific-binding ligand, are preferably substantially transparent to both the excitation and fluorescent radiation.
    Type: Grant
    Filed: June 24, 1994
    Date of Patent: September 19, 2000
    Assignee: Sapidyne, Inc.
    Inventor: Steve J. Lackie
  • Patent number: 6117643
    Abstract: Disclosed are monolithic bioelectronic devices comprising a bioreporter and an OASIC. These bioluminescent bioreporter integrated circuit are useful in detecting substances such as pollutants, explosives, and heavy-metals residing in inhospitable areas such as groundwater, industrial process vessels, and battlefields. Also disclosed are methods and apparatus for environmental pollutant detection, oil exploration, drug discovery, industrial process control, and hazardous chemical monitoring.
    Type: Grant
    Filed: November 25, 1997
    Date of Patent: September 12, 2000
    Assignees: UT Battelle, LLC, The University of Tennessee Research Corp.
    Inventors: Michael L. Simpson, Gary S. Sayler, Michael J. Paulus
  • Patent number: 6103535
    Abstract: An optical fiber is tapered, preferably adiabatically, and has a material coated on it for chemical bonding with fluorophores. When the fluorophores couple with the material, evanescent radiation generated fibers causes the fluorophores to fluoresce, and the fluorescence is coupled back into the fiber.
    Type: Grant
    Filed: May 30, 1997
    Date of Patent: August 15, 2000
    Assignee: University of Maryland
    Inventors: Saeed Pilevar, Christopher C. Davis, Alexander J. Fielding, Frank Portugal
  • Patent number: 6087114
    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: December 9, 1997
    Date of Patent: July 11, 2000
    Assignee: Massachusetts Institute of Technology
    Inventor: Todd H. Rider
  • Patent number: 6068978
    Abstract: Methods, devices, apparatus and kits for amplifying and detecting nucleic acid are provided. The apparatus is a one or two-tier thermal cycling device that operates in conjunction with a reaction/detection unit. A sample is loaded into a reaction chamber of the device which is then mated with a detection chamber to form the reaction/detection unit. A first heating element of the thermal cycling apparatus applies a desired temperature to the reaction/detection device to amplify target nucleic acid in the sample. The reaction mixture is then transferred to the detection chamber by the second heating element and amplified target nucleic acid is immobilized on a support in the detection chamber. Microprocessor control controls the heat applied by the second element independently of the heat applied by the first element. A detection system associated with the apparatus detects and analyzes the immobilized amplified nucleic acid target.
    Type: Grant
    Filed: May 20, 1997
    Date of Patent: May 30, 2000
    Assignee: Abbott Laboratories
    Inventors: Peter Zaun, Stanley R. Bouma, Julian Gordon, John J. Kotlarik, Natalie A. Solomon
  • Patent number: 6040151
    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 22, 1999
    Date of Patent: March 21, 2000
    Assignee: Mercury Diagnostics, Inc.
    Inventors: Joel S. Douglas, Karen R. Drexler
  • Patent number: 6030828
    Abstract: The invention relates to a microsensor for determining the concentration of a primary substrate by measuring the concentration of a secondary substrate. The microsensor comprises a transducer (1) for measuring the secondary substrate. The transducer (1) is surrounded by a first casing (8), which has an opening (9) with a barrier (10). The first casing (8) surrounds a second casing (11), also with an opening (12) with a barrier (13). In the first casing (8) between the barrier (10) and barrier (13), a reaction space (15) is formed. In the reaction space (15) an environment with catalytic components is contained. By measuring the concentration of the secondary substrate, the presence of the primary substrate can be determined.
    Type: Grant
    Filed: May 1, 1998
    Date of Patent: February 29, 2000
    Assignee: Unisense APS.
    Inventors: Lars Riis Damgaard, Niels Peter Revsbech
  • Patent number: 6023540
    Abstract: A microsphere-based analytic chemistry system is disclosed in which microspheres carrying different chemical functionalities may be mixed together while the ability is retained to identify the functionality on each bead using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which the separate microspheres may be optically coupled to discrete fibers or groups of fibers within the bundle. The functionalies are encoded on the separate microspheres using fluorescent dyes and then affixed to wells etched in the end of the bundle. Thus, a single sensor may carry thousands of chemistries. Only those microspheres exhibiting reactions then need to be decoded to identify the corresponding functionality.
