[go: up one dir, main page]

WO2020013318A1 - Substrat ayant une couche de modification et son procédé de fabrication - Google Patents

Substrat ayant une couche de modification et son procédé de fabrication Download PDF

Info

Publication number
WO2020013318A1
WO2020013318A1 PCT/JP2019/027714 JP2019027714W WO2020013318A1 WO 2020013318 A1 WO2020013318 A1 WO 2020013318A1 JP 2019027714 W JP2019027714 W JP 2019027714W WO 2020013318 A1 WO2020013318 A1 WO 2020013318A1
Authority
WO
WIPO (PCT)
Prior art keywords
modified layer
concave portion
substrate
laminated
layer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2019/027714
Other languages
English (en)
Japanese (ja)
Inventor
秀介 佐藤
一木　隆範
真吾 上野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kawasaki Institute of Industrial Promotion
Original Assignee
Kawasaki Institute of Industrial Promotion
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kawasaki Institute of Industrial Promotion filed Critical Kawasaki Institute of Industrial Promotion
Publication of WO2020013318A1 publication Critical patent/WO2020013318A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • 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
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • 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
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters

Definitions

  • the present invention relates to a substrate having a modified layer and a method for manufacturing the same.
  • Non-Patent Document 1 describes a stainless steel substrate having an array of fine through holes.
  • the substrate described in Non-Patent Document 1 is surface-treated so that the inside of the through-hole is hydrophilic and the surface where the through-hole is opened is hydrophobic. It has been reported that the substrate described in Non-Patent Document 1 can easily and quantitatively introduce a liquid into each through hole.
  • Non-Patent Document 2 describes a microchamber.
  • the microchamber described in Non-Patent Document 2 is a well array formed on a glass substrate, and a thin film of polydimethylsiloxane (PDMS) is stacked on a surface where the well is opened. Since the microchamber described in Non-Patent Document 2 has a PDMS layer with high sealing properties, it is reported that each chamber can be sealed by covering with a glass substrate. In addition, it has been reported that since the PDMS layer is sufficiently thin, inhibition of the enzymatic reaction by PDMS is suppressed, and cell-free protein synthesis can be performed efficiently in a microchamber.
  • PDMS polydimethylsiloxane
  • Non-Patent Document 1 the manufacturing process of the substrate described in Non-Patent Document 1 is complicated.
  • the microchamber described in Non-Patent Document 2 is manufactured by a method in which a PDMS layer is stacked on a glass substrate, masked with a photoresist, and a well array is formed by etching. For this reason, it is not possible to manufacture the microchamber described in Non-Patent Document 2 by laminating a modified layer on the surface of a well array that has already been formed.
  • An object of the present invention is to provide a technique for easily stacking a modified layer on the surface of a substrate having a concave portion.
  • the present invention includes the following aspects.
  • the surface where the concave portion is opened is exposed, and a substrate in which the protective layer is laminated on the inner surface of the concave portion is obtained, and the solvent that dissolves the protective layer on the surface where the concave portion is opened Has a permeability, by laminating a first modified layer, and by contacting the solvent with the substrate to remove the protective layer laminated on the inner surface of the concave portion, the concave portion is opened Obtaining a substrate having the first modified layer laminated on a surface to be formed. [2] After obtaining a substrate in which the first modified layer is laminated on the surface where the concave portion opens, a second modified layer is formed on the inner surface of the first modified layer and the concave portion.
  • a method for manufacturing a substrate having a modified layer comprising: laminating a first modified layer on a surface of the substrate having a concave portion where the concave portion opens and an inner surface of the concave portion; By laminating a protective layer on the first modified layer and removing a part of the protective layer and the first modified layer, a surface where the concave portion opens is exposed, and an inner surface of the concave portion is formed.
  • the concave portion is opened by stacking a second modified layer on the surface where the material layer and the concave portion are opened, and by removing the second modified layer laminated on the inner surface of the concave portion.
  • a method for manufacturing a substrate having a modified layer comprising: laminating a first modified layer on a surface of the substrate having a concave portion where the concave portion opens and an inner surface of the concave portion; By laminating a protective layer on the first modified layer and removing a part of the protective layer and the first modified layer, a surface where the concave portion opens is exposed, and an inner surface of the concave portion is formed. Obtaining a substrate in which the first modified layer and the protective layer are laminated in this order, and laminating a second modified layer on the surface where the protective layer and the concave are laminated in the concave portion are opened.
  • FIGS. 4A to 4E are schematic diagrams illustrating a method for manufacturing a substrate according to the first embodiment.
  • (A) And (b) is a schematic diagram which shows the state which made the solvent S contact the board
  • (A)-(c) is a schematic diagram explaining the manufacturing method of the board
  • (A)-(e) is a schematic diagram explaining the manufacturing method of the board
  • A)-(c) is a schematic diagram explaining the manufacturing method of the board
  • (A)-(c) is a schematic diagram explaining the manufacturing method of the board
  • (A)-(c) is a schematic diagram explaining the experimental process of the experimental example 2.
  • (A) is a photograph showing the results of Experimental Example 2.
  • (B) and (c) are fluorescence micrographs showing the results of Experimental Example 2.
  • (A)-(d) is a schematic cross-sectional view explaining the experimental process of Experimental Example 3.
  • (A) is a photograph of the microreactor array chip in Experimental Example 3.
  • (B) is a photograph of the fluid device in Experimental Example 3.
  • (A) and (b) are fluorescence micrographs of the fluorescence of fluorescein observed in Experimental Example 3.
  • (A) shows the result of sending a fluorescein solution and oil to an unmodified microreactor array chip.
  • (B) shows the result of sending the fluorescein solution and the oil to the microreactor array chip having the modified layer.
