Fluid devices

Abstract

The present invention provides a fluid device that allows objects used in a fluid device to be positioned at predetermined locations within the fluid device in a desired manner. [Solution] The fluid device is a laminate formed by stacking and joining a plurality of substrates, comprising a laminate with a flow channel formed inside that includes one or more chambers, and one or more lids that can open and close one or more chambers. The laminate includes a first layer in which the chambers are provided, and a second layer laminated on the first layer, the second layer having a hole that penetrates in the stacking direction in a region facing the chambers, and the lid may have a portion that closes the hole when inserted into the hole.

Description

Technical Field

[0001] The present invention relates to a fluid device.

Background Art

[0002] In recent years, the development of fluid devices in which fine channels and chambers are formed in a substrate has been underway. Fluid devices can be used, for example, in inspection chips that analyze and measure samples by introducing a liquid sample and a reagent into a channel to cause a reaction, or in biomimetic systems (Microphysiological system: MPS) that construct an environment that mimics the function of organs and the state of diseases by culturing cells in a chamber.

[0003] For example, Patent Document 1 discloses a microfluidic device including a first circuit having one or more cell culture compartments and a second circuit having a filtration unit and a reabsorption unit, wherein the two circuits are connected to each other via the filtration unit and the reabsorption unit.

[0004] Patent Document 2 discloses a cell capture method having a cell capture step of using dielectrophoretic force as a driving force for manipulating cells and a step of capturing functional cells by interaction with a substrate or cells fixed to the substrate when manufacturing a plurality of types of cell culture carriers. A cell fixing device having a channel having a cell capture space and a capture mechanism for inducing and capturing cells in a cell adhesion region in the space is also disclosed.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] When culturing cells in a fluid device, it is necessary to place the culture medium in the appropriate location within the flow channels formed inside the fluid device, or to seed the cells. However, the flow channels inside a fluid device are closed spaces except for ports that communicate with the outside of the fluid device. Therefore, it is extremely difficult to place the culture medium (such as collagen) or cells in the desired location within the flow channels.

[0007] Patent Document 2 describes a method in which cells introduced into a channel are captured by dielectrophoretic force and adhered to a cell adhesion region. However, even if cells can be guided to the cell adhesion region using dielectrophoretic force, it is difficult to control the manner in which the cells adhere to that region (for example, the spacing between cells or the degree to which the cells are dispersed).

[0008] The present invention has been made in view of the above, and aims to provide a fluid device that can arrange an object used in a fluid device in a desired manner at a predetermined position within the fluid device. [Means for solving the problem]

[0009] To solve the above problems, one aspect of the present invention provides a fluid device comprising a laminate formed by stacking and joining a plurality of substrates, wherein a flow channel including one or more chambers is formed inside the laminate, and one or more lids that can open and close the one or more chambers.

[0010] In the fluid device described above, the laminate includes a first layer formed from one or more substrates and provided with one or more chambers, and a second layer formed from one or more substrates and laminated on the first layer, wherein one or more holes penetrating in the lamination direction are provided in a region facing the one or more chambers, and the one or more lids may have portions that close the one or more holes by being inserted into them.

[0011] In the fluid device described above, the first layer may be formed such that an introduction passage for introducing liquid into one or more chambers and an outlet passage for discharging liquid from the chambers are connected to the chambers from the side.

[0012] In the fluid device described above, the ends of the introduction passage and the outlet passage may be open on the surface through which one or more lids are opened and closed in the fluid device.

[0013] In the fluid device described above, a plurality of chambers and holes are provided, and the introduction passage and the outlet passage may be in communication with the plurality of chambers.

[0014] In the fluid device described above, the one or more chambers provided in the first layer are provided so as to penetrate the first layer in the stacking direction, and the laminate may further include a third layer located on the opposite side of the first layer from the second layer, having one or more through holes formed in a region facing the one or more chambers, and holding a membrane filter permeable to liquid in the one or more through holes, and a fourth layer formed of one or more substrates and located on the opposite side of the third layer from the first layer, having a flow path formed therein that communicates with the one or more chambers via the membrane filter.

[0015] In the fluid device described above, a plurality of chambers, holes, and through-holes are provided, and the flow path formed in the fourth layer may communicate with a plurality of chambers via the membrane filters held in the plurality of through-holes.

[0016] In the fluid device described above, the one or more chambers provided in the first layer are formed to penetrate the first layer in the stacking direction, and the laminate further includes a third layer located on the opposite side of the first layer from the second layer, with one or more through holes formed in a region facing the one or more chambers, and the one or more through holes holding a membrane filter permeable to liquid; a fourth layer formed of one or more substrates and located on the opposite side of the third layer from the first layer, with one or more second chambers formed to penetrate in the stacking direction, each communicating with the one or more chambers via the membrane filters held in the one or more through holes; and a fifth layer formed of one or more substrates and located on the opposite side of the fourth layer from the third layer, with one or more second holes provided in a region facing the one or more second chambers, penetrating in the stacking direction, and further comprising one or more lids that can open and close each of the one or more second chambers, and each lid having a portion that closes the one or more second holes by being inserted into the one or more second holes.

[0017] In the fluid device described above, the first layer may be formed to connect laterally to the chambers a first introduction passage for introducing liquid into one or more chambers and a first discharge passage for discharging liquid from the chambers, and the fourth layer may be formed to connect laterally to the second chambers a second introduction passage for introducing liquid into one or more second chambers and a second discharge passage for discharging liquid from the second chambers.

[0018] In the fluid device described above, the liquid inlets to the first and second inlet passages, and the liquid outlets from the first and second outlet passages, may both be open on the surface in the fluid device where one or more lids are opened and closed.

[0019] In the above fluid device, the third layer may have two substrates each having the one or more through holes formed therein, and the membrane filter may be sandwiched between the two substrates such that the membrane filter is exposed from the one or more through holes.

[0020] In the above fluid device, the one or more chambers may be chambers for cell culture, and an extracellular matrix may be disposed on the membrane filter.

[0021] In the above fluid device, the one or more lids may be formed of a member having oxygen permeability.

[0022] In the above fluid device, a portion that bulges from the bottom surface side to the top surface side is provided in a part of the flow path, and a through hole that communicates with the outside of the fluid device is formed in a part of the substrate region facing the top of the bulging portion, and the through hole may be blocked by a water-repellent filter.

[0023] At the peripheral portion of the water-repellent filter of the above fluid device, the upper and lower substrates of the water-repellent filter may be welded to the water-repellent filter.

[0024] In the above fluid device, the water-repellent filter may be a porous filter made of a fluororesin.

Advantages of the Invention

[0025] According to the present invention, since a lid capable of opening and closing the chamber is provided, an object used in the fluid device can be arranged in a desired manner at a predetermined position within the fluid device.

