Hydrogel Fluid Device and Method for Manufacturing Hydrogel Fluid Device

Abstract

This hydrogel fluid device has a base material (10), and a polymer material layer (20) that forms a hydrogel and is provided to one surface (10a) of the base material (10). An adhesion region (1a) where the base material (10) and the polymer material layer (20) are adhered and a non-adhesion region (1b) where the base material (10) and the polymer material layer (20) are not adhered are formed at the interface of the base material (10) and the polymer material layer (20). In at least a partial region of the non-adhesion region (1b), there is a sacrificial layer (30) between the base material (10) and the polymer material layer (20).

Description

Technical Field

[0001] The present invention relates to the technology of hydrogel fluid devices and methods for manufacturing hydrogel fluid devices.

Background Art

[0002] Hydrogels have high water content, high flexibility, and high biocompatibility in addition to high substance permeability. Therefore, hydrogels have attracted attention as scaffold materials for regenerative medicine and materials for constructing biomimetic systems. If a tubular three-dimensional structure made of hydrogel can be constructed, the construction of biomimetic systems for tubular tissues such as blood vessels, lymphatic vessels, and intestinal tracts can be expected.

[0003] It has been proposed to mold a hydrogel into a three-dimensional shape, for example, a hollow shape, and use it as a flow path. For example, constructing a biological system in which a liquid is poured into the inside of a flow path formed of a hydrogel and substances in the liquid can be exchanged between the flow path and the hydrogel has been studied.

[0004] As a three-dimensional structure of a hydrogel, Patent Document 1 discloses a laminate having a base material and a hydrogel layer provided on one surface of the base material as a hydrogel forming material, and at the interface between the base material and the hydrogel layer, an adhesion region where the base material and the hydrogel layer adhere and a non-adhesion region where the base material and the hydrogel layer do not adhere are formed.

[0005] As a hydrogel fluid device that utilizes the three-dimensional structure of a hydrogel as a flow path, Patent Document 2 discloses a substrate, a film-like hydrogel provided on the substrate and having an adhesive region that adheres to the substrate and a non-adhesive region that does not adhere to the substrate, and a flow path formed at the interface between the hydrogel and the substrate by the swelling of the first polymer material constituting the hydrogel causing the first polymer material in the non-adhesive region to separate from the substrate, and a bulk gel composed of a second polymer material that covers one surface of the hydrogel outside the flow path and has a lower swelling degree than the first polymer material.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] Understanding the permeation of nutrients, metabolites, and drugs into and out of tubular tissues is important not only for the academic understanding of biological functions but also for drug efficacy evaluation. In order to detect substances that permeate and diffuse inside and outside a tubular tissue-like structure using a hydrogel, it is preferable to provide the solid substrate or the hydrogel with a function for detecting the target substance.

[0008] When imparting the function of detecting a target substance to a hydrogel or a solid substrate, the chemical and physical properties of the hydrogel or the solid substrate change, and the adhesive force between the hydrogel and the solid substrate fluctuates. In the technologies of Patent Document 1 and Patent Document 2, when the adhesive force between the hydrogel and the solid substrate was strong, there was a risk that the hydrogel would not peel off from the interface between the hydrogel and the solid substrate. In that case, free swelling of the hydrogel did not occur, and the flow channel structure of the hydrogel might not be formed.

[0009] In view of the above circumstances, an object of the present invention is to provide a hydrogel fluid device and a method for manufacturing a hydrogel fluid device that can reduce the influence of the composition of the hydrogel and the surface physical properties of the solid substrate and can form a flow channel structure of the hydrogel.

Means for Solving the Problems

[0010] One aspect of the present invention is a method for manufacturing a hydrogel fluid device including a base material and a layer of a polymer material constituting a hydrogel on the base material, wherein on one surface of the base material, an adhesive region where the base material and the layer of the polymer material adhere to each other and a non-adhesive region where the base material and the layer of the polymer material do not adhere to each other are formed, the layer of the polymer material is provided, the polymer material is swollen to separate the polymer material in the non-adhesive region from the base material, a flow channel is formed at the interface between the base material and the layer of the polymer material, the polymer material is made into a hydrogel, and before providing the layer of the polymer material, a first pattern of a sacrificial layer that can be dissolved by applying a solution stimulus is formed on the one surface of the base material, and the first pattern is formed in at least a part of the non-adhesive region, which is a method for manufacturing a hydrogel fluid device.

[0011] One aspect of the present invention has a base material and a layer of a polymer material that constitutes a hydrogel provided on one surface of the base material. At the interface between the base material and the layer of the polymer material, an adhesion region where the base material and the layer of the polymer material adhere and a non-adhesion region where the base material and the layer of the polymer material do not adhere are formed. In at least a part of the non-adhesion region, there is a sacrificial layer between the base material and the layer of the polymer material, which is a hydrogel fluid device.

Effects of the Invention

[0012] According to the above aspect of the present invention, it is possible to provide a hydrogel fluid device and a method for manufacturing a hydrogel fluid device that can reduce the influence of the composition of the hydrogel and the surface physical properties of the solid substrate and form a flow path structure of the hydrogel.

Brief Description of the Drawings

[0013]

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Embodiments for Carrying Out the Invention

[0014] <First Embodiment> Hereinafter, the first embodiment will be described with reference to FIGS. 1 to 19, but the present invention is not limited to the embodiments described below. In the drawings used in the following description, for the sake of easy understanding of the features of the present invention, the main part may be enlarged and shown for convenience, and the dimensional ratios of the respective components are not necessarily the same as the actual ones.

[0015] (Laminated Body) FIG. 1 is a schematic perspective view of a laminated body 100 according to the first embodiment. FIG. 2 is a cross-sectional view taken along the line II-II of FIG. 1. As shown in FIGS. 1 and 2, the laminated body 100 has a base material 10, a layer 20 of a polymer material, and a sacrificial layer 30. Further, at the interface between the base material 10 and the layer 20 of the polymer material, an adhesion region 1a where the base material 10 and the layer 20 of the polymer material adhere to each other and a non-adhesion region 1b where the base material 10 and the layer 20 of the polymer material do not adhere to each other are formed. Also, a region where the sacrificial layer 30 is located becomes a peeling region 1c.

[0016] In the laminate 100 shown in FIGS. 1 and 2, the non-adhesive region 1b is provided in a strip shape on one surface of the base material 10. Further, the sacrificial layer 30 is between the base material 10 and the layer 20 of the polymer material in at least a part of the non-adhesive region. The adhesive regions 1a of the laminate 100 of the present embodiment are provided on both sides in the extending direction of the non-adhesive region 1b. Note that the patterns of the adhesive regions 1a and the non-adhesive regions 1b shown in the figure are examples, and various pattern shapes according to the design can be adopted. Hereinafter, each component will be described.

[0017] Base material The base material 10 supports the layer 20 of the polymer material. The modulus of rigidity of the base material 10 is different from that of the layer 20 of the polymer material. For example, the modulus of rigidity of the base material 10 is higher than that of the layer 20 of the polymer material.

[0018] As the material for forming the base material 10, various materials can be selected regardless of whether they are organic materials such as polysilicon and polyurethane, or inorganic materials such as glass and silicon, as long as the effects of the invention are not impaired. The base material 10 may or may not have light transmissivity.

[0019] Examples of the organic material that is the material for forming the base material 10 include polymer materials and elastomers. Examples of the polymer material include thermoplastic resins such as polyvinyl chloride, polystyrene, ABS resin, and polylactic acid, and thermosetting resins such as polyimide and phenolic resin.

[0020] Examples of the elastomer include polysilicon and synthetic rubber. The base material 10 made of an elastomer is likely to deform according to stress. In the laminate 100 having such a base material 10, the layer 20 of the polymer material can be deformed as the base material 10 deforms.

[0021] As the material for forming the base material 10, a hydrogel having a different swelling degree from the hydrogel that is the material for forming the layer 20 of the polymer material described later can also be used.

[0022] Various additives may be contained in the above organic material, and various functions based on the physical properties of the additives may be added to the base material 10. For example, the organic material may contain carbon nanotubes, gold nanostructures, porphyrin derivatives, polydopamine, indocyanine green, etc., and may be used as the base material 10 that generates heat by receiving light.

[0023] Examples of the inorganic material that is the forming material of the base material 10 include glass with excellent transparency and chemical stability, a conductor that generates heat by being energized, a magnetic metal body that generates heat by stimulation from a magnetic field, a piezoelectric element that generates electricity by stress, and a light-emitting element that emits light by being energized. Examples of the light-emitting element include a light-emitting diode.

[0024] The base material 10 may be subjected to various processes on at least one of the surface and the inside by known microfabrication techniques. For example, the base material 10 may have irregularities or grooves on the surface.

[0025] The surface of the base material 10 may be coated with a thin film made of a metal, an inorganic oxide, or an organic material having an arbitrary function in an arbitrary shape.

[0026] Layer of polymer material The layer 20 of the polymer material constituting the hydrogel is provided on one surface of the base material 10.

[0027] Examples of the polymer material of the layer 20 of the polymer material include water-soluble polymers such as polyacrylamide and polyvinyl alcohol, polysaccharides such as chitosan and alginic acid, and proteins such as collagen and albumin. These materials have a three-dimensional network structure and swell with a solvent contained in most of their volume. A representative solvent in which the polymer material constituting the hydrogel swells is water.

[0028] As the polymer material of the polymer material layer 20, a stimulus-responsive polymer material can be used. Here, "stimulus-responsive" refers to the property that the polymer material constituting the polymer material layer 20 changes its molecular structure in response to stimuli such as heat, light, electricity, and pH. A stimulus-responsive hydrogel changes the three-dimensional network structure of the polymer material constituting the hydrogel and the degree of swelling in response to a stimulus that changes the molecular structure. In the following description, a hydrogel containing a stimulus-responsive polymer material may be referred to as a "stimulus-responsive hydrogel".

[0029] Examples of such stimulus-responsive polymer materials include the following materials. Examples of polymer materials that respond to heat stimuli include poly(N-isopropylacrylamide) and poly(methyl vinyl ether).

[0030] Examples of polymer materials that respond to pH include polyelectrolytes obtained by polymerizing anionic monomers or cationic monomers. Anionic monomers and cationic monomers correspond to the precursors in the present invention.

[0031] Examples of polymer materials that respond to light include polymer materials having spiro pyran or azobenzene in their molecular skeletons.

[0032] Examples of polymer materials that respond to electrical stimuli include polypyrrole, polythiophene, and polyaniline.

[0033] As the polymer material of the polymer material layer 20, a plurality of these polymer materials may be mixed. By mixing a plurality of polymer materials in this way, a hydrogel that responds to multiple stimuli can be obtained.

[0034] By swelling the layer 20 of the polymer material, a hydrogel can be obtained. As the hydrogel after the layer 20 of the polymer material swells, tough hydrogels such as double network gels, slide ring gels, Tetra-PEG gels, and nanoclay gels can also be used. Further, as the hydrogel, an imprint gel in which the network structure of the hydrogel changes by recognizing and binding an arbitrary substance, a conductive hydrogel containing an ionic liquid and a conductive polymer, a photonic crystal gel containing a colloidal crystal and changing color due to a change in the intercrystalline distance, etc. can also be used.

[0035] Regarding the synthesis method of the polymer material of the layer 20 of the polymer material, various known methods can be adopted. For example, when the polymer material is an acrylic polymer material, an acrylic group may be crosslinked when polymerizing an acrylic monomer to form a three-dimensional network structure. The acrylic monomer corresponds to the precursor in the present invention.