  • the present invention relates to a method for manufacturing a substrate having a modified layer, wherein a step of laminating a protective layer on a surface of the substrate having a concave portion where the concave portion opens and an inner surface of the concave portion ( 1a) and a step (1b) of obtaining a substrate in which a surface where the concave portion is opened is exposed by removing a part of the protective layer and the protective layer is laminated on the inner surface of the concave portion; (1c) laminating a first modified layer in which a solvent that dissolves the protective layer is permeable to the surface where the opening is formed, and contacting the solvent with the substrate to form an inner surface of the recess. Removing the protective layer thus laminated to obtain a substrate having the first modified layer laminated on the surface where the concave portion is opened (1d).
  • the modified substrate in which a solvent that dissolves the protective layer is permeable to the surface where the opening is formed
  • Examples of the material of the substrate used in the manufacturing method of the present embodiment include glass; semiconductors such as silicon; metals such as chromium, stainless steel, gold, and magnesium alloy; resins such as polycarbonate and polymethyl methacrylate.
  • the substrate may be composed of one kind of material, or may be composed of a combination of a plurality of materials. Further, the surface of the substrate may be coated with a metal oxide. Examples of the metal oxide include Al 2 O 3 , Ta 2 O 5 , Nb 2 O 5 , ZrO 2 , TiO 2 , HfO 2 , Ni oxide, Cr oxide, Fe oxide, Mn oxide, W oxide, Cu oxide, Ag oxide and the like can be mentioned.
  • the substrate having the concave portion is manufactured by processing the substrate by dry etching using a reactive gas, ion, radical, or the like, wet etching using a reactive liquid, cutting, embossing for pressing a mold against the substrate, or the like. be able to.
  • the recesses form an array in which the recesses are regularly arranged.
  • the concave portion may be formed on only one surface of the substrate, or may be formed on both surfaces.
  • the shape of the concave portion is not particularly limited, and may be, for example, a cylindrical shape, a polyhedral shape (for example, a rectangular parallelepiped, a hexagonal prism, an octagonal prism, or the like), a truncated cone, or a truncated pyramid.
  • the volume per recess may be, for example, from 1 to 1 ⁇ 10 9 fL, for example, from 1 to 1 ⁇ 10 6 fL, and for example, from 1 to 1 ⁇ 10 3 fL.
  • the density of the concave portions on the substrate may be, for example, 1 to 2 ⁇ 10 7 / cm 2 , for example, may be 1 to 2 ⁇ 10 5 / cm 2 , for example, 1 to 2 ⁇ 10 3 / Cm 2 .
  • the shape of the substrate is not particularly limited, and examples thereof include a rectangle, a polygon (for example, a triangle, a pentagon, a hexagon, a polygon of a heptagon or more), a circle, an ellipse, a combination thereof, and the like.
  • the area of the substrate can be appropriately changed depending on the design of the concave portion, and may be, for example, 1 to 1000 cm 2 , for example, 1 to 100 cm 2 .
  • FIGS. 1A to 1E are schematic views illustrating a method for manufacturing a substrate according to the first embodiment. Hereinafter, the manufacturing method of the first embodiment will be described with reference to FIGS.
  • FIG. 1A is a cross-sectional view of a substrate 110 having a recess 120.
  • a protective layer 140 is laminated on the surface 130 of the substrate 110 having the recess 120 and the inner surface 121 of the recess 120.
  • the “surface on which the concave portion is opened” refers to a region other than the concave portion on the surface of the substrate where the concave portion is formed.
  • the protective layer 140 is not particularly limited as long as it is a material which can be easily removed and does not break the shape of the concave portion 120.
  • AZ photoresist Merck
  • SU-8 photoresist MicroChem
  • a metal film such as chromium
  • a paint such as ink.
  • ⁇ ⁇ Lamination of the protective layer 140 can be performed by coating, dipping, spin coating, vapor deposition, spraying, sputter deposition, chemical vapor deposition (CVD), plating, or the like, depending on the material of the protective layer to be used.
  • Step (1b) Subsequently, as shown in FIG. 1C, by removing a part of the protective layer 140, the surface 130 where the concave portion 120 opens was exposed, and the protective layer 140 was laminated on the inner surface 121 of the concave portion 120. Obtain a substrate.
  • Part of the protective layer 140 can be removed by dry etching, wet etching, chemical mechanical polishing, or the like. Such a processing method may be referred to as etch back.
  • etch back As a result, on the surface 130, the material of the substrate 110 is exposed.
  • the recess 120 is filled with the protective layer 140, and the protective layer 140 forms an exposed surface 141 at the opening of the recess 120.
  • the inner surface 121 of the concave portion 120 is in a state where the protective layer 140 is laminated.
  • a first modified layer (indicated by “A” in FIG. 1) is laminated on the surface 130 where the concave portion 120 opens.
  • the first modified layer may be laminated not only on the surface 130 but also on the exposed surface 141 of the protective layer 140.
  • the protective layer 140 is laminated on the inner surface 121 of the recess 120. Therefore, the first modified layer is not laminated on the inner surface 121.
  • the modified layer means a layer of a substance that changes the properties of the surface of the substrate.
  • a modified layer can be laminated on the surface of a hydrophilic substrate to make it hydrophobic.
  • a modified layer can be laminated on the surface of a hydrophobic substrate to make it hydrophilic.
  • the modified layer may be formed from one type of material, or may be formed from a mixture of two or more types of materials. Further, the modified layer may be formed from one layer, or may be formed from a plurality of stacked layers.
  • Step (1d) Subsequently, a solvent that dissolves the protective layer 140 is brought into contact with the substrate on which the first modified layer is laminated, and the protective layer 140 laminated on the inner surface 121 of the concave portion 120 is removed. As a result, as shown in FIG. 1E, it is possible to obtain the substrate 100 in which the first modified layer is stacked on the surface 130 where the recess 120 opens. In the substrate 100, the first modified layer A is not laminated on the inner surface 121 of the recess 120, and the material of the substrate 110 is exposed.
  • the modified layer can be easily laminated only on the surface where the concave portion opens.
  • a material that is permeable to a solvent that dissolves the protective layer 140 is used as the first modified layer.
  • the first modified layer is preferably an extremely thin film from the viewpoint that the solvent that dissolves the protective layer 140 has permeability.
  • an extremely thin film means a film having a thickness of about 0.5 to 1000 nm.
  • the thickness of the extremely thin film is, for example, preferably 0.5 to 10 nm, more preferably 1 to 2 nm. It is particularly preferred that the ultrathin film is a self-assembled monolayer.
