WO2023043105A1 - Biocapteur - Google Patents

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Publication number
WO2023043105A1
WO2023043105A1 PCT/KR2022/013240 KR2022013240W WO2023043105A1 WO 2023043105 A1 WO2023043105 A1 WO 2023043105A1 KR 2022013240 W KR2022013240 W KR 2022013240W WO 2023043105 A1 WO2023043105 A1 WO 2023043105A1
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layer
biosensor
working electrode
barrier layer
viscosity control
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PCT/KR2022/013240
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English (en)
Korean (ko)
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마동희
이영근
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동우화인켐 주식회사
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Publication of WO2023043105A1 publication Critical patent/WO2023043105A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F14/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen
    • C08F14/18—Monomers containing fluorine
    • C08F14/20—Vinyl fluoride
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/14—Esterification
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/34—Introducing sulfur atoms or sulfur-containing groups
    • C08F8/36—Sulfonation; Sulfation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/40—Introducing phosphorus atoms or phosphorus-containing groups
    • 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
    • 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
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/28—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
    • 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
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/32—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving dehydrogenase
    • 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
    • C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material

Definitions

  • the present invention relates to biosensors. More specifically, it relates to a biosensor comprising a working electrode and a reference electrode.
  • Biosensors can use enzymes that react with chemical species contained in bodily fluids (sweat, tears, blood, etc.). When the enzyme reacts with the chemical species to generate current, the current is measured to measure the concentration of the chemical species.
  • glucose oxidase that promotes the oxidation of glucose to gluconolactone or glucose It is based on the immobilization of enzymes such as dehydrogenase.
  • Glucose is a nutrient source for a wide range of organisms, and is a component that plays a fundamental role in energy supply, carbon storage, biosynthesis, and carbon skeleton and cell wall formation.
  • the concentration of glucose contained in body fluids or saliva is measured through potential difference or current measurement. Research on biosensors that do this is being actively conducted.
  • Sensing performance and reliability of the working electrode may be degraded depending on an interfering substance included in bodily fluid or saliva, which is a glucose sensing target. Therefore, there is a need for research and development of a working electrode with improved sensing performance and reliability and a biosensor including the same.
  • An object of the present invention is to provide a biosensor having improved sensing performance and reliability.
  • the working electrode includes a conductive layer formed on the substrate; an enzyme layer formed on the conductive layer and reacting with the measurement target material; a barrier layer formed on the enzyme layer and containing a fluorine-based anionic polymer; and a viscosity control layer formed on the barrier layer.
  • the fluorine-based anionic polymer is polytetrafluoroethylene (PTFE), polyvinylfluoride (PVF), polyvinylidene fluoride (PVDF) and polyethylenetetrafluoro
  • PTFE polytetrafluoroethylene
  • PVDF polyvinylidene fluoride
  • a biosensor which is a compound in which at least one of a carboxyl group, a phosphoric acid group, and a sulfonic acid group is bonded to at least one terminal of polyethylene tetrafluoroethylene (ETFE).
  • fluorine-based anionic polymer includes at least one of Nafion, Aquivion, Flemion, and Aciplex.
  • the viscosity modifier is an anionic surfactant containing a sulfonic acid group, a surfactant containing a substituted or unsubstituted aryl group having 6 to 12 carbon atoms, and a substituted or unsubstituted heteroaryl group having 6 to 12 carbon atoms ( A biosensor comprising at least one of surfactants containing a heteroaryl group).
  • the viscosity modifier includes at least one of Triton X-100, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate (SDS).
  • the conductive layer includes a metal layer and a metal protective layer.
  • the metal layer is gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Sn), molybdenum (Mo), A biosensor comprising at least one of cobalt (Co), palladium (Pd), and alloys thereof.
  • the metal protective layer includes ITO (Indium Tin Oxide) or IZO (Indium Zinc Oxide).
  • the viscosity control layer further comprises a phosphate compound.
  • the working electrode included in the biosensor may include a barrier layer including a fluorine-based anionic polymer on the conductive layer and the enzyme layer.
