Enzyme Or Microbe Electrode Patents (Class 435/817)
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Patent number: 5922188Abstract: A biosensor includes: an insulating substrate; an electrode system formed on the insulating substrate which has a working electrode and a counter electrode; and a reaction layer formed on the insulating substrate which contains an oxidoreductase and an electron acceptor. The electron acceptor is ferricinium ion derived from ferrocene electrolyte.Type: GrantFiled: March 7, 1997Date of Patent: July 13, 1999Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Shin Ikeda, Tomohiro Yamamoto, Toshihiko Yoshioka, Shiro Nankai, Shigeki Joko, Junko Iwata
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Patent number: 5914026Abstract: An implantable sensor comprising a biocompatible electroconductive case which houses a measuring electrode, a reference electrode, an auxiliary electrode, and an electronic circuit for measuring the response of the measuring electrode where the measuring electrode, reference electrode and auxiliary electrode are not in direct electrical contact with one another is provided. The implantable sensor of the present invention is particularly useful as a glucose sensor, especially when an enzyme-containing membrane is included in the measuring electrode.Type: GrantFiled: January 6, 1997Date of Patent: June 22, 1999Assignee: Implanted Biosystems Inc.Inventors: Elmo A. Blubaugh, Jr., Alan R. Brunsman, Kevin L. Houser
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Patent number: 5906921Abstract: A biosensor is disclosed for application to a method for quantitative measurement of a substrate comprising a first step of causing a substrate contained in a sample to react with an oxidoreductase specific to the substrate in the presence of an electron mediator in oxidized state, a second step of applying a potential to a working electrode for reducing the electron mediator in oxidized state that remains not reduced in the first step, and a third step of measuring a reduction current flowing across the working electrode and a counter electrode. The biosensor comprises an electrically insulating base plate, an electrode system having a working electrode and a counter electrode formed on the base plate, and a reaction layer which is formed on or in the vicinity of the electrode system and contains at least an oxidoreductase and an electron mediator, the counter electrode including at least a reductant of a redox compound or an electrolytically oxidizable metal.Type: GrantFiled: September 24, 1998Date of Patent: May 25, 1999Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Shin Ikeda, Toshihiko Yoshioka, Shiro Nankai
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Patent number: 5888805Abstract: A detecting apparatus is disclosed, that comprises plural measurement devices with respective sensors and a support for holding the measurement devices in such a manner that the individual sensors contact a culture broth, the turbidity, dissolved oxygen, dissolved carbon dioxide the temperature, pH, and so forth of the culture broth being obtained by the measurement devices.Type: GrantFiled: May 28, 1997Date of Patent: March 30, 1999Assignees: Rikagaku Kenkyusho, Komatsugawa Chemical Engineering Co., Ltd.Inventors: Isao Endo, Teruyuki Nagamune, Kozo Inoue, Kinichi Kawamura
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Patent number: 5879878Abstract: Electrode membrane combinations for use in biosensors to detect analytes in a sample and methods for making and storing same are disclosed. In one aspect, a method is provided for producing a first layer electrode membrane comprising:(1) Forming a solution containing Linker Lipid A, the disulfide of mercaptoacetic acid (MAAD) or similar molecule, linker Gramicidin B, membrane spanning lipid C (MSL-C) and membrane spanning lipid D (MSL-D) or other suitable linker molecules and other ion channel combinations;(2) Contacting an electrode containing a clean gold surface with the solution, the disulfide containing components in the solution thus adsorbing onto the gold surface of the electrode;(3) Rinsing the electrode with a suitable organic solvent; and(4) Removing the excess organic solvent used for rinsing.Type: GrantFiled: July 23, 1996Date of Patent: March 9, 1999Assignees: Australian Membrane and Biotechnology Research Institute, The University of SydneyInventors: Burkhard Raguse, Ronald John Pace, Lionel George King, Vijoleta Licija Braach-Makavytie, Bruce Cornell
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Patent number: 5876952Abstract: An amperometric glucose biosensor having high sensitivity and accuracy over a wide range of glucose concentrations and a method for the rapid detection of glucose in urine are provided. The biosensor strip comprises an electrically conductive carbon layer, having a first redox mediator, a reagent strip containing an enzyme system for the oxidation of glucose and a second redox mediator, and a silver/silver chloride reference electrode. In a preferred form of the sensor that has high sensitivity, a sensing electrode and a reference electrode are arranged so that the electrically conductive layers of the electrodes are face-to-face and sandwich the reagent strip between them. Screening for glucose is achieved by contacting the sensor with a drop of the patient's urine and comparing the current read-out with a standard calibration curve or by automatically converting the current flow generated by the test sample to units of glucose concentration. The sensor can measure urine glucose concentrations below 3 mg/dl.Type: GrantFiled: December 8, 1997Date of Patent: March 2, 1999Inventor: Paul Shieh
