Enzyme Or Microbe Electrode Patents (Class 435/817)
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Patent number: 5540828Abstract: A method for making a sensing element for use in a sensor or biosensor that amperometrically measures the concentration of an analyte in a liquid, includes the following sequential steps: a) obtaining an electrode; b) immersing the electrode in a solution of monomer that is capable of being electropolymerized into an electrically insulating polymer; c) flowing an electric current from a cathode through the solution to the electrode at a voltage and amperage sufficient to cause the monomer to polymerize on the surface of the electrode, thereby yielding an electrode coated with an adherent layer of electrically insulating polymer; and e) impregnating the polymeric coating on the surface with a sensing agent that is capable, when contacted by a specific analyte in a chemical or biological liquid, of generating an electroactive molecule that can be detected amperometrically.Type: GrantFiled: February 15, 1994Date of Patent: July 30, 1996Inventor: Alexander Yacynych
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Patent number: 5534132Abstract: An amperometric biosensor for the detection of an affinity reaction is described. The sensor includes an electrode having on its testing surface a hydrogel in which a selective binding unit and redox species are immobilized.Type: GrantFiled: May 4, 1995Date of Patent: July 9, 1996Inventors: Mark Vreeke, Patrick Rocca
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Patent number: 5531870Abstract: This invention relates to a process for performing enhanced selectivity potentiometric ion determinations using an asymmetric ion membrane electrode having an asymmetric membrane with a hydrophilic layer fused to an ion-selective layer.Type: GrantFiled: May 5, 1995Date of Patent: July 2, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventor: Geun Sig Cha
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Patent number: 5531878Abstract: Sensor devices comprising enzyme electrodes incorporating a microporous membrane coated with the carbonaceous material known as "diamond-like carbon" (most conveniently deposited by decomposition of a hydrocarbon, induced by radiation or a high electric field). The membrane material is preferably a polycarbonate and its thickness preferably less than 10 microns, and the coating is preferably 0.01 to 5 .mu.m thick. The preferred porosity is provided by pores of the order of 0.05 to 0.01 microns. The coated membrane imparts high resistance to fouling by contact with whole blood, extends the linearity of the electrode response over a substantially greater range, e.g. in the analytical determination of glucose in blood, and combines a high degree of restriction to passage of interferents while retaining high permeability to hydrogen peroxide and oxygen. Most conveniently used for amperometric measurements, especially using a Clark electrode pair, with an "active" anode of platinum.Type: GrantFiled: February 17, 1995Date of Patent: July 2, 1996Assignee: The Victoria University of ManchesterInventors: Pankaj M. Vadgama, Seamus P. J. Higson
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Patent number: 5525511Abstract: An electrochemical biosensor comprising a conductive support member (2) mounted on a substrate (1) and carbon pads (4) overlying the conductors (2) and surmounted by working electrode and reference electrode pads (5) and (6). A membrane (8) applied over the electrodes incorporates a quantity of mediator to facilitate repeated use of the biosensor.Type: GrantFiled: April 28, 1993Date of Patent: June 11, 1996Assignee: Environmental & Medical Products Ltd.Inventor: Eric D'Costa
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Patent number: 5520788Abstract: Improved Newman type enzyme containing laminated membranes are disclosed for use in conjunction with polarographic cells to measure analyte concentration in solutions. The laminated membranes comprise a semipermeable outer, support layer including super large pores of greater than about 200 .ANG. in diameter. The outer layer preferably comprises pore sizes of about 380-750 .ANG. in diameter and has a percentage porosity of about 0.005-0.2%.Type: GrantFiled: January 17, 1995Date of Patent: May 28, 1996Assignee: The Yellow Springs Instrument Company, Inc.Inventor: Jay M. Johnson
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Patent number: 5520787Abstract: The present invention provides a diagnostic flow cell for determining the presence or amount of an analyte which may be contained in a test sample. The flow cell comprises a spacing layer having a longitudinal void disposed between a pair of opposed substrates. The spacing layer and the opposed substrates define a flow channel wherein reagent means can be immobilized. When the immobilized reagent means is contacted with an analyte, the reagent means can produce an electrically, optically, or electrically and optically detectable response to the analyte. Hence, the reagent means that is immobilized within the flow channel can comprise (i) a counter electrode, a reference electrode and a working electrode, (ii) an optically sensitive dye or (iii) a counter electrode, a reference electrode and a working electrode and an optically sensitive dye.Type: GrantFiled: March 3, 1995Date of Patent: May 28, 1996Assignee: Abbott LaboratoriesInventors: Ted J. Hanagan, Lance K. Safford, Steven G. Schultz, Jay R. Ford, Edmund T. Marciniec, Kenneth S. Johnson, John D. Norlie, Jr.