    Type: Grant
    Filed: March 14, 1997
    Date of Patent: February 8, 2000
    Assignee: Trustees of Tufts College
    Inventors: David R. Walt, Karri Lynn Michael
  • Patent number: 6020209
    Abstract: A displacement-type flow immunoassay is performed using a microcapillary sage. 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: April 28, 1997
    Date of Patent: February 1, 2000
    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: 6017696
    Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.
    Type: Grant
    Filed: July 7, 1994
    Date of Patent: January 25, 2000
    Assignee: Nanogen, Inc.
    Inventor: Michael J. Heller
  • Patent number: 6008010
    Abstract: The present invention pertains to an apparatus for holding cells. The apparatus comprises a mechanism for incubating cells having a dynamically controlled closed environment in which the cells are grown, which are maintained in a desired condition and in which cells can be examined while the environment is dynamically controlled and maintained in the desired condition. The apparatus also comprises a mechanism for determining the state of the cells. The determining mechanism is in communication with the incubating mechanism. The present invention pertains to a method for holding cells. The method comprises the steps of incubating the cells in a dynamically controlled closed environment which is maintained in a desired condition and in which the cells can be examined while the environment is dynamically controlled and maintained in the desired condition. Additionally, there is the step of determining the state of the cells.
    Type: Grant
    Filed: November 1, 1996
    Date of Patent: December 28, 1999
    Assignee: University of Pittsburgh
    Inventors: Joel S. Greenberger, Paul A. DiMilla, Michael M. Domach, Raymond K. Houck
  • Patent number: 5994150
    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: November 19, 1997
    Date of Patent: November 30, 1999
    Assignee: Imation Corp.
    Inventors: William A. Challener, Richard R. Ollmann
  • Patent number: 5989923
    Abstract: The invention relates to a sensor (9) comprising a hologram (17) supported on or within a holographic support medium (10).A species to be detected is reactive with a substance disposed throughout, the sensor (9). Optionally, a chemical reactive with a species to be detected or a specific binding conjugate of a species to be detected is disposed throughout part of or all of the sensor (9).The resulting reaction(s) cause(s) variation(s) in the hologram (17) or holographic support medium (10) which in turn varies one or more optical characteristic(s) of the hologram (17).The variation in the optical characteristic(s) of the hologram (17) and/or the holographic support medium (10), preferably give(s) rise to a wavelength shift in incident radiation. The variation of the optical parameter is related to the species to be detected.The advantages of the sensor are that it is cheap, easy to manufacture and, once calibrated, reliable and robust.
    Type: Grant
    Filed: October 28, 1996
    Date of Patent: November 23, 1999
    Assignee: BTG International Limited
    Inventors: Christopher Robin Lowe, Roger Bradley Millington, Jeffrey Blyth, Andrew Geoffrey Mayes
  • Patent number: 5976892
    Abstract: A method for counting cells and microorganisms in a fluid medium, particularly in food and biological fluids, by labelling with a colored or fluorescent label which selectively labels the microorganisms and cells to be detected, and counting the labelled microorganisms and cells, wherein said colored or fluorescent label is a stoichiometric label, particularly a DNA or RNA label, the microorganisms and cells are concentrated at the same time as or prior to counting by means of a fluid medium concentration step, and counting is achieved by measuring the overall brightness of the concentrated medium and comparing it with a calibration curve.
    Type: Grant
    Filed: July 25, 1997
    Date of Patent: November 2, 1999
    Assignee: Biocom, S.A.
    Inventor: Jean-Claude Bisconte
  • Patent number: 5965456
    Abstract: Disclosed is apparatus for detecting the presence of an analyte of interest in a sample, comprising an immobilised binding partner comprising a solid support and a reversibly binding receptor which is capable of binding to the analyte of interest thereby causing a measurable change in a property of the immobilised partner, and detection means for detecting the measurable change and a method for detecting the presence of an analyte of interest.
    Type: Grant
    Filed: April 29, 1997
    Date of Patent: October 12, 1999
    Assignee: Biacore AB
    Inventors: Magnus Malmqvist, Gregory Paul Winter
  • Patent number: 5958704
    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: March 12, 1997
    Date of Patent: September 28, 1999
    Assignee: DDx, Inc.
