[go: up one dir, main page]

WO2023048346A1 - Method for manufacturing microneedle biosensor using inverse mold - Google Patents

Method for manufacturing microneedle biosensor using inverse mold Download PDF

Info

Publication number
WO2023048346A1
WO2023048346A1 PCT/KR2022/000620 KR2022000620W WO2023048346A1 WO 2023048346 A1 WO2023048346 A1 WO 2023048346A1 KR 2022000620 W KR2022000620 W KR 2022000620W WO 2023048346 A1 WO2023048346 A1 WO 2023048346A1
Authority
WO
WIPO (PCT)
Prior art keywords
base
microneedle
forming
mold
circumference
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2022/000620
Other languages
French (fr)
Korean (ko)
Inventor
안준영
장은희
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Albiti Inc
Original Assignee
Albiti Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Albiti Inc filed Critical Albiti Inc
Publication of WO2023048346A1 publication Critical patent/WO2023048346A1/en
Priority to US18/603,502 priority Critical patent/US20240215915A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or 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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or 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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/40—Plastics, e.g. foam or rubber
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B41—PRINTING; LINING MACHINES; TYPEWRITERS; STAMPS
    • B41J—TYPEWRITERS; SELECTIVE PRINTING MECHANISMS, i.e. MECHANISMS PRINTING OTHERWISE THAN FROM A FORME; CORRECTION OF TYPOGRAPHICAL ERRORS
    • B41J3/00—Typewriters or selective printing or marking mechanisms characterised by the purpose for which they are constructed
    • B41J3/407—Typewriters or selective printing or marking mechanisms characterised by the purpose for which they are constructed for marking on special material
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/02—Pretreatment of the material to be coated
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
    • C23C14/14—Metallic material, boron or silicon
    • C23C14/20—Metallic material, boron or silicon on organic substrates
    • 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 using a reverse mold.
  • 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 of manufacturing a microneedle biosensor that can reduce pain for a user when worn with minimal invasion.
  • step S12 After performing the step S12, forming a shadow mask corresponding to the pattern of the working electrode, counter electrode, and reference electrode, and forming a metal layer by sputtering an Au or Au + Ti / Cr adhesive layer (S13); and
  • the step S11 is
  • step (d) injecting and curing PDMS (Polydimethylsiloxane), which is a mold material, after the support layer is dried in step (c), and
  • step (e) separating the cured PDMS mold in step (d) to complete a reverse mold.
  • 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
  • a microneedle biosensor that can reduce pain for a user when worn, enable accurate sensing, and is most suitable for the shape of the skin surface.
  • FIG. 1 is a diagram showing a microneedle biosensor according to an embodiment of the present invention.
  • FIG. 2 is a flow chart showing a microneedle biosensor manufacturing process.
  • FIG. 3 is a diagram explaining step S11 of FIG. 2 .
  • 4 and 5 are diagrams for explaining step S12 of FIG. 2 .
  • 6 and 7 are diagrams for explaining step S13 of FIG. 2 .
  • FIG 8 is a view illustrating a microneedle polymer layer manufactured using a reverse mold according to an embodiment of the present invention.
  • a microneedle biosensor according to an embodiment of the present invention is a minimally invasive microneedle biosensor.
  • 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 biosensor includes a working electrode (WE) 110, a counter electrode (CE) 120, a reference electrode (RE) 130, and an adhesive sheet 200.
  • 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 attached closely.