Brief Description of the Drawings

[0026] [Figure 1A] It is a top view of a fluid device according to a first embodiment. [Figure 1B] It is a cross-sectional view taken along line A-A of FIG. 1A. [Figure 2] It is a perspective view showing a lid of the fluid device shown in FIG. 1. [Figure 3A] This is a top view showing the first layer of the substrate. [Figure 3B] This is a top view showing the upper substrate of the second layer. [Figure 3C] This is a top view showing the lower substrate of the second layer. [Figure 4] This is a schematic diagram illustrating the method of using the fluid device according to the first embodiment. [Figure 5] This is a cross-sectional view of a fluid device according to modified example 1-1. [Figure 6] This is a cross-sectional view of a fluid device relating to modified example 1-2. [Figure 7] This is a cross-sectional view of a fluid device according to modified example 1-3. [Figure 8] This is a cross-sectional view of a fluid device according to modified example 1-4. [Figure 9A] This is a top view of the fluid device relating to Modification 1-5. [Figure 9B] Figure 9A is a cross-sectional view of BB. [Figure 10] This is a cross-sectional view showing a fluid device according to a second embodiment. [Figure 11A] Figure 10 is a top view showing the first layer of the fluid device. [Figure 11B] Figure 10 is a top view showing the third layer of the fluid device. [Figure 11C] Figure 10 is a top view showing the fourth layer of the fluid device. [Figure 12] This is a cross-sectional view of a fluid device according to modified example 2. [Figure 13] This is a perspective view showing a fluid device according to a third embodiment. [Figure 14A] Figure 13 is a top view showing the fluid device. [Figure 14B] Figure 14A is an enlarged partial cross-sectional view along the CC line. [Figure 14C] This is the bottom view of the fluid device shown in Figure 13. [Figure 15] This is a perspective view showing a fluid device with its lid open. [Figure 16] Figure 13 is an exploded perspective view of the fluid device shown. [Figure 17] Figure 13 is a schematic diagram of the shape of the flow channel formed inside the fluid device shown. [Figure 18] Figure 14A is an enlarged partial cross-sectional view along the DD line. [Modes for carrying out the invention]

[0027] The fluid device according to embodiments of the present invention will be described below with reference to the drawings. However, the present invention is not limited to the following embodiments. Furthermore, in each drawing, the same parts are denoted by the same reference numerals.

[0028] The fluid devices according to each embodiment of the present invention described below are laminates formed by stacking and joining a plurality of substrates, comprising a laminate with a flow channel formed inside that includes one or more chambers, and one or more lids that can open and close the one or more chambers. The chambers may be those used for cell culture.

[0029] The drawings referenced in the following description merely provide a schematic representation of the shape, size, and positional relationships to the extent necessary to understand the content of the present invention. That is, the present invention is not limited to the shapes, sizes, and positional relationships exemplified in each drawing. Furthermore, there may be differences in the dimensional relationships and proportions between drawings.

[0030] (First Embodiment) Figure 1A is a top view of a fluid device according to the first embodiment. Figure 1B is a cross-sectional view of AA in Figure 1A. As shown in Figures 1A and 1B, the fluid device 1 according to the first embodiment comprises a laminate formed by stacking and joining a plurality of substrates, and a lid 15. In the first embodiment, the laminate includes a first layer 11 and a second layer 13.

[0031] The first layer 11 is formed from one or more substrates, and the first layer 11 is provided with an opening 111 used as a chamber 11a. The second layer 13 is formed from one or more substrates, and a hole 13a is provided in the region of the second layer 13 facing the opening 111, penetrating in the stacking direction. The lid 15 has a portion (lid body 151) that closes the hole 13a when inserted into the hole 13a, and the chamber 11a can be opened and closed.

[0032] In the first embodiment, an example is described in which one chamber 11a and one lid 15 that can open and close it are provided, but multiple chambers and lids 15 may be provided.

[0033] Furthermore, the first layer 11 is formed to connect to the chamber 11a from the side, with an introduction passage 11b for introducing liquid into the chamber 11a and an outlet passage 11c for discharging liquid from the chamber 11a. The liquid inlet 11d to the introduction passage 11b and the liquid outlet 11e from the outlet passage 11c may be open on the surface in the fluid device 1 where the lid 15 is opened and closed.

[0034] Figure 2 is a perspective view showing the lid 15 of the fluid device 1. As shown in Figure 2, the lid 15 has a lid body 151 that is inserted into the hole 13a of the second layer 13, and a flange portion 152 connected to the lid body 151. Multiple through holes 154 are formed in the flange portion 152 for inserting bolts 153 that fasten the lid 15 to the second layer 13. In Figure 2, the lid body 151 and the flange portion 152 are shown as cylindrical, but their shapes are not limited to cylindrical. For example, the lid body 151 may be cylindrical to match the shape of the chamber 11a, and the flange portion 152 may be a polygonal prism such as a rectangular prism, or it may have a D-cut shape. Alternatively, the chamber 11a and the lid body 151 may have shapes other than cylindrical, such as an elliptical prism.

[0035] The material of the lid 15 is not particularly limited as long as it is a material that does not allow liquid to pass through. From the viewpoint of ease of molding and ease of handling, it is preferable to form the lid 15 with a resin material. Specifically, examples of materials include crystalline resins such as general-purpose resins (polypropylene; PP, polyvinyl chloride; PVC, etc.), engineering plastics (polyethylene terephthalate; PET, cycloolefin polymer; COP, cycloolefin copolymer; COC, etc.), super engineering plastics (polyphenylene sulfide; PPS, polyetheretherketone; PEEK, etc.), and amorphous resins such as general-purpose resins (acrylonitrile butadiene styrene copolymer synthetic resin; ABS, polymethacrylic; PMMA, etc.), engineering plastics (polycarbonate; PC, polyphenylene ether; PPE, etc.), super engineering plastics (polyethersulfone; PES, etc., polymethylpentene: PMP), etc. Since the end face of the lid body 151 comes into contact with the liquid flowing through the chamber 11a, it is preferable to form the lid body 151 from a material that does not cause the elution of resin components into the liquid or the adsorption of components contained in the liquid, such as cycloolefin polymer (COP).

[0036] Furthermore, from the standpoint of observing the inside of the chamber 11a, it is preferable to form the lid 15 from transparent glass or a transparent resin material. Alternatively, from the standpoint of respiration of cells cultured in the chamber 11a, the lid 15 may be formed from an oxygen-permeable material.

[0037] In the first embodiment, the first layer 11 of the fluid device 1 is formed from a single substrate 110. On the other hand, the second layer 13 is formed from two substrates 131 and 132. Figure 3A is a top view showing the substrate 110 of the first layer 11. Figure 3B is a top view showing the upper substrate 131 of the second layer 13. Figure 3C is a top view showing the lower substrate 132 of the second layer 13.

[0038] As shown in Figure 3A, the substrate 110 has a bottomed opening 111 used as a chamber 11a, as well as a groove 112 used as an introduction passage 11b and a groove 113 used as an outlet passage 11c. The connection area between groove 112 and opening 111 (i.e., the connection area between introduction passage 11b and chamber 11a) 114, and the connection area between groove 113 and opening 111 (i.e., the connection area between outlet passage 11c and chamber 11a) 115 may be formed so that the width gradually widens from grooves 112 and 113 toward opening 111. This makes the flow of liquid through chamber 11a smoother and suppresses the generation of vortices and other issues.

