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WO2025183511A1 - Droplet generation device using electrowetting phenomenon - Google Patents

Droplet generation device using electrowetting phenomenon

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Publication number
WO2025183511A1
WO2025183511A1 PCT/KR2025/002841 KR2025002841W WO2025183511A1 WO 2025183511 A1 WO2025183511 A1 WO 2025183511A1 KR 2025002841 W KR2025002841 W KR 2025002841W WO 2025183511 A1 WO2025183511 A1 WO 2025183511A1
Authority
WO
WIPO (PCT)
Prior art keywords
droplet
negative pressure
module
generating device
sample
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.)
Pending
Application number
PCT/KR2025/002841
Other languages
French (fr)
Korean (ko)
Inventor
한기호
박수희
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.)
Industry Academic Cooperation Foundation of Inje University
Original Assignee
Industry Academic Cooperation Foundation of Inje University
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 Industry Academic Cooperation Foundation of Inje University filed Critical Industry Academic Cooperation Foundation of Inje University
Publication of WO2025183511A1 publication Critical patent/WO2025183511A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/087—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting

Definitions

  • the invention relates to a droplet generating device used in polymerase chain reaction (PCR), etc., and more specifically, to a droplet generating device utilizing an electrowetting phenomenon that can form a wide range of droplet sizes based on an electrowetting control environment, and can easily and quickly change and generate a desired droplet size without changing a mechanical structure.
  • PCR polymerase chain reaction
  • Microdroplet technology is a technology field that has recently received significant attention due to its relatively simple preparation process, uniformity of droplets, controllability of droplet size and volume, and high productivity.
  • Microdroplets can be used as reactors in various fields, including cell biology, DNA or nucleic acid analysis, and more.
  • microfluidics utilizes the physical phenomena that occur when fluids flow within microscale structures.
  • Microdroplets have a volume on the nanoliter level, and each can be used as a microreactor. Therefore, by using them, uniform particle synthesis conditions different from the irregular particle synthesis conditions of bulk scale can be provided, and thus research using microdroplets is actively being conducted.
  • the digital PCR method is evaluated as a next-generation PCR detection method with high sensitivity because it enables absolute quantitative detection of a target gene in real time without a standard substance.
  • lab-on-a-chip requires complex functions to implement diverse and precise performance, which complicates the manufacturing process and increases the manufacturing cost of the chip, which is a major obstacle to the commercialization of lab-on-a-chip, which must be used only once.
  • micro-air bubbles that can occur within microfluidic channels interfere with precise fluid control and flow, reducing the reproducibility of lab-on-a-chip, which is one of the main reasons making automation and commercialization of lab-on-a-chip difficult.
  • the present invention which aims to solve the above-mentioned conventional problems, provides a droplet generation device using an electrowetting phenomenon, which can form a wide range of droplet sizes based on an electrowetting control environment, and can easily and quickly change and generate a desired droplet size without changing a mechanical structure.
  • a droplet generating device characterized by including: an electric control applying module that causes electrical control; a droplet generating module that is provided on an upper surface of the electric control applying module and is configured to generate droplets by the electrical control generated from the electric control applying module; and a negative pressure forming means that forms negative pressure on an opposing surface between the electric control applying module and the droplet generating module.
  • the electric control application module includes a patterning electrode formed on the upper surface of the base substrate, and the electric control application module may further include a protective film covering the upper surface of the patterning electrode.
  • the droplet generation module may include a base block; a sample inlet formed in the base block and through which a sample is introduced; an oil inlet and an oil outlet formed at each end of the base block; and a microchannel through which a fluid introduced through the oil inlet and a sample introduced through the sample inlet pass and are discharged through the oil outlet.
  • the oil inlet, the sample inlet, and the oil outlet are provided on the same line, and the microchannel is formed so that the sample flowing in from the sample inlet and the oil flowing in from the oil inlet can meet in a orthogonal direction at a point where they join, and the point where the sample and the oil join can be provided to be located on the upper side of one of the patterning electrodes.
  • the microchannel may further include a high-flow resistance channel section.
  • the negative pressure forming means may include a negative pressure applying portion formed on one side of the base block; and a negative pressure forming channel formed around the lower surface of the base block and connected to the negative pressure applying portion.
  • the present invention has the effect of easily and quickly generating droplets of a desired size through control of electrical environmental factors such as voltage without changing the mechanical structure.
  • FIG. 1 is a drawing showing a droplet generating device using an electrowetting phenomenon according to the present invention, and is a perspective view showing the state before (A) and after (B) separation of an electric control application module and a droplet generating module.
  • Fig. 2 is a cross-sectional view showing a droplet generating device using an electrowetting phenomenon according to the present invention.
  • Figure 3 is a plan view showing an example of the structure of a droplet generation module included in a droplet generation device using an electrowetting phenomenon according to the present invention.
  • Figure 4 is a drawing showing an example of manufacturing a droplet generating device using an electrowetting phenomenon according to the present invention.
  • FIG. 5 is a drawing showing part “A” of FIG. 1, which is a cross-sectional view (A) and a plan view (B) of a microchannel showing active droplet generation of an electrowetting electrode using a droplet generation device utilizing an electrowetting phenomenon according to the present invention.
  • Figure 6 shows snapshots of droplets generated by an electrowetting (EW) voltage of 330 Vpp and 30 kHz, taken at 1.25 ms intervals.
  • EW electrowetting
  • Figure 7 shows a graph and snapshot photographs showing the reproducibility of droplet size using five identical disposable microchannels, showing droplet size as a function of electrowetting voltage.
  • Figure 8 is a graph showing the stepwise modulated droplet size using a square wave amplitude modulated EW voltage with a peak-to-peak (pp) range of 150 V and 330 V (sample and oil flow rates were set to 1 and 1.5 ⁇ L/min, respectively).
  • FIG. 1 is a drawing showing a droplet generating device using an electrowetting phenomenon according to the present invention, and is a perspective view showing a state before (A) and after (B) separation of an electric control application module and a droplet generating module
  • FIG. 2 is a cross-sectional view showing a droplet generating device using an electrowetting phenomenon according to the present invention
  • FIG. 3 is a plan view showing an example of the structure of a droplet generating module included in a droplet generating device using an electrowetting phenomenon according to the present invention
  • FIG. 4 is a drawing showing an example of manufacturing a droplet generating device using an electrowetting phenomenon according to the present invention.
  • FIG. 5 is a cross-sectional view (A) and a plan view (B) of a microchannel showing active droplet generation of an electrowetting electrode using a droplet generating device using an electrowetting phenomenon according to the present invention.
  • the droplet generation device using the electrowetting phenomenon according to the present invention largely includes an electric control application module (100), a droplet generation module (200), and a negative pressure forming means (300).
