Method for manufacturing fluid device, fluid device, method for manufacturing laminated structure, and laminated structure
Laser-welded laminated substrates with alternating resin materials allow precise object placement and formation of channels in fluid devices, addressing uniformity and sensitivity concerns.
Patent Information
- Application Number
- PCT/JP2024/045440
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-26
- Filing Date
- 2024-12-23
- Publication Date
- 2025-07-03
AI Technical Summary
Existing fluid devices face challenges in accurately positioning objects such as collagen membranes or reagents within channels or chambers due to non-uniform flow and formation issues, making it difficult to achieve desired thickness and placement.
A method involving laser-welded laminated substrates with alternating resin materials, one absorbable to laser light and one transparent, allowing precise placement of objects in recesses or through regions, and forming channels or chambers through laser irradiation.
Enables the manufacture of fluid devices with objects positioned accurately at desired locations, ensuring uniform thickness and preventing heat or vibration damage to sensitive materials.
Smart Images

Figure JP2024045440_03072025_PF_FP_ABST
Abstract
Description
Method for manufacturing a fluidic device, a fluidic device, and a method for manufacturing a laminated structure, and a laminated structure
[0001] The present invention relates to a method for manufacturing a fluidic device, a fluidic device, a method for manufacturing a laminated structure, and a laminated structure.
[0002] In recent years, development of fluidic devices in which microchannels and chambers are formed in a substrate has been progressing. Fluidic devices can be used, for example, in test chips that introduce liquid samples and reagents into channels to cause reactions and thereby analyze and measure the samples, or in microphysiological systems (MPSs) that create environments that mimic organ functions or disease states by culturing cells in chambers.
[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 resorption unit, where both circuits are connected to each other via the filtration unit and the resorption unit.
[0004] Special Publication No. 2021-508242
[0005] The channels and chambers in fluidic devices are closed spaces except for ports that communicate with the outside of the device. This makes it difficult to position objects used for testing, cell culture, etc. at desired locations in the channels or chambers. For example, when forming a collagen membrane used for cell culture on the inner wall of a channel, one method is to introduce liquid collagen into the channel and attach it to the channel. However, this method has the risk of causing the liquid to flow unevenly through the channel, resulting in uneven film thickness and the membrane not being formed in the desired area.
[0006] The present invention has been made in consideration of the above, and aims to provide a method for manufacturing a fluidic device and a fluidic device that can position objects used in the fluidic device at desired positions within a flow path or chamber, as well as a method for manufacturing a laminated structure and a laminated structure used in the manufacture of such a fluidic device.
[0007] In order to solve the above problem, one aspect of the present invention is a method for manufacturing a fluidic device, which includes a substrate preparation step of preparing a plurality of substrates including a substrate formed of a resin material that is absorbent to laser light and a substrate formed of a resin material that is transparent to the laser light, wherein for at least one of the plurality of substrates, a recess or a through region that penetrates in the stacking direction is formed on the abutting surface of an adjacent layer when the plurality of substrates are stacked so that the substrates formed of the resin material that is absorbent to the laser light alternate with the substrates formed of the resin material that is transparent to the laser light; a stacking step of forming the stack by stacking the plurality of substrates with objects to be used in the fluidic device placed in the space formed by the recess or the through region; and a joining step of joining the stack by irradiating the laser light to a region of the surface of the stack excluding the recess or the through region, thereby melting at least the surface of the substrate formed of the resin material that is absorbent to the laser light in the region irradiated with the laser light, and welding the plurality of substrates together.
[0008] Another aspect of the present invention is a fluidic device comprising a plurality of substrates including a substrate formed from a resin material that is absorbent to laser light and a substrate formed from a resin material that is transparent to the laser light, the plurality of substrates being stacked so that the substrates formed from the resin material that is absorbent to the laser light and the substrates formed from the resin material that is transparent to the laser light are alternately stacked, and at least any of the plurality of substrates has a recess or a through region that penetrates in the stacking direction, which becomes a flow path or chamber within the fluidic device, on the abutting surface with an adjacent layer, and an object to be used in the fluidic device is placed in the space formed by the recess or the through region, and the abutting surfaces of the plurality of substrates are joined by laser welding.
[0009] Another aspect of the present invention is a method for manufacturing a laminated structure, which includes: a substrate preparation step of preparing three or more transparent substrates formed of a resin material that is transparent to laser light, and two or more intermediate layers formed of a resin material that is absorbing and transparent to laser light; a lamination step of forming a laminate in which the three or more transparent substrates and the two or more intermediate layers are stacked so that the transparent substrates and the intermediate layers are alternately arranged; and a bonding step of irradiating the laminate with laser light from the side of a transparent substrate that is an outer layer of the laminate, and welding the intermediate layer to the transparent substrates above and below the intermediate layer in the area irradiated with the laser light, thereby bonding the three or more transparent substrates and the two or more intermediate layers.
[0010] Another embodiment of the present invention is a method for manufacturing a fluidic device, which includes the method for manufacturing the above-mentioned laminated structure, and the bonding process includes forming a recess or a penetrating area that penetrates in the stacking direction, which becomes a flow path or chamber within the fluidic device, on the abutting surface with the adjacent layer of at least one of the three or more transparent substrates and the two or more intermediate layers.
[0011] Another aspect of the present invention is a laminated structure comprising three or more transparent substrates formed from a resin material that is transparent to laser light, and two or more intermediate layers formed from a resin material that is absorbent and transparent to laser light, wherein the three or more transparent substrates and the two or more intermediate layers are stacked so that the transparent substrates and intermediate layers alternate, and the three or more transparent substrates and the two or more intermediate layers are joined by irradiating laser light from the side of the transparent substrate located on the outer layer of the fluidic device, and welding the intermediate layer to the transparent substrates above and below the intermediate layer in the area irradiated with the laser light.
[0012] Another aspect of the present invention is a fluidic device comprising three or more transparent substrates formed from a resin material that is transparent to laser light, and two or more intermediate layers formed from a resin material that is absorbent and transparent to laser light, wherein the three or more transparent substrates and the two or more intermediate layers are stacked so that the transparent substrates and intermediate layers alternate, and at least one of the three or more transparent substrates and the two or more intermediate layers has a recess or a through region that penetrates in the stacking direction at the abutting surface between the adjacent layers, which recess or chamber becomes a flow path or chamber within the fluidic device, and the three or more transparent substrates and the two or more intermediate layers are joined by irradiating laser light from the side of the transparent substrate located on the outer layer of the fluidic device into the region where at least one of the two or more intermediate layers is located, and welding the intermediate layer to the transparent substrates above and below the intermediate layer in the region irradiated with the laser light.
[0013] According to the present invention, it is possible to manufacture a fluidic device in which an object used in the fluidic device can be placed at a desired position in a flow channel or chamber.
