WO2023048348A1 - Method for manufacturing microneedle biosensor including passivation layer - Google Patents

Method for manufacturing microneedle biosensor including passivation layer Download PDF

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Publication number
WO2023048348A1
WO2023048348A1 PCT/KR2022/001271 KR2022001271W WO2023048348A1 WO 2023048348 A1 WO2023048348 A1 WO 2023048348A1 KR 2022001271 W KR2022001271 W KR 2022001271W WO 2023048348 A1 WO2023048348 A1 WO 2023048348A1
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base
electrode
layer
forming
microneedle
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PCT/KR2022/001271
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French (fr)
Korean (ko)
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안준영
장은희
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주식회사 알비티
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Publication of WO2023048348A1 publication Critical patent/WO2023048348A1/en
Priority to US18/603,502 priority Critical patent/US20240215915A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/155—Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals
    • 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
    • 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

Definitions

  • the present invention relates to a method for manufacturing a microneedle biosensor including a passivation layer.
  • Normal human blood glucose levels are within the range of 70 to 130 mg/dL before meals and within the range of 180 mg/dL after meals. If it exceeds this range, it is classified as hyperglycemia, and if it is below the normal range, it is classified as hypoglycemia.
  • Hyperglycemia is highly correlated with diabetes. Diabetes mellitus refers to a group of metabolic diseases in which high blood sugar levels persist for a long period of time.
  • diabetes In order to diagnose diabetes and manage it so that it does not develop into complications, systematic blood glucose measurement and treatment must be performed simultaneously.
  • diabetes is managed by determining an injection amount of insulin according to a patient's blood sugar level and administering insulin at predetermined time intervals.
  • the blood glucose level of each patient and the change in blood sugar according to insulin administration are different for each individual patient, it is difficult to accurately and efficiently determine the insulin dose, administration time, and interval.
  • CGM continuous glucose monitoring
  • Continuous blood glucose monitoring system was first developed by Medtronic (Minneapolis, MN, USA) and was approved by the US FDA in June 1999.
  • CGM consists of three parts: a blood glucose sensor, a wireless transmitter, and a receiver. The sensor is inserted into the subcutaneous fat to measure sugar in the interstitial fluid.
  • the latest version of the continuous blood glucose monitor shows blood glucose readings in real time, allowing immediate action to be taken.
  • a conventional continuous blood glucose monitoring device includes a sensor inserted into the body to measure blood glucose, a needle for guiding the sensor to be inserted into the body, and a separate applicator coupling structure to apply the sensor module to the body.
  • the sensor is disposed in the hollow of the syringe needle, pierced subcutaneously by the syringe needle, and inserted into the subcutaneous fat.
  • a sensor is placed in the hollow of the syringe needle.
  • Syringe needles are used up to 21 Gauge in size when blood glucose is detected, and since a sensing strip must be placed in the hollow of the syringe needle, a syringe needle used as a sensor needle in a continuous blood glucose measurement device is generally used with a diameter of 600 nm to 800 nm. When the diameter of the sensor needle is 600 nm to 800 nm, there is a problem of causing pain to the user and giving discomfort during continuous use.
  • the present invention has been made to solve the problems of the prior art, and an object of the present invention is to provide a method for manufacturing a microneedle biosensor that can reduce pain for a user when worn with minimal invasion.
  • microneedles are located at the microneedle positions of the working electrode 110, the counter electrode 120, and the reference electrode 130 respectively on plastic adhesive tape and PET (polyethylene terephthalate) layers having an adhesive layer formed on one side of the metal electrode layer.
  • PET polyethylene terephthalate
  • microneedle biosensor manufacturing method including a passivation layer, comprising the step of pressurizing the PET layer with the elastomer and continuing the pressurization on a heated hot plate in that state.
  • the working electrode includes a first base of a circular thin film, a plurality of microneedles protruding vertically on the first base, and a first wiring extending from one end of a circumference of the first base;
  • the counter electrode includes a second base of a thin film strip having a shape concentrically with the first base and forming a part of a second circumference spaced apart from the circumference of the first base by a set distance, and a plurality of vertically protruding on the second base.
  • the reference electrode is spaced apart from the other end of the second base by a set distance and includes a third base of a strip thin film forming a second circumference together with the strip shape of the second base, and a plurality of microcircuits vertically protruding on the third base. It is characterized by comprising a needle and a third wire extending from one end of the third base.
  • the second base occupies 3/4 of the second circumference
  • the third base occupies 1/4 of the second circumference
  • the first wiring extends vertically from one end of the circumference of the first base,
  • the second wire extends from one end of the second base so as to be disposed horizontally with the first wire
  • the third wire is characterized in that it extends from one end of the third base to be disposed horizontally with the first wire.
  • the hot plate is 80-200 °C, characterized in that the elastomer is pressed for 3-60 seconds.
  • a method for manufacturing a microneedle biosensor including a passivation layer most suitable for the skin surface shape which can reduce pain for a user when worn and enable accurate sensing.
  • FIG. 1 is a view showing a microneedle sensor according to an embodiment of the present invention.
  • FIG. 2 is a flowchart showing a microneedle sensor manufacturing process.
  • FIG. 3 is a flow chart showing a thermal imprinting process in a manufacturing process of a PLA microneedle sensor.
  • FIG. 4 is a flow chart showing a UV imprinting process in the manufacturing process of an acrylic microneedle sensor.
  • FIG. 5 is a diagram for explaining step S12 of FIG. 2 .
  • 6 to 9 are diagrams for explaining step S13 of FIG. 2 .
  • FIG. 10 is a diagram showing a state in which step S13 of FIG. 2 has been completed.
  • a microneedle biosensor is a minimally invasive microneedle sensor.
  • the present invention relates to a biosensor in which a microneedle invades the skin and contacts a body fluid to monitor a biosignal.