[0039] As shown in Figure 3B, the substrate 131 has a through hole 133 with a diameter approximately equal to that of the opening 111, and a countersunk portion 134 cut out with a diameter larger than that of the through hole 133. The through hole 133, together with the through hole 139 of the substrate 132 (described later), constitutes a hole 13a that penetrates the second layer 13 in the stacking direction. The countersunk portion 134 is a region for fitting the flange portion 152 of the lid 15. The countersunk portion 134 has a plurality of screw holes 137 for screwing in bolts 153 and a groove 138 for fitting an O-ring 150. Furthermore, the substrate 131 has a through hole 135 that communicates with the groove 112 of the substrate 110, and a through hole 136 that communicates with the groove 113.

[0040] As shown in Figure 3C, the substrate 132 has a through hole 139 with a diameter approximately equal to the opening 111 of the substrate 110, a through hole 140 communicating with the groove 112 of the substrate 110, and a through hole 141 communicating with the groove 113. As will be described later, the substrate 132 is provided for joining the substrate 110 of the first layer 11 and the substrate 132 of the second layer 13 by laser welding. Therefore, when joining the substrate 110 and the substrate 132 using adhesive or the like, or when directly joining the substrate 110 and the substrate 132 by heat welding or ultrasonic welding, it is not essential to provide the substrate 132.

[0041] Next, we will describe the materials of the substrates 110, 131, and 132 that form the fluid device. In the first embodiment, substrates 110 and 131 are formed from a thermoplastic resin material that is transparent to laser light. On the other hand, substrate 132 is formed from a thermoplastic resin material that is absorptive to laser light. Hereinafter, a substrate formed from a thermoplastic resin material that is transparent to laser light will also be referred to as a transparent substrate, and a substrate formed from a thermoplastic resin material that is absorptive to laser light will also be referred to as a colored substrate. However, in this specification, the terms transparent substrate and colored substrate are used according to their properties with respect to laser light, and for example, a transparent substrate is not necessarily completely transparent to the naked eye. Also, a colored substrate may be semi-transparent or otherwise have some light transmittance to the naked eye.

[0042] When transparent substrates 110 and 131 are joined by laser welding via a colored substrate 132, the colored substrate and the transparent substrate may be made of the same type of resin material, or they may be made of different types of resin materials, provided that laser welding is possible.

[0043] Examples of materials that can be used as transparent and colored substrates include general-purpose crystalline resins (polypropylene; PP, polyvinyl chloride; PVC, etc.), engineering plastics (polyethylene terephthalate; PET, cycloolefin polymer; COP, cycloolefin copolymer; COC, etc.), super engineering plastics (polyphenylene sulfide; PPS, polyetheretherketone; PEEK, etc.), and general-purpose amorphous resins (acrylonitrile butadiene styrene copolymer; ABS, polymethacrylic; PMMA, etc.), engineering plastics (polycarbonate; PC, polyphenylene ether; PPE, etc.), super engineering plastics (polyethersulfone; PES, etc., polymethylpentene: PMP), etc.).

[0044] As described above, the colored substrate is formed from a resin material that absorbs laser light, and the transparent substrate is formed from a resin material that transmits laser light. Therefore, the absorption rate of the colored substrate to the laser light is higher than that of the transparent substrate. The wavelength range of the laser light that can be used in the manufacturing process of fluid devices is not particularly limited, but from the viewpoint of versatility and cost, laser light in the visible light range to the infrared light range can be used. A specific example is laser light with a wavelength of about 800 nm to 1100 nm. It is preferable that the transparent substrate has a transmittance of about 20% or more to such laser light. The thickness of the transparent substrate can be determined so that the laser light that has passed through the transparent substrate can sufficiently reach the colored substrate, depending on the structure of the flow channel including the chamber 11a, the introduction channel 11b, and the outlet channel 11c, as well as the type of resin material and additives.

[0045] On the other hand, the colored substrate can be formed from a material colored by adding carbon black or other pigments to the same type of resin as the transparent substrate, or to a resin that can be laser-welded to the transparent substrate.

[0046] Next, we will describe the manufacturing method of the fluid device 1. First, the components of the substrates 110, 131, 132 and the lid 15 are manufactured by injection molding, cutting, or other methods.

[0047] Next, substrates 110, 132, and 131 are stacked with a colored substrate 132 sandwiched in between, and a laser beam is shone onto the area where substrate 132 is in contact with both the upper and lower substrates 110 and 131. As a result, the colored substrate 132 absorbs the laser beam, generates heat, and melts. This heat is also transferred to the interface between the upper and lower substrates 110 and 131, melting the substrates 110 and 131 near the interface. The area irradiated with the laser beam then hardens, and the stacked substrates 110, 132, and 131 are joined together. When irradiating with the laser, a jig or the like may be used to press and adhere the stacked substrates together. The laser irradiation may be performed from either the substrate 110 side or the substrate 131 side.

[0048] Next, the O-ring 150 is fitted into the groove 138 of the substrate 131, the lid 15 (lid body 151) is inserted into the hole 13a, and the lid 15 is fastened to the substrate 131 with bolts 153. This completes the fluid device 1.

[0049] Figure 4 is a schematic diagram illustrating how to use the fluid device 1. The fluid device 1 can be used, for example, as follows: First, with the lid 15 open, a cell culture scaffold 101 is placed on the bottom surface of the chamber 11a, and cells 102 are seeded on it at desired intervals. After confirming that the cells have taken root, the lid 15 is closed and fastened with bolts 153, a tube for supplying liquid such as culture medium is connected to the liquid inlet 11d, and a tube for discharging liquid is connected to the liquid outlet 11e, and the liquid is circulated. The lid 15 can be opened and closed at any time, even while the liquid is circulating.

[0050] As described above, according to the first embodiment, since the fluid device 1 is provided with a lid 15 that can open and close the chamber 11a, by opening the lid 15, it becomes possible to place objects used in the fluid device 1 in a predetermined position (inside the chamber 11a) in a desired manner. Furthermore, it becomes possible to collect cells being cultured at any time.

[0051] Furthermore, according to the first embodiment, a hole 13a is provided in the second layer 13, and the hole 13a is closed by inserting the lid body 151. Therefore, even if the lid 15 is opened while there is liquid in the flow path inside the fluid device 1, the liquid will not spill out of the fluid device 1. Consequently, the lid 15 can be opened and closed at any time, even while the fluid device 1 is in use. This makes it possible, for example, to collect cultured cells at any time.

[0052] Furthermore, according to the first embodiment, the inlet passage 11b and outlet passage 11c are connected to the chamber 11a from the side, and the connection area is formed so that its width gradually widens toward the chamber 11a, thereby allowing the liquid to flow smoothly toward the chamber 11a.

[0053] (Extreme variation 1-1) Figure 5 is a cross-sectional view of a fluid device according to modified example 1-1. As shown in Figure 5, the lid body 155 of the lid 15A may be inserted into the hole 161 of the second layer 13A, and the flange 156 may be placed on the upper surface of the second layer 13A. In this case, it is not necessary to form a dish portion (see dish portion 134 in Figure 1B) in the second layer 13A, so the manufacturing process of the second layer 13A can be simplified.