[0014] 1-3. FIG. 15 is a perspective view illustrating a fluidic device according to Embodiment 1-1. FIG. 16 is an exploded perspective view of the fluidic device shown in FIG. 1. FIG. 17 is a flowchart illustrating a method for manufacturing a fluidic device according to an embodiment. FIG. 18 is a schematic view illustrating a method for manufacturing a fluidic device according to Embodiment 1-1. FIG. 19 is a schematic view illustrating a method for manufacturing a fluidic device according to Embodiment 1-1. FIG. 20 is a schematic view illustrating a method for manufacturing a fluidic device according to Modification 1-1. FIG. 21 is a schematic view illustrating a method for manufacturing a fluidic device according to Modification 1-1. FIG. 22 is a schematic view illustrating a method for manufacturing a fluidic device according to Modification 1-2. FIG. 23 is a schematic view illustrating a method for manufacturing a fluidic device according to Modification 1-2. FIG. 24 is a schematic view illustrating a method for manufacturing a fluidic device according to Embodiment 1-2. FIG. 25 is a schematic view illustrating a method for manufacturing a fluidic device according to Modification 1-3. FIG. 26 is a perspective view illustrating a fluidic device according to Embodiment 2-1. FIG. 27 is an exploded perspective view of the fluidic device shown in FIG. 14. FIG. 28 is a schematic view illustrating a method for manufacturing a fluidic device according to Embodiment 2-1. FIG. 29 is a schematic view illustrating a method for manufacturing a fluidic device according to Embodiment 2-1. FIG. 1 is a schematic diagram illustrating a method for manufacturing a fluidic device according to Modification 2-1. FIG. 2 is a schematic diagram illustrating a method for manufacturing a fluidic device according to Embodiment 2-2. FIG. 3 is a schematic diagram illustrating a method for manufacturing a fluidic device according to Embodiment 2-2. FIG. 4 is a schematic diagram illustrating a method for manufacturing a fluidic device according to Modification 2-2. FIG. 5 is a schematic diagram illustrating a method for manufacturing a fluidic device according to Embodiment 2-3. FIG. 6 is a perspective view showing a fluidic device according to Embodiment 3. A diagram showing the appearance of a fluidic device according to Embodiment 3. An exploded perspective view of a fluidic device according to Embodiment 3. An enlarged cross-sectional view of a fluidic device according to Embodiment 3. An enlarged schematic diagram showing the shape of a flow channel in a fluidic device according to Embodiment 3.
[0015] Hereinafter, a method for manufacturing a fluidic device and a fluidic device according to embodiments of the present invention will be described with reference to the drawings. Note that the present invention is not limited to the following embodiments. In addition, in the description of each drawing, the same parts are designated by the same reference numerals.
[0016] The drawings referred to in the following description merely show the shapes, sizes, and positional relationships in a schematic manner to enable the understanding of the contents 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 parts in which the dimensional relationships and ratios differ between the drawings.
[0017] The fluidic device according to each embodiment described below can be used, for example, as a testing device for detecting a sample substance contained in a specimen sample by an immune reaction, an enzymatic reaction, or the like. The sample substance is, for example, a biomolecule such as nucleic acid, DNA, RNA, peptide, protein, or extracellular endoplasmic reticulum. The fluidic device allows a liquid containing a specimen sample to flow through the inside and mix with a predetermined reagent to cause a reaction. The fluidic device 10 can also be used as a culture device for culturing cells. However, the uses of the fluidic device according to the present invention are not limited to these.
[0018] The fluidic device according to each embodiment described below comprises a plurality of substrates, including a substrate formed of a resin material that is absorptive of laser light and a substrate formed of a resin material that is transmissive to the laser light, stacked so that the substrates formed of the resin material that is absorptive of the laser light and the substrates formed of the resin material that is transmissive to the laser light are alternately stacked. At least one of the plurality of substrates has a recess or a through-hole region that penetrates in the stacking direction, which becomes a flow path or chamber within the fluidic device, on the abutting surface between the adjacent layers, and an object to be used in the fluidic device is placed in the space formed by the recess or the through-hole region. The abutting surfaces of the plurality of substrates are joined by laser welding.
[0019] Thus, the fluidic device can be manufactured as follows: First, a plurality of substrates are prepared, including a substrate formed of a resin material that is absorptive of laser light and a substrate formed of a resin material that is transmissive to the laser light (substrate preparation process). In the substrate preparation process, a recess or a through-hole region that penetrates in the stacking direction is formed on at least one of the plurality of substrates, at the abutting surface of the adjacent layer when the plurality of substrates are stacked so that the substrates formed of the resin material that is absorptive of laser light and the substrates formed of the resin material that is transmissive to laser light are alternately stacked. Of course, the substrate preparation process may also include procuring a substrate in which the recess or through-hole region described above is pre-formed.
[0020] Next, a stack is formed by stacking a plurality of substrates with an object to be used in the fluidic device placed in the space formed by the recess or the through region (stacking step).
[0021] Next, a laser beam is irradiated onto the surface of the laminate excluding the recess or the through-hole region, thereby melting at least the surface of the substrate made of a resin material that absorbs laser beams in the irradiated region, thereby welding the substrates together (a joining step). Hereinafter, an embodiment of such a fluidic device will be described.
[0022] (Embodiment 1-1) Fig. 1 is a perspective view illustrating a fluidic device according to embodiment 1-1, and Fig. 2 is an exploded perspective view of the fluidic device shown in Fig. 1.
[0023] The fluidic device 10 according to embodiment 1-1 includes a first substrate formed of a resin material that is absorptive of laser light, and a second substrate formed of a resin material that is transmissive to laser light and laminated on the first substrate. Hereinafter, a substrate formed of a resin material that is absorptive of laser light will be referred to as a colored substrate, and a substrate formed of a resin material that is transmissive to laser light will be referred to as a transparent substrate. However, in this specification, the terms colored substrate and transparent substrate are used depending on the properties of the substrate relative to laser light. For example, a transparent substrate does not necessarily mean that the substrate is completely transparent visually. Furthermore, a colored substrate may also be somewhat transmissive visually. The materials of the colored substrate and transparent substrate will be described later.
[0024] 1 and 2, which of the two substrates 110 and 120 is a colored substrate and which is a transparent substrate can be appropriately selected depending on the shape of the flow path formed in the substrate, the object to be placed in the flow path, the process for manufacturing the fluidic device, etc. In embodiment 1-1, the substrate 110 is a colored substrate, and the substrate 120 is a colored substrate.
[0025] The colored substrate 110 and the transparent substrate 120 are in contact with each other at their respective main surfaces 111 and 121. Recesses that serve as flow channels or chambers in the fluidic device 10 are formed on at least one of the surfaces (i.e., the main surfaces 111 and 121) where the colored substrate 110 and the transparent substrate 120 are in contact with each other (in FIG. 2 , the main surface 111 of the substrate 110). Specific examples of the recesses include a recess 112 used as a liquid introduction channel, a recess 113 used as a stirring chamber for a reagent, a recess 114 used as an intermediate channel, a recess 115 used as a culture chamber, and a recess 116 used as a liquid discharge channel. Furthermore, three through-holes 122 that communicate with the three recesses 112, respectively, and a through-hole 123 that communicates with the recess 116 are formed on the transparent substrate 120 side. Of course, recesses that serve as flow channels or chambers may also be formed on the main surface 121 side of the transparent substrate 120.
[0026] An object 1 to be used in the fluidic device 10 is placed in the space formed by the recesses 112 to 116 when the colored substrate 110 and the transparent substrate 120 are laminated. The type of object 1 is not particularly limited. For example, when the fluidic device 10 is used as a cell culture device, cells to be cultured, a collagen membrane, or the like can be placed in the recess. For example, collagen, which is a component of the extracellular matrix (ECM), can be placed in the recess. Furthermore, when the fluidic device 10 is used as a testing device, a reagent can be placed in the recess.
[0027] The position where the object 1 is placed within the space (recesses 112 to 116) is not particularly limited. For example, as shown in Fig. 2, the object 1 can be placed on the bottom surface of the recess 115. Alternatively, the object may be placed on the inner wall or ceiling surface of the recess (i.e., the main surface 121 of the transparent substrate 120).
[0028] Furthermore, a through-hole region communicating with the recesses may be formed in the colored substrate 110 or the transparent substrate 120, separate from the recesses 112-116 and through-holes 122, 123, and a diaphragm member made of an elastic material such as rubber or elastomer resin may be disposed in this through-hole region to form a valve or valve pump. Alternatively, a processing substrate that induces a predetermined reaction in a liquid flowing through a flow path may be disposed in the recesses 112-116, separate from the object 1 described above. The processing substrate may be provided with, for example, a DNA array chip, an electric field sensor, a heater, an element for performing chromatography, or the like. The contact surfaces of the colored substrate 110 and the transparent substrate 120 are joined by laser welding.
[0029] Next, the materials forming the colored substrate 110 and the transparent substrate 120 will be described. Both the colored substrate 110 and the transparent substrate 120 are formed from a thermoplastic resin material that can be joined by laser welding. The colored substrate 110 and the transparent substrate 120 may be formed from the same type of resin material, or may be formed from different types of resin materials as long as they can be laser welded.