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Patent number: 5874316Abstract: The present invention provides a membrane the conductivity of which is dependent on the presence or absence of an analyte. The membrane comprises a closely packed array of self-assembling amphiphilic molecules and two ionophore components. A receptor molecule reactive with the analyte is provided on one of the ionophore components. The binding of the analyte to the receptor molecule causes a change in the relationship between the ionophore components such that the flow of ion across the membrane is prevented or allowed. The ionophore components are preferably selected from the group consisting of amphotericin B, gramicidin A monomers and combinations thereof, with gramicidin A monomers being particularly preferred. The present invention also provides a membrane including receptors directed against the Fc region of antibodies. These receptors are preferably derived from polyclonal antibodies.Type: GrantFiled: October 30, 1996Date of Patent: February 23, 1999Assignee: Australian Membrane Biotechnology Research InstituteInventors: Bruce A. Cornell, Vijoleta L. B. Braach-Maksvytis, Ronald J. Pace, Lionel G. King, Burkhard Raguse, Peter D. J. Osman
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Patent number: 5872713Abstract: 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: GrantFiled: October 30, 1997Date of Patent: February 16, 1999Assignee: Mercury Diagnostics, Inc.Inventors: Joel S. Douglas, Karen R. Drexler, Jeffrey N. Roe
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Patent number: 5866353Abstract: A variety of diazacyanine mediators that are soluble in aqueous media and which do not inhibit enzymatic activity are provided for use on the surface of a working electrode of a electrochemical biosensor for electrochemical co-enzyme regeneration. The co-enzyme, dihydronicotinamide adenine dinucleotide (NADH) or dihydronicotinamide adenine dinucleotide phosphate (NADPH), is oxidized to NAD.sup.+ OR NADP.sup.+ which is reduced by an oxidoreductase such as a dehydrogenase acting on a substrate. By applying the mediator together with NADH or NADPH to the surface of the working electrode, the voltage necessary to achieve oxidation is substantially reduced. Biosensor electrodes such as graphite electrodes may be produced-by screen printing techniques.Type: GrantFiled: December 9, 1996Date of Patent: February 2, 1999Assignee: Bayer CorporationInventors: Horst Berneth, Thomas Bocker, Henry Giera, Alison J. Murray, Hans-Ulrich Siegmund
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Patent number: 5861319Abstract: Methods and compositions are provided for specific binding assays in which specific binding reagents are immobilized on a solid phase. Immobilization is facilitated by covalently coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.Type: GrantFiled: October 28, 1994Date of Patent: January 19, 1999Assignee: Dade Behring Inc.Inventors: Spencer H. Lin, Kwok Sum Yu, Pratap Singh, Steven E. Diamond
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Patent number: 5858186Abstract: An electrochemical sensor capable of detecting and quantifying urea in fluids resulting from hemodialysis procedures. The sensor is based upon measurement of the pH change produced in an aqueous environment by the products of the enzyme-catalyzed hydrolysis of urea. The sensor may be fabricated using methods amenable to mass fabrication, resulting in low-cost sensors and thus providing the potential for disposable use. In a typical application, the sensor could be used in treatment centers, in conjunction with an appropriate electronics/computer system, in order to determine the hemodialysis endpoint. The sensor can also be utilized to allow at-home testing to determine if dialysis was necessary. Such a home monitor is similar, in principle, to devices used for blood glucose testing by diabetics, and would require a blood droplet sample by using a finger prick.Type: GrantFiled: December 20, 1996Date of Patent: January 12, 1999Assignee: The Regents of the University of CaliforniaInventor: Robert S. Glass
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Patent number: 5849296Abstract: A protein such as an enzyme or antibody is immobilized by crosslinking crystals of the protein with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. A preferred protein is an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease. Crosslinked enzyme crystals preferably retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred enzyme:Pronase.TM. ratio is 1:40. Enzyme crystals that are crosslinked may be microcrystals having a cross-section of 10.sup.-1 mm or less.Type: GrantFiled: June 7, 1995Date of Patent: December 15, 1998Assignee: Vertex Pharmaceuticals, Inc.Inventors: Manuel A. Navia, Nancy L. St. Clair