  • the biosensor according to an embodiment of the present invention is intended to measure the blood glucose concentration in the interstitial fluid (ISF) of an invaded host, and is meant to be mounted on the skin surface to continuously measure the blood glucose concentration for a set period of time. Not limited.
  • ISF interstitial fluid
  • the microneedle sensor includes a working electrode (WE) 110, a counter electrode (CE) 120, a reference electrode (RE) 130, and an adhesive sheet 200.
  • WE working electrode
  • CE counter electrode
  • RE reference electrode
  • the working electrode 110 includes a circular first base 111, a plurality of microneedles 112 vertically protruding on the first base 111, and a second vertically extending from one end of the first base 111. It includes 1 wire (113).
  • the counter electrode 120 includes a second base 121 concentrically with the first base 111 and formed in a strip shape of a 3/4 circumference spaced apart from the circumference of the first base 111 by a set interval, the second base 121 It includes a plurality of microneedles 122 vertically protruding from the base 121 and a second wire 123 extending from one end of the second base 121 to be disposed horizontally with the first wire 113. .
  • a third base formed in a strip shape of a 1/4 circumference spaced apart from the other end of the second base 121 at a set interval and spaced concentrically with the first base 111 at a set interval from the circumference of the first base 111 131, a plurality of microneedles 132 vertically protruding from the third base 131, extending vertically from one end of the third base 131 to be disposed horizontally with the first wiring 113 and a third wire 133 to
  • the counter electrode 120 and the reference electrode 130 are spaced apart from the working electrode 110 at set intervals and are arranged to surround the working electrode 110 .
  • the working electrode 110, the counter electrode 120, and the reference electrode 130 are attached to the adhesive sheet 200.
  • an adhesive is applied to one surface of a fiber or polymer sheet.
  • the adhesive sheet 200 preferably has elasticity in itself.
  • the working electrode 110, the counter electrode 220, and the reference electrode 130 are attached to a surface on which an adhesive capable of attaching to the skin is applied.
  • the circular working electrode 110 and the counter electrode 120 and the reference electrode 130 are disposed so as to surround the working electrode 110 and form a strap shape spaced apart from the working electrode 110, and a sheet made of a fiber or polymer material. Since the working electrode 110, the counter electrode 220, and the reference electrode 130 are attached to the skin of the human body, which cannot be structurally flat while securing a sufficient effective area for sensing, each flexibly angles the skin. It can be tilted according to the skin contact surface and closely adhered to it.
  • the microneedle biosensor in the case of a sensor with a flat base, when attached to the skin, which is not flat, as time elapses after attachment, a phenomenon in which the edge is lifted due to resilience occurs, but the microneedle biosensor according to an embodiment of the present invention can solve such a problem.
  • the microneedle biosensor manufacturing method includes a microneedle manufacturing process (S10) consisting of a mold and imprint process (S11), a metallization process (S12), and a passivation process (S13), Ag/AgCl, Pt- It includes a post-treatment process (S20) consisting of black, Nafion coating and wiring and packaging processes.
  • S10 microneedle manufacturing process
  • S11 mold and imprint process
  • S12 a metallization process
  • S13 passivation process
  • Ag/AgCl Ag/AgCl
  • Pt- It includes a post-treatment process (S20) consisting of black, Nafion coating and wiring and packaging processes.
  • FIG. 3 is a flowchart illustrating a thermal imprint process (S11) of manufacturing a PLA microneedle layer in the manufacturing process of the microneedle sensor of FIG. 2 .
  • PLA Poly Lactic Acid
  • PLA needles have high elastic modulus and buckling stiffness
  • FIG. 4 is a flowchart illustrating a UV imprinting process for manufacturing an acrylic microneedle layer in the microneedle sensor manufacturing process of FIG. 2 .
  • a mold manufacturing step of forming a groove corresponding to the needle with a laser on a polytetrafluoroethylene (PTFE) block (S111), placing acrylic UV resin on the mold in a vacuum state (S112b), vacuum off After pressing with a press (S113b), a UV curing step (S114b), and a demolding step (S115b) are included.
  • the acrylic microneedle has the advantage of a short manufacturing process of about 5 to 10 minutes, and the acrylic microneedle has the advantage of good adhesion to Au.
  • FIG. 5 is a diagram explaining a metallization process among the manufacturing processes of the microneedle sensor of FIG. 2 .
  • a shadow mask corresponding to the pattern of the working electrode 110, the counter electrode 120, and the reference electrode 130 of FIG. 1 is applied to the polymer microneedle layer manufactured through the imprint process of FIG. 3 or 4. It is characterized by forming a metal electrode layer by forming and sputtering an Au or Au + Ti / Cr adhesive layer.
  • a passivation layer refers to an insulating layer formed to define an area exposed for sensing on a base layer on a metal electrode layer. It is possible to prevent noise that may occur due to the contact of the sensing material to the base area.
  • FIG. 6 is a view for explaining a process after forming a metal electrode layer, characterized in that a sensing layer is formed on an exposed electrode after forming a passivation layer on the metal electrode layer.
  • the working electrode 110, the counter electrode 120, and the reference electrode 130 are formed on a plastic adhesive tape having an adhesive layer formed on one side of the metal electrode layer and a PET (polyethylene terephthalate) layer, respectively.
  • FIG. 9 it consists of a process of pressing the PET layer with an elastomer and continuing the pressing for 3 to 60 seconds on a hot plate heated in that state.
  • the hot plate is preferably 80 to 200 ° C.
  • FIG. 10 shows a SEM picture of the microneedle biosensor in which the process of forming the passivation layer as described above has been completed. As shown, insulation is completed except for the sensing area to prevent noise generation during sensing.

