WO1992004438A1 - Capteur biologique electrochimique - Google Patents

Capteur biologique electrochimique Download PDF

Info

Publication number
WO1992004438A1
WO1992004438A1 PCT/DK1991/000248 DK9100248W WO9204438A1 WO 1992004438 A1 WO1992004438 A1 WO 1992004438A1 DK 9100248 W DK9100248 W DK 9100248W WO 9204438 A1 WO9204438 A1 WO 9204438A1
Authority
WO
WIPO (PCT)
Prior art keywords
layer
cellulose
membrane
substrate
sensor
Prior art date
Application number
PCT/DK1991/000248
Other languages
English (en)
Inventor
Anne Rosengaard Eisenhardt
Anne-Marie Christensen
Original Assignee
Radiometer A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Radiometer A/S filed Critical Radiometer A/S
Publication of WO1992004438A1 publication Critical patent/WO1992004438A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes

Definitions

  • the invention relates to an electrochemical biosensor of the type disclosed in the opening part of claim 1.
  • Electrochemical biosensors have attracted much atten ⁇ tion since a glucose sensor was disclosed for the first time by Clark et al. in "Annals of the New York Academy of Science” 102 (1962) 29-45.
  • Electrochemical biosensors are provided with an immobi ⁇ lized enzyme which is applied to decompose a biochemi ⁇ cal analyte or a substrate - usually by use of oxygen.
  • the concentration or activity of the substrate is measured by such biosensors by determining the consumed quantity of oxygen or the formed quantity of a reaction product from the reaction of the substrate with oxygen, for example hydrogen peroxide.
  • oxygen for example hydrogen peroxide.
  • An example of an electrochemical biosensor is an elec ⁇ trochemical glucose sensor in which the enzyme glucose oxidase is applied to decompose glucose according to the reaction scheme: glucose + 0 2 + H 2 0 grIuc ⁇ se ox ⁇ as %
  • gluconic acid + H_0 2 As seen from the reaction scheme it is possible to measure the concentration or the activity of glucose in a sample by determining either the consumed quantity of oxygen or the formed quantity of hydrogen peroxide.
  • the formed quantity of hydrogen peroxide can be measured polarographically by the oxidation reaction:
  • the H 2 0 2 oxidation current can be used as a measure of the glucose content.
  • Patent No. US 4759828 (Young) as well as by Shichiri M. et al. in "Wearable-type Artificial Endocrine Pancreas with Needle-type Glucose Sensor", Lancet 2. (1982) 1129- 1131 and by Abe H. et al. in the specification of US Patent No. US 4515584.
  • the unique response characteris ⁇ tics of these sensors have been accomplished as a ' result of the fact that a membrane, which limits the diffusion of glucose molecules, is provided between the enzyme and the sample, whose glucose content is to be determined.
  • Biosensors which similarly to the glucose sensor according to Shichiri or Abe comprise a polyurethane membrane exposed to the sample, have now proved to provide generally sensor-independent measuring results when measuring on aqueous samples, but have, in fact, proved to be unable to provide sensor-independent measuring results when the sample is whole blood.
  • the sensors are to a varying degree providing too low measurements on whole blood and on aqueous solutions, which follow whole blood measuring, irrespective of the fact that they were able to measure uniformly on aque- ous solutions prior to whole blood measuring.
  • the purpose of the invention is, therefore, to provide a biosensor which, to a larger extent than the biosen ⁇ sors already known, provides sensor-independent measur- ing results when measuring on whole blood.
  • the most preferred material for the protection layer consists of regenerated cellulose such as cellophane, but a number of cellulose plastic materials such as cellulose ethers or cellulose esters, for example cellulose acetate, cellulose butyrate, cellulose pro- pionate, compounds of esters thereof, and ethyl cellu- lose and other cellulose alkyl and aryl ethers are expected to be suitable as well.
  • cellulose plastic materials such as cellulose ethers or cellulose esters, for example cellulose acetate, cellulose butyrate, cellulose pro- pionate, compounds of esters thereof, and ethyl cellu- lose and other cellulose alkyl and aryl ethers are expected to be suitable as well.
  • Polyhydroxyethyl methacrylate is among other hydrophilic materials which are expected to be suitable as protection layer.
  • Biosensors are applied both for in vitro measuring and in vivo measuring, including extracorporeal measuring where the sample is directed from the patient to a measuring chamber and subsequently back to the patient.
