WO2023043105A1 - Biosensor - Google Patents
Biosensor Download PDFInfo
- 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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- WO
- WIPO (PCT)
- Prior art keywords
- layer
- biosensor
- working electrode
- barrier layer
- viscosity control
- Prior art date
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- 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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Abstract
A biosensor according to an embodiment of the present invention comprises a substrate, a working electrode, and a reference electrode, wherein the working electrode comprises: a conductive layer; an enzyme layer which is formed on the conductive layer and reacts with a substance to be measured; a barrier layer which is formed on the enzyme layer and includes a fluorine-based anionic polymer; and a viscosity adjusting layer which is formed on the barrier layer. Thus, it is possible to improve glucose detection performance and reliability by preventing interfering factors included in the substance to be measured from being adsorbed or aggregated onto the enzyme layer.
Description
본 발명은 바이오 센서에 관한 것이다. 보다 구체적으로는, 작업 전극 및 기준 전극을 포함하는 바이오 센서에 관한 것이다.The present invention relates to biosensors. More specifically, it relates to a biosensor comprising a working electrode and a reference electrode.
인간의 평균 수명이 증가함에 따라, 헬스 케어 산업이 급속히 팽창하고 있다. 특히, 여러 가지 생체 신호들을 편리하게 측정할 수 있는 바이오 센서에 대한 요구가 점차 증가하고 있다.BACKGROUND OF THE INVENTION As the average human lifespan increases, the health care industry is rapidly expanding. In particular, a demand for a biosensor capable of conveniently measuring various biosignals is gradually increasing.
바이오 센서는 체액(땀, 눈물, 혈액 등)에 포함된 화학종들과 반응하는 효소를 사용할 수 있다. 상기 효소가 상기 화학종과 반응하여 전류가 발생하면, 이를 측정하여 해당 화학종의 농도를 측정한다.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.
바이오 센서에 대한 연구들은 예를 들면, 대한민국 등록특허공보 제10-1107506호에 개시된 바와 같이, 글루코스(glucose)의 글루코노락톤 (gluconolactone)으로의 산화를 촉진하는 글루코스 산화 효소(glucose oxidase) 또는 글루코스 탈수소 효소와 같은 효소의 고정에 기반을 두고 있다.Studies on biosensors, for example, as disclosed in Korean Patent Registration No. 10-1107506, glucose oxidase that promotes the oxidation of glucose to gluconolactone or glucose It is based on the immobilization of enzymes such as dehydrogenase.
글루코스는 대부분 유기체의 광범위한 영양 공급원이며, 에너지 공급, 탄소 저장, 생합성 및 탄소 골격 및 세포벽 형성의 기초적인 역할을 수행하는 성분으로서, 전위차 또는 전류 측정을 통해 체액 또는 타액에 포함된 글루코스의 농도를 측정하는 바이오 센서에 대한 연구가 활발히 수행되고 있다.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.
글루코스 센싱 대상체가 되는 체액 또는 타액에 포함된 방해 인자 물질에 따라 작업 전극의 감지 성능 및 신뢰성이 저하될 수 있다. 따라서, 감지 성능 및 신뢰성이 개선된 작업 전극 및 이를 포함하는 바이오 센서의 연구 개발이 필요하다.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.
본 발명의 일 과제는 감지 성능 및 신뢰성이 향상된 바이오 센서를 제공하는 것이다.An object of the present invention is to provide a biosensor having improved sensing performance and reliability.
1. 기판; 및 상기 기판 상에 서로 이격되어 배치된 작업 전극 및 기준 전극을 포함하고, 상기 작업 전극은 상기 기판 상에 형성된 도전층; 상기 도전층 상에 형성되고 측정 대상 물질과 반응하는 효소층; 상기 효소층 상에 형성되고, 불소계 음이온성 고분자를 포함하는 배리어층; 및 상기 배리어층 상에 형성된 점도 조절층을 포함하는, 바이오 센서.1. substrate; and a working electrode and a reference electrode disposed spaced apart from each other on the substrate, wherein 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.
2. 위 1에 있어서, 상기 불소계 음이온성 고분자는 폴리테트라플루오로에틸렌(polytetrafluoroethylene, PTFE), 폴리비닐플루오라이드(polyvinylfluoride, PVF), 폴리비닐리딘플루오라이드(polyvinylidene fluoride, PVDF) 및 폴리에틸렌테트라플루오로에틸렌(polyethylene tetrafluoroethylene, ETFE) 중 적어도 하나의 말단에 카르복실기, 인산기 및 술폰산기 중 적어도 하나가 결합된 화합물인, 바이오 센서.2. In the above 1, the fluorine-based anionic polymer is polytetrafluoroethylene (PTFE), polyvinylfluoride (PVF), polyvinylidene fluoride (PVDF) and polyethylenetetrafluoro 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).
3. 위 1에 있어서, 상기 불소계 음이온성 고분자는 나피온(Nafion), 아퀴비온(Aquivion), 플레미온(Flemion) 및 에이씨플렉스(Aciplex) 중 적어도 하나를 포함하는, 바이오 센서.3. The biosensor according to 1 above, wherein the fluorine-based anionic polymer includes at least one of Nafion, Aquivion, Flemion, and Aciplex.
4. 위 1에 있어서, 상기 점도 조절층은 점도 조절제를 포함하고,4. The method of 1 above, wherein the viscosity control layer includes a viscosity control agent,
상기 점도 조절제는 술폰산기를 함유한 음이온성 계면활성제, 치환 또는 비치환된 탄소수 6 내지 12의 아릴기(aryl group)를 함유한 계면활성제, 및 치환 또는 비치환된 탄소수 6 내지 12의 헤테로아릴기(heteroaryl group)를 함유한 계면활성제 중 적어도 하나를 포함하는, 바이오 센서.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).
5. 위 4에 있어서, 상기 점도 조절제는 Triton X-100, CHAPS(3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) 및 SDS(sodium dodecyl sulfate) 중 적어도 하나를 포함하는, 바이오 센서. 5. The biosensor according to 4 above, wherein the viscosity modifier includes at least one of Triton X-100, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate (SDS).
6. 위 1에 있어서, 상기 효소층은 글루코스 산화 효소(Glucose oxidase) 또는 글루코스 탈수소 효소(Glucose dehydrogenase)를 포함하는, 바이오 센서.6. The biosensor according to 1 above, wherein the enzyme layer includes glucose oxidase or glucose dehydrogenase.
7. 위 1에 있어서, 상기 측정 대상 물질은 타액 내 함유된 글루코스인, 바이오 센서.7. The biosensor according to 1 above, wherein the substance to be measured is glucose contained in saliva.