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Abstract

The present invention provides a method for manufacturing a microneedle biosensor including a passivation layer, the method comprising the steps of: a) forming a mold by forming a groove corresponding to a microneedle shape for each of a working electrode, a counter electrode, and a reference electrode in a solid resin block; b) imprinting the working electrode, the counter electrode, and the reference electrodes, respectively, on the mold by using acryl or PLA; c) forming a shadow mask corresponding to the patterns of the working electrode, the counter electrode, and the reference electrode, and sputtering an Au or Au+Ti/Cr adhesive layer to form a metal electrode layer; and d) forming a passivation layer on the metal electrode layer.

Description

패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법Manufacturing method of microneedle biosensor including passivation layer
본 발명은 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법에 관한 것이다.The present invention relates to a method for manufacturing a microneedle biosensor including a passivation layer.
일반적인 인간의 혈당 농도는 식전 70 내지 130mg/dL 범위 내에 있으며, 식후 180mg/dL의 범위 내에 있다. 이러한 범위를 초과하는 경우를 고혈당증(hyperglycemia)으로 분류하며 정상 범위 미만인 경우 저혈당증(hypoglycemia)으로 분류한다. 고혈당증은 당뇨병과의 연관성이 상당히 높다. 당뇨병(糖尿病)은 높은 혈당 수치가 오랜 기간 지속되는 대사 질환군을 말한다. Normal human blood glucose levels are within the range of 70 to 130 mg/dL before meals and within the range of 180 mg/dL after meals. If it exceeds this range, it is classified as hyperglycemia, and if it is below the normal range, it is classified as hypoglycemia. Hyperglycemia is highly correlated with diabetes. Diabetes mellitus refers to a group of metabolic diseases in which high blood sugar levels persist for a long period of time.
이러한 당뇨병을 진단하고 합병증으로 진전되지 않도록 관리하기 위해서는 체계적인 혈당 측정과 치료가 병행되어야 한다. 통상 당뇨병의 질환 관리는 환자의 혈당 수치에 따라 인슐린 주입량을 정하고 소정 시간 간격으로 인슐린을 투여하여 관리된다. 그런데 환자 각각의 혈당 수치 및 인슐린 투여에 따른 혈당 변화는 개별환자마다 상이하므로 정확하고 효율적인 인슐린 투여량 및 투여 시기, 간격의 결정이 어려운 문제점이 있다.In order to diagnose diabetes and manage it so that it does not develop into complications, systematic blood glucose measurement and treatment must be performed simultaneously. In general, diabetes is managed by determining an injection amount of insulin according to a patient's blood sugar level and administering insulin at predetermined time intervals. However, since the blood glucose level of each patient and the change in blood sugar according to insulin administration are different for each individual patient, it is difficult to accurately and efficiently determine the insulin dose, administration time, and interval.
이러한 문제점을 해결하기 위하여 연속 혈당 모니터링(continuous glucose monitoring; CGM) 시스템을 이용할 수 있다. 연속혈당측정기는 메드트로닉사(Medtronic, Minneapolis,MN, USA)에서 처음 개발되어 1999년 6월 미국 FDA 승인을 받았으며, 혈당 변동폭이 크고, 저혈당이 빈번한 당뇨병 환자들의 치료에 도움을 주고 있다. 연속혈당측정기는 혈당 센서, 무선 전송기, 수신기의 세 부분으로 구성되어 있다. 센서는 피하지방에 삽입되어 세포간질액에서 당을 측정하게 된다. 최근 버전의 연속혈당측정기는 실시간으로 혈당 측정값을 보여주며 즉각적으로 적절한 조치를 취할 수 있게 해주고 있다.To solve this problem, a continuous glucose monitoring (CGM) system may be used. Continuous blood glucose monitoring system was first developed by Medtronic (Minneapolis, MN, USA) and was approved by the US FDA in June 1999. CGM consists of three parts: a blood glucose sensor, a wireless transmitter, and a receiver. The sensor is inserted into the subcutaneous fat to measure sugar in the interstitial fluid. The latest version of the continuous blood glucose monitor shows blood glucose readings in real time, allowing immediate action to be taken.
종래의 연속 혈당 모니터링 장치는 신체에 삽입되어 혈액으로부터 혈당을 측정하는 센서와, 센서가 신체에 삽입되도록 가이드하는 니들과, 센서 모듈을 신체에 적용하기 위해서는 별도의 어플리케이터 결합 구조를 포함한다. 센서는 시린지 니들의 중공에 배치되어 시린지 니들에 의해 피하 피어싱 되어 피하 지방에 삽입된다. 시린지 니들의 중공에 센서가 배치된다. 시린지 니들은 혈당 검출 시 사이즈가 21 Gauge까지 사용되고, 시린지 니들의 중공에 센싱 스트립이 배치되어야 하므로, 연속 혈당 측정 장치의 센서 니들로 사용되는 시린지 니들은 일반적으로 직경이 600nm 내지 800nm까지 사용된다. 센서 니들의 직경이 600nm 내지 800nm가 되면 사용자에게 통증을 유발하여 연속 사용 시 불쾌감을 주는 문제점이 있다.A conventional continuous blood glucose monitoring device includes a sensor inserted into the body to measure blood glucose, a needle for guiding the sensor to be inserted into the body, and a separate applicator coupling structure to apply the sensor module to the body. The sensor is disposed in the hollow of the syringe needle, pierced subcutaneously by the syringe needle, and inserted into the subcutaneous fat. A sensor is placed in the hollow of the syringe needle. Syringe needles are used up to 21 Gauge in size when blood glucose is detected, and since a sensing strip must be placed in the hollow of the syringe needle, a syringe needle used as a sensor needle in a continuous blood glucose measurement device is generally used with a diameter of 600 nm to 800 nm. When the diameter of the sensor needle is 600 nm to 800 nm, there is a problem of causing pain to the user and giving discomfort during continuous use.