  • a barrier layer including a fluorine-based anionic polymer on the conductive layer and the enzyme layer.
  • the working electrode of the biosensor may further include a viscosity control layer on the barrier layer.
  • a viscosity control layer on the barrier layer.
  • Exemplary embodiments including the above-described barrier layer and the viscosity control layer can suppress deterioration in the sensing performance of the working electrode due to the interference factor material without a separate pretreatment or filter device. Accordingly, it is possible to improve sensing performance and reliability of the biosensor while reducing processing time and cost.
  • FIG. 1 and 2 are schematic plan and cross-sectional views illustrating a biosensor according to example embodiments.
  • FIG. 3 is a schematic graph showing sensing performance of biosensors according to exemplary embodiments and comparative examples.
  • Embodiments of the present invention provide a biosensor including a substrate, a working electrode and a reference electrode.
  • FIG. 1 and 2 are schematic plan and cross-sectional views illustrating a biosensor according to example embodiments.
  • FIG. 2 is a schematic cross-sectional view of the biosensor taken along line II' of FIG. 1 in a thickness direction.
  • the biosensor 10 includes a working electrode 100, a reference electrode 200, a substrate 300, and a wire 310. can include
  • the working electrode 100 may be provided as an electrode where an oxidation-reduction reaction of a material to be measured (eg, glucose) of the biosensor 10 occurs.
  • a material to be measured eg, glucose
  • the substrate 300 may serve as a substrate on which the working electrode 100, the reference electrode 200, the wiring 310, and the like are disposed.
  • the substrate 300 may be a base film having flexible properties.
  • the substrate 300 may be a polyester-based resin such as polyethylene terephthalate, polyethylene isophthalate, polyethylene naphthalate, or polybutylene terephthalate; cellulosic resins such as diacetyl cellulose and triacetyl cellulose; polycarbonate-based resin; acrylic resins such as polymethyl (meth)acrylate and polyethyl (meth)acrylate; styrenic resins such as polystyrene and acrylonitrile-styrene copolymer; polyolefin-based resins such as polyethylene, polypropylene, polyolefins having a cyclo-based or norbornene structure, and ethylene-propylene copolymers; vinyl chloride-based resins; amide resins such as nylon and aromatic polyamide; imide-based resins; polyethersulfone-based resins; sulfone-based resins; polyether ether ketone-based resins; sulfurized
  • the thickness of the substrate 300 is not limited, but may be 1 to 500 ⁇ m in consideration of strength, handling, workability, and thinness. Preferably, the thickness of the substrate 300 may be 1 to 300 ⁇ m, more preferably 5 to 200 ⁇ m.
  • a base film used as the substrate 300 may contain one or more additives.
  • Additives may include, for example, an ultraviolet absorber, an antioxidant, a lubricant, a plasticizer, a release agent, an anti-coloring agent, a flame retardant, a nucleating agent, an antistatic agent, a pigment, a colorant, and the like.
  • the base film may include various functional layers such as a hard coating layer, an antireflection layer, and/or a gas barrier layer on one or both surfaces of the film.
  • the base film may be surface treated.
  • the surface treatment may include dry treatment such as plasma treatment, corona treatment, and primer treatment, and chemical treatment such as alkali treatment including saponification treatment.
  • an insulating film may be further formed on the substrate 300 , and the insulating film may be formed around the conductive layer 110 at the same level as the conductive layer 110 .
  • the working electrode 100 may include a conductive layer 110 , an enzyme layer 120 , a barrier layer 130 and a viscosity control layer 140 .
  • the working electrode 100 may sense, for example, an electrical signal generated by a reaction between a material constituting the enzyme layer 120 and a material to be measured.
  • the conductive layer 110 may be disposed on the substrate 300 of the biosensor 10 and provided as a passage through which electrons or holes generated from a chemical reaction of a material to be measured are transferred.
  • the conductive layer 110 may include a metal layer and a metal protection layer.
  • the metal protective layer may be disposed to cover an upper surface of the metal layer.
  • the metal protective layer may be laminated in direct contact with the metal layer.