[0036] The type of the polymerization reaction when polymerizing the acrylic monomer is not particularly limited, but as an example, radical polymerization using a water-soluble photopolymerization initiator can be mentioned. Examples of the water-soluble photoinitiator include 2-oxoglutaric acid, 4'-(2-hydroxyethoxy)-2-hydroxy-2-methylpropiophenone (trade name: Irgacure 2959), lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (abbreviation: LAP), 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (trade name: VA-086), and the like.

[0037] At the time of radical polymerization, a deoxidizer may be added to the reaction system in order to prevent polymerization inhibition by oxygen. Examples of the deoxidizer include a combination of glucose and glucose oxidase. Further, the radical polymerization may be carried out under an inert gas atmosphere such as nitrogen or argon.

[0038] When the polymer material constituting the polymer material layer 20 is a polysaccharide or a protein, a three-dimensional network structure may be formed by physical bonding of the polysaccharide or the protein, or the polysaccharide or the protein may be cross-linked using a cross-linking agent to form a three-dimensional network structure. Examples of the cross-linking agent include glutaraldehyde.

[0039] The shape of the polymer material layer 20 is not particularly limited, and various shapes according to the usage form can be selected. For example, the polymer material layer 20 may be in the form of a film, a plate, a block, or the like. Among them, the shape of the polymer material layer 20 is preferably in the form of a film. The thickness of the polymer material layer 20 is not particularly limited.

[0040] The strength of the polymer material layer 20 can be improved, for example, by increasing the cross-linking of the polymer material constituting the polymer material layer 20 by chemical cross-linking or physical cross-linking.

[0041] The polymer material layer 20 can contain various additives. The type of the additive is not particularly limited as long as it does not inhibit the formation of the hydrogel after swelling. Examples of the additive include drugs, biomolecules for improving biocompatibility, silver nanoparticles and surfactants for expressing antibacterial properties, ionic liquids and conductive polymers for increasing conductivity, and magnetic nanoparticles for reacting to a magnetic field. By adding these additives to the polymer material layer 20, arbitrary functions can be imparted to the hydrogel after swelling.

[0042] sacrificial layer The sacrificial layer 30 is located between the base material 10 and the polymer material layer 20 in at least a partial region of the non-adhesive region 1b. A region of the sacrificial layer 30 becomes a peeling region 1c that peels off upon application of a solution stimulus. If the sacrificial layer 30 can be dissolved by the solution stimulus, the material of the sacrificial layer 30 is not particularly limited. The solution stimulus is not particularly limited as long as it can dissolve the sacrificial layer 30. When the sacrificial layer 30 is calcium alginate, examples of the solution stimulus include an aqueous solution of a chelating agent that binds to calcium ions in the calcium alginate in an aqueous solution. Examples of the calcium chelating agent include ethylenediaminetetraacetic acid (hereinafter referred to as EDTA), glycol ether diamine tetraacetic acid, 1,2-bis(o-aminophenoxide)ethane-N,N,N’,N’-tetraacetic acid, and citric acid. The sacrificial layer 30 is preferably a thin film capable of maintaining adhesion on the surface of the base material 10 in dry and wet environments (particularly under physiological conditions).

[0043] Examples of the material of the sacrificial layer 30 include calcium alginate that dissolves by the addition of ethylenediaminetetraacetic acid (hereinafter referred to as EDTA), glycol ether diamine tetraacetic acid, 1,2-bis(o-aminophenoxide)ethane-N,N,N’,N’-tetraacetic acid, citric acid, etc., which are calcium chelating agents.

[0044] The thickness of the sacrificial layer 30 is not particularly limited as long as a flow path can be formed between the base material 10 and the swollen polymer material layer 20 by the dissolution stimulus.

[0045] (Laminated body after removing the sacrificial layer 30) FIG. 3 and FIG. 4 are explanatory diagrams showing the state in which the sacrificial layer 30 is removed by applying a solution stimulus after swelling the polymer material layer 20 of the laminated body 100. FIG. 3 is a schematic perspective view of the laminated body 100 and corresponds to FIG. 1. FIG. 4 is a cross-sectional view taken along the line IV-IV of FIG. 3 and corresponds to FIG. 2.

[0046] In FIGS. 3 and 4, the swollen polymer material layer is denoted by reference numeral 21. In the following description, for the purpose of distinguishing between before and after swelling of the polymer material layer, the laminate 100 having the polymer material layer 20 before swelling may be referred to as "laminate 100A", and the laminate 100 having the polymer material layer 21 after swelling may be referred to as "laminate 100B". The polymer material layer 21 after swelling is a hydrogel after the polymer material has swelled.

[0047] The thickness of the polymer material layer 21 after swelling is not particularly limited, but it is preferably a thickness that can maintain a structural strength such that it is not crushed by its own weight. In order to maintain a strength sufficient to support its own weight while keeping the thickness of the polymer material layer 21 after swelling thin, the mechanical properties of the polymer material after swelling may be improved by increasing the degree of chemical crosslinking, the degree of physical crosslinking, or the concentration of the polymer in the gel.

[0048] Since the sacrificial layer 30 has dissolved by the application of a solution stimulus, the polymer material layer 21 after swelling of the laminate 100B is not fixed to the base material 10 in the non-adhesive region 1b. Also, the polymer material layer 21 after swelling of the laminate 100B is fixed to the base material 10 in the adhesive region 1a.

[0049] Therefore, in the polymer material layer 21 after swelling, the portion that overlaps the non-adhesive region 1b in a planar manner can freely increase in volume in the extending direction of the non-adhesive region 1b or the direction away from the base material 10 when the volume increases due to swelling. On the other hand, in the polymer material layer 21 after swelling, the portion that overlaps the adhesive region 1a in a planar manner is restricted from increasing in volume in a direction intersecting the extending direction of the adhesive region 1a.

[0050] As a result, in the laminate 100B, the portion that overlaps the non-adhesive region 1b in a planar manner greatly swells and deforms in the direction away from the base material 10 in order to relieve the increase in internal pressure due to the volume increase. Thereby, a flow path 4 surrounded by the polymer material layer 21 after swelling and the base material 10 is formed in the laminate 100B. In FIGS. 3 and 4, the flow path 4 is formed along the non-adhesive region 1b formed in a strip shape.

[0051] The shape of the flow path 4 can be controlled by controlling the pattern shapes of the adhesion region 1a and the non - adhesion region 1b.

[0052] Also, the shape of the flow path 4 can be controlled by adjusting the type of polymer material constituting the polymer material layer 21 after swelling, the ratio of the rigidity modulus of the base material 10 to the rigidity modulus of the polymer material layer 21 after swelling, the thickness of the polymer material layer 21 after swelling, and the like. The rigidity modulus of the polymer material layer 21 after swelling and the swelling ratio of the polymer material layer 21 after swelling can be controlled by changing the type of monomer of the polymer material constituting the polymer material layer 21 after swelling, the type and amount of the cross - linking agent used, and the like.

[0053] The shape change as described above is caused by the difference in the swelling ratio of the polymer material layer 20 of the laminate 100A and the swelling ratio of the polymer material layer 21 after swelling of the laminate 100B. The change between the polymer material layer 20 and the polymer material layer 21 after swelling is reversible. Therefore, in the laminate 100, the shape of the flow path 4 can be controlled by controlling the swelling ratio of the polymer material layer 20. The swelling ratio of the polymer material layer 20 can be controlled by methods such as bringing water into contact with the polymer material layer 20 to cause swelling or drying the polymer material layer 21 after swelling.

[0054] Furthermore, when a stimulus - responsive hydrogel is used as the forming material of the polymer material layer 21 after swelling, the swelling ratio of the polymer material layer 21 after swelling can be changed according to the stimulus input to the polymer material layer 21 after swelling. Thereby, the shape of the flow path 4 can be controlled.

[0055] (Hydrogel Fluid Device) FIG. 5 is a schematic perspective view of a hydrogel fluid device 200 according to an embodiment. FIG. 6 is a cross - sectional view taken along the line VI - VI of the hydrogel fluid device 200. As shown in FIGS. 5 and 6, the hydrogel fluid device 200 includes a base material 10, a polymer material layer 21 after swelling, a flow path 4, and tubular structures 6, 6.

[0056] Tubular Structure The tubular structures 6, 6 are respectively fixed to the first opening surface 4a and the second opening surface 4b of the flow path 4 by adhesives 7, 7. Specifically, at each of the first opening surface 4a and the second opening surface 4b of the flow path 4, the tubular structures 6, 6 are respectively fixed by adhesives 7, 7 between the base material 10 and the swollen polymer material layer 21. The tubular structure 6 is for supplying any fluid into the flow path 4.

[0057] The tubular structure 6 is, for example, a liquid delivery tube. The liquid delivery tube is not particularly limited as long as it can be carried and liquid can be delivered from the outside. The type of the liquid delivery tube is not particularly limited. Examples of the liquid delivery tube include tubes made of polytetrafluoroethylene (PTFE), perfluoroethylene (PFA), polyurethane, polyethylene, silicone, polyimide, etc. The outer diameter of the tubular structure 6 is not particularly limited. However, a tube with an outer diameter approximately the same as the height H of the flow path 4 is desirable.

[0058] The adhesives 7, 7 fix the liquid delivery tube to the flow path 4. That is, the adhesives 7, 7 fix the tubular structure 6 between the base material 10 and the swollen polymer material layer 21. In the hydrogel fluid device 200 as shown in FIG. 6, the adhesives 7, 7 are densely filled in the space in contact with the flow surface 4c of the flow path 4 around the tubular structure 6 at the opening surfaces 4a, 4b at the entrance of the flow path 4. The adhesives 7, 7 preferably have water resistance and adhesiveness to the base material 10 and the swollen polymer material layer 21. Examples of the adhesives 7, 7 include cyanoacrylate adhesives, silicone adhesives, epoxy adhesives, etc.

[0059] The laminate 100 and the hydrogel fluid device 200 have been described above. According to the laminate 100, since the sacrificial layer 30 can be dissolved by applying a solution stimulus, even when the adhesion between the base material 10 and the swollen polymer material layer 21 is high, a flow path 4 with an arbitrary shape can be formed.

[0060] According to the hydrogel fluid device 200, even when the adhesion between the base material 10 and the swollen polymer material layer 21 is high, the flow path 4 is formed. Therefore, the base material 10 and the swollen polymer material layer 21 can be provided with the function of detecting the target substance.

[0061] The hydrogel fluid device 200 can be applied to a wide range of uses such as, for example, a manufacturing system for culturing artificial tissues by supplying nutrients and various differentiation factors to cells through a flow path and diffusing them into a bulk gel; a sensor for detecting a substance diffusing from the flow path by a stimulus-responsive unit encapsulated in the bulk gel.