  • a droplet generating device utilizing an electrowetting phenomenon comprises, as shown in FIGS. 1 to 5, an electric control applying module (100) having a patterning electrode (120) for generating droplets formed therein; a droplet generating module (200) provided on an upper surface of the electric control applying module (100) and configured to generate droplets by electrical control applied from the electric control applying module (100); and a negative pressure forming means (300) for forming negative pressure (vacuum) on an opposing surface between the electric control applying module (100) and the droplet generating module (200).
  • the above electric control application module (100) is a component that forms a patterning electrode (120) for generating droplets and applies a predetermined voltage to the patterning electrode (120) to generate droplets of a predetermined size in the droplet generation module (200).
  • the electric control application module (100) includes a base substrate (110) and a patterning electrode (120) formed in a predetermined pattern on the upper surface of the base substrate (110).
  • the above base material (110) is formed of a glass material.
  • the above patterning electrode (120) is composed of a pair of electrodes, a negative (-) electrode and a positive (+) electrode, formed in the width direction (vertical direction in the drawing) of the base substrate (110).
  • the electric control application module (100) further includes a protective film (130) for protecting the patterning electrode (120).
  • the above protective film (130) may be composed of a polymer material, for example, SU-8 photoresist.
  • the above-mentioned electric control authorization module (100) can be reused for the disposable droplet generation module (200).
  • the above electric control authorization module (100) is a component that can be used permanently and is separated from the disposable droplet generation module (200).
  • the above base block (210) may be composed of PDMS (polydimethylsiloxane).
  • the above oil inlet (231) and oil outlet (232) are formed on the imaginary center line in the longitudinal direction of the base block (210).
  • the above sample inlet (220) is formed on the virtual center line, but is formed at a position close to the oil inlet (231).
  • the above microchannel (240) is formed so that the sample flowing in from the sample inlet (220) and the oil flowing in from the oil inlet (231) can meet in a direction perpendicular to each other at the point where they join.
  • the microchannel (240) is formed at the point where the oil and the sample meet, and the direction in which the sample flows and the direction in which the oil merge become orthogonal to each other at the point of confluence, thereby allowing the formation of droplets.
  • the microchannel (240) includes an oil inlet linear channel portion (241) extending a predetermined length along an imaginary center line from an oil inlet (231), a branch channel portion (242) branching in a V shape from an extended end of the oil inlet linear channel portion (241), a parallel channel portion (243) extending in parallel from each end of the branch channel portion (242), an orthogonal channel portion (244) extending in an facing direction from each end of the parallel extension portion (243), a confluence channel portion (245) joining in a V shape at each end of the orthogonal channel portions (244), an outflow channel portion (246) connected to an oil outlet (232) at the joining end of the confluence channel portion (245), and a sample channel portion (247) having one end connected to the sample inlet portion (220) and the other end joined to the confluence channel portion (245).
  • the above orthogonal channel portion (244) and the joining channel portion (245) are positioned on the upper side of one electrode among a pair of patterning electrodes (120).
  • microchannel (240) may further include a high-flow resistance channel section (248).
  • the above high-flow resistance channel section (248) can be formed as a waveform channel that forms a zigzag waveform in a direction orthogonal to the main channel, i.e., a waveform channel that forms a zigzag U-shaped flow.
  • the above high-flow resistance channel section (248) can be formed in the orthogonal channel section (244), the outflow channel section (246), and the sample channel section (247).
  • the channel size of the high-flow resistance channel section (248) is formed smaller than the channel sizes of other channel sections.
  • a droplet length measurement area capable of measuring the length of the droplet can be configured in the above-mentioned outlet channel section (246).
  • the negative pressure forming means (300) is a component that forms negative pressure (vacuum) on the opposing surface between the electric control application module (100) and the droplet generating module (200).
  • the negative pressure forming means (300) includes a negative pressure applying portion (310) formed on one side of the base block (210), and a negative pressure forming channel (320) formed around the lower surface of the base block (210).
  • This negative pressure forming means (300) applies negative pressure (vacuum formation) to the opposing portion between the electric control application module (100) and the droplet generation module (200), thereby enabling the electric control application module (100) and the droplet generation module (200) to be coupled or separated.
  • the PDMS top plate is cured using the created mold (process (b)).
  • a 2.4 um PET film is attached to the cured PDMS to form a disposable chip channel (process (c)).
  • the process of making an electrical control module which is a reusable component, involves patterning a desired electrode shape on a substrate with a chrome/gold thin film on a 0.7T thick glass (process (d)).
  • a layer acting as a protective film is created using SU-8 (process (e)).
  • the drawing of process (f) shows a vacuum assembly of a disposable chip, a droplet generation module (100), and a reusable electric control application module (200).
  • FIG. 6 is a snapshot of droplets generated by an electrowetting (EW) voltage of 330 Vpp and 30 kHz taken at 1.25 ms intervals
  • FIG. 7 is a graph and snapshot photographs showing the reproducibility of droplet sizes using five identical disposable microchannels, showing the droplet sizes according to the electrowetting voltage
  • FIG. 8 is a graph showing the droplet sizes modulated stepwise using a square wave amplitude modulated EW voltage with a peak-to-peak (pp) range of 150 V and 330 V (the flow rates of the sample and oil were set to 1 and 1.5 ⁇ L/min, respectively).
  • the inventors of the present invention experimentally confirmed that satisfactory droplet generation can be achieved by using the electrowetting phenomenon according to the present invention.
  • the droplet generation device utilizing the electrowetting phenomenon according to the present invention as described above, a relatively wide range of droplet sizes can be formed compared to existing droplet formation methods, and thus, it can be usefully used in micro-droplet formation technologies such as cell biology, DNA, and nucleic acid analysis, and has the advantage of being able to easily and quickly generate droplets having a desired size with control of electrical environmental factors such as voltage without changing the mechanical structure.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Toxicology (AREA)
  • Organic Chemistry (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

The present invention relates to a droplet generation device using an electrowetting phenomenon, wherein droplets with a wide range of sizes can be generated on the basis of an electrowetting control environment, and the droplets can be changed to desired droplet sizes and generated with ease and rapid responsiveness without changing a mechanical structure. The present invention provides a droplet generation device comprising: an electrical control application module for generating electrical control; a droplet generation module provided on the upper surface of the electrical control application module and configured to generate droplets by using the electrical control generated by the electrical control application module; and a negative pressure formation means for forming a negative pressure on opposite surfaces between the electrical control application module and the droplet generation module.

