WO2016140543A1 - Capteur de détection potentiométrique de glucose basé sur des enzymes et son procédé de fabrication - Google Patents

Capteur de détection potentiométrique de glucose basé sur des enzymes et son procédé de fabrication Download PDF

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WO2016140543A1
WO2016140543A1 PCT/KR2016/002180 KR2016002180W WO2016140543A1 WO 2016140543 A1 WO2016140543 A1 WO 2016140543A1 KR 2016002180 W KR2016002180 W KR 2016002180W WO 2016140543 A1 WO2016140543 A1 WO 2016140543A1
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glucose
sensor
enzyme
conductive polymer
electrode
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Korean (ko)
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조철호
심윤보
김광복
정선태
조성제
조재걸
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삼성전자 주식회사
부산대학교 산학협력단
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Publication of WO2016140543A1 publication Critical patent/WO2016140543A1/fr

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3272Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/005Enzyme electrodes involving specific analytes or enzymes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/333Ion-selective electrodes or membranes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416Systems
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose

Definitions

  • the present invention relates to a sensor for detecting potentiometric glucose and a method for manufacturing the same, and more particularly, to an enzyme-based glucose sensor and a method for manufacturing the same, including a metal alloy oxide and an electrically conductive polymer.
  • a sensor is a device that selectively captures a physical quantity or a chemical quantity of a measurement target and converts it into a useful signal.
  • Electrochemical biosensors are used as devices for detecting various analytes in the environment, medicine, and food-related fields by using bioreceptors such as enzymes, microorganisms, and immune bodies. The high response specificity and fast responsiveness make it possible to measure target substances selectively, quickly and accurately.
  • the blood glucose sensor is a type of electrochemical biosensor which measures the concentration of glucose in blood or urine.
  • the conventional commercially available blood glucose sensor is a second generation biosensor using an electrochemical method (time vs. current method).
  • the conventional blood glucose sensor has the advantages of high sensitivity, high selectivity to monosaccharides and easy portability, but has ascorbic acid, dopamine, acetaminophen having an oxidation potential similar to the glucose detection potential. Interfering substances, such as acetaminophen, react to each other, resulting in interference (so-called interfering effects) and inferior sensitivity.
  • the enzymatic potentiometric glucose sensor detects a substance produced by the reaction between glucose and an enzyme and does not need to apply a specific potential, thereby avoiding the interference of the above-mentioned interfering substances.
  • the blood glucose sensor using the potentiometric method has not been studied much compared to the blood glucose sensor using the current measurement method.
  • metal oxides having various nanostructures have been widely applied to enzymatic or non-enzymatic glucose sensors.
  • Early work on metal oxides for glucose detection focused on the use of common electrode materials such as Cu, Ni, Fe, Pt and Au. However, these materials have resulted in fundamental disadvantages such as selectivity, low efficiency and contamination of metal electrode surfaces due to chemisorbed intermediates.
  • the present invention provides a sensor for detecting glucose having a simple and high sensitivity by measuring a potential difference according to an enzyme reaction without applying an external voltage.
  • the present invention also provides a method of manufacturing an enzyme-based potentiometric glucose detection sensor.
  • the present invention also provides a method for simply measuring glucose concentration by measuring the potential difference according to the enzyme reaction without applying an external voltage.
  • the electrode is surface modified with a multi-metal alloy dendrite oxide; A hydrogen ion sensitive conductive polymer formed on the oxide; And a glucose detecting sensor covalently bound to the conductive polymer, wherein the glucose is detected by measuring a potential difference according to an enzyme reaction without applying an external voltage. It provides a sensor for detection.
  • the sensor of the present invention is a sensor having a two-electrode structure and the electrode can be manufactured using a carbon-based material as the working electrode.
  • a carbon-based material for example, carbon ink, graphite, glassy carbon, graphene, or the like may be used as a material of the working electrode, but is not limited thereto.
  • the reference electrode may be a silver electrode (Ag / AgCl), but is not limited thereto.
  • carbon ink may be used as the material of the working electrode and silver ink may be used as the material of the reference electrode.