  • the metal protective layer may prevent the metal layer from being oxidized due to a chemical reaction of a material to be measured.
  • the metal protection layer may prevent the metal layer from directly contacting air, thereby preventing oxidation of a metal component constituting the metal layer. Accordingly, reliability of an electrical signal sensed by the metal layer may be improved.
  • the metal layer may include gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Sn), molybdenum (Mo), It may include at least one of cobalt (Co), palladium (Pd), and alloys thereof.
  • the metal layer may include an Ag-Pd-Cu alloy (APC alloy).
  • APC alloy Ag-Pd-Cu alloy
  • the metal layer may be formed of at least one of Au, Ag, APC alloy (Ag-Pd-Cu alloy), and Pt.
  • electrical conductivity of the conductive layer 110 may be improved and resistance may be reduced. Accordingly, sensing performance of the working electrode 100 may be improved.
  • the thickness of the metal layer may be 500 to 4,000 ⁇ . Within the above thickness range, excellent detection performance of the working electrode 100 can be secured. Preferably, the thickness of the metal layer may be 1,000 to 3,000 ⁇ .
  • the metal protective layer may include indium tin oxide (ITO) or indium zinc oxide (IZO).
  • ITO indium tin oxide
  • IZO indium zinc oxide
  • the metal protective layer may be formed of only indium tin oxide (ITO) or indium zinc oxide (IZO).
  • ITO and IZO have electrical conductivity and are chemically stable, so that the metal layer can be effectively protected from an oxidation-reduction reaction.
  • the thickness of the metal protective layer may be 100 to 800 ⁇ . Within the thickness range, the metal layer can be effectively protected, and electrical conductivity of the conductive layer 110 can be improved. Preferably, the thickness of the metal protective layer may be 300 to 500 ⁇ .
  • the enzyme layer 120 may be disposed on the above-described conductive layer 110 .
  • the enzyme layer 120 may be provided as a layer that generates an electrical signal by chemically reacting with a substance to be measured.
  • a substance to be measured may be glucose.
  • the enzyme layer 120 may include a glucose oxidase or a glucose dehydrogenase.
  • glucose contained in the sample is oxidized by glucose oxidase or glucose dehydrogenase, and the glucose oxidase or glucose dehydrogenase can be reduced. .
  • the electron transporter included in the electron transport layer to be described later oxidizes the reduced glucose oxidase or glucose dehydrogenase and may itself be reduced.
  • the reduced electron transporter may lose electrons and be electrochemically oxidized again, for example at the electrode surface to which a constant voltage is applied. Since the glucose concentration in the sample is proportional to the amount of current generated in the process of oxidizing the electron transporter, the glucose concentration can be measured by measuring the amount of current.
  • the glucose oxidase or glucose dehydrogenase may be immobilized through a binder.
  • the binder may include a binder commonly used in the art, and may include, for example, chitosan.
  • the thickness of the enzyme layer 120 may be 0.5 to 10 ⁇ m, preferably 1 to 5 ⁇ m. In this case, sensing sensitivity and sensing speed may be increased while the upper limit of the sensing concentration is appropriately maintained. Accordingly, sensing performance and reliability of the working electrode 100 may be improved.
  • an electron transport layer including an electron transporter may be further included between the aforementioned conductive layer 110 and the enzyme layer 120 .
  • the electron transport layer may transfer electrons or holes generated from the above-described chemical reaction of the measurement target material to the conductive layer 110 .
  • the electron transporter may include, for example, a material that is oxidized or reduced by accepting electrons/holes generated from a chemical reaction of a material to be measured in the enzyme layer 120 . Electrons/holes may be transferred to the conductive layer 110 through the oxidation or reduction.
  • the electron transporter may include Prussian blue.
  • the electrical sensitivity of the working electrode 100 can be improved due to the high oxidizing property of Prussian blue.
  • the Prussian blue may refer to a blue pigment whose main component is potassium iron (III) hexacyanoferrate (II) acid.
  • the material to be measured by the working electrode 100 may be glucose contained in at least one of saliva, sweat, body fluid, and blood of the human body.