[0062] (Method for manufacturing a hydrogel fluid device) In an example of a method for manufacturing a hydrogel fluid device including a base material 10 and a layer 20 of a polymer material constituting a hydrogel on the base material 10, as shown in FIGS. 7 to 12, before providing the layer 20 of the polymer material, a first pattern 38 of a sacrificial layer 30 that becomes soluble by application of a solution stimulus is formed on one surface 10a of the base material 10. Next, as shown in FIGS. 13 to 17, on one surface 10a of the base material 10, a bonding region 1a where the base material 10 and the layer 20 of the polymer material bond and a non-bonding region 1b where the base material 10 and the layer 20 of the polymer material do not bond are formed, and the layer 20 of the polymer material is provided. After providing the layer 20 of the polymer material, as shown in FIG. 18, by swelling the polymer material in the layer 20 of the polymer material, the polymer material in the non-bonding region 1b is separated from the base material 10, a flow path 4 is formed at the interface between the base material 10 and the layer 20 of the polymer material, and the polymer material is made into a hydrogel. The first pattern 38 is formed in at least a part of the non-bonding region 1b. Also, when forming the flow path 4, by dissolving the first pattern 38 of the sacrificial layer 30 by a solvent stimulus, the polymer material is separated from the base material 10, and the flow path 4 is formed at the interface between the base material 10 and the layer 20 of the polymer material. The layer 20 of the polymer material means a hydrogel before swelling and is distinguished from the hydrogel after swelling. Also, in the method for manufacturing a hydrogel fluid device according to the first embodiment, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a second pattern 15 of an adhesive functional group is formed on one surface 10a of the base material 10, and a first composition 50 containing a first polymerizable monomer having a functional group capable of forming a chemical bond with the adhesive functional group is applied to the one surface 10a, the first polymerizable monomer is polymerized, and the first composition 50 is gelled, whereby the first composition 50 is made into a polymer material. Hereinafter, the method for manufacturing a hydrogel fluid device according to the first embodiment will be described.

[0063] First, a first pattern 38 of the sacrificial layer 30 that can be dissolved by the application of a solution stimulus is formed. Specifically, as shown in FIG. 7, a thin film 31 that can be dissolved by the application of a solution stimulus is formed on the substrate 10. The aspect of the substrate 10 can be the same as that described above. As the substrate 10, for example, a glass substrate can be used. The substrate 10 may be cleaned before forming the thin film 31. As the cleaning method, the substrate 10 may be immersed in an aqueous sodium hydroxide solution, or oxygen plasma may be irradiated.

[0064] As the material of the thin film 31, the same material as that of the sacrificial layer 30 can be used. As the material of the thin film 31, for example, calcium alginate. The thin film 31 can be formed by a known method.

[0065] When the material of the thin film 31 is calcium alginate, the thin film 31 can be formed by the following method. An aqueous sodium alginate solution is dropped onto the substrate 10, and a thin film of sodium alginate is formed on the substrate 10 by spin coating or the like. Next, the substrate 10 on which the sodium alginate thin film is formed is immersed in an aqueous calcium chloride solution. After immersion, by performing washing and drying, a substrate 10 on which a thin film 31 made of calcium alginate is formed can be obtained.

[0066] Next, as shown in FIG. 8, a protective layer 32 is formed on one surface 31a of the thin film 31. The material of the protective layer 32 is not particularly limited as long as it can protect the thin film 31. The material of the protective layer 32 is not particularly limited as long as it does not dissolve in the developing solution of the resist layer described later, and for example, it is polymethyl methacrylate (PMMA). The method of forming the protective layer 32 is not particularly limited. For example, a spin coating method can be used.

[0067] After forming the protective layer 32, a resist layer 40 is formed on one surface 32a of the protective layer 32 as shown in FIG. 9. The resist layer 40 is not particularly limited and is a layer of a positive photoresist. The resist layer 40 can be formed by applying a positive photoresist on the surface of the protective layer 32. The method of applying the positive photoresist is not particularly limited. For example, the spin coating method can be used.

[0068] Next, the resist layer 40 is irradiated with ultraviolet light through a mask (not shown) having a light-shielding portion and a light-transmitting portion. The peak wavelength of the ultraviolet light is not particularly limited as long as it is within the absorption wavelength band of the positive photoresist. By irradiating the ultraviolet light, an exposed region 40A is formed as shown in FIG. 10.

[0069] After forming the exposed region 40A, development is performed, whereby the irradiated portion (exposed region) 40A of the ultraviolet light in the resist layer 40 is removed as shown in FIG. 11, and an opening 40X is formed. Thereby, the pattern of the resist layer 40 is formed on one surface of the protective layer 32.

[0070] Next, through the resist layer 40 in which the opening 40X is formed, an oxygen plasma treatment using oxygen plasma O is performed on the protective layer 32 exposed by the opening 40X. As a result, as shown in FIG. 12, the protective layer 32 and the thin film 31 of the portion exposed by the opening 40X are removed. By removing the thin film 31 of the portion exposed by the opening 40X, the first pattern 38 of the sacrificial layer 30 is formed. The first pattern 38 is formed in at least a part of the non-adhesive region 1b. After forming the thin film 31 on one surface 10a of the substrate 10, by using a lithography technique to form a photoresist in an arbitrary pattern, the first pattern 38 of the sacrificial layer 30 can be formed on one surface 10a of the substrate 10 before providing the polymer material layer 20.

[0071] Next, as shown in FIG. 13, a layer 11 of an adhesive functional group is provided in a region other than the region where the first pattern 38 is formed. Thereby, a second pattern 15 of the adhesive functional group is formed on one surface 10a of the base material 10. Examples of the layer 11 of the adhesive functional group include a layer of a silane coupling agent having an adhesive functional group. Here, the "adhesive functional group" means a functional group that can adhere to the first polymerizable monomer described later. Hereinafter, the layer of the silane coupling agent will be described as an example, but the present invention is not limited thereto. When the surface of the base material 10 is coated with gold, for example, the layer 11 of the adhesive functional group can also be formed by modifying the gold surface with a dithiol such as bis(2-methacryloyl)oxyethyl disulfide and a compound having an acrylic group.

[0072] For example, when an acrylic monomer is used as the first polymerizable monomer, examples of the adhesive functional group include (meth)acrylic groups. In this case, examples of the silane coupling agent include 3-(methacryloyloxy)propyltrimethoxysilane (hereinafter sometimes referred to as TMSPMA).

[0073] The method for forming the layer 11 of the adhesive functional group is not particularly limited. For example, the layer 11 of the adhesive functional group may be formed by applying a silane coupling agent to one surface 10a of the base material 10 after the first pattern 38 is formed, or the base material 10 on which the first pattern 38 is formed may be allowed to stand while being heated in a vacuum container containing droplets of the silane coupling agent to form the layer 11 of the adhesive functional group. The thickness of the layer 11 of the adhesive functional group is not particularly limited. The layer 11 of the adhesive functional group may be, for example, a monomolecular layer of a silane coupling agent.

[0074] After forming the second pattern 15, as shown in FIG. 14, the remaining protective layer 32 and resist layer 40 are removed. The method for removing the protective layer 32 and the resist layer 40 is not particularly limited. For example, the protective layer 32 and the resist layer 40 can be removed by immersing the substrate 10 after forming the second pattern 15 in a solvent capable of dissolving both the protective layer 32 and the resist layer 40. If the protective layer 32 is PMMA and the resist layer 40 is a positive resist, a solvent capable of dissolving both the protective layer 32 and the resist layer 40 is, for example, acetone.

[0075] Next, as shown in FIG. 15, a first composition 50 containing a first polymerizable monomer having a functional group that forms a chemical bond with an adhesive functional group is applied so as to cover the adhesive functional group layer 11 and the sacrificial layer 30. Specifically, a spacer 60 is disposed on one surface 10a where the adhesive functional group layer 11 is formed, and the first composition 50 containing the first polymerizable monomer is dropped onto the one surface 10a of the substrate 10 in the region surrounded by the spacer 60. Then, a seal substrate 70 having ultraviolet transmissivity is placed so as to cover the first composition 50. Thereby, the first composition 50 is spread in the region surrounded by the spacer 60 and applied so as to cover the adhesive functional group layer 11 and the sacrificial layer 30.

[0076] As the seal substrate 70, for example, a glass substrate can be used. The surface of the seal substrate 70 that comes into contact with the first composition 50 may be washed by performing oxygen plasma treatment. One surface 70a of the seal substrate 70 may be, for example, a flat surface in order to keep the surface of the polymer material layer 20 described later smooth, or may be processed into the arbitrary fine three-dimensional shape in order to transfer the arbitrary fine three-dimensional shape to the surface of the polymer material layer 20 described later.

[0077] The first composition 50 includes a first polymerizable monomer, a polymerization initiator, and optionally an organic solvent and a polymerization accelerator. The first polymerizable monomer is a monomer that can generate a polymer by polymerization. And the first polymerizable monomer has a functional group that forms a chemical bond with an adhesive functional group. The first polymerizable monomer becomes the layer 20 of the polymer material constituting the hydrogel by a polymerization reaction. It can also be said that the first composition 50 applied to the substrate is a precursor of the polymer material of the layer 20 of the polymer material. The first polymerizable monomer is not particularly limited as long as it is a compound that can form a network structure of the polymer material of the layer 20 by polymerization. Examples of the first polymerizable monomer include acrylic monomers having an acrylic group. However, the first polymerizable monomer is not limited to this exemplification.

[0078] Examples of the polymerization initiator include a photopolymerization initiator and a thermal polymerization initiator. The polymerization initiator is preferably water-soluble. Examples of the water-soluble photopolymerization initiator include 2-oxoglutaric acid, 4'-(2-hydroxyethoxy)-2-hydroxy-2-methylpropiophenone (Irgacure 2959), lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP), 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] (VA-086), and the like. Examples of the thermal polymerization initiator include ammonium peroxodisulfate (APS), potassium peroxodisulfate (KPS), and the like.

[0079] Examples of the organic solvent include dimethyl sulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide (DMA), ethylene carbonate (EC), and the like.

[0080] Examples of the polymerization accelerator include N,N,N',N'-tetramethylethane-1,2-diamine (TEMED). By using the polymerization accelerator, polymerization can also be carried out within several minutes at room temperature. When using a polymerization accelerator such as TEMED, in order to prevent polymerization inhibition by oxygen, glucose and glucose oxidase may be used as an oxygen scavenger, or the polymerization reaction may be carried out after sufficiently degassing under an inert gas atmosphere such as nitrogen or argon.

[0081] Next, as shown in FIG. 16, by polymerizing the first polymerizable monomer and gelling the first composition 50, the first composition 50 is used as the layer 20 of the polymer material. During gelation, an appropriate stimulus corresponding to the polymerization initiator is applied to the first composition 50 to induce radical polymerization. Thereby, radical polymerization is initiated, and the layer 20 of the polymer material can be provided on one surface 10a of the base material 10. In the following description, taking the case where the first composition 50 contains a photoinitiator as a polymerization initiator as an example, a method for manufacturing a hydrogel fluid device will be described, but the present invention is not limited to the following example.

[0082] As shown in FIG. 16, in the method for manufacturing a hydrogel fluid device according to the first embodiment, ultraviolet rays UV are irradiated through the seal substrate 70. The peak wavelength of the ultraviolet rays UV is not particularly limited as long as it is within the absorption wavelength band of the photoinitiator contained in the first composition 50. The peak wavelength of the ultraviolet rays UV is, for example, 365 nm. By irradiating the ultraviolet rays UV, the first polymerizable monomer is polymerized and the first composition 50 is gelled, so that the first composition 50 is used as the layer 20 of the polymer material.

[0083] As shown in FIG. 17, in the method for manufacturing a hydrogel fluid device according to the first embodiment, due to the gelation of the first composition 50, an adhesion region 1a where the base material 10 and the layer 20 of the polymer material adhere to each other and a non-adhesion region 1b where the base material 10 and the layer 20 of the polymer material do not adhere to each other are formed between the layer 20 of the polymer material and the base material 10. In the first embodiment, the non-adhesion region 1b becomes a peeling region 1c having a sacrificial layer 30.

