Enzyme Or Microbe Electrode Patents (Class 435/817)
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Patent number: 5264092Abstract: The present invention relates to an electrochemical enzyme biosensor for use in liquid mixtures of components for detecting the presence of, or measuring the amount of, one or more selected components. The enzyme electrode of the present invention includes a redox polymer immobilized on an electrode surface, one or more enzymes, at least one of which is a de-hydrogenase, a coenzyme and an electron collector.Type: GrantFiled: October 2, 1991Date of Patent: November 23, 1993Assignee: Moltech CorporationInventors: Terje Skotheim, Yoshiyuki Okamoto, Lo G. Gorton, Hung Sui Lee, Paul Hale
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Patent number: 5262035Abstract: Enzyme electrodes having a surface coated with a film. The film is formed from materials in which a redox enzyme is covalently bonded to a three dimensional molecular structure. The molecular structure is of the class having multiple redox centers, for example, a crosslinked redox polymer.Type: GrantFiled: August 2, 1989Date of Patent: November 16, 1993Assignee: E. Heller and CompanyInventors: Brian A. Gregg, Adam Heller
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Patent number: 5262305Abstract: A biosensor including an interferant-eliminating catalyst and method for analyzing an analyte in a biological sample is disclosed.Type: GrantFiled: September 3, 1991Date of Patent: November 16, 1993Assignee: E. Heller & CompanyInventors: Adam Heller, Ruben Maidan
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Patent number: 5256271Abstract: A microbioelectrode having high performance produced by immobilization by incorporating a biologically active substance in the interior or on the surface of a porous conductive material layer or fine particle layer which has been deposited on the surface of a transducing material. The inventive microbioelectrode demonstrates sufficient output even if the sensor using the electrode is very small in size.Type: GrantFiled: June 17, 1992Date of Patent: October 26, 1993Assignees: Japan as represented by President of National Rehabilitation, Sumitomo Cement Co., Ltd.Inventors: Yoshihito Ikariyama, Shigeru Yamauchi, Tomoaki Yukiashi
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Patent number: 5250419Abstract: This biosensor comprises a membrane (8), in which an enzyme catalyzing the transformation of a substrate used in the cutaneous metabolism is immobilized, means for detecting and measuring a phenomenon caused by said transformation, which is representative of the concentration of the substrate to be measured, with said substrate being brought into contact with the enzymatic membrane (8), and a measuring cell (13), a wall area of which is formed by the membrane (8) and which is capable of being closed, during the measurement, by a cutaneous covering area (15), with the cell (13) being combined with means for making circulate therein a liquid for placing in solution the substrate to be measured. For the measurement, the biosensor is applied to the skin, the buffer is injected into the cell and, once said cell is filled, the detection and the measurement are carried out, then the buffer is again made to circulate in order to remove the solubilized substrate.Type: GrantFiled: August 13, 1991Date of Patent: October 5, 1993Assignee: L'OrealInventors: Dominique Bernard, Michel Kermici, Michel Prunieras
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Patent number: 5244562Abstract: Switching devices (10) comprise a micro-electrode (12 or 16a') coated with a templated polymer (14). For example, the template molecule is glucose and the bulk polymer is a thiophene/boronic acid-substituted thiophene copolymer. The switch is activated or inactivated by the concentration of glucose in a solution (38) contacting the coated micro-electrode. Advantageously, the dimensions of the switch may be very small, 10.sup.-6 or less.Type: GrantFiled: July 31, 1991Date of Patent: September 14, 1993Assignee: Hewlett-Packard CompanyInventor: Dale D. Russell
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Patent number: 5242793Abstract: An electrode comprising an electrically conductive base, and a selectively permeable membrane which is produced by forming a membrane from a mixed solution comprising (a) albumin, (b) at least one type of crosslinking agent and (c) chitosan. The selectively permeable membrane is useful, e.g., in conjuction with an electrode. An enzyme electrode is also provided having the selectively permeable membrane disposed on the electrode and an immobilized enzyme membrane disposed on the selectively permeable membrane. The immobilized enzyme membrane is prepared by incorporating a carboxylate into the solution containing the enzyme and an aldehyde as the crosslinking agent. The crosslinking is effected by heating or drying.Type: GrantFiled: March 7, 1990Date of Patent: September 7, 1993Assignee: Kanzaki Paper Manufacturing Co., Ltd.Inventors: Akio Kariyone, Ryuzo Hayashi, Yoshio Hashizume