  • the working electrode may be modified on the electrode surface of the multi-metal alloy dendrite oxide.
  • multi-metal means two or more metals, preferably an alloy of two or three metals, more preferably a copper-cobalt alloy or a gold-zinc alloy. Can be.
  • the working electrode may be an electrode whose surface is modified with gold-zinc alloy dendrites.
  • the gold-zinc (Au-Zn) alloy dendrites of the present invention have a dendrite structure and can be applied as a preferred electrode in electrochemical devices because of the unique hierarchical structure having a large number of active sites and an extremely high surface area.
  • the gold-zinc alloy dendrites may have an atomic metal content ratio of Au and Zn of 70-90: 30-10.
  • the reaction mechanism for detecting H + produced by the reaction between glucose and glucose oxidase is as follows.
  • the gold-zinc alloy dendrite oxide film serves as an electrode for detecting hydrogen ions to detect glucose.
  • hydrogen ions are generated by oxidizing glucose in the blood, which is a glucose degrading enzyme
  • the gold-zinc alloy dendrites act as probes of hydrogen ions. This mechanism uses the reaction between oxygen and hydrogen ions in the dendrites. Is as follows.
  • the sensor of the present invention can measure the concentration of glucose by measuring the difference in potential between the reference electrode and the dendrite oxide electrode according to the reaction.
  • the sensor of the present invention uses an enzymatic potentiometric method, so it is not necessary to apply a specific potential from the outside, so that the measurement can be performed without an external constant voltage meter and an ammeter, so that the measurement is simple and the manufacturing of the sensor is simple. More importantly, since there is no need to apply a specific potential from the outside, interference of the interfering substances reacting to these potentials can be avoided, thereby preventing the interference effect.
  • the hydrogen ion sensitive conductive polymer may be a conductive polymer including a -COOH or -NH 2 functional group, and a conductive polymer including a carboxyl group is preferable. More preferably, it may be a conductive polymer including terthiophene having excellent physical, chemical, mechanical and electrical properties. Most preferably, the hydrogen ion-sensitive conductive polymer is terthiophene benzoic acid (TTBA), terthiophene carboxylic acid (TTCA), and disthienyl pyrrole benzoic acid ( dithienyl pirol benzoic acid, DTPBA).
  • TTBA terthiophene benzoic acid
  • TTCA terthiophene carboxylic acid
  • DTPBA disthienyl pyrrole benzoic acid
  • the gold-zinc alloy dendrite oxide film is used as a main material for detecting hydrogen ions, and the hydrogen-sensitive conductive polymer is introduced therein to improve the sensitivity of the dendrite oxide film to hydrogen ions and at the same time, the metal oxide surface. To prevent contamination and to stably stabilize the glucose degrading enzymes through peptide bonds.
  • the hydrogen-ion-sensitive conductive polymer having a carboxylic acid dissociates or associates with -COO - and H + in an aqueous solution to act as a receptor for H + , thereby forming a hydrogen-ion-sensitive polymer on the gold-zinc alloy dendrites.
  • Incorporation can significantly improve the sensitivity to potential change with respect to hydrogen ion concentration than with only a dendrite oxide film.
  • the conductive polymer is disposed between the metal and the enzyme to protect the surface of the electrode as well as to protect the enzyme, thereby enhancing the enzyme stability. Can be.
  • the covalent bond between the carboxyl group of the conductive polymer and the amine group of the enzyme can be coupled to the polymer, thereby improving the stability of the enzyme in the sensor to maintain a high selectivity .
  • the glucose degrading enzyme is glucose oxidase, glucose dehydrogenase, glucose hexokinase, glutamic oxalacetic transminase and glutamic pyruvic transaminase. It may be selected from the group consisting of.
  • glucose oxidase requires cofactor flavin adenine dinucleotide (FAD) in order to act as a catalyst for glucose oxidation reaction. It can be used in the form of an enzyme (FAD-GOx). In the catalytic reaction by glucose oxidase, FAD acts as an electron acceptor. In addition, glucose dehydrogenase, glucose hexokinase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and the like, which are involved in glucose metabolism, can be used as glucose degrading enzymes.