[0084] Specifically, by polymerizing the first polymerizable monomer, during the polymerization reaction, the functional group of the first polymerizable monomer reacts with the adhesive functional group of the silane coupling agent in the layer 11 of the adhesive functional group. As a result, in the overlapping portion of the first composition 50 and the second pattern 15 (layer 11 of the adhesive functional group), the polymer material layer 20 after gelation adheres to one surface 10a of the substrate 10, and the adhesion region 1a is formed. On the other hand, in the region of the substrate 10 where the pattern 38 of the sacrificial layer 30 is present, the polymer material layer 20 is separated from the substrate 10, and the non-adhesion region 1b is formed. In the region of the substrate 10 where the pattern 38 of the sacrificial layer 30 is present, the first polymerizable monomers contained in the first composition 50 polymerize with each other. As a result, as shown in FIG. 17, the layer 20 of the polymer material constituting the hydrogel can be provided so that the adhesion region 1a and the non-adhesion region 1b are formed.

[0085] The type of the polymerization reaction during gelation is not particularly limited. Usually, it is selected from polymerization reactions according to the polymerization initiator in the first composition 50. Examples of the polymerization reaction include radical polymerization using a polymerization initiator such as a photoinitiator and a thermal initiator. For example, when the first polymerizable monomer is an acrylic monomer, chemical crosslinking by the polymerization reaction of the acrylic group can be mentioned.

[0086] Next, as shown in FIG. 18, by swelling the polymer material layer 20 and applying a solution stimulus to dissolve the sacrificial layer 30, the polymer material in the non-adhesion region 1b is separated from the substrate 10, and a flow path 4 is formed at the interface between the substrate 10 and the polymer material layer 20, and the polymer material layer 20 is made into a hydrogel. The liquid used for swelling the polymer material layer 20 is not particularly limited and can be appropriately selected according to the polymer material in the polymer material layer 20. For example, an aqueous liquid such as water can be mentioned. When the material of the sacrificial layer 30 is calcium alginate, the sacrificial layer 30 can be removed by immersing it in an EDTA aqueous solution, which is a solution stimulus, and the layer 20 of the polymer material can be swollen to form the flow path 4. Further, when swelling the layer 20 of the polymer material, the unreacted first polymerizable monomer may be removed by diffusing the first polymerizable monomer into the solvent used for swelling.

[0087] Here, when the layer 20 of the polymer material swells, the portion where the layer 20 of the polymer material overlaps with the layer 11 of the adhesive functional group becomes the adhesion region 1a, and the region where the sacrificial layer 30 is located becomes the non - adhesion region 1b. When the sacrificial layer 30 dissolves due to the application of a solution stimulus, the layer 20 of the polymer material is no longer fixed to the base material 10 in the non - adhesion region 1b. Therefore, among the layer 20 of the polymer material, the portion that overlaps with the non - adhesion region 1b in a planar manner can freely increase in volume so as to be separated from the base material 10 in a direction intersecting the extending direction of the non - adhesion region 1b when the volume of the layer 20 of the polymer material increases due to swelling. The layer 20 of the polymer material is fixed to the base material 10 in the adhesion region 1a. Therefore, among the layer 20 of the polymer material, the portion that overlaps with the adhesion region 1a in a planar manner is restricted from increasing in volume in a direction intersecting the extending direction of the non - adhesion region 1b.

[0088] As a result, depending on the degree of swelling of the layer 20 of the polymer material, the layer 20 of the polymer material in the portion overlapping with the non - adhesion region 1b is deformed, separated from the base material 10, and the flow path 4 is formed. For example, as shown in FIG. 18, due to the change in the shape of the layer 20 of the polymer material caused by swelling, the polymer material in the layer 20 of the polymer material is separated from the one surface 10a of the base material 10 so as to bend. In the non-adhesive region 1b after the sacrificial layer 30 has dissolved, the polymer material of the polymer material layer 20 greatly swells freely, thereby alleviating the increase in internal pressure due to the volume increase. Therefore, due to swelling, the polymer material layer 20 greatly bulges and deforms in a direction away from the base material 10. As a result, the polymer material layer 20 is greatly separated from the base material 10 to the opposite side, and the polymer material layer 21 in the non-adhesive region 1b after swelling takes a shape of buckling deformation. Thus, a flow path 4 is formed in the space surrounded by the swollen hydrogel and the base material 10.

[0089] The shape of the flow path 4 can be controlled by appropriately changing the pattern shape of the first pattern 38 and controlling the pattern shapes of the adhesive region 1a and the non-adhesive region 1b. Also, the shape of the flow path 4 can be controlled, for example, by adjusting the type of the polymer material in the polymer material layer 20, the ratio of the rigidity modulus of the base material 10 to the rigidity modulus of the polymer material, the thickness of the polymer material layer 20, and the like. The rigidity modulus and swelling ratio of the polymer material in the polymer material layer 20 can be controlled by changing the type of the first polymerizable monomer used in the first composition, the type and amount of the crosslinking agent, and the like.

[0090] The shape and thickness of the swollen polymer material layer 21 which is a hydrogel can be controlled by adjusting the shape and thickness of the polymer material according to the size, shape, etc. of the spacer 60. Since the shape of the surface 70a of the seal substrate 70 facing the base material 10 is transferred to the swollen polymer material layer 21, the shape of the swollen polymer material layer 21 may be controlled by controlling the shape of the surface 70a.

[0091] The change between the polymer material layer 20 and the swollen polymer material layer 21 is a reversible change. Therefore, the shape of the flow path 4 can also be controlled by changing the swelling ratio of the swollen polymer material layer 21. For example, the swelling ratio of the swollen polymer material layer 21 can be changed by methods such as bringing water into contact with the swollen polymer material layer 21 to cause swelling, or drying the swollen polymer material layer 21. When the layer 21 of the swollen polymer material is an externally-stimuli-responsive hydrogel, the swelling ratio of the layer 21 of the swollen polymer material may be changed according to the stimulus input to the layer 21 of the swollen polymer material, and the shape of the flow path 4 may be controlled.

[0092] Furthermore, in the method for manufacturing the hydrogel fluid device according to the first embodiment, as shown in FIG. 19, a tubular structure 6 is joined to the opening surface of the flow path 4 with an adhesive 7. For the tubular structure 6 and the adhesive 7, the same content as that described in the section of <Hydrogel Fluid Device> above can be adopted.

[0093] The flow path 4 may be coated with a low-swelling gel. By coating, the mechanical properties can be improved. As for the order of joining the tubular structure 6 and the flow path 4, the flow path 4 may be coated with a low-swelling gel to improve the mechanical properties and then the tubular structure 6 may be attached, or the flow path 4 and the tubular structure 6 may be fixed with the adhesive 7 first and then coated with a low-swelling gel to form a hydrogel fluid device. In that case, if leakage occurs from the joint between the tubular structure 6 and the flow path 4, additional joining with an adhesive may be performed.

[0094] In the method for manufacturing the hydrogel fluid device according to the first embodiment described above, a pattern of the sacrificial layer is formed, a layer of the polymer material is provided on one surface of the substrate such that an adhesive region and a non-adhesive region are formed, the polymer material is swollen, and the sacrificial layer 30 is removed, so that the polymer material in the non-adhesive region is separated from the substrate to form a flow path. Here, since the swelling of the polymer material and the dissolution of the sacrificial layer 30 can be carried out by operations such as immersion in an EDTA aqueous solution, the flow path can be formed simply. In the method for manufacturing a hydrogel fluid device according to the first embodiment, due to the presence of the sacrificial layer, even when the adhesion between the base material and the polymer material layer is high, a flow path can be formed. Therefore, they can be arbitrarily selected without considering the chemical composition of the polymer material layer, the surface physical properties of the base material, and the interfacial adhesive force. For example, when a porous thin film is formed on the base material, it is firmly adhered by the formation of an interpenetrating network structure at the interface between the polymer material layer and the base material. By using the sacrificial layer, it becomes possible to easily peel off even in such a case by dissolution stimulation. In addition, the pattern arrangement of the adhesion region and the non-adhesion region can be arbitrarily determined, and a flow path is formed by utilizing the free swelling of the film-like hydrogel. Therefore, flow paths of arbitrary shapes and structures can be formed. Thus, according to the method for manufacturing a hydrogel fluid device, even when the adhesion between the base material and the polymer material layer is high, a flow path can be formed by a simple method.

[0095] <Second Embodiment> Hereinafter, the second embodiment will be described with reference to FIGS. 20 to 33, but the present invention is not limited to the embodiments described below. Hereinafter, the hydrogel fluid device 200A according to the second embodiment will be described. Hereinafter, the same components as those in the first embodiment may be denoted by the same reference numerals, and the description thereof may be omitted.

[0096] (Hydrogel Fluid Device) FIG. 20 is a perspective view of a hydrogel fluid device 200A according to the second embodiment. FIG. 21 is a top view of the hydrogel fluid device 200A after removing the swollen polymer material layer 21. As shown in FIGS. 20 and 21, the hydrogel fluid device 200A includes a substrate 10, a swollen polymer material layer 21, flow paths 4 and 5, and tubular structures 6, 6, and 6. The sacrificial layer 30 of the hydrogel fluid device 200A is located between the polymer material layer 21 and the substrate 10 in at least a part of the non-adhesive region 1b. The hydrogel fluid device 200A has two flow paths 4 and 5, but the flow path 5 is blocked by the sacrificial layer 30. Also, the sacrificial layer 30 is fixed to the swollen polymer material layer 21. The method of fixing the sacrificial layer 30 to the swollen polymer material layer 21 is not particularly limited, and examples include the formation of an interpenetrating structure and adhesion by chemical bonding with the surface of the sacrificial layer.

[0097] The swollen polymer material layer 21 of the hydrogel fluid device 200A is not fixed to the substrate 10 in the non-adhesive region 1b. Also, the swollen polymer material layer 21 of the hydrogel fluid device 200A is fixed to the substrate 10 in the adhesive region 1a. However, in the non-adhesive region 1b, in the region where the sacrificial layer 30 is present, the swollen polymer material layer 21 and the sacrificial layer 30 are fixed, and the sacrificial layer 30 and the substrate 10 are fixed.

[0098] Therefore, in the swollen polymer material layer 21, the portion that does not overlap with the sacrificial layer 30 in a planar manner and overlaps with the non-adhesive region 1b in a planar manner can freely increase in volume in the extending direction of the non-adhesive region 1b and in the direction away from the substrate 10 when the volume increases due to swelling. On the other hand, in the swollen polymer material layer 21, the portion that overlaps with the sacrificial layer 30 and the adhesive region 1a in a planar manner is restricted from increasing in volume in a direction intersecting the extending direction of the non-adhesive region 1b.

[0099] As a result, in the hydrogel fluid device 200A, the portion that does not overlap the sacrificial layer 30 in a planar manner and overlaps the non-adhesive region 1b swells and deforms greatly in a direction away from the base material 10 to relieve the increase in internal pressure due to volume increase, thereby forming a flow path. Further, in the peeling region 1c where the sacrificial layer 30 is present in the non-adhesive region 1b, since no flow path is formed, one of the flow paths 5 is blocked.