    Inventors: Timothy W. Starzl, David W. Nunnery, MaryBeth Robinson, H. John Hanlin
  • Patent number: 5955377
    Abstract: Method for detecting an analyte of interest, comprising the steps of providing a detection device comprising a light reflective or transmissive substrate supporting one or more layers comprising an adhering attachment layer to which is affixed a receptive material which specifically interacts with the analyte of interest; reacting the device with a sample potentially comprising the analyte under conditions in which the analyte binds to the receptive material; and reacting bound analyte with a reagent which creates a mass change on the surface of the device.
    Type: Grant
    Filed: April 17, 1995
    Date of Patent: September 21, 1999
    Assignee: Biostar, Inc.
    Inventors: Diana M. Maul, Gregory R. Bogart
  • Patent number: 5952218
    Abstract: A bottle retaining mechanism holds a culture bottle in place in a cell in an incubating apparatus which agitates the culture bottle and detects the growth of microorganisms in the culture bottle. When a bottle is not present in the cell of the apparatus, the retaining mechanism moves to a position which reflects light from the light emitter to the light detector in an amount greater than the amount of light reflected off of a bottle when present, so as to indicate when a bottle is not present in a cavity of the bottle holder. The retaining mechanism/reflectance flag also is capable of providing a reference signal for auto-calibration purposes. The amount of light reflected from the retaining mechanism/reflectance flag to the light detector in a cell when no bottle is present can be monitored in order to detect changes in the cell. By monitoring such changes in the empty cell, drift from the original cell calibration can be monitored.
    Type: Grant
    Filed: April 2, 1998
    Date of Patent: September 14, 1999
    Assignee: Akzo Nobel, N.V.
    Inventors: Gregory S. Lee, William Adcox, Lanny V. Grade
  • Patent number: 5922284
    Abstract: An agglutination immunoassay method and apparatus therefor in which there are conducted the steps of contacting, in a container, a test sample suspected of containing a desired analyte and a reagent comprising sensitized magnetic-material containing particles capable of reacting with and binding to a desired analyte; precipitating the particles on the bottom of the container by the application of magnetic force; allowing the container to stand at an inclination so as to cause the particles to flow along the bottom of the container to form a developed pattern of the particles; obtaining a representative length of the developed pattern of the particles by an imaging device; and detecting the presence or absence of an immune reaction from the representative length of the pattern of the particles which has flowed from the bottom of the container, thereby detecting the presence or absence of the desired analyte in the test sample.
    Type: Grant
    Filed: May 19, 1998
    Date of Patent: July 13, 1999
    Assignee: Fujirebio Inc.
    Inventors: Yoshihiro Kinoshita, Kazunori Soma, Tomoo Saito
  • Patent number: 5922616
    Abstract: The invention provides a sensor for detecting an analyte comprising a support for a bioreceptor or biomimic and a detection means, wherein the support can retain a bioreceptor or biomimic and the support and the bioreceptor or biomimic and the detection means can be arranged such that when the sensor is placed in a medium containing a substrate, the substrate contacts the bioreceptor or biomimic and reacts to generate a response which is detectable by the detection means and which is relatable to the concentration of the analyte, and the support comprises a non-volatile organic liquid.
    Type: Grant
    Filed: July 23, 1997
    Date of Patent: July 13, 1999
    Assignee: Cranfield University
    Inventors: Manus Joseph Dennison, Jennifer Maeve Hall, Anthony Peter Francis Turner
  • Patent number: 5919712
    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: November 13, 1996
    Date of Patent: July 6, 1999
    Assignee: University of Utah Research Foundation
    Inventors: James N. Herron, Douglas A. Christensen, Hsu-Kun Wang, Karin D. Caldwell, Vera Janatova, Shao-Chie Huang
  • Patent number: 5914245
    Abstract: A MicroColonyImager instrument and solid phase methods to screen cells expressing mutagenized enzymes for enhanced activity. The MicroColonyImager instrument and methods permit high throughput screening of enzyme libraries by time course analyses of single-pixels, using either absorption, fluorescence or FRET. This high throughput assay can detect small differences in enzyme rates within microcolonies grown at a nearly confluent density on an assay disk. Each microcolony is analyzed simultaneously at single-pixel resolution, requiring less than 100 ml substrate/measurement. By simultaneously assaying different substrates tagged with spectrally distinct chromogenic or fluorogenic reporters, the substrate specificity of an enzyme can be changed.
    Type: Grant
    Filed: June 16, 1998
    Date of Patent: June 22, 1999
    Assignee: Kairos Scientific Inc.