  • FIG. 2A shows a state in which a solvent S for dissolving the protective layer 140 is brought into contact with a substrate on which a first modified layer (indicated by “A” in FIG.
  • FIG. 4 is a schematic view showing a state in which a protective layer 140 laminated on the substrate is removed.
  • the solvent S permeates through the first modified layer, and the protective layer 140 laminated on the inner surface 121 of the recess 120 is formed. Can be removed. Further, the first modified layer laminated on the exposed surface 141 of the protective layer 140 is also removed together with the protective layer 140. On the other hand, the first modified layer laminated on the surface 130 where the concave portion 120 opens remains without being separated by the solvent S.
  • FIG. 2B is a schematic diagram illustrating a case where the solvent S has no permeability to the first modified layer. As shown in FIG. 2B, when the solvent S cannot pass through the first modified layer, the protective layer 140 laminated on the inner surface 121 of the recess 120 cannot be removed.
  • the first modified layer is preferably an extremely thin film.
  • the material for forming the first modified layer can be appropriately selected according to the material of the substrate 110.
  • Specific materials for forming the first modified layer include biomolecules, biomolecule capturing molecules, biomolecules or materials other than biomolecule capturing molecules.
  • biomolecules include nucleic acids, peptides, antibodies, antibody fragments, enzymes, and the like.
  • the biomolecule capturing molecule include a nucleic acid aptamer, a peptide aptamer, an antibody, and an antibody fragment.
  • Materials other than biomolecules or biomolecule capturing molecules include, for example, organic silanes having a methyl group terminus such as hexamethyldisilazane (HMDS), tetraethyl orthosilicate (TEOS), and tetramethylsilane (TMS); Organosilane having an amino group terminus such as aminopropyltriethoxysilane (APTES); Organosilane having a fluoroalkyl group terminus such as perfluoroalkylsilane; Glycidyl group terminus such as 3-glycidoxypropyltrimethoxysilane (GLYMO) Alkanethiols such as sulfopetine 3-undecanethiol; alkylphosphonic acids such as octadecylphosphonic acid; phosphoric acid esters such as tricresyl phosphite; fatty acids such as stearic acid; Anatate; thermoplastic resin such as acrylic resin; thermosetting
  • the lamination of the first modified layer can be performed by coating, dipping, spin coating, spraying, sputter deposition, chemical vapor deposition (CVD), plating, or the like, depending on the material of the first modified layer to be used. it can.
  • the first modified layer may be a layer made of a biomolecule or a biomolecule capturing molecule itself, or may be a layer made of a material other than a biomolecule or a biomolecule capturing molecule. Further, a biomolecule or a biomolecule capturing molecule, or a material other than the biomolecule or the biomolecule capturing molecule may be further bound to the first modified layer.
  • the above-mentioned alkanethiol, alkylphosphonic acid, phosphate ester, etc. may be further bonded to the first modified layer made of the above-mentioned metal or metal oxide film.
  • the first modified layer made of the above-mentioned metal or the like may be modified to an OH group terminal, and further, the above-mentioned isocyanate or the like may be bonded.
  • the surface of the above-mentioned first modified layer may be modified to an amino group terminal, and further, the above-mentioned fatty acid, a chelating agent such as nitrilotriacetic acid (NTA), carboxymethyl aspartic acid (CMA) or the like may be bound thereto.
  • NTA nitrilotriacetic acid
  • CMA carboxymethyl aspartic acid
  • nickel ions may be coordinated to nitrilotriacetic acid (NTA), and cobalt ions may be further coordinated to carboxymethyl aspartic acid (CMA).
  • NTA nitrilotriacetic acid
  • CMA carboxymethyl aspartic acid
  • a biomolecule or a biomolecule-capturing molecule may be further bound to the first modified layer made of a material other than the biomolecule or the biomolecule-capturing molecule.
  • a biomolecule or a biomolecule capturing molecule may be further bound to the modified layer.
  • Biomolecules or biomolecule capturing molecules are the same as those described above, and include, for example, nucleic acids, peptides, proteins and the like.
  • the nucleic acid and the peptide may be a nucleic acid aptamer and a peptide aptamer, respectively.
  • the protein include an antibody, an antibody fragment, and an enzyme.
  • nucleic acids, peptides, and proteins may each be a component of a mutant library.
  • the terms “protein” and “peptide” are used without strict distinction, and may be referred to as a peptide or a protein depending on the number of amino acids.
  • the binding of the biomolecule to the first modified layer is performed by, for example, binding by a chemical crosslinker; binding by an antigen-antibody reaction; binding by a protein capture molecule; avidin-biotin binding; binding of a histidine tag to nickel ions. Can be performed.
  • protein capture molecules to be bound to the first modified layer include avidin; biotin; metal ions such as nickel and cobalt; maltose; guanine nucleotides; glutathione; and antigens.
  • the binding of the protein capture molecule to the first modified layer can be performed by utilizing, for example, the binding by a chemical crosslinker.
  • the solvent for dissolving the protective layer 140 can be appropriately selected according to the material of the protective layer 140 to be used.
  • water N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), ⁇ -Butyrolactone, propylene glycol monomethyl ether (PGME), propylene glycol monomethyl ether acetate (PGMEA), butyl carbitol (BDG), monoethanolamine (MEA), methanol, ethanol, denatured ethanol, 2-propanol (IPA), methyl lactate Organic solvents such as ethyl lactate, ethyl acetate, butyl acetate, acetone, 2-butanone (MEK), 4-methyl-2-pentanone (MIBK), acetone; sodium hydroxide solution, potassium hydroxide solution, tetramethylammonium hydroxy (TMAH), alkaline solutions such as aqueous ammonia; acids such as acetic acid, citric acid solution, glycolic acid solution
  • the protective layer 140 when the protective layer 140 is a resist, an organic solvent or the like can be used according to the material of the resist.
  • an organic solvent or the like when the protective layer 140 is a metal film, an alkali solution, an acid solution, or the like can be used.
  • an organic solvent, or the like when the protective layer 140 is a paint, water, an organic solvent, or the like can be used depending on the material of the paint.
  • the manufacturing method of the second embodiment is mainly different from the manufacturing method of the first embodiment in that a second modified layer is further laminated on the substrate 100 manufactured by the manufacturing method of the first embodiment.
  • the manufacturing method according to the second embodiment includes, after the step (1d) of the first embodiment, a step (2a) of laminating a second modified layer on the inner surface 121 of the first modified layer and the recess 120.