[0100] FIG. 22 is a diagram for explaining the change in the liquid feeding direction in the hydrogel fluid device 200A due to solution stimulation. Since the flow path 5 before the application of solution stimulation is blocked, as shown in the left diagram of FIG. 22, the liquid feeding direction is in one direction. By dissolving the first pattern 38 of the sacrificial layer 30 by solution stimulation, the polymer material can be separated from the base material 10, and a flow path 5 can be formed at the interface between the base material 10 and the layer 20 of the polymer material. When the sacrificial layer 30 is calcium alginate, when an EDTA solution is flowed, the sacrificial layer 30 at the branch point of the flow path 5 is dissolved, thereby forming the flow path 5. As a result, as shown in the right diagram of FIG. 22, the flowing direction is divided into two.

[0101] As described above, according to the hydrogel fluid device 200A, since the sacrificial layer 30 is provided in a part of the flow path, liquid feeding can be started at an arbitrary timing. Further, when having a plurality of flow paths, by applying solution stimulation for dissolving the sacrificial layer 30, the liquid feeding direction in the hydrogel fluid device 200A can be changed at an arbitrary timing.

[0102] (Method for manufacturing a hydrogel fluid device) Next, a method for manufacturing a hydrogel fluid device according to the second embodiment will be described. In an example of a method for manufacturing a hydrogel fluid device including a base material 10 and a layer 20 of a polymer material constituting the hydrogel on the base material 10, as shown in FIGS. 23 to 32, on one surface 10a of the base material 10, an adhesive region 1a where the base material 10 and the layer 20 of the polymer material adhere to each other and a non-adhesive region 1b where the base material 10 and the layer 20 of the polymer material do not adhere to each other are formed, and the layer 20 of the polymer material is provided. As shown in FIG. 29, before providing the layer 20 of the polymer material, a first pattern 38 of a sacrificial layer 30 that can be dissolved by applying a solution stimulus is formed on one surface 10a of the base material 10. After providing the layer 20 of the polymer material, as shown in FIG. 33, by swelling the polymer material in the layer 20 of the polymer material, the polymer material in the non-adhesive region is separated from the base material, a flow path 4 is formed at the interface between the base material 10 and the layer 20 of the polymer material, and the polymer material is made into a hydrogel. The first pattern 38 is formed in at least a part of the non-adhesive region 1b. Further, in the method for manufacturing a hydrogel fluid device according to the second embodiment, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a second pattern 15 of an adhesive functional group is formed on one surface 10a of the base material 10, and a first composition 50 containing a first polymerizable monomer having a functional group capable of forming a chemical bond with the adhesive functional group is applied to the one surface 10a, the first polymerizable monomer is polymerized, and the first composition 50 is gelled to make the first composition 50 into a polymer material. Hereinafter, a method for manufacturing a hydrogel fluid device according to the second embodiment will be described.

[0103] In the method for manufacturing a hydrogel fluid device according to the second embodiment, first, as shown in FIGS. 23 to 28, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a second pattern 15 of an adhesive functional group is formed on one surface 10a of the base material 10. Specifically, as shown in FIG. 23, a layer 11 of an adhesive functional group is provided on one surface 10a of the base material 10. By the layer 11 of the adhesive functional group, the adhesive functional group is presented on one surface 10a of the base material 10. The details and preferred embodiments of the base material 10 can be the same as those described in the section of (laminated body) of the first embodiment. For example, the base material 10 may be a glass substrate.

[0104] As the layer 11 of the adhesive functional group, for example, a layer of a silane coupling agent having an adhesive functional group can be mentioned. For example, when an acrylic monomer is used as the first polymerizable monomer, examples of the adhesive functional group can include (meth)acrylic groups. In this case, examples of the silane coupling agent include 3-(methacryloyloxy)propyltrimethoxysilane.

[0105] The method for forming the layer 11 of the adhesive functional group is not particularly limited. For example, one surface 10a of the base material 10 is washed with an aqueous sodium hydroxide solution, and after 3-(methacryloyloxy)propyltrimethoxysilane is activated by oxygen plasma or piranha cleaning, the layer 11 of the adhesive functional group can be formed by applying a silane coupling agent to the one surface 10a of the base material 10. Piranha cleaning is a general term referring to a cleaning method using a mixed solution of concentrated sulfuric acid and an aqueous hydrogen peroxide solution.

[0106] Next, as shown in FIG. 24, a resist layer 40 is further provided on one surface 11b of the layer 11 of the adhesive functional group. The resist layer 40 is not particularly limited. For example, it is a layer of a positive photoresist. In this case, the resist layer 40 can be formed by applying a positive photoresist to the surface of the layer 11 of the adhesive functional group. The coating method of the positive photoresist is not particularly limited. For example, the spin coating method can be used.

[0107] Next, ultraviolet rays are irradiated to the resist layer 40 through a mask having a light-shielding portion and a light-transmitting portion. The peak wavelength of the irradiated ultraviolet rays is not particularly limited as long as it is within the absorption wavelength band of the positive photoresist. Thereby, an exposed region 40A is formed as shown in FIG. 25.

[0108] Next, as shown in FIG. 26, after ultraviolet irradiation and development, the exposed region 40A is removed and the opening 40X is formed. As a result, the pattern of the resist layer 40 is formed on one surface of the adhesive functional group layer 11.

[0109] Next, as shown in FIG. 27, an oxygen plasma treatment using oxygen plasma O is performed on the adhesive functional group layer 11 exposed by the opening 40X through the resist layer 40 in which the opening 40X is formed. As a result, the silane coupling agent of the adhesive functional group layer 11 in the portion exposed by the opening 40X is removed.

[0110] Next, as shown in FIG. 28, by removing the resist layer 40, the adhesive functional group layer 11 having the second pattern 15 is obtained (lift-off). The shape of the second pattern 15 can be appropriately adjusted by changing the shape of the light-transmitting portion in the mask M. After presenting the adhesive functional group on one surface 10a of the substrate 10, by forming a photoresist in an arbitrary pattern using lithography technology, the second pattern 15 of the adhesive functional group can be formed on one surface 10a of the substrate 10.

[0111] Next, as shown in FIG. 29, the first pattern 38 of the sacrificial layer 30 is formed using the inkjet printer 90. As a result, before providing the polymer material layer 20, the first pattern 38 of the sacrificial layer that can be dissolved by applying a solution stimulus can be formed on one surface 10a of the substrate 10. Next, as shown in FIG. 30, a first composition 50 containing a first polymerizable monomer having a functional group that forms a chemical bond with an adhesive functional group is applied so as to cover the layer 11 of the adhesive functional group and the first pattern 38. Specifically, a spacer 60 is disposed on one surface 10a where the layer 11 of the adhesive functional group is formed, and the first composition 50 containing the first polymerizable monomer is dropped onto one surface 10a of the base material 10 in the region surrounded by the spacer 60. Then, a seal substrate 70 having ultraviolet permeability is placed so as to cover the first composition 50. Thereby, the first composition 50 is spread over the region surrounded by the spacer 60 and applied so as to cover the layer 11 of the adhesive functional group and the first pattern 38 of the sacrificial layer 30. As the first composition 50, the one used in the first embodiment can be used.

[0112] As the seal substrate 70, for example, a glass substrate can be used. The surface of the seal substrate 70 that comes into contact with the first composition 50 is preferably cleaned by performing oxygen plasma treatment. One surface 70a of the seal substrate 70 may be, for example, a flat surface in order to keep the surface of the polymer material layer 20 described later smooth, or may be processed into the arbitrary fine three-dimensional shape in order to transfer the arbitrary fine three-dimensional shape to the surface of the polymer material layer 20 described later.

[0113] Next, as shown in FIG. 31, the first polymerizable monomer is polymerized and the first composition 50 is gelled, whereby the first composition 50 is used as the polymer material layer 20. At the time of gelation, an appropriate stimulus according to the polymerization initiator is applied to the first composition 50 to induce radical polymerization. Thereby, radical polymerization is started, and the polymer material layer 20 can be provided on one surface 10a of the base material 10.

[0114] As shown in FIG. 31, in the method for manufacturing the hydrogel fluid device of the second embodiment, ultraviolet rays UV are irradiated through the seal substrate 70. The peak wavelength of the ultraviolet rays UV is not particularly limited as long as it is within the absorption wavelength band range of the photopolymerization initiator contained in the first composition 50. The peak wavelength of the ultraviolet rays UV is, for example, 365 nm. By irradiating ultraviolet (UV) light to polymerize the first polymerizable monomer and gelating the first composition 50, the first composition 50 is made into a layer 20 of a polymer material.

[0115] As shown in FIG. 32, in the method for manufacturing a hydrogel fluid device according to the second embodiment, by gelating the first composition 50, an adhesion region 1a where the base material 10 and the polymer material layer 20 adhere to each other and a non - adhesion region 1b where the base material 10 and the polymer material layer 20 do not adhere to each other are formed between the polymer material layer 20 and the base material 10. Further, in at least a part of the non - adhesion region 1b, a sacrificial layer 30 is provided between the base material 10 and the polymer material layer 20. The region where the sacrificial layer 30 is located becomes a peeling region 1c.

[0116] Specifically, by polymerizing the first polymerizable monomer, during the polymerization reaction, the functional group of the first polymerizable monomer reacts with the adhesive functional group of the silane coupling agent in the layer 11. As a result, in the portion where the first composition 50 and the second pattern 15 (layer 11) overlap, the polymer material layer 20 after gelation adheres to one surface 10a of the base material 10, and the adhesion region 1a is formed. On the other hand, in the portion where the second pattern 15 is not formed, the polymer material layer 20 does not adhere to one surface 10a of the base material 10, and the non - adhesion region 1b is formed. On the other hand, in the region of the base material 10 where the pattern 38 of the sacrificial layer 30 is present, the polymer material layer 20 is separated from the base material 10. In the non - adhesion region 1b of the base material 10, the first polymerizable monomers contained in the first composition 50 polymerize with each other. As a result, as shown in FIG. 32, the polymer material layer 20 constituting the hydrogel can be provided so that the adhesion region 1a and the non - adhesion region 1b are formed.

[0117] Next, as shown in FIG. 33, by swelling the polymer material layer 20, the polymer material in the non - adhesion region 1b is separated from the base material 10, a flow path 4 is formed at the interface between the base material 10 and the polymer material layer 20, and the polymer material is made into a hydrogel. That is, the polymer material layer 20 becomes the polymer material layer 21 after swelling. The liquid used for swelling the polymer material is not particularly limited and can be appropriately selected according to the polymer in the polymer material layer 20. For example, an aqueous liquid such as water can be mentioned.

[0118] For example, by immersing the polymer material layer 20 shown in FIG. 32 together with the substrate 10 in a large excess amount of pure water, the polymer material can be swollen with water to remove the unreacted first polymerizable monomer from the polymer material. Thereby, a swollen polymer material layer 21 in which the polymer material is swollen with water can be obtained.

[0119] Here, when the polymer material swells, in the polymer material layer 20, the portion overlapping the adhesive functional group layer 11 becomes the adhesive region 1a, and the portion not overlapping the adhesive functional group layer 11 becomes the non-adhesive region 1b. The polymer material layer 20 is not fixed to the substrate 10 in the region of the non-adhesive region 1b where the sacrificial layer 30 is absent. Therefore, in the polymer material layer 20, the portion that does not overlap the sacrificial layer 30 planarly and overlaps the non-adhesive region 1b planarly can freely increase in volume in a direction intersecting the extending direction of the non-adhesive region 1b when the volume increases due to the swelling of the polymer material. The polymer material layer 20 is fixed to the substrate 10 in the adhesive region 1a. Further, the polymer material layer 20 is fixed to the sacrificial layer 30 in the region (peeling region) 1c overlapping the sacrificial layer 30. Further, the sacrificial layer 30 is fixed to the substrate 10. Therefore, in the polymer material layer 20, the portion overlapping the sacrificial layer 30 planarly and the portion overlapping the adhesive region 1a planarly restrict the volume increase of the polymer material layer 20 in a direction intersecting the extending direction of the non-adhesive region 1b.

