WO2019082471A1 - マイクロチップ - Google Patents

マイクロチップ

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Publication number
WO2019082471A1
WO2019082471A1 PCT/JP2018/029538 JP2018029538W WO2019082471A1 WO 2019082471 A1 WO2019082471 A1 WO 2019082471A1 JP 2018029538 W JP2018029538 W JP 2018029538W WO 2019082471 A1 WO2019082471 A1 WO 2019082471A1
Authority
WO
WIPO (PCT)
Prior art keywords
substrate
microchip
flow path
bonding
side wall
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/JP2018/029538
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
廣瀬　賢一
誠 山中
鈴木　信二
健治 畠山
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.)
Ushio Denki KK
Original Assignee
Ushio Denki KK
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 Ushio Denki KK filed Critical Ushio Denki KK
Priority to EP18871454.7A priority Critical patent/EP3702789A4/en
Priority to US16/758,362 priority patent/US11542157B2/en
Priority to CN201880069788.8A priority patent/CN111295591B/zh
Publication of WO2019082471A1 publication Critical patent/WO2019082471A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00055—Grooves
    • B81C1/00071—Channels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2201/00—Manufacture or treatment of microstructural devices or systems
    • B81C2201/01—Manufacture or treatment of microstructural devices or systems in or on a substrate
    • B81C2201/0174—Manufacture or treatment of microstructural devices or systems in or on a substrate for making multi-layered devices, film deposition or growing
    • B81C2201/019—Bonding or gluing multiple substrate layers

