WO2015098719A1 - Thermally conductive microchemical chip - Google Patents

Thermally conductive microchemical chip Download PDF

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Publication number
WO2015098719A1
WO2015098719A1 PCT/JP2014/083648 JP2014083648W WO2015098719A1 WO 2015098719 A1 WO2015098719 A1 WO 2015098719A1 JP 2014083648 W JP2014083648 W JP 2014083648W WO 2015098719 A1 WO2015098719 A1 WO 2015098719A1
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WO
WIPO (PCT)
Prior art keywords
flow path
substrate sheet
thermally conductive
sheet
silicone rubber
Prior art date
Application number
PCT/JP2014/083648
Other languages
French (fr)
Japanese (ja)
Inventor
和久 高木
高野　努
優也 生方
Original Assignee
株式会社朝日Ｆｒ研究所
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Application filed by 株式会社朝日Ｆｒ研究所 filed Critical 株式会社朝日Ｆｒ研究所
Priority to JP2015554815A priority Critical patent/JP6131337B2/en
Publication of WO2015098719A1 publication Critical patent/WO2015098719A1/en

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    • 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
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44756—Apparatus specially adapted therefor
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • 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
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • 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
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)
    • G01N2035/00366—Several different temperatures used
    • 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
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid

Definitions

  • the present invention relates to a device for analyzing a trace amount by using a biological specimen as a test substance and flowing the biocomponents through a fine flow path, and a raw material component of a useful substance such as a bio ingredient exhibiting a pharmacological action and a reagent such as a reaction substrate. It is used by attaching to a microreactor that chemically synthesizes these useful substances in a micro-reactor, or a microbiochemical processor for cell growth, etc.
  • the present invention relates to a thermally conductive microchemical chip that conducts to the inside of a flow path.
  • test sample that is a biological sample such as blood or urine in a microliter order
  • the amount of enzyme reaction that acts on the substrate in the sample and its base mass are determined as the enzyme or substrate.
  • a microbiochip is used for quantification based on the degree of coloring by a reagent that develops color.
  • an enzyme-containing membrane is used to convert the amount of enzyme reaction into an electrical signal with an electrode to quantify the substrate mass, DNA extraction and its polymerase chain reaction (PCR) amplification, ion concentration measurement, nucleic acid, sugar
  • PCR polymerase chain reaction
  • ion concentration measurement ion concentration measurement
  • nucleic acid sugar
  • microreactor chip is used when microsynthesis of protein or peptide is performed on the order of ⁇ M.
  • microbiochemical chips are used for growing useful cells and viruses and attaching cancer cells for examination.
  • Microchemical chips such as microbiochips, microreactor chips, and microbiochemical chips pressurize and feed fluid samples such as specimens such as suspensions and solutions, liquid reagents and cell fluids, As a reaction channel for flowing, mixing, reacting, separating, adhering, and detecting, it has a groove-like fine channel.
  • a microchemical chip is a fine channel of several tens to several hundreds ⁇ m on an inorganic base material such as a stainless steel base, silicon base, quartz base or glass base, or an organic base such as a resin base or a rubber base. Is formed by cutting or etching.
  • a microchemical chip formed of an organic substrate has a fine flow path and is formed of a highly transparent plastic resin as in Patent Document 1. Since a resin base material and a rubber base material are easy to mold and cut, a microchemical chip formed by sticking them with an adhesive or heat-sealing them is suitable for mass production. In particular, it is convenient for optical system analysis when it is formed of a transparent organic substrate or inorganic substrate.
  • a metal thin film such as an aluminum foil may be bonded to the back surface of the microchemical chip via an adhesive layer. Since the metal thin film has good thermal conductivity, it dissipates heat when it is necessary to cool the microchemical chip, and conducts heat when the microchemical chip is heated with a heater.
  • inorganic and organic substrates and metal thin films are only bonded by physical interaction due to intermolecular forces via an adhesive layer, they are bonded with a strong bonding force as much as a covalent bond. Not. Therefore, when a specimen, a reagent, or a sample is pressurized and fed into a fine channel, the thermal expansion coefficient between the inorganic base material and the metal thin film is different, or the fine channel is expanded according to the high pressure. Due to the fact that the metal thin film cannot follow the deformation of the organic base material, the inorganic base material, the organic base material, and the metal thin film are easily peeled off to form a gap.
  • the heat inside the microchemical chip cannot be dissipated sufficiently and uniformly, and because the sample, reagent, and sample are decomposed in the flow path of the microchemical chip, microanalysis cannot be performed accurately, Insufficient trace synthesis leaves raw material components and reaction substrates or induces side reactions, kills living cells, or degrades viruses.
  • the gap it is difficult to conduct heat when the microchemical chip is heated with a heater, it cannot be heated sufficiently and uniformly, and the sample or reagent does not react in the microchemical chip and the microanalysis cannot be performed accurately.
  • the raw material components and reaction substrate do not react due to insufficient microsynthesis.
  • the metal thin film does not transmit light, even if the microchemical chip is formed at a corner using a transparent organic or inorganic substrate, it cannot be used for optical system analysis.
  • a precious sample such as a small amount of a biological sample, a thin and small amount of a reagent, or a sample such as a delicate cell or virus can be pressurized with a high pressure or a capillary tube.
  • a fine flow path that flows due to the phenomenon is reliably formed, can be accurately and reliably sent to the flow path as desired, and when it is allowed to cool, it should not be exposed to high temperatures due to heat dissipation or heated by a heater It can be heated in some cases, and it can accurately and easily analyze, react, incubate, and amplify biocomponents, useful chemicals in reagents, and samples of cells and viruses in a short period of time.
  • An object is to provide a simple and small thermally conductive microchemical chip that can be manufactured.
  • the thermally conductive microchemical chip of the present invention made to achieve the above object is a flow in which a fluid sample selected from a specimen, a reagent, and a sample is injected by pressurization and / or capillary action to cause a chemical reaction and / or a chemical action.
  • a flow path maintenance substrate sheet that opens a delivery hole connected to the flow path and supports the flow path supporting substrate sheet covering the flow path in contact with the uppermost surface and / or the lowermost surface thereof, and is stacked, Directly and / or by at least one of dry treatment and molecular adhesive treatment selected from corona treatment, plasma treatment and ultraviolet irradiation treatment on at least any sheet surface It is joined and integrated by indirect covalent bonding via the molecular adhesive, and the flow path and the delivery hole of each of the flow path carrying substrate sheet and the flow path maintenance substrate sheet flow.
  • the ultraviolet irradiation treatment is not limited as long as it is a treatment for irradiating ultraviolet rays, but may be a general ultraviolet ray treatment (UV treatment) for irradiating ultraviolet rays in a wide wavelength region or a plurality of wavelengths, and is regarded as a single wavelength.
  • UV treatment general ultraviolet ray treatment
  • Excimer ultraviolet treatment excimer UV treatment
  • excimer ultraviolet rays to be applied may be used.
  • the thermally conductive microchemical chip may be one in which at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
  • the silicone rubber may contain a platinum catalyst.
  • the silicone rubber may contain a silane coupling agent having 6 to 12 carbon atoms having a vinylmethoxysilyl group.
  • At least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet includes diatomaceous earth, mica, talc and / or kaolin.
  • At least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet includes at least one flame retardant selected from antimony trioxide and aluminum hydroxide. Also good.
  • the covalent bond may be an ether bond.
  • the thermally conductive microchemical chip includes a silicone rubber raw material composition in which at least a part of the flow path supporting substrate sheet or the flow path maintaining substrate sheet is blended with glass beads and / or zeolite, and silicone in which a water-soluble alcohol is blended. It may be a foamable silicone rubber sheet formed of at least one selected from the composition.
  • the thermally conductive microchemical chip is formed of silicone rubber in which at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is dispersed with anatase type or rutile type titanium oxide particles, It may be a highly reflective silicone rubber sheet having a reflectance of 80 to 100%.
  • At least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is made of silicone rubber, ethylene-propylene-diene-methylene copolymer rubber, butyl rubber, acrylonitrile-butadiene copolymer.
  • the gas permeability of at least one of oxygen gas, nitrogen gas, carbon dioxide gas and water vapor is set to 500-0. It may be a low gas permeable silicone rubber sheet of 05 (cc / cm 2 / mm / sec / cm ⁇ Hg ⁇ 10 10 ).
  • At least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is a peroxide crosslinked silicone rubber, an addition crosslinked silicone rubber, a condensation crosslinked silicone rubber, a radiation crosslinked or an electron beam crosslinked. It may be formed of any one selected from silicone rubbers and co-blends of any of these silicone rubbers and olefinic rubbers.
  • the thermally conductive microchemical chip may be one in which a part of the flow path is enlarged to form a liquid reservoir.
  • the method for producing a thermally conductive microchemical chip according to the present invention includes a chemical reaction in which a fluid sample selected from a specimen, a reagent, and a sample is poured into a single or a plurality of rubber channel support substrate sheets by pressurization and / or capillary action.
  • a flow path forming step for providing a flow path for chemical action, and formed with rubber, resin, metal, ceramics and / or glass, and having a delivery hole connected to the flow path, At least one of the delivery hole forming step for forming the sandwiched flow path maintenance substrate sheet and the flow path carrying substrate sheet and the flow path maintenance substrate sheet, corona treatment, plasma treatment, and ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and at least one of the flow path carrying substrate sheet and the flow path maintenance substrate sheet under normal pressure, increased pressure, or reduced pressure.
  • the delivery hole forming step for forming the sandwiched flow path maintenance substrate sheet and the flow path carrying substrate sheet and the flow path maintenance substrate sheet, corona treatment, plasma treatment, and ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and at least one of the flow path carrying substrate sheet and the flow path maintenance substrate sheet under normal pressure, increased pressure, or reduced pressure.
  • the method for producing a heat conductive microchemical chip may be one in which at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
  • the heat-conductive microchemical chip of the present invention is sufficient because the heat-conductive sheet made of silicone rubber is easy to dissipate heat when a flowing sample is poured into its fine flow path by pressurization at high pressure or capillary action. Allow to cool. Therefore, precious specimens such as trace amounts of biological specimens, fluid specimens such as dilute and trace amounts of reagents, delicate cell / virus samples, etc. are not exposed to high temperatures, but are unexpectedly decomposed or made impurities by side reactions. It can be analyzed, reacted, cultured and amplified as desired without being killed or decomposed. In addition, even when the heat conductive microchemical chip is intentionally heated by a heater, the heat conductive sheet made of silicone rubber is easy to conduct heat, so that it can be quickly heated and maintained at an appropriate temperature.
  • the channel-carrying substrate sheet and the channel-maintaining substrate sheet are directly bonded to each other by a strong bond by a direct chemical intermolecular bond, that is, an ether bond. It is firmly joined at the joint surface outside the flow path region. For this reason, a fine flow path that allows the fluid sample to flow under high pressure without leaking is reliably formed.
  • This thermally conductive microchemical chip is a linear combination of straight lines and curved lines on each of one or a plurality of flow path carrying substrate sheets, and a complicated pattern shape that is enlarged or converged or branched at the end or halfway.
  • a fine flow path with a width of 5 ⁇ m to 5 mm can be precisely formed. Even when such a fine flow path is provided, when the fluid, which is a specimen or a reagent, is pressurized and sent and flows through the flow path, the flow path supporting substrate sheet and the flow path maintaining substrate sheet are Since it does not peel off, this thermally conductive microchemical chip is not damaged.
  • This thermally conductive microchemical chip can be used in a fine flow path at a pressure of normal pressure to about 5 atm. Even when a fluid or gaseous sample, reagent, cell fluid, or other fluid sample is sent, it is cooled to 120 ° C under ice cooling. Even if samples and reagents are fed repeatedly while heating and cooling in the low to high temperature range of 0 to 100 ° C or 20 to 120 ° C for general purposes, the flow path breaks due to the rubber elasticity of the flow path support substrate sheet do not do.
  • thermoly conductive microchemical chip it is possible to send a fluid sample, which is a specimen, a reagent, or a sample, to a desired flow path reliably and accurately while maintaining a desired temperature.
  • useful substances such as biocomponents in the specimen can be analyzed accurately and simply in a short period of time, or raw materials components of useful substances such as biocomponents exhibiting pharmacological action and reagents such as reaction substrates can be reacted as intended. Or cultivate and amplify cells and whistles.
  • This thermally conductive microchemical chip makes the flow path of the flow path carrying substrate sheet fine and suppresses contact between the specimen, reagent or sample and the flow path carrying substrate sheet or flow path maintenance substrate sheet as much as possible. Unexpected contamination and adsorption of reagents and samples can be prevented.
  • thermally conductive microchemical chip When this thermally conductive microchemical chip is used in a disposable manner, there is no fear of contamination due to mixing of another specimen, reagent or sample, and a reliable result can be obtained.
  • This thermally conductive microchemical chip has an outer shape of several mm to several tens of cm square, is extremely small, and can have a simple structure.
  • This thermally conductive microchemical chip has a large number of series, parallel, or branched flow paths in a planar and / or three-dimensional shape, and is provided with a large number of inlets and outlets so that a plurality of reaction processes are connected in series or in parallel. Or it can be made into a multi-function which goes through three-dimensional and infinite length and breadth. Therefore, a plurality of types of qualitative / quantitative analyzes can be quickly performed not only indoors but also outdoors using a portable analyzer without using a large analyzer.
  • thermoly conductive microchemical chip of the present invention it is very simple and can produce a high-quality and homogeneous thermally conductive microchemical chip in a large quantity at a low yield with a high yield.
  • a method for producing a thermally conductive microchemical chip uses a thermally conductive sheet containing a thermally conductive filler powder, when it is not to be exposed to high temperature due to heat dissipation when it is allowed to cool, or when it is to be heated with a heater.
  • a heat conductive microchemical chip that can be heated can be easily manufactured.
  • the channel-carrying substrate sheet and the channel-maintaining substrate sheet directly form a covalent bond such as an ether bond by contact outside the channel region, which is simpler than the adhesive. Strongly joined to.
  • Such molecular adhesion does not require heating at such a high temperature as to cause the thermoplastic resin to be thermally fused, and is sufficiently induced if heated for a short time at a temperature lower than the thermal fusion temperature. Therefore, there is no refractive index variation or thermal deformation / distortion that hinders the accuracy of optical analysis.
  • FIG. 1 An example of the thermally conductive microchemical chip 1 to which the present invention is applied is as shown in FIG. 1 showing the process of manufacturing the polyimide channel maintaining substrate sheet 10 that also serves as a cover, and a polyimide channel that also serves as a bottom support.
  • a silicone rubber flow path carrying substrate sheet 20 having fine flow paths is overlapped with the maintenance substrate sheet 30 and is flexible.
  • the flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection portion 21, the flow sample discharge portion 22, and the flow path 26 pressurize a flow sample selected from a specimen, a reagent, and a sample to cause a chemical reaction.
  • the flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection part 21, the flow sample discharge part 22, and the flow path 26 are connected to the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20. And / or recessed in a groove shape on the back surface, or penetrating in a groove shape or a hole shape.
  • the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are joined and integrated.
  • the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are obtained by superimposing the joint surfaces thereof by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). is there.
  • the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 are subjected to corona treatment except for the flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection portion 21, the flow sample discharge portion 22, and the flow passage 26.
  • Active groups generated by plasma treatment or ultraviolet irradiation treatment for example, reactive active groups such as hydroxyl groups (—OH) and hydroxysilyl groups (—SiOH) are shared. It is integrated so that it cannot be peeled by direct chemical bonding and strong bonding.
  • Such an ether bond is preferably an ether bond by dehydration of OH groups.
  • the flow path carrying substrate sheet 20 is formed by molding from a composition containing a silicone rubber raw material component.
  • the main component of the silicone rubber in the channel-carrying substrate sheet 20 is peroxide-crosslinked silicone rubber, addition-crosslinked silicone rubber, condensation-crosslinked silicone rubber, or a co-blend of these silicone rubber and olefin rubber.
  • any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are selected from aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride, boron nitride, and aluminum nitride. It is a thermally conductive sheet containing conductive filler powder.
  • the heat conductive filler powder is contained in the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 in an amount of 50 to 95% by weight, respectively.
  • the heat conductive filler powder preferably has an average particle size of 0.2 to 50 ⁇ m.
  • any or all of the channel-carrying substrate sheets 20 may be easily covalently bonded to each other with active groups generated by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment).
  • Platinum catalyst for example, 1,3-divinyl-1,1,3,3-tetramethyldisiloxane platinum (0) catalyst (Pt (dvs)) 2.1-2.4% xylene solution (product of Gelest)
  • Pt (dvs) 1,3-divinyl-1,1,3,3-tetramethyldisiloxane platinum (0) catalyst (Pt (dvs)) 2.1-2.4% xylene solution (product of Gelest)
  • Such a platinum complex is preferably contained at a concentration of 10 to 1000 ppm in terms of platinum.
  • any or all of the channel-carrying substrate sheets 20 contain 2 to 6 units of a silane coupling agent having a vinylalkoxysilyl group having a vinylalkoxysilyl group, for example, polyvinyl methoxysiloxane at a concentration of 0.5 to 10 parts by weight. It is preferable to include.
  • the vinyl group of the silane coupling agent and the vinyl group or hydrogensiloxane group in the silicone rubber polymer can be more strongly bonded by a covalent bond different from the ether bond covalently bonded by a peroxide or a platinum catalyst. At this time, it is preferable that a platinum catalyst is contained because it becomes easier to covalently bond.
  • any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made of antimony trioxide and aluminum hydroxide, which have a flame retardant action, to impart a flame retardant function. It may be included. These powders are included in the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 in an amount of 5 to 50% by weight and preferably have an average particle size of 5 to 20 ⁇ m.
  • any or all of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 contain 0.5 to 30% by weight of silicone oil, for example, polydimethylsiloxane, methylphenylsiloxane, or fluorosilicone oil. May be. Silicone oil is added to silicone rubber in order to provide an effect of easily adding a filler.
  • any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 may be formed of foamable silicone rubber so that the reflectance can be increased and the function of the valve can be expressed.
  • the foamable silicone rubber is formed by molding from a silicone rubber composition containing a foamable silicone rubber component exemplified by a silicone rubber composition containing glass beads and zeolite and a silicone composition containing a water-soluble alcohol. Yes.
  • Either or all of the flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 have a high reflectance so that detection can be performed with high sensitivity by light such as fluorescence detection.
  • the rutile-type titanium oxide particles may be dispersed and molded, and may be formed by molding from a silicone rubber composition containing a high reflectance component exemplified by the titanium oxide-containing silicone composition. As a result, the reflectivity of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is 80 to 100%.
  • the flow path carrying substrate sheet 20 may be formed of other rubber. Silicone rubber, ethylene-propylene-diene-methylene copolymer so that the channel-carrying substrate sheet 20 has low gas permeability so that it is not affected by external oxygen, carbon dioxide, water vapor (humidity), etc. It is preferably formed of rubber (EPDM), butyl rubber, acrylonitrile-butadiene copolymer rubber (NBR), fluorine rubber, styrene-butadiene copolymer rubber (SBR), or hydrin rubber.
  • EPDM rubber
  • butyl rubber acrylonitrile-butadiene copolymer rubber
  • NBR acrylonitrile-butadiene copolymer rubber
  • SBR styrene-butadiene copolymer rubber
  • the flow path carrying substrate sheet 20 has a gas permeability of at least one of oxygen gas, nitrogen gas, carbon dioxide gas and water vapor of 500 to 0.05 (cc / cm 2 / mm / sec / cm ⁇ It becomes a low gas permeable silicone rubber sheet of Hg ⁇ 10 10 ).
  • the flow path maintaining substrate sheet 20 may be formed of a cycloolefin polymer (COP), an aluminum foil, an aluminum plate, or a glass plate. It may be formed of silicone exemplified as a material for use, and may be formed including a flame retardant.
  • COP cycloolefin polymer
  • the flow path maintaining substrate sheet 20 may be formed of silicone exemplified as a material for use, and may be formed including a flame retardant.
  • the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 may be joined and integrated by covalent bonding via a molecular adhesive.
  • the molecular adhesive means that the functional group in the molecule chemically reacts with the adherend by covalent bonding, so that the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made to be a single molecule or a polymolecule. It is directly bonded through a covalent bond by the molecular adhesive molecule.
  • the molecular adhesive forms a covalent bond by chemically reacting with the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 having two functional groups as adherends. And, specifically, various coupling agents including a silane coupling agent.
  • molecular adhesives such as triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol (TES), aminoethylaminopropyl trimethoxysilane;
  • a triazine compound having a trialkoxysilylalkylamino group such as a triethoxysilylpropylamino group and a mercapto group or an azide group, the following chemical formula (I) (In formula (I), W may be a spacer group, for example, an alkylene group which may have a substituent, an aminoalkylene group, or a direct bond.
  • Y is an OH group or A reactive functional group that generates an OH group by decomposition or elimination, such as a trialkoxyalkyl group
  • -Z is -N 3 or -NR 1 R 2 (provided that R 1 and R 2 are the same or different; H or an alkyl group, —R 3 Si (R 4 ) m (OR 5 ) 3-m
  • R 3 and R 4 are alkyl groups, R 5 is H or an alkyl group, and m is 0 to 2.
  • An alkylene group , An alkoxy group and an alkyl group are linear, branched and / or cyclic hydrocarbon groups having 1 to 12 carbon atoms which may have a substituent;
  • An epoxy compound having a trialkyloxysilylalkyl group; Vinyl represented by CH 2 CH-Si (OCH 3 ) 2 -O- [Si (OCH 3 ) 2 -O
  • the flow path maintaining substrate sheet 10/30 and the flow path supporting substrate sheet 20 are made of silicone rubber, it is sufficient to perform corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). Since active groups are expressed, they may be joined directly, but may be joined using a molecular adhesive such as the silane coupling agent.
  • the flow path maintaining substrate sheet 10/30 is a resin made of non-silicone rubber, it is dipped in a 0.05 to 1% by weight alcohol solution such as a methanol solution of a molecular adhesive such as the silane coupling agent and dried. Then, it is preferable to be joined. If the concentration of the molecular adhesive solution is too high, the joint surface between the two sheets will be peeled off, and if it is too thin, the two sheets cannot be sufficiently joined.
  • a groove-like microchannel 26 is formed through the front and back surfaces of the channel-carrying substrate sheet 20 by pressurizing and flowing a fluid sample, which is a liquid or gaseous specimen or reagent, to cause a chemical reaction.
  • the micro flow path 26 extends from the flow sample injection sites 21a and 21b, which are the starting point ends, and merges downstream, and from there to a tributary that extends to the flow sample discharge site 22a and a main flow that extends to the flow sample discharge sites 22b and 22c.
  • the main flow is branched and extends downstream to the flow sample discharge portions 22b and 22c which are the end points at the downstream end.
  • the upper surface 24 and the lower surface 25 of the channel-carrying substrate sheet 20 are activated by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) outside the region of the fine flow passage 26. ing.
  • Injection holes 11a and 11b and fluid sample discharge holes 12a, 12b, and 12c are opened.
  • the lower surface 15 of the cover flow path maintenance substrate sheet 10 facing the flow path carrying substrate sheet 20 is outside the region of the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b and 12c, and the surface thereof is corona. It is activated by treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment).
  • the upper surface 34 of the flow path maintenance substrate sheet 30 for supporting the bottom surface facing the flow path carrying substrate sheet 20 is entirely corona-treated, plasma-treated or ultraviolet-irradiated (general UV treatment or excimer UV treatment). It has been activated.
  • the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 facing each other are chemically directly bonded.
  • the joint surfaces are subjected to corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). Then, after overlapping at normal pressure, it may be covalently bonded under normal pressure, but may be covalently bonded under reduced pressure or under pressure.
  • the active groups such as OH of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 or the reactive functional group of the silane coupling agent that reacts with them is under reduced pressure or vacuum conditions, for example, 50 torr.
  • At least one of the sheets 10 is stacked with one or a plurality of flow path maintaining substrate sheets 10, 30 supporting the one or more flow path supporting substrate sheets 20 in contact with the uppermost surface and / or the lowermost surface thereof.
  • dry treatment selected from corona treatment, plasma treatment and ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and / or molecular adhesive treatment on the surface of 20 or 30 They are joined and integrated by an indirect covalent bond via an adhesive.
  • dry treatment or molecular adhesive treatment may be applied, or they may be continuously and alternately applied.
  • it may be bonded only by dry processing, may be bonded by molecular adhesive treatment subsequent to dry processing, may be bonded by molecular adhesion processing following dry processing, and further by dry processing, They may be joined only by the adhesive treatment, may be joined by a dry treatment subsequent to the molecular adhesive treatment, or may be joined by a dry treatment subsequent to the molecular adhesion treatment and further a molecular adhesion treatment.
  • the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 may be made of only silicone rubber as a rubber component, or may contain non-silicone rubber.
  • the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are mainly composed of peroxide cross-linked silicone rubber, addition cross-linked silicone rubber, silicone rubber exemplified by condensation cross-linked silicone rubber, A silicone rubber elastic sheet produced by putting or stretching a three-dimensional silicone rubber exemplified by a co-blend of silicone rubber and olefin rubber into a molding die or the like and cross-linking as necessary. .
  • These rubber materials have a number average molecular weight of 10,000 to 1,000,000.
  • the peroxide-crosslinked silicone rubber as the material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is not particularly limited as long as it is synthesized using a silicone raw material compound that can be crosslinked with a peroxide-based crosslinking agent.
  • a silicone raw material compound that can be crosslinked with a peroxide-based crosslinking agent Specifically, polydimethylsiloxane, vinylmethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated polydimethylsiloxane, vinyl-terminated diphenylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated diethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated trifluoro.
  • peroxide-based crosslinking agent examples include ketone peroxides, diacyl peroxides, hydroperoxides, dialkyl peroxides, peroxyketals, alkyl peresters, and percarbonates.
  • ketone peroxide, peroxyketal, hydroperoxide, dialkyl peroxide, peroxycarbonate, peroxy ester benzoyl peroxide, dicumyl peroxide, dibenzoyl peroxide, t-butyl hydroperoxide, di-t-butyl Hydroperoxide, di (dicyclobenzoyl) peroxide, 2,5-dimethyl-2,5bis (t-butylperoxy) hexane, 2,5-dimethyl-2,5bis (t-butylperoxy) Hexyne, benzophenone, Mihiraaketon, dimethylaminobenzoic acid ethyl ester, benzoin ethyl ether.
  • the amount of peroxide-based crosslinking agent used is the type of silicone rubber to be obtained, the properties of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 formed from the silicone rubber, and as required.
  • the amount is appropriately selected according to the properties of the silane coupling agent to be used, but 0.01 to 10 parts by mass, preferably 0.1 to 2 parts by mass is preferably used with respect to 100 parts by mass of the silicone rubber. If it is less than this range, the crosslinking degree is too low to be used as silicone rubber. On the other hand, if the amount is larger than this range, the degree of crosslinking is too high and the elasticity of the silicone rubber is reduced.
  • the addition type silicone rubber as the material of the channel maintaining substrate sheets 10 and 30 and the channel supporting substrate sheet 20 is vinylmethylsiloxane / polydimethylsiloxane copolymer synthesized in the presence of Pt catalyst, vinyl-terminated polydimethylsiloxane, vinyl-terminated diphenylsiloxane.
  • the processing conditions for producing the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 from these compositions vary depending on the type and characteristics of the addition reaction, but are not uniquely determined, but are generally 0 to 200. Heating is performed at a temperature of 1 minute to 24 hours. As a result, additional silicone rubber is obtained as the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20. When the physical properties of the silicone rubber are better under low temperature processing conditions, the reaction time becomes longer. When productivity faster than physical properties is required, the processing is performed at a high temperature for a short time. When machining must be performed within a certain period of time depending on the production process and work environment, the machining temperature is set to a relatively high temperature within the above range in accordance with the desired machining time.
  • Condensation type silicone rubber as a material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is composed of silanol-terminated polydimethylsiloxane, silanol-terminated polydiphenylsiloxane, silanol-terminated polytrily synthesized in the presence of a tin-based catalyst.
  • a composition of a single condensation component comprising a silanol-terminated polysiloxane exemplified by fluoromethylsiloxane, silanol-terminated diphenylsiloxane / dimethylsiloxane copolymer, These silanol-terminated polysiloxanes, tetraacetoxysilane, triacetoxymethylsilane, di-t-butoxydiacetoxysilane, vinyltriacetoxysilane, tetraethoxysilane, trienoxymethylsilane, bis (triethoxysilyl) ethane, tetra -N-propoxysilane, vinyltrimethoxysilane, methyltris (methylethylketoxime) silane, vinyltris (methylethylketoxyimino) silane, vinyltriisopropenooxysilane, triacetoxymethylsilane, tri (ethylmethyl) oxime
  • the processing conditions for preparing the condensation-type silicone rubber from these compositions vary depending on the type and characteristics of the condensation reaction, and therefore cannot be uniquely determined. In general, heating is performed at 0 to 100 ° C. for 10 minutes to 24 hours. Is. Thereby, condensation type silicone rubber is obtained as the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20. When the physical properties of the silicone rubber are better under low temperature processing conditions, the reaction time becomes longer. When productivity faster than physical properties is required, the processing is performed at a high temperature for a short time. When machining must be performed within a certain period of time depending on the production process and work environment, the machining temperature is set to a relatively high temperature within the above range in accordance with the desired machining time.
  • the olefin rubber used in the co-blend of silicone rubber and olefin rubber as the material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is 1,4-cis butadiene rubber, isoprene rubber, styrene Examples include butadiene copolymer rubber, polybutene rubber, polyisobutylene rubber, ethylene / propylene rubber, ethylene-propylene-diene rubber, chlorinated ethylene propylene rubber, and chlorinated butyl rubber.
  • Non-silicone rubber used in the co-blend of silicone rubber and non-silicone rubber as the material of the channel maintaining substrate sheet 10/30 and the channel carrying substrate sheet 20 is ethylene-propylene-diene rubber, natural rubber, 1,4- Cis-butadiene rubber, isoprene rubber, polychloroprene, styrene-butadiene copolymer rubber, hydrogenated styrene-butadiene copolymer rubber, acrylonitrile-butadiene copolymer rubber, hydrogenated acrylonitrile-butadiene copolymer rubber, polybutene rubber, polyisobutylene rubber , Ethylene / propylene rubber, ethylene oxide-epichlorohydrin copolymer rubber, chlorinated polyethylene rubber, chlorosulfonated polyethylene rubber, alkylated chlorosulfonated polyethylene rubber, chloroprene rubber, chlorinated acrylic rubber , Brominated acrylic rubber, fluorine rubber
  • any or all of the flow path maintaining substrate sheets 10, 30, 50 and the flow path supporting substrate sheets 20, 40 contain diatomaceous earth, mica, talc, and / or kaolin, the amount of silicone rubber decreases, Permeation of water is suppressed, and a water-soluble liquid is difficult to permeate and hardly volatilize.
  • the amount of liquid permeation decreases with the amount of diatomaceous earth, mica, talc, and / or kaolin added.
  • said additive is scaly. If it is scale-like, the path through which water vapor passes through the sheet becomes longer, and the transmission of water vapor is suppressed.
  • any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made of silicone rubber, peroxide crosslinked silicone rubber, addition crosslinked silicone rubber, condensation crosslinked silicone rubber, radiation or electron beam crosslinked silicone rubber. It is preferable to use a co-blend product containing the main component of olefin rubber, which is ethylene-propylene-diene rubber (EPDM).
  • the ratio of the main component to the subcomponent is preferably 5 to 100 parts by weight: 100 to 5 parts by weight.
  • Ethylene-propylene-diene rubber may be used alone. When ethylene-propylene-diene rubber is used alone or blended (SEP), a water-soluble liquid is difficult to permeate and hardly volatilize.
  • the fine channel 26 of the channel-carrying substrate sheet 20 has a width of 0.5 ⁇ m to 5 mm, preferably 10 to 1000 ⁇ m, and the shape thereof is not particularly limited. Any of these may be used, and a single unit or a plurality of units may be provided in parallel.
  • the thicknesses of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are preferably 5 to 100 ⁇ m. Since the fine channel 26 is narrow and the thickness of the channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 is thin, the contact area between the specimen or reagent and the rubber sheet can be minimized. It is possible to prevent contamination of the specimen or reagent due to leakage of the rubber component from the rubber sheet and adsorption to the rubber component.
  • the flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 are non-reactive resins such as polytetrafluoro so that at least the wall surface 27 of the fine flow path 26 does not contaminate or adsorb the specimen or reagent.
  • Fluorine resin such as ethylene resin, phosphate resin such as 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, coated or deposited with paraxylylene resin such as parylene, or non-reactive inorganic material such as titanium dioxide or silicon dioxide If the inorganic material is vapor-deposited, the contact between the rubber sheet and the specimen or reagent can be completely avoided, so that the specimen or reagent can be further prevented from being contaminated or adsorbed.
  • MPC 2-methacryloyloxyethyl phosphorylcholine
  • the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintaining substrate sheet 10 and the flow sample injection portions 21a and 21b and the flow sample discharge portions 22a, 22b, and 22c of the flow path holding substrate sheet 20
  • the fine channel 26 is opened by laser processing.
  • the heat conductive microchemical chip 1 may have a protective base sheet (not shown) covering the upper and lower flow path maintaining substrate sheets 10 and 30.
  • the protective base sheet is made of ceramic, glass, or resin in addition to metal, and may be formed in a single plate shape or thin layer shape, or these may be laminated.
  • the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 were subjected to corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and directly joined and integrated by covalent bonding. In the same manner as described above, various activation treatments may be performed so as to join and integrate the upper and lower flow path maintenance substrate sheets 10 and 30.
  • the protective base sheet holes are made corresponding to the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintenance substrate sheet 10.
  • the protective base sheet is relatively stable with respect to the specimen and the reagent, but it is preferable that the portion in contact with the specimen and the reagent is formed of resin, coated, or laminated.
  • Examples of the metal forming the protective base sheet include gold, silver, copper, iron, cobalt, silicon, lead, manganese, tungsten, tantalum, platinum, cadmium, tin, palladium, nickel, chromium, titanium, zinc, aluminum, and magnesium. Metals, binary, ternary and multicomponent alloys of these metals.
  • the ceramics forming the protective base sheet are silver, copper, iron, cobalt, silicon, lead, manganese, tungsten, tantalum, platinum, cadmium, tin, palladium, nickel, chromium, indium, titanium, zinc, calcium, barium, aluminum And oxides, nitrides, and carbides of metals such as magnesium, sodium, and potassium, and simple substances or composites thereof.
  • Examples of the glass forming the protective base sheet include quartz, borosilicate glass, and alkali-free glass.
  • the resin forming the protective base sheet is polycarbonate resin, cycloolefin resin, acrylic resin, epoxy resin, polyethylene terephthalate resin, polybutene terephthalate resin, cellulose and its derivatives, hydroxyethyl cellulose, starch, cellulose diacetate, surface saponified acetic acid Vinyl resin, low density polyethylene, high density polyethylene, i-polypropylene, petroleum resin, polystyrene, s-polystyrene, chroman indene resin, terpene resin, styrene / divinylbenzene copolymer, ABS resin, polymethyl acrylate, polyacryl Ethyl acetate, polyacrylonitrile, polymethyl methacrylate, polyethyl methacrylate, polycyanoacrylate, polyvinyl acetate, polyvinyl alcohol, polyvinyl formal, polyvinyl chloride Ruacetal, polyvinyl chloride, vinyl chloride / vinyl acetate copo
  • corona discharge treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) is performed. It is activated by being.
  • the protective substrate sheet made of metal, ceramics or glass and the flow path maintenance substrate sheet 10/30 are strongly bonded to each other by an ether bond generated by dehydration of active groups such as hydroxyl groups generated by activation treatment. It is joined.
  • active groups such as a hydroxyl group
  • stacking these activation processes may not be given.
  • the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are directly bonded via an ether bond
  • covalent bonding or hydrogen bonding via a molecular adhesive such as a silane coupling agent
  • They may be joined indirectly by chemical bonds such as
  • one molecule of the silane coupling agent can be interposed between the protective base sheet and the flow path maintaining substrate sheets 10 and 30 to form a chemical bond.
  • the flow path maintaining substrate sheet 10/30 and a protective base material sheet made of metal, ceramics, glass, or resin are corona discharge treatment, plasma treatment, or ultraviolet irradiation treatment (at least one of their joint surfaces).
  • amino group-containing compounds such as triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol (TES), aminoethylaminopropyl trimethoxysilane;
  • TES triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol
  • a triazine compound having a trialkoxysilylalkylamino group and a mercapto group or azide group a triazine compound represented by the above formula (I), for example, 2,6-diazido-4- ⁇ 3- (triethoxysilyl) propylamino ⁇ -1,3,5-triazine (P-TES); thiol compound having trialkoxysilylalkyl group; epoxy compound having trialkyloxysilylalkyl group.
  • molecular adhesives are commercially available silane coupling agents such as vinyltrimethoxysilane (KBM-1003), vinyltriethoxysilane (KBE-1003), as alkoxy group-containing amino group-free silane coupling agents.
  • Silane coupling agent containing vinyl group and alkoxy group exemplified by: 2- (3,4-epoxycyclohexyl) ethyltrimethoxysilane (KBM-303), 3-glycidoxypropylmethyldimethoxysilane (KBM-402) , 3-glycidoxypropyltrimethoxysilane (KBM-403), 3-glycidoxypropylmethyldiethoxysilane (KBE-402), 3-glycidoxypropyltriethoxysilane (KBE-403) Epoxy group and alkoxy group-containing silane coupling agent; styryl group and alkoxy group-containing silane coupling agent exemplified by p-styryltrimethoxy
  • the amino group-free silane coupling agent having an alkoxy group is a hydrosilyl group (SiH group) -containing alkoxysilyl compound, for example, (CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H, (C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H, (CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (OCH 3 ) 2 OSi (OCH 3 ) 3 , (C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (OCH 3 ) 2 OSi (OCH 3 ) 3 , (C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 H, (CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 H, (iC 3 H 7 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) H 2 , (nC 3 H 7 O) 3 Si
  • vinyl groups and SiH groups may be promoted with a metal catalyst such as a platinum-containing compound to join the base sheet and the rubber sheet.
  • silane coupling agent having an alkoxy group As an amino group-containing silane coupling agent having an alkoxy group, a commercially available silane coupling agent, specifically N-2- (aminoethyl) -3-aminopropylmethyldimethoxysilane (KBM-602), N- 2- (aminoethyl) -3-aminopropyltrimethoxysilane (KBM-603), N-2- (aminoethyl) -3-aminopropyltriethoxysilane (KBE-603), 3-aminopropyltrimethoxysilane ( KBM-903), 3-aminopropyltriethoxysilane (KBE-903), 3-triethoxysilyl-N- (1,3-dimethyl-butylidene) propylamine (KBE-9103), N-phenyl-3-amino Amino group-containing alkoxysilyl compound exemplified by propyltri
  • the protective base sheet is made of metal, ceramics or glass and the flow path maintaining substrate sheet 10/30 is made of silicone rubber, it is preferable that the two are directly joined by an ether bond.
  • the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface.
  • the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are dehydrated to form an ether bond by pressure bonding due to pressurization or decompression.
  • the protective base sheet is formed of metal, ceramics, or glass
  • the flow path maintenance substrate sheet 10/30 is formed of silicone rubber including non-silicone rubber
  • both of them contain no amino group having an alkoxy group. They may be joined by a covalent bond of an oxygen-carbon bond, a carbon-carbon bond, and an oxygen-silicon bond via a silane coupling agent.
  • the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface.
  • a silane coupling agent containing an alkoxy group or an alkoxy group equivalent group and, if necessary, an unsaturated group, an epoxy group, a ureido group, a sulfide group, an isocyanate group and containing no amino group is attached.
  • these covalent bonds are formed at the time of pressure bonding at normal temperature or under reduced pressure at normal temperature or under heating.
  • the protective base sheet is formed of a resin and the flow path maintenance substrate sheets 10 and 30 are formed of a non-silicone rubber containing a silicone rubber, they both have an amino group-containing silane coupling agent having an alkoxy group. Via a covalent bond such as an amide bond or an imino bond with a newly formed carboxyl group or carbonyl group. Also good.
  • the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface.
  • silane coupling agent containing an alkoxy group or an alkoxy group equivalent group and an amino group, so that these can be applied at normal pressure, under pressure or under reduced pressure at room temperature or under heat.
  • a chemical bond is formed.
  • the amino group of the silane coupling agent is easily adsorbed to the resin, and when the resin is a polycarbonate resin, a cycloolefin resin, a polyethylene terephthalate resin, an acrylic resin, or an epoxy resin, the reaction proceeds particularly quickly and quickly. Easy to join firmly.
  • polycarbonate resins and cycloolefin resins are particularly excellent in water resistance.
  • the proximity of the protective substrate sheet hydroxyl group and the active group such as the hydroxyl group of the flow path maintaining substrate sheet 10 or 30 or the reactive functional group of the silane coupling agent that reacts with the active group is reduced under reduced pressure or vacuum condition, for example, 50 torr.
  • reduced pressure conditions for example, 50 torr.
  • under reduced pressure conditions of 50 to 10 torr, or less than 10 torr more specifically, under vacuum conditions of less than 10 torr to less than 1 ⁇ 10 ⁇ 3 torr, preferably less than 10 torr to 1 ⁇ 10 ⁇ 2 torr. It is facilitated by removing the gaseous medium at the contact interface or by further heating the contact interface by applying stress (load), eg 10-200 kgf, to the contact interface. It is preferable that pressure is uniformly applied to the entire bonding surface of the protective base sheet and the flow path maintaining substrate sheets 10 and 30 under reduced pressure or pressurized conditions. If it is out of the above range, the pressure may not be applied uniformly.
  • Such a heat conductive microchemical chip 1 is manufactured as follows with reference to FIG. 1 as an example.
  • a large sheet for a silicone rubber channel carrying substrate sheet / channel maintenance substrate sheet is prepared from the composition containing the heat conductive filler powder and the silicone rubber raw material component.
  • a large sheet for a flow path maintaining substrate sheet is prepared from a resin raw material composition such as a polyimine raw material component. From the large sheet, the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are cut into a rectangular parallelepiped. The flow path carrying substrate sheet 20 is cut out and penetrated by laser processing, and a fine flow path 26 is attached to the flow path carrying substrate sheet 20.
  • the fine flow path 26 is formed by laser processing and extends from the flow sample injection sites 21a and 21b at the starting end, joins downstream, and then extends to the flow sample discharge site 22a, and the main flow extends to the flow sample discharge sites 22b and 22c.
  • the main stream is formed into a shape that extends downstream to the flow sample discharge sites 22b and 22c at the end point and branches.
  • the flow path maintaining substrate sheet 10 for the cover having the same size as the flow path carrying substrate sheet 20 is cut out from the large sheet.
  • the flow sample injection holes 11 a, 11 b and the flow sample discharge holes 12 a, 12 b, respectively, at positions corresponding to the flow sample injection parts 21 a, 21 b and the flow sample discharge parts 22 a, 22 b, 22 c. 12c is opened by laser processing or drilling or punching.
  • the flow path maintenance substrate sheet 30 for supporting the bottom surface is cut out from the large sheet into the same size as the flow path carrying substrate sheet 20.
  • the channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 are washed with alcohol and water.
  • Corona treatment, plasma treatment, or ultraviolet irradiation treatment (general) is performed on the lower surface 15 of the flow path maintenance substrate sheet 10, the upper surface 34 of the flow path maintenance substrate sheet 30, and the upper and lower surfaces 24 and 25 of the flow path support substrate sheet 20.
  • UV treatment or excimer UV treatment When UV treatment or excimer UV treatment), hydroxyl groups are newly generated on the surfaces.
  • the flow path holding substrate sheet 20 is sandwiched between the flow path maintaining substrate sheets 10 and 30 under normal pressure, and the pressure is reduced, for example, 10 torr or less as necessary. Then, if necessary, for example, by pressing at 10 to 200 kgf while heating at 80 to 120 ° C.
  • the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 are based on the raw material composition and may or may not originally have a hydroxyl group. By performing plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment), hydroxyl groups are efficiently generated there.
  • the optimum processing conditions vary depending on the material type and history of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20, but the processing is continued until a surface tension of 55 kJ / m or more is obtained on the surface. is important. Thereby, sufficient adhesive strength is obtained.
  • the corona discharge treatment of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 is performed using, for example, a corona surface modification device (for example, a corona master manufactured by Shinko Electric Measurement Co., Ltd.) Power supply: 100 VAC, output voltage: 0 to 20 kV, oscillation frequency: 0 to 40 kHz, 0.1 to 60 seconds, temperature 0 to 60 ° C.
  • a corona surface modification device for example, a corona master manufactured by Shinko Electric Measurement Co., Ltd.
  • the atmospheric pressure plasma treatment of the flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 is performed using, for example, an atmospheric pressure plasma generator (for example, Matsushita Electric Works, Ltd .: trade name Aiplasuma), for example, plasma processing speed. 10 to 100 mm / s, power supply: 200 or 220 V AC (30 A), compressed air: 0.5 MPa (1 NL / min), 10 kHz / 300 W to 5 GHz, power: 100 W to 400 W, irradiation time: 0.1 to 60 seconds Is called.
  • an atmospheric pressure plasma generator for example, Matsushita Electric Works, Ltd .: trade name Aiplasuma
  • plasma processing speed 10 to 100 mm / s, power supply: 200 or 220 V AC (30 A), compressed air: 0.5 MPa (1 NL / min), 10 kHz / 300 W to 5 GHz, power: 100 W to 400 W, irradiation time: 0.1 to 60 seconds Is called.
  • UV-LED ultraviolet light-emitting diode
  • UV-LED irradiation device for example, UV-LED irradiation device manufactured by OMRON Corporation: trade name ZUV-
  • irradiation time 1 to 60 seconds.
  • the front surface of the flow path maintaining substrate sheet 10 and the back surface of the flow path maintaining substrate sheet 30 are bonded to the molecular adhesive.
  • the protective substrate sheet (not shown) may be contacted. There is no limitation on the dipping and spraying time, and it is important that the substrate surface of the protective substrate sheet is uniformly moistened.
  • the protective substrate sheet with the silane coupling agent is dried in a heated state by placing it in an oven, blowing warm air with a dryer, or irradiating high frequency. Heating and drying are performed at a temperature range of 50 to 250 ° C. for 1 to 60 minutes. If it is less than 50 degreeC, the reaction time of the hydroxyl group produced
  • the immersion and drying may be repeated about 1 to 5 times. As a result, it is possible to sufficiently advance the reaction by shortening the time of dipping and drying per time and increasing the number of reactions.
  • the heat conductive microchemical chip 1 is used as follows, for example, with reference to FIG.
  • the thermally conductive microchemical chip 1 is mounted on a microreactor (not shown).
  • Syringes (not shown) are air-tightly inserted into the flow sample injection holes 11a and 11b of the flow path maintenance substrate sheet 10 for the cover, respectively, and the liquid sample and the liquid reagent separately from each syringe exceed 100 kPa.
  • the fluid sample While being pressurized to 3 MPa or less, the fluid sample is injected into the fine channel 26 through the fluid sample injection sites 21a and 21b. Both flow samples flow through the fine flow channel 26, merge and mix, and react with each other.
  • the waste liquid is discharged from the flow sample discharge hole 12a through the flow sample discharge portion 22a which is a tributary. Branching in the main stream, the flow sample containing the product synthesized in a small amount is discharged from the flow sample discharge holes 12b and 12c through the flow sample discharge portions 22b and 22c, respectively, and the target product is obtained.
  • thermally conductive microchemical chip 1 is shown in FIG. From the composition containing the heat conductive filler powder and the silicone rubber raw material component, a large sheet for the silicone rubber channel maintaining substrate sheet / channel supporting substrate sheet is prepared. From this large sheet, the flow path maintaining substrate sheets 10, 30, 50 and the flow path carrying substrate sheets 20, 40 are cut into substantially rectangular shapes of the same size.
  • the thermally conductive microchemical chip 1 includes a flow path maintaining substrate sheet 10 for a cover, a flow path supporting substrate sheet 20 having a first fine flow path 26, a flow path maintaining substrate sheet 30 for an insole, and a second fine path.
  • the flow path carrying substrate sheet 40 having the flow path 46 and the flow path maintenance substrate sheet 50 for supporting the bottom surface are superposed in this order.
  • Fine channels 26 and 46 are formed on the channel-carrying substrate sheets 20 and 40 so as to penetrate the front and back sides.
  • the microchannel 26 extends from the flow sample injection sites 21a and 21b, which are the starting point ends, in the flow channel carrying substrate sheet 20, and merges downstream, and from there to a tributary extending to the flow sample discharge site 22a, and to the flow sample transfer site 23 It branches into the main stream that extends.
  • the flow path maintaining substrate sheet 30 for the insole has a flow sample transfer hole 33 at a position corresponding to the flow sample transfer portion 23.
  • a check valve may be provided in the flow sample transfer hole 33.
  • the flow path carrying substrate sheet 40 is provided with a flow sample transfer portion 43 at a position corresponding to the flow sample transfer hole 33, and extends and joins the flow sample injection portion 41 a, which is another starting point end, downstream thereof.
  • the microchannel 46 that branches to the flow sample discharge portions 42a and 42b, which are the end points, is formed through the front and back surfaces.
  • a flow sample injection hole 51a and flow sample discharge holes 52a and 52b are opened in the flow path maintenance substrate sheet 50 for supporting the bottom surface at positions corresponding to the flow sample injection portion 41a and the flow sample discharge portions 42a and 42b. Yes.
  • the flow path maintaining substrate sheets 10, 30, 50 and the flow path carrying substrate sheets 20, 40 are directly bonded via ether bonds as in FIG.
  • the flow path maintaining substrate sheets 10, 30, 50 and the flow path supporting substrate sheets 20, 40 may have the above-described materials and shapes, and may be joined via a silane coupling agent.
  • This thermally conductive microchemical chip 1 is used by applying a fluid sample by applying pressure as in the case of FIG.
  • the thermally conductive microchemical chip 1 is inadvertently mixed when injecting flow samples having different molecular weights, composition components, and composition properties in the fine channels 26 and 46 of the plurality of channel-carrying substrate sheets 20 and 40, respectively. Can be prevented.
  • the sample may be appropriately separated when the fluid sample reacts in the fine channels 26 and 46 and the molecular weight of the target substance in the fluid sample changes or the specific gravity of the fluid sample changes.
  • the thermally conductive microchemical chip 1 includes the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 of FIG. It is sandwiched between rigid holders 60a and 60b that are not bent by two resin plates or metal plates. These are screwed and fixed. In the holders 60a and 60b, at the positions corresponding to the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintenance substrate sheets 10 and 30, the injection guide holes 61a and 61b and the discharge guide holes 62a and 62b and 62c are open.
  • the heat conductive microchemical chip 1 is used by applying pressure and feeding the fluid sample into the fine channel 26 in the same manner as in FIG.
  • This heat conductive microchemical chip 1 may have the flow path maintaining substrate sheets 10, 30, and 50 and the flow path supporting substrate sheets 20 and 40 shown in FIG.
  • the heat conductive microchemical chip 1 of FIGS. 1 and 2 may be joined by inserting a heater between the flow path maintaining substrate sheets 10, 30, 50 and the flow path holding substrate sheets 20, 40, A heater may be disposed on or below the holder in FIG. 3 (not shown).
  • the thermally conductive microchemical chip 1 has a sample / reagent / reaction at any one of the flow sample injection sites 21a and 21b, the flow sample discharge sites 22a, 22b and 22c, the flow sample injection site 41a and the flow sample discharge sites 42a and 42b.
  • a sensor such as an electrode for detecting the product may be wired.
  • the holders 60a and 60b may be joined to the flow path maintaining substrate sheets 10 and 30 in contact therewith.
  • FIG. 1 Another embodiment of the thermally conductive microchemical chip 1 is shown in FIG. You may have the liquid storage part 28 in the middle of the microchannel 26.
  • FIG. The liquid reservoir 28 in the middle of the fine channel 26 extends in the middle of the fine channel 26 so that the flowing sample can be trapped.
  • the liquid reservoir 28 can trap the flowing sample for a while and cause a chemical reaction sufficiently.
  • the liquid reservoir 28 has a sufficiently large area so that it can irradiate measurement, detection, or reaction light rays for a fluid sample, such as ultraviolet rays, infrared rays, visible rays, and laser beams.
  • the trap start end and the trap end end are gradually expanded and contracted, respectively, so that the flow of the flowing sample is not hindered.
  • the flow of the flowing sample to the flow path 26 by pressurization is stopped, and heating, heat dissipation or cooling is performed as necessary to sufficiently cause a reaction such as PCR.
  • the flow sample may be adjusted to resume the flow. If the flow sample can react sufficiently in the middle of the flow path, or if it can irradiate light for measurement, detection or reaction for the flow sample, such as ultraviolet rays, infrared rays, visible rays, laser light, etc. Alternatively, if it is not necessary to irradiate these light beams, the fine flow path 26 does not have to have the liquid reservoir 28 as a groove having the same diameter as shown in FIG.
  • thermally conductive microchemical chip 1 to which the present invention is applied is made as a prototype is shown.
  • Example 1 50 parts by weight of SH1005 (trade name, manufactured by Toray Dow Corning Co., Ltd.), which is methyl vinyl silicone rubber as the silicone rubber, and SH200 100cs (product name: manufactured by Toray Dow Corning Co., Ltd.), which is polydimethylsiloxane as the silicone oil.
  • SH1005 trade name, manufactured by Toray Dow Corning Co., Ltd.
  • SH200 100cs product name: manufactured by Toray Dow Corning Co., Ltd.
  • pyroxuma 5301 manufactured by Kyowa Chemical Industry Co., Ltd .; trade name, average particle size 2 ⁇ m
  • pyrokisuma 3320 manufactured by Kyowa Chemical Industry Co., Ltd .; trade name, average grain 200 parts by weight of 20 ⁇ m diameter
  • 50 parts by weight of Heidilite H32 made by Showa Denko KK; trade name) aluminum hydroxide Al (OH) 3 as an additive and VESTA PP (Inoue Lime Industry Co., Ltd.), calcium oxide CaO 10 parts by weight of company-made product name
  • SH851 (trade name, manufactured by Toray Dow Corning Co., Ltd.), which is methyl vinyl silicone rubber, is used as the silicone rubber, and 2,5-dimethyl-2,5-di (t-butyl) is used as the peroxide crosslinking agent.
  • Peroxy) hexane (PC-4) (trade name, 50% silica solution manufactured by Toray Dow Corning Co., Ltd.) 0.5 parts by weight was kneaded to obtain a composition for a sheet of an intermediate layer. This was heated under pressure to form a heat conductive sheet made of silicone rubber to be a flow path carrying substrate sheet.
  • the flow path carrying substrate sheet and the flow path maintaining substrate sheet were formed and bonded to obtain the heat conductive microchemical chip 1 of the present invention.
  • the heat conductive microchemical chip 1 of the present invention thus obtained is used for amplifying deoxyribonucleic acid (DNA).
  • DNA deoxyribonucleic acid
  • the target double-stranded DNA is thermally denatured into a single strand in the first step (94 to 96 ° C), and the primer is converted into a single-stranded DNA in the second step (55 to 60 ° C).
  • Annealing is performed, the extension reaction is advanced in the third stage (72 to 74 ° C.), and this polymerase chain reaction (PCR) is repeated.
  • Heating is performed by a thermocouple, a Peltier element, and infrared irradiation, but since this thermally conductive microchemical chip 1 has a silicone rubber thermally conductive sheet, the temperature rises and falls smoothly, PCR can be performed without delay.
  • a foamable silicone rubber sheet was prepared according to Example 1 of JP-A-2008-94981.
  • a silicone rubber compound was prepared by blending 2 parts by mass of a peroxide vulcanizing agent with 100 parts by mass of silicone rubber and mixing and dispersing with two rolls.
  • To 110 parts by mass of a silicone rubber compound containing a vulcanizing agent 10 parts by mass of trimethylolpropane as a first pore-forming agent and 390 parts by mass of pentaerythritol as a second pore-forming agent are blended, and the can body temperature (T1 )
  • T1 can body temperature
  • a rubber composition was obtained by kneading with a kneader set at 110 ° C.
  • the rubber composition obtained in the kneading process was compression molded in a press mold at a vulcanization temperature (T2) of 170 ° C. for 10 minutes to obtain a sheet-like vulcanized rubber composition having a thickness of 2 mm.
  • T1 ⁇ T2 vulcanization temperature between the vulcanization temperature (T2) and the kneading temperature (T1) was ⁇ 60 ° C.
  • the sheet-like vulcanized rubber composition was washed with warm water and the pore-forming agent was eluted from the vulcanized rubber composition to obtain a foamable silicone rubber sheet as a porous body.
  • the thermal conductive microchemical chip of the present invention has excellent heat dissipation from the inside and heat conductivity from the outside, and it is necessary to quickly analyze the analysis of the patient's biological components in the emergency medical field where it is necessary to know the analysis results.
  • the heat conductive microchemical chip can easily form a flow path having any shape, it can be used for custom-made medical care and identification of DNA analysis of various animals and plants.
  • the microchemical chip obtained by the method for producing the thermally conductive microchemical chip of the present invention is used in the medical field for performing genetic diagnosis and treatment, or a biological sample, mounted on the analyzer or microreactor. It can be used for various analyzes in the field of criminal investigations, microbiological searches using underwater robots in remote areas such as the ocean and lakes, and various synthesis in drug development.
  • 1 is a thermally conductive microchemical chip
  • 10 is a flow path maintenance substrate sheet
  • 11, 11 a, and 11 b are flow sample injection holes
  • 12, 12 a, 12 b, and 12 c are flow sample discharge holes
  • 15 is a bottom surface
  • 20 is a flow path support
  • 21 a, 21 b are fluid sample injection sites
  • 22, 22 a, 22 b, 22 c are fluid sample discharge sites
  • 23 is a fluid sample transport site
  • 24 is an upper surface
  • 25 is a lower surface
  • 26 is a flow path
  • 27 is a wall surface
  • 28 is a liquid reservoir
  • 30 is a flow path maintenance substrate sheet
  • 33 is a flow sample transfer hole
  • 34 is an upper surface
  • 40 is a flow path support substrate sheet
  • 41 a is a flow sample injection site
  • 42 a and 42 b are flow sample discharge sites
  • 43 is a flow sample transfer site
  • 46 is a flow path
  • 50 is a flow path maintenance substrate sheet