본 발명은 상기 종래 기술의 문제점을 해결하기 위하여 안출된 것으로, 최소 침습으로 착용 시 사용자의 통증을 감소시킬 수 있는 마이크로 니들 바이오 센서를 제조하는 방법을 제공하는 것을 목적으로 한다.The present invention has been made to solve the problems of the prior art, and an object of the present invention is to provide a method for manufacturing a microneedle biosensor that can reduce pain for a user when worn with minimal invasion.
본 발명은,The present invention,
a) 고체 수지 블럭에 작업전극, 상대전극, 기준전극 각각의 마이크로 니들 형상에 상응하는 홈을 형성하여 몰드를 형성하는 단계;a) forming a mold by forming grooves corresponding to the shapes of microneedles of each of the working electrode, counter electrode, and reference electrode in the solid resin block;
b) 상기 몰드 상에 아크릴 또는 PLA를 이용하여 상기 작업전극, 상대전극, 기준전극 각각을 임프린트하는 단계;b) imprinting each of the working electrode, counter electrode and reference electrode on the mold using acrylic or PLA;
c) 상기 작업전극, 상대전극, 기준전극의 패턴에 해당되는 섀도우 마스크를 형성하고 Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 전극 레이어를 형성하는 단계; 및c) forming a shadow mask corresponding to the patterns of the working electrode, counter electrode, and reference electrode and sputtering an Au or Au+Ti/Cr adhesive layer to form a metal electrode layer; and
d) 상기 금속 전극 레이어 상에 패시베이션 레이어를 형성하는 단계;를 포함하고,d) forming a passivation layer on the metal electrode layer;
상기 패시베이션 레이어를 형성하는 단계는,Forming the passivation layer,
상기 금속 전극 레이어 상에 일면에 접착층이 형성된 플라스틱 접착 테이프와 PET(폴리에틸렌 테레프탈레이트) 레이어 각각에 상기 작업전극(110), 상대전극(120), 기준전극(130)의 마이크로 니들 위치에 상기 마이크로 니들의 가장 굵은 직경보다 작은 크기로 홀을 형성하는 공정,The microneedles are located at the microneedle positions of the working electrode 110, the counter electrode 120, and the reference electrode 130 respectively on plastic adhesive tape and PET (polyethylene terephthalate) layers having an adhesive layer formed on one side of the metal electrode layer. A process of forming a hole with a size smaller than the thickest diameter of
상기 홀이 형성된 상기 플라스틱 접착 테이프의 접착면이 베이스에 접촉하도록 홀에 상기 마이크로 니들을 삽입하고, 상기 PET 레이어의 홀에 상기 마이크로 니들을 삽입하는 공정,A step of inserting the microneedles into the holes so that the adhesive surface of the plastic adhesive tape formed with the holes comes into contact with the base, and inserting the microneedles into the holes of the PET layer;
상기 엘라스토머로 PET 레이어 상을 가압하고, 그 상태로 가열된 핫플레이트 위에서 가압을 지속하는 공정을 포함하는 것을 특징으로 하는 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법을 제공한다.It provides a microneedle biosensor manufacturing method including a passivation layer, comprising the step of pressurizing the PET layer with the elastomer and continuing the pressurization on a heated hot plate in that state.
상기 작업전극은, 원 형상 박막의 제1베이스, 상기 제1베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 상기 제1베이스의 원주의 일단에서 연장하는 제1배선을 포함하고,The working electrode includes a first base of a circular thin film, a plurality of microneedles protruding vertically on the first base, and a first wiring extending from one end of a circumference of the first base;
상기 상대전극은, 상기 제1베이스와 동심으로 상기 제1베이스의 원주에서 설정거리 이격된 제2원주의 일부를 이루는 형상의 스트립 박막의 제2베이스, 상기 제2베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 및 상기 제1배선과 수평하게 배치되도록 제2베이스의 일단에서 연장하는 제2배선을 포함하고,The counter electrode includes a second base of a thin film strip having a shape concentrically with the first base and forming a part of a second circumference spaced apart from the circumference of the first base by a set distance, and a plurality of vertically protruding on the second base. A microneedle of, and a second wire extending from one end of the second base so as to be disposed horizontally with the first wire,
상기 기준전극은, 상기 제2베이스의 타단에서 설정 간격 이격하고 상기 제2베이스의 스트립 형상과 함께 제2원주를 이루는 스트립 박막의 제3베이스, 상기 제3베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 상기 제3베이스의 일단에서 연장하는 제3배선을 포함하는 것을 특징으로 한다.The reference electrode is spaced apart from the other end of the second base by a set distance and includes a third base of a strip thin film forming a second circumference together with the strip shape of the second base, and a plurality of microcircuits vertically protruding on the third base. It is characterized by comprising a needle and a third wire extending from one end of the third base.
상기 제2 베이스는 상기 제2원주의 3/4을 차지하고 상기 제3 베이스는 상기 제2원주의 1/4을 차지하는 것을 특징으로 한다.The second base occupies 3/4 of the second circumference, and the third base occupies 1/4 of the second circumference.
상기 제1베이스, 상기 제2베이스, 상기 제3베이스의 저면은 접착시트에 부착되는 것을 특징으로 한다.Bottom surfaces of the first base, the second base, and the third base are attached to an adhesive sheet.
상기 제1배선은 상기 제1베이스의 원주의 일단에서 수직으로 연장되고, The first wiring extends vertically from one end of the circumference of the first base,
상기 제2배선은 상기 제1배선과 수평하게 배치되도록 상기 제2베이스의 일단에서 연장되고,The second wire extends from one end of the second base so as to be disposed horizontally with the first wire,
상기 제3배선은 상기 제1배선과 수평하게 배치되도록 상기 제3베이스의 일단에서 연장되는 것을 특징으로 한다.The third wire is characterized in that it extends from one end of the third base to be disposed horizontally with the first wire.
상기 핫플레이트는 80-200 ℃이고, 상기 엘라스토머는 3-60초 동안 가압하는 것을 특징으로 한다.The hot plate is 80-200 ℃, characterized in that the elastomer is pressed for 3-60 seconds.