Description

전기 습윤 현상을 이용한 액적 생성 장치Droplet generation device using electrowetting phenomenon

발명은 중합효소 연쇄반응(PCR: polymerase chain reaction) 등에 이용되는 액적 생성 장치에 관한 것으로, 더욱 상세하게는 전기적 습윤 제어 환경을 기반으로 하여 넓은 범위의 액적 사이즈를 형성할 수 있으며, 기구적 구조물의 변경 없이도 원하는 액적 사이즈로 용이하고 빠른 응답성으로 변경하여 생성할 수 있는 전기 습윤 현상을 이용한 액적 생성 장치에 관한 것이다.The invention relates to a droplet generating device used in polymerase chain reaction (PCR), etc., and more specifically, to a droplet generating device utilizing an electrowetting phenomenon that can form a wide range of droplet sizes based on an electrowetting control environment, and can easily and quickly change and generate a desired droplet size without changing a mechanical structure.

미세 액적 기술은 상대적으로 간단한 준비 과정, 액적의 균일성, 액적 크기 및 부피의 조절 가능성, 높은 생산성 등으로 인해 최근 들어 크게 각광 받고 있는 기술 분야이다.Microdroplet technology is a technology field that has recently received significant attention due to its relatively simple preparation process, uniformity of droplets, controllability of droplet size and volume, and high productivity.

미세 액적은 특히, 세포 생물학, DNA 또는 핵산 분석 등 다양한 분야에 반응기로써 사용될 수 있다. 미세 액적 기술 중, 마이크로 플루이딕 기술은 마이크로 스케일의 구조체 내부에서 유체가 흐를 때 발생하는 물리적 현상을 이용하는 기술이다.Microdroplets can be used as reactors in various fields, including cell biology, DNA or nucleic acid analysis, and more. Among microdroplet technologies, microfluidics utilizes the physical phenomena that occur when fluids flow within microscale structures.

최근 마이크로 스케일의 액적(micro-droplet)을 이용한 입자 생성 기술들이 연구되고 있다. Recently, particle generation technologies using micro-scale droplets are being studied.

마이크로 액적은 나노리터 수준의 부피를 가지고, 각각을 하나의 미세 반응기로 사용할 수 있기 때문에, 이를 이용하면 벌크 스케일의 불규칙한 입자 합성조건과는 다른 균일한 입자 합성 조건을 제공할 수 있어, 마이크로 액적을 이용한 연구가 활발하게 이루어지고 있다.Microdroplets have a volume on the nanoliter level, and each can be used as a microreactor. Therefore, by using them, uniform particle synthesis conditions different from the irregular particle synthesis conditions of bulk scale can be provided, and thus research using microdroplets is actively being conducted.

예를 들면, 중합효소 연쇄반응(PCR)과 아가로스 겔(agarose gel) 전기영동을 이용해 목표 유전자의 존재를 확인하는 기존의 PCR 방법(1세대), 형광물질을 이용하여 목표 유전자의 증폭을 실시간 확인할 수 있는 실시간(real-time) PCR 방법(2세대)과 비교하여 디지털 PCR 방법은 표준물질 없이도 실시간으로 목표 유전자의 절대 정량 검출이 가능하여 매우 민감도가 높은 차세대 PCR 검출 방식으로 평가되고 있다.For example, compared to the conventional PCR method (1st generation) that uses polymerase chain reaction (PCR) and agarose gel electrophoresis to confirm the presence of a target gene, and the real-time PCR method (2nd generation) that uses fluorescent substances to confirm the amplification of a target gene in real time, the digital PCR method is evaluated as a next-generation PCR detection method with high sensitivity because it enables absolute quantitative detection of a target gene in real time without a standard substance.

디지털 PCR의 구현을 위한 상용화된 기술은 현재 몇몇에 불과하며, 이러한 디지털 PCR 구현 방식은 크게 칩과 open-array 평판을 사용하는 미세 격벽 형태와 emulsion PCR을 위한 액적(droplet) 형태 등 2가지로 구분된다.There are currently only a few commercially available technologies for implementing digital PCR, and these digital PCR implementation methods are broadly divided into two types: micro-barrier type using chips and open-array plates, and droplet type for emulsion PCR.

그러나, 현재 상용화된 디지털 PCR 기술의 문제점은 고가의 장비(2-5억원)와 소모칩(3-100만원)으로 인해 일반 대학연구실이나 공공연구 시설로의 도입이 제한적이고, 수동식 액적 생성으로 인해 생성된 액적 개수의 모니터링이 불가능한 단점이 있었다.However, the problem with the currently commercialized digital PCR technology is that its introduction to general university laboratories or public research facilities is limited due to the high cost of equipment (KRW 200-500 million) and consumable chips (KRW 300-1 million), and the manual droplet generation makes it impossible to monitor the number of droplets generated.

이와 같은 수동식 액적 생성방식의 경우 채널 내 공기 방울이나 환경변화에 따른 액적 크기의 불균일로 인한 실험 결과의 정확도가 저하되고, 수동식 액적 생성 시 작동의 이상 유무를 판단할 수 있는 자가진단이 불가능한 문제점이 있었다.In the case of this type of manual droplet generation method, the accuracy of the experimental results is reduced due to non-uniformity in droplet size caused by air bubbles in the channel or environmental changes, and there is a problem in that self-diagnosis to determine whether there is an abnormality in operation during manual droplet generation is impossible.

또한, 능동식 액적 생성을 위해 고가의 유속센서를 반복 사용할 경우 바이오 시료 간 오염이 발생하는 문제점이 있다. Additionally, there is a problem of contamination between bio samples when expensive flow sensors are repeatedly used for active droplet generation.

이러한 문제점은 미세유체 기반의 디지털 PCR 기술뿐만 아니라 대부분의 고성능 랩온어칩(Lab-on-a-Chip)에도 해당하는데, 즉, 랩온어칩은 재사용 시 바이오 시료 간의 오염으로 인해 분석 결과의 오류가 발생할 수 있으므로 반드시 일회용으로 개발 및 사용되어야 한다.This problem applies not only to microfluidic-based digital PCR technology but also to most high-performance lab-on-a-chips, which must be developed and used for single-use purposes because contamination between biosamples can lead to errors in analysis results when reused.

그러나 많은 경우 랩온어칩은 다양하고 정밀한 성능을 구현하기 위해 복잡한 기능들을 요구하게 되며, 이로 인해 제작과정이 복잡하여 칩의 제작비용이 상승하게 됨으로써, 이는 필수적으로 일회용으로 사용되어야 하는 랩온어칩의 상용화에 큰 걸림돌이 된다.However, in many cases, lab-on-a-chip requires complex functions to implement diverse and precise performance, which complicates the manufacturing process and increases the manufacturing cost of the chip, which is a major obstacle to the commercialization of lab-on-a-chip, which must be used only once.