8. 위 1에 있어서, 상기 도전층은 금속층 및 금속 보호층을 포함하는, 바이오 센서.8. The biosensor according to 1 above, wherein the conductive layer includes a metal layer and a metal protective layer.
9. 위 8에 있어서, 상기 금속층은 금(Au), 은(Ag), 구리(Cu), 백금(Pt), 티타늄(Ti), 니켈(Ni), 주석(Sn), 몰리브덴(Mo), 코발트(Co), 팔라듐(Pd) 및 이들의 합금 중 적어도 하나를 포함하는, 바이오 센서.9. In the above 8, 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.
10. 위 8에 있어서, 상기 금속 보호층은 ITO(Indium Tin Oxide) 또는 IZO(Indium Zinc Oxide)를 포함하는, 바이오 센서.10. The biosensor according to 8 above, wherein the metal protective layer includes ITO (Indium Tin Oxide) or IZO (Indium Zinc Oxide).
11. 위 1에 있어서, 상기 도전층 및 상기 효소층 사이에 전자 수송체를 포함하는 전자 수송층이 더 배치되는, 바이오 센서.11. The biosensor according to 1 above, wherein an electron transport layer including an electron transporter is further disposed between the conductive layer and the enzyme layer.
12. 위 11에 있어서, 상기 전자 수송체는 프러시안 블루(Prussian blue)를 포함하는, 바이오 센서.12. The biosensor according to 11 above, wherein the electron transporter includes Prussian blue.
13. 위 1에 있어서, 상기 배리어층은 인산 염 화합물을 더 포함하는, 바이오 센서.13. The biosensor according to 1 above, wherein the barrier layer further comprises a phosphate compound.
14. 위 13에 있어서, 상기 인산 염 화합물의 함량은 상기 배리어층의 총 중량 대비 5 중량% 미만인, 바이오 센서.14. The biosensor according to 13 above, wherein the content of the phosphate compound is less than 5% by weight based on the total weight of the barrier layer.
15. 위 1에 있어서, 상기 점도 조절층은 인산 염 화합물을 더 포함하는, 바이오 센서.15. The biosensor according to 1 above, wherein the viscosity control layer further comprises a phosphate compound.
16. 위 15에 있어서, 상기 인산 염 화합물의 함량은 상기 점도 조절층의 총 중량 대비 5 중량% 미만인, 바이오 센서.16. The biosensor according to 15 above, wherein the content of the phosphate compound is less than 5% by weight based on the total weight of the viscosity control layer.
17. 위 1에 있어서, 상기 배리어층은 상기 측정 대상 물질과 상이한 방해 인자 물질을 밀어내는, 바이오 센서.17. The biosensor according to 1 above, wherein the barrier layer pushes out an interfering material different from the measurement target material.
본 발명의 예시적인 실시예들에 따르면, 바이오 센서에 포함된 작업 전극은 도전층 및 효소층 상에 불소계 음이온성 고분자를 포함하는 배리어층을 포함할 수 있다. 이 경우, 음이온성 뮤신이 글루코스 산화 효소 및 글루코스 탈수소 효소에 흡착되는 것을 억제할 수 있다. 이에 따라, 바이오 센서의 센싱 감도 및 신뢰성이 개선될 수 있다.According to exemplary embodiments of the present invention, 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. In this case, the adsorption of anionic mucin to glucose oxidase and glucose dehydrogenase can be suppressed. Accordingly, sensing sensitivity and reliability of the biosensor may be improved.
예시적인 실시예들에 따르면, 바이오 센서의 작업 전극은 상기 배리어층 상에 점도 조절층을 더 포함할 수 있다. 이 경우, 측정 대상 물질과 상이한 방해 인자 물질이 소수성 결합을 하여 응집되는 것을 억제할 수 있다. 이에 따라, 측정 대상 물질의 감지를 방해하는 응집체가 감소하여 작업 전극의 감도 및 신뢰성이 향상될 수 있다.According to example embodiments, the working electrode of the biosensor may further include a viscosity control layer on the barrier layer. In this case, it is possible to suppress aggregation of an interference factor material different from the measurement target material through hydrophobic bonding. Accordingly, the sensitivity and reliability of the working electrode may be improved by reducing agglomerates that hinder detection of the measurement target material.
상술한 배리어층 및 점도 조절층을 포함하는 예시적인 실시예들은 별도의 전처리 또는 필터 장치 없이 방해 인자 물질에 의한 작업 전극의 감지 성능 저하를 억제할 수 있다. 이에 따라, 처리 시간 및 비용을 절감하면서도 바이오 센서의 감지 성능 및 신뢰성을 개선할 수 있다.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.
도 1 및 도 2는 예시적인 실시예들에 따른 바이오 센서를 나타내는 개략적인 평면도 및 단면도이다.1 and 2 are schematic plan and cross-sectional views illustrating a biosensor according to example embodiments.
도 3은 예시적인 실시예 및 비교예들에 따른 바이오 센서의 감지 성능을 나타내는 개략적인 그래프이다.3 is a schematic graph showing sensing performance of biosensors according to exemplary embodiments and comparative examples.
본 발명의 실시예들은 기판, 작업 전극 및 기준 전극을 포함하는 바이오 센서를 제공한다.Embodiments of the present invention provide a biosensor including a substrate, a working electrode and a reference electrode.
이하 도면을 참고하여, 본 발명의 실시예들을 보다 구체적으로 설명하도록 한다. 다만, 본 명세서에 첨부되는 다음의 도면들은 본 발명의 바람직한 실시예를 예시하는 것이며, 전술한 발명의 내용과 함께 본 발명의 기술사상을 더욱 이해시키는 역할을 하는 것이므로, 본 발명은 그러한 도면에 기재된 사항에만 한정되어 해석되어서는 아니된다.With reference to the following drawings, embodiments of the present invention will be described in more detail. However, the following drawings attached to this specification illustrate preferred embodiments of the present invention, and serve to further understand the technical idea of the present invention together with the contents of the above-described invention, so the present invention is described in such drawings should not be construed as limited to
도 1 및 도 2는 예시적인 실시예들에 따른 바이오 센서를 나타내는 개략적인 평면도 및 단면도이다. 구체적으로, 도 2는 도 1의 I-I' 선을 따라 바이오 센서를 두께 방향으로 절단한 개략적인 단면도이다.1 and 2 are schematic plan and cross-sectional views illustrating a biosensor according to example embodiments. Specifically, FIG. 2 is a schematic cross-sectional view of the biosensor taken along line II' of FIG. 1 in a thickness direction.