  • the glucose detecting sensor of the present invention may further include a Nafion membrane coated on the layer on which the glucose degrading enzyme is formed.
  • the Nafion membrane serves to protect the sensor surface.
  • the Nafion membrane protects the surface from factors affecting pH, thereby increasing the stability of the sensor.
  • Sensors protected by Nafion membranes have the advantage of being stored for a long time.
  • the present invention provides a method for manufacturing a sensor for detecting glucose by measuring the potential difference according to the enzymatic reaction, comprising the steps of: modifying the gold-zinc alloy dendrites on the electrode surface through voltage application; Forming an oxide in an alkaline solution of the gold-zinc alloy dendrites; Modifying the hydrogen-ion (H + ) sensitized conductive polymer via potential injection on the gold-zinc alloy dendrites; It provides a method of manufacturing a sensor for detecting the potentiometric method comprising the step of binding a glucose degrading enzyme to the conductive polymer through a covalent bond.
  • the dendrites may be formed by applying a voltage for 150 to 250 seconds at -0.2V to -0.7V.
  • the alkaline solution may be used without limitation as long as it includes a -OH group, but preferably NaOH, KOH, NH 4 OH, LiOH, Mg (OH) 2 , Ca (OH) 2 , Ba (OH) 2 , Al (OH) 3 And the like can be used.
  • the hydrogen-ion-sensitive conductive polymer and glucose degrading enzyme used in the sensor manufacturing method of the present invention are as described above, and the method of preparing the polymer film of TTCA and DTPBA on the metal dendrites is the same as that of TTBA.
  • the sensor manufacturing method of the present invention may further include a step of activating the carboxyl group of the conductive polymer by treating the catalyst with the polymer-modified electrode after the step of modifying the polymer and before the step of binding the glucose degrading enzyme.
  • the catalyst can be used without limitation so long as it is a catalyst for making a peptide bond, and is used as a crosslinking agent.
  • at least one from the group consisting of EDC (1-Ethyl-3- [3- (dimethylamino) propyl] carbodiimide hydrochloride), NHS (N-hydroxysuccinimide), and glutaldehyde (glutaldehyde) may be used. no.
  • the step of coupling the glucose degrading enzyme to the conductive polymer through a covalent bond by reacting the sugar oxidase on the electrode having the carboxyl group activated by the carboxyl group and the amine group of the sugar oxidase of the conductive polymer It can be made in such a way to form a covalent bond between them.
  • the method of manufacturing the glucose detecting sensor may further include coating a Nafion membrane on the layer on which the glucose degrading enzyme is formed.
  • the present invention provides a method for measuring glucose concentration by measuring a potential difference according to an enzyme reaction without applying an external voltage, wherein the enzyme is a sugar oxidase and is a gold-modified electrode on a surface of an electrode as a probe of hydrogen ions. It provides a method for measuring glucose concentration, characterized in that using zinc alloy dendrites oxide and hydrogen ion sensitive conductive polymer.
  • the glucose concentration measuring method it is not necessary to apply an external voltage, thereby eliminating the influence of an interfering substance reacting to the same voltage, and measuring the potential difference using a natural oxidation method through an enzymatic reaction rather than an artificial oxidation method. This makes the measurement simpler and more precise.
  • the sensor for detecting glucose of the present invention uses the potentiometric method to overcome the disadvantage that the external constant voltage meter and the current meter used by the conventional sensor are degraded by the interference material, so that the application of the external voltage is unnecessary, so that the blocking effect of the interference material is not required.
  • Figure 1 shows a schematic diagram of the production of potentiometric blood glucose sensor.
  • Figure 2 shows (A) Au-Zn alloy dendrite electrodeposition curve through voltage application, (B) electrochemical polymerization curve of pTTBA using cyclic voltammetry.
  • FIG. 3 shows (A) Au-Zn DOx, (B) Au-Zn DOx / pTTBA, (C) Au-Zn DOx / pTTBA / FAD-GOx, and Au-Zn DOx / pTTBA / FAD-GOx / Nafion SEM surface photo.