    Inventors: Edward J. Bylina, William J. Coleman, Michael R. Dilworth, Christopher M. Silva, Mary M. Yang, Douglas C. Youvan
  • Patent number: 5912134
    Abstract: A cartridge is provided to present a biological sample for analysis by an imaging instrument. The cartridge of the invention utilizes a series of channels, capillaries, reservoirs and stop junctions to precisely move a sample, reagent and diluent through the cartridge as a function of the sum of capillary, gravitational and low centrifugal forces. The operator applies a precise amount of sample to the cartridge; therefore, the cartridge fluidics need not meter the sample prior to dilution. A practical and cost effective cartridge and assay process is disclosed which overcomes many of the limitations of the prior art. Such a cartridge is especially useful with fixed volume assays which permit low centrifugal accelerations to move the fluids within the cartridge.
    Type: Grant
    Filed: January 14, 1997
    Date of Patent: June 15, 1999
    Assignee: Biometric Imaging, Inc.
    Inventor: Robert J. Shartle
  • Patent number: 5891658
    Abstract: Simplicity, sensitivity and versatility of optical sensors based on competitive immunoassays using antibody-antigen reactions are achieved by solid-state, single-step reactions which permit accurate sensitive qualitative and quantitative information to be obtained without human participation. All of the chemistry-biochemistry is an inherent part of the sensor. A direct reaction occurs when the sample (antigen) is brought in contact with the sensor. The sensitivity of the competitive immunoassay optical sensor is controlled and increased by selecting a tag for the antigen or altering the attachment of a tag to an antigen so that the binding of tagged antigen to an antibody is decreased relative to the binding of untagged antigen to the antibody. The user can vary size, molecular weight and geometric configuration of the tagged antigen.
    Type: Grant
    Filed: June 27, 1996
    Date of Patent: April 6, 1999
    Assignee: FCI--FiberChem, Inc.
    Inventors: Stanley M. Klainer, Stephen L. Coulter, Geoffrey F. Hewitt
  • Patent number: 5872713
    Abstract: An analyte detection system is provided with calibration information uniquely specific to the set of test strips to which the sample is to be applied. The calibration information may be stored in permanent memory of the testing device, such that the device is discarded after use of all the test strips in a kit, or it may be stored in a calibration chip accompanying the set of test strips and distributed therewith, thereby enabling re-use of the testing device with a different set of test strips and associated calibration chip.
    Type: Grant
    Filed: October 30, 1997
    Date of Patent: February 16, 1999
    Assignee: Mercury Diagnostics, Inc.
    Inventors: Joel S. Douglas, Karen R. Drexler, Jeffrey N. Roe
  • Patent number: 5869272
    Abstract: Method for the determination of chlamydial or gram negative bacterial antigen comprising contacting a sample potentially containing extracted antigen with an optically active surface comprising an attachment layer, and a layer of non-specific protein.
    Type: Grant
    Filed: May 31, 1995
    Date of Patent: February 9, 1999
    Assignee: Biostar, Inc.
    Inventors: Gregory R. Bogart, Garret R. Moddel, Diana M. Maul, Jeffrey B. Etter, Mark Crosby
  • Patent number: 5866433
    Abstract: An optochemical fluorescence sensor with a biorecognitive layer for measuring the concentration of one or more analytes in a sample is provided with at least one island layer which is applied on a sensor substrate. The islands of the island layer are in the form of electrically-conductive material and have a diameter of less than 300 nm, the biorecognitive layer being directly applied on the island layer or bound via a spacer film. In addition, an analyte-specific fluorescent compound is provided which may be added to the sample or is provided in the sensor itself. The biorecognitive layer can bind the analyte to be measured directly or by means of analyte-binding molecules, the originally low quantum yield of the fluorescent compound increasing strongly in the vicinity of the island layer.
    Type: Grant
    Filed: March 14, 1996
    Date of Patent: February 2, 1999
    Assignee: AVL Medical Instruments AG
    Inventors: Thomas Schalkhammer, Fritz Pittner, Alfred Leitner, Franz Aussenegg, Harald Brunner
  • Patent number: 5863790
    Abstract: A system is used for determining efficacy of a sterilization cycle. A biological sterility indicator exhibits fluorescence in response to biological activity which is indicative of bacterial growth in the biological sterility indicator. The biological sterility indicator is exposed to the sterilization cycle and is placed in a fluorescence reading apparatus. The fluorescence from the biological sterility indicator is read to obtain a first fluorescence reading. The fluorescence from the biological sterility indicator is re-read to obtain a second fluorescence reading. The efficacy of the sterilization cycle is determined based on the first and second fluorescence readings.