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Patent number: 5849174Abstract: A method for indicating the concentration of a substance in solution includes passing an alternating voltage between a first electrode structure having coated thereon a polymer and a second separate counter electrode in the solution. The polymer is in one of an oxidized and a reduced state, between which states its conductivity varies. Changes in the conductivity of the polymer coating are measured, the measurement being representative of the state of the polymer and thereby of the concentration of the substance in the solution. Electrodes for use in this method are also described.Type: GrantFiled: June 11, 1997Date of Patent: December 15, 1998Assignee: Medisense, Inc.Inventors: Gurdial Singh Sanghera, Philip Nigel Bartlett, Peter Robert Birkin
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Patent number: 5846702Abstract: A new group of Os(II) and Os(III) compounds useful as redox mediators in electrochemical biosensors. These compounds have 1) low oxidation potential, 2) fast reaction kinetics between the electroactive center of an enzyme and the compound, 3) slow oxidation of osmium by oxygen, and 4) excellent solubility in aqueous medium. These mediators are particularly useful as a component of a reagent used in an electrochemical biosensor, wherein the biosensor is useful for measuring analytes from a biological fluid, such as blood.Type: GrantFiled: December 20, 1996Date of Patent: December 8, 1998Assignee: Boehringer Mannheim CorporationInventors: Zhi David Deng, Gerald F. Sigler, Nigel A. Surridge, Christopher D. Wilsey, Robert J. McEnroe, Walter W. Jernigan, Rebecca W. Muddiman
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Patent number: 5846814Abstract: The new membrane biosensors consist of a solid A as a support, a lipid bilayer B as a membrane, spacers C incorporated between A and B and a receptor D embedded in the lipid bilayer. The new membrane biosensors are characterized in particular by their spacer C, which consists of a molecule of ethanolamine which forms an ester bond to the phosphatide group of the lipid bilayer B, an oligopeptide in helical or pleated sheet structure formed from 4-20 C.sub.2 -C.sub.10 -.alpha.-amino acids and a reactive group which enters into a chemical or physicochemical bond with the support A.Type: GrantFiled: February 20, 1997Date of Patent: December 8, 1998Assignee: Bayer AktiengesllschaftInventors: Hans-Joachim Galla, Claudia Steinem, Karsten Reihs
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Patent number: 5846744Abstract: A sensor format is based on impedance analysis of polymer coatings of electrodes. A detectable signal is produced by the effect of a reactive or catalytic species at or very near the polymer coated electrode. The reactive or catalytic species directly or indirectly effects a reaction with the polymer layers, whereby the polymer layer becomes porous and thus causes a measurable change in electrical properties of the electrode surface.Type: GrantFiled: January 16, 1996Date of Patent: December 8, 1998Assignee: Cambridge Life Sciences PLCInventors: Dale Athey, Calum J. McNeil, Ronald D. Armstrong, William Henry Mullen
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Patent number: 5842983Abstract: Biosensor for amperometric measurements wherein the measuring electrode (34) is made of an electrically conductive carrier made of carbon which is saturated with a platinum metal in colloidal form wherein a lead-off contact (10) of vitreous carbon runs from the measuring electrode (34). The porous carrier (6) is saturated with an enzyme suitably glucose oxidase for the determination of glucose wherein the surface of the carrier (68) is protected against the environment by a membrane (70).Type: GrantFiled: August 15, 1996Date of Patent: December 1, 1998Assignee: Fresenius AGInventors: Petra Abel, Wolfgang Allendorfer
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Patent number: 5837446Abstract: An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over he dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments.Type: GrantFiled: June 7, 1995Date of Patent: November 17, 1998Assignee: i-STAT CorporationInventors: Stephen N. Cozzette, Graham Davis, Jeanne Itak, Imants R. Lauks, Sylvia Piznik, Nicolaas Smit, Susan Steiner, Paul Van Der Werf, Henry J. Wieck, Randall M. Mier, deceased
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Patent number: 5837454Abstract: An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over the dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments.Type: GrantFiled: June 7, 1995Date of Patent: November 17, 1998Assignee: i-STAT CorporationInventors: Stephen N. Cozzette, Graham Davis, Imants R. Lauks, Randall M. Mier, deceased, Sylvia Piznik, Nicolaas Smit, Paul Van Der Werf, Henry J. Wieck, Susan Steiner, Jeanne Itak
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Patent number: 5834224Abstract: An electrochemical sensor is provided containing a supporting material having a surface of noble metal such as gold or palladium to which is bound an enzyme such as glucose oxidase via binding molecules. The binding molecules are in the form of a homogenous monolayer and are bound to the metal surface by anchor groups such as thiol, disulphide or phosphine groups. The enzyme is linked to the binding molecules by an ionic bond, a covalent bond or a metal-chelate bond. The binding molecules may contain a spacer such as an alkylene chain. Coverage of the binding molecules on the metal surface is less than the maximum coverage to optimize enzyme coverage, decrease response time of the sensor and increase signal yield per surface area. The monolayer may contain diluent molecules which are not linked to an enzyme and which are bound to the metal surface via anchor groups.Type: GrantFiled: August 23, 1995Date of Patent: November 10, 1998Assignee: Boehringer Mannhein GmbHInventors: Petra Ruger, Dorothee Ambrosius, Bernd Schmidt, Peter Sluka, Hans-Joachim Guder, Erhard Kopetzki