[0030] Specific examples of materials that can be used for the colored substrate 110 and the transparent substrate 120 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, polyether ether ketone; PEEK, etc.), and general-purpose amorphous resins (acrylonitrile butadiene styrene copolymer synthetic resin; ABS, polymethacrylate; PMMA, etc.), engineering plastics (polycarbonate; PC, polyphenylene ether; PPE, etc.), super engineering plastics (polyethersulfone; PES, etc.), polymethylpentene (PMP), etc.
[0031] As described above, the colored substrate 110 is formed of a resin material that is absorptive of laser light, and the transparent substrate 120 is formed of a resin material that is transmissive to laser light. That is, the colored substrate 110 has a higher absorptivity for laser light than the transparent substrate 120. While there are no particular limitations on the wavelength band of laser light that can be used in the manufacturing process of a fluidic device, laser light in the visible to infrared range can be used from the standpoints of versatility and cost. A specific example is laser light with a wavelength of approximately 800 nm to 1100 nm. The transparent substrate 120 preferably has a transmittance of approximately 20% or more for such laser light. The thickness of the transparent substrate 120 is determined depending on the type of resin material, additives, etc., so that the laser light that passes through the transparent substrate 120 can sufficiently reach the colored substrate 110.
[0032] On the other hand, the colored substrate 110 is formed from the same type of resin as the transparent substrate 120, or from a material that is colored by adding carbon black or other pigments to a resin that can be laser welded to the transparent substrate 120.
[0033] Next, a method for manufacturing the fluidic device 10 will be described. Fig. 3 is a flowchart illustrating a method for manufacturing the fluidic device according to one embodiment. Figs. 4 and 5 are schematic views illustrating a method for manufacturing the fluidic device 10.
[0034] First, a colored substrate 110 made of a resin material that is absorptive of laser light and a transparent substrate 120 made of a resin material that is transparent to laser light and that can be laminated on the colored substrate 110 are prepared, and a recess (e.g., recess 115) that will become a flow path or chamber in the fluid device is formed on at least one of the main surfaces 111, 121 that are the contact surfaces between the colored substrate 110 and the transparent substrate 120 (substrate preparation step S10). At this time, a through region may be formed and necessary parts (e.g., diaphragms, etc.) may be attached.
[0035] Next, as shown in Fig. 4, the colored substrate 110 and the transparent substrate 120 are laminated together, with an object to be used in the fluidic device 10 being placed in the space formed by the recess when the colored substrate 110 and the transparent substrate 120 are laminated together (lamination step S20). In Fig. 4, the object 1 is placed on the bottom surface of the recess 115 formed in the colored substrate 110.
[0036] The placement of the object in the recess may be determined appropriately depending on the application of the fluidic device 10, the type of object, and the like. For example, as shown in FIG. 4 , the object 1 may be placed only in the center of the bottom surface of the recess 115, the object 1 may be spread across the entire bottom surface, or the object 1 may be placed on the inner wall of the recess 115. Depending on the application of the fluidic device 10 and the type of object, for example, a solid object may simply be placed in the recess, or the object may be fixed with an adhesive or the like to prevent movement within the recess. For example, a gel-like substance may be applied to the bottom, inner wall, and ceiling surfaces of the recess (main surface 121 in FIG. 4 ), or a liquid substance may be applied to the interior of the recess and then dried to form a film. Alternatively, multiple types of objects may be placed in the recess. For example, a collagen film may be formed on the bottom surface of the recess, and cells to be cultured may be placed on top of it.
[0037] Next, as shown in Fig. 5, a laser beam L is irradiated from the transparent substrate 120 side toward the contact surfaces of the colored substrate 110 and the transparent substrate 120 to the laminate 10a, excluding the recesses 112-116. The colored substrate 110 and the transparent substrate 120 are then welded together in the irradiated areas with the laser beam L, thereby joining the substrates (joining step S30). At this time, the laminate 10a may be pressed and tightly attached using a jig or the like. This completes the fluidic device 10 shown in Fig. 1.
[0038] The area to be irradiated with the laser light L does not necessarily have to be the entire contact surface. For example, by irradiating the laser light L at least to the area around the recesses 112 to 116, it is possible to improve the sealing properties of the flow channels and chambers formed by the recesses 112 to 116 and prevent liquid from leaking to the joining surface. Furthermore, by irradiating the vicinity of the outer periphery of the contact surface with the laser light L, it is possible to prevent impurities from entering the interior of the fluidic device 10 from the outside.
[0039] There is no particular limitation on the scanning method of the laser light L. For example, a method may be used in which the laminate 10a is placed on a fixed stage and the irradiation direction of the laser light L is changed by a galvano scanner. Alternatively, a method may be used in which the irradiation direction of the laser light L is fixed, while the laminate is placed on a movable stage and the movable stage is moved to move the irradiation area of the laser light L relative to the laminate 10a.
[0040] As described above, according to embodiment 1-1, it is possible to easily manufacture a fluidic device in which an object used in the fluidic device is arranged at a desired position in a flow channel or chamber.
[0041] Furthermore, according to embodiment 1-1, the colored substrate 110 and the transparent substrate 120 are joined by laser welding, so that it is possible to suppress the influence on objects placed in the fluidic device.
[0042] Here, means for fixing the stacked substrates together include fastening using bolts or the like, adhesives, heat welding, ultrasonic welding, and laser welding. Among these, when using bolts or the like, fastening is time-consuming and there is a risk of liquid leaking from the flow path. In contrast, if a sealing member such as an O-ring is used to prevent leakage, the number of parts increases and the assembly time also increases. There is also a concern about impurities leaching out from the sealing member.
[0043] Furthermore, when an adhesive is used, the manufacturing process is lengthened due to the waiting time required for the adhesive to harden, and there is also the concern that the adhesive may leach into the liquid flowing through the flow channel.
[0044] When thermal welding is used, the entire laminate 10a is heated, and therefore, there is a possibility that an object placed in the recess may be damaged by the heat. Therefore, when thermal welding is used, there is a risk that the object that can be placed inside may be limited.
[0045] When ultrasonic welding is used, the entire laminate 10a is heated, and there is a possibility that an object placed in the recess is subjected to vibrations caused by ultrasonic waves.
[0046] In contrast to these methods, when laser welding is used, the region of the interface between the colored substrate 110 and the transparent substrate 120 irradiated with laser light is locally heated, thereby suppressing the thermal effects on objects placed in the recesses. Therefore, even objects that are sensitive to heat or easily affected by vibration, such as enzymes, living cells, and collagen, can be encapsulated in the fluidic device 10. Furthermore, in the case of welding, resin materials are directly joined together, preventing impurities from being mixed into the liquid flowing through the flow path.
[0047] Furthermore, according to embodiment 1-1, since an object is placed in the recess in an open state before the substrates are laminated, it is possible to manufacture a fluidic device in which an object is enclosed in a desired position and state in a flow channel or chamber. As a specific example, it is possible to arrange a collagen membrane of a desired thickness in a desired pattern in a flow channel or chamber.
[0048] 6 and 7 are schematic diagrams illustrating a method for manufacturing a fluidic device according to Modification 1-1. In the above-described embodiment 1-1, the recesses 112 to 116 are formed on the colored substrate 110 side, but the recesses may be formed on the transparent substrate side.
[0049] 6, for example, recesses 132 that become flow paths or chambers are formed on a main surface 131 of a transparent substrate 130, and desired objects 3a, 3b, and 3c are disposed in these recesses 132. The types and disposition methods of the objects 3a, 3b, and 3c are the same as those described in the above embodiment 1-1.
[0050] 7, a laminate 11 is formed by laminating a colored substrate 140 on a transparent substrate 130 on which objects 3a, 3b, and 3c are arranged, and laser light L is irradiated from the transparent substrate 130 side toward the contact surfaces (main surfaces 131, 141) of both substrates, in an area excluding the recessed portion 132. As a result, the colored substrate 140 and the transparent substrate 130 are welded together in the area irradiated with the laser light L, thereby completing the fluidic device.