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Patent number: 5240571Abstract: The concentration of NADH or NADPH in a test solution is determined by adding a redox coupling agent, preferably 2,6 dichloroindophenol DCIP, to the test solution. The coupling agent reacts with the NADH or NADPH to form an electroactive coupling agent (DCIPH.sub.2) which is then detected electrochemically at a lower voltage than would be required to detect the NADH or NADPH. This can be used to detect NADH or NADPH formed by any well known enzymatic or immunoassay method which produces NADH as a detectable product. This has particular application to biological fluids such as whole blood which does not require any treatment of the test sample prior to electrochemical analysis. In particular, red blood cells do not have to be removed from whole blood samples to provide reliable data.Type: GrantFiled: April 24, 1991Date of Patent: August 31, 1993Assignee: University of CincinnatiInventors: William R. Heineman, Hua-Tang Tang, H. Brian Halsall, Amadeo J. Pesce
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Patent number: 5236567Abstract: An enzyme sensor, which comprises an enzyme-modified electrode and a counter electrode, wherein the enzyme-modified electrode comprises, as electrode components, an enzyme and/or an enzyme-containing substance and mediator. The enzyme sensor is useful in analysis, such as the analysis of compounds in foods or components in the living body, the diagnosis of diseases and the control of reaction processes. The preparation of the enzyme-modified electrode is also described.Type: GrantFiled: May 24, 1990Date of Patent: August 17, 1993Assignee: Nakano Vinegar Co., Ltd.Inventors: Akira Nanba, Masahiro Fukaya, Hajime Okumura, Yoshiya Kawamura
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Patent number: 5236570Abstract: An anion exchange membrane for ionic macromolecules, specifically heparin, which is formed of a polymeric matrix material, an anion exchange material suitable for heparin detection, and a plasticizer can be employed in an electrochemical sensor arrangement to directly measure the concentration of heparin ions in blood or blood fluid. Potentiometric response to heparin has been observed with membranes comprising 30-70 wt. % polymeric matrix material, such as polyvinyl chloride, 0.1-12 wt. % quaternary ammonium salt, such as tridodecyl methyl ammonium chloride, and 30-70 wt. % of a plasticizer, such as dioctyl sebacate.Type: GrantFiled: March 10, 1992Date of Patent: August 17, 1993Assignee: University of MichiganInventors: Shu-Ching Ma, Mark E. Meyerhoff, Victor C. Yang
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Patent number: 5234566Abstract: The present invention provides a biosensor comprising at least one lipid membrane, each membrane including at least one gated ion channel. The membranes comprise a closely packed array of self-assembly amphophilic molecules and the gated ion channel has a conductance which is dependent upon an electric field applied across the membrane. The biosensor of the present invention may comprise a plurality of discrete membranes each including at least one gated ion channel. The conductance of each of the membranes is measurable independently of the conductance of the other membranes.Type: GrantFiled: April 18, 1991Date of Patent: August 10, 1993Assignee: Australian Membrane and Biotechnology Research Institute Ltd.Inventors: Peter D. J. Osman, Bruce A. Cornell, Burkhard Raguse, Lionel G. King
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Patent number: 5232856Abstract: An electroporation apparatus provides for the electroporation of cells attached to an electrode. The electrode may be transparent to allow cell viewing. If the electrode exhibits a voltage drop a constant electrical field may be obtained over the cell layer by controlling the position or character of the opposed electrode. Alternately, cells may be electroporated under an electrical field which varies in a continuous, geometrically uniform manner over the cell layer.Type: GrantFiled: July 30, 1990Date of Patent: August 3, 1993Inventor: Kevin L. Firth
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Patent number: 5231028Abstract: Enzyme electrodes are described which are of reduced sensitivity to alcohol. The electrodes comprise a porous resin-bonded layer of powdered carbon or graphite, onto which the enzyme is immobilized, that layer containing either finely divided platinum oxide, or finely divided platinum the surface of which is provided with a thin oxide film, e.g. by an anodisation process, the finely divided platinum oxide or anodised platinum being uniformly dispersed throughout the resin-bonded carbon or graphite layer and preferably preadsorbed onto the surface of the powdered carbon or graphite prior to bonding. Also disclosed is a method of making such electrodes by a polarization treatment of a preassembled platinized electrode.Type: GrantFiled: July 5, 1989Date of Patent: July 27, 1993Assignee: Cambridge Life Sciences plcInventor: William H. Mullen
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Patent number: 5229282Abstract: The present invention relates to a process of preparation of a biosensor comprising forming an electrode system mainly containing carbon on an insulating base plate, treating the surface of electrode system with an organic solvent, and then arranging a reaction layer on the electrode system to give a unified element. The reaction layer contains an enzyme, electron acceptor and a hydrophilic polymer. Treatment with the organic solvent improves adhesion of the reaction layer to the electrode system. The electrode system contains a working electrode and a counter electrode. The electrode system is formed from a carbon paste containing a resin binder. Treatment is preferably carried out by wiping the surface of the electrodes with a material impregnated by the organic solvent.Type: GrantFiled: November 26, 1990Date of Patent: July 20, 1993Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Toshihiko Yoshioka, Mariko Kawaguri, Shiro Nankai