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Patent number: 5520786Abstract: Disclosed is an improved electrode suitable for the electrochemical regeneration of the co-enzymes NADH and NADPH. The electrode has imparted on its surface a mediator function which is a 3-phenylimino-3H-phenothiazine or a 3-phenylimino-3H-phenoxazine. Also disclosed is a method of improving the performance of a biochemical fuel cell which operates with a dehydrogenase as a catalyst and a co-enzyme as the energy-transferring redox couple which involves using the improved electrode in the fuel cell.Type: GrantFiled: June 6, 1995Date of Patent: May 28, 1996Assignee: Bayer CorporationInventors: Michael L. Bloczynski, Paul F. Corey, Yingping Deng, Alison J. Murray, Matthew K. Musho, Hans-Ulrich Siegmund
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Patent number: 5518893Abstract: The biochemical oxygen demand (BOD) of aqueous liquids containing organic matter is determined. A microorganism culture is aerated to exhaust the organic matter available to the microorganisms. An aqueous liquid test sample containing organic matter is added to the exhausted culture to measure the amount of oxygen consumed by the microorganisms. The determination of biochemical oxygen demand (BOD) of the sample is determined in as little as 20 minutes. An apparatus is provided for determining BOD comprising a magnetic stirrer, an aerating instrument, a dissolved oxygen/temperature sensor, tubing pumps and a quick biochemical oxygen demand (QBOD) bottle. The BOD may be automatically calculated using the apparatus.Type: GrantFiled: March 11, 1994Date of Patent: May 21, 1996Assignee: Yukong LimitedInventors: Yong-Seok Park, Hyung-Charn Kim, Sung-Hong Kim, Yong-Taek Yi
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Patent number: 5514601Abstract: A method of and apparatus for the presence of a target species in a sample taken from or consisting of a mixture of species, comprising the steps of introducing one or more electrical diodes into the mixture prior to taking the sample from the mixture, in such a manner that the presence of diodes in the sample is dependent on the presence of the target species in the sample; passing an alternating electrical signal having a known waveform through the sample; and detecting the modification of the waveform of the signal emerging from the sample due to the presence of the diode or diodes in the sample.Type: GrantFiled: January 17, 1995Date of Patent: May 7, 1996Assignee: Boehringer Mannheim GmbHInventor: Paul J. Reilly
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Patent number: 5508171Abstract: A new electrochemical biosensor and method of its use. The electrochemical biosensor has a pair of electrodes consisting of a working electrode and a counter electrode made of the same electrically conducting materials. The counter electrode may be the same size or smaller than the working electrode. The biosensor includes a sample receiving portion wherein a portion of the electrode surfaces is covered by a reagent that includes a redox mediator and an enzyme. A fluid that contains an analyte is added to the sample receiving portion. A reaction involving the analyte, enzyme and redox mediator occurs. After this reaction is complete, an electrical potential difference is applied between the electrodes. Diffusion limited current is measured and correlated to the concentration of analyte in the fluid.Type: GrantFiled: February 22, 1994Date of Patent: April 16, 1996Assignee: Boehringer Mannheim CorporationInventors: P. Douglas Walling, Joseph E. Bateson, Lance S. Kuhn, M. Luann Ochs, Kent M. Kost, Martin T. Gerber, Klaus H. Pollmann, Chi-Neng A. Han
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Patent number: 5501956Abstract: Enzyme or substrate determinations can be achieved by employing an organic second substrate, which produces a product which may be coupled with a metal inorganic redox couple capable of interacting with and affecting the potential of a metal electrode on a semiconductor surface. Particularly, hydrogen peroxide or indoxyl phosphate are coupled with iron- or ruthenium-containing ionic redox couples for determination with a noble metal electrode.Type: GrantFiled: January 24, 1994Date of Patent: March 26, 1996Assignee: Molecular Devices CorporationInventors: Henry G. Wada, Harden M. McConnell, Dean G. Hafeman
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Patent number: 5500188Abstract: Photoresponsive devices including a photoresponsive electrode are provided, and methods for their use to measure changes in environment at a site at or about the surface of the photoresponsive device. By employing a source of light for irradiating a site on the surface and means for biasing the photoresponsive electrode in relation to a counterelectrode, a variation in electrical signal can be related to a change in a medium in photoresponsive modulation relationship to the photoresponsive electrode surface.Type: GrantFiled: January 24, 1994Date of Patent: March 19, 1996Assignee: Molecular Devices CorporationInventors: Dean G. Hafeman, John W. Parce, Harden M. McConnell