[0051] 8 and 9 are schematic diagrams for explaining a method for manufacturing a fluidic device according to Modification 1-2. In the above-described Embodiment 1-1 and Modification 1-1, an object is placed in the formed recess, but an object may be placed on the substrate side facing the recess.
[0052] 8, when a colored substrate 150 and a transparent substrate 160 are laminated, an object 1 is placed in an area on the colored substrate 150 side of a space formed by a recess 162 formed in the transparent substrate 160. The type and placement method of the object 1 are the same as those described in the above embodiment 1-1.
[0053] 9, a laminate 12 is formed by laminating a transparent substrate 160 on a colored substrate 150 on which an object 1 is placed, and laser light L is irradiated from the transparent substrate 160 side toward the contact surfaces (main surfaces 151, 161) of both substrates, excluding the recess 162. As a result, the colored substrate 150 and the transparent substrate 160 are welded together in the area irradiated with the laser light L, thereby completing the fluidic device.
[0054] 10 and 11 are schematic diagrams illustrating a method for manufacturing a fluidic device according to embodiment 1-2. The fluidic device according to embodiment 1-2 is formed by a three-layer substrate, and can be manufactured as follows.
[0055] First, as described in Embodiment 1-1 and Modifications 1-1 and 1-2, a laminate in which two substrate layers are laser welded together is prepared. Figure 10 shows the laminate 11 exemplified in Modification 1-1. A transparent substrate 210 is prepared that can be laminated on the main surface 142 of the colored substrate 140, i.e., the surface opposite the main surface 141 on which the transparent substrate 130 is laminated. A recess 212 that will become a flow path or chamber in the fluidic device is then formed on the surface (main surface 211) of the transparent substrate 210 that abuts against the colored substrate 140.
[0056] Then, the object 2 to be used in the fluidic device is placed in the space formed by the recess 212 when the transparent substrate 210 is laminated on the colored substrate 140. The type and arrangement method of the object 2 are the same as those described in the above embodiment 1-1. Then, in this state, the transparent substrate 210 is laminated on the colored substrate 140. Laser light L is irradiated onto this laminate 20 from the transparent substrate 210 side toward the abutting surface (main surfaces 142, 211) with the colored substrate 140, in an area excluding the recess 212. As a result, the colored substrate 140 and the transparent substrate 210 are welded together in the area irradiated with the laser light L, and a fluidic device is completed in which three substrate layers, the transparent substrate 130, the colored substrate 140, and the transparent substrate 210, are bonded together.
[0057] According to the embodiment 1-2, by making the fluidic device a three-layer structure, it becomes possible to form channels and chambers with more complex structures. In the embodiment 1-2, the recess 212 is formed on the transparent substrate 210 side, but the recess may be formed on the colored substrate 140 side, or the recess may be formed on both substrates.
[0058] 12 and 13 are schematic diagrams illustrating a method for manufacturing a fluidic device according to Modification 1-3. The fluidic device according to Modification 1-3 is formed of three substrate layers, and a through-hole region is formed in the colored substrate disposed between the substrate layers, penetrating the substrate layers in the stacking direction, thereby connecting the flow channels formed in the upper substrate and the lower substrate. Such a fluidic device can be manufactured as follows.
[0059] That is, first, as shown in Figure 12, two transparent substrates 220, 240 and a colored substrate 230 are prepared, and recesses and through-holes that will become flow channels and chambers are formed in each substrate. An object to be used in the fluidic device is placed in the space formed by the recesses when these substrates are stacked. In Figure 12, an object 4a is placed in a recess 222 formed in the main surface 221 of the transparent substrate 220. Furthermore, a through-hole 233 is formed in the colored substrate 230, and a recess 234 is formed on the main surface 231 side. The transparent substrate 240 has through-holes 242, 243 formed therein, and a recess 244 is formed on the main surface 241 side, and an object 4b is placed in this recess 244.
[0060] Then, the transparent substrate 220 is laminated on the main surface 231 side of the colored substrate 230, and a laser beam is irradiated from the transparent substrate 220 toward the contact surfaces (main surfaces 221, 232) of both substrates to weld them together. Next, as shown in Fig. 13, the transparent substrate 240 is laminated on the main surface 232 side of the colored substrate 230, and a laser beam is irradiated toward the contact surfaces (main surfaces 232, 241) of both substrates to weld them together. In this way, the three-layer substrates of the transparent substrate 220, colored substrate 230, and transparent substrate 240 are joined together, and a fluidic device is completed that allows liquid to flow between the three-layer substrates.
[0061] (Embodiment 2-1) Fig. 14 is a perspective view illustrating a fluidic device according to embodiment 2-1, and Fig. 15 is an exploded perspective view of the fluidic device shown in Fig. 14.
[0062] The fluidic device 30 according to the embodiment 2-1 includes a first substrate made of a resin material that is transparent to laser light, an intermediate layer made of a resin material that is absorptive to laser light and laminated on the first substrate, and a second substrate made of a resin material that is transparent to laser light and laminated on the intermediate layer. Hereinafter, the substrate made of a resin material that is transparent to laser light will also be referred to as a transparent substrate.
[0063] The material used for the transparent substrate is the same as that described in embodiment 1-1. The material used for the intermediate layer is the same as the material used for the colored substrate in embodiment 1-1. The two transparent substrates and the intermediate layer used in embodiment 2-1 may be made of the same type of resin material, or may be made of different types of resin material as long as they can be laser welded.
[0064] At least one of the main surface 311 of one transparent substrate 310, which is the surface that abuts against the intermediate layer 320, and the main surface 331 of the other transparent substrate 330, which is the surface that abuts against the intermediate layer 320, has recesses that become flow paths or chambers within the fluidic device 30. In Figure 15, recesses 312 to 316 formed in the main surface 311 of the transparent substrate 310 are shown. In addition, the intermediate layer 320 and the transparent substrate 330 are formed with through holes 323 and 332 that respectively communicate with the three recesses 312 formed in the transparent substrate 310, and through holes 324 and 333 that communicate with the recess 316. Of course, a recess may also be formed in the main surface 331 of the transparent substrate 330.
[0065] An object to be used in the fluidic device 30 is placed in the space formed by the recess when the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330 are laminated together. In Fig. 15, an object 1 is placed in the recess 315. The type of object placed in the recess, the placement of the object within the recess, etc. are the same as those described in embodiment 1-1.
[0066] Naturally, in embodiment 2-1, similarly to embodiment 1-1, a valve or a valve pump may be formed by further forming a through region in the transparent substrates 310 and 330 and arranging a diaphragm member therein, or an arbitrary processing substrate may be arranged in the recess apart from the object 1. The transparent substrate 310, intermediate layer 320, and transparent substrate 330 are joined by laser welding.
[0067] Next, a method for manufacturing the fluidic device 30 will be described. Figures 16 and 17 are schematic diagrams for explaining a method for manufacturing the fluidic device 30.
[0068] First, a transparent substrate 310 formed from a resin material that is transparent to laser light, an intermediate layer 320 formed from a resin material that is absorbent to laser light and that can be stacked on the transparent substrate 310, and a transparent substrate 330 formed from a resin material that is transparent to laser light and that can be stacked on the intermediate layer 320 are prepared, and a recess (e.g., recess 315) that will become a flow path or chamber in the fluid device is formed on at least one of the main surface 311 of the transparent substrate 310 and the main surface 331 of the transparent substrate 330 (substrate preparation process).
[0069] The thickness of the transparent substrates 310 and 330 preferably has a transmittance of approximately 20% or more for the laser light used in the subsequent bonding step. Therefore, the thickness of the transparent substrates 310 and 330 is determined depending on the type of resin material, additives, etc., so that the laser light transmitted through the transparent substrate 310 or the transparent substrate 330 can sufficiently reach the intermediate layer 320.