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Patent number: 5830341Abstract: The present invention provides for electrode assemblies and methods in which electron transfer between a redox reaction product and an electrically conductive electrode material is facilitated by a metallo macrocyclic compound, preferably a metallo isoindole ringed compound and more preferably a ferro isoindole ringed compound. The redox reaction is usually catalysized by a redox enzyme, such as an oxidase.Type: GrantFiled: January 23, 1996Date of Patent: November 3, 1998Inventor: Markas A. T. Gilmartin
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Patent number: 5807471Abstract: A ion selective electrode is formed by an electrode having a first membrane with a diffusion rate selective to heparin or other polyions, and a selective polymeric coating thereon having a polyion diffusion rate lower than the polyion diffusion rate of the first membrane. The electrode is sensitive to solutions containing low polyion concentrations such as low heparin concentrations.Type: GrantFiled: April 30, 1996Date of Patent: September 15, 1998Assignee: Medtronic, Inc.Inventors: Michael Dror, Robert F. Baugh, Peter Ross Schaad
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Patent number: 5804400Abstract: A rapid single step assay suitable for the detection or quantification of enzymes, in particular, hydrolases, especially, aminopeptidases and esterases. The enzymatic reaction causes the cleavage of a metal ligand labelled hydrolase substrate. The cleaved ligand alters the electrochemiluminescence of bidentate aromatic heterocyclic nitrogen-containing ligand reagent. The change in electrochemiluminescence correlates to the presence of hydrolase activity present in the sample. The assay can be performed on an IGEN Origen.RTM. Analyzer.Type: GrantFiled: February 5, 1996Date of Patent: September 8, 1998Assignee: Igen International, Inc.Inventors: Mark Martin, Liwen Dong
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Patent number: 5804048Abstract: An improved electrode assembly is disclosed for use in assaying glucose in solution, e.g., in undiluted whole blood. The assembly includes a sensor electrode and a special overlaying multi-layer membrane that can be sterilized by gamma radiation without reducing the activity of a glucose oxidase enzyme located in an intermediate layer of the membrane. An outer layer of the membrane is formed with microscopic pores having a predetermined density and predetermined size, for reliably controlling the flux of glucose and oxygen from the solution to the intermediate layer, where they react in the presence of the glucose oxidase enzyme to form reactions products that include hydrogen peroxide. The outer layer thus functions as a diffusion barrier, to eliminate the adverse effects of any oxygen deficit that might be present. In addition, an inner layer of the membrane functions as an interference barrier, for controlling the permeation of the hydrogen peroxide reaction product to the underlying electrode.Type: GrantFiled: August 15, 1996Date of Patent: September 8, 1998Assignee: Via Medical CorporationInventors: David K. Wong, Joseph Y. Lucisano
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Patent number: 5804047Abstract: An enzyme sensor system capable of quantitatively determining a particular component contained in a biological sample in a rapid and easy manner is disclosed. More particularly, an electrically conductive enzyme, an enzyme-immobilized electrode using the same and a composition for use in the preparation of the enzyme electrode are disclosed. The composition for an enzyme-immobilized electrode according to the present invention enables electrodes of various patterns to be produced by screen printing.Type: GrantFiled: December 16, 1994Date of Patent: September 8, 1998Assignees: Dai Nippon Printing Co., Ltd., Isao KarubeInventors: Isao Karube, Susan Anne Clark, Ryohei Nagata
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Patent number: 5798030Abstract: The present invention relates to a novel biosensor comprising an electrode membrane combination. This novel biosensor employs compounds include a linker lipid for use in attaching a membrane including a plurality of ionophores to an electrode and providing a space between the membrane and the electrode, the electrode being either in part or totally made up of the linker lipid. The linker lipid comprises within the same molecule a hydrophobic region capable of spanning the membrane, an attachment group used to attach the molecule to an electrode surface, a hydrophilic region intermediate said hydrophobic region and the attachment group and a polar head group region attached to the hydrophobic region at a site remote from the hydrophilic region.Type: GrantFiled: April 9, 1997Date of Patent: August 25, 1998Assignees: Australian Membrane and Biotechnology Research Institute, University of SydneyInventors: Burkhard Raguse, Bruce A Cornell, Vijoleta L Braach-Maksvytis, Ronald J Pace