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Patent number: 5500351Abstract: A biosensor for detecting metal ions of elements such as Hg, Cr, As, Tc, Cu, Ag, Se, V, Mo and U which are capable of being reduced to metal by a reductase enzyme. The reductase enzyme is contained in an immobilized enzyme composition also including a cofactor and a coenzyme. The cofactor, for example NADPH, is oxidized by a reaction coupled with the reductase reduction of the metal ions and the cofactor in its oxidized state, e.g., NADP.sup.+, is re-reduced thereby maintaining a supply of the reduced state cofactor by action of the coenzyme in a further oxidation reaction coupled with the cofactor reduction. The further oxidation reaction may be oxidation of an alcohol to an aldehyde brought about by a dehydrogenase coenzyme. The oxidation brought about by the coenzyme, i.e., the amount of oxidized product, is a measure of the amount of oxidized state cofactor produced which, in turn, is a measure of the concentration of metal ions being detected.Type: GrantFiled: July 18, 1994Date of Patent: March 19, 1996Assignee: British Nuclear Fuels PLCInventors: Harry Eccles, Geoffrey W. Garnham, Christopher R. Lowe, Neil C. Bruce
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Patent number: 5498542Abstract: Disclosed is an electrode suitable for the electrochemical regeneration of the co-enzymes NADH and NADPH. The electrode has imparted on its surface a mediator function which is a 3-methylene-3H-phenothiazine or a 3-methylene-3H-phenoxazine compound.Type: GrantFiled: September 29, 1994Date of Patent: March 12, 1996Assignee: Bayer CorporationInventors: Paul F. Corey, Matthew K. Musho
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Patent number: 5496697Abstract: Methods and apparatus are disclosed for detecting the effects of cell affecting agents on living cells. The method steps include providing living cells that are retained in a micro flow chamber. The micro flow chamber is adapted for either continuous or intermittent flow of solutions or suspensions in intimate contact with the cells. The solutions or suspensions, which contain a cell affecting agent, are then flowed in intimate contact with the cells and the pit is measured.Type: GrantFiled: September 8, 1993Date of Patent: March 5, 1996Assignee: Molecular Devices CorporationInventors: John W. Parce, Harden M. McConnell, Gillian M. K. Humphries, Karen M. Kercso, John C. Owicki, Josef E. Kercso
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Patent number: 5494562Abstract: A solid state, multi-use electrochemical sensor having an electrically nonconductive substrate, a working electrode, and a semi-permeable membrane covering the working electrode. The working electrode includes an electrically conductive material adhered to a portion of the substrate. A first portion of the conductive material is covered with an electrically insulating dielectric coating, and a second portion of the conductive material is covered with an active layer. The active layer includes a catalytically active quantity of an enzyme carried by platinized carbon powder particles, which are distributed throughout the active layer. A sensor package for incorporating a sensor is provided.Type: GrantFiled: June 27, 1994Date of Patent: February 27, 1996Assignee: Ciba Corning Diagnostics Corp.Inventors: Thomas C. Maley, Paul A. D'Orazio, Bonnie C. Dalzell, Peter G. Edelman, James E. Flaherty, Richard W. Mason, Robert R. McCaffrey
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Patent number: 5494831Abstract: A electrochemical immunosensor system is provided which uses electrical signals to measure binding events. The system includes an immunosensor having a sensing electrode in contact with a fluid containing an analyte concentration. A quantity of antibodies or other binding agent is adsorbed on or otherwise affixed to the electrode surface such that a portion of the antibodies of the binding agent binds a portion of the analyte to form complexes on the electrode surface. Signal generating means develop an electrical signal at the sensing electrode such that a response current is produced through the sensing electrode. The response current has measurable signal characteristics which are dependent upon the number of complexes formed, and therefore the analyte concentration within the fluid.Type: GrantFiled: August 30, 1993Date of Patent: February 27, 1996Assignee: Hughes Aircraft CompanyInventor: Andrew Kindler
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Patent number: 5491083Abstract: Poly(fluoroalkyl) sugar reagents are prepared containing a sugar such as a monosaccharide or a disaccharide to which are bonded a plurality of fluoroalkyl anchor groups capable of attaching to a fluorocarbon surface, and either a reactive group capable of covalent coupling to a biomolecule such as an enzyme or a charged group to form an ion-exchanger or a non-ionic group to give a neutral fluorosurfactant. A spacer may be between the reactive group and the sugar. The poly(fluoroalkyl) sugar reagents are strongly adsorbed onto fluorocarbon surfaces to provide supports for such applications as separation and immobilization of biomolecules such as enzymes, carrying out heterogeneous diagnostic assays, and preparation of biosensors.Type: GrantFiled: October 5, 1994Date of Patent: February 13, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventors: Rene Arentzen, Prabhakar K. Jadhav, Robert K. Kobos, Bruce E. Smart