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Abstract

Provided is a thermally conductive microchemical chip wherein: a fine flow path in which a very small amount of a precious specimen, reagent, or sample is caused to flow by pressurization at high pressure, or by a capillary phenomenon, is formed reliably; the specimen/reagent/sample can be sent into the flow path accurately and reliably and as desired; the specimen/reagent/sample is not exposed to high temperatures by heat dissipation in cases where the same is to be cooled, or the specimen/reagent/sample can be heated in cases where the temperature thereof is to be raised with a heater; and the specimen, reagent, or sample can be analyzed/reacted/cultured/amplified accurately and easily and in a short time. This thermally conductive microchemical chip (1) is made by: overlapping flow-path-supporting substrate sheets (10; 30) and a flow-path-retaining substrate sheet (20) that have, formed therein, recessed flow paths (11a-b; 12a-c; 21a-b; 22a-c; 26) into which a fluid sample is introduced by pressurization and in which the fluid sample is subjected to a chemical reaction; and integrating the flow-path-supporting substrate sheets and the flow-path-retaining substrate sheet by directly joining the substrate sheets by a covalent bond by subjecting the substrate sheets to a corona treatment, a plasma treatment, or an ultraviolet irradiation treatment. One of the flow-path-retaining substrate sheet (20) and the flow-path-supporting substrate sheets (10; 30) is a silicone-rubber-made thermally conductive sheet including a thermally conductive filler powder such as aluminum oxide.