  • a step (2a) of laminating a second modified layer on the inner surface 121 of the first modified layer and the recess 120 By removing the second modified layer laminated on the first modified layer, the first modified layer is laminated on the surface 130 where the concave 120 is opened, and the second modified layer is formed on the inner surface 121 of the concave 120.
  • (2b) obtaining a substrate on which the modified layer is laminated.
  • FIGS. 3A to 3C are schematic views illustrating a method for manufacturing a substrate according to the second embodiment.
  • the manufacturing method of the second embodiment will be described with reference to FIGS.
  • FIG. 3A is a cross-sectional view of the substrate 100 obtained in the step (1d) of the first embodiment, and corresponds to the substrate 100 shown in FIG.
  • a first modified layer (indicated by “A” in FIG. 3) is laminated on a surface 130 where the recess 120 opens.
  • the first modified layer A is not laminated on the inner surface 121 of the recess 120, and the material of the substrate 110 is exposed.
  • the first modified layer A laminated on the surface 130 of the substrate 100 and the second modified layer are indicated by “B”.
  • the first modified layer A and the second modified layer B are laminated on the substrate 110 in this order.
  • the second modified layer B is laminated on the substrate 110.
  • the material of the second modified layer can be appropriately selected according to the material of the first modified layer. After being laminated on the first modified layer A, only the second modified layer B is formed. Can be used.
  • the material of the second modified layer can be appropriately selected from the same materials as those exemplified for the first modified layer.
  • the lamination of the second modified layer can be performed by coating, dipping, spin coating, spraying, sputter deposition, chemical vapor deposition (CVD), plating, or the like, depending on the material of the second modified layer to be used. it can.
  • the second modified layer B may be a layer composed of a biomolecule or a biomolecule capturing molecule itself, or a layer composed of a material other than a biomolecule or a biomolecule capturing molecule. It may be.
  • the second modified layer B includes a biomolecule or a biomolecule capturing molecule, or a biomolecule or a biomolecule capturing molecule. Other materials may be further bonded.
  • the binding of the biomolecule to the second modified layer B can be performed in the same manner as the binding of the biomolecule to the first modified layer A described above.
  • the binding by a chemical crosslinker or the antigen-antibody reaction The binding can be performed by utilizing binding, binding by a protein capture molecule, avidin-biotin binding, binding between a histidine tag and a nickel ion, or the like.
  • the protein capture molecules to be bound to the second modified layer B are the same as those exemplified for the first modified layer in the production method of the first embodiment, for example, avidin; biotin; nickel, cobalt, etc. Metal ions; maltose; guanine nucleotides; glutathione; antigens and the like.
  • the binding of the protein capture molecule to the second modified layer B is the same as the binding of the protein capture molecule to the first modified layer in the production method of the first embodiment, for example, the binding by a chemical crosslinker. This can be done by using.
  • Step (2b) Subsequently, in this step, by removing the second modified layer B laminated on the first modified layer A, the first modified layer A is laminated on the surface 130 where the recess 120 opens, The substrate 200 in which the second modified layer B is laminated on the inner surface 121 of the recess 120 is obtained. In this step, the second modified layer B laminated on the first modified layer A is removed, but the second modified layer B laminated on the inner surface 121 of the recess 120 remains.
  • the removal of the second modified layer B can be performed by a method such as removal with a solvent.
  • the solvent can be appropriately selected according to the material of the second modified layer B, the material of the first modified layer A, and the like, and is the same as that described in the manufacturing method of the first embodiment.
  • the second modified layer B laminated on the first modified layer A is removed, but the second modified layer B laminated on the inner surface 121 of the recess 120 remains.
  • the reasons are, for example, as follows. That is, on the surface 130, the interaction between the material of the substrate 110 and the first modified layer A and the interaction between the modified layer A and the second modified layer B laminated on the modified layer A are performed. This is because the action is different.
  • examples of the interaction include chemical bonding, electrostatic interaction, frictional resistance, and adhesion. Due to the difference between these interactions, the adhesive force between the material of the substrate 110 and the first modified layer A is larger than the adhesive force between the first modified layer A and the second modified layer B.
  • different modified layers can be easily laminated on the inner surface of the concave portion and the surface where the concave portion opens.
  • the manufacturing method of the third embodiment mainly differs from the manufacturing method of the first embodiment in the position where the modified layer is stacked. Specifically, in the manufacturing method of the first embodiment, the modified layer is laminated on the surface 130 where the concave portion 120 opens. On the other hand, in the manufacturing method of the third embodiment, the modified layer is laminated on the inner surface 121 of the recess 120.
  • a step (3a) of laminating a first modified layer on a surface of the substrate having a concave portion where the concave portion is opened and an inner surface of the concave portion includes the steps of: A step (3b) of laminating a protective layer on the layer, and removing a part of the protective layer and the first modified layer, thereby exposing a surface where the concave portion is opened, and forming an inner surface of the concave portion with the surface. A step (3c) of obtaining a substrate in which the first modified layer and the protective layer are laminated in this order, and contacting the substrate with a solvent that dissolves the protective layer to form the substrate laminated on the inner surface of the concave portion. A step (3d) of obtaining a substrate having the first modified layer laminated on the inner surface of the recess by removing the protective layer to expose a surface where the recess opens.
  • FIGS. 4A to 4E are schematic views illustrating a method for manufacturing a substrate according to the third embodiment.
  • the manufacturing method of the third embodiment will be described with reference to FIGS.
  • FIG. 4A is a cross-sectional view of the substrate 110 having the recess 120.
  • a first modified layer in FIG. 4, “1” is formed on the surface 130 of the substrate 110 having the recess 120 and the inner surface 121 of the recess 120.