    Type: Grant
    Filed: May 30, 1997
    Date of Patent: January 26, 1999
    Assignee: Minnesota Mining and Manfacturing Company
    Inventor: Phillip A. Bolea
  • Patent number: 5858800
    Abstract: An exciting light 2 is introduced within a slab-type optical waveguide 1, an evanescent wave due to the exciting light 2 excites fluorescent light, and among the fluorescent light, a fluorescent light which is radiated in a direction which direction crosses the exciting light 2 by a predetermined angle, is detected by a fluorescent light detector 4. Consequently, the exciting light and the fluorescent light are spacially separated so as to reduce stray light, and an arrangement of an optical system is simplified.
    Type: Grant
    Filed: March 22, 1996
    Date of Patent: January 12, 1999
    Inventors: Kazuhisa Shigemori, Kenji Masuda
  • Patent number: 5856203
    Abstract: Sensor devices for use in assaying for a ligand in a sample are described, the devices comprising: i) a discrete zone ("the measurement zone") on a region of which ("the measurement region") is immobilized directly or indirectly a first specific binding partner for the ligand under assay (or a reagent precomplexed with or capable of forming a complex with a specific binding partner for the ligand under assay), which zone additionally contains in releasable form, a first known amount of an optionally labelled second specific binding partner for the ligand under assay, the second specific binding partner being directed to an epitope of the ligand assay different to the epitope to which the first specific binding partner is directed; and ii) a second discrete zone ("the reference zone") on a region of which is immobilized directly or indirectly a first specific binding partner for the ligand under assay (or a reagent precomplexed with or capable of forming a complex with a specific binding partner for the ligand
    Type: Grant
    Filed: July 17, 1996
    Date of Patent: January 5, 1999
    Assignee: Applied Research Systems ARS Holding NV
    Inventors: Grenville Arthur Robinson, Janys Fletcher
  • Patent number: 5853666
    Abstract: A sample card transport station moves a test sample card from an incubation station for the card to a transmittance and fluorescence optical station in a sample testing machine. The sample card transport station has a drive belt and an associated stepper motor. The belt supports the card from one side of the card. A ledge having a card slot is disposed above the belt. The card is snugly received within the card slot, and supported from below by the drive belt and rollers for the belt. When the motor turns the belt, the belt grips the card and slides the card along the slot to the optical stations, without any slippage between the belt and the card. This construction provides for precise control over the movement of the card.The fluorescence station has a linear flash lamp that illuminates a column of the wells of the cards simultaneously. A reference detector and dichromatic beam splitter design is used to insure that the fluorescence measurements are independent of lamp output changes over time.
    Type: Grant
    Filed: February 12, 1997
    Date of Patent: December 29, 1998
    Assignee: bioMerieux Vitek, Inc.
    Inventors: William Ernest Seaton, Mark Joseph Fanning, David B. Shine, Craig Drager
  • Patent number: 5852126
    Abstract: The invention is directed to compositions containing at least one olefinic monomer, at least one polymer prepared form an olefinic monomer, an indicator dye to the basic structure of which an olefinic polymerisable group is covalently bonded directly or via a bridge group, at least one diolefinic cross-linking agent, and an effective amount of a polymerisation initiator; to polymerisates of the compositions, the polymerisates being in the form of interpenetrating networks; to membranes and unsupported films prepared from the polymerisates; to carrier materials coated with the compositions and polymerisates; to optical sensors prepared from the polymerisates; and to methods of determining ions and/or gases in solutions and/or blood.
    Type: Grant
    Filed: October 30, 1996
    Date of Patent: December 22, 1998
    Assignee: Novartis AG
    Inventors: Steven Barnard, Marizel Rouilly
  • Patent number: 5846842
    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: April 30, 1996
    Date of Patent: December 8, 1998
    Assignee: University of Utah Research Foundation
    Inventors: James N. Herron, Douglas A. Christensen, Karin D. Caldwell, Vera Janatova, Shao-Chie Huang, Hsu-Kun Wang
  • Patent number: 5846843
    Abstract: A long range surface plasmon resonance sensor for use in biological, biochemical or chemical testing. The sensor includes a first dielectric medium and a second dielectric medium having an index of refraction approximately matching the first dielectric medium. A double-grating structure is located between the first dielectric medium and the second dielectric medium. A beam of electromagnetic radiation is introduced into the second dielectric medium in a manner which causes long range surface plasmon resonance to occur such that the beam of radiation suffers attenuated total reflection. The characteristics of the resonance dependent upon the reaction between the bonding layer and the targeted bonding molecule are then detected.