  • 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 process (S11), an imprint process (S12), a metallization process (S13), and a passivation process (S14), and Ag/ It includes a post-processing process (S20) consisting of AgCl, Pt-black, Nafion coating and wiring and packaging processes.
  • S10 microneedle manufacturing process
  • S12 an imprint process
  • S13 a metallization process
  • S14 passivation process
  • Ag/ It includes a post-processing process (S20) consisting of AgCl, Pt-black, Nafion coating and wiring and packaging processes.
  • FIG. 3 is a view showing a mold process (S11) of the manufacturing process of the microneedle biosensor of FIG. 2 .
  • the mold process (S11) includes (a) forming the first microneedle polymer layer 10, (b) disposing the first microneedle polymer layer 10 in a mold-shaped container, and (c) placing the first microneedle polymer layer 10 in the container. Forming the support layer 20 on the primary microneedle polymer layer 10, (d) after the support layer 20 is dried, injecting and curing the mold material PDMS (Polydimethylsiloxane), (e) the above A step of completing the reverse mold 300 by separating the PDMS mold cured in the step.
  • Step (f) is a step of forming the final microneedle polymer layer 10', after manufacturing the reverse mold 300 through the mold process of S11, the final microneedle polymer layer through the imprint process of FIG. 4 or 5 (10').
  • FIG. 4 is a flow chart showing a thermal imprint process (S12) for manufacturing PLA microneedles.
  • the release agent coating step (S112a) of coating the release agent on the reverse mold 300 manufactured in the mold manufacturing step (S111) of FIG. It consists of forming a PLA layer on and pressing with ceramic (S114a), baking in a 200 ° C. vacuum oven (S115a), and pressing with a press after vacuuming off (S116a).
  • PLA Poly Lactic Acid
  • PLA needles have high elastic modulus and buckling stiffness.
  • FIG. 5 shows an imprint process using acrylic UV resin, an imprint process for manufacturing acrylic microneedles in the manufacturing process of the microneedle biosensor of FIG. 2 .
  • 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. 6 and 7 are diagrams illustrating a metallization process in the manufacturing process of the microneedle biosensor of FIG. 2 .
  • an adhesive is applied on the final microneedle polymer layer 10' manufactured through the imprint process of FIG. 3 or 4, and the working electrode 110 of FIG. 1, the counter electrode 120, A shadow mask corresponding to the pattern of the reference electrode 130 is formed (FIG. 7(a)), a metal layer is formed by sputtering an Au or Au+Ti/Cr adhesive layer, and (b) the working electrode 110 , the counter electrode 120 and the reference electrode 130 are formed.
  • FIG. 8 shows the effect of forming the microneedle polymer layer using the reverse mold 300 as described above.
  • 8(a) shows a microneedle polymer layer manufactured using a mold formed by conventional laser etching
  • FIG. 8(b) shows a microneedle polymer layer according to an embodiment of the present invention.
  • the microneedle polymer layer of Jongle of FIG. 8 (a) is a metal electrode layer deposited on the microneedle biosensor, or the needle protrudes vertically from the base and stress is concentrated on the needle root, resulting in damage to the needle.
  • the microneedle polymer layer 10' is formed using the inverse mold 300 manufactured according to the embodiment of the present invention, the circumference of the needle root is reinforced and the microneedle biosensor can increase durability.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Veterinary Medicine (AREA)
  • Medical Informatics (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Optics & Photonics (AREA)
  • Mechanical Engineering (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Manufacturing & Machinery (AREA)
  • Electrochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Emergency Medicine (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