도 1 및 도 2를 참조하면, 예시적인 실시예들에 따른 바이오 센서(10)는 작업 전극(working electrode, 100), 기준 전극(reference electrode, 200), 기판(300) 및 배선(310)을 포함할 수 있다.Referring to FIGS. 1 and 2 , the biosensor 10 according to exemplary embodiments includes a working electrode 100, a reference electrode 200, a substrate 300, and a wire 310. can include
예를 들면, 작업 전극(100)은 바이오 센서(10)의 측정 대상 물질(예를 들면, 글루코스)의 산화-환원 반응이 일어나는 전극으로 제공될 수 있다.For example, 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.
기판(300)은 작업 전극(100), 기준 전극(200), 배선(310) 등이 배치되는 기재로 제공될 수 있다.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.
예를 들어, 기판(300)은 플렉서블 특성을 갖는 기재 필름일 수 있다.For example, the substrate 300 may be a base film having flexible properties.
예를 들면, 기판(300)은 폴리에틸렌테레프탈레이트, 폴리에틸렌이소프탈레이트, 폴리에틸렌나프탈레이트, 폴리부틸렌테레프탈레이트 등의 폴리에스테르계 수지; 디아세틸셀룰로오스, 트리아세틸셀룰로오스 등의 셀룰로오스계 수지; 폴리카보네이트계 수지; 폴리메틸(메타)아크릴레이트, 폴리에틸(메타)아크릴레이트 등의 아크릴계 수지; 폴리스티렌, 아크릴로니트릴-스티렌 공중합체 등의 스티렌계 수지; 폴리에틸렌, 폴리프로필렌, 시클로계 또는 노보넨 구조를 갖는 폴리올레핀, 에틸렌-프로필렌 공중합체 등의 폴리올레핀계 수지; 염화비닐계 수지; 나일론, 방향족 폴리아미드 등의 아미드계 수지; 이미드계 수지; 폴리에테르술폰계 수지; 술폰계 수지; 폴리에테르에테르케톤계 수지; 황화 폴리페닐렌계 수지; 비닐알코올계 수지; 염화비닐리덴계 수지; 비닐부티랄계 수지; 알릴레이트계 수지; 폴리옥시메틸렌계 수지; 에폭시계 수지 등과 같은 열가소성 수지로 구성된 필름을 들 수 있으며, 상기 열가소성 수지의 블렌드물로 구성된 필름이 사용될 수 있다. 또한, 상기 기판(300)은 (메타)아크릴계, 우레탄계, 아크릴우레탄계, 에폭시계, 실리콘계 등의 열경화성 수지 또는 자외선 경화형 수지로 된 필름을 포함할 수 있다.For example, 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 polyphenylene-based resins; vinyl alcohol-based resin; vinylidene chloride-based resins; vinyl butyral-based resins; allylate-based resins; polyoxymethylene-based resin; A film composed of a thermoplastic resin such as an epoxy resin may be used, and a film composed of a blend of the thermoplastic resin may be used. In addition, the substrate 300 may include a film made of a thermosetting resin or an ultraviolet curable resin such as (meth)acrylic, urethane, acrylurethane, epoxy, or silicon.
기판(300)의 두께는 제한되지 않으나, 강도, 취급성, 작업성, 박층성 등을 고려하여 1 내지 500 ㎛일 수 있다. 바람직하게는, 기판(300)의 두께는 1 내지 300 ㎛일 수 있고, 더욱 바람직하게는 5 내지 200 ㎛일 수 있다.The thickness of the substrate 300 is not limited, but may be 1 to 500 μm in consideration of strength, handling, workability, and thinness. Preferably, the thickness of the substrate 300 may be 1 to 300 μm, more preferably 5 to 200 μm.
예를 들면, 기판(300)으로 사용되는 기재 필름에는 1종 이상의 첨가제가 함유될 수 있다. 첨가제는 예를 들면, 자외선흡수제, 산화방지제, 윤활제, 가소제, 이형제, 착색방지제, 난연제, 핵제, 대전방지제, 안료, 착색제 등을 포함할 수 있다.For example, 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.
일부 실시예들에 있어서, 상기 기재 필름은 필름의 일면 또는 양면에 하드코팅층, 반사방지층 및/또는 가스 배리어층과 같은 다양한 기능성층을 포함할 수 있다.In some embodiments, 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.
일부 실시예들에 있어서, 상기 기재 필름은 표면 처리될 수 있다. 예를 들면, 표면 처리는 플라즈마(plasma) 처리, 코로나(corona) 처리, 프라이머(primer) 처리 등의 건식 처리, 검화 처리를 포함하는 알칼리 처리 등의 화학 처리를 포함할 수 있다.In some embodiments, the base film may be surface treated. For example, 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.
예를 들면, 기판(300) 상에 절연막이 더 형성될 수 있고, 상기 절연막은 도전층(110)과 동일 레벨에서 도전층(110)의 주변부에 형성될 수 있다.For example, 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 .
도 2에 도시된 바와 같이, 작업 전극(100)은 도전층(110), 효소층(120), 배리어층(130) 및 점도 조절층(140)을 포함할 수 있다.As shown in FIG. 2 , the working electrode 100 may include a conductive layer 110 , an enzyme layer 120 , a barrier layer 130 and a viscosity control layer 140 .
작업 전극(100)은 예를 들면, 효소층(120)을 구성하는 물질 및 측정 대상 물질의 반응에 의해 발생된 전기적 신호를 감지할 수 있다.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.
예시적인 실시예들에 있어서, 도전층(110)은 바이오 센서(10)의 기판(300) 상에 배치되어 측정 대상 물질의 화학 반응에서 발생한 전자 또는 정공이 전달되는 통로로 제공될 수 있다.In example embodiments, 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.
일부 실시예들에 있어서, 도전층(110)은 금속층 및 금속 보호층을 포함할 수 있다. 상기 금속 보호층은 상기 금속층의 상면을 커버하도록 배치될 수 있다.In some embodiments, 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.
예를 들면, 상기 금속 보호층은 상기 금속층과 직접 접촉하여 적층될 수 있다. 상기 금속 보호층은 측정 대상 물질의 화학 반응으로 인해 상기 금속층이 산화되는 것을 방지할 수 있다.For example, 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.
예를 들면, 상기 금속 보호층은 상기 금속층이 대기와 직접 접촉하는 것을 방지하여 상기 금속층을 구성하는 금속 성분의 산화를 방지할 수 있다. 따라서, 상기 금속층에 의해 감지되는 전기적 신호의 신뢰성이 향상될 수 있다.For example, 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.
일부 실시예들에 있어서, 상기 금속층은 금(Au), 은(Ag), 구리(Cu), 백금(Pt), 티타늄(Ti), 니켈(Ni), 주석(Sn), 몰리브덴(Mo), 코발트(Co), 팔라듐(Pd) 및 이들의 합금 중 적어도 하나를 포함할 수 있다.In some embodiments, 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.