Description

熱伝導性マイクロ化学チップThermally conductive microchemical chip
　本発明は、生体由来検体を被験物としそのバイオ成分を微細流路に流して微量分析する装置や、薬理作用を示すバイオ成分等の有用物質の原材料成分や反応基質等の試薬を微細流路に流してこれら有用物質を化学的に微量合成するマイクロリアクターや、細胞増殖等のためのマイクロ生化学処理器に装着して用いられ、流路内部の熱を外界に放熱したり外部の熱を流路内部に伝導したりする熱伝導性マイクロ化学チップに関する。 The present invention relates to a device for analyzing a trace amount by using a biological specimen as a test substance and flowing the biocomponents through a fine flow path, and a raw material component of a useful substance such as a bio ingredient exhibiting a pharmacological action and a reagent such as a reaction substrate. It is used by attaching to a microreactor that chemically synthesizes these useful substances in a micro-reactor, or a microbiochemical processor for cell growth, etc. The present invention relates to a thermally conductive microchemical chip that conducts to the inside of a flow path.
　血液や尿などの生体由来検体である被験物をμＬオーダーの微量だけ用いて、酵素の特異的基質選択性を利用し、検体中の基質と作用する酵素反応量やその基質量を酵素又は基質で発色する試薬による着色程度で定量するのに、マイクロバイオチップが用いられている。また、酵素含有膜を用い酵素反応量を電極で電気信号に変換して基質量を定量したりする分析や、ＤＮＡ抽出・そのポリメラーゼ連鎖反応（ＰＣＲ）増幅や、イオン濃度測定や、核酸、糖、タンパク質又はペプチドの微量合成などをμＭオーダーで行う際に、マイクロリアクターチップが用いられている。また、有用細胞やウィルスを増殖させたり、検査のために癌細胞を付着させたりするのに、マイクロ生化学チップが用いられている。 Using a test sample that is a biological sample such as blood or urine in a microliter order, using the specific substrate selectivity of the enzyme, the amount of enzyme reaction that acts on the substrate in the sample and its base mass are determined as the enzyme or substrate. A microbiochip is used for quantification based on the degree of coloring by a reagent that develops color. In addition, an enzyme-containing membrane is used to convert the amount of enzyme reaction into an electrical signal with an electrode to quantify the substrate mass, DNA extraction and its polymerase chain reaction (PCR) amplification, ion concentration measurement, nucleic acid, sugar A microreactor chip is used when microsynthesis of protein or peptide is performed on the order of μM. In addition, microbiochemical chips are used for growing useful cells and viruses and attaching cancer cells for examination.
　このマイクロバイオチップやマイクロリアクターチップやマイクロ生化学チップなどのマイクロ化学チップは、懸濁液や溶液である検体や液体である試薬や細胞液のような試料などの流動試料を加圧して送り込み、流動させて混合、反応、分離、付着、検出するための反応チャンネルとして、溝状の微細流路を有している。 Microchemical chips such as microbiochips, microreactor chips, and microbiochemical chips pressurize and feed fluid samples such as specimens such as suspensions and solutions, liquid reagents and cell fluids, As a reaction channel for flowing, mixing, reacting, separating, adhering, and detecting, it has a groove-like fine channel.
　マイクロ化学チップは、ステンレス基材、シリコン基材、石英基材又はガラス基材である無機基材や、樹脂基材又はゴム基材である有機基材に、数１０～数１００μｍの微細流路を切削やエッチングで形成したものである。 A microchemical chip is a fine channel of several tens to several hundreds μm on an inorganic base material such as a stainless steel base, silicon base, quartz base or glass base, or an organic base such as a resin base or a rubber base. Is formed by cutting or etching.
　例えば、有機基材で形成されたマイクロ化学チップは、特許文献１のように、微細流路を有し、透明性の高いプラスチック樹脂で形成されたものである。樹脂基材やゴム基材は成形や切削加工が容易いので、それらを接着剤で貼付し又は熱融着して形成したマイクロ化学チップは、大量生産に適している。特に透明な有機基材又は無機基材で形成されていると、光学系分析に便利である。 For example, a microchemical chip formed of an organic substrate has a fine flow path and is formed of a highly transparent plastic resin as in Patent Document 1. Since a resin base material and a rubber base material are easy to mold and cut, a microchemical chip formed by sticking them with an adhesive or heat-sealing them is suitable for mass production. In particular, it is convenient for optical system analysis when it is formed of a transparent organic substrate or inorganic substrate.
　このような微細流路に検体や試薬を高圧に加圧して送り込むと、高圧の圧力と微細流路での摩擦とによって希少で貴重な検体や試薬や試料が昇温し変質する恐れがある。そこで、マイクロ化学チップの裏面に、アルミニウム箔のような金属薄膜が接着剤層を介して接着されることがある。金属薄膜は熱伝導性が良いので、マイクロ化学チップを放冷する必要があるとき熱を放熱し、マイクロ化学チップをヒーターで加熱するとき熱を伝導する。 When a specimen or reagent is pressurized and fed into such a fine channel, the rare and valuable specimen, reagent or sample may be heated and deteriorated due to the high pressure and friction in the fine channel. Therefore, a metal thin film such as an aluminum foil may be bonded to the back surface of the microchemical chip via an adhesive layer. Since the metal thin film has good thermal conductivity, it dissipates heat when it is necessary to cool the microchemical chip, and conducts heat when the microchemical chip is heated with a heater.
　このような無機基材や有機基材と金属薄膜とは、接着剤層を介し分子間力による物理的な相互作用により接着されているに過ぎないから、共有結合ほどの強い結合力で接着されていない。そのため、微細流路に検体や試薬や試料を高圧に加圧して送り込む際に、無機基材と金属薄膜との間の熱膨張率が相違することや、高圧による微細流路の膨張に応じた有機基材の変形に金属薄膜が追従できないことに起因して、無機基材や有機基材と金属薄膜とが、剥がれて隙間を生じ易い。その隙間のため、マイクロ化学チップ内部の熱を十分で均一に放熱ができず、マイクロ化学チップの流路内で検体や試薬や試料が分解等の所為で、微量分析が正確にできなかったり、微量合成が不十分で原材料成分や反応基質が残存し又は副反応を誘発したり、生きた細胞が死滅したりウィルスが分解したりする。一方、その隙間のため、マイクロ化学チップをヒーターで加熱するとき熱を伝導し難く、充分で均一に加熱できず、マイクロ化学チップ内で検体や試薬が反応せず微量分析が正確にできなかったり、微量合成が不十分で原材料成分や反応基質が反応しなかったりする。さらに、金属薄膜は光を透過しないので、マイクロ化学チップが透明な有機基材又は無機基材を用いて折角形成されていても、光学系分析に供することができなくなってしまう。 Since such inorganic and organic substrates and metal thin films are only bonded by physical interaction due to intermolecular forces via an adhesive layer, they are bonded with a strong bonding force as much as a covalent bond. Not. Therefore, when a specimen, a reagent, or a sample is pressurized and fed into a fine channel, the thermal expansion coefficient between the inorganic base material and the metal thin film is different, or the fine channel is expanded according to the high pressure. Due to the fact that the metal thin film cannot follow the deformation of the organic base material, the inorganic base material, the organic base material, and the metal thin film are easily peeled off to form a gap. Because of the gap, the heat inside the microchemical chip cannot be dissipated sufficiently and uniformly, and because the sample, reagent, and sample are decomposed in the flow path of the microchemical chip, microanalysis cannot be performed accurately, Insufficient trace synthesis leaves raw material components and reaction substrates or induces side reactions, kills living cells, or degrades viruses. On the other hand, due to the gap, it is difficult to conduct heat when the microchemical chip is heated with a heater, it cannot be heated sufficiently and uniformly, and the sample or reagent does not react in the microchemical chip and the microanalysis cannot be performed accurately. The raw material components and reaction substrate do not react due to insufficient microsynthesis. Furthermore, since the metal thin film does not transmit light, even if the microchemical chip is formed at a corner using a transparent organic or inorganic substrate, it cannot be used for optical system analysis.
特開２００６－２１８６１１号公報JP 2006-218611 A
　本発明は前記の課題を解決するためになされたもので、微量の生体由来検体のような貴重な検体や稀薄で微量の試薬や繊細な細胞・ウィルスなどの試料を高圧での加圧や毛細管現象で流動させる微細な流路が確実に形成され、精度良くかつ確実に所望通りに流路へ送り込むことができ、放冷すべき場合に放熱によって高温に晒されず又はヒーターで昇温すべき場合に加熱でき、その検体中のバイオ成分や試薬の有用物質や細胞・ウィルス等の試料を正確かつ簡便に短期間で分析したり反応させたり培養・増幅させたりでき、歩留まり良く大量かつ均質に製造できる簡易で小型の熱伝導性マイクロ化学チップを、提供することを目的とする。 The present invention has been made in order to solve the above-mentioned problems. A precious sample such as a small amount of a biological sample, a thin and small amount of a reagent, or a sample such as a delicate cell or virus can be pressurized with a high pressure or a capillary tube. A fine flow path that flows due to the phenomenon is reliably formed, can be accurately and reliably sent to the flow path as desired, and when it is allowed to cool, it should not be exposed to high temperatures due to heat dissipation or heated by a heater It can be heated in some cases, and it can accurately and easily analyze, react, incubate, and amplify biocomponents, useful chemicals in reagents, and samples of cells and viruses in a short period of time. An object is to provide a simple and small thermally conductive microchemical chip that can be manufactured.
　前記の目的を達成するためになされた本発明の熱伝導性マイクロ化学チップは、検体、試薬及び試料から選ばれる流動試料を加圧及び／又は毛細管現象により流し込み化学反応及び／又は化学作用させる流路を凹んで及び／又は貫孔してゴム、樹脂、金属、セラミックス及び／又はガラスで形成された単数又は複数の流路担持基板シートと、ゴム、樹脂、金属、セラミックス及び／又はガラスで形成され、前記流路に繋がる受渡穴を開けており前記流路を覆う前記流路担持基板シートをその最上面及び／又は最下面に接して担持する流路維持基板シートとが、重ねられて、少なくとも何れかのシート表面でコロナ処理、プラズマ処理及び紫外線照射処理から選ばれる乾式処理と分子接着剤処理との少なくとも何れかによる直接的な及び／又は前記分子接着剤を介した間接的な共有結合により、接合して一体化しており、前記流路担持基板シートと前記流路維持基板シートとのそれぞれの前記流路と前記受渡穴とが、流動試料注入口から流動試料排出口へ立体的に順次繋がり、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、酸化アルミニウム、酸化マグネシウム、酸化亜鉛、グラファイトカーボン、チッ化ケイ素、チッ化ホウ素及びチッ化アルミニウムから選ばれる少なくとも何れかの熱伝導性フィラー粉末を含んだ熱伝導性シートであるというものである。紫外線照射処理とは、紫外線を照射する処理であれば限定されないが、広域波長域又は複数波長の紫外線を照射する一般的な紫外線処理(ＵＶ処理)であってもよく、単一波長と見做せるエキシマ紫外線を照射するエキシマ紫外線処理（エキシマＵＶ処理）であってもよい。 The thermally conductive microchemical chip of the present invention made to achieve the above object is a flow in which a fluid sample selected from a specimen, a reagent, and a sample is injected by pressurization and / or capillary action to cause a chemical reaction and / or a chemical action. Recessed and / or through-hole formed with rubber or resin, metal, ceramics and / or glass and one or more flow path supporting substrate sheets and rubber, resin, metal, ceramics and / or glass And a flow path maintenance substrate sheet that opens a delivery hole connected to the flow path and supports the flow path supporting substrate sheet covering the flow path in contact with the uppermost surface and / or the lowermost surface thereof, and is stacked, Directly and / or by at least one of dry treatment and molecular adhesive treatment selected from corona treatment, plasma treatment and ultraviolet irradiation treatment on at least any sheet surface It is joined and integrated by indirect covalent bonding via the molecular adhesive, and the flow path and the delivery hole of each of the flow path carrying substrate sheet and the flow path maintenance substrate sheet flow. Three-dimensionally connected from the sample inlet to the flow sample outlet, and at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is made of aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride , A heat conductive sheet containing at least one heat conductive filler powder selected from boron nitride and aluminum nitride. The ultraviolet irradiation treatment is not limited as long as it is a treatment for irradiating ultraviolet rays, but may be a general ultraviolet ray treatment (UV treatment) for irradiating ultraviolet rays in a wide wavelength region or a plurality of wavelengths, and is regarded as a single wavelength. Excimer ultraviolet treatment (excimer UV treatment) for irradiating excimer ultraviolet rays to be applied may be used.
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、シリコーンゴムで形成されているものでもよい。 The thermally conductive microchemical chip may be one in which at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
　熱伝導性マイクロ化学チップは、前記シリコーンゴムが、白金触媒を、含んでいるものでもよい。 In the heat conductive microchemical chip, the silicone rubber may contain a platinum catalyst.
　熱伝導性マイクロ化学チップは、前記シリコーンゴムが、ビニルメトキシシリル基を有する炭素数６～１２のシランカップリング剤を、含んでいるものでもよい。 In the heat conductive microchemical chip, the silicone rubber may contain a silane coupling agent having 6 to 12 carbon atoms having a vinylmethoxysilyl group.
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、珪藻土、マイカ、タルク及び／又はカオリンを含むものであることが好ましい。 In the heat conductive microchemical chip, it is preferable that at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet includes diatomaceous earth, mica, talc and / or kaolin.
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、三酸化アンチモン及び水酸化アルミニウムから選ばれる少なくとも何れかの難燃剤を含むものであってもよい。 In the thermally conductive microchemical chip, at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet includes at least one flame retardant selected from antimony trioxide and aluminum hydroxide. Also good.
　熱伝導性マイクロ化学チップは、前記共有結合が、エーテル結合であるものでもよい。 In the thermally conductive microchemical chip, the covalent bond may be an ether bond.
　熱伝導性マイクロ化学チップは、前記流路担持基板シート又は前記流路維持基板シートの少なくとも一部が、ガラスビーズ及び／又はゼオライトを配合したシリコーンゴム原料組成物と、水溶性アルコールを配合したシリコーン組成物とから選ばれる少なくとも何れかで形成された発泡性シリコーンゴムシートであるものでもよい。 The thermally conductive microchemical chip includes a silicone rubber raw material composition in which at least a part of the flow path supporting substrate sheet or the flow path maintaining substrate sheet is blended with glass beads and / or zeolite, and silicone in which a water-soluble alcohol is blended. It may be a foamable silicone rubber sheet formed of at least one selected from the composition.
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、アナターゼ型又はルチル型の酸化チタン粒子が分散されたシリコーンゴムで形成されることにより、反射率を８０～１００％とする高反射性シリコーンゴムシートであるものでもよい。 The thermally conductive microchemical chip is formed of silicone rubber in which at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is dispersed with anatase type or rutile type titanium oxide particles, It may be a highly reflective silicone rubber sheet having a reflectance of 80 to 100%.
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、シリコーンゴム、エチレン－プロピレン－ジエン－メチレン共重合体ゴム、ブチルゴム、アクリロニトリル－ブタジエン共重合体ゴム、フッ素ゴム、スチレン－ブタジエン共重合体ゴム及び／又はヒドリンゴムで形成されることにより、酸素ガス、窒素ガス、二酸化炭素ガス及び水蒸気の少なくとも何れかのガスのガス透過率を５００～０．０５（cc/cm2/mm/sec/cm・Hg×1010）とする低ガス透過性シリコーンゴムシートであるものでもよい。 In the thermally conductive microchemical chip, at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is made of silicone rubber, ethylene-propylene-diene-methylene copolymer rubber, butyl rubber, acrylonitrile-butadiene copolymer. By being formed of a combined rubber, a fluoro rubber, a styrene-butadiene copolymer rubber and / or a hydrin rubber, the gas permeability of at least one of oxygen gas, nitrogen gas, carbon dioxide gas and water vapor is set to 500-0. It may be a low gas permeable silicone rubber sheet of 05 (cc / cm 2 / mm / sec / cm · Hg × 10 10 ).
　熱伝導性マイクロ化学チップは、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、パーオキサイド架橋シリコーンゴム、付加架橋シリコーンゴム、縮合架橋シリコーンゴム、放射線架橋又は電子線架橋シリコーンゴム及びこれらのうちの何れかのシリコーンゴムとオレフィン系ゴムとの共ブレンド物から選ばれる何れかで形成されているものでもよい。 In the thermally conductive microchemical chip, at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is a peroxide crosslinked silicone rubber, an addition crosslinked silicone rubber, a condensation crosslinked silicone rubber, a radiation crosslinked or an electron beam crosslinked. It may be formed of any one selected from silicone rubbers and co-blends of any of these silicone rubbers and olefinic rubbers.
　熱伝導性マイクロ化学チップは、前記流路の一部が拡径して液溜部となっているものであってもよい。 The thermally conductive microchemical chip may be one in which a part of the flow path is enlarged to form a liquid reservoir.
　本発明の熱伝導性マイクロ化学チップの製造方法は、単数又は複数のゴム製の流路担持基板シートに、検体、試薬及び試料から選ばれる流動試料を加圧及び／又は毛細管現象により流し込み化学反応及び／又は化学作用させる流路を、設ける流路成形工程と、ゴム、樹脂、金属、セラミックス及び／又はガラスで形成され、前記流路に繋がる受渡穴を開けており前記流路担持基板シートを挟む流路維持基板シートを、形成する受渡穴形成工程と、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、コロナ処理、プラズマ処理、及び紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）する処理工程と、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、常圧下、加圧下又は減圧下で重ねて、直接、又は分子接着剤を介した共有結合により、接合して、一体化する接合工程とを有し、酸化アルミニウム、酸化マグネシウム、酸化亜鉛、グラファイトカーボン、チッ化ケイ素、チッ化ホウ素及びチッ化アルミニウムから選ばれる少なくとも何れかの熱伝導性フィラー粉末を含んだシリコーンゴム組成物で成形して、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、熱伝導性シートにするというものである。 The method for producing a thermally conductive microchemical chip according to the present invention includes a chemical reaction in which a fluid sample selected from a specimen, a reagent, and a sample is poured into a single or a plurality of rubber channel support substrate sheets by pressurization and / or capillary action. And / or a flow path forming step for providing a flow path for chemical action, and formed with rubber, resin, metal, ceramics and / or glass, and having a delivery hole connected to the flow path, At least one of the delivery hole forming step for forming the sandwiched flow path maintenance substrate sheet and the flow path carrying substrate sheet and the flow path maintenance substrate sheet, corona treatment, plasma treatment, and ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and at least one of the flow path carrying substrate sheet and the flow path maintenance substrate sheet under normal pressure, increased pressure, or reduced pressure. A joining step for joining and integrating directly or by a covalent bond via a molecular adhesive, aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride, boron nitride and Molded with a silicone rubber composition containing at least one heat conductive filler powder selected from aluminum nitride, and at least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is thermally conductive It is to make a sheet.
　熱伝導性マイクロ化学チップの製造方法は、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、シリコーンゴムで形成するものであってもよい。 The method for producing a heat conductive microchemical chip may be one in which at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
　本発明の熱伝導性マイクロ化学チップは、流動試料を高圧での加圧や毛細管現象によりそれの微細な流路へ流し込んだときに、シリコーンゴム製熱伝導性シートが放熱し易いことによって、充分に放冷する。そのため、微量の生体由来検体のような貴重な検体や稀薄で微量の試薬や繊細な細胞・ウィルスの試料のような流動試料を高温に晒させず、不意に分解したり副反応で不純物にしたり死滅・分解したりすることなく、所望の通り分析したり反応させたり培養・増幅させたりすることができる。また、熱伝導性マイクロ化学チップは、意図的にヒーターで昇温して加熱される場合でも、シリコーンゴム製熱伝導性シートが熱伝導し易いことによって、速やかに加熱され適温に維持できる。 The heat-conductive microchemical chip of the present invention is sufficient because the heat-conductive sheet made of silicone rubber is easy to dissipate heat when a flowing sample is poured into its fine flow path by pressurization at high pressure or capillary action. Allow to cool. Therefore, precious specimens such as trace amounts of biological specimens, fluid specimens such as dilute and trace amounts of reagents, delicate cell / virus samples, etc. are not exposed to high temperatures, but are unexpectedly decomposed or made impurities by side reactions. It can be analyzed, reacted, cultured and amplified as desired without being killed or decomposed. In addition, even when the heat conductive microchemical chip is intentionally heated by a heater, the heat conductive sheet made of silicone rubber is easy to conduct heat, so that it can be quickly heated and maintained at an appropriate temperature.
　この熱伝導性マイクロ化学チップは、流路担持基板シートと流路維持基板シートとが、直接的な化学的分子間結合、即ちエーテル結合のような共有結合による強固な接着で、そのシート上の流路領域外の接合面で確りと接合している。そのため、流動試料を漏らさずに高圧に加圧して流動させる微細な流路が、確実に形成されている。 In this thermally conductive microchemical chip, the channel-carrying substrate sheet and the channel-maintaining substrate sheet are directly bonded to each other by a strong bond by a direct chemical intermolecular bond, that is, an ether bond. It is firmly joined at the joint surface outside the flow path region. For this reason, a fine flow path that allows the fluid sample to flow under high pressure without leaking is reliably formed.
　この熱伝導性マイクロ化学チップは、単数又は複数の流路担持基板シートのそれぞれに直線や曲線を組み合わせた線状やその末端乃至途中で拡大したり集束又は分岐したりした複雑なパターン形状で０．５μｍ～５ｍｍ幅の微細な流路が、精密に形成することができるものである。そのような微細な流路を有していても、検体や試薬である流動体が加圧されて送り込まれその流路で流動する際に、流路担持基板シートと流路維持基板シートとが剥がれないので、この熱伝導性マイクロ化学チップが破損しない。 This thermally conductive microchemical chip is a linear combination of straight lines and curved lines on each of one or a plurality of flow path carrying substrate sheets, and a complicated pattern shape that is enlarged or converged or branched at the end or halfway. A fine flow path with a width of 5 μm to 5 mm can be precisely formed. Even when such a fine flow path is provided, when the fluid, which is a specimen or a reagent, is pressurized and sent and flows through the flow path, the flow path supporting substrate sheet and the flow path maintaining substrate sheet are Since it does not peel off, this thermally conductive microchemical chip is not damaged.
　この熱伝導性マイクロ化学チップは、微細な流路に常圧～５気圧程度の圧力で、液状又はガス状の検体や試薬や細胞液等である流動試料を送り込んでも、氷冷下～１２０℃程度、汎用的には０～１００℃程度又は２０～１２０℃程度の低温乃至高温の温度範囲で加熱冷却を繰り返しながら検体や試薬を送り込んでも、流路担持基板シートのゴム弾性により流路が破損しない。 This thermally conductive microchemical chip can be used in a fine flow path at a pressure of normal pressure to about 5 atm. Even when a fluid or gaseous sample, reagent, cell fluid, or other fluid sample is sent, it is cooled to 120 ° C under ice cooling. Even if samples and reagents are fed repeatedly while heating and cooling in the low to high temperature range of 0 to 100 ° C or 20 to 120 ° C for general purposes, the flow path breaks due to the rubber elasticity of the flow path support substrate sheet do not do.
　この熱伝導性マイクロ化学チップによれば、検体や試薬や試料である流動試料を確実かつ精度良く所望の流路へ、所望の温度に維持しつつ、送り込むことができる。その結果、その検体中のバイオ成分等の有用物質を正確かつ簡便に短期間で分析したり、薬理作用を示すバイオ成分等の有用物質の原材料成分や反応基質等の試薬を目的通りに反応させたり、細胞やウィスルを培養・増幅させたりできる。 According to this thermally conductive microchemical chip, it is possible to send a fluid sample, which is a specimen, a reagent, or a sample, to a desired flow path reliably and accurately while maintaining a desired temperature. As a result, useful substances such as biocomponents in the specimen can be analyzed accurately and simply in a short period of time, or raw materials components of useful substances such as biocomponents exhibiting pharmacological action and reagents such as reaction substrates can be reacted as intended. Or cultivate and amplify cells and whistles.
　この熱伝導性マイクロ化学チップは、流路担持基板シートの流路を微細にして、検体や試薬や試料と流路担持基板シートや流路維持基板シートとの接触を可能な限り抑え、検体や試薬や試料の不意な汚染や吸着を防止することができる。 This thermally conductive microchemical chip makes the flow path of the flow path carrying substrate sheet fine and suppresses contact between the specimen, reagent or sample and the flow path carrying substrate sheet or flow path maintenance substrate sheet as much as possible. Unexpected contamination and adsorption of reagents and samples can be prevented.
　この熱伝導性マイクロ化学チップは、ディスポーザブルで用いられる場合、別な検体や試薬や試料の混入による汚染の恐れが無く、信頼性のある結果を得ることができるものである。 When this thermally conductive microchemical chip is used in a disposable manner, there is no fear of contamination due to mixing of another specimen, reagent or sample, and a reliable result can be obtained.
　この熱伝導性マイクロ化学チップは、外形が数ｍｍ～十数ｃｍ四方で極めて小型であり簡易な構造にすることができるものである。この熱伝導性マイクロ化学チップは、小型でも多数の直列、並列又は分岐した流路を平面状及び／又は立体状に備え、注入口や排出口を多数設けて、複数の反応過程を直列又は並列若しくは立体的かつ縦横無尽に経る多機能にすることができる。そのため大掛かりな分析装置などを用いなくてもポータブルの分析装置を用いて、屋内のみならず屋外でも迅速に複数種の定性・定量分析を行うことができる。さらに、熱伝導性マイクロ化学チップに用いられる分析試薬や反応試薬や培養液等は極微量で済むうえ、フラスコや試験管での分析や反応や培養・増幅に比べて廃液量が格段に少なくなるので、環境保全に資する。 This thermally conductive microchemical chip has an outer shape of several mm to several tens of cm square, is extremely small, and can have a simple structure. This thermally conductive microchemical chip has a large number of series, parallel, or branched flow paths in a planar and / or three-dimensional shape, and is provided with a large number of inlets and outlets so that a plurality of reaction processes are connected in series or in parallel. Or it can be made into a multi-function which goes through three-dimensional and infinite length and breadth. Therefore, a plurality of types of qualitative / quantitative analyzes can be quickly performed not only indoors but also outdoors using a portable analyzer without using a large analyzer. In addition, only a very small amount of analysis reagent, reaction reagent, culture solution, etc. are used for the heat conductive microchemical chip, and the amount of waste liquid is significantly reduced compared to analysis, reaction, culture and amplification in flasks and test tubes. So it contributes to environmental conservation.
　本発明の熱伝導性マイクロ化学チップを製造する方法によれば、極めて簡便であり、短工程で、高品質で均質な熱伝導性マイクロ化学チップを歩留まり良く安価で大量に製造できる。 According to the method for producing a thermally conductive microchemical chip of the present invention, it is very simple and can produce a high-quality and homogeneous thermally conductive microchemical chip in a large quantity at a low yield with a high yield.
　熱伝導性マイクロ化学チップを製造する方法は、熱伝導性フィラー粉末を含んだ熱伝導性シートを用いて、放冷すべき場合に放熱によって高温に晒されず又はヒーターで昇温すべき場合に加熱できる熱伝導性マイクロ化学チップを簡易に製造することができる。この方法によれば、流路担持基板シートと流路維持基板シートとが、その流路領域外で、接触によってエーテル結合のような共有結合を直接形成して、簡便に、接着剤よりも遥かに強力に接合する。このような分子接着は、熱可塑性樹脂を熱融着させる程の高温の加熱を必要とせず、熱融着温度未満で短時間加熱すれば、充分に惹き起される。そのため、光学的分析の精度を妨げる屈折率の変動や熱変形・歪みを生じない。 A method for producing a thermally conductive microchemical chip uses a thermally conductive sheet containing a thermally conductive filler powder, when it is not to be exposed to high temperature due to heat dissipation when it is allowed to cool, or when it is to be heated with a heater. A heat conductive microchemical chip that can be heated can be easily manufactured. According to this method, the channel-carrying substrate sheet and the channel-maintaining substrate sheet directly form a covalent bond such as an ether bond by contact outside the channel region, which is simpler than the adhesive. Strongly joined to. Such molecular adhesion does not require heating at such a high temperature as to cause the thermoplastic resin to be thermally fused, and is sufficiently induced if heated for a short time at a temperature lower than the thermal fusion temperature. Therefore, there is no refractive index variation or thermal deformation / distortion that hinders the accuracy of optical analysis.
本発明を適用する熱伝導性マイクロ化学チップの模式的な分解斜視図である。It is a typical exploded perspective view of the heat conductive microchemical chip to which the present invention is applied. 本発明を適用する別な熱伝導性マイクロ化学チップの模式的な分解斜視図である。It is a typical exploded perspective view of another heat conductive microchemical chip to which the present invention is applied. 本発明を適用する熱伝導性マイクロ化学チップの使用状態を示す斜視図である。It is a perspective view which shows the use condition of the heat conductive microchemical chip to which this invention is applied. 本発明を適用する別な熱伝導性マイクロ化学チップの模式的な分解斜視図である。It is a typical exploded perspective view of another heat conductive microchemical chip to which the present invention is applied. 本発明を適用する別な熱伝導性マイクロ化学チップの模式的な分解斜視図である。It is a typical exploded perspective view of another heat conductive microchemical chip to which the present invention is applied. 本発明を適用する熱伝導性マイクロ化学チップの流路維持基板シートとして用いられ得るシリコーンゴムシートの断熱性についての温度と時間経過との相関を示すグラフである。It is a graph which shows the correlation with the temperature and time progress about the heat insulation of the silicone rubber sheet which can be used as a flow-path maintenance board | substrate sheet | seat of the heat conductive microchemical chip to which this invention is applied.
　以下、本発明を実施するための形態を詳細に説明するが、本発明の範囲はこれらの形態に限定されるものではない。 Hereinafter, modes for carrying out the present invention will be described in detail, but the scope of the present invention is not limited to these modes.
　本発明を適用する熱伝導性マイクロ化学チップ１の一例は、それの製造途中を示す図１の通り、カバー用を兼ねるポリイミド製流路維持基板シート１０と、底面支持用を兼ねるポリイミド製流路維持基板シート３０との間に、微細な流路を有するシリコーンゴム製流路担持基板シート２０が、重ね合わされた可撓性のものである。 An example of the thermally conductive microchemical chip 1 to which the present invention is applied is as shown in FIG. 1 showing the process of manufacturing the polyimide channel maintaining substrate sheet 10 that also serves as a cover, and a polyimide channel that also serves as a bottom support. A silicone rubber flow path carrying substrate sheet 20 having fine flow paths is overlapped with the maintenance substrate sheet 30 and is flexible.
　流動試料注入穴１１・流動試料排出穴１２・流動試料注入部位２１・流動試料排出部位２２・流路２６は、検体、試薬及び試料から選ばれる流動試料を加圧して流し込み化学反応させるものである。流動試料注入穴１１・流動試料排出穴１２・流動試料注入部位２１・流動試料排出部位２２・流路２６は、流路維持基板シート１０・３０及び流路担持基板シート２０に、おもて面及び／又はうら面で溝状に凹んで、又は溝状若しくは孔状に貫通して形成されている。 The flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection portion 21, the flow sample discharge portion 22, and the flow path 26 pressurize a flow sample selected from a specimen, a reagent, and a sample to cause a chemical reaction. . The flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection part 21, the flow sample discharge part 22, and the flow path 26 are connected to the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20. And / or recessed in a groove shape on the back surface, or penetrating in a groove shape or a hole shape.
　流路維持基板シート１０・３０及び流路担持基板シート２０は、接合して一体化している。流路維持基板シート１０・３０及び流路担持基板シート２０は、その接合面がコロナ処理、プラズマ処理、又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されて、重ねられたものである。流路維持基板シート１０・３０及び流路担持基板シート２０は、流動試料注入穴１１・流動試料排出穴１２・流動試料注入部位２１・流動試料排出部位２２・流路２６以外で、コロナ処理、プラズマ処理、又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されて生じた活性基、例えば水酸基（－ＯＨ）やヒドロキシシリル基（－ＳｉＯＨ）のような反応性活性基同士が、共有結合により直接、化学結合して、強固に接合することにより、剥離不能に一体化している。このようなエーテル結合は、ＯＨ基同士の脱水によるエーテル結合であることが好ましい。 The flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are joined and integrated. The flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are obtained by superimposing the joint surfaces thereof by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). is there. The flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 are subjected to corona treatment except for the flow sample injection hole 11, the flow sample discharge hole 12, the flow sample injection portion 21, the flow sample discharge portion 22, and the flow passage 26. Active groups generated by plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment), for example, reactive active groups such as hydroxyl groups (—OH) and hydroxysilyl groups (—SiOH) are shared. It is integrated so that it cannot be peeled by direct chemical bonding and strong bonding. Such an ether bond is preferably an ether bond by dehydration of OH groups.
　流路担持基板シート２０は、シリコーンゴム原材料成分を含有する組成物から成形されて形成されている。 The flow path carrying substrate sheet 20 is formed by molding from a composition containing a silicone rubber raw material component.
　流路担持基板シート２０中のシリコーンゴムは、主成分が、パーオキサイド架橋シリコーンゴム、付加架橋シリコーンゴム、縮合架橋シリコーンゴム、又はこれらのシリコーンゴムとオレフィン系ゴムとの共ブレンド物である。 The main component of the silicone rubber in the channel-carrying substrate sheet 20 is peroxide-crosslinked silicone rubber, addition-crosslinked silicone rubber, condensation-crosslinked silicone rubber, or a co-blend of these silicone rubber and olefin rubber.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、酸化アルミニウム、酸化マグネシウム、酸化亜鉛、グラファイトカーボン、チッ化ケイ素、チッ化ホウ素、及びチッ化アルミニウムから選ばれる熱伝導性フィラー粉末を含んだ熱伝導性シートとなっている。熱伝導性フィラー粉末は、流路維持基板シート１０・３０及び流路担持基板シート２０中、それぞれ５０～９５重量％含まれる。熱伝導性フィラー粉末は、平均粒径０．２～５０μｍであることが好ましい。 Any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are selected from aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride, boron nitride, and aluminum nitride. It is a thermally conductive sheet containing conductive filler powder. The heat conductive filler powder is contained in the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 in an amount of 50 to 95% by weight, respectively. The heat conductive filler powder preferably has an average particle size of 0.2 to 50 μm.
　流路担持基板シート２０の何れか又は全てが、コロナ処理、プラズマ処理、又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されて生じた活性基同士で、共有結合し易くなるように、白金触媒、例えば１，３－ジビニル－１，１，３，３－テトラメチルジシロキサン白金（０）触媒（Ｐｔ（ｄｖｓ））２．１－２．４％キシレン溶液（Ｇｅｌｅｓｔ社製品）のような白金錯体を、白金換算で１０～１０００ｐｐｍの濃度で含んでいることが好ましい。 Any or all of the channel-carrying substrate sheets 20 may be easily covalently bonded to each other with active groups generated by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). Platinum catalyst, for example, 1,3-divinyl-1,1,3,3-tetramethyldisiloxane platinum (0) catalyst (Pt (dvs)) 2.1-2.4% xylene solution (product of Gelest) Such a platinum complex is preferably contained at a concentration of 10 to 1000 ppm in terms of platinum.
　流路担持基板シート２０の何れか又は全てが、ビニルアルコキシシリル基を有するビニルアルコキシシランユニットが２～６ユニットのシランカップリング剤、例えばポリビニルメトキシシロキサンを、０．５～１０重量部の濃度で含んでいることが好ましい。シランカップリング剤のビニル基と、シリコーンゴムポリマー内のビニル基やハイドロジェンシロキサン基とがパーオキサイドや白金触媒により共有結合するエーテル結合とは別な共有結合によって一層強固に接合できるようになる。このとき、白金触媒を含んでいると一層、共有結合し易くなるので好ましい。 Any or all of the channel-carrying substrate sheets 20 contain 2 to 6 units of a silane coupling agent having a vinylalkoxysilyl group having a vinylalkoxysilyl group, for example, polyvinyl methoxysiloxane at a concentration of 0.5 to 10 parts by weight. It is preferable to include. The vinyl group of the silane coupling agent and the vinyl group or hydrogensiloxane group in the silicone rubber polymer can be more strongly bonded by a covalent bond different from the ether bond covalently bonded by a peroxide or a platinum catalyst. At this time, it is preferable that a platinum catalyst is contained because it becomes easier to covalently bond.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、難燃性の作用をする三酸化アンチモン、水酸化アルミニウムである粉末を、難燃性の機能付与のため、含ませていてもよい。これら粉末は、流路維持基板シート１０・３０及び流路担持基板シート２０中、５～５０重量％含まれ、平均粒径５～２０μｍとすることが好ましい。 Any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made of antimony trioxide and aluminum hydroxide, which have a flame retardant action, to impart a flame retardant function. It may be included. These powders are included in the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 in an amount of 5 to 50% by weight and preferably have an average particle size of 5 to 20 μm.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、シリコーンオイル、例えば、ポリジメチルシロキサン、メチルフェニルシロキサン、又はフルオロシリコーンオイルを、０．５～３０重量％含んでいてもよい。シリコーンオイルは、充填剤を添加し易い作用を付与するためにシリコーンゴムに添加されるものである。 Any or all of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 contain 0.5 to 30% by weight of silicone oil, for example, polydimethylsiloxane, methylphenylsiloxane, or fluorosilicone oil. May be. Silicone oil is added to silicone rubber in order to provide an effect of easily adding a filler.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、反射率を高めたりバルブの機能を発現させたりできるように、発泡性シリコーンゴムで形成されていてもよい。発泡性シリコーンゴムは、ガラスビーズやゼオライトを配合したシリコーンゴム組成物、水溶性アルコールを配合したシリコーン組成物で例示される発泡性シリコーンゴム成分を含有するシリコーンゴム組成物から成形されて形成されている。 Any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 may be formed of foamable silicone rubber so that the reflectance can be increased and the function of the valve can be expressed. The foamable silicone rubber is formed by molding from a silicone rubber composition containing a foamable silicone rubber component exemplified by a silicone rubber composition containing glass beads and zeolite and a silicone composition containing a water-soluble alcohol. Yes.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、高い反射率を有することにより蛍光検出等の光で検出を高感度ですることができるように、アナターゼ型又はルチル型の酸化チタン粒子が分散されて成形されており、酸化チタン含有シリコーン組成物で例示される高反射率発現成分を含有するシリコーンゴム組成物から成形されて形成されていてもよい。これにより、流路維持基板シート１０・３０及び流路担持基板シート２０の反射率が、８０～１００％となる。 Either or all of the flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 have a high reflectance so that detection can be performed with high sensitivity by light such as fluorescence detection. The rutile-type titanium oxide particles may be dispersed and molded, and may be formed by molding from a silicone rubber composition containing a high reflectance component exemplified by the titanium oxide-containing silicone composition. As a result, the reflectivity of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is 80 to 100%.