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Patent number: 5798031Abstract: The present invention concerns an electrochemical sensor made up of an insulating base having an electrode layer on its surface and a lid of deformable material which comprises a concave area in the central portion thereof, so that when it is mated with the base, the lid and base form a capillary space containing the electrode layer. When the electrode layer is in operative contact with a reaction layer comprising an enzyme which will cause the production of mobile electrons when contacted with a suitable analyte, the concentration of analyte, e.g. glucose in blood, can be measured by measuring the current created by the flow of mobile electrons when contacted with a suitable analyte, the concentration of analyte, e.g. glucose in blood, can be measured by measuring the current created by the flow of mobile electrons.Type: GrantFiled: May 12, 1997Date of Patent: August 25, 1998Assignee: Bayer CorporationInventors: Steven C. Charlton, Larry D. Johnson, Matthew K. Musho, Dennis Slomski
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Process for the continuous enzymatic extraction of hydrophobic products and device suitable therefor
Patent number: 5795750Abstract: In a process for the continuous enzyme-catalyticzed enzymatic production of hydrophobic products in an aqueous solution of a reaction mixture, the product is extracted from the product containing reaction mixture by way of a product-permeable microporous membrane into an organic solvent and the product-depleted reaction mixture is recycled.Type: GrantFiled: April 7, 1997Date of Patent: August 18, 1998Assignee: Forschungzentrum Julich GmbHInventors: Wolfgang Kruse, Udo Kragl, Christian Wandrey -
Patent number: 5795453Abstract: The present invention provides for electrode assemblies and methods in which electron transfer between a redox reaction product and an electrically conductive electrode material is facilitated by a metallo macrocyclic compound, preferably a metallo isoindole ringed compound and more preferably a ferro isoindole ringed compound. The redox reaction is usually catalysized by a redox enzyme, such as an oxidase.Type: GrantFiled: January 23, 1996Date of Patent: August 18, 1998Inventor: Markas A. T. Gilmartin
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Patent number: 5783056Abstract: In the case of the electrochemical enzyme biosensor comprising noble metal electrodes, an electrochemical oxidation of pyridine nucleotides takes place, in particular of NADH. The noble metal electrodes have a microtexture rich in surface pores and having catalytic properties, as a result of which the overpotential required for electrochemical oxidation of the pyridine nucleotides is reduced. Owing to these microtextures, the surface area of an electrode is from 3 to 10 times larger than its geometric surface area.Type: GrantFiled: November 20, 1995Date of Patent: July 21, 1998Assignee: Bayer CorporationInventors: Norbert Hampp, Anton Silber, Christoph Brauchle
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Patent number: 5779867Abstract: A self contained glucose sensor is provided that generally comprises a strip type glucose sensing electrode having an active surface comprising an organic conducting redox salt dispersed in a polymeric membrane, with the membrane coating a conductive strip and a strip type Ag/AgCl reference electrode having its active surface separated from physical contact with the strip type glucose sensor and a carrier strip of water absorbent paper or film containing an enzyme system and an oxidizable dye. The water absorbent carrier strip is in simultaneous contact with both the active surface of the strip type glucose electrode and the active surface of the strip type reference electrode. When an aqueous solution containing glucose is brought in contact with the carrier strip containing the enzyme system an electrical potential, proportional to the concentration of glucose in the solution, is created which can be detected by an electrometer or other suitable device.Type: GrantFiled: May 31, 1996Date of Patent: July 14, 1998Assignee: Biomedix, Inc.Inventor: Paul Shieh
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Patent number: 5776324Abstract: An electrochemical biosensor for determining the level of a target chemical in a biological fluid includes an electrochemical system including a enzyme substrate which reacts with the target chemical to yield a system signal related to the concentration in the biological fluid of said target chemical. The biosensor includes a first membrane for immobilizing the enzyme substrate. The first membrane has a porosity permitting passage therethrough of the target chemical to react with the enzyme substrate and a surface exposed to the biological fluid characterized by electron donor site susceptible to facilitating attachment thereon of proteins and fibrin which impair the system signal. A second membrane is bonded to the electron donor sites of the first membrane.Type: GrantFiled: May 17, 1996Date of Patent: July 7, 1998Assignee: Encelle, Inc.Inventor: Anton-Lewis Usala