  • FIG. 6 shows a glucose detection sensitivity graph for interfering substances.
  • Figure 7 shows the calibration curve according to the addition of glucose to the specific simulated blood (medium).
  • Figure 8 shows the calibration curve using three concentrations of simulated blood (low, medium, high) for the detection of glucose in real blood.
  • test examples and examples are provided only for the purpose of illustration in order to facilitate understanding of the present invention, and the scope and scope of the present invention is not limited by the following examples.
  • Example 1 using the multi-metal oxide and the hydrogen-sensitive conductive polymer according to the present invention Potentiometric method Manufacturing of Blood Glucose Sensors
  • FIG. 1 shows a process of preparing a potentiometric glucose sensor.
  • 30mM Gold (III) Chloride trihydrate and 30mM Zinc chloride were dissolved together in 0.1M sodium sulfate, and then a precursor solution was prepared by adjusting the pH to 4.0 with 0.1M sodium hydroxide solution.
  • a precursor solution was prepared by adjusting the pH to 4.0 with 0.1M sodium hydroxide solution.
  • FIG. 2A After applying voltage at -0.5V for 200 seconds (FIG. 2A) to form gold-zinc alloy dendrites on the screen printed carbon electrode, the electrode surface was washed with ethanol and tertiary distilled water.
  • Gold-zinc alloy dendrite oxide film is formed by scanning 7 times from + 0.0V to + 1.5V using linear current-voltage method to form gold-zinc alloy dendrite oxide film, and then distilled water and ethanol Washed.
  • 1 mM TTBA a H + sensitized polymer monomer, was added to a mixed solvent of di (propylene glycol) methyl ether and tri (propylene glycol) methyl ether (1: 1). After melting, 5 ⁇ L was dropped onto the gold-zinc alloy dendrites, dried at 40 ° C., and then electrochemically polymerized in a 0.1 M phosphate buffer (pH 7.4) by a cyclic current-voltage method.
  • the scanning potential range was 0.0V to + 1.6V, and the scanning speed was sweep three times at 100 mv / s to form a polymer film (FIG. 2B).
  • the electrode of the potentiometric blood glucose sensor was used as a screen print electrode composed of a working electrode and a reference electrode, the working electrode using carbon ink, and the reference electrode was prepared using silver ink.
  • the pTTBA-formed electrode was added to a solution of 10.0 mM EDC (1-Ethyl-3- [3- (dimethylamino) propyl] carbodiimide hydrochloride) and 10.0 mM NHS (N-hydroxysuccinimide) in 0.1 M phosphate buffer (pH 7.4).
  • the reaction was carried out at 30 ° C. for 6 hours to activate the carboxyl acid group of pTTBA.
  • a 10 ⁇ L solution of FAD-GOx (6 mg / mL) was dropped on the surface of pTTBA and reacted for 12 hours at 4 ° C. to form a covalent bond between the carboxyl acid group of pTTBA and the amine group of FAD-GOx.
  • Enzyme cluster formation was also used to increase the amount of enzyme adsorption on the sensor surface.
  • the solution to be used for the enzyme cluster formation method is glutaaldehyde as a crosslinking agent between ammonium sulfate (ammonium sulfate (0.55 mg / mL)) and enzymes (FAD-GOx) as a precipitant of enzyme in FAD-GOx (6mg / mL) solution. , 0.5%) was prepared. 10 ⁇ L of the enzyme cluster solution was dropped onto the surface of the screen-printed carbon electrode modified to FAD-GOx and reacted at 4 ° C. at 12 hr. Enzyme adsorption was increased through covalent bonds between amine groups between FAD-GOx. Finally, 1 ⁇ L of Nafion (1.0%) was coated on the enzyme layer to prepare a blood glucose sensor.
  • FIG. 3 is a SEM surface photograph of each modification step of the sensor.
  • (A) it was possible to observe the gold-zinc dendrite structure having a multi-tree of gold-zinc.
  • (B) is a surface photograph of H + sensitive polymer electrodeposited by cyclic voltammetry on gold-zinc dendrites. H + sensitive polymer is formed between the branch trees of gold-zinc dendrites. It was confirmed that the size of the dry and the voids are reduced.