　流路担持基板シート２０が、その他のゴムで形成されていてもよい。流路担持基板シート２０が、低いガス透過性を有することにより、外界の酸素や二酸化炭素や水蒸気（湿気）等の影響を受けないように、シリコーンゴム、エチレン－プロピレン－ジエン－メチレン共重合体ゴム（ＥＰＤＭ）、ブチルゴム、アクリロニトリル－ブタジエン共重合体ゴム（ＮＢＲ）、フッ素ゴム、スチレン－ブタジエン共重合体ゴム（ＳＢＲ）、ヒドリンゴムで形成されることが好ましい。具体的には、シリコーンゴムにＥＰＤＭやマイカやタルクのような鱗片状のフィラーをブレンドした組成物や、ブチルゴム、ＮＢＲ、ＥＰＤＭ、ＮＢＲ、フッ素ゴム、ＳＢＲ、ヒドリンで例示される低ガス透過性発現成分を含有するシリコーンゴム組成物から成形されて形成されていてもよい。これにより、流路担持基板シート２０が、酸素ガス、窒素ガス、二酸化炭素ガス及び水蒸気の少なくとも何れかのガスのガス透過率を５００～０．０５（cc/cm2/mm/sec/cm・Hg×1010）とする低ガス透過性シリコーンゴムシートとなる。 The flow path carrying substrate sheet 20 may be formed of other rubber. Silicone rubber, ethylene-propylene-diene-methylene copolymer so that the channel-carrying substrate sheet 20 has low gas permeability so that it is not affected by external oxygen, carbon dioxide, water vapor (humidity), etc. It is preferably formed of rubber (EPDM), butyl rubber, acrylonitrile-butadiene copolymer rubber (NBR), fluorine rubber, styrene-butadiene copolymer rubber (SBR), or hydrin rubber. Specifically, a composition in which a scale-like filler such as EPDM, mica and talc is blended with silicone rubber, and low gas permeability manifested by butyl rubber, NBR, EPDM, NBR, fluororubber, SBR and hydrin You may form and shape | mold from the silicone rubber composition containing a component. Thereby, the flow path carrying substrate sheet 20 has a gas permeability of at least one of oxygen gas, nitrogen gas, carbon dioxide gas and water vapor of 500 to 0.05 (cc / cm 2 / mm / sec / cm · It becomes a low gas permeable silicone rubber sheet of Hg × 10 10 ).
　流路維持基板シート１０・３０が、ポリイミドで形成された例を示したが、シクロオレフィンポリマー（ＣＯＰ）やアルミニウム箔又はアルミニウム板やガラス板で形成されていてもよく、流路担持基板シート２０用の材質として例示したシリコーンで形成されていてもよく難燃剤等を含んで形成されていてもよい。 Although the example in which the flow path maintaining substrate sheets 10 and 30 are formed of polyimide has been shown, the flow path maintaining substrate sheet 20 may be formed of a cycloolefin polymer (COP), an aluminum foil, an aluminum plate, or a glass plate. It may be formed of silicone exemplified as a material for use, and may be formed including a flame retardant.
　流路維持基板シート１０・３０及び流路担持基板シート２０は、分子接着剤を介した共有結合により、接合して一体化していてもよい。 The flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 may be joined and integrated by covalent bonding via a molecular adhesive.
　分子接着剤とは、その分子中の官能基が被着体と共有結合による化学反応することによって、流路維持基板シート１０・３０及び流路担持基板シート２０とを、単分子乃至は多分子の分子接着剤分子による共有結合を介して直接結合するものである。分子接着剤は、二つの官能基が被着体である流路維持基板シート１０・３０と流路担持基板シート２０とに夫々化学反応して共有結合を形成するもので、このような両官能性の分子の総称であり、具体的には、シランカップリング剤をはじめとする各種カップリング剤が挙げられる。 The molecular adhesive means that the functional group in the molecule chemically reacts with the adherend by covalent bonding, so that the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made to be a single molecule or a polymolecule. It is directly bonded through a covalent bond by the molecular adhesive molecule. The molecular adhesive forms a covalent bond by chemically reacting with the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 having two functional groups as adherends. And, specifically, various coupling agents including a silane coupling agent.
　分子接着剤は、より具体的には、
トリエトキシシリルプロピルアミノ－１，３，５－トリアジン－２，４－ジチオール（ＴＥＳ）、アミノエチルアミノプロピル トリメトキシシランのようなアミノ基含有化合物；
トリエトキシシリルプロピルアミノ基のようなトリアルコキシシリルアルキルアミノ基とメルカプト基又はアジド基とを有するトリアジン化合物、下記化学式(Ｉ)
Figure JPOXMLDOC01-appb-C000001
 （式(Ｉ)中、Ｗは、スペーサ基、例えば置換基を有していてもよいアルキレン基、アミノアルキレン基であってもよく、直接結合であってもよい。Ｙは、ＯＨ基又は加水分解や脱離によりＯＨ基を生成する反応性官能基、例えばトリアルコキシアルキル基である。－Ｚは、－Ｎ３又は－ＮＲ１Ｒ２である（但し、Ｒ１，Ｒ２は同一又は異なりＨ又はアルキル基、－Ｒ３Ｓｉ（Ｒ４）ｍ（ＯＲ５）３－ｍ[Ｒ３，Ｒ４はアルキル基、Ｒ５はＨ又はアルキル基、ｍは０～２]。なお、アルキレン基、アルコキシ、アルキル基は、置換基を有していてもよい炭素数１～１２の直鎖状、分岐鎖状及び／又は環状の炭化水素基である。）で表わされるトリアジン化合物；
トリアルコキシシリルアルキル基を有するチオール化合物；
トリアルキルオキシシリルアルキル基を有するエポキシ化合物；
CH2=CH-Si(OCH3)2-O-[Si(OCH3)2-O-]n-Si(OCH3)2-CH=CH2　(n=1.8～5.7)で例示されるビニルアルコキシシロキサンポリマーのようなシランカップリング剤
が挙げられる。 More specifically, molecular adhesives
Amino group-containing compounds such as triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol (TES), aminoethylaminopropyl trimethoxysilane;
A triazine compound having a trialkoxysilylalkylamino group such as a triethoxysilylpropylamino group and a mercapto group or an azide group, the following chemical formula (I)
Figure JPOXMLDOC01-appb-C000001
 (In formula (I), W may be a spacer group, for example, an alkylene group which may have a substituent, an aminoalkylene group, or a direct bond. Y is an OH group or A reactive functional group that generates an OH group by decomposition or elimination, such as a trialkoxyalkyl group, -Z is -N 3 or -NR 1 R 2 (provided that R 1 and R 2 are the same or different; H or an alkyl group, —R 3 Si (R 4 ) m (OR 5 ) 3-m [R 3 and R 4 are alkyl groups, R 5 is H or an alkyl group, and m is 0 to 2.] An alkylene group , An alkoxy group and an alkyl group are linear, branched and / or cyclic hydrocarbon groups having 1 to 12 carbon atoms which may have a substituent;
A thiol compound having a trialkoxysilylalkyl group;
An epoxy compound having a trialkyloxysilylalkyl group;
Vinyl represented by CH 2 = CH-Si (OCH 3 ) 2 -O- [Si (OCH 3 ) 2 -O-] n -Si (OCH 3 ) 2 -CH = CH 2 (n = 1.8 to 5.7) Examples include silane coupling agents such as alkoxysiloxane polymers.
　流路維持基板シート１０・３０及び流路担持基板シート２０が、シリコーンゴムである場合、コロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されるだけで、十分に活性基が発現するので直接接合してもよいが、前記シランカップリング剤のような分子接着剤を用いて、接合してもよい。一方、流路維持基板シート１０・３０が非シリコーンゴム製の樹脂である場合、前記シランカップリング剤のような分子接着剤の０．０５～１重量％のアルコール溶液例えばメタノール溶液へ浸漬され乾燥された後、接合されることが好ましい。分子接着剤の溶液の濃度は、高過ぎると、両シート間での接合面が剥がれることとなり、薄過ぎると両シートを十分に接合できなくなってしまう。 When the flow path maintaining substrate sheet 10/30 and the flow path supporting substrate sheet 20 are made of silicone rubber, it is sufficient to perform corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). Since active groups are expressed, they may be joined directly, but may be joined using a molecular adhesive such as the silane coupling agent. On the other hand, when the flow path maintaining substrate sheet 10/30 is a resin made of non-silicone rubber, it is dipped in a 0.05 to 1% by weight alcohol solution such as a methanol solution of a molecular adhesive such as the silane coupling agent and dried. Then, it is preferable to be joined. If the concentration of the molecular adhesive solution is too high, the joint surface between the two sheets will be peeled off, and if it is too thin, the two sheets cannot be sufficiently joined.
　流路担持基板シート２０に、液状又はガス状の検体や試薬である流動試料を加圧して流し込み化学反応させる溝状の微細流路２６が、表裏を貫通して形成されている。微細流路２６は、始点末端である流動試料注入部位２１ａ・２１ｂからそれぞれ延びて下流で合流し、そこから流動試料排出部位２２ａへ延びる支流と、流動試料排出部位２２ｂ及び２２ｃへ延びる本流とに分岐して、本流がその下流で終点末端である流動試料排出部位２２ｂ及び２２ｃへ延びて分岐したものである。流路担持基板シート２０の上面２４と下面２５とは、微細流路２６領域外で、その表面がコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）で活性化されている。 A groove-like microchannel 26 is formed through the front and back surfaces of the channel-carrying substrate sheet 20 by pressurizing and flowing a fluid sample, which is a liquid or gaseous specimen or reagent, to cause a chemical reaction. The micro flow path 26 extends from the flow sample injection sites 21a and 21b, which are the starting point ends, and merges downstream, and from there to a tributary that extends to the flow sample discharge site 22a and a main flow that extends to the flow sample discharge sites 22b and 22c. The main flow is branched and extends downstream to the flow sample discharge portions 22b and 22c which are the end points at the downstream end. The upper surface 24 and the lower surface 25 of the channel-carrying substrate sheet 20 are activated by corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) outside the region of the fine flow passage 26. ing.
　流路担持基板シート２０に重なる同じ大きさのカバー用の流路維持基板シート１０に、流動試料注入部位２１ａ・２１ｂと流動試料排出部位２２ａ・２２ｂ・２２ｃとに対応する位置で、それぞれ流動試料注入穴１１ａ・１１ｂと流動試料排出穴１２ａ・１２ｂ・１２ｃとが、開いている。流路担持基板シート２０へ向いたカバー用の流路維持基板シート１０の下面１５は、流動試料注入穴１１ａ・１１ｂと流動試料排出穴１２ａ・１２ｂ・１２ｃとの領域外で、その表面がコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）で活性化されている。 A flow sample at a position corresponding to the flow sample injection site 21a, 21b and the flow sample discharge site 22a, 22b, 22c on the flow channel maintenance substrate sheet 10 for a cover of the same size overlapping the flow channel carrying substrate sheet 20, respectively. Injection holes 11a and 11b and fluid sample discharge holes 12a, 12b, and 12c are opened. The lower surface 15 of the cover flow path maintenance substrate sheet 10 facing the flow path carrying substrate sheet 20 is outside the region of the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b and 12c, and the surface thereof is corona. It is activated by treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment).
　流路担持基板シート２０へ向いた底面支持用の流路維持基板シート３０の上面３４は、その表面の全面がコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）で活性化されている。 The upper surface 34 of the flow path maintenance substrate sheet 30 for supporting the bottom surface facing the flow path carrying substrate sheet 20 is entirely corona-treated, plasma-treated or ultraviolet-irradiated (general UV treatment or excimer UV treatment). It has been activated.
　流路維持基板シート１０・３０と流路担持基板シート２０との表面で、活性化されて生成し又は元来有する水酸基のような活性基同士が、脱水して強固な共有結合であるエーテル結合を生じ、対峙し合う流路維持基板シート１０・３０と流路担持基板シート２０とを化学的に直接、接合している。 Ether bonds in which active groups such as hydroxyl groups that are activated or originally formed on the surfaces of the channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 are dehydrated to form strong covalent bonds. The flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 facing each other are chemically directly bonded.
　流路維持基板シート１０・３０及び流路担持基板シート２０は、接合して一体化する際、その接合面がコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されて、常圧で重ねられた後、常圧下のまま共有結合させてもよいが、減圧下又は加圧下で共有結合させてもよい。流路維持基板シート１０・３０及び流路担持基板シート２０のＯＨのような活性基、又はそれらに反応するシランカップリング剤の反応性官能基との接近は、減圧乃至真空条件下、例えば５０ｔｏｒｒ以下、より具体的には５０～１０ｔｏｒｒの減圧条件、又は１０ｔｏｒｒ未満、より具体的には、１０ｔｏｒｒ未満～１×１０－３ｔｏｒｒ、好ましくは１０ｔｏｒｒ未満～１×１０－２ｔｏｒｒの真空条件下で、その接触界面の気体媒体を除去することによって、又はその接触界面に応力（荷重）、例えば１０～２００ｋｇｆを加えることによって、さらに接触界面を加熱することによって、促進される。減圧又は加圧条件で、流路維持基板シート１０・３０と流路担持基板シート２０との接合面全面に、均一に圧力が掛ることが好ましい。上記範囲を外れると、均一に圧力が掛らない恐れがある。 When the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 are joined and integrated, the joint surfaces are subjected to corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment). Then, after overlapping at normal pressure, it may be covalently bonded under normal pressure, but may be covalently bonded under reduced pressure or under pressure. Access to the active groups such as OH of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 or the reactive functional group of the silane coupling agent that reacts with them is under reduced pressure or vacuum conditions, for example, 50 torr. Hereinafter, more specifically, under reduced pressure conditions of 50 to 10 torr, or less than 10 torr, more specifically, under vacuum conditions of less than 10 torr to less than 1 × 10 −3 torr, preferably less than 10 torr to 1 × 10 −2 torr. It is facilitated by removing the gaseous medium at the contact interface or by further heating the contact interface by applying stress (load), eg 10-200 kgf, to the contact interface. It is preferable that pressure is uniformly applied to the entire bonding surface between the flow path maintaining substrate sheets 10 and 30 and the flow path holding substrate sheet 20 under reduced pressure or pressurized conditions. If it is out of the above range, the pressure may not be applied uniformly.
　単数又は複数の流路担持基板シート２０をその最上面及び／又は最下面に接して担持する単数又は複数の流路維持基板シート１０・３０とが、重ねられて、少なくとも何れかのシート１０・２０・３０の表面でコロナ処理、プラズマ処理及び紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）から選ばれる乾式処理と分子接着剤処理との少なくとも何れかによる直接的な及び／又は前記分子接着剤を介した間接的な共有結合により、接合して一体化している。そのために、乾式処理と分子接着剤処理との何れかのみを施してもよく、それらを連続的に交互に施してもよい。例えば、乾式処理のみで接合していてもよく、乾式処理に引き続く分子接着剤処理で接合していてもよく、乾式処理に引き続く分子接着処理とさらに乾式処理とで接合していてもよく、分子接着剤処理のみで接合していてもよく、分子接着剤処理に引き続く乾式処理で接合していてもよく、分子接着処理引き続く乾式処理とさらに分子接着処理とで接合していてもよい。 At least one of the sheets 10... Is stacked with one or a plurality of flow path maintaining substrate sheets 10, 30 supporting the one or more flow path supporting substrate sheets 20 in contact with the uppermost surface and / or the lowermost surface thereof. Directly and / or said molecules by dry treatment selected from corona treatment, plasma treatment and ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and / or molecular adhesive treatment on the surface of 20 or 30 They are joined and integrated by an indirect covalent bond via an adhesive. For that purpose, either dry treatment or molecular adhesive treatment may be applied, or they may be continuously and alternately applied. For example, it may be bonded only by dry processing, may be bonded by molecular adhesive treatment subsequent to dry processing, may be bonded by molecular adhesion processing following dry processing, and further by dry processing, They may be joined only by the adhesive treatment, may be joined by a dry treatment subsequent to the molecular adhesive treatment, or may be joined by a dry treatment subsequent to the molecular adhesion treatment and further a molecular adhesion treatment.
　流路維持基板シート１０・３０及び流路担持基板シート２０は、ゴム成分として、シリコーンゴムのみから成っていてもよく、非シリコーンゴムを含んでいてもよい。流路維持基板シート１０・３０及び流路担持基板シート２０は、具体的には、主としてパーオキサイド架橋型シリコーンゴム、付加架橋型シリコーンゴム、縮合架橋型シリコーンゴムで例示されるシリコーンゴム、これらのシリコーンゴムとオレフィン系ゴムとの共ブレンド物で例示される三次元化シリコーンゴムを、成形金型等に入れ又は延伸して、必要に応じ架橋させることにより、製造されたシリコーンゴム弾性シートである。これらゴム素材は、数平均分子量で１万～１００万のものである。 The flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 may be made of only silicone rubber as a rubber component, or may contain non-silicone rubber. Specifically, the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are mainly composed of peroxide cross-linked silicone rubber, addition cross-linked silicone rubber, silicone rubber exemplified by condensation cross-linked silicone rubber, A silicone rubber elastic sheet produced by putting or stretching a three-dimensional silicone rubber exemplified by a co-blend of silicone rubber and olefin rubber into a molding die or the like and cross-linking as necessary. . These rubber materials have a number average molecular weight of 10,000 to 1,000,000.
　流路維持基板シート１０・３０及び流路担持基板シート２０の素材のパーオキサイド架橋型シリコーンゴムは、パーオキサイド系架橋剤で架橋できるシリコーン原料化合物を用いて合成されたものであれば特に限定されないが、具体的には、ポリジメチルシロキサン、ビニルメチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ポリジメチルシロキサン、ビニル末端ジフェニルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ジエチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端トリフロロプロピルメチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ポリフェニルメチルシロキサン、ビニルメチルシロキサン／ジメチルシロキサンコポリマー、トリメチルシロキサン基末端ジメチルシロキサン／ビニルメチルシロキサンコポリマー、トリメチルシロキサン基末端ジメチルシロキサン／ビニルメチルシロキサン／ジフェニルシロキサンコポリマー、トリメチルシロキサン基末端ジメチルシロキサン／ビニルメチルシロキサン／ジトリフロロプロピルメチルシロキサンコポリマー、トリメチルシロキサン基末端ポリビニルメチルシロキサン、メタアクリロキシプロピル基末端ポリジメチルシロキサン、アクリロキシプロピル基末端ポリジメチルシロキサン、（メタアクリロキシプロピル）メチルシロキサン／ジメチルシロキサンコポリマー、（アクリロキシプロピル）メチルシロキサン／ジメチルシロキサンコポリマーが挙げられる。 The peroxide-crosslinked silicone rubber as the material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is not particularly limited as long as it is synthesized using a silicone raw material compound that can be crosslinked with a peroxide-based crosslinking agent. Specifically, polydimethylsiloxane, vinylmethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated polydimethylsiloxane, vinyl-terminated diphenylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated diethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated trifluoro. Propylmethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated polyphenylmethylsiloxane, vinylmethylsiloxane / dimethylsiloxane copolymer, trimethylsiloxane-terminated di Cylsiloxane / vinylmethylsiloxane copolymer, trimethylsiloxane-terminated dimethylsiloxane / vinylmethylsiloxane / diphenylsiloxane copolymer, trimethylsiloxane-terminated dimethylsiloxane / vinylmethylsiloxane / ditrifluoropropylmethylsiloxane copolymer, trimethylsiloxane-terminated polyvinylmethylsiloxane, meta Examples include acryloxypropyl group-terminated polydimethylsiloxane, acryloxypropyl group-terminated polydimethylsiloxane, (methacryloxypropyl) methylsiloxane / dimethylsiloxane copolymer, and (acryloxypropyl) methylsiloxane / dimethylsiloxane copolymer.
　共存させるパーオキサイド系架橋剤として、例えばケトンパーオキサイド類、ジアシルパーオキサイド類、ハイドロパーオキサイド類、ジアルキルパーオキサイド類、パーオキシケタール類、アルキルパーエステル類、パーカーボネート類が挙げられ、より具体的には、ケトンパーオキサイド、ペルオキシケタール、ヒドロパーオキサイド、ジアルキルパーオキサイド、ペルオキシカルボナート、ペルオキシエステル、過酸化ベンゾイル、ジクミルパーオキサイド、ジベンゾイルパーオキサイド、ｔ－ブチルヒドロパーオキサイド、ジｔ－ブチルヒドロパーオキサイド、ジ（ジシクロベンゾイル）パーオキサイド、２，５－ジメチル－２，５ビス（ｔ－ブチルペルオキシ）ヘキサン、２，５－ジメチル－２，５ビス（ｔ－ブチルペルオキシ）ヘキシン、ベンゾフェノン、ミヒラアーケトン、ジメチルアミノ安息香酸エチルエステル、ベンゾインエチルエーテルが挙げられる。 Examples of the peroxide-based crosslinking agent to be coexisted include ketone peroxides, diacyl peroxides, hydroperoxides, dialkyl peroxides, peroxyketals, alkyl peresters, and percarbonates. Include ketone peroxide, peroxyketal, hydroperoxide, dialkyl peroxide, peroxycarbonate, peroxy ester, benzoyl peroxide, dicumyl peroxide, dibenzoyl peroxide, t-butyl hydroperoxide, di-t-butyl Hydroperoxide, di (dicyclobenzoyl) peroxide, 2,5-dimethyl-2,5bis (t-butylperoxy) hexane, 2,5-dimethyl-2,5bis (t-butylperoxy) Hexyne, benzophenone, Mihiraaketon, dimethylaminobenzoic acid ethyl ester, benzoin ethyl ether.
　パーオキサイド系架橋剤の使用量は、得られるシリコーンゴムの種類や、そのシリコーンゴムで成形された流路維持基板シート１０・３０及び流路担持基板シート２０の性質や、必要に応じて使用されるシランカップリング剤の性質に応じて適宜選択されるが、シリコーンゴム１００質量部に対し、０．０１～１０質量部、好ましくは０．１～２質量部用いられることが好ましい。この範囲よりも少ないと、架橋度が低すぎてシリコーンゴムとして使用できない。一方、この範囲よりも多いと、架橋度が高すぎてシリコーンゴムの弾性が低減してしまう。 The amount of peroxide-based crosslinking agent used is the type of silicone rubber to be obtained, the properties of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 formed from the silicone rubber, and as required. The amount is appropriately selected according to the properties of the silane coupling agent to be used, but 0.01 to 10 parts by mass, preferably 0.1 to 2 parts by mass is preferably used with respect to 100 parts by mass of the silicone rubber. If it is less than this range, the crosslinking degree is too low to be used as silicone rubber. On the other hand, if the amount is larger than this range, the degree of crosslinking is too high and the elasticity of the silicone rubber is reduced.
　流路維持基板シート１０・３０及び流路担持基板シート２０の素材の付加型シリコーンゴムは、Ｐｔ触媒存在下で合成したビニルメチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ポリジメチルシロキサン、ビニル末端ジフェニルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ジエチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端トリフロロプロピルメチルシロキサン／ポリジメチルシロキサンコポリマー、ビニル末端ポリフェニルメチルシロキサン、ビニルメチルシロキサン／ジメチルシロキサンコポリマー、トリメチルシロキサン基末端ジメチルシロキサン／ビニルメチルシロキサン／ジフェニルシロキサンコポリマー、トリメチルシロキサン基末端ジメチルシロキサン／ビニルメチルシロキサン／ジトリフロロプロピルメチルシロキサンコポリマー、トリメチルシロキサン基末端ポリビニルメチルシロキサンなどのビニル基含有ポリシロキサンと、Ｈ末端ポリシロキサン、メチルＨシロキサン／ジメチルシロキサンコポリマー、ポリメチルＨシロキサン、ポリエチルＨシロキサン、Ｈ末端ポリフェニル（ジメチルＨシロキシ）シロキサン、メチルＨシロキサン／フェニルメチルシロキサンコポリマー、メチルＨシロキサン／オクチルメチルシロキサンコポリマーで例示されるＨ基含有ポリシロキサンの組成物、
　アミノプロピル末端ポリジメチルシロキサン、アミノプロピルメチルシロキサン／ジメチルシロキサンコポリマー、アミノエチルアミノイソブチルメチルシロキサン／ジメチルシロキサンコポリマー、アミノエチルアミノプロピルメトキシシロキサン／ジメチルシロキサンコポリマー、ジメチルアミノ末端ポリジメチルシロキサンで例示されるアミノ基含有ポリシロキサンと、エポキシプロピル末端ポリジメチルシロキサン、（エポキシシクロヘキシルエチル）メチルシロキサン／ジメチルシロキサンコポリマーで例示されるエポキシ基含有ポリシロキサン、琥珀酸無水物末端ポリジメチルシロキサンで例示される酸無水物基含有ポリシロキサン及びトルイルジイソシアナート、１，６－ヘキサメチレンジイソシアナートなどのイソシアナート基含有化合物との組成物から得られるものである。 The addition type silicone rubber as the material of the channel maintaining substrate sheets 10 and 30 and the channel supporting substrate sheet 20 is vinylmethylsiloxane / polydimethylsiloxane copolymer synthesized in the presence of Pt catalyst, vinyl-terminated polydimethylsiloxane, vinyl-terminated diphenylsiloxane. / Polydimethylsiloxane copolymer, vinyl-terminated diethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated trifluoropropylmethylsiloxane / polydimethylsiloxane copolymer, vinyl-terminated polyphenylmethylsiloxane, vinylmethylsiloxane / dimethylsiloxane copolymer, trimethylsiloxane-terminated dimethylsiloxane / Vinylmethylsiloxane / diphenylsiloxane copolymer, trimethylsiloxane-terminated dimethylsiloxane / vinylmethyl Vinyl group-containing polysiloxanes such as Loxane / ditrifluoropropylmethylsiloxane copolymer, trimethylsiloxane group-terminated polyvinylmethylsiloxane, and H-terminal polysiloxane, methyl Hsiloxane / dimethylsiloxane copolymer, polymethylHsiloxane, polyethylHsiloxane, H-terminal polyphenyl Compositions of H-group-containing polysiloxanes exemplified by (dimethylHsiloxy) siloxane, methylHsiloxane / phenylmethylsiloxane copolymer, methylHsiloxane / octylmethylsiloxane copolymer;
Amino groups exemplified by aminopropyl-terminated polydimethylsiloxane, aminopropylmethylsiloxane / dimethylsiloxane copolymer, aminoethylaminoisobutylmethylsiloxane / dimethylsiloxane copolymer, aminoethylaminopropylmethoxysiloxane / dimethylsiloxane copolymer, dimethylamino-terminated polydimethylsiloxane Containing polysiloxane, epoxypropyl-terminated polydimethylsiloxane, epoxy group-containing polysiloxane exemplified by (epoxycyclohexylethyl) methylsiloxane / dimethylsiloxane copolymer, acid anhydride group containing oxalic anhydride-terminated polydimethylsiloxane Isocyanates such as polysiloxane and toluyl diisocyanate, 1,6-hexamethylene diisocyanate It is obtained from the composition of the group containing compounds.
　これらの組成物から流路維持基板シート１０・３０及び流路担持基板シート２０を作製する加工条件は、付加反応の種類及び特性によって異なるので一義的には決められないが、一般には０～２００℃で、１分間～２４時間加熱するというものである。これにより流路維持基板シート１０・３０及び流路担持基板シート２０として付加型シリコーンゴムが得られる。低温の加工条件の方が、シリコーンゴムの物性が良い場合には、反応時間が長くなる。物性よりも素早い生産性が要求される場合には、高温で短時間の加工条件で行われる。生産過程や作業環境によって、一定の時間内に加工しなければならない場合には、所望の加工時間に合わせ、加工温度を前記範囲内の比較的高い温度に設定して、行われる。 The processing conditions for producing the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 from these compositions vary depending on the type and characteristics of the addition reaction, but are not uniquely determined, but are generally 0 to 200. Heating is performed at a temperature of 1 minute to 24 hours. As a result, additional silicone rubber is obtained as the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20. When the physical properties of the silicone rubber are better under low temperature processing conditions, the reaction time becomes longer. When productivity faster than physical properties is required, the processing is performed at a high temperature for a short time. When machining must be performed within a certain period of time depending on the production process and work environment, the machining temperature is set to a relatively high temperature within the above range in accordance with the desired machining time.
　流路維持基板シート１０・３０及び流路担持基板シート２０の素材の縮合型シリコーンゴムは、スズ系触媒の存在下で合成されたシラノール末端ポリジメチルシロキサン、シラノール末端ポリジフェニルシロキサン、シラノール末端ポリトリフロロメチルシロキサン、シラノール末端ジフェニルシロキサン／ジメチルシロキサンコポリマーで例示されるシラノール基末端ポリシロキサンからなる単独縮合成分の組成物、
　これらのシラノール基末端ポリシロキサンと、テトラアセトキシシラン、トリアセトキシメチルシラン、ジｔ－ブトキシジアセトキシシラン、ビニルトリアセトキシシラン、テトラエトキシシラン、トリエノキシメチルシラン、ビス（トリエトキシシリル）エタン、テトラ－ｎ－プロポキシシラン、ビニルトリメトキシシラン、メチルトリス（メチルエチルケトキシム）シラン、ビニルトリス（メチルエチルケトキシイミノ）シラン、ビニルトリイソプロペノイキシシラン、トリアセトキシメチルシラン、トリ（エチルメチル）オキシムメチルシラン、ビス（Ｎ－メチルベンゾアミド）エトキシメチルシラン、トリス（シクロヘキシルアミノ）メチルシラン、トリアセトアミドメチルシラン、トリジメチルアミノメチルシランで例示される架橋剤との組成物、
　これらのシラノール基末端ポリシロキサンと、クロル末端ポリジメチルシロキサン、ジアセトキシメチル末端ポリジメチルシロキサン、末端ポリシロキサンで例示される末端ブロックポリシロキサンの組成物から得られるものである。 Condensation type silicone rubber as a material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is composed of silanol-terminated polydimethylsiloxane, silanol-terminated polydiphenylsiloxane, silanol-terminated polytrily synthesized in the presence of a tin-based catalyst. A composition of a single condensation component comprising a silanol-terminated polysiloxane exemplified by fluoromethylsiloxane, silanol-terminated diphenylsiloxane / dimethylsiloxane copolymer,
These silanol-terminated polysiloxanes, tetraacetoxysilane, triacetoxymethylsilane, di-t-butoxydiacetoxysilane, vinyltriacetoxysilane, tetraethoxysilane, trienoxymethylsilane, bis (triethoxysilyl) ethane, tetra -N-propoxysilane, vinyltrimethoxysilane, methyltris (methylethylketoxime) silane, vinyltris (methylethylketoxyimino) silane, vinyltriisopropenooxysilane, triacetoxymethylsilane, tri (ethylmethyl) oximemethylsilane, bis ( N-methylbenzoamido) ethoxymethylsilane, tris (cyclohexylamino) methylsilane, triacetamidomethylsilane, tridimethylaminomethylsilane The composition of the agent,
The silanol group-terminated polysiloxane is obtained from a composition of a terminal block polysiloxane exemplified by chloro-terminated polydimethylsiloxane, diacetoxymethyl-terminated polydimethylsiloxane, and terminal polysiloxane.
　これらの組成物から縮合型シリコーンゴムを調製する加工条件は、縮合反応の種類及び特性によって異なるので一義的には決められないが、一般には０～１００℃で、１０分間～２４時間加熱するというものである。これにより流路維持基板シート１０・３０及び流路担持基板シート２０として縮合型シリコーンゴムが得られる。低温の加工条件の方が、シリコーンゴムの物性が良い場合には、反応時間が長くなる。物性よりも素早い生産性が要求される場合には、高温で短時間の加工条件で行われる。生産過程や作業環境によって、一定の時間内に加工しなければならない場合には、所望の加工時間に合わせ、加工温度を前記範囲内の比較的高い温度に設定して、行われる。 The processing conditions for preparing the condensation-type silicone rubber from these compositions vary depending on the type and characteristics of the condensation reaction, and therefore cannot be uniquely determined. In general, heating is performed at 0 to 100 ° C. for 10 minutes to 24 hours. Is. Thereby, condensation type silicone rubber is obtained as the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20. When the physical properties of the silicone rubber are better under low temperature processing conditions, the reaction time becomes longer. When productivity faster than physical properties is required, the processing is performed at a high temperature for a short time. When machining must be performed within a certain period of time depending on the production process and work environment, the machining temperature is set to a relatively high temperature within the above range in accordance with the desired machining time.
　流路維持基板シート１０・３０及び流路担持基板シート２０の素材のシリコーンゴムとオレフィン系ゴムとの共ブレンド物に用いられるオレフィン系ゴムは、１，４‐シスブタジエンゴム、イソプレンゴム、スチレン・ブタジエン共重合ゴム、ポリブテンゴム、ポリイソブチレンゴム、エチレン・プロピレンゴム、エチレン－プロピレン‐ジエンゴム、塩素化エチレンプロピレンゴム、塩素化ブチルゴムが挙げられる。 The olefin rubber used in the co-blend of silicone rubber and olefin rubber as the material of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is 1,4-cis butadiene rubber, isoprene rubber, styrene Examples include butadiene copolymer rubber, polybutene rubber, polyisobutylene rubber, ethylene / propylene rubber, ethylene-propylene-diene rubber, chlorinated ethylene propylene rubber, and chlorinated butyl rubber.
　流路維持基板シート１０・３０及び流路担持基板シート２０の素材のシリコーンゴムと非シリコーンゴムとの共ブレンド物に用いられる非シリコーンゴムは、エチレン－プロピレン－ジエンゴム、天然ゴム、１，４‐シスブタジエンゴム、イソプレンゴム、ポリクロロプレン、スチレン・ブタジエン共重合ゴム、水素添加スチレン・ブタジエン共重合ゴム、アクリルニトリル・ブタジエン共重合ゴム、水素添加アクリルニトリル・ブタジエン共重合ゴム、ポリブテンゴム、ポリイソブチレンゴム、エチレン・プロピレンゴム、エチレンオキサイド－エピクロロヒドリン共重合体ゴム、塩素化ポリエチレンゴム、クロルスルフォン化ポリエチレンゴム、アルキル化クロルスルフォン化ポリエチレンゴム、クロロプレンゴム、塩素化アクリルゴム、臭素化アクリルゴム、フッ素ゴム、エピクロルヒドリンとその共重合ゴム、塩素化エチレンプロピレンゴム、塩素化ブチルゴム、臭素化ブチルゴムテトラフロロエチレン、ヘキサフロロプピレン、フッ化ビニリデン及びテトラフルオロロエチレンなどの単独重合体ゴム及びこれらの二元及び三元共重合体ゴム、エチレン／テトラフルオロエチレン共重合ゴム、プロピレン／テトラフルオロエチレン共重合ゴム、エチレンアクリルゴム、エポキシゴム、ウレタンゴム、両末端不飽和基エラストマー等の線状重合体で例示される原料ゴム状物質の配合物を架橋させたものが挙げられる。これらは単独で用いられても複数混合して用いられてもよい。 Non-silicone rubber used in the co-blend of silicone rubber and non-silicone rubber as the material of the channel maintaining substrate sheet 10/30 and the channel carrying substrate sheet 20 is ethylene-propylene-diene rubber, natural rubber, 1,4- Cis-butadiene rubber, isoprene rubber, polychloroprene, styrene-butadiene copolymer rubber, hydrogenated styrene-butadiene copolymer rubber, acrylonitrile-butadiene copolymer rubber, hydrogenated acrylonitrile-butadiene copolymer rubber, polybutene rubber, polyisobutylene rubber , Ethylene / propylene rubber, ethylene oxide-epichlorohydrin copolymer rubber, chlorinated polyethylene rubber, chlorosulfonated polyethylene rubber, alkylated chlorosulfonated polyethylene rubber, chloroprene rubber, chlorinated acrylic rubber , Brominated acrylic rubber, fluorine rubber, epichlorohydrin and its copolymer rubber, chlorinated ethylene propylene rubber, chlorinated butyl rubber, brominated butyl rubber, tetrafluoroethylene, hexafluoropropylene, vinylidene fluoride, tetrafluoroethylene, etc. Combined rubber and these binary and ternary copolymer rubbers, ethylene / tetrafluoroethylene copolymer rubber, propylene / tetrafluoroethylene copolymer rubber, ethylene acrylic rubber, epoxy rubber, urethane rubber, both-end unsaturated group elastomer, etc. And those obtained by crosslinking a blend of raw rubber materials exemplified by the linear polymer. These may be used alone or in combination.
　流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０の何れか又は全てが、珪藻土、マイカ、タルク、及び／又はカオリンを含んでいると、シリコーンゴム分が少なくなり、水蒸気の透過が抑制され、水溶性の液体が透過し難く揮発し難いこととなる。液体の透過量は、珪藻土、マイカ、タルク、及び／又はカオリンの添加量に伴い、低下する。また、上記の添加物が鱗片状であるとなお良い。鱗片状であると、水蒸気がシート内を透過する経路がより長くなり、水蒸気の透過が抑制される。 If any or all of the flow path maintaining substrate sheets 10, 30, 50 and the flow path supporting substrate sheets 20, 40 contain diatomaceous earth, mica, talc, and / or kaolin, the amount of silicone rubber decreases, Permeation of water is suppressed, and a water-soluble liquid is difficult to permeate and hardly volatilize. The amount of liquid permeation decreases with the amount of diatomaceous earth, mica, talc, and / or kaolin added. Moreover, it is more preferable that said additive is scaly. If it is scale-like, the path through which water vapor passes through the sheet becomes longer, and the transmission of water vapor is suppressed.
　流路維持基板シート１０・３０及び流路担持基板シート２０の何れか又は全てが、シリコーンゴムをパーオキサイド架橋シリコーンゴム、付加架橋シリコーンゴム、縮合架橋シリコーンゴム、放射線や電子線架橋シリコーンゴムの何れかを主成分とし、エチレン－プロピレン－ジエンゴム（ＥＰＤＭ）であるオレフィン系ゴムを従成分とする共ブレンド物であることが好ましい。その主成分と従成分との比は、５～１００重量部：１００～５重量部であることが好ましい。エチレン－プロピレン－ジエンゴムを単独で用いてもよい。エチレン－プロピレン－ジエンゴムが単独で用いられ又はブレンド（ＳＥＰ）されて用いられていると、水溶性の液体が透過し難く揮発し難いこととなる。 Any or all of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are made of silicone rubber, peroxide crosslinked silicone rubber, addition crosslinked silicone rubber, condensation crosslinked silicone rubber, radiation or electron beam crosslinked silicone rubber. It is preferable to use a co-blend product containing the main component of olefin rubber, which is ethylene-propylene-diene rubber (EPDM). The ratio of the main component to the subcomponent is preferably 5 to 100 parts by weight: 100 to 5 parts by weight. Ethylene-propylene-diene rubber may be used alone. When ethylene-propylene-diene rubber is used alone or blended (SEP), a water-soluble liquid is difficult to permeate and hardly volatilize.
　流路担持基板シート２０の微細流路２６は、幅が０．５μｍ～５ｍｍ、好ましくは１０～１０００μｍであり、その形状が特に限定されず、連続線状及び／又は分岐線状で直線・曲線の何れでもよく、単数又は複数並列して設けられていてもよい。流路維持基板シート１０・３０及び流路担持基板シート２０の厚さは、５～１００μｍであることが好ましい。微細流路２６は、幅が狭く、流路維持基板シート１０・３０及び流路担持基板シート２０の厚さが薄いので、検体や試薬とゴムシートとの接触面積を最小限に抑えることができ、ゴムシートからのゴム成分の遺漏による検体や試薬の汚染、ゴム成分への吸着を防止することができる。流路維持基板シート１０・３０及び流路担持基板シート２０は、少なくとも微細流路２６の壁面２７が、検体や試薬を汚染したり吸着したりしないように、非反応性樹脂、例えばポリテトラフルオロエチレン樹脂のようなフッ素樹脂、２-メタクリロイルオキシエチルホスホリルコリン(ＭＰＣ)ポリマーのようなリン酸系樹脂、パリレンのようなパラキシリレン樹脂でコーティング又は蒸着され、又は非反応性無機物、例えば二酸化チタンや二酸化ケイ素のような無機物で蒸着されていると、ゴムシートと検体や試薬との接触が完全に避けられるので、検体や試薬の汚染や吸着がより一層防止できる。 The fine channel 26 of the channel-carrying substrate sheet 20 has a width of 0.5 μm to 5 mm, preferably 10 to 1000 μm, and the shape thereof is not particularly limited. Any of these may be used, and a single unit or a plurality of units may be provided in parallel. The thicknesses of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are preferably 5 to 100 μm. Since the fine channel 26 is narrow and the thickness of the channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 is thin, the contact area between the specimen or reagent and the rubber sheet can be minimized. It is possible to prevent contamination of the specimen or reagent due to leakage of the rubber component from the rubber sheet and adsorption to the rubber component. The flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 are non-reactive resins such as polytetrafluoro so that at least the wall surface 27 of the fine flow path 26 does not contaminate or adsorb the specimen or reagent. Fluorine resin such as ethylene resin, phosphate resin such as 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, coated or deposited with paraxylylene resin such as parylene, or non-reactive inorganic material such as titanium dioxide or silicon dioxide If the inorganic material is vapor-deposited, the contact between the rubber sheet and the specimen or reagent can be completely avoided, so that the specimen or reagent can be further prevented from being contaminated or adsorbed.
　流路維持基板シート１０の流動試料注入穴１１ａ・１１ｂと流動試料排出穴１２ａ・１２ｂ・１２ｃ、流路担持基板シート２０の流動試料注入部位２１ａ・２１ｂと流動試料排出部位２２ａ・２２ｂ・２２ｃと微細流路２６は、レーザー加工で貫通して開けられる。 The flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintaining substrate sheet 10, and the flow sample injection portions 21a and 21b and the flow sample discharge portions 22a, 22b, and 22c of the flow path holding substrate sheet 20 The fine channel 26 is opened by laser processing.
　熱伝導性マイクロ化学チップ１は、上下の流路維持基板シート１０・３０を覆って、保護基材シート（不図示）を有していてもよい。保護基材シートは、金属の他、セラミックス、ガラス、樹脂で形成されたもので、単一の板状、薄層状に形成されていてもよく、これらがラミネート加工されていてもよい。流路維持基板シート１０・３０及び流路担持基板シート２０をコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されて共有結合により直接、接合して一体化したのと同様に、各種活性化処理して、上下の流路維持基板シート１０・３０へ接合して一体化したものであってもよい。保護基材シートには、流路維持基板シート１０の流動試料注入穴１１ａ・１１ｂと流動試料排出穴１２ａ・１２ｂ・１２ｃとに対応して、穴が開けられる。保護基材シートは、検体や試薬に対し比較的安定であるが、検体や試薬に接する部位が、樹脂で形成され、コーティングされ、又はラミネート加工されていることが好ましい。 The heat conductive microchemical chip 1 may have a protective base sheet (not shown) covering the upper and lower flow path maintaining substrate sheets 10 and 30. The protective base sheet is made of ceramic, glass, or resin in addition to metal, and may be formed in a single plate shape or thin layer shape, or these may be laminated. The flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 were subjected to corona treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) and directly joined and integrated by covalent bonding. In the same manner as described above, various activation treatments may be performed so as to join and integrate the upper and lower flow path maintenance substrate sheets 10 and 30. In the protective base sheet, holes are made corresponding to the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintenance substrate sheet 10. The protective base sheet is relatively stable with respect to the specimen and the reagent, but it is preferable that the portion in contact with the specimen and the reagent is formed of resin, coated, or laminated.
　保護基材シートを成す金属は、金、銀、銅、鉄、コバルト、シリコン、鉛、マンガン、タングステン、タンタル、白金、カドミウム、スズ、パラジウム、ニッケル、クロム、チタン、亜鉛、アルミニウム、マグネシウムで例示される金属、これら金属の二元、三元及び多元合金が挙げられる。 Examples of the metal forming the protective base sheet include gold, silver, copper, iron, cobalt, silicon, lead, manganese, tungsten, tantalum, platinum, cadmium, tin, palladium, nickel, chromium, titanium, zinc, aluminum, and magnesium. Metals, binary, ternary and multicomponent alloys of these metals.
　保護基材シートを成すセラミックスは、銀、銅、鉄、コバルト、シリコン、鉛、マンガン、タングステン、タンタル、白金、カドミウム、スズ、パラジウム、ニッケル、クロム、インジウム、チタン、亜鉛、カルシウム、バリウム、アルミニウム、マグネシウム、ナトリウム、カリウムなどの金属の酸化物、窒化物、及び炭化物、それらの単体又は複合体が挙げられる。 The ceramics forming the protective base sheet are silver, copper, iron, cobalt, silicon, lead, manganese, tungsten, tantalum, platinum, cadmium, tin, palladium, nickel, chromium, indium, titanium, zinc, calcium, barium, aluminum And oxides, nitrides, and carbides of metals such as magnesium, sodium, and potassium, and simple substances or composites thereof.
　保護基材シートを成すガラスは、石英、硼珪酸ガラス、無アルカリガラスが挙げられる。 Examples of the glass forming the protective base sheet include quartz, borosilicate glass, and alkali-free glass.