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Patent number: 5489515Abstract: A device for analyzing the metabolism of cells includes a supporting base which carries a pH measuring electrode, a control electrode designed for proton exchange with the liquid, a reference electrode, and a counterelectrode, and which, together with at least one other part, confines a hollow space containing the cells and a liquid. The electrodes are connected to electronic circuit elements. In the course of an analysis the pH value of the liquid is determined by means of the pH measuring electrode and the reference electrode. Between the control electrode and the counterelectrode an electric current is passed through the liquid and controlled such that the pH of the liquid is maintained at a constant preset value beneficial to the cells, by proton exchange with the control electrode. In addition, the amount of charge required for generating the current during the measuring period is determined to obtain a measure for the intensity of the metabolic process and thus for the vitality of the cells.Type: GrantFiled: December 5, 1994Date of Patent: February 6, 1996Assignee: AVL Medical Instruments AGInventors: Rudolf Hatschek, Erich W. F. Heitz
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Patent number: 5476776Abstract: A reusable, miniature, implantable electrochemical sensor, a method of making the same, and a powder therefor are provided. Enzyme material is immobilized on bulk particulate matter, and a reaction chamber of the sensor is then filled therewith. The sensor is implanted in an environment where it comes into contact with a specific component of a fluid with which the enzyme material chemically reacts to produce electrical signals for measuring the reaction. The method preferred for preparing the powder which is used in the electrochemical sensor involves first covalently bonding a quantity of an enzyme to fine particles in powder form to immobilize the enzyme is cross-linked to a non-enzyme protein with a cross-linking agent. Finally, the particles are added containing the immobilized enzyme cross-linked to a protein from the first step to the enzyme cross-linked to a protein from the second step to obtain the powder.Type: GrantFiled: July 15, 1994Date of Patent: December 19, 1995Assignee: University of New MexicoInventor: Ebtisam S. Wilkins
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Patent number: 5468620Abstract: Methods of glycosylation analysis are described in which a sample containing one or more specific oligosaccharide(s) (the analyte) is contacted with a surface on which is immobilized a glycosidase specific for the analyte and/or a specific binding partner for a product of the action of a glycosidase on the analyte. The surface may be the active surface of a biosensor, e.g., a biosensor based on the principle of frustrated total reflection.Type: GrantFiled: November 29, 1993Date of Patent: November 21, 1995Assignee: Fisons PLCInventors: James O. Molloy, Denise V. Pollard-Knight
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Patent number: 5468366Abstract: The present invention provides a new device for use in measuring lead levels in biological and environmental samples. Using square wave coulometry and colloidal gold particles impregnated on carbon electrodes, the present invention provides a rapid, reliable, portable and inexpensive means of detecting low lead levels. The colloidal gold modified electrodes have microelectrode array characteristics and produce significantly higher stripping detection signals for lead than are produced at bulk gold electrode surfaces. The method is effective in determining levels of lead down to at least 5 .mu.g/dL in blood samples as small as 10 .mu.L.Type: GrantFiled: September 30, 1994Date of Patent: November 21, 1995Assignee: Andcare, Inc.Inventors: Steven Wegner, Michael A. Harpold, Terence M. McCaffrey, Susan E. Morris, Marek Wojciechowski, Junguo Zhao, Robert W. Henkens, Najih Naser, John P. O'Daly
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Patent number: 5468605Abstract: One aspect of the invention is the method of operating a microphysiometer including a plunger assembly having a plunger body with a microchamber at one end for receiving a sample and a passage in the plunger body communicating with the microchamber comprises passing a medium transversely through the-sample in the microchamber. Another aspect of the invention is the construction of the plunger assembly wherein the sample is positioned in the microchamber and the passage and microchamber are constructed and arranged so that medium flow is transverse through the sample. The sample may be a tissue slice retained between a pair of screens or membranes, adherent cells on a mesh screen or non-adherent cells retained in a chamber defined by a washer and a pair of screens or membranes.Type: GrantFiled: October 15, 1993Date of Patent: November 21, 1995Assignee: Molecular Devices Corp.Inventors: Albert K. M. Harris, Gregory L. Kirk, John C. Owicki, Timothy D. Dawes, Richard C. Kuo
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Patent number: 5466589Abstract: The present invention is directed to coated substrates having a coating of biological macromolecules, preferably proteins, which are capable of being immobilized on a substrate surface and have a marker. These proteins usually are mutant proteins obtained by mutagenesis of the gene encoding a random positioning protein. When a mutant protein molecule is immobilized on the substrate, the marker of the mutant protein molecule is in a select spatial relationship with both the substrate and the markers of adjacent protein molecules. A substrate coated with an oriented layer of the mutant proteins exhibits improved or different properties when compared to a substrate having a randomly positioned layer of proteins thereon.Type: GrantFiled: September 11, 1992Date of Patent: November 14, 1995Assignee: Biotechnology Research & Development CorporationInventors: Jill M. Olinger, Stephen G. Sligar, Mark A. McLean, Paul W. Bohn, Patrick Stayton