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Patent number: 5773270Abstract: A system for electrochemical measurement of glucose concentration in an undiluted test sample, e.g. blood is provided containing a sensor including a three-layered contiguous membrane. The membrane has a thickness of 50 to 130 microns, and is composed of a 1 to 10 micron thick first layer, a 10 to 30 micron thick second layer having an average pore diameter of 15 nanometers and a 40 to 80 micron thick third layer containing glucose oxidase. The third layer is less dense than the first and second layers and the first layer is more dense than the second layer. The layers of the membrane are fused together such that no clear distinction can be made between the layers at the boundary. The sensor is calibrated in a standard glucose solution which includes catalase as a hydrogen peroxide scavenger, and the sensor has a response that is linear throughout the concentration range of glucose in an undiluted sample.Type: GrantFiled: May 17, 1994Date of Patent: June 30, 1998Assignee: Chiron Diagnostics CorporationInventors: Paul A. D'Orazio, David Sogin
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Patent number: 5770439Abstract: A biosensor is produced by depositing thick film pastes by screen-printing on a substrate to produce thick-film conductivity electrodes, and immobilizing enzymes on the electrodes. In specific embodiments, the substrate is an unfired ceramic, a fired ceramic or a plastic, the paste is a noble metal paste, enzyme immobilization is with a bifunctional reagent, a plurality of different enzymes are immobilized on different electrodes, and/or the electrodes are printed as parallel lines or in the image of a comb or concentric circles. A multi-dimensional biosensor is prepared by forming thick film paste electrodes containing an immobilized enzyme on a plurality of separate substrates, disposing the separate substrates one on top of the other in a vertical stack, pressing the stacked substrates together and curing the paste.Type: GrantFiled: September 28, 1992Date of Patent: June 23, 1998Assignee: Gesellschaft fur Biotechnologische Forschung mbB (GBF)Inventors: Ursula Bilitewski, Wiebke Drewes, Franz Bechtold
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Patent number: 5766934Abstract: Chemical and biological sensors are provided that convert the chemical potential energy of an analyte into a proportionate electrical signal through the transducer action of a microfabricated device with an integral electroconductive polymer film. The microsensor devices possess a coplanar arrangement of at least one, and typically three, microfabricated interdigitated microsensor electrode arrays each with line and space dimensions that may range from 2-20 .mu.m and is typically 10 .mu.m, a platinized platinum counter electrode of area at least 10 times the area of the interdigitated microsensor electrode array and a chloridized silver/silver chloride reference electrode. Chemical and biological sensors constructed according to the present invention employ a thin electrically conducting polymer film that is specifically attached via covalent bond formation to the interdigitated microsensor electrode component of the devices.Type: GrantFiled: October 4, 1994Date of Patent: June 16, 1998Inventor: Anthony Guiseppi-Elie
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Patent number: 5766960Abstract: A membrane comprising a closely packed array of self-assembling amphiphilic molecules, and is characterized in that it incorporates a plurality of ion channels, and/or at least a proportion of the self-assembling molecules comprise a receptor molecule conjugated with a supporting entity. The ion channel is selected from the group consisting of peptides capable of forming helices and aggregates thereof, corronands, cryptands, podands and combinations thereof. In the amphiphilic molecules comprising a receptor molecule conjugated with a supporting entity, the receptor molecule has a receptor site and is selected from the group consisting of immunoglobulins, antibodies, antibody fragments, dyes enzymes and lectins. "The supporting entity is selected from the group consisting of a lipid head group, a hydrocarbon chain(s), a cross-linkable molecule and a membrane protein. The supporting entity is attached to the receptor molecule at tan end remote from the receptor site.Type: GrantFiled: May 23, 1995Date of Patent: June 16, 1998Assignee: Australian Membrane and Biotechnology Research InstituteInventors: Bruce Andrew Cornell, Vijoleta Lucija Bronislava Braach-Maksvytis
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Patent number: 5759796Abstract: A method is described for the determination of lactic acid in organic materials of alimentary interest that involves reacting, in a buffered aqueous medium, a sample of the said materials, or a solution obtained by extracting them, with an enzyme system comprising L(+) lactate oxidase, D(-) lactate dehydrogenase and horseradish peroxidase and measuring the concentration of any oxygen produced as a result of the oxidation of the lactic acid contained in the said sample with an amperometric electrode that is selective for oxygen.A biosensor that can be used to put the above method into effect is also described.Type: GrantFiled: May 9, 1996Date of Patent: June 2, 1998Assignee: CO.RI.AL. S.C.P.A.Inventors: Alfredo Azzoni, Corrado Belicchi, Barbara Cavalieri, Franco Mazzei, Claudio Botre'