예를 들면, 상기 금속층은 APC 합금(Ag-Pd-Cu alloy)을 포함할 수 있다. For example, the metal layer may include an Ag-Pd-Cu alloy (APC alloy).
일 실시예에 있어서, 상기 금속층은 Au, Ag, APC 합금(Ag-Pd-Cu alloy) 및 Pt 중 적어도 하나로 형성될 수도 있다. 이 경우, 도전층(110)의 전기 전도성이 향상되어 저항이 감소될 수 있다. 이에 따라, 작업 전극(100)의 감지 성능을 향상시킬 수 있다.In one embodiment, the metal layer may be formed of at least one of Au, Ag, APC alloy (Ag-Pd-Cu alloy), and Pt. In this case, 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.
일부 실시예들에 있어서, 상기 금속층의 두께는 500 내지 4,000 Å일 수 있다. 상기 두께 범위 내에서 작업 전극(100)의 우수한 검출 성능을 확보할 수 있다. 바람직하게는, 상기 금속층의 두께는 1,000 내지 3,000 Å일 수 있다.In some embodiments, the thickness of the metal layer may be 500 to 4,000 Å. 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 Å.
일부 실시예들에 있어서, 상기 금속 보호층은 ITO(Indium Tin Oxide) 또는 IZO(Indium Zinc Oxide)를 포함할 수 있다. 예를 들면, 상기 금속 보호층은 ITO(Indium Tin Oxide) 또는 IZO(Indium Zinc Oxide)만으로 형성될 수 있다. 상기 ITO 및 IZO는 전기 전도성을 가지면서도 화학적으로 안정하여 상기 금속층을 산화-환원 반응으로부터 효과적으로 보호할 수 있다.In some embodiments, the metal protective layer may include indium tin oxide (ITO) or indium zinc oxide (IZO). For example, the metal protective layer may be formed of only indium tin oxide (ITO) or indium zinc oxide (IZO). The ITO and IZO have electrical conductivity and are chemically stable, so that the metal layer can be effectively protected from an oxidation-reduction reaction.
일부 실시예들에 있어서, 상기 금속 보호층의 두께는 100 내지 800 Å일 수 있다. 상기 두께 범위 내에서 상기 금속층을 효과적으로 보호할 수 있으며, 도전층(110)의 전기 전도성을 향상시킬 수 있다. 바람직하게는, 상기 금속 보호층의 두께는 300 내지 500 Å일 수 있다.In some embodiments, the thickness of the metal protective layer may be 100 to 800 Å. 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 Å.
예시적인 실시예들에 있어서, 상술한 도전층(110) 상에 효소층(120)이 배치될 수 있다.In example embodiments, the enzyme layer 120 may be disposed on the above-described conductive layer 110 .
예를 들면, 효소층(120)은 측정 대상 물질과 화학 반응하여 전기적 신호를 발생시키는 층으로 제공될 수 있다.For example, the enzyme layer 120 may be provided as a layer that generates an electrical signal by chemically reacting with a substance to be measured.
예시적인 실시예들에 있어서, 측정 대상 물질은 글루코스일 수 있다.In example embodiments, a substance to be measured may be glucose.
일부 실시예들에 있어서, 효소층(120)은 글루코스 산화 효소 또는 글루코스 탈수소 효소를 포함할 수 있다.In some embodiments, the enzyme layer 120 may include a glucose oxidase or a glucose dehydrogenase.
예를 들면, 측정 대상 물질인 시료가 작업 전극(100)에 접촉하면, 시료에 포함되어 있는 글루코스가 글루코스 산화 효소 또는 글루코스 탈수소 효소에 의하여 산화되고, 글루코스 산화 효소 또는 글루코스 탈수소 효소는 환원될 수 있다.For example, when a sample, which is a material to be measured, contacts the working electrode 100, glucose contained in the sample is oxidized by glucose oxidase or glucose dehydrogenase, and the glucose oxidase or glucose dehydrogenase can be reduced. .
이 경우, 후술할 전자 수송층에 포함된 전자 수송체는 환원된 글루코스 산화 효소 또는 글루코스 탈수소 효소를 산화시키고, 자신은 환원될 수 있다. 환원된 전자 수송체는 예를 들면, 일정 전압이 가해진 전극 표면에서 전자를 잃고 전기화학적으로 다시 산화될 수 있다. 시료 내의 글루코스 농도는 전자 수송체가 산화되는 과정에서 발생되는 전류량에 비례하므로, 이 전류량을 측정함으로써 글루코스 농도를 측정할 수 있다.In this case, 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.
일부 실시예들에 있어서, 상기 글루코스 산화 효소 또는 글루코스 탈수소 효소는 바인더를 통해 고정될 수 있다. 상기 바인더는 당분야에서 통상적으로 사용되는 바인더를 포함할 수 있으며, 예를 들면, 키토산을 포함할 수 있다.In some embodiments, 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.
일부 실시예들에 있어서, 효소층(120)의 두께는 0.5 내지 10 ㎛일 수 있고, 바람직하게는 1 내지 5 ㎛일 수 있다. 이 경우, 센싱 농도의 상한이 적절히 유지되면서 센싱 감도 및 센싱 속도가 증가할 수 있다. 이에 따라, 작업 전극(100)의 감지 성능 및 신뢰성이 개선될 수 있다.In some embodiments, the thickness of the enzyme layer 120 may be 0.5 to 10 μm, preferably 1 to 5 μm. 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.
일부 실시예들에 있어서, 상술한 도전층(110) 및 효소층(120) 사이에 전자 수송체를 포함하는 전자 수송층이 더 포함될 수 있다.In some embodiments, an electron transport layer including an electron transporter may be further included between the aforementioned conductive layer 110 and the enzyme layer 120 .
예를 들면, 상기 전자 수송층은 상술한 측정 대상 물질의 화학 반응에서 발생한 전자 또는 정공을 도전층(110)까지 전달할 수 있다.For example, 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 .
전자 수송체는 예를 들면, 효소층(120)에서 일어나는 측정 대상 물질의 화학 반응에서 발생한 전자/정공을 수용하여 산화 또는 환원되는 물질을 포함할 수 있다. 상기 산화 또는 환원을 통해 전자/정공을 도전층(110)에 전달할 수 있다.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.
예를 들면, 전자 수송체는 프러시안 블루(Prussian blue)를 포함할 수 있다. 이 경우, 프러시안 블루의 높은 산화성으로 인하여 작업 전극(100)의 전기적 감도를 향상시킬 수 있다.For example, the electron transporter may include Prussian blue. In this case, the electrical sensitivity of the working electrode 100 can be improved due to the high oxidizing property of Prussian blue.