  • a protection layer of cellophane is particularly suit- able for such in vivo measuring as the material is strong, stands disinfection, is non-toxic, and has good bio-compability.
  • the protection layer has a thickness rang- ing up to 100 ⁇ m, particularly 10-50 ⁇ m, and especially 12-25 ⁇ m. It is preferred to apply a protection layer being as thin as possible owing to i.a. the response time of the biosensors. In the biosensor according to the invention this may be achieved by providing the protection layer by chemical modification of the sur ⁇ face of the substrate-limiting layer turning away from the enzyme so that the surface by this chemical modifi ⁇ cation is provided with the hydrophilic properties according to the invention. In a preferred embodiment the protection layer and the substrate-limiting layer are lying closely together.
  • the preferred substrate- limiting layer comprises a polyurethane layer whose slightly adhesive surface is able to hold the cellulose layer.
  • the sensor membrane is constituted by a CuprophaneTM-glucose oxi- dase-Cuprophane membrane, and the main purpose of the Cuprophane membranes is to retain the enzyme glucose oxidase at an electrode surface.
  • an electrochemical glucose sensor with a cello ⁇ phane membrane is disclosed.
  • the glucose sensor is intended for measuring on blood, and the membrane serves to retain the enzyme glucose oxidase at the same side of the membrane as the anode and to keep the enzymes of blood, for example the H 2 0 2 -cleaving cata- lase, from the H 2 0 2 formed by the enzymatic glucose conversion.
  • an electrochemical glucose sensor is disclosed with a multi-layer membrane in which one of the layers comprises a thin, dense layer that prevents low-molecular agents, which similarly to H 2 0 2 are oxid- able at the anode potential of glucose sensor, from getting into contact with the*working surface of the anode.
  • oxidable, low-molecular agents are uric acid, ascorbic acid, and various drugs, par- ticularly paracetamol.
  • the thin layer should be so thin that it is essential to use a less dense layer as carrier layer.
  • Cuprophane, cellulose acetate, or polymerized protein are suggested for this layer, and a hydrophobic material such as silicone rubber or a hydrophilic material such as cellulose acetate is suggested for the thin, dense layer.
  • a glucose sensor is disclosed with a multi-layer mem ⁇ brane in which the layer nearest the anode or the inner layer comprises a layer of silicone rubber, methyl methacrylate or cellulose acetate which cf. the above- mentioned prevents oxidable agents from getting into contact with the anode.
  • the layer nearest the sample or the outer layer constitutes a diffusion barrier, partly preventing passage of high-molecular agents and partly giving mechanical strength. Porous polycarbonate or methyl methacrylate is suggested.
  • An enzyme preparation is present between the inner layer and the outer layer.
  • a glucose sensor is disclosed with a multi-layer membrane consisting of an inner filter membrane, an enzyme membrane, and an outer asymmetri- cal, semipermeable membrane produced from cellulose acetate comprising a thin, semipermeable outer layer and a thick, porous inner layer.
  • the asymmetrical, semipermeable membrane is said to improve the stability of the sensor when measuring on whole blood compared to a sensor with a usual semipermeable outer membrane of reproduced cellulose or polycarbonate.
  • the linearity range of the sensor is not disclosed, only measurements on blood containing 0.2 mM glucose, that is a glucose content far below the clinically interesting values.
  • an amperometric sensor for example a glucose sensor with an outer cellophane membrane and a layer of a polymer containing chemically bound glucose oxidase.
  • the sensor is said to be suit ⁇ able for blood analysis, and the cellophane membrane is said to be permeable for the chemical compound which is determined by the sensor, but the specification con ⁇ tains no data for the sensor.
  • the present invention is exemplified by a glucose sensor only, it is considered equally useful in connection with other biosensors measuring the concen ⁇ tration or activity of a biochemical analyte or a substrate by means of an immobilized enzyme.
  • the invention is considered applicable in con ⁇ nection with biosensors for the following biochemical analytes, the respective immobilized enzymes being men ⁇ tioned right after the analyte: lactate/lactate oxi- dase, cholesterol/cholesterol oxidase, hypoxanthine/- hypoxanthine oxidase and pyruvate/pyruvate oxidase.
  • the working electrode is constituted by platinum anode with an exposed working surface onto which is provided a coating of cellulose acetate.