  • a ") is formed on the surface 130 of the substrate 110 having the recess 120 and the inner surface 121 of the recess 120.
  • the substrate having the concave portion and the first modified layer are the same as those in the manufacturing method of the first embodiment.
  • a protective layer 140 is laminated on the first modified layer.
  • the protective layer 140 is the same as that in the manufacturing method of the first embodiment.
  • Step (3c) Subsequently, as shown in FIG. 4D, by removing a part of the protective layer 140 and the first modified layer, the surface 130 where the concave portion 120 is opened is exposed, and the inner surface 121 of the concave portion 120 is exposed. A substrate in which the first modified layer and the protective layer 140 are stacked in this order is obtained.
  • the removal of the protective layer 140 can be performed in the same manner as in the manufacturing method of the first embodiment.
  • the material of the substrate 110 is exposed.
  • the first modified layer and the protective layer 140 are stacked on the substrate 110 in this order.
  • Step (3d) Subsequently, a solvent that dissolves the protective layer 140 is brought into contact with the substrate on which the first modified layer is laminated, and the protective layer 140 laminated on the inner surface 121 of the concave portion 120 is removed.
  • the solvent for dissolving the protective layer 140 is the same as that in the manufacturing method of the first embodiment.
  • FIG. 4E a substrate 300 is obtained in which the surface 130 where the recess 120 is opened is exposed and the first modified layer is laminated on the inner surface 121 of the recess 120.
  • the material of the substrate 110 is exposed on the surface 130.
  • a first modified layer is laminated on the inner surface 121 of the recess 120.
  • the modified layer can be easily laminated only on the inner surface of the concave portion.
  • the solvent that dissolves the protective layer 140 does not need to pass through the modified layer. Therefore, the modified layer does not need to be an ultrathin film, but may be an ultrathin film.
  • the manufacturing method of the fourth embodiment is mainly different from the manufacturing method of the third embodiment in that a second modified layer is further laminated on the substrate 300 manufactured by the manufacturing method of the third embodiment.
  • the first modified layer laminated on the inner surface 121 of the concave portion 120 and the surface 130 where the concave portion 120 opens have the second The step (4a) of laminating the modified layer, and removing the second modified layer laminated on the inner surface 121 of the concave portion 120, the second modified layer is laminated on the surface 130 where the concave portion opens. Obtaining a substrate in which the first modified layer is laminated on the inner surface 121 of the concave portion 120 (4b).
  • FIGS. 5A to 5C are schematic views illustrating a method for manufacturing a substrate according to the fourth embodiment.
  • the manufacturing method of the fourth embodiment will be described with reference to FIGS.
  • FIG. 5A is a cross-sectional view of the substrate 300 obtained in the step (3d) of the third embodiment, and corresponds to the substrate 300 shown in FIG. As shown in FIG. 5A, in the substrate 300, the material of the substrate 110 is exposed on the surface 130 where the concave portion 120 is opened, and the first modified layer (in FIG. , "A") are stacked.
  • the first modified layer A and the surface 130 laminated on the inner surface 121 of the concave portion 120 of the substrate 300 are provided with a second modified layer (in FIG. 5). , "B").
  • the second modified layer B is stacked on the substrate 110.
  • the first modified layer A and the second modified layer B are laminated on the substrate 110 in this order.
  • Step (4b) Subsequently, in this step, by removing the second modified layer B laminated on the inner surface 121 of the concave portion 120, the second modified layer B is laminated on the surface 130, and the inner surface 121 of the concave portion 120 is removed. To obtain a substrate 400 on which the first modified layer A is laminated.
  • the removal of the second modified layer B can be performed by a method such as removal with a solvent.
  • the solvent can be appropriately selected according to the material of the second modified layer B, the material of the first modified layer A, and the like, and is the same as that described in the manufacturing method of the first embodiment.
  • the second modified layer B laminated on the first modified layer A is removed, but the second modified layer B laminated on the surface 130 where the concave portion 120 opens remains.
  • the reasons are, for example, as follows. That is, in the recess 120, the interaction between the material of the substrate 110 and the first modified layer A and the interaction between the modified layer A and the second modified layer B laminated on the modified layer A are performed. This is because the action is different.
  • examples of the interaction include chemical bonding, electrostatic interaction, frictional resistance, and adhesion. Due to the difference between these interactions, the adhesive force between the material of the substrate 110 and the first modified layer A is larger than the adhesive force between the first modified layer A and the second modified layer B.
  • the material of the second modified layer B can be appropriately selected from the same materials as those exemplified for the first modified layer in the manufacturing method of the first embodiment. it can.
  • the solvent that dissolves the protective layer 140 does not need to permeate the first modified layer, Further, the solvent for removing the second modified layer does not need to permeate the first modified layer.
  • the first modified layer and the second modified layer in the fourth embodiment may or may not be very thin films.
  • the thickness of the first modified layer and the second modified layer in the fourth embodiment may be, for example, 0.5 to 100,000 nm, for example, 0.5 to 1,000 nm. For example, it may be 0.5 to 10 nm.
  • the thickness of the first modified layer disposed on the inner surface of the concave portion is also limited by the volume of the concave portion. For example, when the inside of the concave portion is filled with the first modified layer, the function as the concave portion is lost.
  • the concave portion has a cubic shape with a side length of 1,000 nm.
  • the volume of the cubic concave portion having a length of one side of 1,000 nm is 1 fL.
  • the thickness of the modified layer laminated on the inner surface of the concave portion is less than 500 nm, which is half the length of one side, the inside of the concave portion is filled with the modified layer.
  • the concave portion has a cubic shape with a side length of 10 ⁇ m
  • the volume of the concave portion is 1 ⁇ 10 3 fL.
  • even a modified layer having a thickness of about 1,000 nm can be stacked without filling the inside of the concave portion.