상기 프러시안 블루는 헥사시아노철(II)산철(III)칼륨이 주성분인 청색 안료를 의미할 수 있다.The Prussian blue may refer to a blue pigment whose main component is potassium iron (III) hexacyanoferrate (II) acid.
예를 들면, 작업 전극(100)의 측정 대상 물질은 인체의 타액, 땀, 체액 및 혈액 중 적어도 하나에 함유된 글루코스일 수 있다. 일 실시예에 있어서, 상기 측정 대상 물질은 타액 내 함유된 글루코스일 수 있다.For example, 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. In one embodiment, the substance to be measured may be glucose contained in saliva.
예를 들면, 상기 타액 내 함유된 음이온성 뮤신(mucin)은 측정 대상 물질을 감지할 때 방해 인자 물질로 기능할 수 있다. 이 경우, 상기 뮤신은 효소층(120)의 글루코스 산화 효소 또는 글루코스 탈수소 효소와 흡착될 수 있다. 이에 따라, 작업 전극(100)의 센싱 감도 및 신뢰성이 저하될 수 있다.For example, anionic mucin contained in the saliva may function as a disturbance factor when sensing a target substance to be measured. In this case, 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.
예를 들면, 상기 뮤신을 포함하는 타액 내 방해 인자 물질을 제거하기 위하여 원심분리, 방해 인자 물질 추출 또는 실린지 필터링(Syringe filtering) 등의 방법이 사용될 수 있다. 그러나, 상기 방법은 시료(예를 들면, 타액)를 별도로 전처리하거나 필터 처리한 후 센싱 전극에 접촉시키므로 감지 시간 및 비용이 증가할 수 있다.For example, methods such as centrifugation, extraction of interfering factors, or syringe filtering may be used to remove interfering substances in the mucin-containing saliva. However, since the above method contacts the sensing electrode after separately pre-processing or filtering the sample (eg, saliva), sensing time and cost may increase.
본 발명의 예시적인 실시예들에 있어서, 효소층(120) 상에 불소계 음이온성 고분자를 포함하는 배리어층(130)이 형성될 수 있다.In exemplary embodiments of the present invention, a barrier layer 130 including a fluorine-based anionic polymer may be formed on the enzyme layer 120 .
일부 실시예들에 있어서, 상기 배리어층(130)은 측정 대상 물질과 상이한 방해 인자 물질을 밀어낼 수 있다.In some embodiments, the barrier layer 130 may push out an interference factor material different from a measurement target material.
예를 들면, 상기 불소계 음이온성 고분자는 음이온 간 척력에 의해 타액 내 음이온성 뮤신을 밀어내어 효소층(120)과 접촉하는 것을 방지할 수 있다. 이 경우, 뮤신이 글루코스 산화 효소 및 글루코스 탈수소 효소에 흡착되는 것을 억제할 수 있다. 이에 따라, 작업 전극(100)의 센싱 감도 및 신뢰성이 개선될 수 있다.For example, 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. In this case, 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.
일부 실시예들에 있어서, 상기 불소계 음이온성 고분자는 폴리테트라플루오로에틸렌(polytetrafluoroethylene, PTFE), 폴리비닐플루오라이드(polyvinylfluoride, PVF), 폴리비닐리딘플루오라이드(polyvinylidene fluoride, PVDF) 및 폴리에틸렌테트라플루오로에틸렌(polyethylene tetrafluoroethylene, ETFE) 중 적어도 하나의 말단에 카르복실기(-COOH), 인산기(-PO3H2) 및 술폰산기(-SO3H) 중 적어도 하나가 결합된 화합물일 수 있다.In some embodiments, 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).
예를 들면, 상기 불소계 음이온성 고분자는 나피온(Nafion), 아퀴비온(Aquivion), 플레미온(Flemion) 및 에이씨플렉스(Aciplex) 중 적어도 하나를 포함할 수 있다. 이 경우, 방해 인자 물질이 효소층(120)에 흡착되는 것을 방지하면서도 이온 교환을 통해 측정 대상 물질을 원활히 통과시킬 수 있다. 이에 따라, 작업 전극(100)의 센싱 감도가 개선될 수 있다.For example, the fluorine-based anionic polymer may include at least one of Nafion, Aquivion, Flemion, and Aciplex. In this case, 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.
예시적인 실시예들에 있어서, 상술한 불소계 음이온성 고분자 및 완충 용액을 혼합하여 불소계 음이온성 고분자 수용액을 형성할 수 있다.In exemplary embodiments, 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.
예를 들면, 상기 완충 용액은 PBS(Phosphate buffered saline) 완충 용액을 포함할 수 있다.For example, the buffer solution may include a Phosphate Buffered Saline (PBS) buffer solution.
예를 들면, 상기 불소계 음이온성 고분자 수용액에 투입되는 불소계 음이온성 고분자의 함량은 완충 용액 총 중량 대비 0.1 내지 5 중량%일 수 있다. 이 경우, 방해 인자 물질(예를 들면, 뮤신)을 충분히 제거하면서도 수용액의 산도가 저하되어 효소 활성도가 감소하는 것을 억제할 수 있다. 이에 따라, 작업 전극(100)의 감지 성능 및 신뢰성을 함께 개선할 수 있다.For example, 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. In this case, it is possible to suppress a decrease in enzyme activity due to a decrease in acidity of the aqueous solution while sufficiently removing interfering substances (eg, mucin). Accordingly, the sensing performance and reliability of the working electrode 100 may be improved together.
예를 들면, 형성된 불소계 음이온성 고분자 수용액을 효소층(120) 상에 도포 및 건조하여 배리어층(130)을 형성할 수 있다.For example, the barrier layer 130 may be formed by coating and drying the formed fluorine-based anionic polymer aqueous solution on the enzyme layer 120 .
상기 도포는 해당 기술 분야에서 통상적으로 사용되는 도포법이 사용될 수 있으며, 예를 들면 다양한 프린팅 방법이 사용될 수 있다.For the application, a coating method commonly used in the art may be used, and various printing methods may be used, for example.
일부 실시예들에 있어서, 배리어층(130)은 완충 용액에서 유래한 인산 염 화합물을 더 포함할 수 있다. 이 경우, 인산 염 화합물이 불소계 음이온성 고분자가 효소층(120) 상에 고정되도록 기여할 수 있다. 이에 따라, 배리어층(130)이 효소층(120) 상에 더 안정적으로 형성될 수 있다.In some embodiments, the barrier layer 130 may further include a phosphate compound derived from a buffer solution. In this case, 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 .