[0070] On the other hand, the thickness of the intermediate layer 320 may be such that the intermediate layer 320 can be heated and melted throughout its entire thickness direction by laser light that reaches the intermediate layer 320 through the transparent substrate 310 or the transparent substrate 330. As an example, when the intermediate layer 320 is made of polycarbonate, the thickness of the intermediate layer 320 can be set to approximately 0.01 mm to 0.25 mm. If the thickness is greater than 0.25 mm, it may be difficult to melt the intermediate layer 320 throughout its entire thickness direction by laser light irradiation.
[0071] 16, the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330 are stacked together, with an object to be used in the fluidic device 30 being placed in the space formed by the recess when the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330 are stacked (stacking step). In FIG. 16, the object 1 is placed on the bottom surface of the recess 315.
[0072] 17, laser light L is irradiated onto the laminate 30a, which is obtained by laminating the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330. The laser light L may be irradiated from either the transparent substrate 310 side or the transparent substrate 330 side, and this may be determined appropriately depending on the arrangement of the object 1 in the recess. At this time, the laminate 30a may be pressed and adhered using a jig or the like.
[0073] The laser light L is irradiated into the region where the intermediate layer 320 abuts both the transparent substrates 310 and 330 (i.e., the region where the recesses 312 to 316 are not formed). At this time, the laser light may be irradiated onto the entire region where the recesses 312 to 316 are not formed, or may be irradiated onto only a portion of the region. For example, by irradiating the laser light L onto at least the region surrounding the recesses 312 to 316, the sealing properties of the flow paths and chambers formed by the recesses 312 to 316 can be improved. The wavelength of the laser light L used, the scanning method of the laser light L, and the like are the same as those in embodiment 1-1. Furthermore, the irradiation conditions, such as the output power of the laser light, are set appropriately depending on the material, thickness, and the like of the intermediate layer 320.
[0074] When the intermediate layer 320 is irradiated with the laser light L, the intermediate layer 320 absorbs the laser light L in the irradiated region of the laser light L, generates heat, and melts throughout the entire thickness direction. Accordingly, the transparent substrates 310 and 320 in the regions in contact with the heated and melted intermediate layer 320 also melt. Thereafter, as the irradiated region of the laser light L moves, the molten resin material solidifies, and the transparent substrate 310 and the intermediate layer 320, and the intermediate layer 320 and the transparent substrate 330 are simultaneously welded together, thereby bonding the transparent substrates 310, the intermediate layer 320, and the transparent substrates 330 together (bonding process). Note that simultaneous welding is not limited to welding the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330 simultaneously on the time axis, but can be considered to be simultaneous welding if the resin material melted by irradiation with the laser light L solidifies during the time the irradiation area of the laser light L moves, and the transparent substrate 310, the intermediate layer 320, and the transparent substrate 330 are welded together. In this way, the fluidic device 30 shown in FIG. 14 is completed.
[0075] According to embodiment 2-1, a laminate 30a is formed in which an intermediate layer 320 made of a resin material that is absorptive of laser light is disposed between two transparent substrates 310, 330, and by irradiating this laminate 30a with laser light, the intermediate layer 320 is melted throughout its thickness in the irradiated region of the laser light, and the intermediate layer 320 can be welded to the two substrates simultaneously. In other words, a three-layer structure can be joined by a single laser welding process.
[0076] 18 and 19 are schematic diagrams illustrating a method for manufacturing a fluidic device according to Modification 2-1. In the above-described embodiment 2-1, recesses are formed in only one of the transparent substrates, but recesses may be formed in both of the two transparent substrates, and an object to be used in the fluidic device may be placed in each recess.
[0077] 18, for example, an object 1 is placed in a recess 342 formed in a main surface 341 of one transparent substrate 340, and an object 2 different from the object 1 is placed in a recess 362 formed in a main surface 361 of the other transparent substrate 360. As shown in Fig. 19, by irradiating laser light onto a laminate 31 having an intermediate layer 350 sandwiched between the thus prepared transparent substrates 340 and 360, the transparent substrate 340, the intermediate layer 350, and the transparent substrate 360 can be welded simultaneously.
[0078] In Figures 18 and 19, the object 2 is placed on the bottom surface of the recess 362, but the object 2 may also be placed on the main surface 351 side of the intermediate layer 350 that forms a space together with the recess 362 in the laminate 31.
[0079] 20 and 21 are schematic diagrams illustrating a method for manufacturing a fluidic device according to embodiment 2-2. Similar to embodiment 2-1, the fluidic device according to embodiment 2-2 is made up of three layers: two transparent substrates and an intermediate layer, but the flow paths or chambers of the fluidic device are formed in the intermediate layer. Such a fluidic device can be manufactured as follows.
[0080] 20, a transparent substrate 410, an intermediate layer 420 that can be laminated on the transparent substrate 410, and a transparent substrate 430 that can be laminated on the intermediate layer 420 are prepared. Then, a through-region 423 that will become a flow path or chamber in the fluidic device is formed on the main surface of the intermediate layer 420 so as to penetrate the main surface in the lamination direction (substrate preparation process). The materials and thickness conditions of the transparent substrates 410, 430, and intermediate layer 420 are the same as those of the transparent substrates 310, 330, and intermediate layer 320 in embodiment 2-1, respectively.
[0081] Next, the transparent substrates 410, the intermediate layer 420, and the transparent substrates 430 are stacked in a state in which an object to be used in the fluidic device is placed in the space formed by the through-hole region 423 when the transparent substrates 410, the intermediate layer 420, and the transparent substrates 430 are stacked (stacking process). In Figures 19 and 20, the object 5 is placed on the main surface 411 of one of the transparent substrates 410, which forms a space together with the through-hole region 423. Of course, the object 5 may be placed on the main surface 431 of the other transparent substrate 430, or on both main surfaces 411 and 431. The type and placement method of the object 5 are the same as those described in the above embodiment 1-1.
[0082] Next, the laminate 40 is irradiated with laser light L from the transparent substrate 410 or 430 side toward the intermediate layer 420, in the region where the intermediate layer 420 abuts both the transparent substrates 410 and 430 (i.e., the region where the through-hole region 423 is not formed). This simultaneously welds the transparent substrate 410, the intermediate layer 420, and the transparent substrate 430 in the region irradiated with the laser light L, and bonds these three layers together. In this manner, a fluidic device having a flow path or chamber in the intermediate layer is completed. The region irradiated with the laser light L may be the entire region where the through-hole region 423 is not formed, or only a portion of the region. For example, by irradiating at least the region surrounding the through-hole region 423 with the laser light L, the sealing properties of the flow path or chamber formed by the through-hole region 423 can be improved.
[0083] 22 and 23 are schematic diagrams illustrating a method for manufacturing a fluidic device according to Modification 2-2. As described in the above-described embodiment 2-1 and Modification 2-1, in a three-layer fluidic device including an intermediate layer, recesses formed in two transparent substrates may be connected by a through region formed in the intermediate layer.
[0084] 22 , an object 6 a is placed in a recess 442 formed in a main surface 441 of one transparent substrate 440, and an object 6 b is placed in a recess 463 formed in a main surface 461 of the other transparent substrate 460. Furthermore, a through region 453 is formed in the intermediate layer 450, which communicates with the recess 442 and the recess 463 in the laminate 41 when the transparent substrates 440, 450, and 460 are laminated.
[0085] 23 is irradiated with laser light L from the transparent substrate 440 or transparent substrate 460 side toward the intermediate layer 450 in the region where the intermediate layer 450 abuts both the transparent substrates 440 and 460 (i.e., the region where the recesses 442 and 463 and the through-region 453 are not formed). As a result, the transparent substrate 440, the intermediate layer 450, and the transparent substrate 460 are simultaneously welded in the region irradiated with the laser light L, and these three layers are bonded together. In this way, a fluidic device is completed in which the recesses 442 and 463 formed in the transparent substrates 440 and 460, respectively, are connected by the through-region 453 of the intermediate layer 450.