상기와 같이 구성된 본 발명의 실시예에 따르면, 착용 시 사용자의 통증을 감소시킬 수 있으면서 정확한 센싱이 가능하며 피부 표면 형상에 가장 적합한 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법을 제공할 수 있다. According to an embodiment of the present invention configured as described above, it is possible to provide a method for manufacturing a microneedle biosensor including a passivation layer most suitable for the skin surface shape, which can reduce pain for a user when worn and enable accurate sensing.
도 1 은 본 발명의 실시예에 따른 마이크로 니들 센서를 나타낸 도면이다.1 is a view showing a microneedle sensor according to an embodiment of the present invention.
도 2 는 마이크로 니들 센서 제조 공정을 나타낸 흐름도이다.2 is a flowchart showing a microneedle sensor manufacturing process.
도 3 는 PLA 마이크로 니들 센서 제조 공정 중 열 임프린트 공정을 나타낸 흐름도이다.3 is a flow chart showing a thermal imprinting process in a manufacturing process of a PLA microneedle sensor.
도 4 은 아크릴 마이크로 니들 센서 제조 공정 중 UV 임프린트 공정을 나타낸 흐름도이다.4 is a flow chart showing a UV imprinting process in the manufacturing process of an acrylic microneedle sensor.
도 5 는 도 2의 S12 단계를 설명하기 위한 도면이다.FIG. 5 is a diagram for explaining step S12 of FIG. 2 .
도 6 내지 9 는 도 2의 S13 단계를 설명하기 위한 도면이다.6 to 9 are diagrams for explaining step S13 of FIG. 2 .
도 10 은 도 2의 S13 단계를 완료한 상태를 나타낸 도면이다.FIG. 10 is a diagram showing a state in which step S13 of FIG. 2 has been completed.
본 발명에 대해 첨부된 도면을 참조하여 상세히 설명하면 다음과 같다. 여기서, 동일한 구성에 대해서는 동일부호를 사용하며, 반복되는 설명, 본 발명의 요지를 불필요하게 흐릴 수 있는 공지 기능 및 구성에 대한 상세한 설명은 생략한다. 본 발명의 실시형태는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해서 제공되는 것이다. 따라서, 도면에서의 요소들의 형상 및 크기 등은 보다 명확한 설명을 위해 과장될 수 있다.The present invention will be described in detail with reference to the accompanying drawings. Here, the same reference numerals are used for the same components, and repeated descriptions and detailed descriptions of well-known functions and configurations that may unnecessarily obscure the gist of the present invention are omitted. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art. Accordingly, the shapes and sizes of elements in the drawings may be exaggerated for clarity.
본 발명의 실시예에 따른 마이크로 니들 바이오센서는 최소 침습형 마이크로 니들 센서이다. 본 발명은, 마이크로니들이 피부에 침습하여 체액과 접촉하여 생체신호를 모니터링하는 바이오센서에 관한 것이다. 본 발명의 실시예에 따른 바이오센서는 침습된 호스트의 간질액(interstitial fluid, ISF)에서 혈당 농도를 측정하기 위한 것으로, 설정기간 연속하여 혈당 농도를 측정하기 위해 피부 표면에 장착되는 것을 의미하지만 이에 제한되지 않는다. A microneedle biosensor according to an embodiment of the present invention is a minimally invasive microneedle sensor. The present invention relates to a biosensor in which a microneedle invades the skin and contacts a body fluid to monitor a biosignal. The biosensor according to an embodiment of the present invention is intended to measure the blood glucose concentration in the interstitial fluid (ISF) of an invaded host, and is meant to be mounted on the skin surface to continuously measure the blood glucose concentration for a set period of time. Not limited.
도 1 은 본 발명의 실시예에 따른 마이크로 니들 센서를 나타낸 도면이다. 도시되는 바와 같이, 마이크로 니들 센서는 작업전극(WE;Working Electrode)(110), 상대전극(CE; Counter Electrode)(120), 기준전극(RE; Reference Electrode)(130), 접착시트(200)를 포함한다. 작업전극(110)은 원형 제1베이스(111), 상기 제1베이스(111) 상에 수직으로 돌출되는 복수의 마이크로니들(112), 상기 제1베이스(111)의 일단에서 수직으로 연장하는 제1배선(113)을 포함한다. 상대전극(120)은 상기 제1베이스(111)와 동심으로 상기 제1베이스(111)의 원주에서 설정간격 이격된 3/4 원주의 스트립 형상으로 형성되는 제2베이스(121), 상기 제2베이스(121) 상에 수직으로 돌출되는 복수의 마이크로니들(122), 상기 제1배선(113)과 수평하게 배치되도록 제2베이스(121)의 일단에서 연장하는 제2배선(123)을 포함한다. 상기 제2베이스(121)의 타단에서 설정간격 이격하고 제1베이스(111)와 동심으로 상기 제1베이스(111)의 원주와 설정 간격 이격된 1/4 원주의 스트립 형상으로 형성되는 제3베이스(131), 상기 제3베이스(131) 상에 수직으로 돌출되는 복수의 마이크로 니들(132), 상기 제1배선(113)과 수평하게 배치되도록 상기 제3베이스(131)의 일단에서 수직으로 연장하는 제3배선(133)을 포함한다.1 is a view showing a microneedle sensor according to an embodiment of the present invention. As shown, the microneedle sensor includes a working electrode (WE) 110, a counter electrode (CE) 120, a reference electrode (RE) 130, and an adhesive sheet 200. includes The working electrode 110 includes a circular first base 111, a plurality of microneedles 112 vertically protruding on the first base 111, and a second vertically extending from one end of the first base 111. It includes 1 wire (113). The counter electrode 120 includes a second base 121 concentrically with the first base 111 and formed in a strip shape of a 3/4 circumference spaced apart from the circumference of the first base 111 by a set interval, the second base 121 It includes a plurality of microneedles 122 vertically protruding from the base 121 and a second wire 123 extending from one end of the second base 121 to be disposed horizontally with the first wire 113. . A third base formed in a strip shape of a 1/4 circumference spaced apart from the other end of the second base 121 at a set interval and spaced concentrically with the first base 111 at a set interval from the circumference of the first base 111 131, a plurality of microneedles 132 vertically protruding from the third base 131, extending vertically from one end of the third base 131 to be disposed horizontally with the first wiring 113 and a third wire 133 to