  • the substance to be measured may be glucose contained in saliva.
  • anionic mucin contained in the saliva may function as a disturbance factor when sensing a target substance to be measured.
  • the mucin may be adsorbed with the glucose oxidase or glucose dehydrogenase of the enzyme layer 120 . Accordingly, sensing sensitivity and reliability of the working electrode 100 may decrease.
  • methods such as centrifugation, extraction of interfering factors, or syringe filtering may be used to remove interfering substances in the mucin-containing saliva.
  • the above method contacts the sensing electrode after separately pre-processing or filtering the sample (eg, saliva), sensing time and cost may increase.
  • a barrier layer 130 including a fluorine-based anionic polymer may be formed on the enzyme layer 120 .
  • the barrier layer 130 may push out an interference factor material different from a measurement target material.
  • the fluorine-based anionic polymer can prevent contact with the enzyme layer 120 by pushing out anionic mucin in saliva by repulsive force between anions.
  • the adsorption of mucin to glucose oxidase and glucose dehydrogenase can be suppressed. Accordingly, sensing sensitivity and reliability of the working electrode 100 may be improved.
  • the fluorine-based anionic polymer is polytetrafluoroethylene (PTFE), polyvinylfluoride (PVF), polyvinylidene fluoride (PVDF) and polyethylenetetrafluoro It may be a compound in which at least one of a carboxyl group (-COOH), a phosphoric acid group (-PO 3 H 2 ), and a sulfonic acid group (-SO 3 H) is bonded to at least one terminal of ethylene (polyethylene tetrafluoroethylene, ETFE).
  • PTFE polytetrafluoroethylene
  • PVDF polyvinylidene fluoride
  • ETFE polyethylene tetrafluoroethylene
  • the fluorine-based anionic polymer may include at least one of Nafion, Aquivion, Flemion, and Aciplex.
  • the material to be measured can be smoothly passed through ion exchange while preventing the interfering factor material from adsorbing to the enzyme layer 120 . Accordingly, sensing sensitivity of the working electrode 100 may be improved.
  • an aqueous solution of the fluorine-based anionic polymer may be formed by mixing the above-described fluorine-based anionic polymer and a buffer solution.
  • the buffer solution may include a Phosphate Buffered Saline (PBS) buffer solution.
  • PBS Phosphate Buffered Saline
  • the content of the fluorine-based anionic polymer added to the aqueous solution of the fluorine-based anionic polymer may be 0.1 to 5% by weight based on the total weight of the buffer solution.
  • the barrier layer 130 may be formed by coating and drying the formed fluorine-based anionic polymer aqueous solution on the enzyme layer 120 .
  • a coating method commonly used in the art may be used, and various printing methods may be used, for example.
  • the barrier layer 130 may further include a phosphate compound derived from a buffer solution.
  • the phosphate compound may contribute to fixing the fluorine-based anionic polymer on the enzyme layer 120 . Accordingly, the barrier layer 130 may be more stably formed on the enzyme layer 120 .
  • the amount of the phosphate compound may be less than 5% by weight, preferably 0.5 to 3% by weight, based on the total weight of the barrier layer 130 . Accordingly, mechanical stability of the barrier layer 130 may be improved while preventing interfering substances from adsorbing to the enzyme layer 120 .
  • interfering factor substances eg, mucins
  • the agglomerates may interfere with the reaction of the measuring target material and the working electrode 100 on the surface of the electrode. Accordingly, sensitivity and reliability of the working electrode 100 may decrease.
  • a viscosity control layer 140 may be formed on the barrier layer 130 .
  • the viscosity control layer 140 may include a viscosity control agent to suppress aggregation of the above-described interference factor material. Accordingly, the sensitivity and reliability of the working electrode 100 may be improved by reducing agglomerates that hinder detection of the measurement target material.
  • the viscosity of a sample eg, saliva
  • the viscosity modifier e.g, water
  • the reaction rate and accuracy in the enzyme layer 120 may be increased by reducing the reaction between the measurement target material and other materials. Accordingly, sensing performance and sensing efficiency of the working electrode 100 may be improved.