[0054] (Variations 1-2) Figure 6 is a cross-sectional view of a fluid device according to modified example 1-2. As shown in Figure 6, the diameter of the lid body 157 of the lid 15B and the hole 162 of the second layer 13B into which it is inserted may be larger than the diameter of the chamber 11a. In this case, when the lid 15B is opened, the connection between the inlet passage 11b and the chamber 11a, and the connection between the outlet passage 11c and the chamber 11a can also be exposed, making it possible to take measures against any objects accumulating in these connection points.

[0055] (Variations 1-3) Figure 7 is a cross-sectional view of a fluid device according to modified example 1-3. As shown in Figure 7, the diameter of the lid body 158 of the lid 15C and the hole 163 of the second layer 13C into which it is inserted may be smaller than the diameter of the chamber 11a. In this case, the area of ​​the chamber 11a exposed when the lid 15C is open can be reduced, thereby suppressing the impact on the inside of the chamber 11a due to the opening and closing of the lid 15C.

[0056] (Variations 1-4) Figure 8 is a cross-sectional view of a fluid device according to modified example 1-4. The fluid device 2 shown in Figure 8 comprises a first layer 17 formed from a plurality of substrates, a second layer 13 laminated on the first layer 17, and a lid 15. The configuration of the second layer 13 and the lid 15 is the same as in the first embodiment.

[0057] The first layer 17 includes substrates 171, 173, and 175 formed from transparent substrates, and substrates 172 and 174 formed from colored substrates. In the first layer 17, the substrates 171, 172, 173, 174, and 175 are stacked in an alternating order between transparent substrates and colored substrates.

[0058] The bottommost substrate 171 is provided with a bottomed opening 176 used as a chamber 17a, and the upper substrates 172, 173, 174, and 175 are provided with through holes 177, 178, 189, and 180. These openings 176 and through holes 177-180 form a chamber 117a. In addition, the substrate 173 located in the center of the first layer 17 has a groove 181 used as a liquid introduction passage 17b to the chamber 17a and a groove 182 used as a liquid discharge passage 17c from the chamber 17a. Furthermore, the substrates 174 and 175, which are above substrate 173, have through holes 183 and 184 communicating with groove 181 and through holes 185 and 186 communicating with groove 182.

[0059] In these modified examples 1-4, the substrates 172, 174, and 132 are colored substrates made of a resin material that has both absorption and a certain degree of transmittance to laser light. More specifically, for substrates 172, 174, and 132, a resin material with a laser light transmittance of, for example, 50% or less (absorption rate of 50% or more) is preferably used. On the other hand, for substrates 171, 173, 175, and 131, a highly transparent resin material that hardly absorbs laser light is preferably used. In the fluid device 2, such transparent substrates and colored substrates are alternately laminated.

[0060] In this case, a laminate formed by alternately stacking transparent substrates 171, 173, 175, and 131 with colored substrates 172, 174, and 132 can be welded together with a single laser irradiation. This is because a portion of the laser light irradiated onto the upper substrate is absorbed by that substrate, generating heat, but the remaining laser light passes through that substrate and reaches the lower substrate.

[0061] As a specific example, a combination of a transparent COP (cycloolefin polymer) plate or sheet material can be used as a transparent substrate (substrates 171, 173, 175, 131), and a translucent black COP sheet can be used as a colored substrate (substrates 172, 174, 132). The thickness of the transparent substrate is not particularly limited; for example, a transparent COP sheet with a thickness of about 0.1 mm to 0.2 mm or a transparent COP plate material with a thickness of several mm can be used. On the other hand, the thickness of the translucent black COP sheet is preferably about 0.01 mm to 0.2 mm, and more preferably about 0.02 mm to 0.1 mm. By setting the thickness of the black COP sheet within this range, when irradiated with laser light, the black COP sheet absorbs the laser light and generates sufficient heat, welding to the transparent substrates above and below it, while also allowing the laser light to pass through and reach the lower black COP sheet. Of course, the thickness of the transparent substrate and the substrate is not limited to these, and can be appropriately set according to the structure of the fluid device, taking into consideration the resin material used as the transparent substrate and the transparency to laser light.

[0062] As shown in this modified example 1-4, by forming the first layer 17 with a plurality of substrates 171-175, the inlet path 17b and outlet path 17c can be connected to the chamber 17a at a desired height, thereby increasing the degree of freedom in flow path design.

[0063] Furthermore, by using a resin material as the colored substrate that has both laser light absorption and a certain degree of laser light transmission, it becomes possible to weld a laminate containing two or more colored substrates with a single laser irradiation.

[0064] (Variations 1-5) Figure 9A is a cross-sectional view of a fluid device according to modified example 1-5. Figure 9B is a cross-sectional view of BB in Figure 9A. The fluid device 3 shown in Figures 9A and 9B has two chambers. Specifically, the fluid device 3 comprises a first layer 19 with two openings 191 and 192 used as chambers 19a and 19b, a second layer 20 stacked on the first layer 19 and having two holes 20a and 20b that penetrate in the stacking direction in two regions facing the openings 191 and 192, and lids 21a and 21b that can open and close the chambers 19a and 19b, respectively. The configuration of each of the lids 21a and 21b is the same as the configuration of the lid 15 described in the first embodiment.

[0065] The first layer 19 has an introduction channel 19c for introducing liquid into chamber 19a, a flow path 19d connecting chamber 19a and chamber 19b, and an outlet channel 19e for discharging liquid from chamber 19b. In other words, the liquid introduction channel 19a and outlet channel 19e are in communication with the two chambers 19a and 19b, and by introducing liquid such as culture medium into the introduction channel 19a, the liquid can be sequentially perfused into chambers 19a and 19b.

[0066] According to these modifications 1-5, by providing two interconnected chambers 19a and 19b within a single fluid device 3, it becomes possible to co-culture cells. Furthermore, according to these modifications, by providing lids 21a and 21b that can be opened and closed for each of the two chambers 19a and 19b, it becomes possible to place cells in each chamber 19a and 19b in a desired manner at a desired timing, or to perform necessary treatments.

[0067] In this modified example 1-5, an example in which two chambers 19a and 19b are provided was described, but the number of chambers may be three or more.

[0068] (Extreme Variations 1-6) In the first embodiment, the lid 15 is fastened to the second layer 13 by bolts 153, but the method of fixing the bolts 153 is not limited to this. For example, a structure in which the lid 15 is fitted and locked to the second layer 13 by locking claws (a so-called claw locking structure) may be used. Also, in the first embodiment, the lid 15 is made removable from the second layer 13, but for example, a hinge may be used so that a part of the lid 15 is connected to the second layer 13 even when it is open.

[0069] (Second embodiment) Figure 10 is a cross-sectional view showing a fluid device according to a second embodiment. As shown in Figure 10, the fluid device 4 according to the second embodiment comprises a laminate formed by stacking and joining a plurality of substrates, and a lid 15. In the fluid device 4, the laminate includes a first layer 41, a second layer 42, a third layer 43, and a fourth layer 44. Figure 11A is a top view showing the first layer 41. Figure 11B is a top view showing the third layer 43. Figure 11C is a top view showing the fourth layer 44.