The present invention comprises the steps of: (S11) forming a mold for forming a microneedle polymer layer; (S12) imprinting each of a working electrode, a counter electrode, and a reference electrode on the mold by using acrylic or PLA; and after performing the S12 step, (S13) forming a shadow mask corresponding to a pattern of the working electrode, the counter electrode, and the reference electrode, and forming a metal layer by sputtering an Au or Au+Ti/Cr adhesive layer.

Description

역몰드를 이용한 마이크로 니들 바이오 센서 제조 방법Microneedle biosensor manufacturing method using reverse mold

본 발명은 역몰드를 이용한 마이크로 니들 바이오 센서 제조 방법에 관한 것이다.The present invention relates to a method for manufacturing a microneedle biosensor using a reverse mold.

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 센서의 제조 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 of manufacturing a microneedle biosensor that can reduce pain for a user when worn with minimal invasion.

상기와 같은 목적을 달성하기 위하여 본 발명은,In order to achieve the above object, the present invention,

마이크로 니들 폴리머 레이어를 형성하기 위한 몰드를 형성하는 단계(S11);Forming a mold for forming a microneedle polymer layer (S11);

상기 몰드 상에 아크릴 또는 PLA를 이용하여 작업전극, 상대전극, 기준전극 각각을 임프린트하는 단계(S12); 및imprinting a working electrode, a counter electrode, and a reference electrode on the mold using acrylic or PLA (S12); and

상기 S12 단계 수행 후, 상기 작업전극, 상대전극, 기준전극의 패턴에 해당되는 섀도우 마스크를 형성하고 Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 레이어를 형성하는 단계(S13);를 포함하고After performing the step S12, forming a shadow mask corresponding to the pattern of the working electrode, counter electrode, and reference electrode, and forming a metal layer by sputtering an Au or Au + Ti / Cr adhesive layer (S13); and

상기 S11 단계는 The step S11 is

(a) 1차 마이크로 니들 폴리머 레이어 형성 단계,(a) forming a first microneedle polymer layer;

(b) 상기 1차 마이크로 니들 폴리머 레이어를 몰드 형상의 용기 내에 배치하는 단계,(b) disposing the first microneedle polymer layer in a mold-shaped container;

(c) 용기에 배치된 1차 마이크로 니들 폴리머 레이어 상에 서포트 레이어를 형성하는 단계, (c) forming a support layer on the first microneedle polymer layer disposed in the container;

(d) 상기 (c) 단계에서 서포트 레이어가 건조 된 후 몰드 재료인 PDMS(Polydimethylsiloxane)를 투입하고 경화시키는 단계, 및 (d) injecting and curing PDMS (Polydimethylsiloxane), which is a mold material, after the support layer is dried in step (c), and

(e) 상기 (d) 단계에서 경화된 PDMS 몰드를 분리하여 역몰드를 완성하는 단계를 포함하는 것을 특징으로 하는 마이크로 니들 바이오 센서 제조 방법을 제공한다.(e) separating the cured PDMS mold in step (d) to complete a reverse mold.

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 S13 단계 수행 후 상기 금속 레이어 상에 패시베이션 레이어를 형성하는 단계를 추가로 포함하는 것을 특징으로 한다.It is characterized in that it further comprises the step of forming a passivation layer on the metal layer after performing the step S13.

상기와 같이 구성된 본 발명의 실시예에 따르면, 착용 시 사용자의 통증을 감소시킬 수 있으면서 정확한 센싱이 가능하며 피부 표면 형상에 가장 적합한 마이크로 니들 바이오 센서를 제조하는 방법을 제공할 수 있다. According to an embodiment of the present invention configured as described above, it is possible to provide a method of manufacturing a microneedle biosensor that can reduce pain for a user when worn, enable accurate sensing, and is most suitable for the shape of the skin surface.

상기와 같이 구성된 본 발명의 실시예에 따르면, 마이크로 니들 뿌리 부분의 응력 집중을 회피하여 내구도가 높은 마이크로 니들 바이오 센서를 제조하는 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 having high durability by avoiding stress concentration at the root of the microneedle.

상기와 같이 구성된 본 발명의 실시예에 따르면, 서포트 레이어 제조 공정을 생략하여 생산 수율을 증가시킬 수 있는 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 microneedle biosensor manufacturing method capable of increasing production yield by omitting the support layer manufacturing process.

도 1 은 본 발명의 실시예에 따른 마이크로 니들 바이오 센서를 나타낸 도면이다.1 is a diagram showing a microneedle biosensor according to an embodiment of the present invention.

도 2 는 마이크로 니들 바이오 센서 제조 공정을 나타낸 흐름도이다.2 is a flow chart showing a microneedle biosensor manufacturing process.

도 3 은 도 2의 S11 단계를 설명하는 도면이다.FIG. 3 is a diagram explaining step S11 of FIG. 2 .

도 4 및 5 는 도 2의 S12 단계를 설명하는 도면이다.4 and 5 are diagrams for explaining step S12 of FIG. 2 .

도 6 및 7 은 도 2의 S13 단계를 설명하는 도면이다.6 and 7 are diagrams for explaining step S13 of FIG. 2 .

도 8 은 본 발명의 실시예에 따른 역몰드를 이용하여 제조한 마이크로 니들 폴리머 레이어를 설명하는 도면이다.8 is a view illustrating a microneedle polymer layer manufactured using a reverse mold according to an embodiment of the present invention.