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Patent number: 5227042Abstract: An enzyme electrode is prepared with a composite coating on an electrical conductor. The composite coating is formed from a casting solution of a perfluorosulfonic acid polymer, an enzyme, and a carbon supported catalyst. The solution may be cast directly on the conductor surface or may be formed as a membrane and applied to the surface. The perfluorosulfonic acid ionomer formed from the casting solution provides an insoluble biocompatible protective matrix for the enzyme and acts to retain the enzyme for long term availability in the electrode structure. The carbon supported catalyst provides catalytic sites throughout the layer for the oxidation of hydrogen peroxide from the enzyme reactions. The carbon support then provides a conductive path for establishing an electrical signal to the electrical conductor.Type: GrantFiled: May 15, 1992Date of Patent: July 13, 1993Assignee: The United States of America as represented by the United States Department of EnergyInventors: Thomas A. Zawodzinski, Mahlon S. Wilson, Judith Rishpon, Shimshon Gottesfeld
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Patent number: 5225064Abstract: Horseradish peroxidase (HRP) immobilized on colloidal gold and then deposited on an electrode surface can be reduced at a convenient rate at low voltage (Ag/AgCl) without an electron transfer mediator. Bioelectrodes combining both a colloidal gold-adsorbed oxidase and colloidal gold-adsorbed HRP located on an electrode surface are efficient biodetectors, particularly for the measurement of low glucose levels in samples when glucose oxidase is employed as the sensing enzyme. The biodetectors may be employed for mediatorless detection of a wide variety of analytes depending on the oxidase employed.Type: GrantFiled: March 6, 1992Date of Patent: July 6, 1993Assignee: Enzyme Technology Research Group, Inc.Inventors: Robert W. Henkens, Junguo Zhao, John P. O'Daly
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Patent number: 5223124Abstract: The present invention relates generally to the immobilization or incorporation of polypeptides, especially enzymes or other bioactive polypeptides into polymeric matrixes, especially polyurethane, membranes produced by said polymers, and the utilization of such membranes in biosensors. A preferred type of biosensor is the needle sensor designed for in vivo monitoring of glucose which comprises a core platinum anode (2) coated with an insulating lacquer (3), the anode (2) is situated inside a stainless steel reference cathode (4) which is insulated from the anode (2) by a layer of epoxy resin (5) At one end, of the tip, the electrode (1) has a detection surface (6) which is in an acute angle to the general direction of the electrode (1). At the other end, the base, the electrode (2) is provided with terminals (7) and (8) for the anode (2) and cathode (4), respectively.Type: GrantFiled: September 5, 1990Date of Patent: June 29, 1993Assignee: Novo Nordisk A/SInventor: Henrik Ege
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Patent number: 5217900Abstract: A biological reactor which is operated using microorganisms and/or enzymes and used for the oxidative conversion of organic compounds, and in which the organic compounds to be converted are employed in the presence of a biocatalyst in the reactor space (4) (anode space) and the enzymes are regenerated at a polarized electrode (1), the polarization of the electrode (1) being effected by means of a catalyst electrode (2) which is separated from the reactor space (4) by a polyelectrolyte (3) and is located in an electrolyte space (5), wherein the electrode (1) is prepared from an electrically conductive carbon material which has been partially oxidized on the surface at a potential .epsilon..sub.h of from +1.3 to +10 V in an aqueous oxygen-containing mineral acid.Type: GrantFiled: July 13, 1989Date of Patent: June 8, 1993Assignee: BASF AktiengesellschaftInventors: Wolfgang Habermann, Ernst-Heinrich Pommer, Peter Hammes
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Patent number: 5217875Abstract: A method for detecting biological activities in a specimen, for instance a blood sample, employing a sealable container with a culture medium, into which the sample is introduced, wherein metabolic processes are enhanced in the presence of microorganisms in the sample, thereby causing changes to take place in the concentrations of the substances subject to such processes. The concentration changes are measured by optodes that are in direct contact with the sample, and by an excitation and detection assembly assigned to these optodes, to which is connected an evaluation unit for determining concentration changes of the substances over time.Type: GrantFiled: March 29, 1990Date of Patent: June 8, 1993Assignee: AVL AGInventors: Hellfried Karpf, Herbert Smole