또한, 미세유체 채널 내에 발생할 수 있는 미세 공기 방울은 정밀한 유체 제어 및 흐름을 방해하여 랩온어칩의 재현성을 떨어뜨리며, 이는 랩온어칩의 자동화 및 상용화를 어렵게 하는 주요 원인 중 하나이다.In addition, micro-air bubbles that can occur within microfluidic channels interfere with precise fluid control and flow, reducing the reproducibility of lab-on-a-chip, which is one of the main reasons making automation and commercialization of lab-on-a-chip difficult.

현재 세계적으로 이러한 기존의 수동식 액적 생성칩(랩온어칩)이 가지는 문제를 해결하여 미세유체칩 사용의 경제적 부담을 줄이고 바이오 시료 간의 오염을 근본적으로 차단하려는 기술개발이 이루어지고 있으나, 아직은 기술적으로 초기 단계 수준이다.Currently, technology development is underway worldwide to solve the problems of existing manual droplet generation chips (lab-on-a-chip), reduce the economic burden of using microfluidic chips, and fundamentally prevent contamination between bio-samples. However, it is still in its initial stages of technology.

특히, 기존 제안된 액적 생성 방식의 한계에서 벗어나, 미세 액적의 생성에 있어서, 액적 생성을 위한 장치의 기구적 변경 또는 물리적 구성 조합 없이도 액적 사이즈에 대하여 용이하게 생성하고, 또한 넓은 범위에서의 액적 사이즈의 다양한 변경이 가능한 연구와 개발이 필요한 실정이다.In particular, in order to overcome the limitations of existing proposed droplet generation methods, research and development are needed to easily generate droplet sizes without mechanical changes or physical configuration combinations of devices for droplet generation, and to enable various changes in droplet sizes over a wide range.

따라서, 상기한 종래의 문제점을 해결하기 위한 본 발명은, 전기적 습윤 제어 환경을 기반으로 하여 넓은 범위의 액적 사이즈를 형성할 수 있으며, 기구적 구조물의 변경 없이도 원하는 액적 사이즈로 용이하고 빠른 응답성으로 변경하여 생성할 수 있는 전기 습윤 현상을 이용한 액적 생성 장치를 제공하는데 그 목적이 있다.Accordingly, the present invention, which aims to solve the above-mentioned conventional problems, provides a droplet generation device using an electrowetting phenomenon, which can form a wide range of droplet sizes based on an electrowetting control environment, and can easily and quickly change and generate a desired droplet size without changing a mechanical structure.

본 발명의 해결과제는 이상에서 언급한 것들에 한정되지 않으며, 언급되지 아니한 다른 해결과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.The problems solved by the present invention are not limited to those mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

상기 본 발명의 목적들 및 다른 특징들을 달성하기 위한 본 발명의 일 관점에 따르면, 전기적 제어를 일으키는 전기제어 인가 모듈; 상기 전기제어 인가 모듈의 상면에 구비되고, 상기 전기제어 인가 모듈에서 발생되는 전기적 제어에 의해 액적을 생성하도록 구성되는 액적 생성 모듈; 및 상기 전기제어 인가 모듈과 액적 생성 모듈 간의 대향면에서 음압이 형성되도록 하는 음압 형성 수단;을 포함하는 것을 특징으로 하는 액적 생성 장치가 제공된다.According to one aspect of the present invention for achieving the above objects and other features of the present invention, a droplet generating device is provided, characterized by including: an electric control applying module that causes electrical control; a droplet generating module that is provided on an upper surface of the electric control applying module and is configured to generate droplets by the electrical control generated from the electric control applying module; and a negative pressure forming means that forms negative pressure on an opposing surface between the electric control applying module and the droplet generating module.

본 발명에 있어서, 상기 전기제어 인가 모듈은 베이스 기재의 상면에 형성되는 패터닝 전극을 포함하며, 상기 전기제어 인가 모듈은 상기 패터닝 전극의 상면을 커버하는 보호막을 더 포함할 수 있다.In the present invention, the electric control application module includes a patterning electrode formed on the upper surface of the base substrate, and the electric control application module may further include a protective film covering the upper surface of the patterning electrode.

본 발명에 있어서, 상기 액적 생성 모듈은 베이스 블록; 상기 베이스 블록에 형성되며, 시료(sample)가 유입되는 시료 유입구; 상기 베이스 블록의 양단부에 각각 형성되는 오일 유입구와 오일 유출구; 및 오일 유입구를 통해 유입되는 유체, 및 상기 시료 유입구를 통해 유입되는 시료가 통과하여 상기 오일 유출구로 배출되는 마이크로 채널;을 포함할 수 있다.In the present invention, the droplet generation module may include a base block; a sample inlet formed in the base block and through which a sample is introduced; an oil inlet and an oil outlet formed at each end of the base block; and a microchannel through which a fluid introduced through the oil inlet and a sample introduced through the sample inlet pass and are discharged through the oil outlet.

본 발명에 있어서, 상기 오일 유입구와 시료 유입구 및 오일 유출구는 동일 선상에 구비되고, 상기 마이크로 채널은 상기 시료 유입구에서 유입되는 시료와, 상기 오일 유입구에서 유입되는 오일이 합류되는 지점에서 직교하는 방향으로 만날 수 있도록 형성되며, 상기 시료와 오일이 합류되는 지점은 상기 패터닝 전극 중 일측의 전극 상부 측에 위치되게 구비될 수 있다.In the present invention, the oil inlet, the sample inlet, and the oil outlet are provided on the same line, and the microchannel is formed so that the sample flowing in from the sample inlet and the oil flowing in from the oil inlet can meet in a orthogonal direction at a point where they join, and the point where the sample and the oil join can be provided to be located on the upper side of one of the patterning electrodes.

본 발명에 있어서, 상기 마이크로 채널은 고유량 저항 채널부를 더 포함할 수 있다.In the present invention, the microchannel may further include a high-flow resistance channel section.

본 발명에 있어서, 상기 고유량 저항 채널부는 지그재그의 U자형 흐름을 형성하는 파형 채널로 형성될 수 있다.In the present invention, the high-flow resistance channel section can be formed as a wave channel forming a zigzag U-shaped flow.

본 발명에 있어서, 상기 음압 형성 수단은 상기 베이스 블록의 일측에 형성되는 음압 인가부; 및 상기 음압 인가부에 연통되고, 상기 베이스 블록의 하면 둘레에 형성되는 음압 형성 채널;을 포함할 수 있다.In the present invention, the negative pressure forming means may include a negative pressure applying portion formed on one side of the base block; and a negative pressure forming channel formed around the lower surface of the base block and connected to the negative pressure applying portion.

본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치에 의하면 다음과 같은 효과를 제공한다.The droplet generating device using the electrowetting phenomenon according to the present invention provides the following effects.