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 바이오 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 biosensor. 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 바이오 센서를 나타낸 도면이다. 도시되는 바와 같이, 마이크로 니들 바이오 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 diagram showing a microneedle biosensor according to an embodiment of the present invention. As shown, the microneedle biosensor includes a working electrode (WE) 110, a counter electrode (CE) 120, a reference electrode (RE) 130, and an adhesive sheet 200. ). 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 attached closely. 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 바이오 센서 제조 공정을 나타낸 흐름도이다. 도시되는 바와 같이, 마이크로 니들 바이오 센서 제조 방법은 몰드 공정(S11)및 임프린트 공정(S12), 메탈리제이션 공정(S13), 패시베이션 공정(S14)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 biosensor manufacturing process. As shown, the microneedle biosensor manufacturing method includes a microneedle manufacturing process (S10) consisting of a mold process (S11), an imprint process (S12), a metallization process (S13), and a passivation process (S14), and Ag/ It includes a post-processing process (S20) consisting of AgCl, Pt-black, Nafion coating and wiring and packaging processes.

도 3은 도 2의 마이크로 니들 바이오 센서 제조 공정 중 몰드 공정(S11)을 나타낸 도면이다. 몰드 공정(S11)은 (a) 1차 마이크로 니들 폴리머 레이어(10) 형성 단계, (b)1차 마이크로 니들 폴리머 레이어(10)를 몰드 형상의 용기 내에 배치하는 단계, (c)용기에 배치된 1차 마이크로 니들 폴리머 레이어(10) 상에 서포트 레이어(20) 형성하는 단계, (d)서포트 레이어(20)가 건조 된 후 몰드 재료인 PDMS(Polydimethylsiloxane)를 투입하고 경화시키는 단계, (e)상기 단계에서 경화된 PDMS 몰드를 분리하여 역몰드(300)를 완성하는 단계를 포함한다. (f) 단계는 최종 마이크로 니들 폴리머 레이어(10')를 형성하는 단계로, S11의 몰드 공정을 통해 역몰드(300)를 제조한 후 도 4 또는 도 5의 임프린트 공정을 통해 최종 마이크로 니들 폴리머 레이어(10')를 형성한다. FIG. 3 is a view showing a mold process (S11) of the manufacturing process of the microneedle biosensor of FIG. 2 . The mold process (S11) includes (a) forming the first microneedle polymer layer 10, (b) disposing the first microneedle polymer layer 10 in a mold-shaped container, and (c) placing the first microneedle polymer layer 10 in the container. Forming the support layer 20 on the primary microneedle polymer layer 10, (d) after the support layer 20 is dried, injecting and curing the mold material PDMS (Polydimethylsiloxane), (e) the above A step of completing the reverse mold 300 by separating the PDMS mold cured in the step. Step (f) is a step of forming the final microneedle polymer layer 10', after manufacturing the reverse mold 300 through the mold process of S11, the final microneedle polymer layer through the imprint process of FIG. 4 or 5 (10').