  • the concentration of the detection target is measured lower than the actual one due to a reaction between the detection target and another substance (eg, an interference factor substance) in the measurement target material, so that the time and detection accuracy required to measure the same concentration are reduced. It could mean a deterioration.
  • another substance eg, an interference factor substance
  • the viscosity modifier is an anionic surfactant containing a sulfonic acid group, a surfactant containing a substituted or unsubstituted aryl group having 6 to 12 carbon atoms, and a substituted or unsubstituted C 6 to 12 aryl group. It may include at least one of surfactants containing 12 heteroaryl groups.
  • the sulfonic acid group of the anionic surfactant containing a sulfonic acid group and/or the aryl group of the surfactant containing an aryl group separates and separates anionic interfering factors (eg, mucins) to inhibit aggregation. Accordingly, sensitivity and reliability of the working electrode 100 may be improved.
  • the viscosity modifier may include at least one of Triton X-100, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate (SDS).
  • an aqueous viscosity modifier may be formed by mixing the aforementioned viscosity modifier and a buffer solution.
  • the buffer solution may include a PBS buffer solution.
  • the amount of the viscosity modifier added to the aqueous solution of the viscosity modifier may be 0.05 to 10% by weight based on the total weight of the buffer solution.
  • the sensing performance and mechanical stability of the working electrode 100 may be improved together.
  • the viscosity control layer 140 may be formed by coating and drying the formed aqueous viscosity control agent solution on the barrier layer 130 .
  • a coating method commonly used in the art may be used, and various printing methods may be used, for example.
  • the viscosity control layer 140 may further include a phosphate compound derived from a buffer solution.
  • the phosphate compound may contribute to fixing the viscosity modifier on the barrier layer 130 . Accordingly, the viscosity control layer 140 may be more stably formed on the barrier layer 130 .
  • the content of the phosphate compound may be less than 5% by weight, preferably 0.5 to 3% by weight, based on the total weight of the viscosity control layer 140 . Accordingly, the mechanical stability of the viscosity control layer 140 may be improved while preventing the interfering factor from aggregation.
  • the contact angle of the fluorine-based anionic polymer included in the barrier layer 130 may be increased by an internal fluorine component. Accordingly, the viscosity control layer 140 may be more stably formed and fixed on the barrier layer 130 .
  • Exemplary embodiments including the above-described barrier layer 130 and the viscosity control layer 140 show that the detection performance of the working electrode 100 is reduced by the interference factor material in the sample (eg, saliva) without a separate pretreatment or filter device. degradation can be prevented. Accordingly, it is possible to improve sensing performance and reliability of the working electrode 100 while reducing processing time and cost.
  • the interference factor material in the sample eg, saliva
  • the reference electrode 200 may be formed to correspond to the working electrode (working electrode 100).
  • the reference electrode 200 may be disposed around the working electrode 100 and electrically separated from the working electrode 100 .
  • the reference electrode 200 may provide a reference value for a current value or potential value measured by the working electrode 100 when measuring glucose, for example.
  • the degree of glucose oxidation-reduction reaction occurring at the working electrode 100 can be specified using the potential value of the reference electrode 200 as a reference value.
  • the concentration of the component to be measured can be derived from the changed amount of current.
  • the reference electrode 200 may include a reference electrode conductive layer 210 substantially the same as the conductive layer 110 of the working electrode 100 .
  • the reference electrode material layer 220 may be stacked on the reference electrode conductive layer 210 to form the reference electrode 200 .
  • the reference electrode material layer may include, for example, Ag/AgCl paste.
  • the wire 310 may be connected to the working electrode 100 and the reference electrode 200 respectively.
  • the wiring 310 connected to the working electrode 100 and the wiring 310 connected to the reference electrode 200 may be electrically separated from each other.
  • the wire 310 may be integrally formed with the working electrode 100 and the reference electrode 200 .
  • the working electrode 100 and the wiring 310 may be formed together by forming a metal film on the substrate 300 and patterning the metal film.
  • the wire 310 may be formed of substantially the same material as the metal layer of the working electrode 100 .