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Patent number: 5217594Abstract: The invention relates to novel b of detecting metal ion concentrations less than about 10 .mu.g/dl fluid. Biosensors based on the enzyme isocitrate dehydrogenase are particularly suited for detecting trace lead ion concentrations in water and in blood. Bioelectrodes are fabricated from surface deposited colloidal gold adsorbed enzyme that retains high catalytic activity Other aspects of the invention include detection devices for convenient and rapid measurement of metal ions.Type: GrantFiled: January 15, 1992Date of Patent: June 8, 1993Assignee: Enzyme Technology Research Group, Inc.Inventors: Robert W. Henkens, Junguo Zhao, John P. O'Daly
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Patent number: 5208154Abstract: Methods and techniques are described for reversibly binding charged biological particles in a fluid medium to an electrode surface. The methods are useful in a variety of applications. The biological materials may include microbes, proteins, and viruses. The electrode surface may consist of reversibly electroactive materials such as polyvinylferrocene, silicon-linked ferrocene or quinone.Type: GrantFiled: April 8, 1991Date of Patent: May 4, 1993Assignee: The United States of America as represented by the Department of EnergyInventors: Paul F. Weaver, Arthur J. Frank
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Patent number: 5206170Abstract: In a sulfur dioxide detector using SO.sub.2 -oxidant microbes, a bio-membrane is located at one end of an oxygen concentration sensor, the bio-membrane containing the SO.sub.2 -oxidant microbes between an immobilized membrane and a gas permeable membrane. The sensor has an electrode in contact with the immobilized membrane. A dish-shaped or frusto-conical cell has an open end which is in contact with the gas permeable membrane so that SO.sub.2 -laden solution supplied to the cell causes sulfurous acid to oxidize to sulfuric acid as the SO.sub.2 permeates through the bio-membrane so as to change an output from the sensor. An inlet and outlet hole are formed on a sidewall of the cell. The outlet hole is located to be always directly above the inlet hole so as to drain foam formed when the SO.sub.2 -laden solution is supplied to the cell through the inlet hole and drained from the outlet hole.Type: GrantFiled: October 1, 1991Date of Patent: April 27, 1993Assignee: Nakano Vinegar Co., Ltd.Inventors: Takeshi Sato, Nobuko Kubo, Hirofumi Akano, Yoshiya Kawamura, Shigesada Iijima
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Patent number: 5206145Abstract: An apparatus is provided for measuring the concentration of a substance in a sample solution. The apparatus comprises first electrode means, second electrode means and an enzyme channel between the first and second electrode means. The enzyme channel contains an enzyme for catalyzing a reaction of the substance whose concentration is to be measured. In use, a known volume of the sample solution is presented to the first electrode means in a test solution including an excess of a mediator, one of reduction or oxidation of the mediator being coupled to the reaction of the substance. The first electrode means is arranged to ensure that the mediator is respectively completely oxidized or reduced, and also to remove any interferent species. The test solution is then passed through the enzyme channel so as to permit reaction of all of the substance present in the solution, whereby a quantity of the mediator is respectively reduced or oxidized.Type: GrantFiled: August 23, 1991Date of Patent: April 27, 1993Assignee: Thorn EMI plcInventor: Alan F. Cattell
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Patent number: 5206135Abstract: A process for the detection of herbicides that inhibit acetolactate synthase (EC 4.1.3.18) by use of the enzyme, a suitable substrate (pyruvate, .alpha.-aceto-lactate, .alpha.-ketobutyrate, or .alpha.-aceto-.alpha.-hydroxybutyrate), and an oxygen-sensitive electrode is disclosed.Type: GrantFiled: December 28, 1990Date of Patent: April 27, 1993Assignee: E. I. Du Pont de Nemours and CompanyInventors: Lynn M. Abell, John V. Schloss
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Patent number: 5204239Abstract: Biosensors for qualitative and quantitative analysis comprise an amphipathic liquid crystalline membrane composed of a lipid bilayer attached to a recording electrode via bridging anchoring molecules. The lipid bilayer is doped with biologic or synthetic ion channels and is in continuous contact with a bulk aqueous medium on both its surfaces. The bridging anchoring molecules may contain a phospholipid moiety linked to a polyoxylakylene chain terminated with a thiol or thioether residue.Type: GrantFiled: January 9, 1991Date of Patent: April 20, 1993Assignee: Yeda Research and Development Co., Ltd.Inventors: Carlos Gitler, Itzhak Yuli
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Patent number: 5202261Abstract: A conductive sensor and its use in a diagnostic assay are disclosed. The miniaturized conductive sensor, utilizing a conducting polymer, is used in a diagnostic device to determine the presence or concentration of a predetermined analyte in a liquid test sample, wherein the predetermined analyte, like glucose, is assayed by an oxidase interaction. The interaction between the oxidase and a small amount of the predetermined analyte in the test sample generates, either directly or indirectly, a dopant compound in a reaction zone of the conductive sensor. The dopant compound then migrates to the detection zone of the conductive sensor of the diagnostic device to oxidize the conducting polymer and convert the conducting polymer from an insulating form to a conducting form. The resulting increase in conductivity of the conducting polymer is measured, then the conductivity increase is correlated to the concentration of the predetermined analyte in the test sample.Type: GrantFiled: November 18, 1991Date of Patent: April 13, 1993Assignee: Miles Inc.Inventors: Matthew K. Musho, J. Oakey Noell, Pius H. Tse