[0120] As a result, according to the swelling degree of the polymer material, the polymer material in the portion overlapping the non-adhesive region 1b is deformed, separated from the substrate 10, and the flow path 4 is formed. For example, as shown in FIG. 33, as a result of the shape change of the polymer material due to the swelling of the polymer material, the polymer material is separated from the one surface 10a of the substrate 10 so as to bend. In the non - adhesive region 1b without the sacrificial layer 30, since the polymer material swells freely to a large extent, in order to relieve the increase in internal pressure due to the volume increase, it greatly bulges and deforms in the direction away from the base material 10. As a result, the polymer material is greatly separated from the base material 10 to the opposite side, and the layer 21 of the polymer material after swelling in the non - adhesive region 1b takes a buckled - deformed shape. In this way, the flow path 4 is formed in the space surrounded by the layer 21 of the polymer material after swelling and the base material 10.

[0121] In the method for manufacturing a hydrogel fluid device according to the second embodiment described above, a pattern of the sacrificial layer can be formed in a part of the region where the flow path is to be formed. Thereby, a hydrogel fluid device capable of liquid feeding at an arbitrary timing can be manufactured. Also, by forming a sacrificial layer in a part of the region of the flow path, the flow of liquid feeding can be changed at an arbitrary timing. In addition, the pattern arrangement of the adhesive region and the non - adhesive region can be arbitrarily determined, and the flow path is formed by utilizing the free swelling of the film - shaped hydrogel. Therefore, flow paths of arbitrary shapes and structures can be formed. In this way, according to the method for manufacturing a hydrogel fluid device of the second embodiment, a flow path capable of changing the liquid feeding direction at an arbitrary timing can be formed by a simple method.

[0122] <Third Embodiment> Hereinafter, the third embodiment will be described with reference to FIGS. 34 to 36, but the present invention is not limited to the embodiments described below. Hereinafter, the hydrogel fluid device 200B according to the third embodiment will be described. The same components as those in the first and second embodiments may be denoted by the same reference numerals, and the description thereof may be omitted.

[0123] (Hydrogel Fluid Device) FIG. 34 is a perspective view of the hydrogel fluid device 200B according to the third embodiment. FIG. 35 is a top view of the hydrogel fluid device 200B after removing the swollen polymer material layer 21. As shown in FIGS. 34 and 35, the hydrogel fluid device 200B includes a substrate 10, a swollen polymer material layer 21, a sacrificial layer 30, a flow path 4, and tubular structures 6, 6. The sacrificial layer 30 of the hydrogel fluid device 200B is located between the polymer material layer 21 and the substrate 10 in at least a part of the non-adhesive region 1b. The hydrogel fluid device 200B includes a reservoir 8 at a position branched from the flow path 4. The reservoir 8 is filled with the sacrificial layer 30. Further, the sacrificial layer 30 of the third embodiment contains a drug 95.

[0124] The swollen polymer material layer 21 of the hydrogel fluid device 200B is not fixed to the substrate 10 in the non-adhesive region 1b. Also, the swollen polymer material layer 21 of the hydrogel fluid device 200B is fixed to the substrate 10 in the adhesive region 1a. However, in the non-adhesive region 1b, in the region where the sacrificial layer 30 is present, the swollen polymer material layer 21 and the sacrificial layer 30 are fixed, and the sacrificial layer 30 and the substrate 10 are fixed.

[0125] Therefore, in the swollen polymer material layer 21, the portion that does not overlap the sacrificial layer 30 in a planar manner and overlaps the non-adhesive region 1b in a planar manner can freely increase in volume in the extending direction of the non-adhesive region 1b and in the direction away from the substrate 10 when the volume increases due to swelling. On the other hand, in the swollen polymer material layer 21, the portion that overlaps the sacrificial layer 30 and the adhesive region 1a in a planar manner is restricted from increasing in volume in a direction intersecting the extending direction of the non-adhesive region 1b.

[0126] As a result, in the hydrogel fluid device 200, the portion that does not overlap the sacrificial layer 30 in a planar manner and overlaps the non-adhesive region 1b in a planar manner forms a flow path by greatly swelling and deforming in the direction away from the substrate 10 in order to relieve the increase in internal pressure due to the volume increase.

[0127] FIG. 36 is a diagram for explaining the flow of the drug 95 released from the reservoir 8 of the hydrogel fluid device 200B by solution stimulation. The reservoir 8 before the application of solution stimulation is filled with the sacrificial layer 30. Here, when the sacrificial layer 30 is calcium alginate and an EDTA solution is flowed through the flow path 4, the sacrificial layer 30 at the branch point of the flow path 4 is dissolved. As a result, the sacrificial layer 30 in the reservoir 8 is dissolved. By dissolving the sacrificial layer 30, the drug 95 in the sacrificial layer 30 is released into the flow path 4. The drug 95 can be appropriately selected according to the purpose.

[0128] As described above, according to the hydrogel fluid device 200B, since the sacrificial layer 30 is provided in the reservoir, the drug can be released at an arbitrary timing. The hydrogel fluid device 200B can be manufactured by the same method as the manufacturing method of the hydrogel fluid device according to the second embodiment.

[0129] <Fourth Embodiment> Hereinafter, the fourth embodiment will be described with reference to FIGS. 37 to 43, but the present invention is not limited to the embodiments described below. Hereinafter, the hydrogel fluid device 200C according to the fourth embodiment will be described. Note that the same components as those in the first to third embodiments may be denoted by the same reference numerals, and the description thereof may be omitted.

[0130] (Manufacturing Method of Hydrogel Fluid Device) In an example of a method for manufacturing a hydrogel fluid device including a base material 10 and a layer 20 of a polymer material that constitutes a hydrogel on the base material 10, next, as shown in FIGS. 37 to 42, on one surface 10a of the base material 10, an adhesion region 1a where the base material 10 and the layer 20 of the polymer material adhere to each other and a non-adhesion region 1b where the base material 10 and the layer 20 of the polymer material do not adhere to each other are formed, and the layer 20 of the polymer material is provided. As shown in FIGS. 37 and 38, before providing the layer 20 of the polymer material, a first pattern 38 of a sacrificial layer 30 that can be dissolved by applying a solution stimulus is formed on one surface 10a of the base material 10. After providing the layer 20 of the polymer material, as shown in FIG. 43, by swelling the polymer material in the layer 20 of the polymer material, the polymer material in the non-adhesion region is separated from the base material, a flow path 4 is formed at the interface between the base material 10 and the layer 20 of the polymer material, and the polymer material is made into a hydrogel. Further, in the method for manufacturing a hydrogel fluid device according to the fourth embodiment, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a layer 80 of a polymerization initiator is formed on one surface 10a of the base material 10, and a second composition 52 containing a second polymerizable monomer capable of forming a chemical bond with the polymerization initiator is applied on one surface of the layer 80 of the polymerization initiator, the second polymerizable monomer is polymerized, and the second composition 52 is gelled, whereby an adhesion region 1a is formed at a portion where the layer 80 of the polymerization initiator and the second composition 52 overlap, and the second composition 52 is made into a polymer material. Hereinafter, the method for manufacturing a hydrogel fluid device according to the fourth embodiment will be described.

[0131] First, in the same manner as the method for manufacturing a hydrogel fluid device of the first embodiment, a first pattern 38 of a sacrificial layer 30 is formed as shown in FIG. 37. Next, as shown in FIG. 38, the protective layer 32 and the resist layer 40 are removed. As a result, before providing the layer 20 of the polymer material, a first pattern 38 of a sacrificial layer 30 that can be dissolved by applying a solution stimulus is formed on one surface 10a of the base material 10. After removing the protective layer 32 and the resist layer 40, when providing the layer 20 of the polymer material on one surface 10a of the base material 10 as shown in FIG. 39, a layer 80 of a photoinitiator is formed on one surface 10a of the base material 10.

[0132] Specifically, a coating film (not shown) of a photopolymerization initiator solution is formed on one surface 10a of the base material 10. As the base material 10, it is preferable to use a resin substrate such as an elastomer or a polymer film that can be infiltrated by an organic solvent. Examples of the organic solvent that can infiltrate the resin substrate include polar solvents such as methanol, ethanol, and acetone.

[0133] In the method for manufacturing the hydrogel fluid device according to the fourth embodiment, a hydrogen abstraction type photopolymerization initiator is used as the photopolymerization initiator. Examples of the hydrogen abstraction type photopolymerization initiator include benzophenone, Michler's ketone, Michler's ethyl ketone, and the like. Examples of the solvent of the photopolymerization initiator solution include polar solvents such as ethanol and acetone.

[0134] As shown in FIG. 39, the solvent is removed from the coating film to provide a layer 80 of the photopolymerization initiator on the base material 10. Further, since the polar solvent used in the photopolymerization initiator solution can infiltrate the resin substrate, a part of the photopolymerization initiator is impregnated into the inside of the resin substrate as the solvent infiltrates the resin substrate.

[0135] Next, as shown in FIG. 40, the spacer 60 is arranged, and a second composition 52 containing a second polymerizable monomer that forms a chemical bond with the polymerization initiator is dropped into the region surrounded by the spacer 60. Then, an ultraviolet ray transmissive seal substrate 70 is covered, and the second composition 52 is spread and applied to the region surrounded by the spacer 60. Note that a part of the layer 80 of the photopolymerization initiator may be covered with a mask material. A paraffin film can be used as the mask material. The mask material can be arranged at a portion where the non-adhesive region 1b is to be formed.

[0136] The second composition 52 includes a second polymerizable monomer, a hydrogen abstraction type photoinitiator, and an organic solvent as needed. However, when the concentration of the hydrogen abstraction type photoinitiator contained in the photoinitiator layer 80 is sufficiently high, the second composition 52 may not contain the hydrogen abstraction type photoinitiator. "The concentration is sufficiently high" refers to a case where, for example, the concentration of the photoinitiator in the photoinitiator solution used for forming the coating film is 10% by mass or more.

[0137] The second polymerizable monomer is a monomer that can generate a polymer by polymerization. And the second polymerizable monomer has a functional group that forms a chemical bond with the photoinitiator. The second polymerizable monomer becomes a polymer material constituting the hydrogel by a polymerization reaction. The second polymerizable monomer is not particularly limited as long as it is a compound that can form a network structure of a polymer material by polymerization. Examples of the second polymerizable monomer include acrylic monomers having an acrylic group. However, the second polymerizable monomer is not limited to this exemplification.

[0138] Next, as shown in FIG. 40, by polymerizing the second polymerizable monomer and gelling the second composition 52, an adhesion region is formed in a portion overlapping the photoinitiator layer 80, and the second composition 52 is made into a polymer material layer 20.

[0139] Specifically, as shown in FIG. 41, ultraviolet rays UV are irradiated through the seal substrate 70. The peak wavelength of the ultraviolet rays UV is included in the absorption wavelength band of the photoinitiator contained in the photoinitiator layer 80. The peak wavelength of the ultraviolet rays UV is, for example, 365 nm.