Definitions

  • the present invention relates to a microchip in which a first substrate and a second substrate made of resin are respectively joined.
  • the microreactor comprises a microchip in which a microscale analysis channel or the like is formed by a semiconductor microfabrication technique on a small substrate made of, for example, silicon, silicone resin or glass.
  • a reaction analysis system using such a microreactor is referred to as a micro total analysis system (hereinafter referred to as " ⁇ TAS").
  • ⁇ TAS micro total analysis system
  • a microchip suitable for various applications can be configured by providing functional regions having various functions, such as a reaction region in which a reagent is disposed, in a flow path called a microchannel.
  • Applications of microchips include genetic analysis, clinical diagnostics, chemistry such as drug screening, biochemistry, medicine, medicine, analysis in the field of veterinary medicine, or synthesis of compounds or environmental measurement.
  • Such a microchip typically has a structure in which a pair of substrates are adhered to face each other. Then, on the surface of at least one of the substrates, fine flow paths of, for example, 10 to several hundred ⁇ m in width and 10 to several hundreds ⁇ m in depth are formed.
  • a glass substrate is mainly used because it is easy to manufacture and optical detection is also possible. Further, recently, development of microchips using a resin substrate which is lightweight but is less likely to be damaged compared to a glass substrate and which is inexpensive is being promoted.
  • FIG. 10A is a plan view showing the configuration of an example of a conventional microchip
  • FIG. 10B is an end view taken along the line AA of FIG. 10A
  • FIG. 10C is an end view taken along the line BB of FIG. 10A.
  • This microchip consists of a first substrate 70 having an inlet 72 for injecting a sample and an outlet 73 for discharging a sample, and a second substrate 75.
  • a flow path forming step 74 for forming a flow path 71 connecting the inlet 72 and the outlet 73 is formed on the surface of the first substrate 70.
  • the second substrate 75 is in the form of a flat plate having a flat surface.
  • first substrate 70 and the second substrate 75 are bonded in a state in which the respective surfaces are in close contact with each other, so that a flow surrounded by the bonding portion between the first substrate 70 and the second substrate 75 A microchip having a channel 71 is obtained.
  • Patent No. 3714338 gazette Unexamined-Japanese-Patent No. 2006-187730 JP, 2008-19348, A International Publication No. 2008/087800 Patent No. 5152361 gazette
  • the above-mentioned microchip has the following problems.
  • the first substrate 70 and the second substrate 75 to be used are used. Since the area is large, warpage is likely to occur, and in the pressure treatment and the heat treatment, the bonding surface of the first substrate 70 and the second substrate 75 is likely to be undulated. Therefore, in the bonding portion of the obtained microchip, a good bonding state can not be obtained, and as a result, there is a problem that the sample leaks out of the flow path 71.
  • the present invention has been made based on the above circumstances, and an object thereof is to provide a good bonding state at the bonding portion between the first substrate and the second substrate even if the size is large.
  • the microchip according to the present invention is formed by joining a first substrate made of resin and a second substrate made of resin, and at least a step for forming a flow path formed on the first substrate, and the first substrate and the second substrate.
  • theta 2> may satisfy 90 °.
  • the first substrate made of a resin and the second substrate made of a resin are joined, and at least the step for forming a flow path formed on the first substrate forms the first chip.
  • a portion approaching the joint surface continuous with the side wall surface has a C-chamfered shape or a R-chamfered shape.
  • a bonding portion between the first substrate and the second substrate is formed in at least a part of the peripheral portion of the first substrate and the second substrate. preferable.
  • the microchip of the present invention even when the size is large, a good bonding state can be achieved at the bonding portion between the first substrate and the second substrate. Moreover, when manufacturing the microchip, it is not necessary to increase the pressing force, to increase the heating temperature, or to extend the heating time, so it is possible to ensure the desired form of the flow path. It can be formed.
  • FIG. 2 is a cross-sectional end view taken along the line AA of FIG. 1A.
  • FIG. 2 is a cross-sectional end view taken along the line BB in FIG. 1A.
  • FIG. 2 is an explanatory cross-sectional view showing an enlarged main part of the microchip shown in FIG. It is an explanatory sectional view showing the 1st substrate and the 2nd substrate before being joined. It is explanatory drawing which shows the structure in 2nd Embodiment of the microchip of this invention. It is sectional drawing for description which expands and shows the principal part in the modification of the microchip which concerns on 1st Embodiment.
  • FIG. 8B is a cross-sectional end view taken along line AA of FIG. 8A.
  • FIG. 8B is a cross-sectional end view taken along the line BB in FIG. 8A.
  • FIG. 10B is a cross-sectional end view taken along line AA of FIG. 10A.
  • FIG. 10B is a cross-sectional end view taken along the line BB in FIG. 10A.
  • First Embodiment 1A is a plan view showing the configuration of the microchip according to the first embodiment of the present invention
  • FIG. 1B is a cross-sectional end view taken along the line AA of FIG. 1A
  • FIG. 1C is a cross-sectional end view taken along the line BB of FIG. is there.
  • the microchip 10 is formed of a plate-like body in which a first substrate 11 made of resin and a second substrate 15 made of resin are joined.
  • a flow path forming step 12 is formed on the surface (the lower surface in FIG. 1C) in contact with the second substrate 15.
  • the surface (upper surface in FIG. 1C) of the second substrate 15 in contact with the first substrate 11 is flat.