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Patent number: 5466575Abstract: 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: September 10, 1992Date of Patent: November 14, 1995Assignee: i-Stat CorporationInventors: Stephen N. Cozzette, Graham Davis, Imants R. Lauks, Randall M. Mier, Sylvia Piznik, Nicolaas Smit, Paul Van Der Werf, Henry J. Wieck
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Patent number: 5453171Abstract: An anion exchange membrane for ionic macromolecules, specifically heparin, which is formed of a polymeric matrix material and an anion exchange material suitable for heparin detection 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. Moreover, a solid state sensor employs tridodecyl methyl ammonium chloride (TDMAC) dissolved in a polymeric compound, such as silicone rubber, to form a membrane which is responsive to heparin concentration.Type: GrantFiled: August 16, 1993Date of Patent: September 26, 1995Assignee: The Board of Regents of the University of MichiganInventors: Shu-Ching Ma, Mark E. Meyerhoff, Victor C. Yang
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Patent number: 5443701Abstract: An analytical method for determining the presence or concentration of an analyte in a liquid medium is provided in which electrons are transferred from an electrode material of an electrode to the redox center of an enzyme, by the mediation of an electron mediator, whereby in the presence of an analyte the enzyme calalyzed a redox reaction in which the analyte is converted into a product. By measuring either the concentration or the product or the charge which flows in this process, the presence and/or concentration of the analyte in the medium is determined. Either or both of the enzyme and the electron mediator are immobilized on the electrode.Type: GrantFiled: August 23, 1993Date of Patent: August 22, 1995Assignee: Yissum Research Development Company of Hebrew University of JerusalemInventors: Itamar Willner, Evgeny Katz, Azalia Riklin, Ron Kasher, Benjamin Shoham
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Patent number: 5437973Abstract: A sensor of the enzyme-electrode type containing a layer of porous material of restricted permeability between the enzyme and a sample to be analysed. The porous material has a percentage porosity not greater than 5% and preferably in the range 0.005% to 0.5%.Type: GrantFiled: May 7, 1993Date of Patent: August 1, 1995Assignee: The Victoria University of ManchesterInventors: Pankaj M. Vadgama, Stephen Churchouse, William Mullen
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Patent number: 5437999Abstract: A method for fabricating high-resolution, biocompatible electrodes is disclosed, allowing production of an electrochemical sensor which is capable of precise analyte concentration determination on a very small sample size. Electrically conducting material is affixed to a first insulating substrate. A second insulating substrate is then affixed to the electrically conducting material and patterned using photolithography to define an electrode area. Alternatively, the electrically conducting material may be screen printed directly onto a standard printed circuit board substrate in the case of a counter or reference electrode. In either case, the substrate may be rigid or flexible. When the electrodes produced in accordance with the present invention are then used in an electrochemical sensor which includes a reagent, the small and highly-defined electrode areas permit highly-accurate electrochemical analyte measurements to be performed on very small sample sizes.Type: GrantFiled: February 22, 1994Date of Patent: August 1, 1995Assignee: Boehringer Mannheim CorporationInventors: Eric R. Diebold, Richard J. Kordal, Nigel A. Surridge, Christopher D. Wilsey
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Patent number: 5431160Abstract: A reusable, miniature, implantable electrochemical sensor, a method of making the same, and a powder therefor are provided. Enzyme material is immobilized on bulk particulate matter, and a reaction chamber of the sensor is then filled therewith. The sensor is implanted in an environment where it comes into contact with a specific component of a fluid with which the enzyme material chemically reacts to produce electrical signals for measuring the reaction.Type: GrantFiled: November 9, 1993Date of Patent: July 11, 1995Assignee: University of New MexicoInventor: Ebtisam S. Wilkins
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Patent number: 5431806Abstract: A small oxygen electrode and a method of bonding a fluorine resin film are disclosed. This small oxygen electrode includes a flat electrode substrate having at least two electrodes (a working electrode and a counter electrode) formed thereon, and a container substrate having dents formed to confront the two electrodes and contain an electrolyte therein. The container substrate is bonded to the flat electrode substrate, so that the dent confronting the electrode constituting the working electrode has a through hole extending to the side opposite to the flat electrode substrate and a gas-permeable film is formed to cover the through hole. By using this dent structure, the preparation of an oxygen electrode can be conducted while maintaining a wafer form throughout the process, and formation of an electrode pattern can be facilitated.Type: GrantFiled: November 17, 1993Date of Patent: July 11, 1995Assignee: Fujitsu LimitedInventors: Hiroaki Suzuki, Akio Sugama, Naomi Kojima