상대전극(120)과 기준전극(130)은 설정간격 작업전극(110)에서 이격되어 작업전극(110)을 둘러싸도록 배치된다. 상기 작업전극(110), 상대전극(120), 기준전극(130)은 접착시트(200) 상에 부착된다. 접착시트(200)는 섬유 또는 폴리머 재질의 시트의 일면에 접착제가 도포되는 것이 바람직하다. 접착시트(200)는 시트 자체에 탄성을 가지는 것이 바람직하다. 접착시트(200)는 피부에 부착 가능한 접착제가 도포된 면에 작업전극(110), 상대전극(220), 기준전극(130)이 부착된다. 원형의 작업전극(110)과 작업전극(110)에서 이격되어 스트랩 형상으로 형성되어 작업전극(110)을 둘러싸도록 상대전극(120)과 기준전극(130)이 배치되고, 섬유 또는 폴리머 재질의 시트에 부착되므로 작업전극(110), 상대전극(220), 기준전극(130)이 센싱을 위하나 유효 면적을 충분히 확보하면서도 구조적으로 평면이 될 수 없는 인체의 피부에 부착 시 각각 유연하게 피부의 각도에 따라 기울어져 피부 접촉면에 밀접하게 부착될 수 있다. 즉, 베이스가 평면인 센서의 경우 평면이 아닌 피부에 부착 시 부착후 시간이 경과할 수록 회복력 때문에 가장자리가 들리는 현상이 발생하나, 본 발명의 실시예에 따른 마이크로니들 바이오 센서는 그러한 문제점을 해결할 수 있게 된다.The counter electrode 120 and the reference electrode 130 are spaced apart from the working electrode 110 at set intervals and are arranged to surround the working electrode 110 . The working electrode 110, the counter electrode 120, and the reference electrode 130 are attached to the adhesive sheet 200. In the adhesive sheet 200, it is preferable that an adhesive is applied to one surface of a fiber or polymer sheet. The adhesive sheet 200 preferably has elasticity in itself. In the adhesive sheet 200, the working electrode 110, the counter electrode 220, and the reference electrode 130 are attached to a surface on which an adhesive capable of attaching to the skin is applied. The circular working electrode 110 and the counter electrode 120 and the reference electrode 130 are disposed so as to surround the working electrode 110 and form a strap shape spaced apart from the working electrode 110, and a sheet made of a fiber or polymer material. Since the working electrode 110, the counter electrode 220, and the reference electrode 130 are attached to the skin of the human body, which cannot be structurally flat while securing a sufficient effective area for sensing, each flexibly angles the skin. It can be tilted according to the skin contact surface and closely adhered to it. That is, in the case of a sensor with a flat base, when attached to the skin, which is not flat, as time elapses after attachment, a phenomenon in which the edge is lifted due to resilience occurs, but the microneedle biosensor according to an embodiment of the present invention can solve such a problem. there will be
도 2는 마이크로 니들 센서 제조 공정을 나타낸 흐름도이다. 도시되는 바와 같이, 마이크로 니들 바이오 센서 제조 방법은 몰드 및 임프린트 공정(S11), 메탈리제이션 공정(S12), 패시베이션 공정(S13)으로 구성된 마이크로 니들 제조 공정(S10)과, Ag/AgCl, Pt-black, 나피온 코팅 및 와이어링과 패키지 공정으로 구성된 후처리 공정(S20)을 포함한다. 2 is a flow chart showing a microneedle sensor manufacturing process. As shown, the microneedle biosensor manufacturing method includes a microneedle manufacturing process (S10) consisting of a mold and imprint process (S11), a metallization process (S12), and a passivation process (S13), Ag/AgCl, Pt- It includes a post-treatment process (S20) consisting of black, Nafion coating and wiring and packaging processes.
도 3은 도 2의 마이크로 니들 센서 제조 공정 중 PLA 마이크로 니들 레이어를 제조하는 열 임프린트 공정(S11)을 나타낸 흐름도이다. 도시되는 바와 같이, 레이저로 니들에 상응하는 형상의 홈을 폴리테트라플루오로에틸렌(Polytetrafluoroethylene, PTFE) 블럭에 형성하는 몰드 제조단계(S111), 몰드에 이형제를 코팅하는 이형제 코팅 단계(S112a), 이형제 건조 단계(S113a), 홈이 형성된 몰드 상에 PLA 레이어를 형성하고 세라믹으로 가압하는 단계(S114a), 200℃ 진공 오븐에서 베이크하는 단계(S115a), 진공 오프 후 프레스로 가압하는 단계(S116a)로 구성된다. 친환경성·무독성·생분해성·생물호환성 재질인 PLA(Poly Lactic Acid) 마이크로니들이 형성된다. PLA 니들은 높은 탄성계수와 좌굴 강성을 가지고 있다. FIG. 3 is a flowchart illustrating a thermal imprint process (S11) of manufacturing a PLA microneedle layer in the manufacturing process of the microneedle sensor of FIG. 2 . As shown, a mold manufacturing step (S111) of forming a groove having a shape corresponding to a needle in a polytetrafluoroethylene (PTFE) block with a laser (S111), a release agent coating step (S112a) of coating a release agent on the mold, and a release agent A drying step (S113a), a step of forming a PLA layer on a grooved mold and pressing it with ceramic (S114a), a step of baking in a vacuum oven at 200 ° C (S115a), and a step of pressing with a press after turning off the vacuum (S116a). It consists of PLA (Poly Lactic Acid) microneedle, which is an eco-friendly, non-toxic, biodegradable and biocompatible material, is formed. PLA needles have high elastic modulus and buckling stiffness.