도 4는 PLA 마이크로니들을 제조하는 열 임프린트 공정(S12)을 나타낸 흐름도이다. 도시되는 바와 같이, 도 3의 몰드 제조단계(S111)에서 제조된 역몰드(300) 에 이형제를 코팅하는 이형제 코팅 단계(S112a), 이형제 건조 단계(S113a), 홈이 형성된 역몰드(300) 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. 4 is a flow chart showing a thermal imprint process (S12) for manufacturing PLA microneedles. 3, the release agent coating step (S112a) of coating the release agent on the reverse mold 300 manufactured in the mold manufacturing step (S111) of FIG. It consists of forming a PLA layer on and pressing with ceramic (S114a), baking in a 200 ° C. vacuum oven (S115a), and pressing with a press after vacuuming off (S116a). 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 5는 도 2의 마이크로 니들 바이오 센서 제조 공정 중 아크릴 마이크로 니들을 제조하는 임프린트 공정 아크릴 UV 레진을 이용하는 임프린트 공정을 나타낸다. 도 3의 몰드 제조단계(S111)에서 제조된 역몰드(300) 상에 아크릴 UV 레진을 진공 상태에서 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. 5 shows an imprint process using acrylic UV resin, an imprint process for manufacturing acrylic microneedles in the manufacturing process of the microneedle biosensor of FIG. 2 . Placing acrylic UV resin in a vacuum state on the inverse mold 300 prepared in the mold manufacturing step (S111) of FIG. 3 (S112b), pressing with a press after vacuum off (S113b), UV curing step (S114b) ), and a demolding step (S115b). 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 6 및 7은 도 2의 마이크로 니들 바이오 센서 제조 공정 중 메탈리제이션 공정을 나타낸 도면이다. 메탈리제이션 공정은 도 3 또는 4의 임프린트 공정을 통해 제조된 최종 마이크로 니들 폴리머 레이어(10') 상에 접착제(adhesion)를 도포하고, 도 1의 작업전극(110), 상대전극(120), 기준전극(130)의 패턴에 해당되는 섀도우 마스크(mask)를 형성하고(도 7의 (a)) Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 레이어를 형성하여(b) 작업전극(110), 상대전극(120), 기준전극(130)을 형성한다. 6 and 7 are diagrams illustrating a metallization process in the manufacturing process of the microneedle biosensor of FIG. 2 . In the metallization process, an adhesive is applied on the final microneedle polymer layer 10' manufactured through the imprint process of FIG. 3 or 4, and the working electrode 110 of FIG. 1, the counter electrode 120, A shadow mask corresponding to the pattern of the reference electrode 130 is formed (FIG. 7(a)), a metal layer is formed by sputtering an Au or Au+Ti/Cr adhesive layer, and (b) the working electrode 110 , the counter electrode 120 and the reference electrode 130 are formed.

도 8은 전술한 바와 같이 역몰드(300)를 이용하여 마이크로 니들 폴리머 레이어를 형성한 효과를 나타낸다. 도 8(a)는 종래의 레이저 식각으로 형성한 몰드를 이용하여 제조된 마이크로 니들 폴리머 레이어를나타내고, 도 8(b)는 본 발명의 실시예에 따른 마이크로 니들 폴리머 레이어를 나타낸다. 도시된 바와 같이, 도8(a)의 종레의 마이크로 니들 폴리머 레이어는, 베이스에서 니들이 수직으로 돌출하여 니들 뿌리에 응력이 집중되어 니들에 손상이 가거나, 마이크로 니들 바이오 센서 상에 증착되는 금속 전극 레이어가 절단되어 정확한 센싱에 문제가 발생할 수 있으나, 본 발명의 실시예에 따라 제조된 역몰드(300)를 이용하여 마이크로 니들 폴리머 레이어(10')를 형성하면 니들 뿌리 둘레가 보강되어 마이크로 니들 바이오 센서의 내구도를 증가시킬 수 있게 된다.8 shows the effect of forming the microneedle polymer layer using the reverse mold 300 as described above. 8(a) shows a microneedle polymer layer manufactured using a mold formed by conventional laser etching, and FIG. 8(b) shows a microneedle polymer layer according to an embodiment of the present invention. As shown, the microneedle polymer layer of Jongle of FIG. 8 (a) is a metal electrode layer deposited on the microneedle biosensor, or the needle protrudes vertically from the base and stress is concentrated on the needle root, resulting in damage to the needle. However, if the microneedle polymer layer 10' is formed using the inverse mold 300 manufactured according to the embodiment of the present invention, the circumference of the needle root is reinforced and the microneedle biosensor can increase durability.

Claims (4)