[0070] The first layer 41 is formed from one or more substrates. In the second embodiment, an example is described in which the first layer 41 is formed from one substrate 410, but the first layer 41 may be formed from multiple substrates. As shown in Figures 10 and 11A, the first layer 41 is provided with an opening 411 used as a chamber 41a, which penetrates the first layer 41 in the stacking direction. The substrate 410 also has through holes 412 and 413 that communicate with the flow path 44a, which will be described later. In the second embodiment, the substrate 410 is made of a transparent substrate so that the fluid device 4 is joined by laser welding.

[0071] The second layer 42 is formed from one or more substrates, and a hole 13a is provided in the region of the second layer 42 facing the opening 411, extending through in the stacking direction. The lid 15 has a portion (lid body 151) that closes the hole 13a when inserted into it, and the chamber 41a can be opened and closed. The configuration of the second layer 13 and the lid 15 is the same as that described in the first embodiment.

[0072] The third layer 43 is located on the opposite side of the first layer 41 from the second layer 13. Through holes are formed in the region of the third layer 43 facing the chamber 41a, and a membrane filter 435 that is permeable to liquid is held in these through holes. More specifically, as shown in Figure 11B, the third layer 43 includes two substrates 431 and 432, each having through holes 433 and 434 formed in the region facing the opening 411, and the membrane filter 435 is sandwiched between the two substrates 431 and 432 such that a portion of it is exposed through the through holes 433 and 434. More specifically, a filter holding substrate 437 is placed between the substrates 431 and 432, with a through hole 436 formed therein that matches the outer circumference of the membrane filter, and the membrane filter 435 is fitted into this through hole 436. Furthermore, through holes 438 and 439 that communicate with the flow path 44a, which will be described later, are formed in the two substrates 431 and 432 and the filter holding substrate 437. In the second embodiment, since the fluid device 4 is joined by laser welding, the substrates 431 and 432 are formed from colored substrates made of a resin material that has both absorption and a certain degree of transparency to laser light. On the other hand, the filter holding substrate 437, which is sandwiched between the substrates 431 and 432, is formed from a transparent substrate.

[0073] The membrane filter 435 is a porous material made of, for example, resin or protein, and is used as a scaffold for cell culture. As the membrane filter 435, for example, the Vitrigel® membrane "ad-MED Vitrigel® 2" sold by Kanto Chemical Co., Ltd. can be used. The Vitrigel® membrane sold by the company has a mesh-like structure in which collagen fibers are intertwined and acts as an extracellular matrix that serves as a scaffold for cultured cells. Of course, it is also possible to use materials other than the Vitrigel® membrane as the membrane filter 435. For example, a mesh material made of resin fibers may be used as the membrane filter 435. In addition, an extracellular matrix may be placed on at least the opening 411 side of the membrane filter 435. Specifically, for example, liquid or gel-like collagen may be applied to the opening 411 side of the membrane filter 435.

[0074] The fourth layer 44 is formed from one or more substrates. In the second embodiment, an example is described in which the fourth layer 44 is formed from one substrate 440, but the fourth layer 44 may be formed from multiple substrates. The fourth layer 44 is located on the opposite side of the first layer 41 of the third layer 43. As shown in Figure 11C, the fourth layer 44 has a flow channel 44a that communicates with the opening 411 of the first layer via a membrane filter 435 held in through holes 433, 434. In the second embodiment, the substrate 440 is formed from a transparent substrate.

[0075] As shown in Figure 11C, the flow path 44a is composed of grooves 441, 442, and 443. The central groove 442 has a width approximately the same as the diameter of the through holes 433, 434 and the opening 411. This allows for the exchange of liquid between the flow path 44a and the chamber 41a via the membrane filter 435 located in the through holes 433 and 434.

[0076] One end 445 of groove 441, connected to the central groove 442, communicates with through holes 438, 412, 140, and 135 formed in the upper substrate, while the other end 446 of groove 443 communicates with through holes 439, 413, 141, and 136 formed in the upper substrate. Therefore, by connecting liquid supply tubes to the liquid inlet 44b and liquid outlet 44c provided on the upper surface of the second layer 13 on which the lid 15 is placed, liquid can be circulated through the flow path 44a.

[0077] In the second embodiment, an example is described in which there is one opening 411 used as the chamber 41a, one hole 13a, and one lid 15, but there may be multiple of each.

[0078] Such a fluid device 4 can be manufactured by laser welding in the same manner as in the above-described modifications 1-4. Specifically, substrates 131, 410, 440 and a filter holding substrate 437 are manufactured from a transparent substrate, while substrates 132 and 431, 432 are manufactured from a colored substrate made of a resin material that has both absorption and a certain degree of transparency to laser light. Then, substrates 440, substrate 432, a filter holding substrate 437 holding a membrane filter 435, substrate 431, substrate 410, substrate 132, and substrate 131 are stacked in this order so that the transparent substrate and the colored substrate alternate, and laser light is irradiated onto this stack of substrates. This allows the stack of substrates to be joined by laser welding. When irradiating with laser light, it is preferable to scan the laser light while avoiding the area of ​​aperture 411. This prevents thermal deterioration of the membrane filter 435. Next, the O-ring 150 is fitted into the groove 138 of the substrate 131, the lid 15 (lid body 151) is inserted into the hole 13a (through hole 133, 139), and the lid 15 is fastened to the substrate 131 with bolts 153. This completes the fluid device 4.

[0079] As described above, according to the second embodiment, a fluid device 4 in which the membrane filter 435 is pre-placed inside can be easily manufactured.

[0080] Furthermore, according to the second embodiment, by using a transparent substrate and a colored substrate made of a resin material that absorbs laser light but also transmits laser light to a certain extent, layers made up of multiple substrates can be joined by a single laser welding.

[0081] Furthermore, when joining the substrates constituting the fluid device 4 by thermal welding or ultrasonic welding, it is preferable to apply collagen to the membrane filter 435 after joining to arrange the extracellular matrix, etc., in order to suppress the effects of heat during welding.

[0082] Furthermore, in the second embodiment, the membrane filter 435 is placed in the through-hole of the filter holding substrate 437, and the membrane filter 435 together with the filter holding substrate 437 is sandwiched between the substrates 431 and 432. However, the membrane filter 435 may be directly sandwiched between the substrates 431 and 432 without using the filter holding substrate 437.

[0083] (Modification 2) Figure 12 is a cross-sectional view of the fluid device according to Modification 2. The top view of the fluid device according to Modification 2 is the same as that of Figure 9A. The fluid device 5 shown in Figure 12 has two chambers. Specifically, the fluid device 5 comprises a first layer 45 through which two openings 451 and 452, used as chambers 45a and 45b, pass; a second layer 20 stacked on the first layer 45, with two holes 20a and 20b that penetrate in the stacking direction in two regions facing the openings 451 and 452; lids 21a and 21b that can open and close the chambers 45a and 45b, respectively; and a third layer 46 and a fourth layer 47 located on the opposite side of the first layer 45 from the second layer 20. The configuration of each of the lids 21a and 21b is the same as the configuration of the lid 15 described in the first embodiment.