첫째, 본 발명은 기존 액적 형성 방식에 비하여 상대적으로 넓은 범위의 액적 사이즈를 형성할 수 있어 세포 생물학, DNA, 핵산 분석 등 미세 액적 형성 기술에 유용하게 이용할 수 있는 효과가 있다.First, the present invention can form a relatively wide range of droplet sizes compared to existing droplet formation methods, and thus has the effect of being useful for micro-droplet formation technologies such as cell biology, DNA, and nucleic acid analysis.

둘째, 본 발명은 기구적 구조물의 변경 없이도 전압과 같은 전기적 환경 인자의 제어를 통해 원하는 사이즈를 갖는 액적을 용이하고 빠른 응답성으로 생성할 수 있는 효과가 있다.Second, the present invention has the effect of easily and quickly generating droplets of a desired size through control of electrical environmental factors such as voltage without changing the mechanical structure.

본 발명의 효과는 이상에서 언급된 것들에 한정되지 않으며, 언급되지 아니한 다른 해결과제들은 아래의 기재로부터 당업자에게 명확하게 이해되어 질 수 있을 것이다.The effects of the present invention are not limited to those mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

도 1은 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 나타내는 도면으로, 전기제어 인가 모듈과 액적 생성 모듈의 분리 전(A) 및 분리 후(B)의 상태를 나타내는 사시도이다.FIG. 1 is a drawing showing a droplet generating device using an electrowetting phenomenon according to the present invention, and is a perspective view showing the state before (A) and after (B) separation of an electric control application module and a droplet generating module.

도 2는 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 나타내는 단면도이다.Fig. 2 is a cross-sectional view showing a droplet generating device using an electrowetting phenomenon according to the present invention.

도 3은 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치에 포함되는 액적 생성 모듈의 구조 예를 나타내는 평면도이다.Figure 3 is a plan view showing an example of the structure of a droplet generation module included in a droplet generation device using an electrowetting phenomenon according to the present invention.

도 4는 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치의 제작 예를 나타내는 도면이다.Figure 4 is a drawing showing an example of manufacturing a droplet generating device using an electrowetting phenomenon according to the present invention.

도 5는 도 1의 "A"부를 나타내는 도면으로, 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 이용하여 전기습윤 전극의 활성 액적 생성을 보여주는 마이크로 채널의 단면도(A) 및 평면도(B)이다.FIG. 5 is a drawing showing part “A” of FIG. 1, which is a cross-sectional view (A) and a plan view (B) of a microchannel showing active droplet generation of an electrowetting electrode using a droplet generation device utilizing an electrowetting phenomenon according to the present invention.

도 6은 330Vpp 및 30kHz의 전기습윤(EW) 전압에 의해 생성된 액적의 스냅샷을 1.25ms 간격으로 촬영한 것이다.Figure 6 shows snapshots of droplets generated by an electrowetting (EW) voltage of 330 Vpp and 30 kHz, taken at 1.25 ms intervals.

도 7은 5개의 동일한 일회용 마이크로채널을 사용한 액적 크기의 재현성을 나타내는 그래프와 스냅샷 사진으로서 전기습윤 전압에 따른 액적 크기를 보여주는 것이다.Figure 7 shows a graph and snapshot photographs showing the reproducibility of droplet size using five identical disposable microchannels, showing droplet size as a function of electrowetting voltage.

도 8은 150V 및 330V의 피크 대 피크(pp) 범위를 갖는 구형파 진폭 변조 EW 전압을 사용하여 단계적으로 변조된 액적 크기를 나타내는 그래프(샘플과 오일의 유속은 각각 1 및 1.5μL/min으로 설정)이다.Figure 8 is a graph showing the stepwise modulated droplet size using a square wave amplitude modulated EW voltage with a peak-to-peak (pp) range of 150 V and 330 V (sample and oil flow rates were set to 1 and 1.5 μL/min, respectively).

이하, 본 발명의 바람직한 실시 예에 따른 전기 습윤 현상을 이용한 액적 생성 장치에 대하여 첨부 도면을 참조하여 상세히 설명한다.Hereinafter, a droplet generating device utilizing an electrowetting phenomenon according to a preferred embodiment of the present invention will be described in detail with reference to the attached drawings.

도 1은 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 나타내는 도면으로, 전기제어 인가 모듈과 액적 생성 모듈의 분리 전(A) 및 분리 후(B)의 상태를 나타내는 사시도이고, 도 2는 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 나타내는 단면도이고, 도 3은 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치에 포함되는 액적 생성 모듈의 구조 예를 나타내는 평면도이며, 도 4는 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치의 제작 예를 나타내는 도면이다. 도 5는 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치를 이용하여 전기습윤 전극의 활성 액적 생성을 보여주는 마이크로 채널의 단면도(A) 및 평면도(B)이다.FIG. 1 is a drawing showing a droplet generating device using an electrowetting phenomenon according to the present invention, and is a perspective view showing a state before (A) and after (B) separation of an electric control application module and a droplet generating module, FIG. 2 is a cross-sectional view showing a droplet generating device using an electrowetting phenomenon according to the present invention, FIG. 3 is a plan view showing an example of the structure of a droplet generating module included in a droplet generating device using an electrowetting phenomenon according to the present invention, and FIG. 4 is a drawing showing an example of manufacturing a droplet generating device using an electrowetting phenomenon according to the present invention. FIG. 5 is a cross-sectional view (A) and a plan view (B) of a microchannel showing active droplet generation of an electrowetting electrode using a droplet generating device using an electrowetting phenomenon according to the present invention.

본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치는, 도 1 내지 도 5에 나타낸 바와 같이, 크게 전기제어 인가 모듈(100)과, 액적 생성 모듈(200), 및 음압 형성 수단(300)을 포함한다.The droplet generation device using the electrowetting phenomenon according to the present invention, as shown in FIGS. 1 to 5, largely includes an electric control application module (100), a droplet generation module (200), and a negative pressure forming means (300).

구체적으로, 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치는, 도 1 내지 도 5에 나타낸 바와 같이, 액적 생성을 위한 패터닝 전극(120)이 형성된 전기제어 인가 모듈(100); 상기 전기제어 인가 모듈(100)의 상면에 구비되고, 상기 전기제어 인가 모듈(100)에서 인가되는 전기적 제어에 의해 액적을 생성하도록 구성되는 액적 생성 모듈(200); 및 상기 전기제어 인가 모듈(100)과 액적 생성 모듈(200) 간의 대향면에서 음압(진공)이 형성되도록 하는 음압 형성 수단(300);을 포함한다.Specifically, a droplet generating device utilizing an electrowetting phenomenon according to the present invention comprises, as shown in FIGS. 1 to 5, an electric control applying module (100) having a patterning electrode (120) for generating droplets formed therein; a droplet generating module (200) provided on an upper surface of the electric control applying module (100) and configured to generate droplets by electrical control applied from the electric control applying module (100); and a negative pressure forming means (300) for forming negative pressure (vacuum) on an opposing surface between the electric control applying module (100) and the droplet generating module (200).

상기 전기제어 인가 모듈(100)은 액적 생성을 위한 패터닝 전극(120)이 형성되어 패터닝 전극(120)에 소정 전압을 인가하여 액적 생성 모듈(200)에서 소정 크기의 액적이 생성되도록 하기 위한 구성부이다.The above electric control application module (100) is a component that forms a patterning electrode (120) for generating droplets and applies a predetermined voltage to the patterning electrode (120) to generate droplets of a predetermined size in the droplet generation module (200).

구체적으로, 상기 전기제어 인가 모듈(100)은 베이스 기재(110), 및 상기 베이스 기재(110)의 상면에 소정 패턴으로 형성되는 패터닝 전극(120)을 포함한다.Specifically, the electric control application module (100) includes a base substrate (110) and a patterning electrode (120) formed in a predetermined pattern on the upper surface of the base substrate (110).

상기 베이스 기재(110)는 유리 기재로 형성된다.The above base material (110) is formed of a glass material.

상기 패터닝 전극(120)은 상기 베이스 기재(110)의 폭방향(도면에서 세로 방향)으로 형성되는 음(-) 전극과 양(+) 전극의 한 쌍의 전극으로 구성된다.The above patterning electrode (120) is composed of a pair of electrodes, a negative (-) electrode and a positive (+) electrode, formed in the width direction (vertical direction in the drawing) of the base substrate (110).

또한, 상기 전기제어 인가 모듈(100)은 상기 패터닝 전극(120)을 보호하기 위한 보호막(130)을 더 포함한다.In addition, the electric control application module (100) further includes a protective film (130) for protecting the patterning electrode (120).

상기 보호막(130)은 폴리머 재질, 예를 들면 SU-8 포토레지스트로 구성될 수 있다.The above protective film (130) may be composed of a polymer material, for example, SU-8 photoresist.

상기한 전기제어 인가 모듈(100)은 일회용인 액적 생성 모듈(200)에 대하여 재생하여 사용할 수 있다. The above-mentioned electric control authorization module (100) can be reused for the disposable droplet generation module (200).

다시 말해서, 상기 전기제어 인가 모듈(100)은 일회용의 액적 생성 모듈(200)과 별도로 분리되어 영구 사용이 가능한 구성부이다.In other words, the above electric control authorization module (100) is a component that can be used permanently and is separated from the disposable droplet generation module (200).

다음으로, 상기 액적 생성 모듈(200)은 상기 전기제어 인가 모듈(100)의 상면에 구비되고, 상기 전기제어 인가 모듈(100)에서 인가되는 전기적 제어에 의해 마이크로 채널로 유입된 유체를 소정 사이즈의 액적으로 생성하도록 구성되는 구성부이다.Next, the droplet generation module (200) is a component provided on the upper surface of the electric control application module (100) and configured to generate a fluid introduced into a microchannel into droplets of a predetermined size by electrical control applied from the electric control application module (100).

구체적으로, 상기 액적 생성 모듈(200)은 베이스 블록(210)과, 상기 베이스 블록(210)에 형성되며, 시료(sample)가 유입되는 시료 유입구(220)와, 상기 베이스 블록(210)의 양단부에 각각 형성되는 오일 유입구(231)와 오일 유출구(232), 및 상기 오일 유입구(231)를 통해 유입되는 유체, 및 상기 시료 유입구(220)를 통해 유입되는 시료가 통과하여 상기 오일 유출구(232)로 배출되는 마이크로 채널(240)을 포함한다.Specifically, the droplet generation module (200) includes a base block (210), a sample inlet (220) formed in the base block (210) and through which a sample is introduced, an oil inlet (231) and an oil outlet (232) formed at each end of the base block (210), and a microchannel (240) through which a fluid introduced through the oil inlet (231) and a sample introduced through the sample inlet (220) pass and are discharged through the oil outlet (232).

상기 베이스 블록(210)은 PDMS(polydimethylsiloxane)로 구성될 수 있다.The above base block (210) may be composed of PDMS (polydimethylsiloxane).

상기 오일 유입구(231)와 오일 유출구(232)는 베이스 블록(210)의 길이방향의 가상의 중심 라인 상에 형성된다.The above oil inlet (231) and oil outlet (232) are formed on the imaginary center line in the longitudinal direction of the base block (210).

상기 시료 유입구(220)는 상기 가상의 중심 라인 상에 형성되되, 상기 오일 유입구(231) 측에 가까운 위치에 형성된다.The above sample inlet (220) is formed on the virtual center line, but is formed at a position close to the oil inlet (231).

상기 마이크로 채널(240)은 시료 유입구(220)에서 유입되는 시료와, 상기 오일 유입구(231)에서 유입되는 오일이 합류되는 지점에서 직교하는 방향으로 만날 수 있도록 형성된다.The above microchannel (240) is formed so that the sample flowing in from the sample inlet (220) and the oil flowing in from the oil inlet (231) can meet in a direction perpendicular to each other at the point where they join.

다시 말해서, 상기 마이크로 채널(240)은 액적 생성을 위한 대략 '+'형 액적 생성구조가 오일과 시료가 만나는 지점에 형성되고, 합류지점에서 시료가 흘러가는 방향과 오일이 합류되는 방향이 직교하게 됨으로써 액적이 형성될 수 있다.In other words, the microchannel (240) is formed at the point where the oil and the sample meet, and the direction in which the sample flows and the direction in which the oil merge become orthogonal to each other at the point of confluence, thereby allowing the formation of droplets.

구체적으로, 상기 마이크로 채널(240)은 오일 유입구(231)에서 가상의 중심 라인을 따라 소정 길이 연장되는 오일유입 선형 채널부(241)와, 상기 오일유입 선형 채널부(241)의 연장 단부에서 V자형으로 분지되는 분지 채널부(242)와, 상기 분지 채널부(242)의 각 단부에서 평행하는 연장되는 평행 채널부(243)와, 상기 평행 연장부(243)의 각 단부에서 마주하는 방향으로 연장되는 직교 채널부(244)와, 상기 직교 채널부(244) 각각의 단부에서 V자형으로 합류하는 합류 채널부(245)와, 상기 합류 채널부(245)의 합류 단부에서 오일 유출구(232)에 연결되는 유출 채널부(246), 및 일단부는 상기 시료 유입부(220)에 연결되고 타단부는 상기 합류 채널부(245)에 합류되는 시료 채널부(247)를 포함한다.Specifically, the microchannel (240) includes an oil inlet linear channel portion (241) extending a predetermined length along an imaginary center line from an oil inlet (231), a branch channel portion (242) branching in a V shape from an extended end of the oil inlet linear channel portion (241), a parallel channel portion (243) extending in parallel from each end of the branch channel portion (242), an orthogonal channel portion (244) extending in an facing direction from each end of the parallel extension portion (243), a confluence channel portion (245) joining in a V shape at each end of the orthogonal channel portions (244), an outflow channel portion (246) connected to an oil outlet (232) at the joining end of the confluence channel portion (245), and a sample channel portion (247) having one end connected to the sample inlet portion (220) and the other end joined to the confluence channel portion (245).