[0086] 24 and 25 are schematic diagrams illustrating a method for manufacturing a fluidic device according to embodiment 2-3. The fluidic device according to embodiment 2-3 has an additional layer added to the three-layer fluidic devices including two transparent substrates and an intermediate layer described in embodiments 2-1 and 2-2 and modifications 2-1 and 2-2.
[0087] Such a fluidic device can be manufactured as follows: In the following, a case where a layer is added to the fluidic device (structure in which the laminate 41 is bonded) described in Modification 2-2 will be described.
[0088] First, an intermediate layer 510 formed of a resin material that is absorptive of laser light and that can be laminated on one of the transparent substrates of the laminate 41, and a transparent substrate 520 that can be laminated on the intermediate layer 510, are prepared. In embodiment 2-3, the intermediate layer 510 and the transparent substrate 520 are laminated on the transparent substrate 460 side shown in FIG. 24. Then, a recess that will become a flow path or chamber in the fluidic device is formed on at least one of the surfaces of the transparent substrate 460 that abuts on the intermediate layer 510 (main surface 462) and the transparent substrate 520 that abuts on the intermediate layer 510 (main surface 521) (second substrate preparation process). In FIG. 24, a recess 464 is formed on the main surface 462 of the transparent substrate 460, and a recess 522 is formed on the main surface 521 of the transparent substrate 520.
[0089] 25, an intermediate layer 510 and a transparent substrate 520 are laminated on the laminate 41. At this time, if necessary, an object to be used in the fluidic device may be placed in the space formed by the recess 464 and the recess 522 in the laminate 50 formed by laminating these substrates.
[0090] Next, laser light L is irradiated onto the laminate 50 from the transparent substrate 520 side toward the intermediate layer 510 within a region where the intermediate layer 510 abuts both of the transparent substrates 460, 520 (i.e., a region where the recesses 464, 522 are not formed). As a result, the transparent substrate 460, the intermediate layer 510, and the transparent substrate 520 are simultaneously welded in the region irradiated with the laser light L, and the intermediate layer 510 and the transparent substrate 520 are bonded to the laminate 50. In this way, a five-layer fluidic device is completed in total.
[0091] Furthermore, it is possible to increase the number of layers in the fluidic device by stacking another intermediate layer and a transparent substrate on the transparent substrates on both ends of the joined laminate and irradiating them with laser light.
[0092] (Variation 2-3) In the above-described embodiment 2-3, recesses that become flow paths or chambers in the fluid device are formed in the transparent substrates 460, 520, but similar to embodiment 2-2, a through-hole region may be formed in the intermediate layer 510 so as to penetrate in the stacking direction. Alternatively, similar to variation 2-2, recesses may be formed in the transparent substrates 460, 520 and a through-hole region may be formed in the intermediate layer 510, and the recesses of the transparent substrates 460, 520 may be connected by the through-hole region in the intermediate layer 510.
[0093] (Embodiment 3) FIG. 26 is a perspective view showing a fluidic device according to embodiment 3 of the present invention. FIG. 27 is a diagram showing the external appearance of the fluidic device. Of these, FIG. 27(a) is a top view, FIG. 27(b) is a side view, and FIG. 27(c) is a bottom view. FIG. 28 is an exploded perspective view of the fluidic device. FIG. 29 is an enlarged cross-sectional view of the fluidic device, showing the A-A cross section of FIG. 27(a). FIG. 30 is a schematic diagram showing an enlarged view of the shape of the flow channel within the fluidic device. Note that in FIG. 29, the vertical and horizontal enlargement ratios are not the same as those in FIG. 27(b) to make it easier to understand the structure of the fluidic device. Furthermore, in FIG. 29, portions of the flow channels located at the rear and front of the A-A cross section (see FIG. 30) are indicated by dashed double-dashed lines.
[0094] In the above-described embodiments 2-3, an additional intermediate layer made of a resin material that absorbs laser light and an additional transparent substrate are stacked on a transparent substrate that constitutes a structure that becomes a fluidic device. Laser light is irradiated from the additional transparent substrate side, and the additional intermediate layer and additional transparent substrate are laser-welded to the structure, thereby sequentially increasing the number of layers in the fluidic device. However, by using a resin material that is both laser-absorbent and somewhat laser-transparent as the intermediate layer, it is also possible to weld three or more transparent substrates and two or more intermediate layers with a single laser irradiation. In this case, it is preferable to use a resin material for the intermediate layer that has a laser light transmittance of, for example, 50% or less (absorption rate of 50% or more). Furthermore, it is preferable to use a highly transparent resin material that barely absorbs laser light as the transparent substrate.
[0095] As a specific example, a combination of a transparent COP (cycloolefin polymer) plate or sheet material as the transparent substrate and a translucent black COP sheet as the intermediate layer can be used. The thickness of the transparent substrate is not particularly limited, and for example, a transparent COP sheet approximately 0.1 mm to 0.2 mm thick or a transparent COP plate material approximately several mm thick can be used. On the other hand, the thickness of the translucent black COP sheet is preferably approximately 0.01 mm to 0.2 mm, and more preferably approximately 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 it to the transparent substrates above and below it while allowing the laser light to pass through and reach the black COP sheet below it.
[0096] Of course, the thickness of the transparent substrate and intermediate layer is not limited to these, and can be set appropriately according to the structure of the fluidic device, taking into consideration the resin material used for the transparent substrate and intermediate layer and their transparency to laser light.
[0097] 26 to 29 has a structure of nine layers in total, including a transparent substrate and an intermediate layer, and is fabricated by welding these nine layers together with a single laser irradiation. The size of the fluidic device 60 is not particularly limited, but as an example, the width of the fluidic device 60 (in the horizontal direction of FIG. 26(a)) can be about 70 mm to 80 mm, and the thickness can be about 20 mm to 30 mm.
[0098] More specifically, the fluidic device 60 includes multiple types of transparent substrates with different thicknesses. Specifically, the transparent sheets 601, 605, and 609 are approximately 0.1 to 0.2 mm thick, and the transparent plates 603 and 607 are approximately 2 to 3 mm thick. The transparent sheets 601, 605, and 609 and the transparent plates 603 and 607 are made of the same type of resin material (e.g., COP) and differ only in thickness.
[0099] The fluid device 60 also includes, as intermediate layers, semi-transparent black sheets (for example, COP sheets) 602, 604, 606, and 608 each having a thickness of, for example, about 0.1 mm.
[0100] These transparent sheets 601, 605, 609, transparent plate materials 603, 607, and translucent black sheets 602, 604, 606, 608 are formed in advance with grooves (groove-shaped through-regions) 611 that become flow paths 631, 632, 633, 634 (see Figures 29 and 30), through-regions 612 that become cell culture chambers 635 (see Figure 29), and through-holes 613 that become entrances and exits 636 for flow paths 631, 632, 633, 634, so as to penetrate in the stacking direction.
[0101] Furthermore, a through-hole region 614 is formed in the transparent sheet 605 located at the center of the layer, and an ECM (extracellular matrix) membrane structure 620 is embedded in this through-hole region 614 as an object used in the fluidic device 60. The ECM membrane structure 620 is a membrane filter 622, a collagen membrane-shaped component, held by a frame-shaped support member 621. The membrane filter 622 acts as an extracellular matrix that serves as a scaffold for the cultured cells. For example, the Vitrigel® membrane "ad-MED Vitrigel® 2" sold by Kanto Chemical Co., Inc. can be used as the membrane filter 622. The Vitrigel® membrane sold by the same company has a mesh-like structure in which collagen fibers are entangled. Note that, although the membrane filter 622 and the support member 621 are circular and ring-shaped, respectively, in Figures 26 to 30, the shapes of these components are not particularly limited. For example, a rectangular membrane filter may be held by a rectangular frame-shaped support member. Furthermore, the membrane filter 622 may be a filter member made of nonwoven fabric, polyester, polyethylene terephthalate (PET), or the like.