[0084] The third layer 46 includes two substrates 461 and 462, and through holes 463 and 464 are formed in two regions of each substrate 461 and 462 corresponding to chambers 45a and 45b. A filter holding substrate 465 is positioned between the two substrates 461 and 462. Two through holes 466 and 467 are formed in two regions of the filter holding substrate 465 corresponding to chambers 45a and 45b, and two membrane filters 468 and 469 are fitted into these through holes 466 and 467, respectively. As a result, the two membrane filters 468 and 469 are sandwiched between substrates 461 and 462 such that a portion of them is exposed through the through holes 463 and 464 of the substrates 461 and 462.

[0085] In the fourth layer 47, a channel 47a is formed that communicates with two openings 451 and 452 formed in the first layer through through holes 463 and 464 in the substrates 461 and 462. In the channel 47a, similar to the channel 44a shown in Figure 11C, the width of the region of the channel 47a facing the openings 451 and 452 may be approximately the same width as the openings 451 and 452.

[0086] According to this modified example 2, by providing two chambers 45a and 45b that communicate with each other via a channel 47a within a single fluid device 5, it becomes possible to co-culture cells. Furthermore, according to this modified example 2, by providing lids 21a and 21b that can be opened and closed for the two chambers 45a and 45b, it becomes possible to place cells in each chamber 45a and 45b in a desired manner at a desired timing.

[0087] In this modified example 2, an example in which two chambers 45a and 45b are provided was described, but the number of chambers may be three or more.

[0088] (Third embodiment) Figure 13 is a perspective view showing a fluid device according to a third embodiment. Figure 14A is a top view showing the same fluid device. Figure 14B is an enlarged partial cross-sectional view along the CC line shown in Figure 14A. Figure 14C is a bottom view showing the same fluid device. Figure 15 is a perspective view showing the fluid device with the lid open. Figure 16 is an exploded perspective view of the same fluid device. Figure 17 is a schematic diagram of the shape of the flow channels formed inside the fluid device. Figure 18 is an enlarged partial cross-sectional view along the DD line shown in Figure 14A.

[0089] As shown in Figures 13 to 16, the fluid device 6 according to the third embodiment comprises a laminate formed by stacking and joining multiple substrates, and lids 66 and 67. In the fluid device 6, the laminate includes a first layer 61, a second layer 62, a third layer 63, a fourth layer 64, and a fifth layer 65. Each layer is formed from one or more substrates.

[0090] The first layer 61 is formed such that a chamber 61a penetrates it in the stacking direction. More specifically, in the third embodiment, the first layer 61 is formed of two substrates 611 and 612, and openings 613 and 614 are provided in these substrates 611 and 612 that penetrate in the stacking direction. A portion of these openings 613 and 614 (the region facing the membrane filter 635, which will be described later) is used as the chamber 61a, and the regions on both sides are used as the liquid introduction passage 711 and the liquid outlet passage 712 to the chamber 61a (see Figure 17). By providing such openings 613 and 614, the introduction passage 711 and the outlet passage 712 can be connected to the chamber 61a from the side.

[0091] The second layer 62 is formed by three substrates 621, 622, and 623. A hole 624 is provided in the region of substrate 621 facing the chamber 61a, extending through in the stacking direction.

[0092] The lid 66 allows the chamber 61a to be opened and closed, and has a portion (lid body 661) that closes the hole 624 when inserted into the hole 624, and a flange portion 662. In the second layer 62, the substrates 622 and 623 laminated on the substrate 621 are provided with openings 625 and 626 into which the flange portion 662 can be inserted. The substrate 621 also has a groove 627 formed therein for fitting an O-ring 682. The lid 66 is structured to be fastened with bolts 683.

[0093] The third layer 63 is located on the opposite side of the first layer 61 from the second layer 62. Through-holes are formed in the region of the third layer 63 facing the chamber 61a, and a membrane filter 635 that is permeable to liquid is held in these through-holes. The membrane filter 635 is a porous material used as a scaffold for cell culture, similar to the membrane filter 435 in the second embodiment. The membrane filter 635 may have a mesh-like structure in which collagen fibers are intertwined, such as a Vitrigel® membrane. Extracellular matrix such as collagen may also be arranged on both sides of the membrane filter 635. The membrane filter 635 may be held by a holding member 684 such as a resin substrate.

[0094] More specifically, the third layer 63 includes two substrates 631 and 632, each having through holes 633 and 634 formed in the region facing the chamber 61a, and the membrane filter 635 is sandwiched between the two substrates 631 and 632 so as to be exposed through the through holes 633 and 634. More specifically, a filter holding substrate 637 is positioned between the substrates 631 and 632, with a through hole 636 formed therein that matches the outer circumference of the holding member 684 of the membrane filter 635, and the holding member 684 of the membrane filter 635 is fitted into this through hole 636.

[0095] The fourth layer 64 is located on the opposite side of the third layer 63 from the first layer 61. The fourth layer 64 has a chamber (second chamber) 64a that penetrates in the stacking direction and communicates with the chamber 61a of the first layer 61 via a membrane filter 635 held in through holes 633, 634 of the third layer 63. Specifically, in the third embodiment, the fourth layer 64 is formed from two substrates 641, 642, and these substrates 641, 642 have openings 643, 644 that penetrate in the stacking direction. A portion of these openings 643, 644 (the region facing the membrane filter 635) is used as the chamber 64a, and the regions on both sides are used as the liquid introduction passage 721 and the liquid outlet passage 722 to the chamber 64a. By providing such openings 643, 644, the introduction passage 721 and the outlet passage 722 can be connected to the chamber 64a from the side.

[0096] The fifth layer 65 is located on the opposite side of the fourth layer 64 from the third layer 63. In the third embodiment, the fifth layer 65 is formed from three substrates 651, 652, and 653. In the fourth layer 64, a hole (second hole) 654 is provided in the region facing the chamber 64a, penetrating in the stacking direction.

[0097] The lid 67 allows the chamber 64a to be opened and closed and has a portion (lid body 671) that closes the hole 654 when inserted into the hole 654 and a flange portion 672. In the fifth layer 65, the substrates 652 and 653 laminated on the substrate 651 are provided with openings 655 and 656 into which the flange portion 672 can be inserted. The substrate 651 also has a groove 657 formed therein for fitting an O-ring 682. The lid 67 is structured to be fastened with bolts 683.

[0098] In the third embodiment, an example is described in which one chamber 61a and one lid 66 that can open and close the chamber 61a, and one second chamber 64a communicating with the chamber 61a and one lid 67 that can open and close the second chamber 64a are provided, but multiple of these may be provided.

[0099] Furthermore, through holes 681 for alignment may be formed in all substrates forming the fluid device 6. In addition, a channel for de-aeration may be provided in the fluid device 6. The configuration of the channel for de-aeration will be described later.

[0100] As shown in Figures 14A and 16, in the third embodiment, the fluid device 6 is formed by alternately stacked transparent substrates and colored substrates. The colored substrate is made of a resin material that absorbs laser light while also being somewhat transparent to laser light. Specifically, substrates 623, 621, 611, filter holding substrate 637, and substrates 641, 651, 653 are formed of transparent substrates, while substrates 622, 612, 631, 632, 642, 652 are formed of colored substrates. As for the lids 66 and 67, from the viewpoint of observing cells cultured in chambers 61a and 64a, they may be made of transparent glass or transparent resin material, and from the viewpoint of cell respiration, they may be made of an oxygen-permeable material.