    Type: Grant
    Filed: November 18, 1996
    Date of Patent: December 8, 1998
    Assignee: The University of Toledo
    Inventor: Henry John Simon
  • Patent number: 5843644
    Abstract: A method of direct extraction of cellular material from a tissue sample which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extracted zone(s) of cells is subjected to analysis. The overall process of identifying, extracting, transporting, and analyzing the extracted zones(s) of cells can be fully automated.
    Type: Grant
    Filed: March 1, 1994
    Date of Patent: December 1, 1998
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Lance A. Liotta, Zhengping Zhuang, Michael R. Buck, William G. Stetler-Stevenson, Irina A. Lubensky, Mark J. Roth
  • Patent number: 5840572
    Abstract: A system for measuring toxicity levels of a solution includes a water proof sample container transparent to visible light which holds an aqueous test solution containing bioluminescent organisms. A light tight chamber has a cavity which holds the sample container and includes a light port. A stress generating system positioned in the sample container generates pressure pulses which stimulate the organisms to generate light emissions. A light detector system mounted to the light tight chamber in a light tight manner detects light emissions generated in the sample container which propagate through the light port and are received by the light detector system. The light detector system generates an electric pulse in response to detecting each detected light emission. A controller enables the stress generating system and the light detector system, and then counts the electric pulses within a predetermined period of time.
    Type: Grant
    Filed: July 29, 1996
    Date of Patent: November 24, 1998
    Assignee: United States of America as represented by the Secretary of the Navy
    Inventors: Hugh D. Copeland, David Lapota, Dena E. Rosenberger, Gary F. Mastny
  • Patent number: 5837200
    Abstract: The sorting device is able to sort biological objects, particularly cells or viruses, in liquids as a function of physically measurable criteria or properties. The sorting apparatus is provided with a feed inlet (1) for the biological liquid which branches into a microstructured system of multi-parallel main channels (3) and sorting modules (4) each with a switch unit for distribution to two different outlet channels (19,20). Inside a sorting module (4), at least one sensor (9,10) is arranged on each main channel, and a sorting actuator (12) controlled by the relevant sensor is arranged on each switch unit (11). Finally, each outlet channel (20) is connected to a collecting channel (6) for the unselected biological cells or viruses, and each outlet channel (19) is connected to a collecting channel (5) for the selected cells or viruses. If the cells or viruses are magnetically marked, it is possible to dispense with the sensor (9,10) on the main channels (3).
    Type: Grant
    Filed: May 24, 1996
    Date of Patent: November 17, 1998
    Assignee: Bayer Aktiengesellschaft
    Inventors: Edgar Diessel, Walter Weichel
  • Patent number: 5834218
    Abstract: The invention relates to a biochemical sensor including a substrate on which yeast cells are deposited which are capable of capturing one type of molecules (M) and of producing a chemical entity (P) at the outcome of the capture; it also includes means for detecting the entity (P). The yeast cells employed are yeast cells obtained by genetic manipulation, in which the capture sites have been adapted to the type of molecules (M).
    Type: Grant
    Filed: October 11, 1996
    Date of Patent: November 10, 1998
    Assignee: Thomson-CSF
    Inventor: Jacques Gremillet
  • Patent number: 5830766
    Abstract: A method of assaying for a ligand in a sample involves incubating the sample in contact with a specific binding partner for the ligand carried on one surface of an optical structure, irradiating the structure at a suitable angle or range of angles to the normal such that the resonance and/or total internal reflection of the radiation occurs within the optical structure and/or the layer of specific binding partner, and analyzing the radiation in order to determine whether, and if desired the extent to which and/or rate at which the generated radiation and/or optical characteristics of the optical structure are altered by complex formation.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: November 3, 1998
    Assignee: Ares-Serono Research & Development Ltd. Partnership
    Inventors: John Worthington Attridge, Ian Alexander Shanks