  • the flow path 17 surrounded by the bonding portion 16 between the first substrate 11 and the second substrate 15 by the flow path forming step 12 formed in the first substrate 11. Is formed.
  • One end of the flow path 17 is connected to the injection port 14 formed in the first substrate 11, and the other end of the flow path 17 is connected to the discharge port 19 formed in the first substrate 11.
  • the noncontact portion step 13 is formed so as to surround the bonding portion 16, and the noncontact portion step 13 Between the substrate 11 and the second substrate 15, a noncontact portion 18 surrounding the bonding portion 16 is formed.
  • a silicone resin such as polydimethylsiloxane, a cycloolefin resin, an acrylic resin or the like can be used.
  • the thickness of each of the first substrate 11 and the second substrate 15 is not particularly limited, and is, for example, 0.5 to 7 mm.
  • the width of the flow path 17 (in the illustrated example, the width of the flow path forming step 12) is, for example, 0.1 to 3 mm.
  • the height of the flow path 17 (the depth of the flow path forming step 12 in the illustrated example) is, for example, 0.05 to 1 mm.
  • an angle ⁇ 1 between the side wall surface 12 a of the flow path forming step 12 and the bonding surface 10 a continuous thereto (hereinafter simply referred to as “angle also referred to as theta 1 ".) it is assumed to satisfy the ⁇ 1> 90 °, preferably 120 ° ⁇ ⁇ 1> 90 ° , more preferably 100 ° ⁇ ⁇ 1> 90 ° . If the angle theta 1 is 90 ° or less, when the first substrate 11 manufactured by injection molding, there is a possibility that the first substrate 11 does not come off from the mold.
  • the angle ⁇ 1 when the angle ⁇ 1 is excessive, the area of the bottom 12 c (the upper surface of the flow path 17 in FIG. 2) of the flow path forming step 12 decreases and the side wall surface 12 a which is a slope in the flow path 17 is occupied. Since the ratio increases, variations occur due to the flow velocity distribution of the sample to be circulated and the deviation of the reaction rate. Therefore, a predetermined action such as a biochemical reaction of a sample generated in the flow path 17 can not be realized. In addition, when performing optical observation with an optical microscope, the side wall surface 12a is refracted to make observation difficult, and the observable region is only the bottom portion 12c with a reduced area, so that accurate observation can not be performed, etc. It occurs.
  • a plan view of the microchip 10, the area S 1 of the microchip 10, and the area S 2 of the joint surface 10a is, it is preferable to satisfy the S 2 / S 1 ⁇ 0.5, more preferably 0 .03 ⁇ S 2 / S 1 ⁇ 0.3.
  • the bonding area becomes large, so that it is difficult to absorb warpage and waviness.
  • the width of the bonding surface 10a between the flow path 17 and the non-contacting portion 18 is preferably 50 ⁇ m or more, more preferably 500 to 2000 ⁇ m.
  • the width of the bonding surface 10a is less than 50 ⁇ m, the bonding surface 10a itself becomes small, and thus the first substrate 11 and the second substrate 15 which have been bonded by mechanical stress are easily peeled off. .
  • the pressure at the joint surface 10a may be high, and the joint 16 may be crushed or cracked.
  • the above-mentioned microchip 10 can be manufactured, for example, as follows. First, as shown in FIG. 3, the first substrate 11 and the second substrate 15 made of resin are manufactured. A step 12 for flow path formation and a step 13 for noncontact portion are formed on the surface of the first substrate 11. On the other hand, the surface of the second substrate 15 is flat. As a method of manufacturing the first substrate 11 and the second substrate 15, resin molding methods such as an injection molding method and a cast molding method can be appropriately selected according to the resin used. Then, a surface activation process is performed on the surfaces to be bonded surfaces of each of the first substrate 11 and the second substrate 15. As this surface activation process, an ultraviolet irradiation process of irradiating vacuum ultraviolet rays having a wavelength of 200 nm or less, or a plasma process of contacting atmospheric pressure plasma from an atmospheric pressure plasma apparatus can be used.
  • an excimer lamp such as a xenon excimer lamp having a bright line at a wavelength of 172 nm, a low pressure mercury lamp having a central wavelength of 185 nm, a wavelength of 120 to 200 nm
  • Deuterium lamps having a strong emission spectrum in the range can be suitably used.
  • the illuminance of the vacuum ultraviolet light applied to the surface of each of the first substrate 11 and the second substrate 15 is, for example, 10 to 500 mW / cm 2 .
  • the irradiation time of vacuum ultraviolet light to the surface of each of the first substrate 11 and the second substrate 15 is appropriately set in accordance with the resin constituting the first substrate 11 and the second substrate 15, but 5 to 6 seconds.
  • the plasma generation gas one containing nitrogen gas, argon gas, etc. as a main component and containing 0.01 to 5% by volume of oxygen gas should be used. preferable.
  • a mixed gas of nitrogen gas and clean dry air (CDA) The operating conditions of the atmospheric pressure plasma apparatus used for plasma processing are, for example, a frequency of 20 to 70 kHz, a voltage of 5 to 15 kVp-p, and a power value of 0.5 to 2 kW.
  • the processing time by atmospheric pressure plasma is, for example, 5 to 100 seconds.
  • the first substrate 11 and the second substrate 15 thus surface-activated are laminated such that their respective surfaces are in contact with each other. Then, the first substrate 11 and the second substrate 15 are bonded by heating as necessary in a state of being pressed in the thickness direction by its own weight or by applying pressure from the outside.
  • specific conditions of pressurization and heating are appropriately set according to the materials constituting the first substrate 11 and the second substrate 15. Specifically, the pressure is, for example, 0.1 to 10 MPa, and the heating temperature is, for example, 40 to 130 ° C.
  • the angle theta 1 is, satisfies ⁇ 1> 90 °.