　保護基材シートを成す樹脂は、ポリカーボネート樹脂、シクロオレフィン樹脂、アクリル樹脂、エポキシ樹脂、ポリエチレンテレフタレート樹脂、ポリブテレンテレフタレート樹脂、セルロース及びその誘導体、ヒドロキシエチルセルロース、デンプン、二酢酸セルロース、表面ケン化酢酸ビニル樹脂、低密度ポリエチレン、高密度ポリエチレン、ｉ－ポリプロピレン、石油樹脂、ポリスチレン、ｓ－ポリスチレン、クロマン・インデン樹脂、テルペン樹脂、スチレン・ジビニルベンゼン共重合体、ＡＢＳ樹脂、ポリアクリル酸メチル、ポリアクリル酸エチル、ポリアクリルニトリル、ポリメタクリル酸メチル、ポリメタクリル酸エチル、ポリシアノアクリレート、ポリ酢酸ビニル、ポリビニルアルコール、ポリビニルホルマール、ポリビニルアセタール、ポリ塩化ビニル、塩化ビニル・酢酸ビニル共重合体、塩化ビニル・エチレン共重合体、ポリフッ化ビニリデン、フッ化ビニリデン・エチレン共重合体、フッ化ビニリデン・プロピレン共重合体、１，４‐トランスポリブタジエン、ポリオキシメチレン、ポリエチレングリコール、ポリプロピレングリコール、フェノール・ホルマリン樹脂、クレゾール・フォルマリン樹脂、レゾルシン樹脂、メラミン樹脂、キシレン樹脂、トルエン樹脂、グリプタル樹脂、変性グリプタル樹脂、不飽和ポリエステル樹脂、アリルエステル樹脂、６－ナイロン、６，６－ナイロン、６，１０－ナイロン、ポリイミド、ポリアミド、ポリベンズイミダゾール、ポリアミドイミド、ケイ素樹脂、シリコーンゴム、シリコーン樹脂、フラン樹脂、ポリウレタン樹脂、ポリフェニレンオキサイド、ポリジメチルフェニレンオキサイド、ポリフェニレンオキサイドまたはポリジメチルフェニレンオキサイドとトリアリルイソシアヌルブレンド物、（ポリフェニレンオキサイドまたはポリジメチルフェニレンオキサイド、トリアリルイソシアヌル、パーオキサイド）ブレンド物、ポリキシレン、ポリフェニレンスルファイド（ＰＰＳ）、ポリスルホン（ＰＳＦ）、ポリエーテルスルホン（ＰＥＳ）、ポリエーテルエーテルケトン（ＰＥＥＫ）、ポリイミド（ＰＰＩ、カプトン）、ポリテトラフルオロエチレン（ＰＴＦＥ）、液晶樹脂、ケブラー繊維、炭素繊維とこれら複数材料のブレンド物で例示される高分子材料、その架橋物が挙げられる。 The resin forming the protective base sheet is polycarbonate resin, cycloolefin resin, acrylic resin, epoxy resin, polyethylene terephthalate resin, polybutene terephthalate resin, cellulose and its derivatives, hydroxyethyl cellulose, starch, cellulose diacetate, surface saponified acetic acid Vinyl resin, low density polyethylene, high density polyethylene, i-polypropylene, petroleum resin, polystyrene, s-polystyrene, chroman indene resin, terpene resin, styrene / divinylbenzene copolymer, ABS resin, polymethyl acrylate, polyacryl Ethyl acetate, polyacrylonitrile, polymethyl methacrylate, polyethyl methacrylate, polycyanoacrylate, polyvinyl acetate, polyvinyl alcohol, polyvinyl formal, polyvinyl chloride Ruacetal, polyvinyl chloride, vinyl chloride / vinyl acetate copolymer, vinyl chloride / ethylene copolymer, polyvinylidene fluoride, vinylidene fluoride / ethylene copolymer, vinylidene fluoride / propylene copolymer, 1,4- Transpolybutadiene, polyoxymethylene, polyethylene glycol, polypropylene glycol, phenol / formalin resin, cresol / formalin resin, resorcin resin, melamine resin, xylene resin, toluene resin, glyphal resin, modified glyphal resin, unsaturated polyester resin, allyl ester Resin, 6-nylon, 6,6-nylon, 6,10-nylon, polyimide, polyamide, polybenzimidazole, polyamideimide, silicon resin, silicone rubber, silicone resin, furan resin, poly Retan resin, polyphenylene oxide, polydimethylphenylene oxide, polyphenylene oxide or polydimethylphenylene oxide and triallyl isocyanuric blend, (polyphenylene oxide or polydimethylphenylene oxide, triallyl isocyanuric, peroxide) blend, polyxylene, polyphenylene sulfide (PPS), polysulfone (PSF), polyethersulfone (PES), polyetheretherketone (PEEK), polyimide (PPI, Kapton), polytetrafluoroethylene (PTFE), liquid crystal resin, Kevlar fiber, carbon fiber and more Examples thereof include a polymer material exemplified by a blend of materials and a crosslinked product thereof.
　保護基材シートと流路維持基板シート１０・３０との接合面を人為的に活性化する場合、コロナ放電処理、プラズマ処理、又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）が施されることによって活性化する。金属、セラミックス又はガラス製の保護基材シートと、流路維持基板シート１０・３０とは、それぞれ活性化処置されて生じた活性基例えば水酸基同士が、脱水して生成したエーテル結合によって、強固に接合している。なお、両者の積層だけでエーテル結合し得るほど水酸基等の活性基が予め十分に露出できている場合これら活性化処理が施されていなくてもよい。 When artificially activating the joint surface between the protective base sheet and the flow path maintaining substrate sheets 10 and 30, corona discharge treatment, plasma treatment, or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) is performed. It is activated by being. The protective substrate sheet made of metal, ceramics or glass and the flow path maintenance substrate sheet 10/30 are strongly bonded to each other by an ether bond generated by dehydration of active groups such as hydroxyl groups generated by activation treatment. It is joined. In addition, when active groups, such as a hydroxyl group, are fully exposed beforehand so that an ether bond can be carried out only by both lamination | stacking, these activation processes may not be given.
　保護基材シートと流路維持基板シート１０・３０とが、エーテル結合を介して直接的に接合している例を示したが、分子接着剤例えばシランカップリング剤を介した共有結合や水素結合のような化学結合によって間接的に接合していてもよい。この場合、シランカップリング剤の１分子が保護基材シートと流路維持基板シート１０・３０とに介在して化学結合を形成することができる。例えば、流路維持基板シート１０・３０と、金属、セラミックス、ガラス又は樹脂製の保護基材シートとが、それらの接合面の少なくとも何れかで、コロナ放電処理、プラズマ処理、又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）によって活性化されており、アミノ基、及び／又は炭素数１～４のアルコキシ基若しくはそれと同様に水酸基と反応してエーテル基を生成し得る加水分解性でアルコキシ基等価基を、有するシランカップリング剤を介した該化学結合により、接合している。 Although the example in which the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are directly bonded via an ether bond has been shown, covalent bonding or hydrogen bonding via a molecular adhesive such as a silane coupling agent has been shown. They may be joined indirectly by chemical bonds such as In this case, one molecule of the silane coupling agent can be interposed between the protective base sheet and the flow path maintaining substrate sheets 10 and 30 to form a chemical bond. For example, the flow path maintaining substrate sheet 10/30 and a protective base material sheet made of metal, ceramics, glass, or resin are corona discharge treatment, plasma treatment, or ultraviolet irradiation treatment (at least one of their joint surfaces). It is activated by general UV treatment and excimer UV treatment), and is hydrolyzable that can react with an amino group and / or an alkoxy group having 1 to 4 carbon atoms or a hydroxyl group in the same manner to form an ether group. Bonding is performed by the chemical bond via a silane coupling agent having an alkoxy group equivalent group.
　分子接着剤として、トリエトキシシリルプロピルアミノ－１，３，５－トリアジン－２，４－ジチオール（ＴＥＳ）、アミノエチルアミノプロピル トリメトキシシランのようなアミノ基含有化合物；トリエトキシシリルプロピルアミノ基のようなトリアルコキシシリルアルキルアミノ基とメルカプト基又はアジド基とを有するトリアジン化合物、前記化学式(Ｉ)で表わされるトリアジン化合物、例えば２，６－ジアジド－４－｛３－（トリエトキシシリル）プロピルアミノ｝－１，３，５－トリアジン（Ｐ－ＴＥＳ）；トリアルコキシシリルアルキル基を有するチオール化合物；トリアルキルオキシシリルアルキル基を有するエポキシ化合物が挙げられる。 As molecular adhesives, amino group-containing compounds such as triethoxysilylpropylamino-1,3,5-triazine-2,4-dithiol (TES), aminoethylaminopropyl trimethoxysilane; A triazine compound having a trialkoxysilylalkylamino group and a mercapto group or azide group, a triazine compound represented by the above formula (I), for example, 2,6-diazido-4- {3- (triethoxysilyl) propylamino } -1,3,5-triazine (P-TES); thiol compound having trialkoxysilylalkyl group; epoxy compound having trialkyloxysilylalkyl group.
　また分子接着剤は、アルコキシ基を有するアミノ基非含有のシランカップリング剤として、市販のシランカップリング剤、具体的にはビニルトリメトキシシラン(KBM-1003)、ビニルトリエトキシシラン(KBE-1003)で例示されるビニル基及びアルコキシ基含有シランカップリング剤；2-(3,4-エポキシシクロヘキシル)エチルトリメトキシシラン(KBM-303)、3-グリシドキシプロピルメチルジメトキシシラン(KBM-402)、3-グリシドキシプロピルトリメトキシシラン(KBM-403)、3-グリシドキシプロピルメチルジエトキシシラン(KBE-402)、3-グリシドキシプロピルトリエトキシシラン(KBE-403)で例示されるエポキシ基及びアルコキシ基含有シランカップリング剤；p-スチリルトリメトキシシラン(KBM-1403)で例示されるスチリル基及びアルコキシ基含有シランカップリング剤；3-メタクリロキシプロピルメチルジメトキシシラン(KBM-502)、3-メタクリロキシプロピルトリメトキシシラン(KBM-503)、3-メタクリロキシプロピルメチルジエトキシシラン(KBE-502)、3-メタクリロキシプロピルメチルジエトキシシラン(KBE-503)、3-アクリロキシプロピルトリメトキシシラン(KBM-5103)で例示される(メタ)アクリル基及びアルコキシ基含有シランカップリング剤；3-ウレイドプロピルトリエトキシシラン(KBE-585)で例示されるウレイド基及びアルコキシ含有シランカップリング剤；3-メルカプトプロピルメチルジメトキシシラン(KBM-802)、3-メルカプトプロピルトリメトキシシラン(KBM-803)で例示されるメルカプト基及びアルコキシ含有シランカップリング剤；ビス(トリエトキシシリルプロピル)テトラスルフィド(KBE-846)で例示されるスルフィド基及びアルコキシ含有シランカップリング剤；3-イソシアネートプロピルトリエトキシシラン(KBE-9007)で例示されるイソシアネート基及びアルコキシ含有シランカップリング剤（以上、何れも信越シリコーン株式会社製；商品名）が挙げられ、またビニルトリアセトキシシラン(Z-6075)で例示されるビニル基及びアセトキシ含有シランカップリング剤；アリルトリメトキシシラン(Z-6825)で例示されるアリル基及びアルコキシ含有シランカップリング剤；メチルトリメトキシシラン(Z-6366)、ジメチルジメトキシシラン(Z-6329)、トリメチルメトキシシラン(Z-6013)、メチルトリエトキシシラン(Z-6383)、メチルトリフェノキシシラン(Z-6721)、エチルトリメトキシシラン(Z-6321)、n-プロピルトリメトキシシラン(Z-6265)、ジイソプロピルジメトキシシラン(Z-6258)、イソブチルトリメトキシシラン(Z-2306)、ジイソブチルジメトキシシラン(Z-6275)、イソブチルトリエトキシシラン(Z-6403)、n-ヘキシトリメトキシシラン(Z-6583)、n-ヘキシトリエトキシシラン(Z-6586)、シクロヘキシルメチルジメトキシシラン(Z-6187)、n-オクチルトリエトキシシラン(Z-6341)、n-デシルトリメトキシシラン(Z-6210)で例示されるアルキル基及びアルコキシ基含有シランカップリング剤；フェニルトリメトキシシラン(Z-6124)で例示されるアリール基及びアルコキシ基含有シランカップリング剤；n-オクチルジメチルクロロシラン(ACS-8)で例示されるアルキル基及びクロロシラン基含有シランカップリング剤；テトラエトキシシラン(Z-6697)で例示されるアルコキシシランであるシランカップリング剤（以上、何れも東レ・ダウコーニング株式会社製；商品名）が挙げられる。 Further, molecular adhesives are commercially available silane coupling agents such as vinyltrimethoxysilane (KBM-1003), vinyltriethoxysilane (KBE-1003), as alkoxy group-containing amino group-free silane coupling agents. ) Silane coupling agent containing vinyl group and alkoxy group exemplified by: 2- (3,4-epoxycyclohexyl) ethyltrimethoxysilane (KBM-303), 3-glycidoxypropylmethyldimethoxysilane (KBM-402) , 3-glycidoxypropyltrimethoxysilane (KBM-403), 3-glycidoxypropylmethyldiethoxysilane (KBE-402), 3-glycidoxypropyltriethoxysilane (KBE-403) Epoxy group and alkoxy group-containing silane coupling agent; styryl group and alkoxy group-containing silane coupling agent exemplified by p-styryltrimethoxysilane (KBM-1403); Tacryloxypropylmethyldimethoxysilane (KBM-502), 3-methacryloxypropyltrimethoxysilane (KBM-503), 3-methacryloxypropylmethyldiethoxysilane (KBE-502), 3-methacryloxypropylmethyldiethoxysilane (KBE-503), a (meth) acrylic group and alkoxy group-containing silane coupling agent exemplified by 3-acryloxypropyltrimethoxysilane (KBM-5103); 3-ureidopropyltriethoxysilane (KBE-585) Exemplified ureido group and alkoxy-containing silane coupling agent; 3-mercaptopropylmethyldimethoxysilane (KBM-802), mercapto group exemplified by 3-mercaptopropyltrimethoxysilane (KBM-803) and alkoxy-containing silane coupling Agents: sulfide groups and amines exemplified by bis (triethoxysilylpropyl) tetrasulfide (KBE-846) Koxy-containing silane coupling agents; isocyanate groups exemplified by 3-isocyanatopropyltriethoxysilane (KBE-9007) and alkoxy-containing silane coupling agents (all of which are manufactured by Shin-Etsu Silicone Co., Ltd .; trade names), Further, vinyl group and acetoxy-containing silane coupling agents exemplified by vinyltriacetoxysilane (Z-6075); allyl group and alkoxy-containing silane coupling agents exemplified by allyltrimethoxysilane (Z-6825); methyltrimethoxy Silane (Z-6366), dimethyldimethoxysilane (Z-6329), trimethylmethoxysilane (Z-6013), methyltriethoxysilane (Z-6383), methyltriphenoxysilane (Z-6721), ethyltrimethoxysilane ( Z-6321), n-propyltrimethoxysilane (Z-6265), diisopropyldimethoxysilane (Z-6258), isobutylto Methoxysilane (Z-2306), diisobutyldimethoxysilane (Z-6275), isobutyltriethoxysilane (Z-6403), n-hexyltrimethoxysilane (Z-6583), n-hexyltriethoxysilane (Z-6586) Alkyl group and alkoxy group-containing silane coupling agent exemplified by cyclohexylmethyldimethoxysilane (Z-6187), n-octyltriethoxysilane (Z-6341), n-decyltrimethoxysilane (Z-6210); phenyl An aryl group and alkoxy group-containing silane coupling agent exemplified by trimethoxysilane (Z-6124); an alkyl group and chlorosilane group-containing silane coupling agent exemplified by n-octyldimethylchlorosilane (ACS-8); tetraethoxy Examples include silane coupling agents that are alkoxysilanes exemplified by silane (Z-6697) (all of which are manufactured by Toray Dow Corning Co., Ltd .; trade names). It is.
　アルコキシ基を有するアミノ基非含有のシランカップリング剤は、ヒドロシリル基（SiH基）含有アルコキシシリル化合物、例えば、
(CH3O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(CH3O)3SiCH2CH2CH2Si(OCH3)2OSi(OCH3)3、
(C2H5O)3SiCH2CH2CH2Si(OCH3)2OSi(OCH3)3、
(C2H5O)3SiCH2CH2CH2Si(CH3)2H、
(CH3O)3SiCH2CH2CH2Si(CH3)2H、
(i-C3H7O)3SiCH2CH2CH2Si(CH3)H２、
(n-C3H7O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2Si(CH3)2Si(CH3)2H、
(n-C4H9O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(t-C4H9O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)2CH3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(CH3O)2CH3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2Si(CH3)2Si(CH3)2H、
CH3O(CH3)2SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(n-C3H7)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(i-C3H7O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(n-C4H9)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(t-C4H9O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2CH2CH2CH2CH2Si(CH3)2OSi(CH3)2H、
(C2H5O)3SiCH2CH2CH2CH2CH2CH2CH2CH2CH2CH2Si(CH3)2OSi(CH3)2H、
(CH3O)3SiCH2C6H4CH2CH2Si(CH3)2C6H4Si(CH3)2H、
(CH3O)2CH3SiCH2C6H4CH2CH2Si(CH3)2C6H4Si(CH3)2H、
CH3O(CH3)2SiCH2C6H4CH2CH2Si(CH3)2C6H4Si(CH3)2H、
(C2H5O)3SiCH2C6H4CH2CH2Si(CH3)2C6H4Si(CH3)2H、
(C2H5O)3SiCH2CH2CH2Si(CH3)2C6H4OC6H4Si(CH3)2H、
(C2H5O)3SiCH2CH2CH2Si(CH3)2C2H4Si(CH3)2H、
(C2H5O)3SiCH2CH2CH2Si(CH3)2O[Si(CH3)2O]p1Si(CH3)2H、
C2H5O(CH3)2SiCH2CH2CH2Si(CH3)2O[Si(CH3)2O]p2Si(C2H5)2H、
(C2H5O)2CH3SiCH2CH2CH2Si(CH3)2O[Si(CH3)2O]p3Si(CH3)2H、
(CH3)3SiOSiH(CH3)O[SiH(CH3)O]p4Si(CH3)3、
(CH3)3SiO[(C2H5OSi(CH3)CH2CH2CH2)SiCH3]O[SiH(CH3)O]p5Si(CH3)3、
(CH3)3SiO[(C2H5OSiOCH3CH2CH2CH2)SiCH3]O[SiH(CH3)O]p6Si(CH3)3、
(CH3)3SiO[(C2H5OSi(CH3)CH2CH2CH2)SiCH3]O[SiH(CH3)O]p7Si(CH3)3、
(CH3)3SiO[(Si(OC2H5)2CH2CH2CH2)SiCH3]O[SiH(CH3)O]p8Si(CH3)3、
(CH3)3SiOSi(OC2H5)2O[SiH(CH3)O]p9[Si(CH3)2O]q1Si(CH3)3、
(CH3)3SiO[(C2H5Osi(CH3)CH2CH2CH2CH2CH2CH2)Si(CH3)O][SiH(CH3)O]p10[Si(CH3)2O]q2Si(CH3)3、
(CH3)3SiO[(Si(OCH3)3CH2CH2CH2CH2CH2CH2)Si(CH3)O][SiH(CH3)O]p11[Si(CH3)2O]q3Si(CH3)3、
(CH3)3SiOSi(OC2H5)2O[SiH(C2H5)O]p12Si(CH3)3、
(CH3)3SiO[(Si(OC2H5)2CH2CH2CH2CH2CH2CH2)Si(C2H5)]O[SiH(C2H5)O]p13Si(CH3)3、
(CH3)3SiO[(C2H5OSi(CH3)CH2CH2CH2CH2CH2CH2)Si(C2H5)]O[SiH(C2H5)O]p14Si(CH3)3、
C2H5OSi(CH3)2CH2CH2CH2CH2CH2CH2(CH3)2SiO[HSi(CH3)2OSiC6H5O]p15Si(CH3)2H、
Si(OCH3)3CH2CH2CH2CH2CH2CH2(CH3)2SiO[HSi(CH3)2OSiC6H5O]p16Si(CH3)2H、
H(CH3)2SiO[(C2H5OSi(CH3)2CH2CH2CH2)Si(CH3)O][HSiCH3O]p17Si(CH3)2H、
H(CH3)2SiO[(C2H5OSi(CH3)2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p18Si(CH3)2H、
H(CH3)2SiO[(C2H5OSi(CH3)2CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p19Si(CH3)2H、
H(CH3)2SiO[(C2H5OSi(CH3)2CH2CH2CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p20Si(CH3)2H、
H(CH3)2SiO[(C2H5OSi(CH3)2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p21Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2C6H4CH2CH2)Si(CH3)O][HSiCH3O]p22Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2C6H4CH2CH2CH2)Si(CH3)O][HSiCH3O]p23Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2C6H4CH2CH2)Si(CH3)O][HSiCH3O]p24Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3C6H4CH2CH2)Si(CH3)O][HSiCH3O]p25Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2CH2)Si(CH3)O][HSiCH3O]p26Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p27Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p28Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p29Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2)Si(CH3)O][HSiCH3O]p30Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2C6H4CH2CH2)Si(CH3)O][HSiCH3O]p31Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2C6H4CH2CH2CH2)Si(CH3)O][HSiCH3O]p32Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2C6H4CH2CH2)Si(CH3)O][HSiCH3O]p33Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3C6H4CH2CH2)Si(CH3)O][HSiCH3O]p34Si(CH3)2H、
H(CH3)2SiO[(Si(OCH3)3CH2CH2C6H4CH2CH2)Si(CH3)O][HSiCH3O]p35Si(CH3)2H、
H(CH3)2SiO[(CH3O)Si(CH3)CH2CH2CH2CH2CH2CH2Si(CH3)2OSiC6H5O]p36[HSi(CH3)2OSiC6H5O]q4Si(CH3)2H、
H(CH3)2SiO[Si(OCH3)2CH2CH2CH2CH2CH2CH2Si(CH3)2OSiC6H5O]p37[HSi(CH3)2OSiC6H5O]q5Si(CH3)2H、
C2H5O(CH3)2SiO[SiH(CH3)O]p38[SiCH3(C6H5)O]q6Si(CH3)2H、
Si(OC2H5)3CH2CH2CH2CH2CH2CH2(CH3)2SiO[SiH(CH3)O]p39[SiCH3(C6H5)O]q7Si(CH3)2H、
C2H5OSi(CH3)2CH2CH2CH2CH2CH2CH2(CH3)2SiO[SiH(CH3)O]p40[SiCH3(C6H5)O]q8Si(CH3)2H、
H(CH3)2SiO(C2H5O)Si(CH3)O[SiH(CH3)O]p41[SiCH3(C6H5)O]q9Si(CH3)2H、
H(CH3)2SiO[Si(OC2H5)3CH2CH2CH2Si(CH3)]O[SiH(CH3)O]p42[SiCH3(C6H5)O]q10Si(CH3)2H
であってもよい。これらの基中、p1～p42及びq1～q10は１～１００までの数である。一つの分子に、ヒドロシリル基を、１～９９個有していることが好ましい。 The amino group-free silane coupling agent having an alkoxy group is a hydrosilyl group (SiH group) -containing alkoxysilyl compound, for example,
(CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (OCH 3 ) 2 OSi (OCH 3 ) 3 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (OCH 3 ) 2 OSi (OCH 3 ) 3 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 H,
(CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 H,
(iC 3 H 7 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) H 2 ,
(nC 3 H 7 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 Si (CH 3 ) 2 Si (CH 3 ) 2 H,
(nC 4 H 9 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(tC 4 H 9 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 2 CH 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(CH 3 O) 2 CH 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 Si (CH 3 ) 2 Si (CH 3 ) 2 H,
CH 3 O (CH 3 ) 2 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(nC 3 H 7 ) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(iC 3 H 7 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(nC 4 H 9 ) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(tC 4 H 9 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 H,
(CH 3 O) 3 SiCH 2 C 6 H 4 CH 2 CH 2 Si (CH 3 ) 2 C 6 H 4 Si (CH 3 ) 2 H,
(CH 3 O) 2 CH 3 SiCH 2 C 6 H 4 CH 2 CH 2 Si (CH 3 ) 2 C 6 H 4 Si (CH 3 ) 2 H,
CH 3 O (CH 3 ) 2 SiCH 2 C 6 H 4 CH 2 CH 2 Si (CH 3 ) 2 C 6 H 4 Si (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 C 6 H 4 CH 2 CH 2 Si (CH 3 ) 2 C 6 H 4 Si (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 C 6 H 4 OC 6 H 4 Si (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 C 2 H 4 Si (CH 3 ) 2 H,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 O [Si (CH 3 ) 2 O] p1 Si (CH 3 ) 2 H,
C 2 H 5 O (CH 3 ) 2 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 O [Si (CH 3 ) 2 O] p2 Si (C 2 H 5 ) 2 H,
(C 2 H 5 O) 2 CH 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 O [Si (CH 3 ) 2 O] p3 Si (CH 3 ) 2 H,
(CH 3 ) 3 SiOSiH (CH 3 ) O [SiH (CH 3 ) O] p4 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(C 2 H 5 OSi (CH 3 ) CH 2 CH 2 CH 2 ) SiCH 3 ] O [SiH (CH 3 ) O] p5 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(C 2 H 5 OSiOCH 3 CH 2 CH 2 CH 2 ) SiCH 3 ] O [SiH (CH 3 ) O] p6 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(C 2 H 5 OSi (CH 3 ) CH 2 CH 2 CH 2 ) SiCH 3 ] O [SiH (CH 3 ) O] p7 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(Si (OC 2 H 5 ) 2 CH 2 CH 2 CH 2 ) SiCH 3 ] O [SiH (CH 3 ) O] p8 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiOSi (OC 2 H 5 ) 2 O [SiH (CH 3 ) O] p9 [Si (CH 3 ) 2 O] q1 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(C 2 H 5 Osi (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [SiH (CH 3 ) O] p10 [Si (CH 3 ) 2 O] q2 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [SiH (CH 3 ) O] p11 [Si (CH 3 ) 2 O] q3 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiOSi (OC 2 H 5 ) 2 O [SiH (C 2 H 5 ) O] p12 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(Si (OC 2 H 5 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (C 2 H 5 )] O [SiH (C 2 H 5 ) O] p13 Si (CH 3 ) 3 ,
(CH 3 ) 3 SiO [(C 2 H 5 OSi (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (C 2 H 5 )] O [SiH (C 2 H 5 ) O] p14 Si (CH 3 ) 3 ,
C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 (CH 3 ) 2 SiO [HSi (CH 3 ) 2 OSiC 6 H 5 O] p15 Si (CH 3 ) 2 H,
Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 (CH 3 ) 2 SiO [HSi (CH 3 ) 2 OSiC 6 H 5 O] p16 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p17 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p18 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p19 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p20 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p21 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p22 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 C 6 H 4 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p23 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p24 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p25 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p26 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p27 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p28 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p29 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p30 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p31 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 C 6 H 4 CH 2 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p32 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p33 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p34 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(Si (OCH 3 ) 3 CH 2 CH 2 C 6 H 4 CH 2 CH 2 ) Si (CH 3 ) O] [HSiCH 3 O] p35 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [(CH 3 O) Si (CH 3 ) CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 Si (CH 3 ) 2 OSiC 6 H 5 O] p36 [HSi (CH 3 ) 2 OSiC 6 H 5 O] q4 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [Si (OCH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 Si (CH 3 ) 2 OSiC 6 H 5 O] p37 [HSi (CH 3 ) 2 OSiC 6 H 5 O] q5 Si (CH 3 ) 2 H,
C 2 H 5 O (CH 3 ) 2 SiO [SiH (CH 3 ) O] p38 [SiCH 3 (C 6 H 5 ) O] q6 Si (CH 3 ) 2 H,
Si (OC 2 H 5 ) 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 (CH 3 ) 2 SiO [SiH (CH 3 ) O] p39 [SiCH 3 (C 6 H 5 ) O] q7 Si (CH 3 ) 2 H,
C 2 H 5 OSi (CH 3 ) 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 (CH 3 ) 2 SiO [SiH (CH 3 ) O] p40 [SiCH 3 (C 6 H 5 ) O] q8 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO (C 2 H 5 O) Si (CH 3 ) O [SiH (CH 3 ) O] p41 [SiCH 3 (C 6 H 5 ) O] q9 Si (CH 3 ) 2 H,
H (CH 3 ) 2 SiO [Si (OC 2 H 5 ) 3 CH 2 CH 2 CH 2 Si (CH 3 )] O [SiH (CH 3 ) O] p42 [SiCH 3 (C 6 H 5 ) O] q10 Si (CH 3 ) 2 H
It may be. In these groups, p1 to p42 and q1 to q10 are numbers from 1 to 100. One molecule preferably has 1 to 99 hydrosilyl groups.
　アルコキシ基を有するアミノ基非含有のシランカップリング剤は、ヒドロシリル基を含有するアルコキシシリル化合物、例えば、
(C2H5O)3SiCH2CH=CH2、
(CH3O)3SiCH2CH2CH=CH2、
(C2H5O)3SiCH2CH2CH=CH2、
(CH3O)3SiCH2CH2CH2CH2CH=CH2、
(C2H5O)3SiCH2CH2CH2CH2CH=CH2、
(C2H5O)3SiCH2CH2CH2CH2CH2CH2CH=CH2、
(CH3O)3SiCH2(CH2)7CH=CH2、
(C2H5O)2Si(CH=CH2)OSi(OC2H5)CH=CH2、
(CH3O)3SiCH2CH2C6H4CH=CH2、
(CH3O)2Si(CH=CH2)O[SiOCH3(CH=CH2)O]t1Si(OCH3)2CH=CH2、
(C2H5O)2Si(CH=CH2)O[SiOC2H5(CH=CH2)O]t2Si(OC2H5)3、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2[Si(CH3)2O]t3CH=CH2、
(CH3O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2[Si(CH3)2O]t4CH=CH2、
CH3O(CH3)2SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2[Si(CH3)2O]t5CH=CH2、
(C2H5O)2CH3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2[Si(CH3)2O]t6CH=CH、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2[Si(CH3)2O]t7CH=CH、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2(Si(CH3)3O)Si(CH3)O[SiCH3(-)O]u1Si(CH3)3CH=CH2、
(C2H5O)3SiCH2CH2CH2Si(CH3)2OSi(CH3)2CH2CH2(Si(CH3)3O)Si(CH3)O[SiCH3(-)O]u2[Si(CH3)2O]t8Si(CH3)3CH=CH2、
(C2H5O)2Si(CH=CH2)O[SiCH3(OC2H5)O]u3Si(OC2H5)2CH=CH2、
(C2H5O)2Si(CH=CH2)O[Si(OC2H5)2O]u4Si(OC2H5)2CH=CH2、
(C2H5O)2Si(CH=CH2)O[Si(OC2H5)2O]u5Si(OC2H5)2CH=CH2
が挙げられる。これらの基中、t1～t8及びu1～u5は１～３０までの数である。一つの分子に、ビニル基を、１～３０個有していることが好ましい。 An amino group-free silane coupling agent having an alkoxy group is an alkoxysilyl compound containing a hydrosilyl group, for example,
(C 2 H 5 O) 3 SiCH 2 CH = CH 2 ,
(CH 3 O) 3 SiCH 2 CH 2 CH = CH 2 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH = CH 2 ,
(CH 3 O) 3 SiCH 2 CH 2 CH 2 CH 2 CH = CH 2 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 CH 2 CH = CH 2 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH = CH 2 ,
(CH 3 O) 3 SiCH 2 (CH 2 ) 7 CH = CH 2 ,
(C 2 H 5 O) 2 Si (CH = CH 2 ) OSi (OC 2 H 5 ) CH = CH 2 ,
(CH 3 O) 3 SiCH 2 CH 2 C 6 H 4 CH = CH 2 ,
(CH 3 O) 2 Si (CH = CH 2 ) O [SiOCH 3 (CH = CH 2 ) O] t1 Si (OCH 3 ) 2 CH = CH 2 ,
(C 2 H 5 O) 2 Si (CH = CH 2 ) O [SiOC 2 H 5 (CH = CH 2 ) O] t2 Si (OC 2 H 5 ) 3 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 [Si (CH 3 ) 2 O] t3 CH = CH 2 ,
(CH 3 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 [Si (CH 3 ) 2 O] t4 CH = CH 2 ,
CH 3 O (CH 3 ) 2 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 [Si (CH 3 ) 2 O] t5 CH = CH 2 ,
(C 2 H 5 O) 2 CH 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 [Si (CH 3 ) 2 O] t6 CH = CH,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 [Si (CH 3 ) 2 O] t7 CH = CH,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 (Si (CH 3 ) 3 O) Si (CH 3 ) O [SiCH 3 (- ) O] u1 Si (CH 3 ) 3 CH = CH 2 ,
(C 2 H 5 O) 3 SiCH 2 CH 2 CH 2 Si (CH 3 ) 2 OSi (CH 3 ) 2 CH 2 CH 2 (Si (CH 3 ) 3 O) Si (CH 3 ) O [SiCH 3 (- ) O] u2 [Si (CH 3 ) 2 O] t8 Si (CH 3 ) 3 CH = CH 2 ,
(C 2 H 5 O) 2 Si (CH = CH 2 ) O [SiCH 3 (OC 2 H 5 ) O] u3 Si (OC 2 H 5 ) 2 CH = CH 2 ,
(C 2 H 5 O) 2 Si (CH = CH 2 ) O [Si (OC 2 H 5 ) 2 O] u4 Si (OC 2 H 5 ) 2 CH = CH 2 ,
(C 2 H 5 O) 2 Si (CH = CH 2 ) O [Si (OC 2 H 5 ) 2 O] u5 Si (OC 2 H 5 ) 2 CH = CH 2
Is mentioned. In these groups, t1 to t8 and u1 to u5 are numbers from 1 to 30. One molecule preferably has 1 to 30 vinyl groups.
　これらのビニル基とＳｉＨ基とを金属触媒、例えば白金含有化合物で反応促進し、基材シートとゴムシートとを接合してもよい。 These vinyl groups and SiH groups may be promoted with a metal catalyst such as a platinum-containing compound to join the base sheet and the rubber sheet.
　アルコキシ基を有するアミノ基非含有のシランカップリング剤として、アルコキシシリル基を両末端に含有するアルコキシシリル化合物、例えば、
(C2H5O)3SiCH2CH2Si(OC2H5)3、
(C2H5O)2CH3SiCH2CH2Si(OC2H5)3、
(C2H5O)3SiCH=CHSi(OC2H5)3、
(CH3O)3SiCH2CH2Si(OCH3)3(CH3O)3SiCH2CH2C6H4CH2CH2Si(OCH3)3、
(CH3O)3Si[CH2CH2]3Si(OCH3)3、
(CH3O)2Si[CH2CH2]4Si(OCH3)3、
(C2H5O)2Si(OC2H5)2、
(CH3O)2CH3SiCH2CH2Si(OCH3)2CH3、
(C2H5O)2CH3SiOSi(OC2H5)2CH3、
(CH3O)3SiO[Si(OCH3)2O]v1Si(OCH3)3、
(C2H5O)3SiO[Si(OC2H5)2O]v2Si(OC2H5)3、
(C3H7O)3SiO[Si(OC3H7)2O]v3Si(OC3H7)3
であってもよい。これらの基中、v1～v3は０～３０までの数である。 As an amino group-free silane coupling agent having an alkoxy group, an alkoxysilyl compound containing an alkoxysilyl group at both ends, for example,
(C 2 H 5 O) 3 SiCH 2 CH 2 Si (OC 2 H 5 ) 3 ,
(C 2 H 5 O) 2 CH 3 SiCH 2 CH 2 Si (OC 2 H 5 ) 3 ,
(C 2 H 5 O) 3 SiCH = CHSi (OC 2 H 5 ) 3 ,
(CH 3 O) 3 SiCH 2 CH 2 Si (OCH 3 ) 3 (CH 3 O) 3 SiCH 2 CH 2 C 6 H 4 CH 2 CH 2 Si (OCH 3 ) 3 ,
(CH 3 O) 3 Si [CH 2 CH 2 ] 3 Si (OCH 3 ) 3 ,
(CH 3 O) 2 Si [CH 2 CH 2 ] 4 Si (OCH 3 ) 3 ,
(C 2 H 5 O) 2 Si (OC 2 H 5 ) 2 ,
(CH 3 O) 2 CH 3 SiCH 2 CH 2 Si (OCH 3 ) 2 CH 3 ,
(C 2 H 5 O) 2 CH 3 SiOSi (OC 2 H 5 ) 2 CH 3 ,
(CH 3 O) 3 SiO [Si (OCH 3 ) 2 O] v1 Si (OCH 3 ) 3 ,
(C 2 H 5 O) 3 SiO [Si (OC 2 H 5 ) 2 O] v2 Si (OC 2 H 5 ) 3 ,
(C 3 H 7 O) 3 SiO [Si (OC 3 H 7 ) 2 O] v3 Si (OC 3 H 7 ) 3
It may be. In these groups, v1 to v3 are numbers from 0 to 30.
　アルコキシ基を有するアミノ基非含有のシランカップリング剤として、加水分解性基含有シリル基を含有するアルコキシシリル化合物、例えば、
CH3Si(OCOCH3)3、(CH3)2Si(OCOCH3)2、n-C3H7Si(OCOCH3)3、CH2=CHCH2Si(OCOCH3)3、C6H5Si(OCOCH3)3、CF3CF2CH2CH2Si(OCOCH3)3、CH2=CHCH2Si(OCOCH3)3、CH3OSi(OCOCH3)3、C2H5OSi(OCOCH3)3、CH3Si(OCOC3H7)3、CH3Si[OC(CH3)=CH2]3、(CH3)2Si[OC(CH3)=CH2]3、n-C3H7Si[OC(CH3)=CH2]3、CH2=CHCH2Si[OC(CH3)=CH2]3、C6H5Si[OC(CH3)=CH2]3、CF3CF2CH2CH2Si[OC(CH3)=CH2]3、CH2=CHCH2Si[OC(CH3)=CH2]3、CH3OSi[OC(CH3)=CH2]3、C2H5OSi[OC(CH3)=CH2]3、CH3Si[ON=C(CH3)C2H5]3、（CH3）2Si[ON=C(CH3)C2H5]2、n-C3H7Si[ON=C(CH3)C2H5]3、CH2=CHCH2Si[ON=C(CH3)C2H5]3、C6H5Si[ON=C(CH3)C2H5]3、CF3CF2CH2CH2Si[ON=C(CH3)C2H5]3、CH2=CHCH2Si[ON=C(CH3)C2H5]3、CH3OSi[ON=C(CH3)C2H5]3、C2H5OSi[ON=C(CH3)C2H5]]3、CH3Si[ON=C(CH3)C2H5]3、CH3Si[N(CH3)]3、(CH3)2Si[N(CH3)]2、n-C3H7Si[N(CH3)]3、CH2=CHCH2Si[N(CH3)]3、C6H5Si[N(CH3)]3、CF3CF2CH2CH2Si[N(CH3)]3、CH2=CHCH2Si[N(CH3)]3、CH3OSi[N(CH3)]3、C2H5OSi[N(CH3)]3、CH3Si[N(CH3)]3などの昜加水分解性オルガノシランであってもよい。 As an amino group-free silane coupling agent having an alkoxy group, an alkoxysilyl compound containing a hydrolyzable group-containing silyl group, for example,
CH 3 Si (OCOCH 3 ) 3 , (CH 3 ) 2 Si (OCOCH 3 ) 2 , nC 3 H 7 Si (OCOCH 3 ) 3 , CH 2 = CHCH 2 Si (OCOCH 3 ) 3 , C 6 H 5 Si ( OCOCH 3 ) 3 , CF 3 CF 2 CH 2 CH 2 Si (OCOCH 3 ) 3 , CH 2 = CHCH 2 Si (OCOCH 3 ) 3 , CH 3 OSi (OCOCH 3 ) 3 , C 2 H 5 OSi (OCOCH 3 ) 3 , CH 3 Si (OCOC 3 H 7 ) 3 , CH 3 Si [OC (CH 3 ) = CH 2 ] 3 , (CH 3 ) 2 Si [OC (CH 3 ) = CH 2 ] 3 , nC 3 H 7 Si [OC (CH 3 ) = CH 2 ] 3 , CH 2 = CHCH 2 Si [OC (CH 3 ) = CH 2 ] 3 , C 6 H 5 Si [OC (CH 3 ) = CH 2 ] 3 , CF 3 CF 2 CH 2 CH 2 Si [OC (CH 3 ) = CH 2 ] 3 , CH 2 = CHCH 2 Si [OC (CH 3 ) = CH 2 ] 3 , CH 3 OSi [OC (CH 3 ) = CH 2 ] 3 , C 2 H 5 OSi [OC (CH 3 ) = CH 2 ] 3 , CH 3 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , (CH 3 ) 2 Si [ON = C (CH 3 ) C 2 H 5 ] 2 , nC 3 H 7 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , CH 2 = CHCH 2 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , C 6 H 5 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , CF 3 CF 2 CH 2 CH 2 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , CH 2 = CHCH 2 Si [ ON = C (CH 3 ) C 2 H 5 ] 3 , CH 3 OSi [ON = C (CH 3 ) C 2 H 5 ] 3 , C 2 H 5 OSi [ON = C (CH 3 ) C 2 H 5 ] ] 3 , CH 3 Si [ON = C (CH 3 ) C 2 H 5 ] 3 , CH 3 Si [ N (CH 3 )] 3 , (CH 3 ) 2 Si [N (CH 3 )] 2 , nC 3 H 7 Si [N (CH 3 )] 3 , CH 2 = CHCH 2 Si [N (CH 3 )] 3 , C 6 H 5 Si [N (CH 3 )] 3 , CF 3 CF 2 CH 2 CH 2 Si [N (CH 3 )] 3 , CH 2 = CHCH 2 Si [N (CH 3 )] 3 , CH It may be a hydrolyzable organosilane such as 3 OSi [N (CH 3 )] 3 , C 2 H 5 OSi [N (CH 3 )] 3 , CH 3 Si [N (CH 3 )] 3 .
　このアルコキシ基を有するアミノ基含有のシランカップリング剤として、市販のシランカップリング剤、具体的にはN-2-(アミノエチル)-3-アミノプロピルメチルジメトキシシラン(KBM-602)、N-2-(アミノエチル)-3-アミノプロピルトリメトキシシラン(KBM-603)、N-2-(アミノエチル)-3-アミノプロピルトリエトキシシラン(KBE-603)、3-アミノプロピルトリメトキシシラン(KBM-903)、3-アミノプロピルトリエトキシシラン(KBE-903)、3-トリエトキシシリル-Ｎ-(1,3-ジメチル-ブチリデン)プロピルアミン(KBE-9103)、N-フェニル-3-アミノプロピルトリメトキシシラン(KBM-573)、N-(ビニルベンジル)-2-アミノエチル-3-アミノプロピルトリメトキシシランの塩酸塩(KBM-575)で例示されるアミノ基含有アルコキシシリル化合物（以上、信越シリコーン株式会社製；商品名）が挙げられ、また3-アミノプロピルトリメトキシシラン(Z-6610)、3-アミノプロピルトリメトキシシラン(Z-6611)、3-(2-アミノエチル)アミノプロピルトリメトキシシラン(Z-6094)、3-フェニルアミノプロピルトリメトキシシラン(Z-6883)、N-[3-(トリメトキシシリル)プロピル]-N’-[(エテニルフェニル)メチル-1,2-エタンジアミン・塩酸塩(Z-6032) で例示されるアミノ基含有アルコキシシリル化合物（以上、東レ・ダウコーニング株式会社製；商品名）が挙げられる。 As an amino group-containing silane coupling agent having an alkoxy group, a commercially available silane coupling agent, specifically N-2- (aminoethyl) -3-aminopropylmethyldimethoxysilane (KBM-602), N- 2- (aminoethyl) -3-aminopropyltrimethoxysilane (KBM-603), N-2- (aminoethyl) -3-aminopropyltriethoxysilane (KBE-603), 3-aminopropyltrimethoxysilane ( KBM-903), 3-aminopropyltriethoxysilane (KBE-903), 3-triethoxysilyl-N- (1,3-dimethyl-butylidene) propylamine (KBE-9103), N-phenyl-3-amino Amino group-containing alkoxysilyl compound exemplified by propyltrimethoxysilane (KBM-573), N- (vinylbenzyl) -2-aminoethyl-3-aminopropyltrimethoxysilane hydrochloride (KBM-575) Shin-Etsu Silicone Co., Ltd .; trade name) 3-aminopropyltrimethoxysilane (Z-6610), 3-aminopropyltrimethoxysilane (Z-6611), 3- (2-aminoethyl) aminopropyltrimethoxysilane (Z-6094), 3-phenylamino Exemplified by propyltrimethoxysilane (Z-6883), N- [3- (trimethoxysilyl) propyl] -N '-[(ethenylphenyl) methyl-1,2-ethanediamine hydrochloride (Z-6032) An amino group-containing alkoxysilyl compound (manufactured by Toray Dow Corning Co., Ltd .; trade name).
　保護基材シートが金属、セラミックス又はガラスで形成されており、流路維持基板シート１０・３０がシリコーンゴムで形成されている場合、両者は直接エーテル結合で接合されていることが好ましい。この場合、保護基材シートと流路維持基板シート１０・３０とがコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されてその表面で水酸基のような活性基を生じており、加圧又は減圧による圧着によって、保護基材シートと流路維持基板シート１０・３０とが、脱水してエーテル結合を形成している。 When the protective base sheet is made of metal, ceramics or glass and the flow path maintaining substrate sheet 10/30 is made of silicone rubber, it is preferable that the two are directly joined by an ether bond. In this case, the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface. The protective base sheet and the flow path maintaining substrate sheets 10 and 30 are dehydrated to form an ether bond by pressure bonding due to pressurization or decompression.
　保護基材シートが金属、セラミックス又はガラスで形成されており、流路維持基板シート１０・３０が非シリコーンゴムを含むシリコーンゴムで形成されている場合、両者はアルコキシ基を有するアミノ基非含有のシランカップリング剤を介した酸素－炭素結合、炭素－炭素結合、酸素－珪素結合の共有結合で、接合されていてもよい。この場合、保護基材シートと流路維持基板シート１０・３０とがコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されてその表面で水酸基のような活性基を生じており、アルコキシ基又はアルコキシ基等価基と、必要に応じ不飽和基、エポキシ基、ウレイド基、スルフィド基、イソシアネート基とを含有しアミノ基非含有のシランカップリング剤が付されていることによって、常圧・加圧又は減圧下で、常温又は加熱による圧着の際に、これら共有結合を形成している。 When the protective base sheet is formed of metal, ceramics, or glass, and the flow path maintenance substrate sheet 10/30 is formed of silicone rubber including non-silicone rubber, both of them contain no amino group having an alkoxy group. They may be joined by a covalent bond of an oxygen-carbon bond, a carbon-carbon bond, and an oxygen-silicon bond via a silane coupling agent. In this case, the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface. A silane coupling agent containing an alkoxy group or an alkoxy group equivalent group and, if necessary, an unsaturated group, an epoxy group, a ureido group, a sulfide group, an isocyanate group and containing no amino group is attached. Thus, these covalent bonds are formed at the time of pressure bonding at normal temperature or under reduced pressure at normal temperature or under heating.
　保護基材シートが樹脂で形成されており、流路維持基板シート１０・３０がシリコーンゴムを含む非シリコーンゴムで形成されている場合、両者はアルコキシ基を有するアミノ基含有のシランカップリング剤を介した酸素－珪素結合の共有結合と、水酸基－アミノ基の水素結合との化学結合、新たに形成したカルボキシル基やカルボニル基とのアミド結合やイミノ結合のような共有結合で、接合されていてもよい。この場合、保護基材シートと流路維持基板シート１０・３０とがコロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）されてその表面で水酸基のような活性基を生じており、アルコキシ基又はアルコキシ基等価基とアミノ基とを含有するシランカップリング剤が付されていることによって、常圧・加圧又は減圧下で、常温又は加熱による圧着の際に、これら化学結合を形成している。この場合、シランカップリング剤のアミノ基が樹脂に吸着し易くなり、樹脂がポリカーボネート樹脂、シクロオレフィン樹脂、ポリエチレンテレフタレート樹脂、アクリル樹脂、又はエポキシ樹脂のとき、特にその反応が進行するため、迅速かつ強固に接合し易い。中でもポリカーボネート樹脂、シクロオレフィン樹脂であると、とりわけ耐水性に優れる。 When the protective base sheet is formed of a resin and the flow path maintenance substrate sheets 10 and 30 are formed of a non-silicone rubber containing a silicone rubber, they both have an amino group-containing silane coupling agent having an alkoxy group. Via a covalent bond such as an amide bond or an imino bond with a newly formed carboxyl group or carbonyl group. Also good. In this case, the protective base sheet and the flow path maintaining substrate sheets 10 and 30 are subjected to corona treatment, plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment) to form an active group such as a hydroxyl group on the surface. Are generated, and are attached with a silane coupling agent containing an alkoxy group or an alkoxy group equivalent group and an amino group, so that these can be applied at normal pressure, under pressure or under reduced pressure at room temperature or under heat. A chemical bond is formed. In this case, the amino group of the silane coupling agent is easily adsorbed to the resin, and when the resin is a polycarbonate resin, a cycloolefin resin, a polyethylene terephthalate resin, an acrylic resin, or an epoxy resin, the reaction proceeds particularly quickly and quickly. Easy to join firmly. Of these, polycarbonate resins and cycloolefin resins are particularly excellent in water resistance.
　保護基材シート水酸基と流路維持基板シート１０・３０の水酸基とのような活性基、又はそれらに反応するシランカップリング剤の反応性官能基との接近は、減圧乃至真空条件下、例えば５０ｔｏｒｒ以下、より具体的には５０～１０ｔｏｒｒの減圧条件、又は１０ｔｏｒｒ未満、より具体的には、１０ｔｏｒｒ未満～１×１０－３ｔｏｒｒ、好ましくは１０ｔｏｒｒ未満～１×１０－２ｔｏｒｒの真空条件下で、その接触界面の気体媒体を除去することによって、又はその接触界面に応力（荷重）、例えば１０～２００ｋｇｆを加えることによって、さらに接触界面を加熱することによって、促進される。減圧又は加圧条件で、保護基材シートと流路維持基板シート１０・３０の接合面全面に、均一に圧力が掛ることが好ましい。上記範囲を外れると、均一に圧力が掛らない恐れがある。 The proximity of the protective substrate sheet hydroxyl group and the active group such as the hydroxyl group of the flow path maintaining substrate sheet 10 or 30 or the reactive functional group of the silane coupling agent that reacts with the active group is reduced under reduced pressure or vacuum condition, for example, 50 torr. Hereinafter, more specifically, under reduced pressure conditions of 50 to 10 torr, or less than 10 torr, more specifically, under vacuum conditions of less than 10 torr to less than 1 × 10 −3 torr, preferably less than 10 torr to 1 × 10 −2 torr. It is facilitated by removing the gaseous medium at the contact interface or by further heating the contact interface by applying stress (load), eg 10-200 kgf, to the contact interface. It is preferable that pressure is uniformly applied to the entire bonding surface of the protective base sheet and the flow path maintaining substrate sheets 10 and 30 under reduced pressure or pressurized conditions. If it is out of the above range, the pressure may not be applied uniformly.