  • This coating prevents low-molecular agents such as for example ascorbic acid and paracetamol, which can be oxidized by the potential of the working electrode, from reaching the working electrode, being oxidated and consequently interfering with the substrate determina ⁇ tion.
  • a very thin layer having a thickness of for example 2-25, preferably 3-15 and particularly 5-10 ⁇ m has now proved sufficient to prevent the interfering agents from interfering the glucose determination.
  • the layer should be as thin as possible owing to the re ⁇ sponse time of the sensor which increases with increas ⁇ ing thickness of the cellulose acetate layer.
  • the substrate-limiting layer consists of a hydrophobic plastic layer, particularly a polyurethane layer.
  • the thickness of the hydrophobic plastic layer is pre ⁇ ferably 0.1-10 ⁇ m, particularly 0.2-5 ⁇ m and especially 0.5-3 ⁇ m.
  • the invention also relates to the type of sensor mem ⁇ brane stated in the opening part of claim 8 having the characteristic features stated in claims 8, 9, 10, 11, and 12.
  • FIG. 1 is a view of the sensor according to the inven ⁇ tion located in a measuring chamber
  • FIG. 2 is an exploded view of an embodiment of the sensor according to the invention.
  • FIG. 3 is a view of the sensor membrane in the sensor according to the invention.
  • the sensor 1 according to the invention shown in FIG. 1 is arranged in such way that the front 2 of the sensor constitutes one of the walls in a measuring chamber 3.
  • An inlet channel 4 opens into the measuring chamber 3, and an outlet channel 5 extends from the measuring chamber.
  • the measuring chamber 3 is not in contact with the environment when the sensor 1 is mounted.
  • the sensor 1 is located in a tubular part 6 which projects from a surface 7 of the block in which the measuring chamber 3 is provided.
  • the measuring chamber 3 is located in the surface 7 and encircled by the tubular part 6.
  • the block 8 with the measuring chamber 3 shown in FIG. 1 is the type which is applied in the blood gas ana ⁇ lyzer ABL500 manufactured and sold by RADIOMETER A/S, Copenhagen, Denmark.
  • the block contains several serial ⁇ ly connected measuring chambers with inlet channels and outlet channels of the same configuration as the ea- suring chamber 3, the inlet channel 4, and the outlet channel 5.
  • FIG. 2 shows an embodiment in further detail of the sensor 1 according to the invention.
  • the sensor con- sists of a base part 9, a jacket 10, a membrane 11, a membrane ring 12. Apart from the membrane 11 and the cellulose acetate coating mentioned below and the fact that the Pt-wire has a differing thickness, the sensor is constructed similarly to a sensor which is manu- factured and sold by RADIOMETER A/S, Copenhagen, Denmark under the designation E909.
  • the base part 9 comprises a working electrode 13 in the form of a 250 ⁇ m platinum wire 17 melted into a glass rod 16. Further, the base part comprises an Ag/AgCl reference electrode 14 in the form of an annular coat ⁇ ing on the glass rod 16. At the front of the glass rod 16 the platinum wire 17 is exposed, and a not shown coating of cellulose acetate is applied to this end of the glass rod 16 as further described below in Example 1. At the rear the sensor 1 is provided with a connec ⁇ tor 15 with electrically conductive connection to the working electrode 13 and the reference electrode 14. Further, the base part comprises a locking means 18 with a rim 19 that serves to maintain the jacket 10 on the base part 9 according to the snap lock principle. Finally, at the front 2 of the locking means 18 facing the sensor is provided a rubber seal 20 which seals the compartment 21 formed when the jacket 10 is mounted on the base part 9.
  • the jacket 10 which is made from a transparent plastic material, is tubular and slightly conical and has a projecting part 22 on the inner surface of its broad end adapted to interlock with the locking means 18.
  • the membrane 11 shown in further detail in FIG. 3 consists of a laminated membrane comprising a 14 ⁇ m protection layer 24 of cellophane, a 1 ⁇ m polyurethane layer 25, an approximately 1 ⁇ m glucose oxidase layer 26, and a 1 ⁇ m poly lrethane inner layer 27.
  • the mem ⁇ brane has a greater area than the small aperture in the jacket 10 and is consequently able to cover this aper ⁇ ture and be wrapped around the outer of the jacket 10 onto which it is pasted and further held by the mem ⁇ brane ring 12.
  • the protection layer 24 is turned outwards and the inner layer 27 against the aperture of the jacket 10.