  • thermoplastic resins such as acrylic resins; thermosetting resins such as epoxy resins; biomolecules such as nucleic acids, peptides, antibodies, antibody fragments, and enzymes; nucleic acid aptamers and peptide aptamers
  • a biomolecule capturing molecule such as an antibody, an antibody fragment, etc .; a silane coupling agent to which the biomolecule or the biomolecule capturing molecule is bound; a metal such as chromium, gold, and aluminum; a metal oxide such as aluminum oxide; Included paste materials; silicone polymers such as PDMS.
  • different modified layers can be easily laminated on the inner surface of the concave portion and the surface where the concave portion opens.
  • the manufacturing method according to the fifth embodiment is similar to the manufacturing method according to the fourth embodiment in the final manufactured substrate, but differs in a part of the manufacturing process.
  • the manufacturing method according to the fifth embodiment includes, after the step (3c) of the third embodiment, a step of stacking a second modified layer on the protective layer 140 stacked on the recess 120 and the surface 130 where the recess 120 opens. (5a), the protective layer 140 laminated on the concave portion 120 and the second modified layer laminated on the protective layer 140 are removed, so that the second modified layer is laminated on the surface 130 where the concave portion 120 opens. And obtaining a substrate in which the first modified layer is laminated on the inner surface 121 of the concave portion (5b).
  • FIGS. 6A to 6C are schematic views illustrating a method for manufacturing a substrate according to the fifth embodiment.
  • the manufacturing method of the fifth embodiment will be described with reference to FIGS.
  • FIG. 6A is a cross-sectional view showing a state where the step (3c) of the third embodiment has been completed, and corresponds to FIG. 4D.
  • the material of the substrate 110 is exposed on the surface 130 of the substrate 110 where the concave portion 120 is open, and the first modified layer (in FIG. "A") and the protective layer 140 are stacked in this order.
  • a second modified layer (B" in FIG. 6) is provided on the protective layer 140 laminated on the concave portion 120 and on the surface 130 where the concave portion 120 opens. ).
  • the second modified layer B is stacked on the substrate 110.
  • the first modified layer A, the protective layer 140, and the second modified layer B are stacked on the substrate 110 in this order.
  • Step (5b) Subsequently, in this step, the protective layer 140 laminated on the concave portion 120 and the second modified layer B laminated on the protective layer 140 are removed, so that the surface 130 where the concave portion 120 is opened has a second modified surface.
  • the substrate 400 is obtained in which the layer B is stacked and the first modified layer A is stacked on the inner surface 121 of the concave portion.
  • a material that is permeable to a solvent that dissolves the protective layer 140 is used as the second modified layer B.
  • the second modified layer B is preferably an extremely thin film from the viewpoint that the solvent that dissolves the protective layer 140 has transparency.
  • the extremely thin film is the same as that described above in the manufacturing method of the first embodiment.
  • the removal of the protective layer 140 and the second modified layer B can be performed by a method such as removal with a solvent that dissolves the protective layer 140.
  • the solvent can be appropriately selected according to the material of the protective layer 140, the material of the first modified layer A, the material of the second modified layer B, and the like, and those described above in the manufacturing method of the first embodiment. Is the same as
  • the second modified layer B laminated on the protective layer 140 is removed, but the second modified layer B laminated on the surface 130 where the concave portion 120 opens remains.
  • the reasons are, for example, as follows. That is, in the recess 120, a sufficiently large adhesive force acts due to the interaction between the material of the substrate 110 and the first modified layer A, so that the first modified layer laminated on the inner surface 121 of the recess 120 is formed. A remains, and the protective layer 140 and the second modified layer B laminated on the protective layer 140 are removed.
  • examples of the interaction include chemical bonding, electrostatic interaction, frictional resistance, and adhesion.
  • a sufficiently large adhesive force acts due to the interaction between the material of the substrate 110 and the second modified layer B, so that the second modified layer B laminated on the surface 130 remains.
  • the material of the second modified layer B can be appropriately selected from the same materials as those exemplified for the first modified layer in the manufacturing method of the first embodiment. it can.
  • the present invention provides a substrate having a concave portion, wherein a first modified layer is laminated on a surface where the concave portion opens, and a volume per one of the concave portions is 1 to 1 ⁇ . a 10 9 fL, the first modified layer is very thin, providing a substrate.
  • the extremely thin film is the same as that described above in the manufacturing method of the first embodiment.
  • the substrate of the present embodiment is a substrate having a modified layer, wherein the substrate has a concave portion, and a first modified layer is stacked on a surface of the substrate where the concave portion opens, and the substrate has a concave portion.
  • the volume per one is 1 to 1 ⁇ 10 9 fL, and it can be said that the first modified layer is an extremely thin substrate.
  • the substrate of the present embodiment is a substrate having a concave portion, in which the surface where the concave portion is opened is modified, and the volume per one concave portion is 1 to 1 ⁇ 10 9 fL. You can also.
  • that the surface of the substrate is modified means that a property different from the material of the substrate is imparted to the surface of the substrate.
  • the modified portion of the surface where the concave portion opens can be said to be the first modified layer. Further, the first modified layer is an extremely thin film.
  • the volume per recess may be, for example, 1 to 1 ⁇ 10 6 fL, or may be, for example, 1 to 1 ⁇ 10 3 fL.
  • the substrate of the present embodiment can be manufactured by the manufacturing method of the first embodiment described above.
  • a plurality of recesses exist on the substrate, and it is preferable that the recesses form an array in which the recesses are regularly arranged.
  • the concave portion may be formed on only one surface of the substrate, or may be formed on both surfaces.
  • the size, shape, and number of recesses, the size, shape, and material of the substrate are the same as those described above in the manufacturing method of the first embodiment. Further, the material of the substrate may be exposed on the inner surface of the concave portion, or the second modified layer may be laminated on the inner surface of the concave portion.