　このような熱伝導性マイクロ化学チップ１は、その一例である図１を参照すると、以下のようにして作製される。 Such a heat conductive microchemical chip 1 is manufactured as follows with reference to FIG. 1 as an example.
　熱伝導性フィラー粉末とシリコーンゴム原料成分とを含んだ組成物から、シリコーンゴム製流路担持基板シート・流路維持基板シート用の大型シートを作製する。又はポリイミン原料成分のような樹脂原料組成物から、流路維持基板シート用の大型シートを作製する。大型シートから、流路維持基板シート１０・３０及び流路担持基板シート２０を長方体に切り出す。この流路担持基板シート２０をレーザー加工でくり抜いて貫通させて、流路担持基板シート２０に微細流路２６を付す。その微細流路２６は、レーザー加工で、始点末端の流動試料注入部位２１ａ・２１ｂから延びて下流で合流しそこから流動試料排出部位２２ａへ延びる支流と、流動試料排出部位２２ｂ及び２２ｃへ延びる本流とを有しその本流がその下流で終点末端の流動試料排出部位２２ｂ及び２２ｃへ延びて分岐している形状に、形成される。次に、大型シートから別途、流路担持基板シート２０と同じ大きさのカバー用の流路維持基板シート１０を切り出す。その流路維持基板シート１０に、流動試料注入部位２１ａ・２１ｂと流動試料排出部位２２ａ・２２ｂ・２２ｃとに対応する位置で、それぞれ流動試料注入穴１１ａ・１１ｂと流動試料排出穴１２ａ・１２ｂ・１２ｃとを、レーザー加工又はドリル穿孔又は打ち抜きにより、開口する。次いで、大型シートから別途、底面支持用の流路維持基板シート３０を、流路担持基板シート２０と同じ大きさに切り出す。 From the composition containing the heat conductive filler powder and the silicone rubber raw material component, a large sheet for a silicone rubber channel carrying substrate sheet / channel maintenance substrate sheet is prepared. Alternatively, a large sheet for a flow path maintaining substrate sheet is prepared from a resin raw material composition such as a polyimine raw material component. From the large sheet, the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 are cut into a rectangular parallelepiped. The flow path carrying substrate sheet 20 is cut out and penetrated by laser processing, and a fine flow path 26 is attached to the flow path carrying substrate sheet 20. The fine flow path 26 is formed by laser processing and extends from the flow sample injection sites 21a and 21b at the starting end, joins downstream, and then extends to the flow sample discharge site 22a, and the main flow extends to the flow sample discharge sites 22b and 22c. The main stream is formed into a shape that extends downstream to the flow sample discharge sites 22b and 22c at the end point and branches. Next, the flow path maintaining substrate sheet 10 for the cover having the same size as the flow path carrying substrate sheet 20 is cut out from the large sheet. In the flow path maintenance substrate sheet 10, the flow sample injection holes 11 a, 11 b and the flow sample discharge holes 12 a, 12 b, respectively, at positions corresponding to the flow sample injection parts 21 a, 21 b and the flow sample discharge parts 22 a, 22 b, 22 c. 12c is opened by laser processing or drilling or punching. Next, the flow path maintenance substrate sheet 30 for supporting the bottom surface is cut out from the large sheet into the same size as the flow path carrying substrate sheet 20.
　流路維持基板シート１０・３０及び流路担持基板シート２０を、アルコール、水で洗浄する。流路維持基板シート１０の下面１５と、流路維持基板シート３０の上面３４と、流路担持基板シート２０の上下両面２４・２５とを、コロナ処理、プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）すると、それら表面に、新たに水酸基が生じる。流路維持基板シート１０・３０の間に、流路担持基板シート２０を常圧下で挟み込み、必要に応じ例えば１０ｔｏｒｒ以下減圧する。次いで必要に応じ例えば１０～２００ｋｇｆでプレスしながら例えば８０～１２０℃で加熱して熱圧着させると、流路維持基板シート１０・３０の水酸基と流路担持基板シート２０の水酸基とが脱水してエーテル結合を生じる結果、接合し、熱伝導性マイクロ化学チップ１が得られる。 The channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 are washed with alcohol and water. Corona treatment, plasma treatment, or ultraviolet irradiation treatment (general) is performed on the lower surface 15 of the flow path maintenance substrate sheet 10, the upper surface 34 of the flow path maintenance substrate sheet 30, and the upper and lower surfaces 24 and 25 of the flow path support substrate sheet 20. When UV treatment or excimer UV treatment), hydroxyl groups are newly generated on the surfaces. The flow path holding substrate sheet 20 is sandwiched between the flow path maintaining substrate sheets 10 and 30 under normal pressure, and the pressure is reduced, for example, 10 torr or less as necessary. Then, if necessary, for example, by pressing at 10 to 200 kgf while heating at 80 to 120 ° C. and thermocompression bonding, the hydroxyl groups of the flow path maintaining substrate sheets 10 and 30 and the hydroxyl groups of the flow path supporting substrate sheet 20 are dehydrated. As a result of forming an ether bond, bonding and thermal conductive microchemical chip 1 are obtained.
　なお、流路維持基板シート１０・３０及び流路担持基板シート２０にコロナ放電を施した例を示したが、大気圧プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）を施してもよい。これらの処理によって有機の流路維持基板シート１０・３０及び流路担持基板シート２０表面に、水酸基である活性基が生成したり、さらにカルボキシル基、カルボニル基で例示される活性基が生成したりする。 In addition, although the example which performed the corona discharge to the flow-path maintenance board | substrate sheet | seat 30 * 30 and the flow-path holding | maintenance board | substrate sheet | seat 20 was shown, atmospheric pressure plasma processing or ultraviolet irradiation processing (general UV processing and excimer UV processing) was performed. May be. By these treatments, an active group that is a hydroxyl group is generated on the surfaces of the organic channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20, or an active group exemplified by a carboxyl group and a carbonyl group is generated. To do.
　流路維持基板シート１０・３０及び流路担持基板シート２０は、原料組成に基づき、元々水酸基を有するものと有しないものとがあるが、これら表面に水酸基を有しなくともコロナ放電、大気圧プラズマ処理又は紫外線照射処理（一般的なＵＶ処理やエキシマＵＶ処理）の処理を施すことにより、そこに水酸基が効率よく生成される。 The flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 are based on the raw material composition and may or may not originally have a hydroxyl group. By performing plasma treatment or ultraviolet irradiation treatment (general UV treatment or excimer UV treatment), hydroxyl groups are efficiently generated there.
　それらの最適処理条件は、流路維持基板シート１０・３０及び流路担持基板シート２０の材質の種類や履歴によって異なるが、その表面に５５ｋＪ/ｍ以上の表面張力が得られるまで処理し続けることが重要である。これにより、十分な接着強度が得られる。 The optimum processing conditions vary depending on the material type and history of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20, but the processing is continued until a surface tension of 55 kJ / m or more is obtained on the surface. is important. Thereby, sufficient adhesive strength is obtained.
　具体的には、流路維持基板シート１０・３０及び流路担持基板シート２０のコロナ放電処理は、コロナ表面改質装置（例えば、信光電気計測（株）製コロナマスター）を用いて、例えば、電源：AC100V、出力電圧：0～20ｋV、発振周波数：0～40kHzで0.1～60秒、温度0～60℃の条件で行われる。 Specifically, the corona discharge treatment of the flow path maintenance substrate sheets 10 and 30 and the flow path support substrate sheet 20 is performed using, for example, a corona surface modification device (for example, a corona master manufactured by Shinko Electric Measurement Co., Ltd.) Power supply: 100 VAC, output voltage: 0 to 20 kV, oscillation frequency: 0 to 40 kHz, 0.1 to 60 seconds, temperature 0 to 60 ° C.
　流路維持基板シート１０・３０及び流路担持基板シート２０の大気圧プラズマ処理は、大気圧プラズマ発生装置（例えば、松下電工（株）製：商品名Aiplasuma）を用いて、例えば、プラズマ処理速度10～100mm/s,電源：200　又は　220V　AC（30A）、圧縮エア：0.5MPa(1NL/min)、10kHz/300W～5GHz、電力：100W～400W、照射時間：0.1～60秒の条件で行われる。 The atmospheric pressure plasma treatment of the flow path maintaining substrate sheets 10 and 30 and the flow path carrying substrate sheet 20 is performed using, for example, an atmospheric pressure plasma generator (for example, Matsushita Electric Works, Ltd .: trade name Aiplasuma), for example, plasma processing speed. 10 to 100 mm / s, power supply: 200 or 220 V AC (30 A), compressed air: 0.5 MPa (1 NL / min), 10 kHz / 300 W to 5 GHz, power: 100 W to 400 W, irradiation time: 0.1 to 60 seconds Is called.
　流路維持基板シート１０・３０及び流路担持基板シート２０の紫外線照射は、紫外線－発光ダイオード（UV-LED）照射装置（例えば、（株）オムロン製のUV-LED照射装置：商品名ZUV-C30H）を用いて、例えば、波長：200～400nm、電源：100V　AC、光源ピーク照度：400～3000mW/cm2、照射時間：1～60秒の条件で行われる。 Ultraviolet irradiation of the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 is performed using an ultraviolet light-emitting diode (UV-LED) irradiation device (for example, UV-LED irradiation device manufactured by OMRON Corporation: trade name ZUV-) C30H), for example, under the conditions of wavelength: 200 to 400 nm, power source: 100 V AC, light source peak illuminance: 400 to 3000 mW / cm 2 , irradiation time: 1 to 60 seconds.
　なお、流路維持基板シート１０・３０及び流路担持基板シート２０を接合した後、流路維持基板シート１０のおもて面と、流路維持基板シート３０のうら面とを、分子接着剤であるシランカップリング剤溶液で浸漬又は噴霧してから、保護基材シート（不図示）に接触させてもよい。浸漬及び噴霧の時間に制限はなく、保護基材シートの基材表面が一様に湿潤していることが重要である。 After the flow path maintaining substrate sheets 10 and 30 and the flow path holding substrate sheet 20 are joined, the front surface of the flow path maintaining substrate sheet 10 and the back surface of the flow path maintaining substrate sheet 30 are bonded to the molecular adhesive. After immersing or spraying with a silane coupling agent solution, the protective substrate sheet (not shown) may be contacted. There is no limitation on the dipping and spraying time, and it is important that the substrate surface of the protective substrate sheet is uniformly moistened.
　シランカップリング剤を付した保護基材シートを、オーブンに入れたり、ドライヤーで温風を送風したり、高周波を照射したりすることにより、加熱しながら乾燥する。加熱・乾燥は、50～250℃の温度範囲で、1～60分間行われる。50℃未満では、保護基材シート表面に生成した水酸基とシランカップリング剤との反応時間が長くかかりすぎて、生産性が低下し、コストの高騰を招く。一方、250℃を超えると、加熱乾燥時間が短くても保護基材シート表面が変形したり、分解したりしてしまう。1分間未満の加熱乾燥では熱の伝達が不十分であるため、保護基材シート表面の水酸基とシランカップリング剤との結合が不十分となる。一方、60分間を超えると生産性が低下する。 The protective substrate sheet with the silane coupling agent is dried in a heated state by placing it in an oven, blowing warm air with a dryer, or irradiating high frequency. Heating and drying are performed at a temperature range of 50 to 250 ° C. for 1 to 60 minutes. If it is less than 50 degreeC, the reaction time of the hydroxyl group produced | generated on the surface of a protection base material sheet and a silane coupling agent will take too long, productivity will fall, and the cost will rise. On the other hand, when the temperature exceeds 250 ° C., the surface of the protective base sheet is deformed or decomposed even if the heat drying time is short. Since heat transfer is insufficient in heat drying for less than 1 minute, the bonding between the hydroxyl group on the surface of the protective substrate sheet and the silane coupling agent becomes insufficient. On the other hand, when it exceeds 60 minutes, productivity falls.
　保護基材シート表面の水酸基とシランカップリング剤との反応が不十分な場合には、前記浸漬と乾燥とを１～５回程度繰り返してもよい。それにより１回当たりの浸漬及び乾燥時間を短縮し、反応回数を増やす方が反応を十分に進行させることができる。 If the reaction between the hydroxyl group on the surface of the protective substrate sheet and the silane coupling agent is insufficient, the immersion and drying may be repeated about 1 to 5 times. As a result, it is possible to sufficiently advance the reaction by shortening the time of dipping and drying per time and increasing the number of reactions.
　熱伝導性マイクロ化学チップ１は、例えば微量合成の例について図１を参照して説明すると、以下のようにして使用される。熱伝導性マイクロ化学チップ１をマイクロリアクター（不図示）に装着する。カバー用の流路維持基板シート１０の流動試料注入穴１１ａ・１１ｂにそれぞれシリンジ（不図示）を気密に刺し、各シリンジから別々にそれぞれ液状検体と液状試薬とである流動試料を、１００ｋＰａを超え３ＭＰａ以下に加圧しながら流動試料注入部位２１ａ・２１ｂを経て、微細流路２６に送り込む。両流動試料は、微細流路２６を流れて合流して混合され、互いに反応する。必要に応じ支流である流動試料排出部位２２ａを経て流動試料排出穴１２ａから、廃液を排出する。本流で分岐し、流動試料排出部位２２ｂ・２２ｃを経て流動試料排出穴１２ｂ・１２ｃから、微量合成された生成物を含む流動試料をそれぞれ排出し、目的物を得る。 The heat conductive microchemical chip 1 is used as follows, for example, with reference to FIG. The thermally conductive microchemical chip 1 is mounted on a microreactor (not shown). Syringes (not shown) are air-tightly inserted into the flow sample injection holes 11a and 11b of the flow path maintenance substrate sheet 10 for the cover, respectively, and the liquid sample and the liquid reagent separately from each syringe exceed 100 kPa. While being pressurized to 3 MPa or less, the fluid sample is injected into the fine channel 26 through the fluid sample injection sites 21a and 21b. Both flow samples flow through the fine flow channel 26, merge and mix, and react with each other. If necessary, the waste liquid is discharged from the flow sample discharge hole 12a through the flow sample discharge portion 22a which is a tributary. Branching in the main stream, the flow sample containing the product synthesized in a small amount is discharged from the flow sample discharge holes 12b and 12c through the flow sample discharge portions 22b and 22c, respectively, and the target product is obtained.
　熱伝導性マイクロ化学チップ１の別な態様を、図２に示す。熱伝導性フィラー粉末とシリコーンゴム原料成分とを含んだ組成物から、シリコーンゴム製流路維持基板シート・流路担持基板シート用の大型シートを作製する。この大型シートから流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０を同じ大きさの略矩形に切り出す。この熱伝導性マイクロ化学チップ１はカバー用の流路維持基板シート１０、第一の微細流路２６を有する流路担持基板シート２０、中敷用の流路維持基板シート３０、第二の微細流路４６を有する流路担持基板シート４０、底面支持用の流路維持基板シート５０の順で重ね合わされたものである。 Another embodiment of the thermally conductive microchemical chip 1 is shown in FIG. From the composition containing the heat conductive filler powder and the silicone rubber raw material component, a large sheet for the silicone rubber channel maintaining substrate sheet / channel supporting substrate sheet is prepared. From this large sheet, the flow path maintaining substrate sheets 10, 30, 50 and the flow path carrying substrate sheets 20, 40 are cut into substantially rectangular shapes of the same size. The thermally conductive microchemical chip 1 includes a flow path maintaining substrate sheet 10 for a cover, a flow path supporting substrate sheet 20 having a first fine flow path 26, a flow path maintaining substrate sheet 30 for an insole, and a second fine path. The flow path carrying substrate sheet 40 having the flow path 46 and the flow path maintenance substrate sheet 50 for supporting the bottom surface are superposed in this order.
　流路担持基板シート２０・４０に、微細流路２６・４６が表裏を貫通して形成されている。微細流路２６は流路担持基板シート２０で始点末端である流動試料注入部位２１ａ・２１ｂからそれぞれ延びて下流で合流し、そこから流動試料排出部位２２ａへ延びる支流と、流動試料移送部位２３へ延びる本流とに分岐している。中敷用の流路維持基板シート３０は、その流動試料移送部位２３に対応する位置で、流動試料移送穴３３が開けられている。流動試料移送穴３３に逆止弁が設けられていてもよい。流路担持基板シート４０は、その流動試料移送穴３３に対応する位置で、流動試料移入部位４３が設けられ、そこへ別な始点末端である流動試料注入部位４１ａから延びて合流し、その下流で終点末端である流動試料排出部位４２ａ及び４２ｂへ延びて分岐した微細流路４６が、表裏を貫通して形成されている。底面支持用の流路維持基板シート５０に、流動試料注入部位４１ａと流動試料排出部位４２ａ及び４２ｂとに対応した位置で、流動試料注入穴５１ａと流動試料排出穴５２ａ・５２ｂとが開けられている。流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０は、図１と同様に、エーテル結合を介して、直接接合されている。流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０は、前記の素材、形状でもよく、シランカップリング剤を介して接合されていてもよい。この熱伝導性マイクロ化学チップ１は、図１のものと同様に加圧して流動体試料を送り込んで使用される。熱伝導性マイクロ化学チップ１は、複数の流路担持基板シート２０・４０の各微細流路２６・４６で、分子量や組成成分や組成物性が異なる流動試料をそれぞれ注入する際に、不意な混入を防ぐことができる。また、流動試料が微細流路２６・４６で反応して、流動試料内の目的物質の分子量が変化したり流動試料の比重が変化したりしたときに、適宜分離するものであってもよい。 Fine channels 26 and 46 are formed on the channel-carrying substrate sheets 20 and 40 so as to penetrate the front and back sides. The microchannel 26 extends from the flow sample injection sites 21a and 21b, which are the starting point ends, in the flow channel carrying substrate sheet 20, and merges downstream, and from there to a tributary extending to the flow sample discharge site 22a, and to the flow sample transfer site 23 It branches into the main stream that extends. The flow path maintaining substrate sheet 30 for the insole has a flow sample transfer hole 33 at a position corresponding to the flow sample transfer portion 23. A check valve may be provided in the flow sample transfer hole 33. The flow path carrying substrate sheet 40 is provided with a flow sample transfer portion 43 at a position corresponding to the flow sample transfer hole 33, and extends and joins the flow sample injection portion 41 a, which is another starting point end, downstream thereof. The microchannel 46 that branches to the flow sample discharge portions 42a and 42b, which are the end points, is formed through the front and back surfaces. A flow sample injection hole 51a and flow sample discharge holes 52a and 52b are opened in the flow path maintenance substrate sheet 50 for supporting the bottom surface at positions corresponding to the flow sample injection portion 41a and the flow sample discharge portions 42a and 42b. Yes. The flow path maintaining substrate sheets 10, 30, 50 and the flow path carrying substrate sheets 20, 40 are directly bonded via ether bonds as in FIG. The flow path maintaining substrate sheets 10, 30, 50 and the flow path supporting substrate sheets 20, 40 may have the above-described materials and shapes, and may be joined via a silane coupling agent. This thermally conductive microchemical chip 1 is used by applying a fluid sample by applying pressure as in the case of FIG. The thermally conductive microchemical chip 1 is inadvertently mixed when injecting flow samples having different molecular weights, composition components, and composition properties in the fine channels 26 and 46 of the plurality of channel-carrying substrate sheets 20 and 40, respectively. Can be prevented. Alternatively, the sample may be appropriately separated when the fluid sample reacts in the fine channels 26 and 46 and the molecular weight of the target substance in the fluid sample changes or the specific gravity of the fluid sample changes.
　熱伝導性マイクロ化学チップ１の別な態様を、図３に示す。この熱伝導性マイクロ化学チップ１は、図１の流路維持基板シート１０・３０及び流路担持基板シート２０を有してなり、流路維持基板シート１０・３０及び流路担持基板シート２０が、２枚の樹脂板又は金属板で撓まない剛直なホルダー６０ａ・６０ｂで挟まれている。これらは、螺子止めされ、固定されている。ホルダー６０ａ・６０ｂに、流路維持基板シート１０・３０の流動試料注入穴１１ａ・１１ｂや流動試料排出穴１２ａ・１２ｂ・１２ｃと対応した位置で、注入誘導穴６１ａ・６１ｂと排出誘導穴６２ａ・６２ｂ・６２ｃとが、開口している。この熱伝導性マイクロ化学チップ１は、図１のものと同様に加圧して流動体試料を微細流路２６に送り込んで使用される。ホルダー６０ａ・６０ｂは、可撓性の流路維持基板シート１０・３０及び流路担持基板シート２０を、撓まないように矯正しつつ、微細流路２６に流動体試料が流れる程度に締め付けている。この熱伝導性マイクロ化学チップ１は、図２に示す流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０を有するものであってもよい。図１～２の熱伝導性マイクロ化学チップ１は、流路維持基板シート１０・３０・５０及び流路担持基板シート２０・４０との間に加熱ヒーターが挿入されて接合されていてもよく、図３のホルダー上又は下に加熱ヒーターが配置されていてもよい（不図示）。熱伝導性マイクロ化学チップ１は、流動試料注入部位２１ａ・２１ｂ、流動試料排出部位２２ａ・２２ｂ・２２ｃ、流動試料注入部位４１ａ、流動試料排出部位４２ａ・４２ｂの何れかに、検体・試薬・反応生成物を検知する電極等のセンサーが配線されていてもよい。ホルダー６０ａ・６０ｂが、それに接する流路維持基板シート１０・３０に、同様に、接合していてもよい。 Another embodiment of the thermally conductive microchemical chip 1 is shown in FIG. The thermally conductive microchemical chip 1 includes the flow path maintaining substrate sheets 10 and 30 and the flow path supporting substrate sheet 20 of FIG. It is sandwiched between rigid holders 60a and 60b that are not bent by two resin plates or metal plates. These are screwed and fixed. In the holders 60a and 60b, at the positions corresponding to the flow sample injection holes 11a and 11b and the flow sample discharge holes 12a, 12b, and 12c of the flow path maintenance substrate sheets 10 and 30, the injection guide holes 61a and 61b and the discharge guide holes 62a and 62b and 62c are open. The heat conductive microchemical chip 1 is used by applying pressure and feeding the fluid sample into the fine channel 26 in the same manner as in FIG. The holders 60a and 60b are clamped so that the fluid sample flows into the fine channel 26 while correcting the flexible channel maintaining substrate sheets 10 and 30 and the channel carrying substrate sheet 20 so as not to bend. Yes. This heat conductive microchemical chip 1 may have the flow path maintaining substrate sheets 10, 30, and 50 and the flow path supporting substrate sheets 20 and 40 shown in FIG. The heat conductive microchemical chip 1 of FIGS. 1 and 2 may be joined by inserting a heater between the flow path maintaining substrate sheets 10, 30, 50 and the flow path holding substrate sheets 20, 40, A heater may be disposed on or below the holder in FIG. 3 (not shown). The thermally conductive microchemical chip 1 has a sample / reagent / reaction at any one of the flow sample injection sites 21a and 21b, the flow sample discharge sites 22a, 22b and 22c, the flow sample injection site 41a and the flow sample discharge sites 42a and 42b. A sensor such as an electrode for detecting the product may be wired. Similarly, the holders 60a and 60b may be joined to the flow path maintaining substrate sheets 10 and 30 in contact therewith.
　熱伝導性マイクロ化学チップ１の別な態様を、図４に示す。微細流路２６の途中の液溜部２８を有していてもよい。微細流路２６の途中の液溜部２８は、流動試料をトラップできるように微細流路２６の途中で広がっている。液溜部２８は、流入した流動試料を暫しトラップして化学反応を充分に起こさせることができる。また、液溜部２８は、流動試料のための測定用・検出用又は反応用の光線、例えば紫外線・赤外線・可視光線・レーザー光等を照射できる程度に十分に広い面積を有している。液溜部２８は、トラップ開始端部とトラップ終了端部とが夫々、徐々に拡径・縮径しており、流動試料の流れを阻害しないようになっている。液溜部２８内に流動試料が流れ込んできたら、加圧による流路２６への流動試料の流動を停止させ、必要に応じ加熱・放熱乃至冷却して、反応例えばＰＣＲを充分に起こさせてから、流動試料の流動を再開するように調整するようになっていてもよい。流路途中で流動試料が十分に反応できるのであれば、又は、流動試料のための測定用・検出用又は反応用の光線、例えば紫外線・赤外線・可視光線・レーザー光等を照射できるのであれば、若しくはこれら光線を照射する必要がないのであれば、図１のように、微細流路２６は同径のままの溝で液溜部２８を有しなくてもよい。 Another embodiment of the thermally conductive microchemical chip 1 is shown in FIG. You may have the liquid storage part 28 in the middle of the microchannel 26. FIG. The liquid reservoir 28 in the middle of the fine channel 26 extends in the middle of the fine channel 26 so that the flowing sample can be trapped. The liquid reservoir 28 can trap the flowing sample for a while and cause a chemical reaction sufficiently. In addition, the liquid reservoir 28 has a sufficiently large area so that it can irradiate measurement, detection, or reaction light rays for a fluid sample, such as ultraviolet rays, infrared rays, visible rays, and laser beams. In the liquid reservoir 28, the trap start end and the trap end end are gradually expanded and contracted, respectively, so that the flow of the flowing sample is not hindered. When the flowing sample has flowed into the liquid reservoir 28, the flow of the flowing sample to the flow path 26 by pressurization is stopped, and heating, heat dissipation or cooling is performed as necessary to sufficiently cause a reaction such as PCR. The flow sample may be adjusted to resume the flow. If the flow sample can react sufficiently in the middle of the flow path, or if it can irradiate light for measurement, detection or reaction for the flow sample, such as ultraviolet rays, infrared rays, visible rays, laser light, etc. Alternatively, if it is not necessary to irradiate these light beams, the fine flow path 26 does not have to have the liquid reservoir 28 as a groove having the same diameter as shown in FIG.
　以下に、本発明を適用する熱伝導性マイクロ化学チップ１を試作した例を示す。 Hereinafter, an example in which a thermally conductive microchemical chip 1 to which the present invention is applied is made as a prototype is shown.
（実施例１）
　シリコーンゴムとしてメチルビニルシリコーンゴムであるＳＨ１００５（東レ・ダウコーニング株式会社製；商品名）の５０重量部、シリコーンオイルとしてポリジメチルシロキサンであるＳＨ２００　１００ｃｓ（東レ・ダウコーニング株式会社製；商品名）の５０重量部、熱伝導性フィラーとして酸化マグネシウムであるパイロキスマ５３０１（協和化学工業株式会社製；商品名、平均粒径２μｍ）５０重量部及びパイロキスマ３３２０（協和化学工業株式会社製；商品名、平均粒径２０μｍ）の２００重量部、添加剤として水酸化アルミニウムＡｌ(ＯＨ)３であるハイジライトＨ３２（昭和電工株式会社製；商品名）５０重量部及び酸化カルシウムＣａＯであるＶＥＳＴＡ　ＰＰ（井上石灰工業株式会社製；商品名）の１０重量部、白金触媒として白金錯体である（ＧＥＬＥＳＴ社製白金カルボニルシクロビニルメチルシロキサン錯体ビニルメチル環状シロキサン溶液の０．０１重量部とを、混練し、シリコーンゴム製熱伝導性シート用の組成物を得た。これを、加圧加熱し、流路維持基板シートとなるシリコーンゴム製熱伝導性シートとした。 Example 1
50 parts by weight of SH1005 (trade name, manufactured by Toray Dow Corning Co., Ltd.), which is methyl vinyl silicone rubber as the silicone rubber, and SH200 100cs (product name: manufactured by Toray Dow Corning Co., Ltd.), which is polydimethylsiloxane as the silicone oil. 50 parts by weight, pyroxuma 5301 (manufactured by Kyowa Chemical Industry Co., Ltd .; trade name, average particle size 2 μm), which is magnesium oxide as a thermally conductive filler, and 50 parts by weight of pyrokisuma 3320 (manufactured by Kyowa Chemical Industry Co., Ltd .; trade name, average grain) 200 parts by weight of 20 μm diameter), 50 parts by weight of Heidilite H32 (made by Showa Denko KK; trade name) aluminum hydroxide Al (OH) 3 as an additive and VESTA PP (Inoue Lime Industry Co., Ltd.), calcium oxide CaO 10 parts by weight of company-made product name), platinum touch As a platinum complex (0.01 parts by weight of a platinum carbonylcyclovinylmethylsiloxane complex vinylmethyl cyclic siloxane solution manufactured by GELEST) was kneaded to obtain a composition for a thermal conductive sheet made of silicone rubber. Then, it was heated under pressure to obtain a silicone rubber thermal conductive sheet to be a flow path maintaining substrate sheet.
　一方、シリコーンゴムとしてメチルビニルシリコーンゴムであるＳＨ８５１（東レ・ダウコーニング株式会社製；商品名）の１００重量部、パーオキサイド系架橋剤として２，５－ジメチル－２，５－ジ（ｔ－ブチルパーオキシ）ヘキサンであるＰＣ－４（東レダウコーニング社製；商品名、５０％シリカ溶液）の０．５重量部とを、混練し、中間層のシート用の組成物を得た。これを、加圧加熱し、流路担持基板シートとなるシリコーンゴム製熱伝導性シートした。 On the other hand, 100 parts by weight of SH851 (trade name, manufactured by Toray Dow Corning Co., Ltd.), which is methyl vinyl silicone rubber, is used as the silicone rubber, and 2,5-dimethyl-2,5-di (t-butyl) is used as the peroxide crosslinking agent. Peroxy) hexane (PC-4) (trade name, 50% silica solution manufactured by Toray Dow Corning Co., Ltd.) 0.5 parts by weight was kneaded to obtain a composition for a sheet of an intermediate layer. This was heated under pressure to form a heat conductive sheet made of silicone rubber to be a flow path carrying substrate sheet.
　図１～３、又は図４のように流路担持基板シートと流路維持基板シートとを形成し、接着させて、本発明の熱伝導性マイクロ化学チップ１を得た。 As shown in FIGS. 1 to 3 or 4, the flow path carrying substrate sheet and the flow path maintaining substrate sheet were formed and bonded to obtain the heat conductive microchemical chip 1 of the present invention.
　図１の流路維持基板シート３０に、上記熱伝導シートを接着させたものと上記通常のＳＨ８５１Ｕで作製したシートを張り合わせたものとの比較では、ＰＣＲの回数を３０回行うための時間が約１．５倍かかることが分かった。 In the comparison between the sheet having the heat conducting sheet adhered to the flow path maintaining substrate sheet 30 in FIG. 1 and the sheet laminated with the normal SH851U, the time required for performing the PCR 30 times is about It was found that it took 1.5 times.
　このようにして得られた本発明の熱伝導性マイクロ化学チップ１は、デオキシリボ核酸（ＤＮＡ）を増幅するために用いられる。ＤＮＡを増幅するのに、第１段階（９４～９６℃）で、標的二本鎖ＤＮＡを熱変性して一本鎖とし、第２段階（５５～６０℃）でプライマーを一本鎖ＤＮＡにアニーリングさせ、第３段階（７２～７４℃）で伸長反応を進め、このポリメラーゼ連鎖反応（ＰＣＲ）を繰り返す。加熱は、熱電対、ペルチェ素子、赤外線照射により行われるが、この熱伝導性マイクロ化学チップ１がシリコーンゴム製熱伝導性シートを有していることから、温度の上昇下降がスムーズに行われ、ＰＣＲを滞りなく行うことができる。 The heat conductive microchemical chip 1 of the present invention thus obtained is used for amplifying deoxyribonucleic acid (DNA). To amplify the DNA, the target double-stranded DNA is thermally denatured into a single strand in the first step (94 to 96 ° C), and the primer is converted into a single-stranded DNA in the second step (55 to 60 ° C). Annealing is performed, the extension reaction is advanced in the third stage (72 to 74 ° C.), and this polymerase chain reaction (PCR) is repeated. Heating is performed by a thermocouple, a Peltier element, and infrared irradiation, but since this thermally conductive microchemical chip 1 has a silicone rubber thermally conductive sheet, the temperature rises and falls smoothly, PCR can be performed without delay.
　なお、本発明を適用外であって、シリコーンゴム製熱伝導性シートに代えて熱伝導性フィラー粉末未含有のゴムシートを用いた熱伝導性マイクロ化学チップでは、温度の上昇下降がスムーズに行われず、ＰＣＲを滞りなく行うことができないため、反応時間が遅く、効率が悪いものであった。 In addition, in the heat conductive microchemical chip using the rubber sheet not containing the heat conductive filler powder instead of the silicone rubber heat conductive sheet, the temperature rises and falls smoothly. As a result, the PCR could not be performed without delay, so the reaction time was slow and the efficiency was poor.
（実施例２：熱伝導性と断熱性の検討）
(1)シリコーンゴムシートの調製
　シリコーンゴムとしてメチルビニルシリコーンゴムであるＳＨ８５１Ｕ（東レ・ダウコーニング株式会社製；商品名）の１００重量部、パーオキサイド系架橋剤として、２，５－ジメチル－２，５－ジ（ｔ－ブチルパーオキシ）ヘキサンであるＲＣ－４（東レ・ダウコーニング株式会社製；商品名、５０％シリカ溶液）の０．５重量部とを、混練し、シート用の組成物を得た。これを加圧加熱し、シリコーンゴムシートを作製した。 (Example 2: Examination of thermal conductivity and heat insulation)
(1) Preparation of silicone rubber sheet 100 parts by weight of SH851U (manufactured by Toray Dow Corning Co., Ltd .; trade name) which is methyl vinyl silicone rubber as silicone rubber, and 2,5-dimethyl-2, A composition for a sheet is kneaded with 0.5 part by weight of RC-4 (trade name, 50% silica solution) manufactured by Toray Dow Corning Co., Ltd., which is 5-di (t-butylperoxy) hexane. Got. This was heated under pressure to produce a silicone rubber sheet.
(2)熱伝導性シリコーンゴムシートの調製
　シリコーンゴムとしてメチルビニルシリコーンゴムであるＳＨ１００５（東レ・ダウコーニング株式会社製；商品名）の５０重量部、シリコーンオイルとしてポリジメチルシロキサンであるＳＨ２００　１００ｃｓ（東レ・ダウコーニング株式会社製；商品名）の５０重量部、熱伝導性フィラーとして酸化マグネシウムであるパイロキスマ５３０１（協和化学工業株式会社製；商品名、平均粒径２μｍ）５０重量部及びパイロキスマ３３２０（協和化学工業株式会社製；商品名、平均粒径２０μｍ）の２００重量部、添加剤として水酸化アルミニウムＡｌ（ＯＨ）３であるハイジライトＨ３２（昭和電工株式会社製；商品名）５０重量部及び酸化カルシウムＣａＯであるＶＥＳＴＡ　ＰＰ（井上石灰工業株式会社製；商品名）の１０重量部、白金触媒として白金錯体である（ＧＥＬＥＳＴ社製白金カルボニルシクロビニルメチルシロキサン錯体ビニルメチル環状シロキサン溶液の０．０１重量部とを、混練し、シリコーンゴム製熱伝導性シート用の組成物を得た。これを、加圧加熱し、流路維持基板シートとなるシリコーンゴム製熱伝導性シートとした。 (2) Preparation of thermally conductive silicone rubber sheet 50 parts by weight of SH1005 (made by Toray Dow Corning Co., Ltd .; trade name) which is methyl vinyl silicone rubber as silicone rubber, and SH200 100cs (Toray) which is polydimethylsiloxane as silicone oil -50 parts by weight of Dow Corning Co., Ltd. (trade name), pyroxuma 5301 (manufactured by Kyowa Chemical Industry Co., Ltd .; trade name, average particle size 2 μm), which is magnesium oxide as a thermally conductive filler, and Pyroxma 3320 (Kyowa) 200 parts by weight of Chemical Industry Co., Ltd .; trade name, average particle size of 20 μm), 50 parts by weight of Hydrite H32 (trade name) made by aluminum hydroxide Al (OH) 3 as an additive and oxidation VESTA PP (Inoue Lime Industry) which is calcium CaO 10 parts by weight of a formula company; trade name) and 0.01 parts by weight of a platinum carbonylcyclovinylmethylsiloxane complex vinylmethyl cyclic siloxane solution manufactured by GELEST as a platinum catalyst are kneaded and made of silicone rubber A composition for a thermally conductive sheet was obtained, which was heated under pressure to obtain a silicone rubber thermally conductive sheet to be a flow path maintaining substrate sheet.
(3)発泡性シリコーンゴムシートの調製
　発泡性シリコーンゴムシートを、特開２００８－９４９８１号公報の実施例１に準じて調製した。シリコーンゴム１００質量部に、過酸化物加硫剤２質量部を配合し、二本ロールで混合分散させて、シリコーンゴムコンパウンドを調製した。加硫剤を含むシリコーンゴムコンパウンド１１０質量部に、第１の気孔形成剤としてトリメチロールプロパン１０質量部と、第２の気孔形成剤としてペンタエリスリトール３９０質量部とを配合し、缶体温度（Ｔ１）１１０℃に設定されたニーダーで１０分間混練して気孔形成剤を混合分散させたゴム組成物を得た。混練工程で得られたゴム組成物を、プレス金型内で加硫温度（Ｔ２）１７０℃で１０分間圧縮成形して厚さ２ｍｍのシート状の加硫ゴム組成物を得た。混練温度（Ｔ１）に対する加硫温度（Ｔ２）の差（Ｔ１－Ｔ２）は、－６０℃とした。シート状の加硫ゴム組成物を、温水を用いて水洗し、加硫ゴム組成物中から気孔形成剤を溶出させ、多孔体である発泡性シリコーンゴムシートとした。 (3) Preparation of foamable silicone rubber sheet A foamable silicone rubber sheet was prepared according to Example 1 of JP-A-2008-94981. A silicone rubber compound was prepared by blending 2 parts by mass of a peroxide vulcanizing agent with 100 parts by mass of silicone rubber and mixing and dispersing with two rolls. To 110 parts by mass of a silicone rubber compound containing a vulcanizing agent, 10 parts by mass of trimethylolpropane as a first pore-forming agent and 390 parts by mass of pentaerythritol as a second pore-forming agent are blended, and the can body temperature (T1 ) A rubber composition was obtained by kneading with a kneader set at 110 ° C. for 10 minutes to mix and disperse the pore forming agent. The rubber composition obtained in the kneading process was compression molded in a press mold at a vulcanization temperature (T2) of 170 ° C. for 10 minutes to obtain a sheet-like vulcanized rubber composition having a thickness of 2 mm. The difference (T1−T2) between the vulcanization temperature (T2) and the kneading temperature (T1) was −60 ° C. The sheet-like vulcanized rubber composition was washed with warm water and the pore-forming agent was eluted from the vulcanized rubber composition to obtain a foamable silicone rubber sheet as a porous body.
(4)断熱性測定
　１００℃に加熱した金属板上に、夫々厚さ（ｔ）が２．０ｍｍである、シリコーンゴムシートと、熱伝導性シリコーンゴムシートと、発泡性シリコーンゴムとを置き、温度上昇の経時変化を測定した。その結果を図６に示す。 (4) Measurement of heat insulation On a metal plate heated to 100 ° C., a silicone rubber sheet having a thickness (t) of 2.0 mm, a thermally conductive silicone rubber sheet, and a foamable silicone rubber were placed. The change in temperature with time was measured. The result is shown in FIG.
　図６から明らかな通り、熱伝導性シリコーンゴムシートでは短時間での温度上昇が確認でき、発泡性シリコーンゴムシートでは、温度上昇が遅くなることが確認できた。このことから、三次元マイクロ化学チップに放熱ゴム材料を用いることで、温度応答性が上がり、温度サイクルをかける際の時間短縮が可能になることが分かった。また、発泡性ゴム材料を用いることによりチップ内を異なる温度に設定する際、温度の干渉を低減することが可能となることが分かった。 As is clear from FIG. 6, it was confirmed that the temperature increase in a short time was confirmed in the heat conductive silicone rubber sheet, and the temperature increase was slow in the foamable silicone rubber sheet. From this, it was found that the use of a heat-dissipating rubber material for the three-dimensional microchemical chip improves the temperature responsiveness and shortens the time for applying a temperature cycle. It has also been found that the use of a foam rubber material can reduce the temperature interference when the inside of the chip is set to a different temperature.
　本発明の熱伝導性マイクロ化学チップは、内部からの放熱性や外部からの熱伝導性に優れており、迅速に分析結果を知る必要がある救急医療現場での患者の生体成分の分析、犯罪現場で微量な血痕・体液・毛髪・生体組織細胞等の遺留品からＤＮＡを抽出し、そのＤＮＡを増やすＰＣＲ増幅し、電気泳動でＤＮＡを特定するＤＮＡ解析、新規医薬品探索のための各種医薬候補品の物性・薬効評価、オーダーメイド医療のための診断、ペプチドやＤＮＡや機能性低分子の微量合成、幹細胞やウィルス等の培養や増殖などに、用いられる。 The thermal conductive microchemical chip of the present invention has excellent heat dissipation from the inside and heat conductivity from the outside, and it is necessary to quickly analyze the analysis of the patient's biological components in the emergency medical field where it is necessary to know the analysis results. Extraction of DNA from traces of blood stains, body fluids, hair, biological tissue cells, etc. on site, PCR amplification to increase the DNA, DNA analysis that identifies DNA by electrophoresis, various drug candidates for new drug discovery It is used for evaluation of physical properties and drug efficacy of products, diagnosis for custom-made medicine, microsynthesis of peptides, DNA and functional low molecules, culture and proliferation of stem cells and viruses.
　熱伝導性マイクロ化学チップは、簡便に自在な形状の流路を形成できるものなので、オーダーメイドの診療や、種々の動植物のＤＮＡ分析などの同定に、用いることができる。 Since the heat conductive microchemical chip can easily form a flow path having any shape, it can be used for custom-made medical care and identification of DNA analysis of various animals and plants.
　本発明の熱伝導性マイクロ化学チップを製造する方法で得られたこのマイクロ化学チップは、それらの分析装置やマイクロリアクターに装着して、遺伝子診察・治療を行う医療分野や、生体試料を用いた犯罪捜査分野における各種分析、海洋や湖沼等の遠隔地での水中ロボットを用いた微生物探索、医薬品開発における各種合成に用いることができる。 The microchemical chip obtained by the method for producing the thermally conductive microchemical chip of the present invention is used in the medical field for performing genetic diagnosis and treatment, or a biological sample, mounted on the analyzer or microreactor. It can be used for various analyzes in the field of criminal investigations, microbiological searches using underwater robots in remote areas such as the ocean and lakes, and various synthesis in drug development.
　１は熱伝導性マイクロ化学チップ、１０は流路維持基板シート、１１・１１ａ・１１ｂは流動試料注入穴、１２・１２ａ・１２ｂ・１２ｃは流動試料排出穴、１５は下面、２０は流路担持基板シート、２１・２１ａ・２１ｂは流動試料注入部位、２２・２２ａ・２２ｂ・２２ｃは流動試料排出部位、２３は流動試料移送部位、２４は上面、２５は下面、２６は流路、２７は壁面、２８は液溜部、３０は流路維持基板シート、３３は流動試料移送穴、３４は上面、４０は流路担持基板シート、４１ａは流動試料注入部位、４２ａ・４２ｂは流動試料排出部位、４３は流動試料移入部位、４６は流路、５０は流路維持基板シート、５１ａは流動試料注入穴、５２ａ・５２ｂは流動試料排出穴、６０ａ・６０ｂはホルダー、６１ａ・６１ｂは注入誘導穴、６２ａ・６２ｂ・６２ｃは排出誘導穴である。 1 is a thermally conductive microchemical chip, 10 is a flow path maintenance substrate sheet, 11, 11 a, and 11 b are flow sample injection holes, 12, 12 a, 12 b, and 12 c are flow sample discharge holes, 15 is a bottom surface, and 20 is a flow path support 21, 21 a, 21 b are fluid sample injection sites, 22, 22 a, 22 b, 22 c are fluid sample discharge sites, 23 is a fluid sample transport site, 24 is an upper surface, 25 is a lower surface, 26 is a flow path, and 27 is a wall surface , 28 is a liquid reservoir, 30 is a flow path maintenance substrate sheet, 33 is a flow sample transfer hole, 34 is an upper surface, 40 is a flow path support substrate sheet, 41 a is a flow sample injection site, 42 a and 42 b are flow sample discharge sites, 43 is a flow sample transfer site, 46 is a flow path, 50 is a flow path maintenance substrate sheet, 51a is a flow sample injection hole, 52a and 52b are flow sample discharge holes, 60a and 60b are holders, and 61a and 61b are injections Shirubeana, 62a · 62b · 62c is discharged guide hole.