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Patent number: 5429735Abstract: A method of making and an amperometric electrode are provided. An electrode carbon ink is applied to a polymer substrate to form a working electrode. The substrate carrying the working electrode is placed in a gas plasma cleaner, such as an oxygen or nitrogen plasma, to clean the working electrode. A high radio frequency signal excites the gas plasma for a short exposure time in a range between 10 seconds and 30 seconds. Then a reagent layer is deposited to the plasma treated working electrode.Type: GrantFiled: June 27, 1994Date of Patent: July 4, 1995Assignee: Miles Inc.Inventors: Larry D. Johnson, Alison J. Murray, Matthew K. Musho
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Patent number: 5429726Abstract: Improved methods and compositions are provided to inhibit interference from formaldehyde in polarographic analytic methods. In the enzymatic oxidation of methanol to hydrogen peroxide and formaldehyde, formaldehyde serves as an interfering agent in systems where the oxygen consumed or the hydrogen peroxide produced is polarographically measured. To inhibit this interference, an amine-containing formaldehyde scavenger is added to the test system. Preferably, the scavenger comprises a polyalkyleneimine such as polyethyleneimine having a molecular weight of between about 200-1,000,000 amu. The invention is particularly well-suited for use in polarographic analytical apparatus wherein laminated membrane type enzyme electrodes are used to perform amperometric measurement with alcohol oxidase enzyme used as the oxidoreductase enzyme.Type: GrantFiled: July 5, 1994Date of Patent: July 4, 1995Assignee: The Yellow Springs Instrument Company, Inc.Inventors: Jay M. Johnson, Robert B. Spokane
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Patent number: 5427912Abstract: An immunoassay diagnostic kit, method, and apparatus for electrochemically determining the concentration of an analyte in a sample. A mixture is formed which includes the sample, an enzyme-acceptor polypeptide, an enzyme-donor polypeptide linked to an analyte analog (enzyme-donor polypeptide conjugate), a labeled substrate, and an antibody specific for the analyte to be measured. The analyte and the enzyme-donor polypeptide conjugate competitively bind to the antibody. When the enzyme-donor polypeptide conjugate is not bound to antibody, it will spontaneously combine with the enzyme acceptor polypeptide to form an active enzyme complex. The active enzyme hydrolyzes the labeled substrate, resulting in the generation of an electroactive label, which can then be oxidized at the surface of an electrode. A current resulting from the oxidation of the electroactive compound can be measured and correlated to the concentration of the analyte in the sample.Type: GrantFiled: August 27, 1993Date of Patent: June 27, 1995Assignees: Boehringer Mannheim Corporation, Boehringer Mannheim GmbHInventors: Mary E. Brown, Lance S. Kuhn, Robert J. McEnroe, Rebecca W. Muddiman, Mary L. Ochs
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Patent number: 5426042Abstract: A BOD analyzer is prepared having a microbe sensor containing an oxygen electrode and a microbe membrane. The microbe membrane is made by immobilizing microorganisms belonging to the genus Klebsiella in the membrane. Specifically, the BOD analyzer has a flow cell equipped with a microbe sensor containing an oxygen electrode and a microbe membrane, and a liquid passage which is connected with an entrance of the flow cell and which is equipped with an outlet. The microbe membrane is made by immobilizing microorganisms belonging to Klebsiella oxytoca 12092 strain in a porous hydrophilic membrane having an average pore size of 0.65-3 .mu.m in diameter by using at least one gelating agent selected from alginic acid or salts thereof, agar, gellan gum, xathane gum, gelatine, carageenan, locust bean gum, methylcellulose, pectin, or pullulan. The BOD analyzer can be used for batch or continuous BOD analysis and enables carrying out BOD analysis in a short period of time.Type: GrantFiled: January 7, 1994Date of Patent: June 20, 1995Assignee: Nakano Vinegar Co., Ltd.Inventors: Shigeru Maeda, Akira Ohki, Takeshi Sato, Naho Kato, Hirofumi Akano, Yoshiya Kawamura, Keizo Hatagaki, Yasushi Takahashi, Mikio Yamada, Hajime Okumura
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Patent number: 5422246Abstract: An electrode is composed of a membrane, provided with open pores running through said membrane, the walls of the pores having an electrically conducting polymer coating, containing a redox enzyme bound thereto. In these type of electrodes a direct electron transfer is possible between the redox enzyme, e.g. glucose oxidase, and the electrically conducting polymer, e.g. polypyrrole. Such an electrode, which can be produced in a simple manner, has extensive application possibilities such as, for example, in a biosensor or in a production installation for the preparation of specific chemicals. As starting materials for the electrodes of the invention, use can be made of marketed porous membrane materials as well as of latex particles. The walls of the pores of porous membrane and the interstices of the latex particles respectively are provided with a thin layer of the electrically conducting polymer which in turn is provided with a redox enzyme suitable for the pursued aim.Type: GrantFiled: June 14, 1993Date of Patent: June 6, 1995Assignee: Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek TnoInventors: Cornelis G. J. Koopal, Richardus B. M. Schasfoort, Roeland J. M. Nolte