  • the fact that the second modified layer is laminated on the inner surface of the concave portion can be said to mean that the inner surface of the concave portion has been modified. Further, it can be said that the modified portion of the inner surface of the concave portion is the second modified layer.
  • the first modified layer and the second modified layer may be layers composed of biomolecules or biomolecule capturing molecules themselves, or layers composed of materials other than biomolecules or biomolecule capturing molecules. .
  • the first modified layer or the second modified layer includes a biomolecule or a biomolecule capturing molecule, or a biomolecule. Materials other than molecules or biomolecule capture molecules may be further bound.
  • the substrate of the present embodiment may be a substrate in which biomolecules are fixed to the first modified layer or the second modified layer.
  • the substrate of the present embodiment can be suitably used for a reaction of a biomolecule.
  • the reaction of the biomolecule is not particularly limited, and examples thereof include an enzyme reaction, an antigen-antibody reaction, gene transcription, and translation of mRNA.
  • the substrate of the present embodiment may be used for measurement and analysis of biomolecules after the reaction.
  • the second modified layer laminated on the inner surface of the concave portion may include an enzyme.
  • the enzyme reaction can be performed in the concave portion by introducing the enzyme substrate into the concave portion. Thereafter, the enzyme activity can be measured by detecting a signal corresponding to the enzyme reaction.
  • the enzyme may be an enzyme variant constituting an enzyme variant library.
  • an enzyme can be screened on a large scale by performing an enzymatic reaction by immobilizing an enzyme variant having a different amino acid sequence in each concave portion in which concave portions on the substrate form an array.
  • Example 1 (Production of a substrate having a modified layer) A microreactor array chip was prepared in which the inner surface of the concave portion was hydrophilic and the surface where the concave portion opened was modified to be hydrophobic.
  • a dry etching process was used to manufacture a substrate in which 1 million cylindrical concave portions (microreactors) having a diameter of 4 ⁇ m and a height of 4 ⁇ m were arranged at a pitch of 10 ⁇ m on one surface of a quartz substrate having a width of 30 mm and a length of 30 mm. .
  • a photoresist was laminated on the surface of the substrate where the concave portions are opened and on the inner surface of the concave portions. Subsequently, soft baking was performed to form a protective layer.
  • a modified layer was formed on the surface where the concave portion opens. Specifically, first, an organic silane was laminated. The lamination of the organic silane was performed by spin coating. Subsequently, baking was performed to form an extremely hydrophobic thin film on the surface where the concave portion was opened. This very thin film is the modified layer.
  • the substrate was immersed in a solvent to remove the protective layer laminated on the inner surface of the concave portion and the extra modified layer.
  • a microreactor array chip having a modified layer in which a hydrophobic ultrathin film was laminated on the surface where the concave portion was opened and the inner surface of the concave portion was quartz was obtained.
  • FIGS. 7A to 7C are schematic diagrams illustrating the experimental process.
  • FIG. 7A the fluorescein solution F was dropped on the surface of the microreactor array chip manufactured in Experimental Example 1. Subsequently, as shown in FIG. 7B, while extruding the fluorescein solution on one surface of the blade BL, the oil M was spread on the other surface, and the fluorescein solution was sealed in the microreactor array.
  • FIG. 7C is a schematic diagram showing a state where the fluorescein solution is sealed in the microreactor array.
  • microreactor array chip was observed with a fluorescence microscope, and the state of inclusion of the fluorescein solution was observed.
  • FIG. 8A is a photograph showing a state in which a fluorescein solution is dropped on the surface of a microreactor array chip. As shown in FIG. 8A, since the fluorescein solution was water-repellent, it was confirmed that the surface of the microreactor array chip where the concave portion was opened was modified to be hydrophobic.
  • FIGS. 8 (b) and 8 (c) are fluorescence micrographs showing the fluorescence of fluorescein. As a result, fluorescence of fluorescein was confirmed inside the microreactor array sealed with oil. This result indicates that the liquid is contained inside the microreactor array, and indicates that the inner surface of the microreactor array is hydrophilic.
  • the modified layer could be easily laminated on the substrate on which the concave portion was already formed, and the inner surface of the concave portion could be modified to be hydrophilic and the surface where the concave portion was opened could be modified to be hydrophobic. .
  • FIGS. 9 (a) to 9 (d) are schematic cross-sectional views illustrating an experimental process.
  • the lid member 910 was arranged so as to face the recess 120 of the microreactor array chip manufactured in Experimental Example 1, and the fluid device 900 was assembled.
  • the lid member 910 was manufactured by cutting a groove serving as a flow path on a plastic plate (methyl methacrylate-styrene copolymer resin plate, JSP) using a cutting machine.
  • JSP methyl methacrylate-styrene copolymer resin plate
  • the lid member 910 was laminated on the surface 130 of the microreactor array chip where the concave portion 120 was opened so that the cut surface 911 of the lid member 910 was opposed. As a result, the groove formed in the lid member 910 formed the flow path 920. Subsequently, the introduction part 930 was arranged at one end of the flow path 920, and the discharge part 940 was arranged at the other end.
  • a syringe pump was connected to the discharge unit 940, and suction was performed at a flow rate of 100 ⁇ L / min.
  • the fluorescein solution F was introduced into the channel 920.
  • oil M was introduced into the flow path 920 as shown in FIG. 9C.
  • FIG. 10A is a photograph of a microreactor array chip.
  • FIG. 10B is a photograph of the fluid device 900.
  • a fluid device similar to the fluid device 900 using an unmodified microreactor array chip is the same as the microreactor array chip manufactured in Experimental Example 1 except that the fluid device has no modified layer. Was prepared, and the fluorescein solution and the oil were fed.
  • FIGS. 11A and 11B are fluorescence micrographs of the fluorescence of fluorescein.
  • FIG. 11A shows the result of sending a fluorescein solution and oil to an unmodified microreactor array chip.
  • FIG. 11B shows the result of sending a fluorescein solution and oil to a microreactor array chip having a modified layer.
  • the bright spots in the array pattern indicate microreactors (microwells) containing a fluorescein solution.
  • the area other than the array pattern indicates the chip surface outside the microreactor.