[0102] Such a fluidic device 60 can be manufactured as follows. First, transparent sheets 601, 605, and 609 and transparent plate materials 603 and 607 are prepared as transparent substrates, and translucent black sheets 602, 604, 606, and 608 are prepared as intermediate layers. Grooves (recesses) and through-holes that will become flow channels and chambers (culture chambers) are formed on the main surfaces of these components as needed (substrate preparation process). Furthermore, an ECM membrane structure 620 is previously fitted into the through-holes 614 of the transparent sheet 605. Of course, the substrate preparation process may also include procuring transparent substrates and intermediate layers with grooves (recesses) and through-holes already formed.
[0103] 28, these components are stacked alternately with transparent substrates (transparent sheets 601, 605, 609 or transparent plate materials 603, 307) and intermediate layers (black sheets 602, 604, 606, 608) (stacking step). Laser light is then irradiated from the transparent substrate side (e.g., the transparent sheet 609 side) that is the outer layer of this stack into the area where at least one of the intermediate layers 602, 604, 606, 608 is located (bonding step). At this time, it is preferable to irradiate the laser light onto an area excluding the ECM membrane structure 620.
[0104] As described above, the black sheets 602, 604, 606, and 608 are translucent, absorbing some of the laser light and generating heat while transmitting the remaining laser light. Therefore, even in areas where multiple black sheets 602, 604, 606, and 608 overlap as viewed from the outer layer side of the laminate, the laser light can reach all of these black sheets. As a result, in the areas irradiated with the laser light, the black sheets are heated and melted throughout their thickness, welding the black sheets 602, 604, 606, and 608 to the transparent substrates (transparent sheets 601, 605, and 609 or transparent plates 603 and 607) above and below them. In this way, the transparent sheets 601, 605, and 609, the transparent plates 603 and 607, and the translucent black sheets 602, 604, 606, and 608 are joined together, completing the fluidic device 60 with the ECM membrane structure 620 already disposed therein.
[0105] According to embodiment 3, by using a translucent black sheet as the intermediate layer, it is possible to produce a structure in which three or more transparent substrate layers and two or more intermediate layers are stacked by a single laser irradiation.
[0106] Furthermore, in the third embodiment, the ECM membrane structure 620 is fitted in advance into the through-hole region 614 of the transparent sheet 605, and this transparent sheet 605 is then laminated with other layers. Therefore, by forming through-hole regions 612 that will become the culture chamber 635 in the upper and lower layers of the transparent sheet 605, the ECM membrane structure 620 can be placed in a floating state within the culture chamber 635 (see FIG. 29 ). In other words, a two-layer culture chamber 635 partitioned by the ECM membrane structure 620 can be formed.
[0107] Furthermore, because the fluidic device 60 according to embodiment 3 has a multilayer structure, it is possible to easily form channels with complex paths inside the device while miniaturizing the entire device. For example, even when all of the open ends (gateways 636) of the channel 631 for introducing liquid into the upper culture chamber and the channel 632 for introducing liquid out of the upper culture chamber (see FIG. 29 ) and the channel 633 for introducing liquid into the lower culture chamber and the channel 634 for introducing liquid out of the lower culture chamber (see FIG. 30 ) are provided on the upper surface of the fluidic device 60, the fluidic device 60 can be fabricated without requiring a complex cutting process by laminating a transparent substrate or intermediate layer in which a groove or a through region has been formed in advance.
[0108] Furthermore, according to the third embodiment, a translucent black sheet is used as the intermediate layer, so that the channels 631 to 634 and the culture chamber 635 provided inside the fluidic device 60 can be seen from the outside of the fluidic device 60. In other words, the fluidic device 60 allows the cultured cells to be visually observed, and is therefore also suitable for use as a micro physiological system (MPS).
[0109] In the third embodiment, similarly to the first and second embodiments, a channel or a chamber can be provided in the fluidic device by forming a recess in the main surface of the transparent substrate (transparent plate or transparent sheet) or the intermediate layer. Furthermore, in the third embodiment, in addition to the ECM membrane structure 620, sample substances, reagents, cells, and the like may also be disposed as substances used in the fluidic device. In this case, the transparent substrate and the intermediate layer are laminated with these objects disposed in the spaces formed by the recesses or through-hole regions formed in the transparent substrate or the intermediate layer, and laser light is irradiated from the side of the transparent substrate positioned as the outer layer of the laminate.
[0110] The method for manufacturing a fluidic device described in the third embodiment uses a method for manufacturing a laminated structure for bonding a plurality of substrates. This method for manufacturing a laminated structure can also be applied to a method for manufacturing a fluidic device in which no objects (cells, collagen membranes, reagents, etc.) used in the fluidic device are pre-placed inside, and to a method for manufacturing a structure other than a fluidic device.
[0111] That is, three or more transparent substrates formed from a resin material that is transparent to laser light and two or more intermediate layers formed from a resin material that is absorbing and transparent to laser light are prepared (substrate preparation process), the three or more transparent substrates and the two or more intermediate layers are stacked so that the transparent substrates and the intermediate layers are alternately stacked (stacking process), and laser light is irradiated onto the stack from the side of the transparent substrate located on the outer layer of the stack, and the intermediate layer and the transparent substrates above and below the intermediate layer are welded in the area irradiated with the laser light, thereby joining the three or more transparent substrates and the two or more intermediate layers (joining process), thereby manufacturing a laminated structure.
[0112] The materials used for the transparent substrate and intermediate layer, as well as the properties, thickness, and other conditions thereof, are the same as those described in the third embodiment.
[0113] The present invention is not limited to the above-described embodiments and modifications, and can be embodied in various other forms without departing from the spirit of the present invention. For example, some components may be removed from all of the components shown in the above embodiments and modifications, or the components shown in the above embodiments and modifications may be appropriately combined.
[0114] 1, 2, 3a, 3b, 3c, 4a, 4b, 5, 6a, 6b...Object, 10, 30, 60...Fluid device, 10a, 11, 12, 20, 30a, 31, 40... 41, 50... Laminate, 110... Substrate (colored substrate), 111, 121, 131, 141, 142, 151, 161, 211, 221, 232, 241, 311 331, 341, 351, 361, 41, 431, 441, 461, 462, 521...Main surface, 112 to 116, 132, 162, 212, 222, 234, 244, 312 to 316, 342, 362, 442, 463, 464, 522...Recess, 120...Substrate (transparent substrate), 122, 123, 242, 323, 3 24, 332, 333, 613...through hole, 233, 423, 453, 612, 614...penetrating area, 130, 160, 210, 220, 240, 310, 3 20, 330, 340, 360, 410, 430, 440, 460, 520...Transparent substrate, 140, 150, 230... Colored substrate, 320, 350, 420, 4 50, 510... Intermediate layer, 601, 605, 609... Transparent sheet, 603, 607... Transparent plate material, 602, 604, 606, 608... Black sheet, 611... Groove, 620... ECM membrane structure, 621... Support member, 622... Membrane filter, 631, 632, 633, 634... Flow path, 635... Culture chamber, 636... Inlet / outlet
Claims
1. A method for manufacturing a fluid device, comprising: A substrate preparation step of preparing a plurality of substrates including a substrate formed of a resin material having absorbability with respect to laser light and a substrate formed of a resin material having transparency with respect to the laser light, wherein, for at least any one of the plurality of substrates, when the plurality of substrates are laminated such that the substrate formed of the resin material having absorbability with respect to the laser light and the substrate formed of the resin material having transparency with respect to the laser light alternate, a recess serving as a flow path or a chamber in the fluid device or a through region penetrating in the lamination direction is formed on the contact surface with the layer that will be adjacent; A lamination step of forming the laminate by laminating the plurality of substrates in a state where an object used in the fluid device is disposed in a space formed by the recess or the through region; A bonding step of bonding the laminate by melting at least the surface of the substrate formed of the resin material having absorbability with respect to the laser light in the region irradiated with the laser light by irradiating the laminate with the laser light from the surface of the laminate to a region excluding the recess or the through region, thereby welding the plurality of substrates.