[0140] By irradiating ultraviolet ray UV2, a photoinitiator is reacted in a predetermined pattern. By irradiating ultraviolet ray UV2, in a portion where the photoinitiator layer 80 and the second composition 52 overlap, the photoinitiator in the photoinitiator layer 80 extracts a hydrogen atom from the base material 10. As a result, radicals, which are reaction starting points, are generated in the base material 10. The monomer contained in the second composition 52 polymerizes starting from the radicals generated in the base material 10, and a polymer material is obtained. Therefore, the polymer material is adhered to the base material 10 at the portion overlapping with the photoinitiator layer 80.

[0141] On the other hand, in a region where the sacrificial layer 30 exists, with the sacrificial layer 30 interposed therebetween, the polymer material layer 20 and the base material 10 are separated. Therefore, the polymer material layer 20 is not directly adhered to the base material 10.

[0142] When a mask material is used, in a portion where the mask materials of the photoinitiator layer 80 overlap, that is, in a portion where the photoinitiator layer 80 and the second composition 52 do not overlap, the ultraviolet ray UV2 is blocked, and the extraction of hydrogen atoms from the base material 10 by the photoinitiator does not occur. Even if hydrogen atoms are extracted from the base material 10 and radicals are generated, the second composition 52 is not in contact. Therefore, the generated radicals do not react with the second polymerizable monomer in the second composition 52. Therefore, in a portion where the photoinitiator layer 80 and the light-blocking portion of the mask material overlap, the second polymerizable monomers contained in the second composition 52 polymerize with each other without bonding to the base material 10.

[0143] Next, as shown in FIG. 42, the seal substrate 70 is removed. In this way, in the method for manufacturing a hydrogel fluid device according to the fourth embodiment, the layer 20 of the polymer material constituting the hydrogel is provided so that an adhesion region 1a that adheres to the base material 10 and a non-adhesion region 1b that does not adhere to the base material 10 are formed.

[0144] Next, in the same manner as the manufacturing method of the hydrogel fluid device of the first embodiment, the sacrificial layer 30 is dissolved and the polymer material layer 20 is swollen as shown in FIG. 43. Thereafter, the tubular structure 6 is fixed with the adhesive 7, and the hydrogel fluid device 200 can be obtained.

[0145] According to the manufacturing method of the hydrogel fluid device of the fourth embodiment, even when the adhesion between the base material and the polymer material layer is high, a flow path can be formed.

[0146] <Fifth Embodiment> Hereinafter, the fifth embodiment will be described with reference to FIGS. 44 to 46, but the present invention is not limited to the embodiments described below. Hereinafter, the manufacturing method of the hydrogel fluid device according to the fifth embodiment will be described. Note that the same components as those in the first to fourth embodiments may be denoted by the same reference numerals, and the description thereof may be omitted.

[0147] (Manufacturing Method of Hydrogel Fluid Device) In an example of a method for manufacturing a hydrogel fluid device including a base material 10 and a layer 20 of a polymer material that constitutes a hydrogel on the base material 10, next, as shown in FIGS. 44 to 46, on one surface 10a of the base material 10, an adhesion region 1a where the base material 10 and the layer 20 of the polymer material adhere to each other and a non-adhesion region 1b where the base material 10 and the layer 20 of the polymer material do not adhere to each other are formed, and the layer 20 of the polymer material is provided. As shown in FIG. 45, before providing the layer 20 of the polymer material, a first pattern 38 of a sacrificial layer 30 that can be dissolved by applying a solution stimulus is formed on one surface 10a of the base material 10. After providing the layer 20 of the polymer material, by swelling the polymer material in the layer 20 of the polymer material, the polymer material in the non-adhesion region is separated from the base material, a flow path 4 is formed at the interface between the base material 10 and the layer 20 of the polymer material, and the polymer material is made into a hydrogel. Further, in the method for manufacturing a hydrogel fluid device according to the fifth embodiment, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a third pattern 25 of a gel-entering polymer or an adhesive molecule is formed on one surface 10a of the base material 10, a sheet material 75 using the polymer material as a forming material is disposed on one surface 10a of the base material 10 on which the third pattern 25 is formed, and the sheet material 75 and the gel-entering polymer or the adhesive molecule are brought into contact with each other. Hereinafter, the method for manufacturing a hydrogel fluid device according to the fifth embodiment will be described.

[0148] In the method for manufacturing a hydrogel fluid device according to the fifth embodiment, first, when providing the layer 20 of the polymer material on one surface 10a of the base material 10, a third pattern 25 of a layer 85 of a gel-entering polymer is formed on one surface 10a of the base material 10.

[0149] Specifically, as shown in FIG. 44, a layer 11 of a silane coupling agent having a pattern shape is formed on one surface 10a of the base material 10. As the method for forming the silane coupling agent and the pattern, the same content as that described in the method for manufacturing a hydrogel fluid device according to the first aspect can be adopted.

[0150] Thereafter, a layer 85 of a gel-entrapping polymer is formed on the surface of the layer 11 of the adhesive functional group to form a pattern of the gel-entrapping polymer. Examples of the gel-entrapping polymer include chitosan, alginic acid, polyvinyl alcohol, etc. Note that, instead of the layer 85 of the gel-entrapping polymer, a layer of an adhesive molecule may be formed. Examples of the adhesive molecule include compounds such as cyanoacrylate-based compounds. In the formation of the layer 85 of the gel-entrapping polymer, the grafting to method or the grafting from method can be used. Thereby, the adhesive functional group of the silane coupling agent and the gel-entrapping polymer can be reacted.

[0151] Next, as shown in FIG. 45, a first pattern 38 of the sacrificial layer 30 is formed using an inkjet printer 90. Thereby, before providing the layer 20 of the polymer material, the first pattern 38 of the sacrificial layer 30 that can be dissolved by applying a solution stimulus is formed on one surface 10a of the substrate 10.

[0152] Next, as shown in FIG. 46, a sheet material 75 using a polymer material as a forming material is disposed on one surface 10a of the substrate 10 so as to cover the pattern-shaped layer 85 of the gel-entrapping polymer and the sacrificial layer 30. Thereafter, the sheet material 75 is brought into contact with the gel-entrapping polymer. When the layer 85 of the gel-entrapping polymer comes into contact with the sheet material 75, the gel-entrapping polymer contained in the layer 85 of the gel-entrapping polymer penetrates into the sheet material 75 and entangles with the network structure of the polymer material. Thereby, the gel-entrapping polymer and the hydrogel are physically or chemically bonded, and the sheet material 75 and the substrate 10 can be adhered.

[0153] When bringing the sheet material 75 into contact with the layer 85 of the gel-entrapping polymer, the pH of the polymer material constituting the sheet material 75 may be changed, or a low-molecular crosslinking agent typified by glutaraldehyde may be simultaneously diffused into the sheet material 75. Thereby, physical bonding or chemical bonding between the gel-entrapping polymers is formed, and the gel-entrapping polymer and the polymer material in the sheet material 75 can be adhered more firmly.

[0154] Next, in the same manner as the method for manufacturing the hydrogel fluid device of the second embodiment, the polymer material layer 20 is swollen. Thereafter, a hydrogel fluid device can be manufactured. The tubular structure 6 can be fixed with the adhesive 7 to obtain a hydrogel fluid device.

[0155] According to the method for manufacturing the hydrogel fluid device of the fifth embodiment, even when the adhesion between the base material and the polymer material layer is high, a flow path can be formed. Further, according to the method for manufacturing the hydrogel fluid device of the fourth embodiment, a sacrificial layer 30 can be formed in a part of the flow path.

[0156] As described above, some embodiments of the present invention have been described with reference to the drawings, but the present invention is not limited to the above-described embodiments and examples. The various shapes, combinations, etc. of each configuration shown in the above examples are merely examples, and various modifications can be made based on design requirements and the like without departing from the gist of the present invention. And the embodiments obtained by arbitrarily and appropriately combining the technical means disclosed in the above-described embodiments are also included in the technical scope of the present invention. As a specific example of the combination, one aspect of the present invention can also be said to relate to the following [1] to [7].

[0157] [1] A method for manufacturing a hydrogel fluid device including a base material and a layer of a polymer material constituting a hydrogel on the base material, wherein on the one surface of the base material, an adhesive region where the base material and the polymer material layer adhere and a non-adhesive region where the base material and the polymer material layer do not adhere are formed, the polymer material layer is provided, the polymer material is swollen to separate the polymer material in the non-adhesive region from the base material, a flow path is formed at the interface between the base material and the polymer material layer, the polymer material is made into a hydrogel, and before providing the polymer material layer, a first pattern of a sacrificial layer that can be dissolved by applying a solution stimulus is formed on one surface of the base material, and the first pattern is formed in at least a part of the non-adhesive region. A method for manufacturing a hydrogel fluid device. [2] When providing the layer of the polymer material on the one surface of the substrate, a second pattern of an adhesive functional group is formed on the one surface of the substrate, a first composition containing a first polymerizable monomer having a functional group capable of forming a chemical bond with the adhesive functional group is applied to the one surface, the first polymerizable monomer is polymerized, and the first composition is gelled, thereby making the first composition the polymer material. The method for manufacturing the hydrogel fluid device according to [1]. [3] When providing the layer of the polymer material on the one surface of the substrate, a layer of a polymerization initiator is formed on the one surface of the substrate, a second composition containing a second polymerizable monomer capable of forming a chemical bond with the polymerization initiator is applied to one surface of the layer of the polymerization initiator, the second polymerizable monomer is polymerized, and the second composition is gelled, thereby forming the adhesion region at a portion where the layer of the polymerization initiator and the second composition overlap, and making the second composition the polymer material. The method for manufacturing the hydrogel fluid device according to [1]. [4] When providing the layer of the polymer material on the one surface of the substrate, a third pattern of a gel-entrapping polymer or an adhesive molecule is formed on the one surface of the substrate, a sheet material using the polymer material as a forming material is disposed on the one surface of the substrate on which the third pattern is formed, and the sheet material and the gel-entrapping polymer or the adhesive molecule are brought into contact with each other. The method for manufacturing the hydrogel fluid device according to [1]. [5] By dissolving the first pattern by solvent stimulation, the polymer material is separated from the substrate, and a flow path is formed at the interface between the substrate and the layer of the polymer material. The method for manufacturing the hydrogel fluid device according to any one of [1] to [4]. [6] The method for manufacturing the hydrogel fluid device according to any one of [1] to [5], wherein the sacrificial layer contains a drug. [7] A substrate, and a layer of a polymer material constituting a hydrogel provided on one surface of the substrate, It has, and at the interface between the base material and the layer of the polymer material, an adhesion region where the base material and the layer of the polymer material adhere, and a non-adhesion region where the base material and the layer of the polymer material do not adhere are formed. In at least a part of the non-adhesion region, a sacrificial layer is provided between the base material and the layer of the polymer material. A hydrogel fluid device.

Example

[0158] Hereinafter, the present invention will be specifically described by way of examples. However, the present invention is not limited to the following description.

[0159] (Example 1) The glass substrate was cleaned with sodium hydroxide and oxygen plasma. A sodium alginate solution was dropped onto the cleaned glass substrate, and a thin film of sodium alginate was formed by spin coating. This substrate was used as a spin-coated substrate.