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Patent number: 5759364Abstract: Disclosed is an electrochemical sensor which is made up of an insulating base plate bearing an electrode on its surface which reacts with an analyte to produce mobile electrons. The base plate is mated with a lid of a deformable material which has a concave area surrounded by a flat surface so that when mated to the base plate there is formed a capillary space into which a fluid test sample can be drawn. The side of the lid facing the base is coated with a polymeric material which serves to bond the lid to the base plate and to increase the hydrophilic nature of the capillary space.Type: GrantFiled: May 2, 1997Date of Patent: June 2, 1998Assignee: Bayer CorporationInventors: Steven C. Charlton, Yingping Deng, Karl-Heinz Hildenbrand, Larry D. Johnson, James J. Venosky
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Patent number: 5753093Abstract: The present invention relates to a novel method for producing an electrode membrane combination. This novel method employs compounds including a linker lipid for use in attaching a membrane including a plurality of ionophores to an electrode and providing a space between the membrane and the electrode, the electrode being either in part or totally made up of the linker lipid. The linker lipid comprises within the same molecule a hydrophobic region capable of spanning the membrane, an attachment group used to attach the molecule to an electrode surface, a hydrophilic region intermediate said hydrophobic region and the attachment group and a polar head group region attached to the hydrophobic region at a site remote from the hydrophilic region.Type: GrantFiled: April 9, 1997Date of Patent: May 19, 1998Assignees: Australian Membrane and Biotechnology Research Institute, University of SydneyInventors: Burkhard Raguse, Bruce A. Cornell, Vijoleta L. Braach-Maksvytis, Ronald J. Pace
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Patent number: 5753454Abstract: Oligosaccharides are structurally characterized utilizing enzymatic digestion with an array of highly specific exoglycosidases followed by electrochemical detection and measurement of the molar quantity of cleaved monosaccharides in each enzymatic digest.Type: GrantFiled: September 12, 1995Date of Patent: May 19, 1998Assignee: Iowa State University Research Foundation, Inc.Inventor: Cheng S. Lee
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Patent number: 5746898Abstract: An electrochemical-enzymatic sensor for the determination of substances, in particular glucose, in body fluids, which possesses a good long-term stability, includes: a sensor electrode of electrocatalytically inactive carbon, a counterelectrode, a reference electrode, an enzyme-containing layer located before the sensor electrode, and a diaphragm of biocompatible, hydrophilic, oxygen-permeable material covering the enzyme layer toward the body fluid and retaining the enzyme.Type: GrantFiled: November 12, 1992Date of Patent: May 5, 1998Assignee: Siemens AktiengesellschaftInventor: Walter Preidel
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Patent number: 5741712Abstract: The present invention provides a biosensor that detects an analyte in a sample by measuring the response of a membrane within which associated ion channels undergo state changes upon interaction between the analyte and the ionic channels. The state change response is detected as result of the change in ionic flow through the membrane.Type: GrantFiled: May 23, 1995Date of Patent: April 21, 1998Assignee: Australian Membrane and Biotechnology Research InstituteInventors: Bruce Andrew Cornell, Vijoleta Lucija Bronislava Braach-Maksvytis
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Patent number: 5741409Abstract: The present invention relates to novel electrode membrane combination. This novel combination employs compounds include a linker lipid for use in attaching a membrane including a plurality of ionophores to an electrode and providing a space between the membrane and the electrode, the electrode being either in part or totally made up of the linker lipid. The linker lipid comprises within the same molecule a hydrophobic region capable of spanning the membrane, an attachment group used to attach the molecule to an electrode surface, a hydrophilic region intermediate said hydrophobic region and the attachment group and a polar head group region attached to the hydrophobic region at a site remote from the hydrophilic region.Type: GrantFiled: April 9, 1997Date of Patent: April 21, 1998Assignees: Australian Membrane and Biotechnology Research Institute, The University of SydneyInventors: Burkhard Raguse, Bruce A Cornell, Vijoleta L Braach-Maksvytis, Ronald J Pace
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Patent number: 5741634Abstract: An enzyme electrode for a chemical sensor includes an electrode including a pair of working electrodes, a reference electrode and a counter-electrode. A first film is formed on one of the working electrodes, which includes a polyvinyl alcohol and a surface-active agent. A second film is formed on the other working electrode including polyvinyl alcohol, surface-active agent and enzyme. An overcoat film of high polymer electrolyer including a pH buffer is formed on the first and second films. The polymerization degree of the polyvinyl alcohol is from 300 to 3000 and the high polymer electrolyer may be alginic acid, polystyrene sulfonic acid or polyacrylic acid, and the pH buffer is a positive ion having a valence of 1.Type: GrantFiled: June 6, 1995Date of Patent: April 21, 1998Assignee: A & D Company LimitedInventors: Yoshiteru Nozoe, Kazuharu Murata