2. The method for manufacturing a fluid device according to claim 1, wherein the plurality of substrates include a first substrate formed of a resin material having absorbability with respect to the laser light and a second substrate formed of a resin material having transparency with respect to the laser light, and the bonding step includes irradiating the laser light from the second substrate side toward the first substrate.
3. The method for manufacturing a fluid device according to claim 2, further comprising, after the bonding step, laminating a third substrate formed of a resin material having transparency with respect to the laser light on the first substrate side and irradiating the laser light from the third substrate side toward the first substrate to weld the first substrate and the third substrate.
4. The plurality of substrates include a first substrate and a second substrate formed of a resin material having transparency to the laser light, and an intermediate layer formed of a resin material having absorbability to the laser light. At least one of the first substrate, the second substrate, and the intermediate layer has the concave portion or the through region formed therein. The lamination step includes laminating the first substrate, the intermediate layer, and the second substrate in this order. The bonding step includes irradiating the laser light from one side of the first substrate and the second substrate. A method for manufacturing a fluid device according to claim 1.
5. The bonding step includes melting the intermediate layer over the entire thickness direction of the intermediate layer in the region irradiated with the laser light. A method for manufacturing a fluid device according to claim 4.
6. The bonding step includes simultaneously welding the first substrate, the intermediate layer, and the second substrate. A method for manufacturing a fluid device according to claim 4 or 5.
7. The thickness of the intermediate layer is 0.01 mm or more and 0.25 mm or less. A method for manufacturing a fluid device according to any one of claims 4 to 6.
8. After the bonding step, a second intermediate layer which is a substrate formed of a resin material having absorbability to the laser light and a third substrate which is a substrate formed of a resin material having transparency to the laser light are laminated in this order on the first substrate side or the second substrate side, and by irradiating the laser light from the third substrate side toward the second intermediate layer, the second intermediate layer and the third substrate are welded to the first substrate or the second substrate. A method for manufacturing a fluid device according to any one of claims 4 to 7 further includes a step of doing so.
9. A fluid device, comprising a plurality of substrates including a substrate formed of a resin material having absorbency with respect to laser light and a substrate formed of a resin material having transparency with respect to the laser light, wherein the substrates formed of the resin material having absorbency with respect to the laser light and the substrates formed of the resin material having transparency with respect to the laser light are laminated alternately; a recess serving as a flow path or a chamber in the fluid device or a through region penetrating in the lamination direction is formed on a contact surface of at least any adjacent layers of the plurality of substrates; an object used in the fluid device is disposed in a space formed by the recess or the through region; and surfaces of the plurality of substrates in contact with each other are joined by laser welding.
10. The plurality of substrates include a first substrate formed of a resin material having absorbency with respect to the laser light, and a second substrate formed of a resin material having transparency with respect to the laser light and laminated on the first substrate, wherein the first substrate is melted in an irradiated region by the laser light irradiated from the second substrate side and is welded to the second substrate. The fluid device according to claim 9.
11. The plurality of substrates include a first substrate formed of a resin material having transparency with respect to the laser light, an intermediate layer formed of a resin material having absorbency with respect to the laser light and laminated on the first substrate, and a second substrate formed of a resin material having transparency with respect to the laser light and laminated on the intermediate layer, wherein the intermediate layer is melted over the entire lamination direction in an irradiated region by the laser light irradiated from either one side of the first substrate and the second substrate and is welded to the first substrate and the second substrate. The fluid device according to claim 9.
12. The object includes at least one of cells cultured in the fluid device and a collagen membrane used for cell culture. The fluid device according to any one of claims 9 to 11.
13. The fluid device according to any one of claims 9 to 11, wherein the object contains a reagent used for inspection in the fluid device.
14. A method for manufacturing a laminated structure, comprising: a substrate preparation step of preparing three or more transparent substrates formed of a resin material having transparency to laser light and two or more intermediate layers formed of a resin material having absorbability and transparency to laser light; a lamination step of laminating the three or more transparent substrates and the two or more intermediate layers so that the transparent substrates and the intermediate layers are alternately arranged to form a laminate; and a bonding step of irradiating the laminate with laser light from the side of the transparent substrate located on the outer layer of the laminate and welding the intermediate layer to the transparent substrates in the upper and lower layers of the intermediate layer in the region irradiated with the laser light, thereby bonding the three or more transparent substrates and the two or more intermediate layers.
15. The method for manufacturing a laminated structure according to claim 14, wherein the bonding step includes melting the intermediate layer over the entire thickness direction of the intermediate layer in the region irradiated with the laser light.
16. The method for manufacturing a laminated structure according to claim 14 or 15, wherein the bonding step includes simultaneously welding the first substrate, the intermediate layer, and the second substrate.
17. The method for manufacturing a laminated structure according to any one of claims 14 to 16, wherein the transmittance of the laser light in the intermediate layer is 50% or less.
18. The method for manufacturing a laminated structure according to any one of claims 14 to 17, wherein the thickness of the intermediate layer is 0.01 mm or more and 0.2 mm or less.
19. A method for manufacturing a fluid device, including the method for manufacturing a laminated structure according to any one of claims 14 to 18, wherein at least one of the three or more transparent substrates and the two or more intermediate layers has a recess serving as a flow path or chamber in the fluid device or a through region penetrating in the lamination direction formed on the contact surface with an adjacent layer.
20. The method for manufacturing a fluid device according to claim 19, wherein the bonding step includes irradiating the laser light in the region where at least one of the two or more intermediate layers is located.
21. The laminating step includes laminating the three or more transparent substrates and the two or more intermediate layers in a state where an object used in the fluid device is disposed in a space formed by the concave portion or the through region, the method for manufacturing a fluid device according to claim 19 or 20.
22. The bonding step includes irradiating the laser light on a region excluding the concave portion or the through region, the method for manufacturing a fluid device according to claim 21.
23. A laminated structure including: three or more transparent substrates formed of a resin material having transparency to laser light; and two or more intermediate layers formed of a resin material having absorbability and transparency to laser light, wherein the three or more transparent substrates and the two or more intermediate layers are laminated such that the transparent substrates and the intermediate layers are alternately arranged, and the three or more transparent substrates and the two or more intermediate layers are bonded by irradiating laser light from a side of the transparent substrate located on an outer layer of the fluid device and welding the intermediate layer and the transparent substrates of the upper and lower layers of the intermediate layer in a region irradiated with the laser light.
24. A fluid device including: three or more transparent substrates formed of a resin material having transparency to laser light; and two or more intermediate layers formed of a resin material having absorbability and transparency to laser light, wherein the three or more transparent substrates and the two or more intermediate layers are laminated such that the transparent substrates and the intermediate layers are alternately arranged, and in at least any one of the three or more transparent substrates and the two or more intermediate layers, a concave portion serving as a flow path or a chamber in the fluid device or a through region penetrating in the lamination direction is formed on a contact surface with an adjacent layer, and the three or more transparent substrates and the two or more intermediate layers are bonded by irradiating laser light from a side of the transparent substrate located on an outer layer of the fluid device into a region where at least any one of the two or more intermediate layers is located and welding the intermediate layer and the transparent substrates of the upper and lower layers of the intermediate layer in a region irradiated with the laser light.
25. The fluid device according to claim 24, wherein an object used in the fluid device is disposed in a space formed by the concave portion or the through region.
26. The fluid device according to claim 25, wherein the object includes at least one of cells cultured in the fluid device and a collagen membrane used for cell culture.
27. The fluid device according to claim 25 or 26, wherein the through region is formed in any one of the two or more intermediate layers, and the object is a membrane structure fitted into the through region.
28. The fluid device according to claim 25, wherein the object includes a reagent used for inspection in the fluid device.
Citation Information
Patent Citations
Microchip
JP2009180577A
Magnetically-assisted test strip cartridge and method for using same
US20060257958A1
Method for joining plastic work pieces
US20070051461A1
Method for Producing a Microfluidic Device
US20130061961A1
Fluid device and system
WO2019180871A1