상기 인산 염 화합물의 함량은 배리어층(130)의 총 중량 대비 5 중량% 미만일 수 있고, 바람직하게는 0.5 내지 3 중량%일 수 있다. 이에 따라, 방해 인자 물질이 효소층(120)에 흡착되는 것을 방지하면서도 배리어층(130)의 기계적 안정성이 향상될 수 있다.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 .
예를 들면, 방해 인자 물질(예를 들면, 뮤신)끼리 소수성 결합을 하여 응집될 수 있다. 이 경우, 응집체가 전극 표면에서 측정 대상 물질 및 작업 전극(100)의 반응을 방해할 수 있다. 이에 따라, 작업 전극(100)의 감도 및 신뢰성이 저하될 수 있다.For example, interfering factor substances (eg, mucins) may be aggregated by hydrophobic bonding. In this case, 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.
본 발명의 예시적인 실시예들에 있어서, 상기 배리어층(130) 상에 점도 조절층(140)이 형성될 수 있다.In exemplary embodiments of the present invention, a viscosity control layer 140 may be formed on the barrier layer 130 .
예를 들면, 점도 조절층(140)은 점도 조절제를 포함하여 상술한 방해 인자 물질의 응집 현상을 억제할 수 있다. 이에 따라, 측정 대상 물질의 감지를 방해하는 응집체가 감소하여 작업 전극(100)의 감도 및 신뢰성이 향상될 수 있다.For example, 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.
예를 들면, 상기 점도 조절제에 의해 시료(예를 들면, 타액)의 점도가 감소되어, 시료 자체의 매트릭스 효과(matrix effect)를 억제할 수 있다. 이 경우, 측정 대상 물질 및 다른 물질과의 반응이 감소하여 효소층(120)에서의 반응 속도 및 정확도가 증가할 수 있다. 이에 따라, 작업 전극(100)의 감지 성능 및 감지 효율이 개선될 수 있다.For example, the viscosity of a sample (eg, saliva) is reduced by the viscosity modifier, so that a matrix effect of the sample itself can be suppressed. In this case, 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.
상기 매트릭스 효과는 감지 타겟 및 측정 대상 물질 내의 다른 물질(예를 들면, 방해 인자 물질) 사이의 반응에 의해 실제보다 감지 타겟의 농도가 낮게 측정되어, 동일한 농도를 측정하는데 소요되는 시간 및 감지 정확도가 저하되는 현상을 의미할 수 있다.In the matrix effect, 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.
일부 실시예들에 있어서, 점도 조절제는 술폰산기를 함유한 음이온성 계면활성제, 치환 또는 비치환된 탄소수 6 내지 12의 아릴기(aryl group)를 함유한 계면활성제, 및 치환 또는 비치환된 탄소수 6 내지 12의 헤테로아릴기(heteroaryl group)를 함유한 계면활성제 중 적어도 하나를 포함할 수 있다. 이 경우, 술폰산기를 함유한 음이온성 계면활성제의 술폰산기 및/또는 아릴기를 함유한 계면활성제의 아릴기가 음이온성 방해 인자(예를 들면, 뮤신)들을 분리 및 이격시켜 응집을 억제할 수 있다. 이에 따라, 작업 전극(100)의 감도 및 신뢰성이 향상될 수 있다.In some embodiments, 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. In this case, 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.
일부 실시예들에 있어서, 점도 조절제는 Triton X-100, CHAPS(3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) 및 SDS(sodium dodecyl sulfate) 중 적어도 하나를 포함할 수 있다.In some embodiments, the viscosity modifier may include at least one of Triton X-100, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate (SDS).
예시적인 실시예들에 있어서, 상술한 점도 조절제 및 완충 용액을 혼합하여 점도 조절제 수용액을 형성할 수 있다.In exemplary embodiments, an aqueous viscosity modifier may be formed by mixing the aforementioned viscosity modifier and a buffer solution.
예를 들면, 상기 완충 용액은 PBS 완충 용액을 포함할 수 있다.For example, the buffer solution may include a PBS buffer solution.
예를 들면, 상기 점도 조절제 수용액에 투입되는 점도 조절제의 함량은 완충 용액 총 중량 대비 0.05 내지 10 중량%일 수 있다. 이 경우, 방해 인자 물질의 응집을 충분히 억제하면서도 점도가 지나치게 저하되어 도포 불량이 발생하는 것을 방지할 수 있다. 이에 따라, 작업 전극(100)의 감지 성능 및 기계적 안정성을 함께 개선할 수 있다.For example, 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. In this case, while sufficiently suppressing the aggregation of the interfering factor substance, it is possible to prevent the occurrence of coating defect due to an excessive decrease in viscosity. Accordingly, the sensing performance and mechanical stability of the working electrode 100 may be improved together.
예를 들면, 형성된 점도 조절제 수용액을 배리어층(130) 상에 도포 및 건조하여 점도 조절층(140)을 형성할 수 있다.For example, the viscosity control layer 140 may be formed by coating and drying the formed aqueous viscosity control agent solution on the barrier layer 130 .
상기 도포는 해당 기술 분야에서 통상적으로 사용되는 도포법이 사용될 수 있으며, 예를 들면 다양한 프린팅 방법이 사용될 수 있다.For the application, a coating method commonly used in the art may be used, and various printing methods may be used, for example.
일부 실시예들에 있어서, 점도 조절층(140)은 완충 용액에서 유래한 인산 염 화합물을 더 포함할 수 있다. 이 경우, 인산 염 화합물이 점도 조절제가 배리어층(130) 상에 고정되도록 기여할 수 있다. 이에 따라, 점도 조절층(140)이 배리어층(130) 상에 더 안정적으로 형성될 수 있다.In some embodiments, the viscosity control layer 140 may further include a phosphate compound derived from a buffer solution. In this case, 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 .
상기 인산 염 화합물의 함량은 점도 조절층(140)의 총 중량 대비 5 중량% 미만일 수 있고, 바람직하게는 0.5 내지 3 중량%일 수 있다. 이에 따라, 방해 인자가 응집되는 것을 방지하면서도 점도 조절층(140)의 기계적 안정성이 향상될 수 있다.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.
예를 들면, 배리어층(130)에 포함된 불소계 음이온성 고분자는 내부 불소 성분에 의해 접촉각이 증가할 수 있다. 이에 따라, 점도 조절층(140)이 배리어층(130) 상에 더욱 안정적으로 형성 및 고정될 수 있다.For example, 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 .
상술한 배리어층(130) 및 점도 조절층(140)을 포함하는 예시적인 실시예들은 별도의 전처리 또는 필터 장치 없이 시료(예를 들면, 타액) 중 방해 인자 물질이 작업 전극(100)의 감지 성능을 저하시키는 것을 억제할 수 있다. 이에 따라, 처리 시간 및 비용을 절감하면서도 작업 전극(100)의 감지 성능 및 신뢰성을 개선할 수 있다.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.