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Patent number: 5731008Abstract: A microbiocidal solution for in vivo and in vitro treatment of microbial infections contains an electrolyzed saline containing regulated amounts of ozone and active chlorine species wherein the ozone content is between about 5 and 100 mg/L and the active chlorine species content of between about 5 and 300 ppm. The active chlorine species contains free chlorine, hypochlorous acid and the hypochlorite ion as measured by a chlorine selective electrode. The solution is prepared by subjecting a 1% or less saline to electrolysis under conditions sufficient to produce the desired active ingredients. The solution is preferably utilized at an isotonic saline concentration and may be adjusted with hypertonic saline. The solution may be used for the in vitro treatment of infected whole blood, blood cells or plasma to reduce contamination and is effective in treatment of fluids infected with HIV, hepatitis and other viral, bacterial and fungal agents.Type: GrantFiled: August 30, 1996Date of Patent: March 24, 1998Assignee: Medical Discoveries, Inc.Inventor: Robert E. Morrow
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Patent number: 5723345Abstract: The present invention provides a general purpose specific binding assay method which has the advantages of highly accurate and quick measurements which exclude the effects of various factors that decrease reliability of the measured values, such as non-specific reactants in test samples, assay conditions and inactivation and the like changes in the activity of reagents. The present invention is further drawn to a specific binding assay device suitable for the practice thereof.Type: GrantFiled: June 27, 1995Date of Patent: March 3, 1998Assignee: Mochida Pharmaceutical Co., Ltd.Inventors: Tadakazu Yamauchi, Hideyuki Terasawa
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Patent number: 5723284Abstract: The present invention relates to a control solution for and a method of testing the performance of an electrochemical sensing device for determining the concentration of an analyte in a blood sample. The device contains a sensing means having a working electrode on which is deposited an enzyme capable of reacting with the analyte to provide electrons and a mediator to shuttle the electrons to the surface of the working electrode. The control solution is formulated so that the device will recognize the control solution as being something other than blood and automatically exclude the results obtained with the control solution from its memory unit.Type: GrantFiled: April 1, 1996Date of Patent: March 3, 1998Assignee: Bayer CorporationInventor: Ling Ye
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Patent number: 5720862Abstract: There is provided a sensor for the measurement of a content of a material in liquid which material is oxidized with an oxidase enzyme in which sensor a reagent layer is formed on an electrode system composed of a measuring electrode and a counter electrode both of which are formed on an insulating substrate, the reagent layer is composed of a hydrophilic polymer layer comprising a hydrophilic polymer and a reactive layer comprising the oxidase enzyme and an electron carrier, and the reagent layer further comprises a phosphate.Type: GrantFiled: April 5, 1996Date of Patent: February 24, 1998Assignee: Kyoto Daiichi Kagaku Co., Ltd.Inventors: Katsumi Hamamoto, Hisashi Okuda
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Patent number: 5711862Abstract: A portable biochemical measurement device including a measurement main body containing an enzyme sensor holder for an enzyme sensor. A cover, mounted on the measurement main body, covers the enzyme sensor holder. The cover contains a chamber filled with a liquid medium to maintain the moisture of the enzyme sensor. Inside the cover are a cartridge and packing, which form the chamber containing the liquid medium. The enzyme sensor holder is inserted into the cover through the packing so that the enzyme sensor is immersed in the liquid medium thereby keeping the enzyme sensor moist.Type: GrantFiled: March 15, 1996Date of Patent: January 27, 1998Assignee: OMRON CorporationInventors: Yusaku Sakoda, Hideki Endo, Satoshi Nakajima
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Patent number: 5711861Abstract: The invention provides an electrochemical sensor system for measuring analyte concentrations in a sample fluid. The invention is particularly useful for measuring analytes such as glucose in a patient. An implantable glucose sensor includes a disc-shaped body containing multiple anodes on opposing sides of the body. Electrodes are connected to a transmitter which transmits radio signals to an external receiver and computer where data is processed to yield relative glucose concentration figures.Type: GrantFiled: November 22, 1995Date of Patent: January 27, 1998Inventors: W. Kenneth Ward, Eric S. Wilgus