  • the membrane 11 is prepared as described below in Example 1. Before mounting the jacket 10 on the base part 9, an electrolyte is introduced having the compound described further in Example 1. The electrolyte establishes the necessary electrical contact between the working elec- trode 13 and the reference electrode 14.
  • the small aperture in the jacket 10 i.e. the aperture covered by the mem ⁇ brane
  • the membrane has a thickness of approximately 17 ⁇ m.
  • the measuring chamber 3 contains approximately 5 ⁇ l sample and has a circular aperture with a maximum diameter of approxi ⁇ mately 3.5 mm at the surface 7.
  • the inlet channel 4 and the outlet channel 5 are tubular bores with a circular cross section of approximately 0.7 mm in diameter.
  • a polarization voltage of +0.625 is applied to the working electrode relatively to the reference electrode, and the measuring set-up is thermostated to 37°C.
  • the working electrode current is registered as a function of time on a not shown printer after transformation of the electrode current to a voltage signal.
  • the signal of the working electrode is collected every half second from 5 to 25 seconds after introduction of the sample into the measuring chamber 3.
  • the values for the signal of the working electrode are processed along with data from a previous calibration and printed as mM glucose. Calibration is performed on aqueous solutions contain- ing 0 mM and 10 mM glucose of the composition explained further under the paragraph Materials and Methods in Example 1.
  • a solution without glucose is applied; partly as rins ⁇ ing fluid in the measuring set-up and partly as cali- bration liquid.
  • This liquid has the following composi ⁇ tion:
  • Calibration Liguid_2_-_10 mM_GjLucose This liquid has the same composition as calibration liquid 1 except that it further contains glucose in a concentration of 10 mM.
  • This solution is applied onto a glass plate through a 0.1 mm slot in a metal box which slowly by the hand is moved across the glass plate. After some time of evapo- ration (approximately 10 minutes) the membrane is removed from the glass plate and washed in ion-e. changed water and put to dry. The thickness of this membrane is approximately 1 ⁇ m.
  • the enzyme solution has the following composition:
  • a solution of High Rejective Cellulose Acetate Membrane S-18914 in Nitromethane is prepared for the cellulose acetate coating on the front of the glass rod.
  • the exact composition of the solution is a trade secret belonging to the manufacturer.Yellow Springs Instru ⁇ ments, Ohio, USA.
  • the solution is applied to the front of the glass rod by a fine brush and dried on standing.
  • the layer thick ⁇ ness is 5-10 ⁇ m.
  • the provided membrane is dried on standing and subse- quently pasted on the jacket of FIG. 2 by LoctiteTM (Cyanoacrylate Adhesive 414) .
  • the two electrodes provide mutually corresponding measurements both when measuring on blood and when measuring on aqueous sample and that the measurements on the aqueous samples before and after the blood sample correspond properly.
  • the sensor has a linearity range of 0.5-30 mM glucose and satisfactory stability. Long-term experiments did not show any sign of deterioration in the measuring performance for membranes which had been stored dryly at room temperature for 9 weeks. Membranes used in the test set-up of FIG. 1 and kept in continually contact with calibration liquid 1 between measuring have proved to maintain the measuring performance after 4 weeks function at 37°C.
  • the two electrodes provide mutually corresponding measurements when measuring the first time on aqueous sample, but provide very different measurements on blood, particularly when measured the second time. It is noted that it is the same blood sample.
  • the measurements on aqueous sample are mutually corresponding prior to the blood measurements, but subsequently both too low and varying from the elec ⁇ trode a to electrode b.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Le capteur biologique comprend une électrode active, une électrode de référence et une membrane comprenant une couche-limite de substrat et une couche d'enzyme. La couche-limite de substrat est pourvue d'une couche de protection présentant des caractéristiques hydrophiles correspondant aux propriétés de la cellulose régénérée ou étant plus hydrophile que la cellulose regénérée. En particulier la couche-limite de substrat se compose d'une couche de polyuréthane, et la couche de protection se compose d'une couche de cellophane.
PCT/DK1991/000248 1990-08-31 1991-08-27 Capteur biologique electrochimique WO1992004438A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK2099/90 1990-08-31
DK209990A DK170103B1 (da) 1990-08-31 1990-08-31 Elektrokemisk biosensor samt biosensormembran