Claims (14)

  1. 　検体、試薬及び試料から選ばれる流動試料を加圧及び／又は毛細管現象により流し込み化学反応及び／又は化学作用させる流路を凹んで及び／又は貫孔してゴム、樹脂、金属、セラミックス及び／又はガラスで形成された単数又は複数の流路担持基板シートと、ゴム、樹脂、金属、セラミックス及び／又はガラスで形成され、前記流路に繋がる受渡穴を開けており前記流路を覆う前記流路担持基板シートをその最上面及び／又は最下面に接して担持する流路維持基板シートとが、重ねられて、少なくとも何れかのシート表面でコロナ処理、プラズマ処理及び紫外線照射処理から選ばれる乾式処理と分子接着剤処理との少なくとも何れかによる直接的な及び／又は前記分子接着剤を介した間接的な共有結合により、接合して一体化しており、前記流路担持基板シートと前記流路維持基板シートとのそれぞれの前記流路と前記受渡穴とが、流動試料注入口から流動試料排出口へ立体的に順次繋がり、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、酸化アルミニウム、酸化マグネシウム、酸化亜鉛、グラファイトカーボン、チッ化ケイ素、チッ化ホウ素及びチッ化アルミニウムから選ばれる少なくとも何れかの熱伝導性フィラー粉末を含んだ熱伝導性シートであることを特徴とする熱伝導性マイクロ化学チップ。 A flow sample selected from a specimen, a reagent, and a sample is poured by pressure and / or capillary action, and a chemical reaction and / or a chemical action channel is recessed and / or penetrated to form rubber, resin, metal, ceramics and / or One or a plurality of flow path supporting substrate sheets formed of glass, and the flow path that is formed of rubber, resin, metal, ceramics, and / or glass and that has a delivery hole connected to the flow path and covers the flow path The flow path maintaining substrate sheet that supports the supporting substrate sheet in contact with the uppermost surface and / or the lowermost surface thereof is stacked, and dry processing selected from at least one of the sheet surfaces from corona treatment, plasma treatment, and ultraviolet irradiation treatment. And / or molecular adhesive treatment directly and / or indirectly through covalent bonding via the molecular adhesive, joined and integrated, The flow path supporting substrate sheet and the flow path maintaining substrate sheet, respectively, the flow path and the delivery hole are three-dimensionally connected from the flow sample inlet to the flow sample discharge port, and the flow path support substrate sheet At least one of the flow path maintaining substrate sheet includes at least one heat conductive filler powder selected from aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride, boron nitride, and aluminum nitride. A thermally conductive microchemical chip characterized by being a thermally conductive sheet.
  2. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、シリコーンゴムで形成されていることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 2. The thermally conductive microchemical chip according to claim 1, wherein at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
  3. 　前記シリコーンゴムが、白金触媒を、含んでいることを特徴とする請求項２に記載の熱伝導性マイクロ化学チップ。 The thermally conductive microchemical chip according to claim 2, wherein the silicone rubber contains a platinum catalyst.
  4. 　前記シリコーンゴムが、ビニルメトキシシリル基を有する炭素数６～１２のシランカップリング剤を、含んでいることを特徴とする請求項２に記載の熱伝導性マイクロ化学チップ。 3. The thermally conductive microchemical chip according to claim 2, wherein the silicone rubber contains a silane coupling agent having 6 to 12 carbon atoms having a vinylmethoxysilyl group.
  5. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、珪藻土、マイカ、タルク及び／又はカオリンを含むことを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 2. The thermally conductive microchemical chip according to claim 1, wherein at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet contains diatomaceous earth, mica, talc and / or kaolin.
  6. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、三酸化アンチモン及び水酸化アルミニウムから選ばれる少なくとも何れかの難燃剤を含むことを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 2. The heat according to claim 1, wherein at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet includes at least one flame retardant selected from antimony trioxide and aluminum hydroxide. Conductive microchemical chip.
  7. 　前記共有結合が、エーテル結合であることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 The thermally conductive microchemical chip according to claim 1, wherein the covalent bond is an ether bond.
  8. 　前記流路担持基板シート又は前記流路維持基板シートの少なくとも一部が、ガラスビーズ及び／又はゼオライトを配合したシリコーンゴム原料組成物と、水溶性アルコールを配合したシリコーン組成物とから選ばれる少なくとも何れかで形成された発泡性シリコーンゴムシートであることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 At least a part of the flow path carrying substrate sheet or the flow path maintaining substrate sheet is selected from a silicone rubber raw material composition containing glass beads and / or zeolite and a silicone composition containing a water-soluble alcohol. The thermally conductive microchemical chip according to claim 1, wherein the thermally conductive microchemical chip is a foamable silicone rubber sheet formed by
  9. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、アナターゼ型又はルチル型の酸化チタン粒子が分散されたシリコーンゴムで形成されることにより、反射率を８０～１００％とする高反射性シリコーンゴムシートであることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 At least one of the channel-carrying substrate sheet and the channel-maintaining substrate sheet is formed of silicone rubber in which anatase-type or rutile-type titanium oxide particles are dispersed, so that the reflectance is 80 to 100%. The thermally conductive microchemical chip according to claim 1, wherein the thermally conductive microchemical chip is a highly reflective silicone rubber sheet.
  10. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、シリコーンゴム、エチレン－プロピレン－ジエン－メチレン共重合体ゴム、ブチルゴム、アクリロニトリル－ブタジエン共重合体ゴム、フッ素ゴム、スチレン－ブタジエン共重合体ゴム及び／又はヒドリンゴムで形成されることにより、酸素ガス、窒素ガス、二酸化炭素ガス及び水蒸気の少なくとも何れかのガスのガス透過率を５００～０．０５（cc/cm2/mm/sec/cm・Hg×1010）とする低ガス透過性シリコーンゴムシートであることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 At least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is made of silicone rubber, ethylene-propylene-diene-methylene copolymer rubber, butyl rubber, acrylonitrile-butadiene copolymer rubber, fluoro rubber, styrene- By being formed of butadiene copolymer rubber and / or hydrin rubber, the gas permeability of at least one of oxygen gas, nitrogen gas, carbon dioxide gas and water vapor is 500 to 0.05 (cc / cm 2 / mm). 2. The thermally conductive microchemical chip according to claim 1, wherein the thermally conductive microchemical chip is a low-gas-permeable silicone rubber sheet at / sec / cm · Hg × 10 10 ).
  11. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかが、パーオキサイド架橋シリコーンゴム、付加架橋シリコーンゴム、縮合架橋シリコーンゴム、放射線架橋又は電子線架橋シリコーンゴム及びこれらのうちの何れかのシリコーンゴムとオレフィン系ゴムとの共ブレンド物から選ばれる何れかで形成されていることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 At least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is a peroxide crosslinked silicone rubber, an addition crosslinked silicone rubber, a condensation crosslinked silicone rubber, a radiation crosslinked or an electron beam crosslinked silicone rubber, and any of these. 2. The thermally conductive microchemical chip according to claim 1, wherein the thermally conductive microchemical chip is formed of any one selected from a co-blend of such silicone rubber and olefin rubber.
  12. 　前記流路の一部が拡径して液溜部となっていることを特徴とする請求項１に記載の熱伝導性マイクロ化学チップ。 2. The thermally conductive microchemical chip according to claim 1, wherein a part of the flow path is enlarged to form a liquid reservoir.
  13. 　単数又は複数のゴム製の流路担持基板シートに、検体、試薬及び試料から選ばれる流動試料を加圧及び／又は毛細管現象により流し込み化学反応及び／又は化学作用させる流路を、設ける流路成形工程と、
    　ゴム、樹脂、金属、セラミックス及び／又はガラスで形成され、前記流路に繋がる受渡穴を開けており前記流路担持基板シートを挟む流路維持基板シートを、形成する受渡穴形成工程と、
    　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、コロナ処理、プラズマ処理、又は紫外線照射処理する処理工程と、
    　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、常圧下、加圧下又は減圧下で重ねて、直接、又は分子接着剤を介した共有結合により、接合して、一体化する接合工程とを有し、
    　酸化アルミニウム、酸化マグネシウム、酸化亜鉛、グラファイトカーボン、チッ化ケイ素、チッ化ホウ素及びチッ化アルミニウムから選ばれる少なくとも何れかの熱伝導性フィラー粉末を含んだシリコーンゴム組成物で成形して、前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、熱伝導性シートにすることを特徴とする熱伝導性マイクロ化学チップの製造方法。     Forming a flow path by providing a flow path for a chemical reaction and / or a chemical action by flowing a flow sample selected from a specimen, a reagent and a sample by pressurization and / or capillary action on one or a plurality of rubber flow path support substrate sheets Process,
    A delivery hole forming step of forming a flow path maintenance substrate sheet formed of rubber, resin, metal, ceramics and / or glass, having a delivery hole connected to the flow path and sandwiching the flow path carrying substrate sheet;
    A treatment step of corona treatment, plasma treatment, or ultraviolet irradiation treatment of at least one of the flow path carrying substrate sheet and the flow path maintenance substrate sheet;
    At least one of the flow path supporting substrate sheet and the flow path maintaining substrate sheet is stacked under normal pressure, under pressure or under reduced pressure, and joined directly or by covalent bonding via a molecular adhesive. A joining process to
    Molded with a silicone rubber composition containing at least one heat conductive filler powder selected from aluminum oxide, magnesium oxide, zinc oxide, graphite carbon, silicon nitride, boron nitride and aluminum nitride, and the flow path A method for producing a thermally conductive microchemical chip, wherein at least one of the carrier substrate sheet and the flow path maintaining substrate sheet is a thermally conductive sheet.
  14. 　前記流路担持基板シートと前記流路維持基板シートとの少なくとも何れかを、シリコーンゴムで形成することを特徴とする請求項１３に記載の熱伝導性マイクロ化学チップの製造方法。 14. The method for producing a thermally conductive microchemical chip according to claim 13, wherein at least one of the flow path carrying substrate sheet and the flow path maintaining substrate sheet is formed of silicone rubber.
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2015098720A1 (en) * 2013-12-27 2017-03-23 株式会社朝日Ｆｒ研究所 3D micro chemical chip
CN107541071A (en) * 2016-06-29 2018-01-05 上海纽帕化工有限公司 A kind of automotive seat foam
CN107734840A (en) * 2017-11-29 2018-02-23 中国电子科技集团公司第二十六研究所 Based on the cold cooling structure of printed circuit board three-dimensional micro-channel array liquid
WO2019187275A1 (en) * 2018-03-30 2019-10-03 住友理工株式会社 Fluid device composite member and method for manufacturing same
WO2020078736A1 (en) * 2018-10-19 2020-04-23 SpinDiag GmbH Sample holder
WO2020137065A1 (en) * 2018-12-28 2020-07-02 株式会社朝日Ｆｒ研究所 Hydrophilically-reinforced molded body made from silicone rubber, and hydrophilically-reinforced joined body using same
WO2021131681A1 (en) * 2019-12-26 2021-07-01 信越化学工業株式会社 Thermally conductive silicone resin composition
WO2024038819A1 (en) * 2022-08-19 2024-02-22 日東電工株式会社 Workpiece holding member and laminate