마이크로 니들 폴리머 레이어를 형성하기 위한 몰드를 형성하는 단계(S11);Forming a mold for forming a microneedle polymer layer (S11); 상기 몰드 상에 아크릴 또는 PLA를 이용하여 상기 작업전극, 상대전극, 기준전극 각각을 임프린트하는 단계(S12); 및imprinting each of the working electrode, counter electrode and reference electrode on the mold using acrylic or PLA (S12); and 상기 S12 단계 수행 후, 상기 작업전극, 상대전극, 기준전극의 패턴에 해당되는 섀도우 마스크를 형성하고 Au 또는 Au+Ti/Cr 접착층을 스퍼터링하여 금속 레이어를 형성하는 단계(S13);를 포함하고After performing the step S12, forming a shadow mask corresponding to the pattern of the working electrode, counter electrode, and reference electrode, and forming a metal layer by sputtering an Au or Au + Ti / Cr adhesive layer (S13); and 상기 a) 단계는 Step a) above (a) 1차 마이크로 니들 폴리머 레이어 형성 단계,(a) forming a first microneedle polymer layer; (b) 상기 1차 마이크로 니들 폴리머 레이어를 몰드 형상의 용기 내에 배치하는 단계,(b) disposing the first microneedle polymer layer in a mold-shaped container; (c) 상기 용기에 배치된 상기 1차 마이크로 니들 폴리머 레이어 상에 서포트 레이어를 형성하는 단계, (c) forming a support layer on the primary microneedle polymer layer disposed in the container; (d) 상기 (c) 단계에서 서포트 레이어가 건조 된 후 몰드 재료인 PDMS(Polydimethylsiloxane)를 투입하고 경화시키는 단계, 및 (d) injecting and curing PDMS (Polydimethylsiloxane), which is a mold material, after the support layer is dried in step (c), and (e) 상기 (d) 단계에서 경화된 PDMS 몰드를 분리하여 역몰드를 완성하는 단계를 포함하는 것을 특징으로 하는 역몰드를 이용한 마이크로 니들 바이오 센서 제조 방법.(e) separating the cured PDMS mold in step (d) to complete the reverse mold. 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 역몰드를 이용한 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 microneedle biosensor manufacturing method using a reverse mold, characterized in that it comprises a needle and a third wire extending from one end of the third base. 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 역몰드를 이용한 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. 제 1 항에 있어서,According to claim 1, 상기 S13 단계 수행 후 상기 금속 레이어 상에 패시베이션 레이어를 형성하는 단계를 추가로 포함하는 것을 특징으로 하는 역몰드를 이용한 마이크로 니들 바이오 센서 제조 방법.The microneedle biosensor manufacturing method using a reverse mold, characterized in that it further comprises the step of forming a passivation layer on the metal layer after performing step S13.
PCT/KR2022/000620 2021-09-15 2022-01-13 Method for manufacturing microneedle biosensor using inverse mold Ceased WO2023048346A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US18/603,502 US20240215915A1 (en) 2021-09-15 2024-03-13 Manufacturing method of microneedle biosensor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020210125475A KR102493415B1 (en) 2021-09-23 2021-09-23 Manufacturing method for micro needle bio sensor using replica mold
KR10-2021-0125475 2021-09-23

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US18/603,502 Continuation US20240215915A1 (en) 2021-09-15 2024-03-13 Manufacturing method of microneedle biosensor

Publications (1)

Publication Number Publication Date
WO2023048346A1 true WO2023048346A1 (en) 2023-03-30

Family

ID=85109076

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/000620 Ceased WO2023048346A1 (en) 2021-09-15 2022-01-13 Method for manufacturing microneedle biosensor using inverse mold

Country Status (3)

Country Link
KR (1) KR102493415B1 (en)
CN (1) CN115856047A (en)
WO (1) WO2023048346A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080076434A (en) * 2007-02-16 2008-08-20 박정철 Biometric information measuring device and manufacturing method thereof
KR20120030055A (en) * 2009-06-10 2012-03-27 히사미쓰 세이야꾸 가부시키가이샤 Microneedle device
KR101484161B1 (en) * 2012-06-27 2015-01-22 연세대학교 산학협력단 Polymer-based nano or micro needle through coating and fabricating method thereof
KR20160123951A (en) * 2015-04-17 2016-10-26 삼성전자주식회사 Biometric information measuring sensor, Biometric information measuring system and Measuring method biometric information using the same
KR20190085586A (en) * 2018-01-11 2019-07-19 부산대학교 산학협력단 microneedle patch comprising titanium nanotube and method for preparing thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102217939B (en) * 2011-05-26 2013-01-09 上海交通大学 Micro tip array electrode used for minimally invasive dynamic glucose monitoring
CN103301092B (en) * 2012-03-06 2014-12-03 中国科学院理化技术研究所 Polymer micro-needle array chip and preparation method and application thereof
KR20160019944A (en) * 2013-06-13 2016-02-22 마이크로데믹스 인코퍼레이티드 Metallic microneedles
KR20170038351A (en) 2015-09-30 2017-04-07 최규동 Continous Glucose Measuremrnt System with Flexsible Probe
EP4458256A3 (en) 2015-12-28 2025-01-08 Medtronic Minimed, Inc. Methods for continuous glucose monitoring
KR101773583B1 (en) 2016-06-03 2017-09-01 주식회사 아이센스 Applicator for Continuous Glucose Monitoring System
KR102044061B1 (en) 2016-12-21 2019-11-12 주식회사 유엑스엔 Continuous glucose monitoring apparatus, continuous glucose monitoring system comprising said apparatus and method using said system
CN112858430B (en) * 2021-01-08 2021-11-26 中山大学 Sensor for detecting plant active small molecules and preparation method

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20080076434A (en) * 2007-02-16 2008-08-20 박정철 Biometric information measuring device and manufacturing method thereof
KR20120030055A (en) * 2009-06-10 2012-03-27 히사미쓰 세이야꾸 가부시키가이샤 Microneedle device
KR101484161B1 (en) * 2012-06-27 2015-01-22 연세대학교 산학협력단 Polymer-based nano or micro needle through coating and fabricating method thereof
KR20160123951A (en) * 2015-04-17 2016-10-26 삼성전자주식회사 Biometric information measuring sensor, Biometric information measuring system and Measuring method biometric information using the same
KR20190085586A (en) * 2018-01-11 2019-07-19 부산대학교 산학협력단 microneedle patch comprising titanium nanotube and method for preparing thereof

Also Published As

Publication number Publication date
CN115856047A (en) 2023-03-28
KR102493415B1 (en) 2023-01-31

Similar Documents

Publication Publication Date Title
KR100528306B1 (en) Minimally invasive detecting device
CA2662950A1 (en) Method and apparatus for providing analyte sensor and data processing device
WO2019119045A1 (en) Anisotropically conductive material for use with a biological surface
KR101785287B1 (en) Microneedle electrode patch and fabrication method of the microneedle electrode patch
EP4327740A1 (en) Microneedle biosensor and manufacturing method for same
KR20170019033A (en) Sensor for measuring biological signal
KR20200004164A (en) Biosensor having minimally invasive needle with simplified fabricating process and method for fabricating the biosensor
EP1792565B1 (en) Selectively exposable miniature probes with integrated sensor arrays for continuous in vivo diagnostics
KR101501283B1 (en) Manufacturing method of microneedles array panel
KR102505313B1 (en) Manufacturing method for micro needle bio sensor with passive layer
KR102497679B1 (en) Manufacturing method for micro needle bio sensor with support layer
KR20190059135A (en) Biosensor capable of measuring biological signals and delivering drugs simultaneously and manufacturing method
WO2023048346A1 (en) Method for manufacturing microneedle biosensor using inverse mold
CN118593890B (en) Band-aid type microneedle patch for glucose monitoring and photo-thermal response drug delivery and preparation method thereof
US20240215915A1 (en) Manufacturing method of microneedle biosensor
KR20230043274A (en) MANUFACTURING METHOD FOR MICRO NEEDLE BIO SENSOR WITH Pt black WORKING ELECTRODE
KR20230043276A (en) MANUFACTURING METHOD FOR MICRO NEEDLE BIO SENSOR WITH Ag/AgCl REFERENCE ELECTRODE
KR20230142400A (en) Micro needle bio sensor and manufacturing method the same
KR20230042871A (en) Continous glucose monitoring system with micro needle bio sensor
KR20230043275A (en) Manufacturing method for micro needle bio sensor with interference shielding layer
KR20220145520A (en) Micro needle bio sensor and manufacturing method the same
JP2025521760A (en) Multiplexed sensor device and method for manufacturing same
Cho et al. Recent Advancements in Flexible Biosensors for Continuous Glucose Monitoring
KR20230042870A (en) Applicator for micro needle bio sensor
KR20160066075A (en) Sensor for measuring biological signal

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22873053

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22873053

Country of ref document: EP

Kind code of ref document: A1