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Patent number: 5198367Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is covalently bonded to a suitable carrier molecule, which is also covalently bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.Type: GrantFiled: June 9, 1989Date of Patent: March 30, 1993Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
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Patent number: 5196340Abstract: An enzyme electrode comprising an enzyme and a coenzyme immobilized in at least one layer is provided. This electrode has an outer membrane preventing the coenzyme from dissipation and so sensitivity and durability can be improved. In an inner membrane containing the enzyme and the coenzyme, a mediator of electron transfer may be added. The enzyme and the coenzyme may be separated in two layers, respectively, in the inner membrane to improve measurement sensitivity.Type: GrantFiled: July 30, 1990Date of Patent: March 23, 1993Assignee: NEC CorporationInventor: Shigeyuki Miyamoto
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Patent number: 5192507Abstract: A method of immobilizing and stabilizing an active biological receptor in a polymeric film and receptor-based biosensors for determining an analyte of interest in a sample. The receptor-based biosensors include a polymeric film having a biological receptor capable of binding an analyte of interest immobilized therein according to the method of the present invention and an electrical means for determining the presence and quantity of the analyte. In particular, acetylcholine receptor and opiate receptor have been immobilized in a polymeric film made by combining the receptor, a material (e.g., bovine serum albumin, gelatin) capable of polymerizing and a polymerizing agent (e.g., glutaradehyde).Type: GrantFiled: March 4, 1991Date of Patent: March 9, 1993Assignee: Arthur D. Little, Inc.Inventors: Richard F. Taylor, Ingrid G. Marenchic, Edward J. Cook
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Patent number: 5190872Abstract: Alcohol oxidase is immobilized by bonding an aminosilane coupling agent to a carrier, bonding a multifunctional aldehyde such as glutaraldehyde to an amino group of the aminosilane, washing the carrier to remove free multifunctional aldehyde and bonding alcohol oxidase to the multifunctional aldehyde bonded to the aminosilane. Washing to remove free multifunctional aldehyde enables immobilizing a one molecule thickness of alcohol oxidase on the carrier since free multifunctional aldehyde is not present to cross-link alcohol oxidase molecules together. A thin layer of alcohol oxidase is advantageous when assaying for alcohol since a thin layer does not retain hydrogen peroxide that can deactivate alcohol oxidase. The carrier preferably contains hydroxyl groups and is porous, and can be a silicate-containing carrier such as diatomaceous earth or fire brick.Type: GrantFiled: August 27, 1990Date of Patent: March 2, 1993Assignee: Kanzaki Paper Mfg. Co., Ltd.Inventors: Yoshio Hashizume, Akio Kariyone, Ryuzo Hayashi, Minako Oka
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Patent number: 5185256Abstract: This invention relates to a biosensor which comprises an insulative base, an electrode system formed on the substrate and primarily made of carbon, and a perforated body having an enzyme and an electron acceptor and integrally combined with the electrode system whereby a concentration of a specific component in a biological liquid sample can be electrochemically measured rapidly and accurately by a simple procedure of mere addition of the liquid sample. Several simple biosensors for measuring a specific component in a liquid sample are known including a sensor of the type in which a change of a dye formed by an enzyme reaction is optically detected and a sensor of the type using an enzyme electrode. These sensors, respectively, involve an interference with colored matters in liquid sample and necessity of washing of an electrode system every measuring procedure. In addition, the sensors are complicated in structure and materials therefor are expensive.Type: GrantFiled: October 15, 1991Date of Patent: February 9, 1993Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Shiro Nankai, Mariko Kawaguri, Takashi Iijima
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Biosensor containing immobilized Zymomonas mobilis cells for measuring glucose, fructose and sucrose
Patent number: 5177012Abstract: A biosensor for the determination of glucose and fructose concentrations is provided. The biosensor is produced by a method which comprises treating Zymomonas mobilis whole cells with an organic solvent such as xylene and n-butanol, immobilizing the treated whole cells onto a support selected from the group consisting of gelatin, collagen, agarose, cellophane and polyacrylamide to give an immobilized whole cell enzyme membrane and adhering the membrane to the surface of a pH electrode to give the biosensor. The resulting biosensor is capable of determning glucose and fructose in high concentrations such as 5 g/L and 50 g/L, respectively. Invertase can be immobilized with the whole cells to provide a biosenser for the determination of sucrose.Type: GrantFiled: August 27, 1990Date of Patent: January 5, 1993Assignee: Korea Advanced Institute of Science & TechnologyInventors: Hak-Sung Kim, Je-Kyun Park -