도 4는 도 2의 마이크로 니들 센서 제조 공정 중 아크릴 마이크로 니들 레이어를 제조하는 UV 임프린트 공정을 나타낸 흐름도이다. 레이저로 니들에 상응하는 형상의 홈을 폴리테트라플루오로에틸렌(Polytetrafluoroethylene, PTFE) 블럭에 형성하는 몰드 제조단계(S111), 진공 상태에서 아크릴 UV 레진을 몰드 상에 배치하는 단계(S112b), 진공 오프 후 프레스로 가압하는 단계(S113b), UV 경화 단계(S114b), 및 디몰딩 단계(S115b)를 포함한다. 아크릴 마이크로 니들은 제조 공정이 5 ~10분정도로 짧은 장점이 있고, 아크릴 마이크로 니들은 Au에 대한 접착성이 좋은 장점이 있다.FIG. 4 is a flowchart illustrating a UV imprinting process for manufacturing an acrylic microneedle layer in the microneedle sensor manufacturing process of FIG. 2 . A mold manufacturing step of forming a groove corresponding to the needle with a laser on a polytetrafluoroethylene (PTFE) block (S111), placing acrylic UV resin on the mold in a vacuum state (S112b), vacuum off After pressing with a press (S113b), a UV curing step (S114b), and a demolding step (S115b) are included. The acrylic microneedle has the advantage of a short manufacturing process of about 5 to 10 minutes, and the acrylic microneedle has the advantage of good adhesion to Au.
도 5 는 도 2의 마이크로 니들 센서 제조 공정 중 메탈리제이션 공정을 설명하는 도면이다. 메탈리제이션 공정은 도 3 또는 4의 임프린트 공정을 통해 제조된 폴리머 마이크로 니들 레이어 상에 도 1의 작업전극(110), 상대전극(120), 기준전극(130)의 패턴에 해당되는 섀도우 마스크를 형성하고 Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 전극 레이어를 형성하는 것을 특징으로 한다. FIG. 5 is a diagram explaining a metallization process among the manufacturing processes of the microneedle sensor of FIG. 2 . In the metallization process, a shadow mask corresponding to the pattern of the working electrode 110, the counter electrode 120, and the reference electrode 130 of FIG. 1 is applied to the polymer microneedle layer manufactured through the imprint process of FIG. 3 or 4. It is characterized by forming a metal electrode layer by forming and sputtering an Au or Au + Ti / Cr adhesive layer.
도 6 내지 9는 도 2의 마이크로 니들 센서 제조 공정 중 패시베이션 레이어 제조 공정을 설명하는 도면이다. 패시베이션 레이어(Passivation layer)는 금속 전극 레이어 상의 베이스 레이어 상에 감지를 위하여 노출되는 영역을 정의 기 위하여 형성되는 절연 레이어를 의미한다. 베이스 영역에 감지 물질 접촉으로 인하여 발생할 수 있는 노이즈를 방지할 수 있게 한다. 6 to 9 are diagrams illustrating a process of manufacturing a passivation layer among manufacturing processes of the microneedle sensor of FIG. 2 . A passivation layer refers to an insulating layer formed to define an area exposed for sensing on a base layer on a metal electrode layer. It is possible to prevent noise that may occur due to the contact of the sensing material to the base area.
도 6 은 금속 전극 레이어 형성 이후 공정을 설명하는 도면으로, 금속 전극 레이어 상에 패시베이션 레이어를 형성한 후 노출된 전극 상에 감지 레이어를 형성하는 것을 특징으로 한다.6 is a view for explaining a process after forming a metal electrode layer, characterized in that a sensing layer is formed on an exposed electrode after forming a passivation layer on the metal electrode layer.
패시베이션 레이어 형성공정은,The passivation layer forming process,
도 7에 도시되는 바와 같이, 금속 전극 레이어 상에 일면에 접착층이 형성된 플라스틱 접착 테이프와 PET(폴리에틸렌 테레프탈레이트) 레이어 각각에 작업전극(110), 상대전극(120), 기준전극(130)의 마이크로 니들 위치에 마이크로 니들의 가장 굵은 직경보다 작은 크기로 홀을 형성하는 공정,As shown in FIG. 7 , the working electrode 110, the counter electrode 120, and the reference electrode 130 are formed on a plastic adhesive tape having an adhesive layer formed on one side of the metal electrode layer and a PET (polyethylene terephthalate) layer, respectively. A process of forming a hole at the needle position with a size smaller than the thickest diameter of the microneedle;
도 8에 도시되는 바와 같이, 홀이 형성된 플라스틱 접착 테이프의 접착면이 베이스에 접촉하도록 홀에 마이크로 니들을 삽입하고, PET 레이어의 홀에 마이크로 니들을 삽입하는 공정,As shown in FIG. 8, a process of inserting a microneedle into a hole such that the adhesive side of the plastic adhesive tape formed with the hole contacts the base, and inserting the microneedle into the hole of the PET layer;
도 9에 도시되는 바와 같이, 엘라스토머로 PET 레이어 상을 가압하고, 그 상태로 가열된 핫플레이트 위에서 3-60초 동안 가압을 지속하는 공정으로 구성된다.As shown in FIG. 9, it consists of a process of pressing the PET layer with an elastomer and continuing the pressing for 3 to 60 seconds on a hot plate heated in that state.
레이저 패터닝 공정을 사용하여 홀을 형성하는 것이 바람직하다. It is preferred to form the holes using a laser patterning process.
핫플레이트는 80 내지 200℃ 인 것이 바람직하다.The hot plate is preferably 80 to 200 ° C.