[0160] After the spin-coated substrate was immersed in an aqueous calcium chloride solution, it was washed with ultrapure water and dried. As a result, a glass substrate with a calcium alginate thin film was obtained.A PMMA thin film and a positive photoresist thin film were laminated in this order on the upper surface of the glass substrate with the calcium alginate thin film by spin coating. After forming the positive photoresist thin film, exposure was performed through a photomask. After exposure, by performing development processing, a pattern of the positive resist (strip shape with a line width of 1 mm) was obtained. After development, the PMMA and calcium alginate thin films were removed by oxygen plasma etching. The substrate after oxygen plasma etching was allowed to stand in a vacuum container containing droplets of 3-(methacryloyloxy)propyltrimethoxysilane (hereinafter, TMSPMA) and reacted at 70 ° C. for 16 hours to obtain an adhesion region on the substrate surface. After forming the adhesion region, the substrate was immersed in acetone to remove the PMMA and the positive resist, and a solid substrate having a surface composed of an adhesion region composed of calcium alginate as a sacrificial layer and a silane coupling agent was obtained (hereinafter, a solid substrate with a sacrificial layer).

[0161] Spacers with a thickness of 80 μm were placed at both ends of the solid substrate with a sacrificial layer, and an aqueous solution composed of acrylamide, methylenebisacrylamide, and LAP was dropped onto the substrate as a precursor solution of the hydrogel. After the solution was dropped, it was covered with a cover glass and irradiated with light of 365 nm to gel the precursor solution. Thereby, a polyacrylamide gel film was obtained.

[0162] After gelation, the cover glass covering the upper surface was removed, and unreacted gel precursor molecules were removed in pure water to obtain a hydrogel laminate composed of a glass substrate and polyacrylamide gel.

[0163] The hydrogel laminate was immersed in a 10 mM EDTA aqueous solution as a dissolution stimulus, and the sacrificial layer composed of calcium alginate dissolved. The polyacrylamide gel on the upper surface of the sacrificial layer peeled off and swelled from the substrate, thereby obtaining a hydrogel flow channel structure. Thereafter, PTFE tubes with an outer diameter of 1 mm were inserted into both ends of the hydrogel flow channel structure, and the swellable film-like gel, the solid substrate, and the tubes were joined with an adhesive to obtain a hydrogel fluid device capable of liquid feeding.

[0164] Fig. 47 shows the observation results by optical microscope of the formation of the hydrogel flow channel structure due to the dissolution of the sacrificial layer. Before applying the dissolution stimulus (the left figure in Fig. 47), no flow channel was formed. By applying the dissolution stimulus thereto, the gel began to partially peel off from the glass substrate (the middle figure in Fig. 47). Furthermore, as time passed, a flow channel structure was formed (the right figure in Fig. 47). From the above, it was confirmed that by using the sacrificial layer, a flow channel can be formed even when the adhesion between the base material and the layer of the polymer material is high.

[0165] (Example 2) The glass substrate cleaned by the same method as in the examples was chemically modified with TMSPMA. A positive photoresist thin film was formed on the upper surface of the substrate after TMSPMA modification by spin coating. After the formation of the positive photoresist thin film, it was patterned by exposure and development. After development, an oxygen plasma etching and an acetone treatment were carried out to obtain a TMSPMA-modified substrate having a glass surface (non-adhesive region) in the shape of a Y-shaped strip with a width of 1 mm (hereinafter, a patterned TMSPMA substrate). Next, sodium alginate was printed by an inkjet printer so as to cover a part of the above-described strip pattern and block a part of the flow path. Similar to Example 1, the substrate on which the sodium alginate pattern was formed was immersed in a calcium chloride solution. As a result, a TMSPMA-patterned substrate having a sacrificial layer made of a calcium alginate thin film was obtained. In the same manner as in Example 1, a polyacrylamide gel film was fabricated on the TMSPMA-patterned substrate having the sacrificial layer. A hydrogel flow path structure was obtained in the non-adhesive region. By adhering tubes at both ends of the flow path in the same manner as in Example 1, the hydrogel fluid device of Example 2 was obtained. The hydrogel fluid device of Example 2 can change the liquid feeding direction by adding an EDTA aqueous solution as a dissolution stimulus at an arbitrary timing so as to have a final concentration of 10 mM.

[0166] Similar to Example 1, the cleaned glass substrate was chemically modified with TMSPMA. Similar to Example 1, a positive photoresist thin film was formed on the upper surface of the TMSPMA-modified substrate by spin coating. After the formation of the positive photoresist thin film, it was patterned by exposure and development. After patterning, an oxygen plasma etching and an acetone treatment were carried out to obtain a patterned TMSPMA substrate having a glass surface (non-adhesive region) in the shape of a partially branched strip with a width of 1 mm (storage portion). Using an inkjet printer, sodium alginate encapsulating a drug was printed so as to cover the reservoir formed in the above-described strip pattern. Similar to Example 1, a substrate on which a pattern of sodium alginate was formed was immersed in a calcium chloride solution. As a result, a TMSPMA-patterned substrate having a sacrificial layer made of a calcium alginate thin film was obtained. In the same manner as in Example 1, a polyacrylamide gel film was fabricated on the TMSPMA-patterned substrate having the sacrificial layer. A hydrogel flow channel structure was obtained in the non-adhesive region. By adhering tubes at both ends of the flow channel in the same manner as in Example 1, the hydrogel fluid device of Example 3 was obtained. In the hydrogel fluid device of Example 3, by adding an aqueous EDTA solution as a dissolution stimulus at an arbitrary timing so as to have a final concentration of 10 mM, the drug can be released from the reservoir to the hydrogel flow channel.

Industrial Applicability

[0167] The hydrogel fluid device and the method for manufacturing the hydrogel fluid device according to the present invention are useful as a cell culture device, a microreactor, and a sensing device that take advantage of the diffusive channel shape, and can be widely applied to fields such as pharmacology, tissue engineering, and chemical engineering.

Explanation of Symbols

[0168] 1a Adhesive region, 1b Non-adhesive region, 4 Flow channel, 10 Substrate, 11 Layer of adhesive functional groups, 15 Second pattern, 20 Layer of polymer material, 21 Layer of swollen polymer material, 25 Third pattern, 30 Sacrificial layer, 32 Protective layer, 38 First pattern, 40 Resist layer, 90 Inkjet printer, 100 Laminate, 200 Hydrogel fluid device

Claims

**Claim 1** A method for manufacturing a hydrogel fluid device, comprising a substrate and a layer of a polymer material constituting a hydrogel on the substrate, wherein the layer of the polymer material is provided on one surface of the substrate such that an adhesion region where the substrate and the layer of the polymer material adhere to each other and a non-adhesion region where the substrate and the layer of the polymer material do not adhere to each other are formed, by swelling the polymer material, separating the polymer material in the non-adhesion region from the substrate, forming a flow path at the interface between the substrate and the layer of the polymer material, and forming the polymer material into a hydrogel, before providing the layer of the polymer material, forming a first pattern of a sacrificial layer that can be dissolved by applying a solution stimulus on the one surface of the substrate, wherein the first pattern is formed in at least a part of the non-adhesion region, A method for manufacturing a hydrogel fluid device, wherein the polymer material is separated from the substrate by dissolving the first pattern only by a solvent stimulus, and a flow path is formed at the interface between the substrate and the layer of the polymer material. **Claim 2** A method for manufacturing a hydrogel fluid device, comprising a substrate and a layer of a polymer material constituting a hydrogel on the substrate, wherein the layer of the polymer material is provided on one surface of the substrate such that an adhesion region where the substrate and the layer of the polymer material adhere to each other and a non-adhesion region where the substrate and the layer of the polymer material do not adhere to each other are formed, by swelling the polymer material, separating the polymer material in the non-adhesion region from the substrate, forming a flow path at the interface between the substrate and the layer of the polymer material, and forming the polymer material into a hydrogel, before providing the layer of the polymer material, forming a first pattern of a sacrificial layer that can be dissolved by applying a solution stimulus on the one surface of the substrate, wherein the first pattern is formed in at least a part of the non-adhesion region, when providing the layer of the polymer material on the one surface of the substrate, forming a second pattern of an adhesive functional group on the one surface of the substrate, and applying a first composition containing a first polymerizable monomer having a functional group capable of forming a chemical bond with the adhesive functional group on the one surface, A method for manufacturing a hydrogel fluid device, wherein the first polymerizable monomer is polymerized and the first composition is gelled to obtain the first composition as the polymer material. Claim 3. A method for manufacturing a hydrogel fluid device, comprising a substrate and a layer of a polymer material constituting the hydrogel on the substrate, wherein: a layer of the polymer material is provided on one surface of the substrate such that an adhesion region where the substrate and the layer of the polymer material adhere to each other and a non-adhesion region where the substrate and the layer of the polymer material do not adhere to each other are formed; by swelling the polymer material, the polymer material in the non-adhesion region is separated from the substrate, a flow path is formed at the interface between the substrate and the layer of the polymer material, and the polymer material is formed into a hydrogel; before providing the layer of the polymer material, a first pattern of a sacrificial layer that becomes soluble by application of a solution stimulus is formed on the one surface of the substrate; the first pattern is formed in at least a part of the non-adhesion region; when providing the layer of the polymer material on the one surface of the substrate, a layer of a polymerization initiator is formed on the one surface of the substrate; a second composition containing a second polymerizable monomer capable of forming a chemical bond with the polymerization initiator is applied to one surface of the layer of the polymerization initiator; by polymerizing the second polymerizable monomer and gelling the second composition, an adhesion region is formed at a portion where the layer of the polymerization initiator and the second composition overlap, and the second composition is used as the polymer material, the method for manufacturing a hydrogel fluid device. Claim 4. A method for manufacturing a hydrogel fluid device, comprising a substrate and a layer of a polymer material constituting the hydrogel on the substrate, wherein: a layer of the polymer material is provided on one surface of the substrate such that an adhesion region where the substrate and the layer of the polymer material adhere to each other and a non-adhesion region where the substrate and the layer of the polymer material do not adhere to each other are formed; by swelling the polymer material, the polymer material in the non-adhesion region is separated from the substrate, a flow path is formed at the interface between the substrate and the layer of the polymer material, and the polymer material is formed into a hydrogel; before providing the layer of the polymer material, a first pattern of a sacrificial layer that becomes soluble by application of a solution stimulus is formed on the one surface of the substrate; the first pattern is formed in at least a part of the non-adhesion region; when providing the layer of the polymer material on the one surface of the substrate, a third pattern of a gel-entrapping polymer or an adhesive molecule is formed on the one surface of the substrate; A sheet material using the polymer material as a forming material is disposed on the one surface of the substrate on which the third pattern is formed. A method for manufacturing a hydrogel fluid device, which comprises bringing the sheet material into contact with the gel-entering polymer or the adhesive molecule. **Claim 5** The method for manufacturing a hydrogel fluid device according to any one of claims 1 to 4, wherein the sacrificial layer contains a drug. **Claim 6** A substrate, A layer of a polymer material constituting a hydrogel provided on one surface of the substrate, characterized by comprising: An adhesive region where the substrate and the polymer material layer are adhered to each other and a non-adhesive region where the substrate and the polymer material layer are not adhered to each other are formed at the interface between the substrate and the polymer material layer. In at least a part of the non-adhesive region, a sacrificial layer is provided between the substrate and the polymer material layer. The sacrificial layer is soluble only by solvent stimulation. A hydrogel fluid device capable of forming a flow path at the interface between the substrate and the polymer material layer by separating the polymer material from the substrate.

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