예시적인 실시예들에 있어서, 기준 전극(200)은 작업 전극(작업 전극(100))에 대응하도록 형성될 수 있다. 예를 들면, 기준 전극(200)은 작업 전극(100) 주변에서 작업 전극(100)과 전기적으로 분리되어 배치될 수 있다.In example embodiments, the reference electrode 200 may be formed to correspond to the working electrode (working electrode 100). For example, the reference electrode 200 may be disposed around the working electrode 100 and electrically separated from the working electrode 100 .
기준 전극(200)은 예를 들면, 글루코스 측정 시 작업 전극(100)에서 측정되는 전류 값 또는 전위 값에 대한 기준치를 제공할 수 있다. 예를 들면, 기준 전극(200)의 전위 값을 기준치로 하여 작업 전극(100)에서 일어나는 글루코스 산화-환원 반응의 정도를 특정할 수 있다. 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. 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.
또한, 기준 전극(200)에서 측정된 전류 값과 작업 전극(100)에서 측정된 전류 값을 비교하여 순수하게 측정 대상 성분에 의해 변화한 전류량을 계산할 수 있다. 이에 따라, 상기 변화한 전류량으로부터 측정 대상 성분의 농도를 도출할 수 있다.In addition, by comparing the current value measured at the reference electrode 200 and the current value measured at the working electrode 100, the amount of current changed purely by the component to be measured can be calculated. Accordingly, the concentration of the component to be measured can be derived from the changed amount of current.
도 2에 도시된 바와 같이, 기준 전극(200)은 작업 전극(100)의 도전층(110)과 실질적으로 동일한 기준 전극 도전층(210)을 포함할 수 있다.As shown in FIG. 2 , 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 .
예시적인 실시예들에 있어서, 기준 전극 도전층(210) 상에 기준 전극 물질층(220)이 적층되어 기준 전극(200)이 형성될 수 있다.In example embodiments, the reference electrode material layer 220 may be stacked on the reference electrode conductive layer 210 to form the reference electrode 200 .
상기 기준 전극 물질 층은 예를 들면, Ag/AgCl 페이스트(paste)를 포함할 수 있다.The reference electrode material layer may include, for example, Ag/AgCl paste.
일부 실시예들에 있어서, 배선(310)은 작업 전극(100) 및 기준 전극(200)에 각각 연결될 수 있다. In some embodiments, the wire 310 may be connected to the working electrode 100 and the reference electrode 200 respectively.
예를 들면, 작업 전극(100)에 연결된 배선(310) 및 기준 전극(200)에 연결된 배선(310)은 서로 전기적으로 분리될 수 있다.For example, 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.
일부 실시예들에 있어서, 배선(310)은 작업 전극(100) 및 기준 전극(200)과 일체로 형성될 수 있다. 기판(300) 상에 금속 막을 형성하고 이를 패터닝하여 작업 전극(100) 및 배선(310)을 함께 형성할 수 있다.In some embodiments, 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.
예를 들면, 배선(310)은 작업 전극(100)의 금속층과 실질적으로 동일한 소재로 형성될 수 있다.For example, the wire 310 may be formed of substantially the same material as the metal layer of the working electrode 100 .
예시적인 실시예들에 있어서, 배선(310)들은 구동 집적 회로(IC) 칩에 연결될 수 있다.In example embodiments, the wires 310 may be connected to a driving integrated circuit (IC) chip.
예를 들면, 작업 전극(100) 및 기준 전극(200)으로부터 측정된 전기적 신호가 배선(310)을 통해 구동 IC 칩에 전달될 수 있으며, 구동 IC 칩이 측정 대상 성분의 농도를 계산할 수 있다.For example, 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.
일부 실시예들에 있어서, 바이오 센서(10)는 온도 센서(320)를 더 포함할 수 있다. 이에 따라, 온도 센서(320)가 배선(310)과 전기적으로 연결되어 온도에 따른 측정 편차를 보정할 수 있다.In some embodiments, 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.
예시적인 실시예들에 따르면, 도전층(110) 및 효소층(120) 상에 불소계 음이온성 고분자를 포함하는 배리어층(130) 및 점도 조절층(140)이 형성된다. 이 경우, 배리어층(130) 및 점도 조절층(140)을 포함하지 않거나, 배리어층(130)만을 포함하고 점도 조절층(140)을 포함하지 않는 경우에 비하여 감지 성능 및 신뢰성이 개선될 수 있다.According to exemplary embodiments, 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 . In this case, 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. .
도 3은 예시적인 실시예 및 비교예들에 따른 바이오 센서의 글루코스 감지 성능을 나타내는 개략적인 그래프이다. 구체적으로, 도 3은 예시적인 실시예 및 비교예들에 있어서, 타액에 포함된 글루코스에 대한 감지 성능을 나타내는 개략적인 그래프이다.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.
도 3을 참조하면, 배리어층(130) 및 점도 조절층(140)을 포함하는 작업 전극(100)(도 3의 실시예)은 배리어층(130) 및 점도 조절층(140)을 포함하지 않는 비교예들에 비하여 우수한 글루코스 감지 성능을 구현하였다.Referring to FIG. 3, the working electrode 100 including the barrier layer 130 and the viscosity control layer 140 (the embodiment of FIG. 3) does not include the barrier layer 130 and the viscosity control layer 140. Compared to comparative examples, excellent glucose sensing performance was implemented.
구체적으로, 상기 실시예는 타액을 별도의 전처리 또는 필터링 없이 배리어층(130) 및 점도 조절층(140)을 포함하지 않는 센서에 투입한 경우(도 3의 비교예 1)에 비하여 현저히 우수한 글루코스 감지 성능이 확인되었다.Specifically, in the above embodiment, compared to the case where saliva was put into a sensor that does not include the barrier layer 130 and the viscosity control layer 140 without separate pretreatment or filtering (Comparative Example 1 in FIG. 3), significantly better glucose detection performance was confirmed.
또한, 상기 실시예는 배리어층(130) 및 점도 조절층(140)을 포함하지 않는 센서에 PVDF 실린지 필터로 필터링(전처리)된 타액을 투입한 경우(도 3의 비교예 2)와 실질적으로 동일하거나 더 우수한 글루코스 감지 성능이 구현되었다. 따라서, 측정 대상에 대한 별도의 전처리 또는 필터링 없이도 우수한 글루코스 감지 성능을 구현할 수 있다. 이에 따라, 처리 시간 및 비용을 절감하면서도 바이오 센서의 감지 성능 및 신뢰성을 개선할 수 있다.In addition, 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.