[0101] Such a fluid device 6 can be manufactured by laser welding in the same manner as in the modified example 1-4. That is, as shown in Figure 16, openings and grooves are formed on each substrate, which is made of a transparent substrate or a colored substrate, and these are stacked together. By irradiating the stack of these substrates with laser light, the stack is joined by laser welding. It is preferable to pre-hold the membrane filter 635 in the filter holding substrate 637 and to scan the laser light while avoiding the area of ​​the membrane filter 635 when irradiating with laser light.

[0102] As shown in Figure 17, the fluid device 6 has two channels 71 and 72 formed three-dimensionally. Of these, channel 71 includes chamber 61a, and channel 72 includes chamber 64a. Channels 71 and 72 are in communication via a membrane filter 635 in the regions of chambers 61a and 64a. Furthermore, the liquid inlets 713 and 723 to channels 71 and 72, and the liquid outlets 714 and 724 from channels 71 and 72, are all open on the upper surface of the fluid device 6 (the opening surface 62a of the lid 66 on the second layer 62 side). By opening all ends of channels 71 and 72 on the upper surface of the fluid device 6 in this way, a perfusion-type cell culture system with two layers of channels can be constructed.

[0103] In the third embodiment, the widths of the inlet passages 711, 721 and outlet passages 712, 722 are the same as the widths of the chambers 61a, 64a. This allows for smoother liquid flow in the vicinity of the chambers 61a, 64a. However, these widths do not necessarily have to be the same; for example, as in the first embodiment (see Figure 1A), the widths of the chambers 61a, 64a may be wider than the inlet passages 711, 721 and outlet passages 712, 722. In this case, the area in the chambers 61a, 64a where cell culture is possible can be increased.

[0104] As shown in Figures 17 and 18, the channels 71 and 72 descend from the liquid inlets 713 and 723 to the bottom (the fifth layer 65, which is the lowest layer). Downstream from there, and upstream of the chambers 61a and 64a, there is a portion that rises to the top (the second layer 62, which is the uppermost layer). This portion that rises from the bottom to the top is the de-aeration channels 715 and 725. As shown in Figure 18, the opening 731 formed in the substrate 622 is the top of the de-aeration channels 715 and 725, and a through hole 732 that communicates with the outside of the fluid device 6 is formed in a part of the area of ​​the substrate 623 that faces this top. This through hole 732 is blocked by a water-repellent filter 73. In detail, a water-repellent filter 72 that is larger than the opening 731 is sandwiched between the substrate 622 and the substrate 623 so as to block the opening 731 and the through hole 732.

[0105] The water-repellent filter 73 is a porous filter made of fluororesin, and is formed from a sheet material made of, for example, polytetrafluoroethylene (PTFE). A porous filter made of fluororesin has both permeability and water repellency, and has the characteristic of allowing gases to pass through but not liquids. Therefore, the liquid flowing through the channels 71 and 72 is pushed upward in the de-aeration channels 715 and 725, and the liquid comes into contact with the water-repellent filter 73 at the top, pressing against it. As a result, the gas contained in the liquid passes through the water-repellent filter 73 and is discharged outside the fluid device 6 from the de-aeration holes 733. This makes it possible to suppress the generation of bubbles in the liquid flowing through the channels 71 and 72.

[0106] At the periphery of the water-repellent filter 73, that is, around the opening 731, the upper and lower substrates 622 and 623 of the water-repellent filter 73 are welded to the water-repellent filter 73. This makes it possible to keep the periphery of the water-repellent filter 73 watertight and prevent leakage of the liquid flowing through the bubble-removing channels 715 and 725 from around the water-repellent filter 73.

[0107] It is generally known that fluororesin-based filters, including the resin itself, are difficult to bond to other materials. For example, fluororesin-based filters are easily detached from adhesives, making it difficult to attach a water-repellent filter to the substrate 623 using adhesive. While mechanically bonding the water-repellent filter to the substrate is also conceivable, this would lead to problems with liquid leakage through gaps. For these reasons, conventionally, it has been practically impossible to apply fluororesin-based filters to de-aeration channels.

[0108] Therefore, in the third embodiment, the water-repellent filter 73 is joined to the substrates 622 and 623 by laser welding. In general, it is difficult to join different types of resin materials by welding. However, because the water-repellent filter 73 is porous, when the substrates 622 and 623 that sandwich the water-repellent filter 73 are melted by laser irradiation, the resin material of the substrates 622 and 623 penetrates into the fine pores of the water-repellent filter 73 and hardens, which acts as an anchoring effect, allowing the water-repellent filter 73 and the substrates 622 and 623 to adhere firmly.

[0109] The water-repellent filter 73 may be black, which has some absorption of laser light, or it may be white, or a color that does not have much absorption of laser light. When fabricating the fluid device 6, the water-repellent filter 73 can be sandwiched between substrates 622 and 623 in a laminate in which transparent substrates and colored substrates are alternately stacked, and the laminate can be welded by irradiating it with laser light.

[0110] As described above, substrate 623 is formed from a transparent substrate, and substrate 622 is formed from a colored substrate. Therefore, when the water-repellent filter 73 is white, the laser light irradiated onto the periphery of the water-repellent filter 73 (around the opening 731) heats up and melts substrate 622, and this heat is conducted to the water-repellent filter 73 and substrate 623, causing substrate 623 to melt as well. On the other hand, when the water-repellent filter 73 is black, the substrate 622 heats up and melts at the periphery of the water-repellent filter 73, and the water-repellent filter 73 itself also heats up, causing substrate 623 to melt due to the heat. In either case, substrates 622 and 623 can be welded to the water-repellent filter 73 in this manner.

[0111] Here, the de-aeration channels 715 and 725 are preferably provided on the upstream side of the chambers 61a and 64a. If the de-aeration channels 715 and 725 were provided on the downstream side of the chambers 61a and 64a, when the lids 66 and 67 of the chambers 61a and 64a were opened while liquid was flowing through the channels 71 and 72, there is a risk that air may enter the channels through the through-holes 732 at the top of the de-aeration channels 715 and 725 via the water-repellent filter 73 due to the difference in air pressure.

[0112] As described above, according to the third embodiment, by providing openable and closable lids 66 and 67 to the fluid device 6 which is provided with two layers of chambers 61a and 64a separated by a membrane filter 635, it becomes possible to place or remove objects such as cells into or from the chambers 61a and 64a as needed.

[0113] In the first to third embodiments and modifications described above, examples were given in which a cell culture chamber is provided within the fluid device. However, in addition to this, chambers for conducting various tests, channels for introducing drugs or the like into the cell culture chamber may also be provided within the fluid device.

[0114] The present invention is not limited to the embodiments and modifications described above, and can be implemented in various other forms without departing from the spirit of the invention. For example, it may be formed by excluding some of the components shown in the above embodiments and modifications, or by appropriately combining the components shown in the above embodiments and modifications.