Landscapes

  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Analytical Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Manufacturing & Machinery (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Physics & Mathematics (AREA)
  • Sustainable Development (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Micromachines (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Laminated Bodies (AREA)

Abstract

L'invention concerne un procédé de fabrication d'un substrat ayant une couche de modification, le procédé comprenant : la stratification d'une couche de protection sur une surface, d'un substrat ayant des évidements, sur laquelle les évidements s'ouvrent, et sur la surface interne des évidements ; le retrait d'une partie de la couche de protection pour obtenir le substrat dans lequel la surface sur laquelle les évidements s'ouvrent est exposée et la couche de protection est stratifiée sur la surface interne des évidements ; la stratification d'une première couche de modification sur la surface sur laquelle les évidements s'ouvrent, la première couche de modification étant perméable à un solvant qui dissout la couche de protection ; et le fait d'amener le solvant en contact avec le substrat pour retirer la couche de protection stratifiée sur la surface interne des évidements pour obtenir un substrat dans lequel la première couche de modification est stratifiée sur la surface sur laquelle les évidements s'ouvrent.
PCT/JP2019/027714 2018-07-13 2019-07-12 Substrat ayant une couche de modification et son procédé de fabrication Ceased WO2020013318A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2018-133677 2018-07-13
JP2018133677A JP7190273B2 (ja) 2018-07-13 2018-07-13 改質層を有する基板の製造方法

Publications (1)

Publication Number Publication Date
WO2020013318A1 true WO2020013318A1 (fr) 2020-01-16

Family

ID=69142696

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/027714 Ceased WO2020013318A1 (fr) 2018-07-13 2019-07-12 Substrat ayant une couche de modification et son procédé de fabrication

Country Status (2)

Country Link
JP (1) JP7190273B2 (fr)
WO (1) WO2020013318A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024072344A1 (fr) 2022-10-01 2024-04-04 Nanografi̇ Nano Teknoloji̇ Anoni̇m Şi̇rketi̇ Procédé de marquage pour le criblage dans différents spectres

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030029723A1 (en) * 2000-12-06 2003-02-13 The Regents Of The University Of California Thin film capillary process and apparatus
US20040043494A1 (en) * 2002-08-30 2004-03-04 Amorese Douglas A. Apparatus for studying arrays
US20050214827A1 (en) * 1996-07-08 2005-09-29 Burstein Technologies, Inc. Assay device and method
JP2016539343A (ja) * 2013-08-30 2016-12-15 イルミナ インコーポレイテッド 親水性または斑状親水性表面上の液滴の操作
JP2018171660A (ja) * 2017-03-31 2018-11-08 住友理工株式会社 流体デバイス用シリコーン部材およびその製造方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050214827A1 (en) * 1996-07-08 2005-09-29 Burstein Technologies, Inc. Assay device and method
US20030029723A1 (en) * 2000-12-06 2003-02-13 The Regents Of The University Of California Thin film capillary process and apparatus
US20040043494A1 (en) * 2002-08-30 2004-03-04 Amorese Douglas A. Apparatus for studying arrays
JP2016539343A (ja) * 2013-08-30 2016-12-15 イルミナ インコーポレイテッド 親水性または斑状親水性表面上の液滴の操作
JP2018171660A (ja) * 2017-03-31 2018-11-08 住友理工株式会社 流体デバイス用シリコーン部材およびその製造方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024072344A1 (fr) 2022-10-01 2024-04-04 Nanografi̇ Nano Teknoloji̇ Anoni̇m Şi̇rketi̇ Procédé de marquage pour le criblage dans différents spectres

Also Published As

Publication number Publication date
JP7190273B2 (ja) 2022-12-15
JP2020010613A (ja) 2020-01-23

Similar Documents

Publication Publication Date Title
US12467895B2 (en) Method of making biochip having a channel
US7419639B2 (en) Multilayer microfluidic device
CN108886053A (zh) 用于纳米孔感测的绝缘体-膜-绝缘体装置的晶片级组装
CN104515737B (zh) 在微流体结构中产生化学物图案的方法
CN102597875B (zh) 用于生产微颗粒的方法
KR20130103715A (ko) 유리형 표면을 갖는 폴리머 기판 및 상기 폴리머 기판으로 제조된 칩
JP2012073269A (ja) 対象液体を捕捉するための局在化区域を備える作業装置
KR20130066138A (ko) 나노채널 구조체를 구비하는 센서 및 그 제조방법
CN112543678A (zh) 图案化微流体装置及其制造方法
JP2004000163A (ja) 細胞の処理に用いるセル
EP1677914B1 (fr) Procede de repartition de gouttes d un liquide d interet sur une surface
WO2020013318A1 (fr) Substrat ayant une couche de modification et son procédé de fabrication
US20220362774A1 (en) Microfluidic chips with one or more vias
CN104736470A (zh) 用于制造微载体的方法
JP2004154769A (ja) バイオミメティックメンブランの製造方法およびバイオミメティックメンブランならびにその応用
FR2861608A1 (fr) Dispositif de travail comportant des zones de travail bordees, laboratoire sur puce et microsysteme
JP2004333404A (ja) マイクロリアクタ及びその製造方法、並びに試料スクリーニング装置
FR2865806A1 (fr) Laboratoire sur puce comprenant un reseau micro-fluidique et un nez d'electronebulisation coplanaires
KR20110095503A (ko) 표면에너지 차이를 이용한 바이오칩 제작방법, 그 제작방법에 의해 제작된 바이오칩, 마이크로 어레이 형성방법 및 친수성 단백질 샘플 디스펜딩 방법
US20210252505A1 (en) Patterned microfluidic devices and methods for manufacturing the same
JPWO2010122720A1 (ja) 流路デバイス
Tripodi Advancements in compartmentalized microfluidic platforms for microwell-assisted digital bioassays
US8414782B2 (en) Process for producing fluorocarbon microstructure, fluorocarbon microstructure, and microsystem
Szili et al. Integration of microplasma and microfluidic technologies for localised microchannel surface modification
Han et al. Stacked SiO 2/Si nanonail array fabricated by spacer technology for biomedical applications

Legal Events

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

Ref document number: 19833343

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19833343

Country of ref document: EP

Kind code of ref document: A1