Claims (17)
- 기판; 및Board; and상기 기판 상에 서로 이격되어 배치된 작업 전극 및 기준 전극을 포함하고,A working electrode and a reference electrode disposed spaced apart from each other on the substrate;상기 작업 전극은The working electrode is상기 기판 상에 형성된 도전층;a conductive layer formed on the substrate;상기 도전층 상에 형성되고 측정 대상 물질과 반응하는 효소층;an enzyme layer formed on the conductive layer and reacting with the measurement target material;상기 효소층 상에 형성되고, 불소계 음이온성 고분자를 포함하는 배리어층; 및a barrier layer formed on the enzyme layer and containing a fluorine-based anionic polymer; and상기 배리어층 상에 형성된 점도 조절층을 포함하는, 바이오 센서.A biosensor comprising a viscosity control layer formed on the barrier layer.
- 청구항 1에 있어서, 상기 불소계 음이온성 고분자는 폴리테트라플루오로에틸렌(polytetrafluoroethylene, PTFE), 폴리비닐플루오라이드(polyvinylfluoride, PVF), 폴리비닐리딘플루오라이드(polyvinylidene fluoride, PVDF) 및 폴리에틸렌테트라플루오로에틸렌(polyethylene tetrafluoroethylene, ETFE) 중 적어도 하나의 말단에 카르복실기, 인산기 및 술폰산기 중 적어도 하나가 결합된 화합물인, 바이오 센서.The method according to claim 1, wherein the fluorine-based anionic polymer is polytetrafluoroethylene (PTFE), polyvinylfluoride (PVF), polyvinylidene fluoride (PVDF) and polyethylenetetrafluoroethylene ( 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).
- 청구항 1에 있어서, 상기 불소계 음이온성 고분자는 나피온(Nafion), 아퀴비온(Aquivion), 플레미온(Flemion) 및 에이씨플렉스(Aciplex) 중 적어도 하나를 포함하는, 바이오 센서.The biosensor of claim 1, wherein the fluorine-based anionic polymer includes at least one of Nafion, Aquivion, Flemion, and Aciplex.
- 청구항 1에 있어서, 상기 점도 조절층은 점도 조절제를 포함하고,The method according to claim 1, wherein the viscosity control layer comprises a viscosity control agent,상기 점도 조절제는 술폰산기를 함유한 음이온성 계면활성제, 치환 또는 비치환된 탄소수 6 내지 12의 아릴기(aryl group)를 함유한 계면활성제, 및 치환 또는 비치환된 탄소수 6 내지 12의 헤테로아릴기(heteroaryl group)를 함유한 계면활성제 중 적어도 하나를 포함하는, 바이오 센서.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).
- 청구항 4에 있어서, 상기 점도 조절제는 Triton X-100, CHAPS(3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) 및 SDS(sodium dodecyl sulfate) 중 적어도 하나를 포함하는, 바이오 센서.The biosensor of claim 4, wherein the viscosity modifier includes at least one of Triton X-100, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate (SDS).
- 청구항 1에 있어서, 상기 효소층은 글루코스 산화 효소(Glucose oxidase) 또는 글루코스 탈수소 효소(Glucose dehydrogenase)를 포함하는, 바이오 센서.The biosensor of claim 1, wherein the enzyme layer includes glucose oxidase or glucose dehydrogenase.
- 청구항 1에 있어서, 상기 측정 대상 물질은 타액 내 함유된 글루코스인, 바이오 센서.The biosensor of claim 1, wherein the substance to be measured is glucose contained in saliva.
- 청구항 1에 있어서, 상기 도전층은 금속층 및 금속 보호층을 포함하는, 바이오 센서.The biosensor of claim 1, wherein the conductive layer includes a metal layer and a metal protective layer.
- 청구항 8에 있어서, 상기 금속층은 금(Au), 은(Ag), 구리(Cu), 백금(Pt), 티타늄(Ti), 니켈(Ni), 주석(Sn), 몰리브덴(Mo), 코발트(Co), 팔라듐(Pd) 및 이들의 합금 중 적어도 하나를 포함하는, 바이오 센서.The method according to claim 8, wherein the metal layer is gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Sn), molybdenum (Mo), cobalt ( A biosensor comprising at least one of Co), palladium (Pd), and alloys thereof.
- 청구항 8에 있어서, 상기 금속 보호층은 ITO(Indium Tin Oxide) 또는 IZO(Indium Zinc Oxide)를 포함하는, 바이오 센서.The biosensor of claim 8, wherein the metal protective layer includes indium tin oxide (ITO) or indium zinc oxide (IZO).
- 청구항 1에 있어서, 상기 도전층 및 상기 효소층 사이에 전자 수송체를 포함하는 전자 수송층이 더 배치되는, 바이오 센서.The biosensor of claim 1, wherein an electron transport layer including an electron transporter is further disposed between the conductive layer and the enzyme layer.
- 청구항 11에 있어서, 상기 전자 수송체는 프러시안 블루(Prussian blue)를 포함하는, 바이오 센서.The biosensor according to claim 11, wherein the electron transporter includes Prussian blue.
- 청구항 1에 있어서, 상기 배리어층은 인산 염 화합물을 더 포함하는, 바이오 센서.The biosensor of claim 1, wherein the barrier layer further comprises a phosphate compound.
- 청구항 13에 있어서, 상기 인산 염 화합물의 함량은 상기 배리어층의 총 중량 대비 5 중량% 미만인, 바이오 센서.The biosensor of claim 13, wherein the content of the phosphate compound is less than 5% by weight based on the total weight of the barrier layer.
- 청구항 1에 있어서, 상기 점도 조절층은 인산 염 화합물을 더 포함하는, 바이오 센서.The biosensor of claim 1, wherein the viscosity control layer further comprises a phosphate compound.
- 청구항 15에 있어서, 상기 인산 염 화합물의 함량은 상기 점도 조절층의 총 중량 대비 5 중량% 미만인, 바이오 센서.The biosensor of claim 15, wherein the content of the phosphate compound is less than 5% by weight based on the total weight of the viscosity control layer.
- 청구항 1에 있어서, 상기 배리어층은 상기 측정 대상 물질과 상이한 방해 인자 물질을 밀어내는, 바이오 센서.The biosensor according to claim 1, wherein the barrier layer pushes out an interfering material different from the measurement target material.
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EP3380833B1 (en) * | 2015-11-27 | 2019-12-25 | Radiometer Medical ApS | An outer layer for enzyme sensors |
KR20180072509A (en) * | 2016-12-21 | 2018-06-29 | 주식회사 동운아나텍 | Device and method for diagnosing using saliva |
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