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005074796A (en) * 2003-08-29 2005-03-24 Sumitomo Bakelite Co Ltd Method for joining microchip substrate and microchip
JP2010527293A (en) * 2007-02-28 2010-08-12 コーニング インコーポレイテッド Method for making a microfluidic device
JP2011053091A (en) * 2009-09-02 2011-03-17 Alps Electric Co Ltd Bonding member and method of manufacturing the same
JP2013188677A (en) * 2012-03-13 2013-09-26 Asahi Fr R&D Co Ltd Microchemical chip

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6131338B2 (en) * 2013-12-27 2017-05-17 株式会社朝日Ｆｒ研究所 3D micro chemical chip

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005074796A (en) * 2003-08-29 2005-03-24 Sumitomo Bakelite Co Ltd Method for joining microchip substrate and microchip
JP2010527293A (en) * 2007-02-28 2010-08-12 コーニング インコーポレイテッド Method for making a microfluidic device
JP2011053091A (en) * 2009-09-02 2011-03-17 Alps Electric Co Ltd Bonding member and method of manufacturing the same
JP2013188677A (en) * 2012-03-13 2013-09-26 Asahi Fr R&D Co Ltd Microchemical chip

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Kitai Tokasei no Koto nado (1", JOURNAL OF THE SOCIETY OF RUBBER INDUSTRY, vol. 55, no. 10, 1982, pages 682 - 684 *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2015098720A1 (en) * 2013-12-27 2017-03-23 株式会社朝日Ｆｒ研究所 3D micro chemical chip
CN107541071A (en) * 2016-06-29 2018-01-05 上海纽帕化工有限公司 A kind of automotive seat foam
CN107734840A (en) * 2017-11-29 2018-02-23 中国电子科技集团公司第二十六研究所 Based on the cold cooling structure of printed circuit board three-dimensional micro-channel array liquid
CN107734840B (en) * 2017-11-29 2023-08-18 中国电子科技集团公司第二十六研究所 Liquid cooling structure based on three-dimensional micro-channel array of printed circuit board
US11548194B2 (en) 2018-03-30 2023-01-10 Sumitomo Riko Company Limited Method for manufacturing fluid device composite member
JP7063682B2 (en) 2018-03-30 2022-05-09 住友理工株式会社 Composite members for fluid devices and their manufacturing methods
JP2019177304A (en) * 2018-03-30 2019-10-17 住友理工株式会社 Composite member for fluid device and method for manufacturing the same
WO2019187275A1 (en) * 2018-03-30 2019-10-03 住友理工株式会社 Fluid device composite member and method for manufacturing same
WO2020078736A1 (en) * 2018-10-19 2020-04-23 SpinDiag GmbH Sample holder
US11654432B2 (en) 2018-10-19 2023-05-23 SpinDiag GmbH Sample container
WO2020137065A1 (en) * 2018-12-28 2020-07-02 株式会社朝日Ｆｒ研究所 Hydrophilically-reinforced molded body made from silicone rubber, and hydrophilically-reinforced joined body using same
JP6749683B1 (en) * 2018-12-28 2020-09-02 株式会社朝日Ｆｒ研究所 Hydrophilic reinforced molded product made of silicone rubber and hydrophilic reinforced joined product using the same
WO2021131681A1 (en) * 2019-12-26 2021-07-01 信越化学工業株式会社 Thermally conductive silicone resin composition
JP2021105116A (en) * 2019-12-26 2021-07-26 信越化学工業株式会社 Heat conductive silicone resin composition
JP7165647B2 (en) 2019-12-26 2022-11-04 信越化学工業株式会社 Thermally conductive silicone resin composition
WO2024038819A1 (en) * 2022-08-19 2024-02-22 日東電工株式会社 Workpiece holding member and laminate

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