  • (C) in Figure 3 is a surface photograph of the FAD-GDH immobilized on the H + sensitive polymer. Referring to (B) of FIG.
  • FIG. 3 (D) is a surface photograph coated with 0.5% Nafion, covering the FAD-GDH layer in the form of a net film, and has a surface that is softer than the surface photograph of FIG.
  • Test Example 2 Potentiometric method Blood glucose sensor Glucose Performance Evaluation of Potential Changes with Concentration
  • Glucose solution of 30mg / dL, 100mg / dL, 200mg / dL, 300mg / dL, 400mg / dL, 500mg / dL dissolved in 0.1M phosphate buffer (pH 7.4) in the blood glucose sensor prepared according to Example 1 was processed to measure the potential change according to the glucose concentration, and the results are shown in FIG. 4.
  • the glucose sensor prepared in Example 1 was treated with a glucose solution having a concentration of 200 mg / dL dissolved in 0.1 M phosphate buffer solution (pH 7.4) to measure glucose potential at various temperatures (15, 16, 20, 25, 30, 35, 40 ° C.) and relative humidity (20, 30, 40, 50, 60, 70, 80%) The results are shown in FIG. 5.
  • FIG. 5A Three blood glucose sensors were measured for each section of temperature and relative humidity.
  • the detection sensitivity was constant in the 20 to 40 ° C. range, but the detection sensitivity was reduced by 24% when compared to 25 ° C. at 15 ° C.
  • FIG. It can be confirmed that the enzyme activity is lowered at a temperature of 20 ° C. or lower, and as a result, the glucose measurement sensitivity is lowered.
  • Figure 5 (A) it was confirmed to maintain a constant glucose detection sensitivity in the relative humidity 20 ⁇ 80% range.
  • FIG. 6 is a graph comparing glucose detection sensitivity in the presence of interfering substances.
  • Interfering substances used in this experiment were ascorbic acid (AA, 5mg / dL), dopamine (DA, 5mg / dL), acetaaminophen (AP, 15mg / dL), four monosaccharides ((mannose (10mg / dL) dL), lactose (10 mg / dL), xylose (10 mg / dL), fructose (30 mg / dL)).
  • Irradiation of the interfering substances was determined by including the respective interfering substances in a glucose solution of 200 mg / dL concentration dissolved in 0.1 M phosphate buffer (pH 7.4).
  • monosaccharides the four types of monosaccharides described above were included in a 200 mg / dL glucose solution, which was 1.2% lower than the mean potential difference value of glucose.
  • Dopamine, acetaaminophen, and ascorbic acid decreased glucose detection sensitivity by 5.2%, 5.5%, and 4.8%, respectively, and these hinders (monosaccharides, DA, AP, and AA) were found in the error range for glucose measurement. It does not matter because it is distributed within.
  • Test Example 5 In mock blood Glucose Concentration measurement
  • FIG. 7 is a calibration curve for glucose concentration (29, 119, 159, 250, 348, 434 mg / dL) of 6 sections of simulated blood using the potentiometric method. Three concentrations were measured for each concentration section. Excellent linearity was observed at the glucose concentration of 29 ⁇ 434 mg / dL.

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Abstract

La présente invention concerne un capteur de détection potentiométrique de glucose basé sur des enzymes, ainsi qu'un procédé de fabrication de celui-ci, ce capteur de détection de glucose détectant le glucose par mesure d'une différence de potentiel en fonction d'une réaction enzymatique, sans l'application d'une tension extérieure, et comprenant : une électrode dont la surface a été modifiée par un oxyde dendritique allié à or-zinc ; un polymère conducteur sensible aux ions hydrogène qui est formé sur l'oxyde ; et une enzyme de dégradation du glucose qui est liée au polymère conducteur par l'intermédiaire d'une liaison covalente.
PCT/KR2016/002180 2015-03-04 2016-03-04 Capteur de détection potentiométrique de glucose basé sur des enzymes et son procédé de fabrication WO2016140543A1 (fr)

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