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Patent number: 5421982Abstract: An electrically conductive polymer gel is composed of a crosslinked polyacrylamide polymer including an electrolytic salt, water and a polyhydric alcohol uniformly dissolved therein, wherein the water and the polyhydric alcohol are major components of said polymer gel. The polyacrylamide series polymer in the gel has properties of being hydrophilic and being a nonelectrolyte. Therefore, a desirable connection between the gel and the electrode can be achieved with low impedance. Moreover, the polyhydric alcohol reduces the drying speed of the electrically conductive polymer gel, thereby preventing an increase in the impedance due to the dryout of the gel. Therefore, the electrically conductive polymer gel of the present invention permits an accurate measurement of an electrical phenomenon in an organism for long periods of time.Type: GrantFiled: September 13, 1993Date of Patent: June 6, 1995Assignee: Sekisui Kaseihin Kogyo Kabushiki KaishaInventors: Toshiki Ikeda, Yoshikazu Kobayashi, Shuichi Sasahara, Takashi Higashi
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Patent number: 5417835Abstract: A polyimide matrix is employed to form a substance-sensitive membrane which is particularly suited for installation on a solid state sensor. Polyimide, dissolved in a solvent, such as N,N-dimethylformamide, or N-methyl-2-pyrrolidone (polyimide encapsulant), is combined with an ionophore, plasticizer, and a lipophilic additive. The ionophore may be a calcium ionophore, an ammonium ionophore, or any other ionophore. The membrane may also incorporate, or may be covered by, a bioactive agent, such as an enzyme, an immunochemical, bacteria, antibody, virus, or antigen. The plasticizer is one or both of dimethyl phthalate and diethylene glycol dibenzoate. The lipophilic additive may be potassium tetrakis(p-chlorophenyl)borate. The resulting substance-sensitive membrane has electrochemical properties which compare favorably to those of conventional PVC membranes, and exhibit significantly greater adhesion to glasses and semiconductor substrate materials.Type: GrantFiled: October 14, 1993Date of Patent: May 23, 1995Assignee: The Board of Regents of The University of MichiganInventors: Richard B. Brown, Geun-Sig Cha
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Patent number: 5413690Abstract: A potentiometric biosensor, test strip, reagent and a potentiometric method for detection or measurement of an analyte from a fluid sample. The biosensor includes indicating and reference electrodes, and a reagent, which overlays a portion of the surface of the indicating electrode. The reagent generally includes an enzyme and a redox mediator. When a fluid sample (e.g., blood) containing an analyte (e.g., glucose) is added to the reagent, the enzyme (e.g., glucose oxidase) catalyzes a reaction involving enzyme, redox mediator (e.g., potassium ferricyanide), and analyte.This reaction may be monitored by monitoring the electrical potential at the indicating electrode surface. (Electrical potential at the indicating electrode surface changes as the concentration of oxidized and reduced forms of the redox mediator change at the indicating electrode surface.Type: GrantFiled: July 23, 1993Date of Patent: May 9, 1995Assignee: Boehringer Mannheim CorporationInventors: Kent M. Kost, Thomas J. Lindsay, John F. Price
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Patent number: 5407554Abstract: An electrochemical sensor having multiple measuring zones (34) that are sequentially insulatable, disposed on the circumference of an insulating disc (1) and associated with each other by peripheral current collectors (16, 17) which extend radially inward up to central zones where they form contacts (23, 24) for a measuring apparatus. The disc-sensor also has a device (6) for rotating the disc, and guide marks for positioning (11) and for isolating (7) the measuring zones (34), and may be contained in a housing (40). The invention is useful in the quantitative analysis of glucose.Type: GrantFiled: April 8, 1994Date of Patent: April 18, 1995Assignee: Asulab S.A.Inventor: Eric Saurer
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Patent number: 5405510Abstract: A portable, ready-for-use analyte measuring device is provided for the measurement of multiple sequential fluid samples. The device has a disposable cartridge, a calibrating fluid external to the cartridge and an analyzer. The cartridge has a housing, inlet for introduction of fluids into the housing, flow cell in fluid connection with the inlet, a waste collection area or reservoir in fluid connection to receive fluids from the flow cell, and at least one flow control means in fluid connection with the reservoir. The flow cell has a flow-through channel with one or more hydrated sensors arranged along the channel that has fluid therein. Also the flow cell has one or more spaced-apart reference electrode containment spaces in conductive contact with a contained quantity of reference fluid for the number of multiple sequential tests for the cartridge. The reference electrode containment space is spaced apart from but in conductive relation with the one or more sensors.Type: GrantFiled: May 17, 1993Date of Patent: April 11, 1995Assignee: PPG Industries, Inc.Inventors: Ronald E. Betts, Douglas R. Savage, Matthew J. Leader