Patent number: 5173165Abstract: The invention relates to an enzyme electrode having a bienzyme system containing fungal peroxidase or horseradish peroxidase and one or more oxidases, and to the use of the electrode.Type: GrantFiled: October 11, 1990Date of Patent: December 22, 1992Assignee: Gesellschaft fur Biotechnologische Forschung mbH (GBF)Inventors: Rolf Schmid, Juozas Kulys
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Patent number: 5171689Abstract: As the conventional simple bio-sensors for measuring the particular component in living bodies, there are those in which a change in dye caused by enzyme reaction is detected optically, but such bio-sensors had a problem that precision is low owing to disturbance of the color of liquid samples. With bio-sensors using an enzyme electrode, the precision was high, but operation of measurement was troublesome. The present invention made it possible to detect the concentration of the particular component electromechanically with rapidity, simplicity and high precision by merely putting a porous substrate containing at least enzyme on the electrode system and impregnating the body with a liquid sample.Type: GrantFiled: April 18, 1989Date of Patent: December 15, 1992Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Mariko Kawaguri, Shiro Nankai, Takashi Iijima
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Patent number: 5166063Abstract: The present invention provides a method for immobilizing biomolecules on a conductive substrate to produce a biosensor.Type: GrantFiled: June 29, 1990Date of Patent: November 24, 1992Assignee: Eli Lilly and CompanyInventor: Kirk W. Johnson
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Patent number: 5160418Abstract: Enzyme electrodes are disclosed consisting essentially of a uniform homogeneous layer of a finely divided platinum group metal or oxide, preferably preadsorbed onto the surface of an activated carbon or grapite powder, and deposited from suspension upon the surface of an electrically conductive substrate and in admixture with an enzyme and optionally a water soluble or water-dispersible binder. Preferably the enzyme electrodes are produced by coating the substrate with a suspension of the enzyme, the finely divided platinum group metal, and if present the carbon or graphite powder and binder, and drying at a temperature below that at which the enzyme is deactivated.Type: GrantFiled: July 18, 1989Date of Patent: November 3, 1992Assignee: Cambridge Life Sciences plcInventor: William H. Mullen
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Patent number: 5158662Abstract: A device and method for detecting and/or continuously measuring the concentration of oxidizable biodegradable substrates in a medium. The device comprises an oxygenated first electrode and a second electrode. The first electrode is capable of carrying microorganisms capable of oxidizing the substrates in the presence of oxygen thus releasing electrons. The electrons are received by the second electrode and detected and/or measured by the device. The rate of electron transfer correlates to the concentration of substrate in the medium providing a method of continuous measurement of the substrate in the medium.Type: GrantFiled: November 19, 1990Date of Patent: October 27, 1992Inventor: Philip S. Osborne
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Patent number: 5156972Abstract: An analyte specific chemical sensor for determining an analyte in a test medium. The sensor comprises a sensing surface which is coated with reversible competitive recognition units (RCRUs) each of which contains as constituent components at least one receptor and at least one ligand, one of which components is an analyte analogue. In these RCRUs the receptor and the ligand are a priori connected to each other, directly or indirectly, in such configuration that even when, for example, an analyte analogue ligand is displaced from the receptor by an analyte ligand, the analogue will still be retained in relatively close proximity to the receptor. In addition, the relative positions of the receptor and the ligand in the RCRU are such that when no analytes are present or when the analyte concentration is at a low level, they are affinity conjugated by a specific affinity interaction.Type: GrantFiled: September 5, 1990Date of Patent: October 20, 1992Assignee: The State of Israel, Atomic Energy Commission, Soreq Nuclear Research CenterInventor: David Issachar
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Patent number: 5149629Abstract: The invention relates to a novel assay for the determination of entities having biological activity and to a device for carrying out such determinations. The assay is a very sensitive one and quantities in the picogram per milliliter range can be determined. The assay is based on chrono-coulometric measurements with sequential measurements of a plurality of samples being carried out with the aid of a multiplexer, in combination with a potentiostat, there being provided suitable electrodes and means for applying a predetermined voltage. One of the electrodes is advantageously a glassy carbon electrode, carbon felt or cloth or carbon paper. Amongst biologically active entities there are antibodies/antigens; hormones/receptors; nuclotides/nucleotide probes, one of the members of such a pair being immobilized on an electrode surface, being tagged with an enzyme providing a signal in coulometric measurements.Type: GrantFiled: April 4, 1988Date of Patent: September 22, 1992Assignee: Ramot University Authority for Applied Research and Industrial Development Ltd.Inventors: Judith Rishpon, Ilara Rosen
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Patent number: 5149630Abstract: An electrochemical specific binding assay of a ligand (e.g., antigen, hapten or antibody) wherein at least one of the components is enzyme-labelled, and which includes the step of determining the extent to which the transfer of electrons between the enzyme substrate and an electrode, associated with the substrate reaction, is perturbed by complex formation or by displacement of any ligand complex relative to unbound enzyme-labelled component.The electron transfer is aided by electron-transfer mediators which can accept electrons from the enzyme and donate them to the electrode or vice versa (e.g. ferrocene) or by electron-transfer promoters which retain the enzyme in close proximity with the electrode without themselves taking up a formal charge.The electrochemical apparatus will typically comprise two or three electrodes, including one working electrode onto which components may advantageously be immobilized.Type: GrantFiled: February 9, 1988Date of Patent: September 22, 1992Inventors: Gordon C. Forrest, Hugh A. O. Hill, Simon J. Rattle, Grenville A. Robinson
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Patent number: 5147781Abstract: The invention relates to an assay for the determination of the enzyme lactate dehydrogenase-5 (LDH5) and to a biosensor for such quantitative determination.The assay is based on the interaction of this enzyme with the substrate lactic acid and nicotine-amine adenine dinucleotide (NAD) to yield pyruvic acid and the reduction product of NAD.Anti-LDH5 antibody is bound to a suitable glassy carbon electrode, this is contacted with the substrate containing LDH5, rinsed, inserted into a NAD solution, connected to an amperometric system, lactic acid is added and the current changes are measured, which are indicative of the quantity of LDH-5.Type: GrantFiled: March 2, 1987Date of Patent: September 15, 1992Inventors: Judith Rishpon, Ilana Rosen, Zeev Hollander
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Patent number: 5137827Abstract: A method is disclosed for detecting the occurrence of a binding or complex-forming reaction between specific substances by utilizing the binding reaction to modify an electrical circuit, and then measuring a change in the electrical state of the circuit. A diagnostic element useful in such a method includes a layer of a biogenic substance, such as an antigen, coated onto a non-conductive base between a pair of electrical conductors superposed on the base. Antibodies which react with the antigen are treated so that they become bound to fine electrically conductive, metallic particles. The electrically conductive particles having antibody bound thereto are then added to the antigen layer deposited on the base and allowed to react therewith. Electrically conductive particles are thereby bound to the base due to the binding reaction between the antigen and antibody to thereby form aggregates of electrically conductive particles which modify the circuit.Type: GrantFiled: September 25, 1990Date of Patent: August 11, 1992Assignee: Midwest Research Technologies, Inc.Inventors: Susan J. Mroczkowski, Kenneth A. Siegesmund, Donald E. Yorde
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Patent number: 5134070Abstract: A method and device are disclosed for culturing of adherent cell monolayer cultures on an electrode surface and subjecting the cells to an electrical field. The device may generally comprises cell culture dish, for example a petri-type dish, having a bottom, with an electrically conductive, optically transparent coating amenable to cell adhesion on the upper surface of the bottom. A metal electrode may contact the underside of the coating and is connected to a source of electrical power. The method involves use of the device for culturing the cells under the intermittent or continuous influence of an electric field, or during the establishment of an electrical field or potential. Further, a method and device are disclosed for the sensing of cell poration, and the use of this information to automate the process of electroporation. Further yet, a device and method are disclosed for use in assisting in the time-correlated mapping of the sequence of serial and parallel gene replication.Type: GrantFiled: October 30, 1990Date of Patent: July 28, 1992Inventor: Dael R. Casnig
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Patent number: 5130009Abstract: In order to produce a small-volume flow measuring cell with good flow characteristics in a sensor device for determining the concentration of a substrate in a sample medium, comprising an enzyme electrode which is covered by a membrane and a reference electrode, both of which are in contact with the measuring cell, the proposal is put forward that the reference electrode be located outside of the membrane cover of the enzyme electrode and that the maximum extension of the flow measuring cell normal to the flow direction of the sample medium essentially be the same as the diameter of the sensitive layer of the enzyme electrode.Type: GrantFiled: January 24, 1990Date of Patent: July 14, 1992Assignee: AVL Medical Instruments AGInventors: Hermann Marsoner, Helmut List, Heinz Kontschieder, Falko Skrabal
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Patent number: 5124253Abstract: A dry strip element for use in an electrochemical assay for determining theophylline in a sample, the test element carrying a working electrode and a reference electrode and separately carrying at the working electrode an alkaline phosphatase and an electroinactive phosphate ester which is a substrate for the alkaline phosphatase and from which an electroactive compound can be released by catalytic activity of the alkaline phosphatase.Type: GrantFiled: September 27, 1989Date of Patent: June 23, 1992Assignee: Medisense, Inc.Inventors: Nicola C. Foulds, Jane M. Wilshere
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Patent number: 5122456Abstract: A method is disclosed for the quantitative determination of 1,4-dihydronicotinamide adenisne dinucleotide (NADH) in solution. The method comprises contacting the NADH-containing solution with an activated carbon electrode, maintaining the carbon electrode at a controlled, fixed potential effective to cause oxidation of NADH at the electrode surface, and measuring the current output from the carbon electrode, wherein there is used a noble metal containing preferably a platinized or palladized activated carbon electrode comprising a porous, heterogeneous, resin-bonded layer of activated carbon or graphite particles comprising the finely divided noble metal preadsorbed thereon and bonded together with a natural or synthetic resin binder, preferably a hydrophobic resin such as polytetrafluoroethylene.Type: GrantFiled: February 24, 1989Date of Patent: June 16, 1992Assignee: Cambridge Life Science plcInventors: Hugh P. Bennetto, Gerard M. Delaney, Jeremy R. Mason, Christopher F. Thurston, John L. Stirling, David R. DeKeyzer, William H. Mullen
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Patent number: 5120420Abstract: A biosensor of the invention comprises an insulating base board (1) having formed thereon, in sequence, leads (2, 3, 3'), an electrode system mainly made of carbon (4, 5, 5'), an insulating layer (6) and a reaction layer (14) composed of an enzyme and an electron acceptor, and being provided thereon with a space (8) defined by a spacer (7) and a cover 9). When a biological sample solution is brought into contact with the inlet (10) of the biosensor having the above-described structure, the sample solution is introduced into its inside, while the air within the space (8) is rapidly discharged through the outlet (11) and, at the same time, the space (8) is filled with the sample solution up to the neighborhood of the outlet. Thus, measurement can be conducted inexpensively at a high speed with a high accuracy through simple procedures without residual bubbles.Type: GrantFiled: November 27, 1989Date of Patent: June 9, 1992Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Shiro Nankai, Mariko Kawaguri, Mayumi Ohtani, Takashi Iijima
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Patent number: 5118404Abstract: An enzyme electrode usable for determining high concentration of analyte in a sample solution is provided, by providing an enzyme-immobilized membrane in the electrode with pH buffer capacity. Durability of the electrode can be improved by using albumin crosslinked by glutaraldehyde as a permeation-restricted membrane in the electrode. Method of using the electrode can be simplified by introducing a stirring step, measuring outputs before and after the stirring step and utilizing difference of measured outputs.Type: GrantFiled: February 27, 1991Date of Patent: June 2, 1992Assignee: NEC CorporationInventor: Atsushi Saito
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Patent number: 5114676Abstract: In order to improve the response behavior of an optical sensor for determining at least one parameter in a liquid or gaseous sample, the sensor including a substrate which is provided with carrier particles and a fluorescent indicator immobilized thereon, the substrate is configured as a polymer film transparent to both excitation and emission radiation, and the individual carrier particles carrying the fluorescent indicator in immobilized form are bonded with only part of their surface to a thin layer of a thermoplastic material adhering to the polymer film and assume thermosetting properties after the carrier particles have been pressed in, whereas the other part of the surface of the carrier particles extend into an optically transparent hydrogel layer which covers the thermoplastic layer and in which the carrier particles are anchored mechanically. Such sensors may easily be attached to the end of an optical waveguide and may be made in any size by a simple punching operation.Type: GrantFiled: July 28, 1989Date of Patent: May 19, 1992Assignee: AVL AGInventors: Marco J. Leiner, Leonie Weiss, Otto S. Wolfbeis
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Patent number: 5106751Abstract: A biochemical sensor includes a material that nucleates as bubbles on the surface of an electrical conductor, optical fiber, or acoustic medium. The nucleating bubbles respectively change the conductivity, refraction, or propagation of such surfaces according to the concentration of the analyte in a solution over the sensor.Type: GrantFiled: May 11, 1989Date of Patent: April 21, 1992Assignee: Biotronic Systems CorporationInventor: Arnold L. Newman