  • pressure is intensively applied to a portion to be the bonding portion 16 in the first substrate 11 and the second substrate 15.
  • a good bonding state can be achieved at the bonding portion 16 between the first substrate 11 and the second substrate 15 even if the size is large.
  • the flow path 17 of the desired form is used. It can be formed reliably.
  • FIG. 4 is an explanatory cross-sectional view showing the configuration of the main part in the second embodiment of the microchip of the present invention.
  • the microchip 10 has the same configuration as the microchip 10 according to the first embodiment except for the following points.
  • a portion approaching the bonding surface 10 a continuing to the respective side wall surfaces 12 a and 13 a (Hereinafter, it is also referred to as “a location near the bonding portion”) 12b and 13b are C-chamfered.
  • the angle theta 1 is, for example, a range of 140 ° ⁇ ⁇ 1 ⁇ 90 ° .
  • the non-contacting portion 18 is formed to surround the bonding portion 16 formed around the flow path 17, and the side wall surface 12a and the non-contacting portion of the flow path forming step 12 Since the portions 12b and 13b in the vicinity of the bonding portion in each of the side wall surfaces 13a of 18 are C-chamfered, when bonding the first substrate 11 and the second substrate 15, the first substrate 11 and the The pressure is concentrated on the portion of the second substrate 15 to be the bonding portion 16. As a result, even if the first substrate 11 and the second substrate 15 are warped, they are bonded in a state in which the surfaces to be bonding surfaces are in close contact with each other.
  • the microchip 10 of the present invention a good bonding state can be achieved at the bonding portion 16 between the first substrate 11 and the second substrate 15 even if the size is large. Moreover, when manufacturing the microchip 10, it is not necessary to increase the pressure, increase the heating temperature, or increase the heating time, so the flow path 17 of the desired form is It can be formed reliably.
  • the angle ⁇ 2 between the side wall surface 13 a of the non-contact portion 18 and the bonding surface 10 a continuous thereto (hereinafter simply referred to as “the angle ⁇ 2 ”
  • the angle ⁇ 2 Preferably satisfy ⁇ 2 > 90 °, more preferably 150 ° ⁇ ⁇ 2 > 90 °, and still more preferably 120 ° ⁇ ⁇ 2 > 90 °.
  • the pressure is higher at the portion to be the bonding portion 16 in the first substrate 11 and the second substrate 15 Join more intensively. Therefore, even when the size is large, a good bonding state can be achieved more reliably at the bonding portion 16 between the first substrate 11 and the second substrate 15.
  • the near portion 13b may have a C-chamfered shape or an R-chamfered shape.
  • the bottom surface and the side wall surface 12a of the flow path forming step 12 are each flat, but as shown in FIG. 7, the bottom surface and the side wall surface 12a are continuous with each other. It may be a curved surface.
  • the angle ⁇ 1 corresponds to the tangent T of the side wall surface 12 a at the intersection of the side wall surface 12 a of the flow path forming step 12 and the bonding surface 10 a in a cross section perpendicular to the direction in which the flow path 17 extends. And the joint surface 10a.
  • the bonding portion 16 between the first substrate 11 and the second substrate 15 may be formed.
  • the width of the bonding surface 10a formed at the peripheral portion of the first substrate 11 and the second substrate 15 is preferably 50 ⁇ m or more, and more preferably 500 to 3000 ⁇ m. It is preferable that the bonding surface 10 a formed in the peripheral portion is bonded with a width larger than the width of the bonding surface 10 a between the flow path 17 and the non-contact portion 18.
  • the microchip 10 can easily withstand mechanical stress applied in the direction in which the first substrate 11 and the second substrate 15 peel off.
  • the area S 2 of the joint surface 10a has a passage 17 and the area of the joint surface 10a between the non-contact portion 18, the first substrate 11 and the second joint surface 10a formed on the periphery of the substrate 15 The sum of the area and
  • the flow path forming step 12 formed on the first substrate 11 and the flow path forming step formed on the second substrate 15 may be formed by the step 20.
  • the angle ⁇ 3 formed by the side wall surface 20 a of the flow path forming step 20 in the second substrate 15 and the bonding surface 10 a continuous thereto is ⁇ 3 > 90. Is preferably 120 °° ⁇ 3 > 90 °, more preferably 100 ° ⁇ ⁇ 3 > 90 °.
  • each of the microchips 10 shown in FIGS. 1 to 9 is an example in which the noncontact portion 18 is formed separately from the flow path 17, in the microchip of the present invention, the noncontact portion is It may double as a flow path.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Manufacturing & Machinery (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Dispersion Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Micromachines (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/JP2018/029538 2017-10-27 2018-08-07 マイクロチップ Ceased WO2019082471A1 (ja)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP18871454.7A EP3702789A4 (en) 2017-10-27 2018-08-07 MICROCHIP
US16/758,362 US11542157B2 (en) 2017-10-27 2018-08-07 Microchip
CN201880069788.8A CN111295591B (zh) 2017-10-27 2018-08-07 微芯片

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2017207839A JP6939415B2 (ja) 2017-10-27 2017-10-27 マイクロチップ
JP2017-207839 2017-10-27

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WO2019082471A1 true WO2019082471A1 (ja) 2019-05-02

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US (1) US11542157B2 (enExample)
EP (1) EP3702789A4 (enExample)
JP (1) JP6939415B2 (enExample)
CN (1) CN111295591B (enExample)
TW (1) TWI806882B (enExample)
WO (1) WO2019082471A1 (enExample)

Cited By (4)

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WO2021039296A1 (ja) * 2019-08-30 2021-03-04 ウシオ電機株式会社 マイクロチップ
JP2021185894A (ja) * 2020-06-04 2021-12-13 ウシオ電機株式会社 マイクロ流体デバイス
JP2021185893A (ja) * 2020-06-04 2021-12-13 ウシオ電機株式会社 マイクロ流体デバイス
EP3964840A4 (en) * 2019-05-23 2022-06-29 Ushio Denki Kabushiki Kaisha Microchip

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