Publications (1)

Publication Number Publication Date
WO1992004438A1 true WO1992004438A1 (fr) 1992-03-19

Family

ID=8110062

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1991/000248 WO1992004438A1 (fr) 1990-08-31 1991-08-27 Capteur biologique electrochimique

Country Status (3)

Country Link
AU (1) AU8521391A (fr)
DK (1) DK170103B1 (fr)
WO (1) WO1992004438A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997004954A1 (fr) * 1995-08-01 1997-02-13 Ysi Incorporated Structure de membrane stratifiee amelioree destinee a des mesures polarographiques et procedes de fabrication de telles structures
US5611900A (en) * 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
US5766839A (en) * 1994-06-17 1998-06-16 Ysi Incorporated Processes for preparing barrier layer films for use in enzyme electrodes and films made thereby
WO2000003222A2 (fr) * 1998-07-09 2000-01-20 Geun Sig Cha Procede de fabrication de biocapteurs a l'aide de polyurethanne hydrophile
US6020052A (en) * 1996-07-30 2000-02-01 Ysi Incorporated Laminated membrane structure for polarographic measurement and methods of making said structures
US6099804A (en) * 1996-03-29 2000-08-08 Radiometer Medical A/S Sensor and membrane for a sensor
WO2006122554A2 (fr) 2005-05-17 2006-11-23 Radiometer Medical Aps Detecteur d'enzymes pourvu d'une couche membranaire de couverture recouverte par un polymere hydrophile
EP2261647A1 (fr) * 2001-05-31 2010-12-15 Instrumentation Laboratory Company Matrice enzymatique réticulée et utilisations associées

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0079502A1 (fr) * 1981-11-05 1983-05-25 Miles Laboratories, Inc. Membrane à couches multiples pour électrode enzymatique, procédé de sa fabrication et structure de cellule polarographique
EP0216577A2 (fr) * 1985-09-16 1987-04-01 Imperial Chemical Industries Plc Senseur
US4759828A (en) * 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
DE3822911A1 (de) * 1987-07-17 1989-01-26 Daikin Ind Ltd Biosensor
DE3824258A1 (de) * 1987-07-23 1989-02-16 Akad Wissenschaften Ddr Modifizierte enzymmembran fuer enzymelektroden mit hoher selektivitaet und verfahren zu ihrer anwendung
EP0327018A2 (fr) * 1988-02-05 1989-08-09 Nova Biomedical Corporation Electrode enzymatique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0079502A1 (fr) * 1981-11-05 1983-05-25 Miles Laboratories, Inc. Membrane à couches multiples pour électrode enzymatique, procédé de sa fabrication et structure de cellule polarographique
EP0216577A2 (fr) * 1985-09-16 1987-04-01 Imperial Chemical Industries Plc Senseur
US4759828A (en) * 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
DE3822911A1 (de) * 1987-07-17 1989-01-26 Daikin Ind Ltd Biosensor
DE3824258A1 (de) * 1987-07-23 1989-02-16 Akad Wissenschaften Ddr Modifizierte enzymmembran fuer enzymelektroden mit hoher selektivitaet und verfahren zu ihrer anwendung
EP0327018A2 (fr) * 1988-02-05 1989-08-09 Nova Biomedical Corporation Electrode enzymatique