그 다음 후처리 공정(S20)을 실시한다.Then, a post-processing step (S20) is performed.
도 10은 상기와 같은 패시베이션 레이어를 형성하는 공정이 완료된 마이크로 니들 바이오 센서의 SEM 사진을 나타낸다. 도시되는 바와 같이, 감지 영역을 제외하고 insulation이 완료되어 감지 시 노이즈 발생을 방지할 수 있게 된다.10 shows a SEM picture of the microneedle biosensor in which the process of forming the passivation layer as described above has been completed. As shown, insulation is completed except for the sensing area to prevent noise generation during sensing.

Claims (4)

  1. a) 고체 수지 블럭에 작업전극, 상대전극, 기준전극 각각의 마이크로 니들 형상에 상응하는 홈을 형성하여 몰드를 형성하는 단계;a) forming a mold by forming grooves corresponding to the shapes of microneedles of each of the working electrode, counter electrode, and reference electrode in the solid resin block;
    b) 상기 몰드 상에 아크릴 또는 PLA를 이용하여 상기 작업전극, 상대전극, 기준전극 각각을 임프린트하는 단계;b) imprinting each of the working electrode, counter electrode and reference electrode on the mold using acrylic or PLA;
    c) 상기 작업전극, 상대전극, 기준전극의 패턴에 해당되는 섀도우 마스크를 형성하고 Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 전극 레이어를 형성하는 단계; 및c) forming a shadow mask corresponding to the patterns of the working electrode, counter electrode, and reference electrode and sputtering an Au or Au+Ti/Cr adhesive layer to form a metal electrode layer; and
    d) 상기 금속 전극 레이어 상에 패시베이션 레이어를 형성하는 단계;를 포함하고,d) forming a passivation layer on the metal electrode layer;
    상기 패시베이션 레이어를 형성하는 단계는,Forming the passivation layer,
    상기 금속 전극 레이어 상에 일면에 접착층이 형성된 플라스틱 접착 테이프와 PET(폴리에틸렌 테레프탈레이트) 레이어 각각에 상기 작업전극, 상대전극, 기준전극의 마이크로 니들 위치에 상기 마이크로 니들의 가장 굵은 직경보다 작은 크기로 홀을 형성하는 공정,A plastic adhesive tape having an adhesive layer formed on one side of the metal electrode layer and a PET (polyethylene terephthalate) layer have holes smaller than the thickest diameter of the microneedles at the microneedle locations of the working electrode, counter electrode, and reference electrode, respectively. The process of forming
    상기 홀이 형성된 상기 플라스틱 접착 테이프의 접착면이 베이스에 접촉하도록 홀에 상기 마이크로 니들을 삽입하고, 상기 PET 레이어의 홀에 상기 마이크로 니들을 삽입하는 공정,A step of inserting the microneedles into the holes so that the adhesive surface of the plastic adhesive tape formed with the holes comes into contact with the base, and inserting the microneedles into the holes of the PET layer;
    상기 엘라스토머로 PET 레이어 상을 가압하고, 그 상태로 가열된 핫플레이트 위에서 가압을 지속하는 공정을 포함하는 것을 특징으로 하는 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법.A method for manufacturing a microneedle biosensor including a passivation layer, comprising a step of pressurizing the PET layer with the elastomer and continuing the pressurization on a heated hot plate in that state.
  2. 제 1 항에 있어서,According to claim 1,
    상기 작업전극은, 원 형상 박막의 제1베이스, 상기 제1베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 상기 제1베이스의 원주의 일단에서 연장하는 제1배선을 포함하고,The working electrode includes a first base of a circular thin film, a plurality of microneedles protruding vertically on the first base, and a first wiring extending from one end of a circumference of the first base;
    상기 상대전극은, 상기 제1베이스와 동심으로 상기 제1베이스의 원주에서 설정거리 이격된 제2원주의 일부를 이루는 형상의 스트립 박막의 제2베이스, 상기 제2베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 및 상기 제1배선과 수평하게 배치되도록 제2베이스의 일단에서 연장하는 제2배선을 포함하고,The counter electrode includes a second base of a thin film strip having a shape concentrically with the first base and forming a part of a second circumference spaced apart from the circumference of the first base by a set distance, and a plurality of vertically protruding on the second base. A microneedle of, and a second wire extending from one end of the second base so as to be disposed horizontally with the first wire,
    상기 기준전극은, 상기 제2베이스의 타단에서 설정 간격 이격하고 상기 제2베이스의 스트립 형상과 함께 제2원주를 이루는 스트립 박막의 제3베이스, 상기 제3베이스 상에 수직으로 돌출되는 복수의 마이크로니들, 상기 제3베이스의 일단에서 연장하는 제3배선을 포함하는 것을 특징으로 하는 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법.The reference electrode is spaced apart from the other end of the second base by a set distance and includes a third base of a strip thin film forming a second circumference together with the strip shape of the second base, and a plurality of microcircuits vertically protruding on the third base. A method for manufacturing a microneedle biosensor comprising a passivation layer comprising a needle and a third wire extending from one end of the third base.
  3. 제 2 항에 있어서,According to claim 2,
    상기 제2 베이스는 상기 제2원주의 3/4을 차지하고 상기 제3 베이스는 상기 제2원주의 1/4을 차지하는 것을 특징으로 하는 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법.The second base occupies 3/4 of the second circumference, and the third base occupies 1/4 of the second circumference.
  4. 제 1 항에 있어서,According to claim 1,
    상기 핫플레이트는 80-200 ℃이고, 상기 엘라스토머는 3 내지 60초 동안 가압하는 것을 특징으로 하는 패시베이션 레이어를 포함하는 마이크로 니들 바이오 센서 제조 방법.The method of manufacturing a microneedle biosensor comprising a passivation layer, characterized in that the hot plate is 80-200 ° C, and the elastomer is pressed for 3 to 60 seconds.
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