상기 직교 채널부(244)와 합류 채널부(245)는 한 쌍의 패터닝 전극(120) 중 일측의 전극 상부 측에 위치되게 구비된다.The above orthogonal channel portion (244) and the joining channel portion (245) are positioned on the upper side of one electrode among a pair of patterning electrodes (120).

또한, 상기 마이크로 채널(240)은 고유량 저항 채널부(248)를 더 포함할 수 있다.Additionally, the microchannel (240) may further include a high-flow resistance channel section (248).

상기 고유량 저항 채널부(248)는 본 채널에 직교하는 방향으로 지그재그(zigzag)로 파형을 이루는 파형 채널, 즉 지그재그의 U자형 흐름을 형성하는 파형 채널로 형성될 수 있다.The above high-flow resistance channel section (248) can be formed as a waveform channel that forms a zigzag waveform in a direction orthogonal to the main channel, i.e., a waveform channel that forms a zigzag U-shaped flow.

상기 고유량 저항 채널부(248)는 직교 채널부(244)와, 유출 채널부(246), 및 시료 채널부(247)에 형성될 수 있다.The above high-flow resistance channel section (248) can be formed in the orthogonal channel section (244), the outflow channel section (246), and the sample channel section (247).

여기에서, 상기 고유량 저항 채널부(248)의 채널 사이즈는 다른 채널부의 채널 사이즈보다 작게 형성된다.Here, the channel size of the high-flow resistance channel section (248) is formed smaller than the channel sizes of other channel sections.

또한, 상기 유출 채널부(246)에는 액적의 길이를 측정할 수 있는 액적길이 측정 영역이 구성될 수 있다.Additionally, a droplet length measurement area capable of measuring the length of the droplet can be configured in the above-mentioned outlet channel section (246).

다음으로, 상기 음압 형성 수단(300)은 상기 전기제어 인가 모듈(100)과 액적 생성 모듈(200) 간의 대향면에서 음압(진공)이 형성되도록 하는 구성부이다.Next, the negative pressure forming means (300) is a component that forms negative pressure (vacuum) on the opposing surface between the electric control application module (100) and the droplet generating module (200).

상기 음압 형성 수단(300)은 상기 베이스 블록(210)의 일측에 형성되는 음압 인가부(310), 및 상기 베이스 블록(210)의 하면 둘레에 형성되는 음압 형성 채널(320)을 포함한다.The negative pressure forming means (300) includes a negative pressure applying portion (310) formed on one side of the base block (210), and a negative pressure forming channel (320) formed around the lower surface of the base block (210).

이러한 음압 형성 수단(300)은 전기제어 인가 모듈(100)과 액적 생성 모듈(200) 간의 대향부에 음압을 인가(진공 형성)함으로써 전기제어 인가 모듈(100)과 액적 생성 모듈(200) 간이 결합 또는 분리 가능한다.This negative pressure forming means (300) applies negative pressure (vacuum formation) to the opposing portion between the electric control application module (100) and the droplet generation module (200), thereby enabling the electric control application module (100) and the droplet generation module (200) to be coupled or separated.

상기 음압 인가부(310)는 외부의 기기에 연결되어 음압을 인가할 수 있으며, 예를 들면 진공펌프와 연결되어 음압을 형성할 수 있다.The above negative pressure applying unit (310) can be connected to an external device to apply negative pressure, and for example, can be connected to a vacuum pump to form negative pressure.

한편, 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치의 제작 예를 도 4를 참고하여 설명한다.Meanwhile, an example of manufacturing a droplet generating device using the electrowetting phenomenon according to the present invention is described with reference to FIG. 4.

크롬 박막이 증착된 1.75 T 두께의 유리 기판(베이스 기재(110))에 SU-8(보호막(130))를 이용해서 칩 구조를 패터닝하고 2 mm 두께의 아크릴바를 붙여서 vacuum 이 잡힐 수 있는 공간을 만들어주어 PDMS 상판을 만들수 있는 몰드를 만든다(공정 (a)).A chip structure is patterned using SU-8 (protective film (130)) on a 1.75 T thick glass substrate (base substrate (110)) on which a chromium thin film is deposited, and a 2 mm thick acrylic bar is attached to create a space where a vacuum can be formed, thereby creating a mold capable of creating a PDMS upper plate (process (a)).

만들어진 몰드로 PDMS상판을 경화시킨다(공정 (b)).The PDMS top plate is cured using the created mold (process (b)).

경화된 PDMS에 2.4 um PET film 붙여서 일회용 칩 채녈을 형성한다(공정 (c)).A 2.4 um PET film is attached to the cured PDMS to form a disposable chip channel (process (c)).

재사용가능한 구성부인 전기제어 인가 모듈을 만드는 공정으로 0.7T두께의 유리 위에 크롬/금 박막이 올라간 기판에 원하는 전극 모양을 패터닝 해준다(공정 (d)).The process of making an electrical control module, which is a reusable component, involves patterning a desired electrode shape on a substrate with a chrome/gold thin film on a 0.7T thick glass (process (d)).

전극을 액체로부터 보호하기 위해서 SU-8으로 보호막 역할을 하는 층을 만들어준다(공정 (e)).To protect the electrode from liquid, a layer acting as a protective film is created using SU-8 (process (e)).

공정 (f)의 그림은 일회용 칩인 액적 생성 모듈(100)과 재사용 가능한 전기제어 인가 모듈(200)을 진공 조립한 것을 나타낸다.The drawing of process (f) shows a vacuum assembly of a disposable chip, a droplet generation module (100), and a reusable electric control application module (200).