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5766839A (en) * 1994-06-17 1998-06-16 Ysi Incorporated Processes for preparing barrier layer films for use in enzyme electrodes and films made thereby
US5611900A (en) * 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
WO1997004954A1 (fr) * 1995-08-01 1997-02-13 Ysi Incorporated Structure de membrane stratifiee amelioree destinee a des mesures polarographiques et procedes de fabrication de telles structures
US6099804A (en) * 1996-03-29 2000-08-08 Radiometer Medical A/S Sensor and membrane for a sensor
US6020052A (en) * 1996-07-30 2000-02-01 Ysi Incorporated Laminated membrane structure for polarographic measurement and methods of making said structures
WO2000003222A2 (fr) * 1998-07-09 2000-01-20 Geun Sig Cha Procede de fabrication de biocapteurs a l'aide de polyurethanne hydrophile
WO2000003222A3 (fr) * 1998-07-09 2000-03-30 Geun Sig Cha Procede de fabrication de biocapteurs a l'aide de polyurethanne hydrophile
US6509148B2 (en) 1998-07-09 2003-01-21 I-Sens, Inc. Method for fabricating biosensors using hydrophilic polyurethane
EP2261647A1 (fr) * 2001-05-31 2010-12-15 Instrumentation Laboratory Company Matrice enzymatique réticulée et utilisations associées
US8426192B2 (en) 2001-05-31 2013-04-23 Instrumentation Laboratory Company Composite membrane containing a cross-linked enzyme matrix for a biosensor
US9388503B2 (en) 2001-05-31 2016-07-12 Instrumentation Laboratory Company Cross-linked enzyme matrix and uses thereof
WO2006122554A2 (fr) 2005-05-17 2006-11-23 Radiometer Medical Aps Detecteur d'enzymes pourvu d'une couche membranaire de couverture recouverte par un polymere hydrophile

Also Published As

Publication number Publication date
DK209990D0 (da) 1990-08-31
AU8521391A (en) 1992-03-30
DK170103B1 (da) 1995-05-22
DK209990A (da) 1992-03-01

Similar Documents

Publication Publication Date Title
Emr et al. Use of polymer films in amperometric biosensors
Coulet Polymeric membranes and coupled enzymes in the design of biosensors
US4886740A (en) Enzyme-electrode sensor with organosilane treated membrane
US5286364A (en) Surface-modified electochemical biosensor
Guerrieri et al. Electrosynthesized non-conducting polymers as permselective membranes in amperometric enzyme electrodes: a glucose biosensor based on a co-crosslinked glucose oxidase/overoxidized polypyrrole bilayer
Mascini et al. Amperometric acetylcholine and choline sensors with immobilized enzymes
Dempsey et al. Electropolymerised o-phenylenediamine film as means of immobilising lactate oxidase for a L-lactate biosensor
EP1817426A1 (fr) Couche de diffusion et d'enzymes pour une application de detection a base d'enzymes
HU177369B (en) Industrial molecule-selective sensing device and method for producing same
Bardeletti et al. Amperometric enzyme electrodes for substrate and enzyme activity determinations
Chen et al. Amperometric tyrosinase biosensor based on a sol–gel-derived titanium oxide–copolymer composite matrix for detection of phenolic compounds
US6706532B2 (en) Membrane for chemical and biosensors
WO1992004438A1 (fr) Capteur biologique electrochimique
CA1109374A (fr) Stabilisation de la galactose-oxydase activee
Eremenko et al. Biosensor based on an enzyme modified electrode for highly-sensitive measurement of polyphenols
Reddy et al. Selective membranes for the construction and optimization of an amperometric oxalate enzyme electrode
Lukachova et al. Non-aqueous enzymology approach for improvement of reagentless mediator-based glucose biosensor
US5545519A (en) Electrolytic analytical methods
Santoni et al. Enzyme electrode for glucose determination in whole blood
Gunasingham et al. Chemically modified cellulose acetate membrane for biosensor applications
Keyes et al. Glucose analysis utilizing immobilized enzymes
US4354913A (en) Molecule selective enzyme electrode
Desai et al. Internal membranes and laminates for adaptation of amperometric enzyme electrodes to direct biofluid analysis
Emregul et al. Immobilization of glucose oxidase onto gelatin for biosensor construction
Popp et al. Sandwich enzyme membranes for amperometric multi-biosensor applications: improvement of linearity and reduction of chemical cross-talk

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP SU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA