WO2018151461A1 - Procédé de fabrication de dispositif microfluidique et dispositif microfluidique - Google Patents

Procédé de fabrication de dispositif microfluidique et dispositif microfluidique Download PDF

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Publication number
WO2018151461A1
WO2018151461A1 PCT/KR2018/001700 KR2018001700W WO2018151461A1 WO 2018151461 A1 WO2018151461 A1 WO 2018151461A1 KR 2018001700 W KR2018001700 W KR 2018001700W WO 2018151461 A1 WO2018151461 A1 WO 2018151461A1
Authority
WO
WIPO (PCT)
Prior art keywords
glass substrate
microfluidic chip
manufacturing
present
exemplary embodiment
Prior art date
Application number
PCT/KR2018/001700
Other languages
English (en)
Inventor
Seok Chung
Hyun Ho Kim
Dong Hee Choi
Do Hyun Nam
Original Assignee
Korea University Research And Business Foundation
Samsung Life Public Welfare Foundation
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 Korea University Research And Business Foundation, Samsung Life Public Welfare Foundation filed Critical Korea University Research And Business Foundation
Publication of WO2018151461A1 publication Critical patent/WO2018151461A1/fr

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    • 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
    • B01L3/502707—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 manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C3/00—Assembling of devices or systems from individually processed components
    • B81C3/001—Bonding of two components
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/16—Microfluidic devices; Capillary tubes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/05—Microfluidics
    • B81B2201/058—Microfluidics not provided for in B81B2201/051 - B81B2201/054
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2203/00—Forming microstructural systems
    • B81C2203/03—Bonding two components
    • B81C2203/038—Bonding techniques not provided for in B81C2203/031 - B81C2203/037

Definitions

  • the present invention relates to a microfluidic chip, and more particularly, to a method for manufacturing a microfluidic chip and a microfluidic chip capable of mass production and automatic production.
  • the PDMS chip configures a microfluidic channel according to a pattern and is used by punching holes manually or using an automatic device or without drilling the holes.
  • An object of the present invention is to provide a method for manufacturing a microfluidic chip capable of reducing a defect rate when a chip is manufactured, enabling high-speed automatic production, and manufacturing a large-capacity chip.
  • Another object of the present invention is to provide a large-capacity microfluidic chip which is manufactured by a high-speed automation system.
  • a method for manufacturing a microfluidic chip including: forming a plurality of holes on a glass substrate by punching; and bonding a silicon device to the glass substrate with the plurality of holes, wherein the silicon device forms a bottom and is located below the glass substrate.
  • a microfluidic chip including a silicon device forming a bottom; and a glass substrate bonded onto the device, wherein the glass substrate has a plurality of holes formed by punching.
  • the method for manufacturing the microfluidic chip according to the exemplary embodiment of the present invention, it is possible to reduce a defect rate when the chip is manufactured and manufacture a microfluidic chip by a high-speed automatic production method.
  • FIG. 1 illustrates a step of providing a silicon substrate and a glass substrate in a manufacturing process of a microfluidic chip according to an exemplary embodiment of the present invention
  • FIG. 2 illustrates a step of performing punching on the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIG.3 illustrates the glass substrate punched by a sand blasting method according to the exemplary embodiment of the present invention
  • FIG. 4 illustrates a PDMS device which is punched to be bonded to the glass substrate of FIG. 3 according to the exemplary embodiment of the present invention
  • FIG. 5 illustrates a step of performing a plasma treatment on the surface of the silicon device and the punched surface of the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIG. 6 illustrates a step of bonding a surface of the silicon device and a surface of the punched glass substrate which are subjected to the plasma treatment in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIGS. 7 and 8 illustrate the bonded glass substrate and PDMS device according to the exemplary embodiment of the present invention
  • FIG. 9 illustrates a step of performing UV-bonding on an upper surface of the punched glass substrate and a surface of a plastic reservoir to be bonded on the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIG. 10 illustrates a state in which the plastic reservoir is bonded on the punched glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIG. 11 illustrates a state in which a gel is injected into the completed microfluidic chip according to the exemplary embodiment of the present invention
  • FIG. 12 illustrates a state in which a cell culture medium is injected into the completed microfluidic chip according to the exemplary embodiment of the present invention.
  • FIG. 13 illustrates the microfluidic chip in which cells are cultured according to the exemplary embodiment of the present invention.
  • FIG. 1 illustrates a step of providing a silicon substrate and a glass substrate in a manufacturing process of a microfluidic chip according to an exemplary embodiment of the present invention.
  • a silicon device 100 is disposed on the lowest side to form a bottom and a glass substrate 200 may be disposed on the silicon device.
  • a poly dimethyl siloxane stamp (PDMS) device will be described as an example of the silicon device 100.
  • the microfluidic chip is manufactured by a method of performing punching on the glass substrate 200 without punching the holes on the surface of the PDMS device 100. The punching may be performed according to a punching line.
  • a cell fluid to be cultured may be injected, stored, and flowed, and a cell culturable pattern 110 may be formed.
  • a post 120 may be formed. The post 120 can prevent leakage of fluid.
  • FIG. 2 illustrates a step of performing punching on the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention.
  • the PDMS device 100 is located at the lowest part of the microfluidic chip, and in the glass substrate 200 bonded to the PDMS device 100, the punching may be performed at a part requiring the holes using sandblasting or other punching methods (for example, laser cutting, drilling, EDM, etc.).
  • FIG.3 illustrates the glass substrate punched by a sand blasting method according to the exemplary embodiment of the present invention
  • FIG. 4 illustrates a PDMS device which is punched to be bonded to the glass substrate of FIG. 3 according to the exemplary embodiment of the present invention.
  • the punching is performed by the sandblasting method and in the PDMS device 100, the punching is not performed.
  • FIG. 5 illustrates a step of performing a plasma treatment on the surface of the silicon device and the punched surface of the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention.
  • the surface of the PDMS device 100 with the pattern 110 and the surface of the glass substrate 200 are surface-modified by using a plasma cleaner and then the two surfaces are bonded to each other by contacting each other.
  • FIG. 6 illustrates a step of bonding the surface of the silicon device and the punched surface of the glass substrate which are subjected to the plasma treatment in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention.
  • the surface of the PDMS device 100 and the surface of the glass substrate 200 are subjected to the plasma treatment and then may be bonded to each other by contacting each other.
  • bonding force between the glass substrate 200 and the PDMS device 100 is enhanced to prevent the cell culture solution from being leaked.
  • FIGS. 7 and 8 illustrate the bonded glass substrate and PDMS device according to the exemplary embodiment of the present invention.
  • FIG.7 is a photograph of the bonded glass substrate 200 and PDMS device 100 taken at the top
  • FIG. 8 is a photograph of the bonded glass substrate 200 and PDMS device 100 taken at the top.
  • the PDMS device 100 and the glass substrate 200 are strongly bonded to each other so as not to be distinguished.
  • FIG. 9 illustrates a step of performing UV-bonding on an upper surface of the punched glass substrate and a surface of a plastic reservoir to be bonded on the glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention
  • FIG. 10 illustrates a state in which the plastic reservoir is bonded on the punched glass substrate in the manufacturing process of the microfluidic chip according to the exemplary embodiment of the present invention.
  • the surface of the glass substrate 200 and the surface of the plastic reservoir 300 are subjected to UV-bond treatment to be bonded to each other by contacting each other.
  • the reservoir 300 may be bonded to the top of the glass substrate so that a plurality of holes formed in the glass substrate 200 may be exposed upward.
  • the reservoir 300 may be made of a material having a smaller density than the glass substrate 200.
  • the reservoir 300 may be made of a plastic material.
  • the reservoir 300 may include a bottomless multi well plate.
  • the glass substrate 200 Since the glass substrate 200 has a relatively larger weight and relatively higher punching cost than the reservoir 300, a separate reservoir is not used, and when a thickness of the glass substrate 200 is increased to form the reservoir, the process cost may be increased and the cells may also be damaged due to the weight thereof. However, when a separate reservoir 300 having a smaller mass than the glass substrate 200 is bonded onto the glass substrate 200, it is possible to prevent the call damage while reducing the process cost.
  • FIG. 11 illustrates a state in which a gel is injected into the completed microfluidic chip according to the exemplary embodiment of the present invention.
  • the gel 130 may be injected into a space between the posts 120 and the gel 130 may be fixed due to surface tension between posts.
  • FIG. 12 illustrates a state in which a cell culture medium is injected into the completed microfluidic chip according to the exemplary embodiment of the present invention.
  • the cell culture medium 400 may be injected into a cell culture solution storage space generated by the PDMS device 100, the glass substrate 200, and the reservoir 300.
  • FIG. 13 illustrates the microfluidic chip in which cells are cultured according to the exemplary embodiment of the present invention.
  • the hydrophobicity is maintained in the chip. Accordingly, a gel or other fluids may be filled in the chip and the cell culture is possible.
  • the method for manufacturing the microfluidic chip according to the exemplary embodiment of the present invention it is possible to reduce a defect rate when the chip is manufactured and manufacture a microfluidic chip by a high-speed automatic production method.
  • the configurations and the method of the described exemplary embodiments may be limitedly applied, but the exemplary embodiments may also be configured by combining selectively all or some of the exemplary embodiments so that various modifications may be made.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Clinical Laboratory Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Sustainable Development (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un procédé de fabrication d'une puce microfluidique et une puce microfluidique permettant une production en série et une production automatique. Le procédé de fabrication d'une puce microfluidique selon un mode de réalisation donné à titre d'exemple de la présente invention peut consister à former une pluralité de trous sur un substrat en verre par perçage ; et à lier un dispositif en silicium au substrat en verre doté de la pluralité de trous, le dispositif en silicium formant un fond et étant situé au-dessous du substrat en verre.
PCT/KR2018/001700 2017-02-15 2018-02-08 Procédé de fabrication de dispositif microfluidique et dispositif microfluidique WO2018151461A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20170020458 2017-02-15
KR10-2017-0020458 2017-02-15

Publications (1)

Publication Number Publication Date
WO2018151461A1 true WO2018151461A1 (fr) 2018-08-23

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5882465A (en) * 1997-06-18 1999-03-16 Caliper Technologies Corp. Method of manufacturing microfluidic devices
US20040200724A1 (en) * 2002-09-19 2004-10-14 Teruo Fujii Microfluidic device
JP2010029790A (ja) * 2008-07-29 2010-02-12 Dainippon Printing Co Ltd エマルジョン形成用マイクロチップおよびその製造方法
US20100323447A1 (en) * 2005-10-18 2010-12-23 The Regents Of The University Of Michigan Microfluidic cell culture device and method for using same
KR20120118680A (ko) * 2011-04-19 2012-10-29 한양대학교 산학협력단 마이크로 미세유체칩 및 이를 이용한 세포배양방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5882465A (en) * 1997-06-18 1999-03-16 Caliper Technologies Corp. Method of manufacturing microfluidic devices
US20040200724A1 (en) * 2002-09-19 2004-10-14 Teruo Fujii Microfluidic device
US20100323447A1 (en) * 2005-10-18 2010-12-23 The Regents Of The University Of Michigan Microfluidic cell culture device and method for using same
JP2010029790A (ja) * 2008-07-29 2010-02-12 Dainippon Printing Co Ltd エマルジョン形成用マイクロチップおよびその製造方法
KR20120118680A (ko) * 2011-04-19 2012-10-29 한양대학교 산학협력단 마이크로 미세유체칩 및 이를 이용한 세포배양방법

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