[0115] As an example, the configuration of the bubble-removing channel described in the third embodiment may be applied to the fluid device according to the first and second embodiments. Alternatively, as another example, the shape of the chamber described in the third embodiment may be applied to the fluid device according to the first and second embodiments, or conversely, the shape of the chamber described in the first and second embodiments may be applied to the third embodiment.

[0116] Furthermore, as yet another example, the configuration of the bubble-removing channel described in the third embodiment may be applied to a fluid device that does not necessarily have a lid.

[0117] (Note 1) A laminate formed by stacking and joining multiple substrates, comprising a laminate in which a channel containing one or more chambers is formed inside, A portion of the aforementioned flow path is provided with a part that rises from the bottom side to the top side, A through-hole is formed in a portion of the substrate region that the top of the raised portion faces, which communicates with the outside of the fluid device. The aforementioned through-hole is blocked by a water-repellent filter. Fluid devices.

[0118] (Note 2) The fluid device according to Appendix 1, wherein the upper and lower substrates of the water-repellent filter are welded to the water-repellent filter at its peripheral edge.

[0119] The water-repellent filter is a porous filter made of fluororesin, as described in Appendix 1 or 2 of the fluid device. [Explanation of Symbols]

[0120] 1·2·3·4·5·6…Fluid device, 11a·17a·19a·19b·41a·45a·45b·61a·64a…Chamber, 11·17·19·41·45·61…First layer, 11b·17b·19a·19c…Introduction path, 11c·17c·19 e... Lead-out path, 13 13 A 13 B 13 C 20 62... Second layer, 13 a 161 162 163 20 a 20 b 624 654... Hole, 15 15 A 15 B 15 C 21 a 21 b 66 67... Lid, 19 d 44 a 47 a 71... 72, 715, 725…channels, 43, 46, 63…third layer, 44, 47, 64…fourth layer, 62a…opening surface, 65…fifth layer, 73…water-repellent filter, 101…scaffolding material, 102…cells, 110, 131, 132, 171, 172, 173, 174, 175, 410, 431, 432, 440, 461, 462, 611, 612, 621, 622, 623, 631, 632, 641, 642, 651, 652, 653…substrate, 111, 176, 191, 192, 411, 451, 452, 613, 614, 6 25·626·643·644·655·656·731…Opening, 112·113·138·181·182·441·442·443·627·657…Groove, 115·115…Connection area, 133·135·136·139·140·141·154·177·178·179·180·183·184·185·186·412·413·433·434·436·438·439·463·464·466·467·633·634·636·681·732…Through hole, 134…Dish part, 137… Screw holes, 150, 682…O-rings, 151, 155, 157, 158, 661, 671…Lid body, 152, 156, 662, 672…Flange, 153, 681…Bolts, 445, 446…Ends, 435, 468, 469, 635…Membrane filters, 437, 465, 637…Filter holding substrate, 684…Holding member, 711, 721…Inlet passage, 712, 722…Outlet passage, 11d, 44b, 713, 723…Liquid inlet, 11e, 44c, 714, 724…Liquid outlet, 715, 725…Bubble removal passage

Claims

1. A laminate formed by stacking and joining multiple substrates, wherein a channel containing one or more chambers is formed inside the laminate, One or more lids that can open and close the one or more chambers, A fluid device equipped with the following features.

2. The laminated body is A first layer formed from one or more substrates, and provided with one or more chambers, A second layer formed from one or more substrates and laminated on the first layer, wherein the second layer has one or more holes that penetrate in the lamination direction in a region facing the one or more chambers, Includes, The one or more lids have a portion that closes the one or more holes by being inserted into them. The fluid device according to claim 1.

3. The fluid device according to claim 2, wherein the first layer is formed such that an introduction passage for introducing liquid into one or more chambers and an outlet passage for discharging liquid from the chambers are connected to the chambers from the side.

4. The fluid device according to claim 3, wherein the ends of the introduction passage and the outlet passage are open on the surface in which one or more lids are opened and closed in the fluid device.

5. Multiple chambers and holes are provided. The introduction path and the exit path are in communication with a plurality of the chambers. The fluid device according to claim 3.

6. The one or more chambers provided in the first layer are provided so as to penetrate the first layer in the stacking direction, The laminated body is A third layer located on the opposite side of the first layer from the second layer, having one or more through holes formed in a region facing one or more chambers, and the third layer holding a membrane filter that is permeable to liquid in one or more through holes, A fourth layer formed from one or more substrates and located on the opposite side of the third layer from the first layer, the fourth layer having a channel formed therein that communicates with one or more chambers via the membrane filter, The fluid device according to claim 2, further comprising:

7. Multiple chambers, holes, and through holes are provided. The flow channels formed in the fourth layer communicate with the multiple chambers via the membrane filters held in the multiple through holes. The fluid device according to claim 6.

8. The one or more chambers provided in the first layer are formed to penetrate the first layer in the stacking direction, The laminated body is A third layer located on the opposite side of the first layer from the second layer, having one or more through holes formed in a region facing one or more chambers, and the third layer holding a membrane filter that is permeable to liquid in one or more through holes, A fourth layer formed from one or more substrates and located on the opposite side of the third layer from the first layer, the fourth layer having one or more second chambers that communicate with the one or more chambers via the membrane filters held in the one or more through holes, formed so as to penetrate in the stacking direction, A fifth layer formed from one or more substrates, located on the opposite side of the third layer of the fourth layer, and having one or more second holes penetrating in the stacking direction in a region facing the one or more second chambers, It further includes, The invention further comprises one or more lids that can open and close each of the one or more second chambers, and each lid has a portion that closes the one or more second holes by being inserted into the one or more second holes. The fluid device according to claim 2.

9. The first layer is formed such that a first inlet passage for introducing liquid into one or more chambers and a first outlet passage for discharging liquid from the chambers are connected to the chambers from the side. The fluid device according to claim 8, wherein the fourth layer is formed to connect laterally to the second chambers a second introduction passage for introducing liquid into one or more second chambers and a second discharge passage for discharging liquid from the second chambers.

10. The fluid device according to claim 9, wherein the liquid inlets to the first and second inlet passages, and the liquid outlets from the first and second outlet passages, are both open on the surface in which one or more lids are opened and closed in the fluid device.

11. The fluid device according to claim 6 or 8, wherein the third layer has two substrates, each having one or more through holes, and the membrane filter is sandwiched between the two substrates such that the membrane filter is exposed through one or more through holes.

12. The one or more chambers mentioned above are chambers for cell culture, The extracellular matrix is ​​arranged in the aforementioned membrane filter. The fluid device according to claim 6 or 8.

13. The fluid device according to any one of claims 1 to 10, wherein one or more of the lids are formed of an oxygen-permeable material.

14. A portion of the aforementioned flow path is provided with a part that rises from the bottom side to the top side, A through-hole is formed in a portion of the substrate region that the top of the raised portion faces, which communicates with the outside of the fluid device. The aforementioned through-hole is blocked by a water-repellent filter. A fluid device according to any one of claims 1 to 10.

15. The fluid device according to claim 14, wherein the upper and lower substrates of the water-repellent filter are welded to the water-repellent filter at the peripheral edge of the water-repellent filter.

16. The fluid device according to claim 14, wherein the water-repellent filter is a porous filter made of fluororesin.

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