  • the wires 310 may be connected to a driving integrated circuit (IC) chip.
  • IC driving integrated circuit
  • electrical signals measured from the working electrode 100 and the reference electrode 200 may be transferred to the driving IC chip through the wiring 310, and the driving IC chip may calculate the concentration of the component to be measured.
  • the biosensor 10 may further include a temperature sensor 320 . Accordingly, the temperature sensor 320 may be electrically connected to the wire 310 to correct a measurement deviation according to temperature.
  • a barrier layer 130 including a fluorine-based anionic polymer and a viscosity control layer 140 are formed on the conductive layer 110 and the enzyme layer 120 .
  • the sensing performance and reliability can be improved compared to the case where the barrier layer 130 and the viscosity control layer 140 are not included, or when only the barrier layer 130 is included and the viscosity control layer 140 is not included. .
  • FIG. 3 is a schematic graph showing glucose sensing performance of a biosensor according to exemplary embodiments and comparative examples. Specifically, FIG. 3 is a schematic graph showing performance of sensing glucose contained in saliva in exemplary embodiments and comparative examples.
  • the working electrode 100 including the barrier layer 130 and the viscosity control layer 140 does not include the barrier layer 130 and the viscosity control layer 140. Compared to comparative examples, excellent glucose sensing performance was implemented.
  • the above embodiment is substantially different from the case of injecting saliva filtered (pre-processed) with a PVDF syringe filter into a sensor that does not include the barrier layer 130 and the viscosity control layer 140 (Comparative Example 2 in FIG. 3). Equal or better glucose sensing performance was achieved. Therefore, excellent glucose sensing performance can be implemented without separate preprocessing or filtering of the measurement target. Accordingly, it is possible to improve sensing performance and reliability of the biosensor while reducing processing time and cost.

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  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Un biocapteur selon un mode de réalisation de la présente invention comprend un substrat, une électrode de travail et une électrode de référence, l'électrode de travail comprenant : une couche conductrice ; une couche enzymatique formée sur la couche conductrice et réagissant avec une substance à mesurer ; une couche barrière formée sur la couche enzymatique et comprenant un polymère anionique à base de fluor ; et une couche de régulation de viscosité formée sur la couche barrière. Ainsi, il est possible d'améliorer les performances et la fiabilité de la détection du glucose en empêchant l'adsorption ou l'agrégation de facteurs d'interférence inclus dans la substance à mesurer sur la couche enzymatique.
PCT/KR2022/013240 2021-09-17 2022-09-05 Biocapteur WO2023043105A1 (fr)

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KR20180072509A (ko) * 2016-12-21 2018-06-29 주식회사 동운아나텍 타액을 이용한 진단 디바이스 및 이를 이용한 분석 방법
EP3380833B1 (fr) * 2015-11-27 2019-12-25 Radiometer Medical ApS Couche externe pour des capteurs d'enzyme
KR20200120286A (ko) * 2019-04-12 2020-10-21 동우 화인켐 주식회사 바이오 센서
KR20210112008A (ko) * 2020-03-04 2021-09-14 동우 화인켐 주식회사 바이오센서 및 이의 제조방법

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KR101107506B1 (ko) 2011-09-08 2012-01-31 한국지질자원연구원 이산화티타늄-그래핀 복합체가 구비된 글루코스 센서

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KR20160146514A (ko) * 2015-06-12 2016-12-21 서울대학교산학협력단 글루코오스 조절 시스템, 상기 글루코오스 조절 시스템의 형성 방법, 및 상기 글루코오스 조절 시스템을 이용한 글루코오스 조절 방법
EP3380833B1 (fr) * 2015-11-27 2019-12-25 Radiometer Medical ApS Couche externe pour des capteurs d'enzyme
KR20180072509A (ko) * 2016-12-21 2018-06-29 주식회사 동운아나텍 타액을 이용한 진단 디바이스 및 이를 이용한 분석 방법
KR20200120286A (ko) * 2019-04-12 2020-10-21 동우 화인켐 주식회사 바이오 센서
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