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Patent number: 5403450Abstract: A method for converting reducible or oxidizable substances from aqueous solution is claimed in which the aqueous solution to be treated is brought into contact with immobilized oxidoreductases, if desired, in the presence of co-immobilized electron carriers and at the same time reduction or oxidation equivalents are supplied. Furthermore a potentiometric cell, in particular a flow cell is claimed which contains an electrode body and immobilized oxidoreductases as well as, if desired, co-immobilized electron carriers.Type: GrantFiled: March 16, 1993Date of Patent: April 4, 1995Assignee: Mobitec Molecular Biologische Technologie GmbHInventors: Robert B. Mellor, Jorg Ronnenberg, Stefan Diekmann
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Patent number: 5403462Abstract: An electrochemical electrode, comprising carbon particles distributed in porous, inorganic ceramic material produced by sol-gel technology, wherein the particles form a continuous network which enables conductivity throughout the sol-gel derived matrices.Type: GrantFiled: June 24, 1993Date of Patent: April 4, 1995Assignee: Yissum Research Development Company of the Hebrew Univeristy of JerusalemInventors: Ovadia Lev, Michael Tsionsky, Genia Gun, Victor Glezer
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Patent number: 5401378Abstract: The present invention relates to electrode membrane combinations for use in biosensors. The membrane is attached to the electrode by means of a linker molecule in a manner such that a hydrophilic space is provided between the membrane and the electrode. The linker molecule comprises within the same molecule a hydrophobic region which constitutes at least a proportion of the amphiphilic molecules making up the membrane or is attached to or is embedded in the membrane, an attachment region attached to the electrode and a hydrophilic region intermediate said hydrophobic and attachment regions. The hydrophilic region spans the space between the membrane and the electrode.Type: GrantFiled: September 21, 1993Date of Patent: March 28, 1995Assignee: Australian Membrane & Biotechnology Research InstituteInventors: Lionel G. King, Burkhard Raguse, Bruce A. Cornell, Ronald J. Pace
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Patent number: 5401377Abstract: An ion-selective electrode having an ion-selective membrane in direct contact with an electrical conductor is provided in which the membrane coats an uninsulated zone surrounded by insulation on the surface of a conductor which is coated with a layer of electrical insulation. The membrane overlays the insulation surrounding the insulation free zone and comprises a polymer which is generally of sufficiently similar composition to that comprising the electrical insulation layer so that it adheres to the insulation forming a membrane with increased structural strength. Embodiments of the electrode containing phosphatidylcholine in the ion-selective membrane have increased sensitivity.Type: GrantFiled: August 6, 1993Date of Patent: March 28, 1995Assignee: Biomedix, Inc.Inventors: Paul Shieh, Dingli Guo, Shek-Hong Lau
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Patent number: 5397451Abstract: A current-detecting type dry-operative ion-selective electrode having a working electrode and a counter electrode which are mounted on an insulating substrate, a first electrolyte layer containing a hydrophilic polymer and an ion-sensitive layer containing a hydrophobic polymer which are formed on the working electrode, and a second electrolyte layer containing a hydrophilic polymer which is laminated over the whole electrode system.Type: GrantFiled: January 27, 1994Date of Patent: March 14, 1995Assignee: Kyoto Daiichi Kagaku Co., Ltd.Inventors: Mitsugi Senda, Katsumi Hamamoto, Hisashi Okuda
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Patent number: 5395504Abstract: A small sensor for an electrochemical measuring system composed of a measuring apparatus (50) having an electronic circuit (60), a connecting device (64), a positioning and advancing device (56, 57) and an eliminating device (59, 53). The apparatus is adapted to receive the sensor (40), which has a plurality of active, successively disposable measuring zones (34). The sensor has applications in the quantitative analysis of glucose in the blood.Type: GrantFiled: February 1, 1994Date of Patent: March 7, 1995Assignee: Asulab S.A.Inventors: Eric Saurer, Erik J. Frenkel, Jean-Paul Randin, Eric Hoffmann
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Patent number: 5391272Abstract: An electro-immunosensor which can be used to determine the presence of a wide range of analytes in solution is described. Also described are methods of determining subnanogram levels of analytes in a one-step procedure. This novel immunosensor comprises an analyte binding agent bound to an electrode and a analyte/enzyme conjugate bound to the analyte binding agent as part of a catalytic electrical circuit. Displacement of the conjugate by analyte causes a proportional decrease in current. The immunosensor may also be adapted to detect two analytes in a single step by using different enzymes conjugated to the analyte binding agents.Type: GrantFiled: March 8, 1994Date of Patent: February 21, 1995Assignee: Andcare, Inc.Inventors: John P. O'Daly, Robert W. Henkens, Junguo Zhao, Honghua Zhang
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Patent number: 5389534Abstract: A biosensor is prepared having a selective detection system containing a biochemical substance such as an enzyme immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.Type: GrantFiled: March 22, 1993Date of Patent: February 14, 1995Assignee: Siemens AktiengesellschaftInventors: Wolfgang von Gentzkow, Hans-Dieter Feucht