도 6은 330Vpp 및 30kHz의 전기습윤(EW) 전압에 의해 생성된 액적의 스냅샷을 1.25ms 간격으로 촬영한 것이고, 도 7은 5개의 동일한 일회용 마이크로채널을 사용한 액적 크기의 재현성을 나타내는 그래프와 스냅샷 사진으로서 전기습윤 전압에 따른 액적 크기를 보여주는 것이며, 도 8은 150V 및 330V의 피크 대 피크(pp) 범위를 갖는 구형파 진폭 변조 EW 전압을 사용하여 단계적으로 변조된 액적 크기를 나타내는 그래프(샘플과 오일의 유속은 각각 1 및 1.5μL/min으로 설정)로서, 본 발명의 발명자는 본 발명에 따른 전기 습윤 현상을 이용하여 만족할 만한 액적 생성을 도출할 수 있음을 실험을 통해 확인하였다.FIG. 6 is a snapshot of droplets generated by an electrowetting (EW) voltage of 330 Vpp and 30 kHz taken at 1.25 ms intervals, FIG. 7 is a graph and snapshot photographs showing the reproducibility of droplet sizes using five identical disposable microchannels, showing the droplet sizes according to the electrowetting voltage, and FIG. 8 is a graph showing the droplet sizes modulated stepwise using a square wave amplitude modulated EW voltage with a peak-to-peak (pp) range of 150 V and 330 V (the flow rates of the sample and oil were set to 1 and 1.5 μL/min, respectively). The inventors of the present invention experimentally confirmed that satisfactory droplet generation can be achieved by using the electrowetting phenomenon according to the present invention.

이상에서 설명한 바와 같은 본 발명에 따른 전기 습윤 현상을 이용한 액적 생성 장치에 의하면, 기존 액적 형성 방식에 비하여 상대적으로 넓은 범위의 액적 사이즈를 형성할 수 있어 세포 생물학, DNA, 핵산 분석 등 미세 액적 형성 기술에 유용하게 이용할 수 있으며, 기구적 구조물의 변경 없이도 전압과 같은 전기적 환경 인자의 제어를 통해 원하는 사이즈를 갖는 액적을 용이하고 빠른 응답성으로 생성할 수 있는 이점이 있다.According to the droplet generation device utilizing the electrowetting phenomenon according to the present invention as described above, a relatively wide range of droplet sizes can be formed compared to existing droplet formation methods, and thus, it can be usefully used in micro-droplet formation technologies such as cell biology, DNA, and nucleic acid analysis, and has the advantage of being able to easily and quickly generate droplets having a desired size with control of electrical environmental factors such as voltage without changing the mechanical structure.

Claims (7)

전기적 제어를 일으키는 전기제어 인가 모듈;An electrical control authorization module that causes electrical control; 상기 전기제어 인가 모듈의 상면에 구비되고, 상기 전기제어 인가 모듈에서 발생되는 전기적 제어에 의해 액적을 생성하도록 구성되는 액적 생성 모듈; 및A droplet generation module provided on the upper surface of the electric control application module and configured to generate droplets by electrical control generated from the electric control application module; and 상기 전기제어 인가 모듈과 액적 생성 모듈 간의 대향면에서 음압이 형성되도록 하는 음압 형성 수단;을 포함하는 것을 특징으로 하는It is characterized by including a negative pressure forming means for forming negative pressure on the opposing surface between the electric control application module and the droplet generating module. 액적 생성 장치.Droplet generating device. 제1항에 있어서,In the first paragraph, 상기 전기제어 인가 모듈은 베이스 기재의 상면에 형성되는 패터닝 전극을 포함하며,The above electric control authorization module includes a patterning electrode formed on the upper surface of the base substrate, 상기 전기제어 인가 모듈은 상기 패터닝 전극의 상면을 커버하는 보호막을 더 포함하는 것을 특징으로 하는The above electric control application module is characterized in that it further includes a protective film covering the upper surface of the patterning electrode. 액적 생성 장치.Droplet generating device. 제1항 또는 제2항에 있어서,In claim 1 or 2, 상기 액적 생성 모듈은The above droplet generation module 베이스 블록;base block; 상기 베이스 블록에 형성되며, 시료(sample)가 유입되는 시료 유입구;A sample inlet formed on the above base block and through which a sample is introduced; 상기 베이스 블록의 양단부에 각각 형성되는 오일 유입구와 오일 유출구; 및Oil inlet and oil outlet formed at each end of the base block; and 오일 유입구를 통해 유입되는 유체, 및 상기 시료 유입구를 통해 유입되는 시료가 통과하여 상기 오일 유출구로 배출되는 마이크로 채널;을 포함하는 것을 특징으로 하는A microchannel through which a fluid flowing in through an oil inlet and a sample flowing in through the sample inlet pass and are discharged to the oil outlet; characterized in that it comprises; 액적 생성 장치.Droplet generating device. 제3항에 있어서,In the third paragraph, 상기 오일 유입구와 시료 유입구 및 오일 유출구는 동일 선상에 구비되고,The above oil inlet, sample inlet and oil outlet are provided on the same line, 상기 마이크로 채널은 상기 시료 유입구에서 유입되는 시료와, 상기 오일 유입구에서 유입되는 오일이 합류되는 지점에서 직교하는 방향으로 만날 수 있도록 형성되며,The above microchannel is formed so that the sample flowing in from the sample inlet and the oil flowing in from the oil inlet can meet in a direction perpendicular to the point where they join, 상기 시료와 오일이 합류되는 지점은 상기 패터닝 전극 중 일측의 전극 상부 측에 위치되게 구비되는 것을 특징으로 하는The point where the sample and oil meet is characterized in that it is located on the upper side of one of the patterning electrodes. 액적 생성 장치.Droplet generating device. 제4항에 있어서,In paragraph 4, 상기 마이크로 채널은 고유량 저항 채널부를 더 포함하는 것을 특징으로 하는The above microchannel is characterized in that it further includes a high-flow resistance channel section. 액적 생성 장치.Droplet generating device. 제5항에 있어서,In paragraph 5, 상기 고유량 저항 채널부는The above high-flow resistance channel section 지그재그의 U자형 흐름을 형성하는 파형 채널로 형성되는 것을 특징으로 하는Characterized by being formed by a wave channel that forms a zigzag U-shaped flow. 액적 생성 장치.Droplet generating device. 제1항에 있어서,In the first paragraph, 상기 음압 형성 수단은The above negative pressure forming means 상기 베이스 블록의 일측에 형성되는 음압 인가부; 및A negative pressure applying portion formed on one side of the base block; and 상기 음압 인가부에 연통되고, 상기 베이스 블록의 하면 둘레에 형성되는 음압 형성 채널;을 포함하는 것을 특징으로 하는characterized in that it includes a negative pressure forming channel that is connected to the negative pressure applying unit and formed around the lower surface of the base block; 액적 생성 장치.Droplet generating device.
PCT/KR2025/002841 2024-02-29 2025-02-28 Droplet generation device using electrowetting phenomenon Pending WO2025183511A1 (en)

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